Bi-functional Caulis polygoni multiflori inhibits Staphylococcus aureus and potentiates the activity of erythromycin in vitro

Bi-functional Caulis polygoni multiflori inhibits Staphylococcus aureus and potentiates the activity of erythromycin in vitro | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Bi-functional Caulis polygoni multiflori inhibits Staphylococcus aureus and potentiates the activity of erythromycin in vitro Zhihui Li, Wenlong Wang, Wenbin Xu, Xiaonan Song, Chengtan Wang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8026576/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Feb, 2026 Read the published version in Scientific Reports → Version 1 posted 17 You are reading this latest preprint version Abstract Staphylococcus aureus(SA), particularly methicillin-resistant staphylococcus aureus (MRSA), represents a major clinical challenge due to its ability to form biofilms, which contribute to treatment failure and recurrent infections. This study evaluated the antibacterial and anti-biofilm activity of the water extract of Caulis Polygoni Multiflori (CPM) against clinical and standard strains of SA. CPM exhibited consistent bacteriostatic and bactericidal effects, with time-kill assays confirming rapid elimination of planktonic bacteria at 2×MIC. Mechanistically, CPM dose-dependently inhibited bacterial adhesion to fibrin and suppressed biofilm formation, though it did not disrupt pre-formed biofilms, likely due to poor penetration into the biofilm matrix. In combination studies, CPM showed clear synergistic or additive effects with erythromycin in broth microdilution assays, but not in disk diffusion tests, possibly reflecting limited diffusion of CPM components in solid media. Importantly, CPM's activity was independent of bacterial resistance profiles. These findings indicate that CPM acts through both direct bactericidal activity and anti-virulence mechanisms, and represents a promising candidate for topical combination therapy against MRSA skin and wound infections. Further studies are needed to elucidate its molecular mechanisms. Biological sciences/Biotechnology Biological sciences/Microbiology Caulis Polygoni Multiflori antibacterial activity synergistic effect MRSA Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION Since its discovery, Staphylococcus aureus (SA)—particularly methicillin-resistant Staphylococcus aureus (MRSA)—has become a major pathogen responsible for both healthcare-associated and community-acquired infections worldwide( 1 ). SA infections can range from mild skin and soft tissue infections to life-threatening conditions such as bacteremia, pneumonia, and endocarditis( 2 ). It represents one of the leading causes of nosocomial infections, especially in intensive care units and among postoperative patients. Meanwhile, the rising incidence of community-associated MRSA poses risks even to healthy individuals. MRSA infection significantly prolongs hospital stays, increases healthcare costs, and is associated with higher mortality rates. MRSA strains continue to evolve, showing expanded resistance profiles and enhanced virulence. Moreover, the unique three-dimensional architecture of biofilms protects the bacteria from antibiotics and host immune defenses, leading to a substantial increase in the minimum inhibitory concentrations (MICs) compared to their planktonic counterparts. As a result, the number of effective therapeutic options is severely limited, often restricting treatment to last-line agents such as vancomycin, linezolid, and daptomycin( 3 ). These drugs, however, are associated with drawbacks including high toxicity, inconvenient routes of administration (e.g., intravenous infusion), and high cost. Compounding this problem, the emergence of MRSA strains with reduced susceptibility to vancomycin poses a critical threat( 4 ). Should these last-resort treatments fail, clinicians may face scenarios with no effective antibiotics available. In summary, MRSA infection is not merely a clinical issue but a multifaceted challenge encompassing medical treatment, public health management, and socioeconomic development. It directly endangers patient lives, consumes considerable healthcare resources, and continually undermines the efficacy of modern antibiotics. Therefore, the development of novel therapeutic strategies is urgently needed. Current research on MRSA treatment has entered a new phase characterized by diversification, comprehensiveness, and precision, with a continuous emergence of innovative therapeutic strategies ranging from novel antibiotics( 5 ) to drug combination( 6 ). In response to the resistance mechanisms of MRSA, considerable efforts are being directed toward developing antibiotics with novel chemical structures or distinct modes of action. Among these, tedizolid( 7 ) a next-generation oxazolidinone( 8 ) exhibits an extended half-life that permits once-daily dosing, thereby improving patient adherence. Daptomycin rapidly exerts bactericidal activity by disrupting bacterial membrane potential and remains effective against stationary-phase bacteria, establishing its role as a key therapeutic option for MRSA bacteremia and complicated skin and soft tissue infections. Omadacycline( 9 ), a glycylcycline-class agent, overcomes common tetracycline resistance mediated by ribosome protection, demonstrating potent activity against multidrug-resistant pathogens, particularly in complicated intra-abdominal infections. Furthermore, fifth-generation cephalosporins such as ceftaroline display unique binding affinity for penicillin-binding protein PBP2a in MRSA, representing the first β-lactam antibiotics with clinically relevant anti-MRSA activity. In response to the global challenge posed by MRSA, traditional Chinese medicine (TCM) has demonstrated significant research potential, owing to its unique theoretical framework and extensive practical experience. Unlike conventional antibiotics with single chemical entities, TCM whether in the form of single herbs or compound formulations—contains a variety of active constituents such as flavonoids, alkaloids, phenolic acids, berberine, baicalin, and emodin ( 10 ) These components can exert antibacterial effects through multiple synergistic mechanisms, including disruption of bacterial cell walls/membranes, inhibition of protein synthesis, interference with energy metabolism, suppression of virulence factor secretion, and degradation of biofilms( 11 , 12 ). This multi-target, "cocktail"-like mode of action reduces the likelihood of resistance development through single genetic mutations, thereby offering a promising strategy to combat drug-resistant infections. The combination of TCM with conventional antibiotics can achieve synergistic effects, enabling antibiotic dose reduction and diminished toxicity while enhancing treatment efficacy( 13 – 15 ). This approach aligns with the “synergistic attenuation” principle, contributing to improved clinical success rates. Another distinctive advantage of TCM in managing infectious diseases lies in its dual function of “Fuzheng Quxie”—not only eliminating pathogens (“Quxie”) but also reinforcing host defenses (“Fuzheng”). Numerous TCM formulations and herbs such as Astragalus( 16 ), Ginseng( 17 ), and Ganoderma( 18 ) have been shown to enhance phagocytic activity of macrophages and neutrophils, modulate cytokine balance, and mobilize the host’s immune system to clear infections. This immunomodulatory role is particularly valuable in the management of chronic and persistent MRSA infections, where immune evasion often complicates eradication. Promoting the use of TCM, which exhibits a low propensity for inducing resistance, can help reduce the reliance on high-intensity antibiotics. By mitigating antibiotic selective pressure at the source, this approach may slow the emergence of superbugs and contribute to the global effort against antimicrobial resistance. Caulis Polygoni Multiflori (CPM, Shǒuwūténg) is a commonly used Chinese herbal medicine with reported applications in hyperglycemia management( 19 ), neuroprotection via inhibition of caspase-8, caspase-3, and caspase-7 to mitigate stroke-induced brain injury( 20 ), and sleep improvement ( 21 ), Notably, the root of the same plant, Polygoni Multiflori Radix, has been documented to exhibit anti-MRSA activity( 22 ), though the underlying molecular mechanisms remain unclear. In this study, we evaluated the anti-MRSA activity of a water extract of Caulis Polygoni Multiflori against clinically isolated methicillin-resistant SA strains using disk diffusion, broth microdilution, checkerboard, and time-kill assays. Additionally, its synergistic interactions with conventional antibiotics were assessed, and a preliminary investigation into its antibacterial mechanism was conducted. MATERIALS AND METHODS Bacterial strains and reagents Seven clinical isolates of SA obtained from the Liaocheng People's Hospital Affiliated to Shandong First Medical University, along with the methicillin-sensitive SA (MSSA) reference strain ATCC 25923, were included in this study. All strains were identified using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS; bioMérieux, Craponne, France) prior to in vitro antimicrobial susceptibility testing. Antibiotic susceptibility profiling was performed using the VITEK 2 Compact System in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines (Edition 35), and minimum inhibitory concentrations (MICs) were interpreted based on CLSI M100-Ed35 breakpoints. The water extract of CPM (TongRenTang Chinese Medicine, China) was prepared by soaking the herb in five times its mass of distilled water for 2 hours, followed by decoction for 2 hours. The resulting extract was subsequently dried at 80 ℃ and stored for future use. Erythromycin was prepared as a stock solution at a concentration of 50 mg/mL in ethanol. Minimum inhibitory concentrations/minimum bactericidal concentrations assay The antimicrobial activities of CPM extract against clinical isolates and reference strains were evaluated using the broth microdilution method( 23 ). Briefly, assays were conducted in 96-well curved-bottom non-treated microplates (NETS, China). Two-fold serial dilutions of CPM or erythromycin (Ery) were prepared in Mueller-Hinton (MH) broth (Hangzhou Microbial Reagent Binhe, China), with concentrations ranging from 50 mg/mL to 0.05 mg/mL in a final volume of 50 µL per well. An equal volume of bacterial suspension was then added to each well, achieving a final volume of 100 µL and a bacterial density of 5×10⁵ CFU/mL. The minimum inhibitory concentration (MIC) was defined as the lowest concentration of the test substance that resulted in complete inhibition of visible growth after 24 hours of incubation. The minimum bactericidal concentration (MBC) was determined as the lowest concentration that resulted in a 99.9% reduction of the initial inoculum, as assessed by subculturing on agar plates. Time-kill curves The bactericidal activity of CPM was further evaluated through time-kill assays using both clinical isolates and reference strains. Bacterial cultures with an initial density of 5–8×10⁶ CFU/mL were exposed to CPM at concentrations of 1/2×MIC, 1×MIC, and 2×MIC. Bacterial counts were determined by quantitative real-time PCR (qPCR) at 0, 2, 4, 8, and 24 hours. A standard curve was established as follows: SA ATCC 25923 was cultured overnight in Mueller-Hinton broth at 37℃ with shaking at 160 rpm. The bacterial suspension was then serially diluted 10-fold, and 100 µL of each dilution was plated on nutrient agar for viable counting. Simultaneously, nucleic acids were extracted from an equivalent volume of the original culture, serially diluted 10-fold, and used as template for qPCR amplification with glyA-specific primers (glyA-F: 5'-gcatcgcaattgatcgtgct-3'; glyA-R: 5'-ttaacaggcgctccatgtgt-3'). The standard curve was generated by plotting threshold cycle (Ct) values against the corresponding colony counts. Fibrinogen-Binding inhibitory assay Both control and clinical strains were cultured overnight and adjusted to an OD600 of 1.0 in sterile Mueller-Hinton broth. Aliquots of 100 µL bacterial suspension were added to 96-well plates pre-coated with rabbit fibrinogen (incubated overnight at 4℃) and incubated for 2 hours at 35℃. After incubation, the supernatant was carefully removed, and adherent cells were gently washed with physiological saline. The biofilm was then stained with 12.5 g/L crystal violet for 10 minutes. Following another gentle wash with physiological saline and air-drying, 0.2 mL of 95% ethanol was added to each well to solubilize the bound dye for 30 minutes. Absorbance was measured at 595 nm for all samples. Bacterial aggregation assay and bacterial particle size detection Control and clinical strains were cultured overnight and adjusted to an OD600 of 1.0 in sterile Mueller-Hinton broth. Bacterial suspensions were then mixed with an equal volume of CPM at various concentrations (0, 0.78, 1.56, and 3.13 mg/mL) and incubated for 15 minutes. After incubation, the supernatants were collected for OD600 measurement. A decrease in supernatant optical density indicates bacterial aggregation, as predominantly single cells remain in suspension. The particle size distribution in the supernatants was further analyzed using a Zetasizer Nano system (Malvern Instruments, UK). Biofilm inhibitory assays SA ATCC 25923 and clinical isolates were cultured overnight and diluted 1:100 in sterile Mueller-Hinton broth. Aliquots of 100 µL of the diluted bacterial suspension were dispensed into a 96-well plate (NEST, China). CPM was added to achieve final concentrations of 0, 1/2×MIC, 1×MIC, and 2×MIC. The plate was incubated statically at 35 ℃ for 24 hours. After incubation, the supernatant was carefully removed, and the adhered biofilms were gently rinsed with physiological saline. Biofilms were stained with 12.5 g/L crystal violet for 10 minutes, followed by another gentle wash with phosphate-buffered saline (PBS) and air-drying. Subsequently, 0.2 mL of 95% ethanol was added to each well and incubated for 30 minutes to solubilize the bound dye. A volume of 100 µL of the dissolved crystal violet solution from each well was transferred to a new 96-well plate, and the absorbance was measured at 595 nm using a microplate reader (Perlong, Beijing, China). The percentage of biofilm inhibition was calculated using the formula: where C represents the mean absorbance of the control wells (without CPM) and T represents the mean absorbance of the treated wells. Biofilm destruction assay This experiment evaluated the ability of CPM to disrupt pre-formed biofilms, following a previously described method with minor modifications( 24 ), Biofilms were cultivated in 96-well plates under static conditions at 35 ℃ for 72 hours. The pre-formed biofilms were then treated with various concentrations of CPM and incubated overnight. After treatment, biofilms were fixed with 75% ethanol and stained with 12.5 g/L crystal violet for 10 minutes to assess antibiofilm activity. Control biofilms were maintained without CPM treatment. Double-disk synergy test The assay was performed based on previously described methods( 25 , 26 ) with minor modifications. Mueller-Hinton agar plates (Detgerm, China) were inoculated with bacterial suspensions of clinical isolated and control strains, adjusted to the 0.5 McFarland turbidity standard. Two 6-mm diameter wells were punched into the agar using a sterile borer. A volume of 80 µL of CPM at a concentration of 125 mg/mL was added into each well. To evaluate synergistic interactions, antibiotic disks containing erythromycin(Ery) (Oxoid, UK), clindamycin(DA) (Oxoid, UK), penicillin(P) (Oxoid, UK), clindamycin(CLI) (Taikang, China), or compound sulfamethoxazole(SXT) (Oxoid, UK) were placed on the inoculated plates at a distance of 15–20 mm (center to center) from the CPM wells. Following 16–20 hours of incubation at 35℃, plates were examined for synergistic effects, which were indicated by an elongation or enlargement of the inhibition zone between the antibiotic disk and the CPM well. Checkerboard synergy assay Synergistic interactions between CPM and erythromycin were evaluated using a checkerboard method adapted from a previous study( 27 , 28 ) with minor modifications. Briefly, 96-well plates were prepared by adding 100 µL of bacterial suspension (1×10⁶ CFU/mL), 50 µL of serially diluted CPM extract, and 50 µL of varying concentrations of erythromycin. The plates were incubated at 37°C for 24 hours, after which the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined as previously described. The fractional inhibitory concentration index (FICI) and fractional bactericidal concentration index (FBCI) were calculated as follows: FICI = (MIC of drug A in combination / MIC of drug A alone) + (MIC of drug B in combination / MIC of drug B alone); FBCI = (MBC of drug A in combination / MBC of drug A alone) + (MBC of drug B in combination / MBC of drug B alone). FIC indices (FICI) and FBCI were interpreted as follows: ≤ 0.5, synergy; >0.5-≤1.0, additive; >1.0-≤2.0, indifference; and > 2.0, antagonism. RESULTS Antimicrobial susceptibility and CPM activity The antimicrobial susceptibility profiles of seven non-duplicate SA clinical isolates and the reference strain ATCC25923 were determined using the VITEK-2 Compact System, as summarized in Table 1 . All seven clinical isolates obtained from sputum, bronchoalveolar lavage fluid, blood, secretions, and ascites were resistant to penicillin. Among them, four (57%) were identified as MRSA, four (57%) were resistant to Ery, and two (28.6%) exhibited a positive D-test. In the evaluation of CPM anti-SA activity, the MIC and MBC values for all clinical isolates were between 3125 µg/mL and 6250 µg/mL, respectively. In comparison, the reference strain ATCC25923 showed slightly lower values, with an MIC of 1562.5 µg/mL and an MBC of 3125 µg/mL (Table 2 ). These results indicated that CPM exhibited consistent inhibitory activity against both methicillin-sensitive and methicillin-resistant SA strains. This observation supported the hypothesis that CPM might act through multiple mechanisms a characteristic that might also contribute to the low propensity of traditional Chinese medicine to induce bacterial resistance( 29 ). Table 1. The Drug susceptibility test results of eight SA strains: D-Test: Erythromycin-Induced Clindamycin Resistance Test; P: Penicillin; VA: Vancomycin; GM: Gentamycin; Ery: Erythromycin; LEV: Levofloxacin; MXF: Moxifloxacin; DA: Clindamycin; SXT: Compound sulfamethoxazole; RA: Rifampicin; LZN: Linezolid; TGC: Tigecycline; OX: Oxacillin; Cefoxitin screen test:Cefoxitin Disk Screen Test for Detection of Methicillin-Resistant Staphylococcus aureus. 1-7 represent clinical isolates and 8 represents ATCC25923. Table 2. The results of CPM and Ery: MIC (minimum inhibitory concentration) , MBC (minimum bactericidal concentration) and synergistic effect in eight SA strains: CPM:Caulis Polygoni Multiflori; Ery: erythromycin; FIC:fractional inhibitory concentration index; FBC:fractional bactericidal concentration index. 1-7 represent clinical isolates and 8 represents ATCC25923. Time kill assay In this experiment, bacterial counts were determined by real-time PCR rather than by plating on nutrient agar. As shown in the results(Fig. 1 ), a slight increase in the growth curve was observed at 1/2×MIC, indicating that bacterial proliferative capacity was restored when the drug concentration fell below the MIC level. This sub-inhibitory concentration environment was insufficient to control the infection and may instead facilitate bacterial survival and regrowth. At 1×MIC, the bacterial growth curve plateaued, representing a critical pharmacological threshold. This indicates that the CPM concentration achieved a net inhibitory effect on the bacterial population, effectively preventing the majority of bacteria from dividing and growing, though without substantially reducing the total viable count. This pattern provides strong evidence that CPM acted as a typical time-dependent antibacterial agent. The marked decline in the curve at 2×MIC clearly demonstrates that CPM not only inhibits bacterial growth but also exerts potent direct bactericidal activity. When the concentration was merely doubled, the effect shifted from "inhibition" to "rapid killing," indicating a steep concentration-effect relationship beyond the MIC. These results strongly suggested that in clinical applications, it was essential not only to maintain T > MIC but also to consider increasing the dosing frequency or prolonging intravenous infusion duration to ensure rapid and effective pathogen clearance. CPM could inhibit Fibrinogen-Binding The 96-well plates were pre-coated with rabbit fibrinogen, followed by the addition of bacterial suspensions and incubation at 35℃ for 2 hours. After removing non-adherent cells by washing, the quantity of bacteria attached to fibrinogen was assessed by crystal violet staining. As expected, CPM inhibited bacterial binding to fibrinogen in a dose-dependent manner(Fig. 2 ). The inhibition rates ranged from 60.7% to 82.23% in the 2×MIC group, from 23.15% to 49.14% in the 1×MIC group, and from 1.81% to 23.20% in the 1/2×MIC group. Since bacterial adhesion represents the initial step in the formation of infectious foci and subsequent biofilms, these results demonstrated that CPM effectively blocked this critical process in a concentration-dependent manner. This suggests that CPM can disarm bacteria by preventing their attachment to host tissues or medical device surfaces, thereby suppressing the development of infections at their origin. CPM inhibited bacterial aggregation and reduced the diameter of bacterial particles Overnight bacterial cultures were adjusted to 1.0 McFarland turbidity and co-incubated with different concentrations of CPM. In the 1×MIC and 2×MIC groups, the bacterial suspensions became visibly clearer to the naked eye, with higher drug concentrations resulting in greater clarity. These observations were consistent with the spectrophotometric measurements(Fig. 3 A and B). Unexpectedly, although the turbidity of the 1/2×MIC group showed no obvious visual difference from the control group, its OD600 values were higher than those of the control, a result contrary to expectations. This discrepancy may be attributed to the failure of the drug to effectively induce bacterial aggregation at this concentration, combined with potential background interference. Surprisingly, particle size analysis revealed a significant reduction in bacterial particle diameter following CPM treatment(Fig. 3 C). Higher drug concentrations resulted in smaller particle sizes. At 2×MIC, no bacterial particles were detected in the supernatants, likely because the particle count fell below the instrument's detection limit. This absence may be explained by extensive bacterial aggregation and subsequent precipitation at the bottom of the tube under high drug concentrations. CPM inhibited biofilm formation In this experiment, three concentrations of CPM were selected. The crystal violet staining method was employed to quantify total biofilm biomass by binding to extracellular polysaccharides, proteins, and nucleic acids within the biofilm matrix. The results demonstrated a dose-dependent lightening of color: lower concentrations corresponded to lower inhibition rates. The inhibition rates ranged from 57.95% to 78.45% in the 2×MIC group, from 30.12% to 54.54% in the 1×MIC group, and from 17.36% to 31.68% in the 1/2×MIC group(Fig. 4 ). These findings clearly illustrated the inhibitory effect of the drug on biofilm formation: at low concentrations, the drug likely interfered with initial bacterial adhesion; as the concentration increased, it further suppressed the secretion of extracellular polymeric substances and the maturation of microcolonies. Finally, at high concentrations, it nearly completely impeded the structural development of biofilms. As expected, the inhibition rates were not correlated with the intrinsic drug susceptibility of the bacteria. This suggests that the drug not only exhibited conventional bactericidal activity against planktonic bacteria but also possessed a crucial capacity to disrupt the collective lifestyle of bacterial communities. Most importantly, no significant difference was observed in the inhibitory effect of the same CPM concentration on biofilm formation across different bacterial strains. CPM could not destroy biofilm In the biofilm disruption assay, after pre-formed biofilms were co-incubated with CPM at concentrations ranging from 1/2×MIC to 2×MIC, no significant reduction in biofilm biomass was observed compared with the control group(Fig. 5 ). A slight increase in staining was even detected in some cases, possibly due to nonspecific binding of the drug to the biofilm matrix. The data indicated that CPM did not exhibit a significant disruptive effect on pre-established biofilms, which represented a notable finding. It is likely that the drug only inhibited the growth of metabolically active bacteria in the outer layer of the biofilm, without effectively killing the internal persister cells or degrading the extracellular polymeric matrix. Consequently, no significant change was observed in the total biomass as measured by crystal violet staining. These results clearly demonstrated that the conventional drug susceptibility concentration (MIC) determined for planktonic bacteria is often inadequate against mature biofilms, underscoring the considerable challenge in treating biofilm-associated infections. Synergistic effect between CPM and Ery In these experiments, the double-disk synergy test was employed to evaluate the synergistic effects between CPM and commonly used clinical antibiotics, including penicillin, erythromycin, clindamycin, and compound sulfamethoxazole. Since the active components of Chinese herbal medicine are mostly large molecules such as polysaccharides( 30 ), alkaloids( 31 ), and flavonoids( 32 ), their ability to diffuse in agar medium is relatively limited. Therefore, when performing synergy testing, the distance between the two drug disks was appropriately reduced. CPM exhibited varying degrees of synergy with three of the antibiotics P, Eyr, and DA but not with SXT, and the effects were not observed in all strains. The highest synergy rate was 50% (4/8) between CPM and Ery. Synergy between CPM and P was detected in two strains, and between CPM and DA in one strain(Fig. 6 ). Subsequently, the synergistic interaction between Ery and CPM was confirmed using the checkerboard dilution method. Surprisingly, CPM and Ery showed synergistic or additive effects in all 8 tested strains. All fractional bactericidal concentrations (FBCs) and fractional inhibitory concentrations (FICs) were below 0.5, except for the FIC of strain ATCC25923(Table 2 ). The discrepancy between the results of the two methods may be attributed to the inadequate diffusion of active components in the agar medium. Discussion SA is one of the most common pathogens in clinical infections, causing conditions ranging from respiratory tract and superficial skin infections to more invasive diseases such as cellulitis, folliculitis, and subcutaneous abscesses( 33 ), MRSA in particular, exhibits resistance to multiple antibiotics and poses a major challenge in clinical practice( 34 ). According to the most recent data from the Chinese Bacterial Resistance Surveillance Network, the detection rate of MRSA was as high as 28.7%( 35 ). Some MRSA strains have been reported to exhibit resistance to vancomycin and other last-resort antibiotics( 36 ).These findings indicate that SA infection has become a serious public health threat and a global problem complicating anti-infective therapy( 37 ). The World Health Organization has listed MRSA as a high-priority pathogen requiring the development of new antibiotics( 38 ). In recent years, there has been growing interest in exploring novel antibacterial agents or combination therapies as alternatives to conventional antibiotics( 39 ). Concurrently, research on the antibacterial properties of traditional Chinese medicine has increased. For example, crude ragweed extract( 40 ), and myricetin( 41 )have been reported to act as effective inhibitors of SA infection. The antibacterial mechanisms include inhibition of SA alpha-hemolysin( 40 , 42 ), and alteration of bacterial surface hydrophobicity( 43 ), etc. CPM has been reported to exhibit antibacterial activity( 44 ), however, over the past decade, no further studies have addressed its antibacterial properties or underlying mechanisms. Therefore, this study conducted a preliminary investigation into the antibacterial activity and mechanism of the water extract of CPM. Clinical isolates along with the standard strain ATCC25923 were selected for the experiments. The results demonstrated that CPM exhibited substantial inhibitory activity against all eight bacterial strains, with MIC values ranging from 1562.5 to 3125 µg/mL and MBC values from 3125 to 6250 µg/mL. The antibacterial activity showed no significant correlation with bacterial resistance profiles, indicating that CPM possesses consistent antibacterial activity against SA. The time-kill curve assay is a powerful phenotypic method that transforms the static activity of antibiotics into a dynamic process( 45 ). Its major value lies in dynamically and quantitatively assessing the rate and extent of killing of a specific pathogen by an antibiotic over a defined period. In this experiment, SA load was quantified using both real-time PCR (for bacterial DNA copies) and culture-based enumeration on nutrient agar plates. These data were used to generate standard curves. The results showed that, compared with the control group, both the 1/2×MIC and 1×MIC concentrations significantly inhibited bacterial proliferation. However, the difference between the proliferation curves of these two treatment groups was less pronounced than expected. In the 2×MIC group, no viable bacteria were detected after 2 hours of exposure, and no regrowth was observed within 24 hours, indicating a strong bactericidal effect at this concentration. These findings further confirmed the efficacy of CPM against both standard and clinical isolates of SA. At infection sites, microorganisms typically exist in two phenotypic states: planktonic (free-living) and biofilm (sessile/attached/aggregated)( 46 ). Planktonic microorganisms can attach to suitable surfaces and develop into biofilm aggregates. Within biofilms, microorganisms adapt to enhance their survival under specific environmental conditions( 47 , 48 ). The densely packed polymeric matrix acts as a physical barrier, impairing wound healing and prolonging the inflammatory phase( 49 ), Meanwhile, biofilm-embedded microorganisms enhance their tolerance to antibiotics and host immune defenses through mechanisms such as plasmid-mediated sharing of resistance genes( 50 ). Fibrin is a major component of blood clots and wound healing matrices. By adhering to fibrin, bacteria achieve initial colonization the "first step" in establishing infection foci and subsequent biofilm formation. The results of this experiment demonstrated that CPM dose-dependently inhibited this binding process, thereby preventing bacterial anchoring to host tissues and blocking the formation of infection foci at their origin. This reflects an anti-virulence strategy: even without directly killing the bacteria, reducing their pathogenicity may assist the host in clearing the infection. The bacterial aggregation constitutes the initial key step in biofilm formation. Thus, the core significance of aggregation inhibition assays lies in directly evaluating a drug’s ability to interfere with this critical pathogenic process, beyond mere bactericidal activity. A drug that inhibits aggregation holds potential to prevent early biofilm formation, offering considerable promise for preventing medical device-related infections and certain chronic infections caused by SA. In this study, we found that compared with the control group, CPM significantly promoted the aggregation of SA, particularly at 2×MIC, where the aggregation rate reached 76.69%–95.07%. Surprisingly, no significant aggregation was observed in the 1/2×MIC group, and the OD value was higher than that of the control. However, visual inspection revealed no marked difference in turbidity between this group and the control. This may indicate that at this concentration, CPM did not effectively inhibit bacterial proliferation but instead increased the detection background. Unexpectedly, after co-incubation with CPM, bacterial particle size decreased significantly, with higher CPM concentrations leading to smaller particles. As is well known, SA typically exists as grape-like clusters during growth. The addition of CPM appeared to disperse bacterial cells prior to reducing their size. Subsequent staining with DMAO/PI (Beyotime, China) showed that CPM treated cells were poorly stained by both DMAO and PI (data not shown), suggesting that the reduction in particle size was not solely due to improved dispersion. Instead, CPM may have altered the cell wall or membrane structure, leading to bacterial contraction or transformation from regular rod/spherical shapes into smaller, denser, irregular forms. However, further experimental validation is required to confirm this hypothesis. The extracellular polymeric substance (EPS) of biofilms functions as a robust "fortress" that effectively limits antibiotic penetration. To evaluate whether CPM can inhibit biofilm formation, we employed crystal violet staining. This method quantifies total biofilm biomass by binding to extracellular polysaccharides, proteins, and nucleic acids within the biofilm matrix. A darker color in the well indicates greater biofilm accumulation, while lighter staining reflects reduced biofilm formation. The dose-dependent decrease in color intensity observed in our results clearly illustrated the inhibitory process of CPM on biofilm development: at lower concentrations, the drug likely interfered with initial bacterial adhesion; with increasing concentration, it further suppressed the secretion of extracellular polymers and the maturation of microcolonies; at high concentrations, it substantially blocked the structural development of most biofilms. These findings indicated that CPM not only exhibited conventional bactericidal activity against planktonic bacteria but also interfered with the collective survival mode of bacteria. CPM dose-dependently inhibited biofilm formation, suggesting its potential to inhibit the protective barrier of bacteria and thereby expose them to attacks from both the drug and the host immune system. This provides new therapeutic strategies and drug candidates for addressing stubborn biofilm-associated infections. It should be noted that crystal violet staining is an endpoint total biomass assay that cannot distinguish whether the drug directly kills adherent bacteria or merely inhibits EPS production without affecting bacterial viability. Therefore, a comprehensive evaluation of the anti-biofilm mechanism of CPM requires integration with additional experimental approaches. Once a biofilm is established, it can enhance the tolerance of SA to antibiotics( 51 ). We therefore evaluated whether CPM could disrupt pre-formed biofilms. Unfortunately, even at 2×MIC, CPM showed no disruptive effect on mature biofilms. This is likely because the active components in traditional Chinese medicine are mostly large molecules with limited penetration into the deep layers of biofilms. Thus, even when the nominal concentration reached 2×MIC, the actual drug concentration inside the biofilm may have been far below the minimum biofilm eradication concentration (MBEC), insufficient to induce a qualitative disruptive effect. As combination therapy is a common clinical strategy for drug-resistant bacterial infections, we also assessed whether CPM could synergize with conventional antibiotics. Observation of inhibition zone morphology revealed that CPM and Ery showed clear synergy in four SA strains, whereas no significant synergy was observed between CPM and SXT in any of the eight strains. In the checkerboard dilution assay, we unexpectedly found that CPM and Ery exhibited varying degrees of synergistic or additive effects across all eight strains. This discrepancy may be attributed to the limited diffusion of active components from CPM in solid media. Nevertheless, this does not preclude the potential of developing CPM and Ery as a topical combination for treating wound infections caused by SA. Conclusion In summary, CPM exhibited potent inhibitory and bactericidal activity against SA, including MRSA. It effectively inhibited biofilm formation by blocking the binding of SA to fibrin and promoting bacterial aggregation. However, CPM did not disrupt pre-formed biofilms. Notably, CPM demonstrated strong synergy with erythromycin, particularly in broth dilution assays, highlighting its potential as a promising topical agent for the treatment of MRSA-related skin and wound infections. However, the specific molecular mechanisms underlying its anti-staphylococcal activity and synergistic effects with erythromycin require further investigation. Declarations Acknowledgements: The determination of bacterial particle size was assisted by Professor Yao Shujuan from Liaocheng University, and we would like to express our sincere gratitude. Author contributions: Yinguang Cao is responsible for experimental design, Zhihui Li and Wenlong Wang are responsible for experimental design and biofilm related experiments, Yan Wang and Zhiqing You are responsible for isolation, collection, preservation, and activation of bacterial strains, Min Feng and Juanjuan Fu are responsible for preparation of CPM and synergism assay. Data availability statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare no competing interests. Funding: Shandong Provincial Natural Science Foundation (ZR2017MH099). References Touaitia, R. et al. Staphylococcus aureus: A Review of the Pathogenesis and Virulence Mechanisms. Antibiot. (Basel) . 14 , 470 (2025). Tong, S. Y. C., Fowler, V. G. Jr, Skalla, L. & Holland, T. L. Management of Staphylococcus aureus Bacteremia: A Review. JAMA 334 , 798–808 (2025). F. 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Additional Declarations No competing interests reported. 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14:08:57","extension":"png","order_by":31,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":49778,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage10.png","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/ccd1f90d03757a78798fde76.png"},{"id":96798099,"identity":"2c3cc99c-20e9-4b83-a0c2-bff4b004f9c4","added_by":"auto","created_at":"2025-11-26 08:08:10","extension":"png","order_by":32,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":50202,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage11.png","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/399c69a60b9f52e5a909edcd.png"},{"id":97135649,"identity":"7cd38565-771f-4dbf-8647-40b3f18cc384","added_by":"auto","created_at":"2025-12-01 09:52:23","extension":"png","order_by":33,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":787751,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage12.png","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/991604bcaf0448592ba38f43.png"},{"id":96798091,"identity":"c03f035b-a5ab-47db-ad77-d8df27ce4657","added_by":"auto","created_at":"2025-11-26 08:08:10","extension":"png","order_by":34,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":66199,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/581be3ab8c8c95d9c592ea4c.png"},{"id":96916852,"identity":"48666601-fef6-4c41-818b-c89db3e6d4d8","added_by":"auto","created_at":"2025-11-27 14:08:58","extension":"png","order_by":35,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":52465,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage14.png","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/ef48144624a2e54b386dc4a0.png"},{"id":96798095,"identity":"70f77873-525b-4c57-a646-528964c8302f","added_by":"auto","created_at":"2025-11-26 08:08:10","extension":"png","order_by":36,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":405437,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/ce572e0912482eb92232232c.png"},{"id":96798098,"identity":"e287b593-1ac5-479c-9daa-b76a37789420","added_by":"auto","created_at":"2025-11-26 08:08:10","extension":"xml","order_by":37,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":133713,"visible":true,"origin":"","legend":"","description":"","filename":"cf3b7908a6ad4347973b618980a783c01structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/be44e9e26173a6836bc628be.xml"},{"id":96798089,"identity":"0c7a7c7f-1d53-4a6a-a66b-d88e3d2b5e2e","added_by":"auto","created_at":"2025-11-26 08:08:10","extension":"html","order_by":38,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":147115,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/90897b1659528f50e429cff9.html"},{"id":96798055,"identity":"2f92dba7-de93-47cd-beb8-141a4a1c6ee7","added_by":"auto","created_at":"2025-11-26 08:08:09","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":118410,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTime kill assays of SA\u003c/strong\u003e: A slight increase in the growth curve was observed at 1/2MIC in all the SA strains, and the marked decline in the curve at 2MIC clearly demonstrates that CPM not only inhibits bacterial growth but also exerts potent direct bactericidal activity. The difference in proliferation curves between groups 1/2 and 1 was not very significant. The letters A-G represent clinical isolates 1-7, respectively, and H was ATCC25923.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/566b48f9462fc3f0e171ed5c.jpg"},{"id":96798056,"identity":"a097d383-6266-4026-9e9f-1a1d1ba4be07","added_by":"auto","created_at":"2025-11-26 08:08:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":180374,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCPM inhibited bacterial binding to fibrinogen: \u003c/strong\u003eAfter co-incubation with CPM, the number of bacterial cells that bind to fibrin significantly decreased, and the inhibition rates ranged from 60.7% to 82.23% in the 2MIC group, from 23.15% to 49.14% in the 1MIC group, and from 1.81% to 23.20% in the 1/2MIC group in a dose-dependent manner. 1-7 represent clinical isolates and 8 represents ATCC25923.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/8f97a81610aca48e0d6377d6.png"},{"id":96916839,"identity":"49d3cf4f-e8c5-4267-af33-ac573dc1b59e","added_by":"auto","created_at":"2025-11-27 14:08:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":230799,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe results of aggregation assay and the diameter of bacterial particles: A：\u003c/strong\u003eIn the 1MIC and 2MIC groups, the OD600 values were significantly lower than the control group, but OD600 value of 1/2MIC was higher than those of the control, 1-7 represent clinical isolates and 8 represents ATCC25923; B: the bacterial suspensions became visibly clearer, with higher drug concentrations resulting in greater clarity and \u0026nbsp;the 1/2MIC group showed no obvious visual difference from the control group to the naked eye; C: higher drug concentrations resulted in smaller particle sizes and no bacterial particles were detected in the supernatants at 2MIC group, 8 groups had similar results, only one of ATCC 25923 was displayed here.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/1aeace979794f56f05b12cbe.png"},{"id":96798069,"identity":"b4091cef-e9cb-4c0f-b3a6-8b99d3fe6323","added_by":"auto","created_at":"2025-11-26 08:08:09","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":62281,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCPM inhibited biofilm formation: \u003c/strong\u003eThe biofilm formation was inhibited strongly in a dose-dependent manner, lower concentrations corresponded to lower inhibition rates. The inhibition rates ranged from 57.95% to 78.45% in the 2×MIC group, from 30.12% to 54.54% in the 1×MIC group, and from 17.36% to 31.68% in the 1/2×MIC group. 1-7 represent clinical isolates and 8 represents ATCC25923.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/dc5ef3b689bb42775625b63e.png"},{"id":96798062,"identity":"bd2c5392-69c0-4ecb-a4b6-7169f3ffafc4","added_by":"auto","created_at":"2025-11-26 08:08:09","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":263384,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe result of biofilm destruction assay: \u003c/strong\u003eCompared with the control group, the OD595 values of most experimental groups did not decrease, but rather increased. Indicating that CPM could not destroy the generated biofilm. 1-7 represent clinical isolates and 8 represents ATCC25923.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/b53524a69a4f4a373c3455ed.png"},{"id":96798057,"identity":"02faf59b-8afb-4eb3-b8a3-856f634ed7d6","added_by":"auto","created_at":"2025-11-26 08:08:09","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":347980,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSynergistic effect of double-disk test: \u003c/strong\u003eThe letters A-G represent clinical isolates 1-7, respectively, and H was ATCC25923. The inhibition zones of CPM were marked in red, while the inhibition zones of other antibiotics were marked in cyan. At the connection, the antibacterial zone clearly protrudes and grows towards the middle area, such as CPM with Ery in B, C, F and G, CPM with P in A and E, CMP with DA in B.\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/f695b60ca6b52c50b2ddcbc5.jpg"},{"id":102785189,"identity":"f1af8067-0a1c-4889-9eb5-1bd8f67118c3","added_by":"auto","created_at":"2026-02-16 16:02:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2020369,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8026576/v1/e67c83d0-7057-4709-a72d-473aec2f8ef9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Bi-functional Caulis polygoni multiflori inhibits Staphylococcus aureus and potentiates the activity of erythromycin in vitro","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eSince its discovery, Staphylococcus aureus (SA)\u0026mdash;particularly methicillin-resistant Staphylococcus aureus (MRSA)\u0026mdash;has become a major pathogen responsible for both healthcare-associated and community-acquired infections worldwide(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). SA infections can range from mild skin and soft tissue infections to life-threatening conditions such as bacteremia, pneumonia, and endocarditis(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). It represents one of the leading causes of nosocomial infections, especially in intensive care units and among postoperative patients. Meanwhile, the rising incidence of community-associated MRSA poses risks even to healthy individuals.\u003c/p\u003e\u003cp\u003eMRSA infection significantly prolongs hospital stays, increases healthcare costs, and is associated with higher mortality rates. MRSA strains continue to evolve, showing expanded resistance profiles and enhanced virulence. Moreover, the unique three-dimensional architecture of biofilms protects the bacteria from antibiotics and host immune defenses, leading to a substantial increase in the minimum inhibitory concentrations (MICs) compared to their planktonic counterparts. As a result, the number of effective therapeutic options is severely limited, often restricting treatment to last-line agents such as vancomycin, linezolid, and daptomycin(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). These drugs, however, are associated with drawbacks including high toxicity, inconvenient routes of administration (e.g., intravenous infusion), and high cost. Compounding this problem, the emergence of MRSA strains with reduced susceptibility to vancomycin poses a critical threat(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Should these last-resort treatments fail, clinicians may face scenarios with no effective antibiotics available.\u003c/p\u003e\u003cp\u003eIn summary, MRSA infection is not merely a clinical issue but a multifaceted challenge encompassing medical treatment, public health management, and socioeconomic development. It directly endangers patient lives, consumes considerable healthcare resources, and continually undermines the efficacy of modern antibiotics. Therefore, the development of novel therapeutic strategies is urgently needed.\u003c/p\u003e\u003cp\u003eCurrent research on MRSA treatment has entered a new phase characterized by diversification, comprehensiveness, and precision, with a continuous emergence of innovative therapeutic strategies ranging from novel antibiotics(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) to drug combination(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In response to the resistance mechanisms of MRSA, considerable efforts are being directed toward developing antibiotics with novel chemical structures or distinct modes of action. Among these, tedizolid(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) a next-generation oxazolidinone(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) exhibits an extended half-life that permits once-daily dosing, thereby improving patient adherence. Daptomycin rapidly exerts bactericidal activity by disrupting bacterial membrane potential and remains effective against stationary-phase bacteria, establishing its role as a key therapeutic option for MRSA bacteremia and complicated skin and soft tissue infections. Omadacycline(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), a glycylcycline-class agent, overcomes common tetracycline resistance mediated by ribosome protection, demonstrating potent activity against multidrug-resistant pathogens, particularly in complicated intra-abdominal infections. Furthermore, fifth-generation cephalosporins such as ceftaroline display unique binding affinity for penicillin-binding protein PBP2a in MRSA, representing the first β-lactam antibiotics with clinically relevant anti-MRSA activity.\u003c/p\u003e\u003cp\u003eIn response to the global challenge posed by MRSA, traditional Chinese medicine (TCM) has demonstrated significant research potential, owing to its unique theoretical framework and extensive practical experience. Unlike conventional antibiotics with single chemical entities, TCM whether in the form of single herbs or compound formulations\u0026mdash;contains a variety of active constituents such as flavonoids, alkaloids, phenolic acids, berberine, baicalin, and emodin (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) These components can exert antibacterial effects through multiple synergistic mechanisms, including disruption of bacterial cell walls/membranes, inhibition of protein synthesis, interference with energy metabolism, suppression of virulence factor secretion, and degradation of biofilms(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). This multi-target, \"cocktail\"-like mode of action reduces the likelihood of resistance development through single genetic mutations, thereby offering a promising strategy to combat drug-resistant infections.\u003c/p\u003e\u003cp\u003eThe combination of TCM with conventional antibiotics can achieve synergistic effects, enabling antibiotic dose reduction and diminished toxicity while enhancing treatment efficacy(\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). This approach aligns with the \u0026ldquo;synergistic attenuation\u0026rdquo; principle, contributing to improved clinical success rates. Another distinctive advantage of TCM in managing infectious diseases lies in its dual function of \u0026ldquo;Fuzheng Quxie\u0026rdquo;\u0026mdash;not only eliminating pathogens (\u0026ldquo;Quxie\u0026rdquo;) but also reinforcing host defenses (\u0026ldquo;Fuzheng\u0026rdquo;). Numerous TCM formulations and herbs such as Astragalus(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), Ginseng(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), and Ganoderma(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) have been shown to enhance phagocytic activity of macrophages and neutrophils, modulate cytokine balance, and mobilize the host\u0026rsquo;s immune system to clear infections. This immunomodulatory role is particularly valuable in the management of chronic and persistent MRSA infections, where immune evasion often complicates eradication.\u003c/p\u003e\u003cp\u003ePromoting the use of TCM, which exhibits a low propensity for inducing resistance, can help reduce the reliance on high-intensity antibiotics. By mitigating antibiotic selective pressure at the source, this approach may slow the emergence of superbugs and contribute to the global effort against antimicrobial resistance.\u003c/p\u003e\u003cp\u003eCaulis Polygoni Multiflori (CPM, Shǒuwūt\u0026eacute;ng) is a commonly used Chinese herbal medicine with reported applications in hyperglycemia management(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), neuroprotection via inhibition of caspase-8, caspase-3, and caspase-7 to mitigate stroke-induced brain injury(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), and sleep improvement (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), Notably, the root of the same plant, Polygoni Multiflori Radix, has been documented to exhibit anti-MRSA activity(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), though the underlying molecular mechanisms remain unclear.\u003c/p\u003e\u003cp\u003eIn this study, we evaluated the anti-MRSA activity of a water extract of Caulis Polygoni Multiflori against clinically isolated methicillin-resistant SA strains using disk diffusion, broth microdilution, checkerboard, and time-kill assays. Additionally, its synergistic interactions with conventional antibiotics were assessed, and a preliminary investigation into its antibacterial mechanism was conducted.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eBacterial strains and reagents\u003c/h2\u003e\u003cp\u003eSeven clinical isolates of SA obtained from the Liaocheng People's Hospital Affiliated to Shandong First Medical University, along with the methicillin-sensitive SA (MSSA) reference strain ATCC 25923, were included in this study. All strains were identified using matrix-assisted laser desorption ionization\u0026ndash;time of flight mass spectrometry (MALDI-TOF MS; bioM\u0026eacute;rieux, Craponne, France) prior to in vitro antimicrobial susceptibility testing. Antibiotic susceptibility profiling was performed using the VITEK 2 Compact System in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines (Edition 35), and minimum inhibitory concentrations (MICs) were interpreted based on CLSI M100-Ed35 breakpoints. The water extract of CPM (TongRenTang Chinese Medicine, China) was prepared by soaking the herb in five times its mass of distilled water for 2 hours, followed by decoction for 2 hours. The resulting extract was subsequently dried at 80 ℃ and stored for future use. Erythromycin was prepared as a stock solution at a concentration of 50 mg/mL in ethanol.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eMinimum inhibitory concentrations/minimum bactericidal concentrations assay\u003c/h3\u003e\n\u003cp\u003eThe antimicrobial activities of CPM extract against clinical isolates and reference strains were evaluated using the broth microdilution method(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Briefly, assays were conducted in 96-well curved-bottom non-treated microplates (NETS, China). Two-fold serial dilutions of CPM or erythromycin (Ery) were prepared in Mueller-Hinton (MH) broth (Hangzhou Microbial Reagent Binhe, China), with concentrations ranging from 50 mg/mL to 0.05 mg/mL in a final volume of 50 \u0026micro;L per well. An equal volume of bacterial suspension was then added to each well, achieving a final volume of 100 \u0026micro;L and a bacterial density of 5\u0026times;10⁵ CFU/mL. The minimum inhibitory concentration (MIC) was defined as the lowest concentration of the test substance that resulted in complete inhibition of visible growth after 24 hours of incubation. The minimum bactericidal concentration (MBC) was determined as the lowest concentration that resulted in a 99.9% reduction of the initial inoculum, as assessed by subculturing on agar plates.\u003c/p\u003e\n\u003ch3\u003eTime-kill curves\u003c/h3\u003e\n\u003cp\u003eThe bactericidal activity of CPM was further evaluated through time-kill assays using both clinical isolates and reference strains. Bacterial cultures with an initial density of 5\u0026ndash;8\u0026times;10⁶ CFU/mL were exposed to CPM at concentrations of 1/2\u0026times;MIC, 1\u0026times;MIC, and 2\u0026times;MIC. Bacterial counts were determined by quantitative real-time PCR (qPCR) at 0, 2, 4, 8, and 24 hours. A standard curve was established as follows: SA ATCC 25923 was cultured overnight in Mueller-Hinton broth at 37℃ with shaking at 160 rpm. The bacterial suspension was then serially diluted 10-fold, and 100 \u0026micro;L of each dilution was plated on nutrient agar for viable counting. Simultaneously, nucleic acids were extracted from an equivalent volume of the original culture, serially diluted 10-fold, and used as template for qPCR amplification with glyA-specific primers (glyA-F: 5'-gcatcgcaattgatcgtgct-3'; glyA-R: 5'-ttaacaggcgctccatgtgt-3'). The standard curve was generated by plotting threshold cycle (Ct) values against the corresponding colony counts.\u003c/p\u003e\n\u003ch3\u003eFibrinogen-Binding inhibitory assay\u003c/h3\u003e\n\u003cp\u003eBoth control and clinical strains were cultured overnight and adjusted to an OD600 of 1.0 in sterile Mueller-Hinton broth. Aliquots of 100 \u0026micro;L bacterial suspension were added to 96-well plates pre-coated with rabbit fibrinogen (incubated overnight at 4℃) and incubated for 2 hours at 35℃. After incubation, the supernatant was carefully removed, and adherent cells were gently washed with physiological saline. The biofilm was then stained with 12.5 g/L crystal violet for 10 minutes. Following another gentle wash with physiological saline and air-drying, 0.2 mL of 95% ethanol was added to each well to solubilize the bound dye for 30 minutes. Absorbance was measured at 595 nm for all samples.\u003c/p\u003e\n\u003ch3\u003eBacterial aggregation assay and bacterial particle size detection\u003c/h3\u003e\n\u003cp\u003eControl and clinical strains were cultured overnight and adjusted to an OD600 of 1.0 in sterile Mueller-Hinton broth. Bacterial suspensions were then mixed with an equal volume of CPM at various concentrations (0, 0.78, 1.56, and 3.13 mg/mL) and incubated for 15 minutes. After incubation, the supernatants were collected for OD600 measurement. A decrease in supernatant optical density indicates bacterial aggregation, as predominantly single cells remain in suspension. The particle size distribution in the supernatants was further analyzed using a Zetasizer Nano system (Malvern Instruments, UK).\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eBiofilm inhibitory assays\u003c/h2\u003e\u003cp\u003eSA ATCC 25923 and clinical isolates were cultured overnight and diluted 1:100 in sterile Mueller-Hinton broth. Aliquots of 100 \u0026micro;L of the diluted bacterial suspension were dispensed into a 96-well plate (NEST, China). CPM was added to achieve final concentrations of 0, 1/2\u0026times;MIC, 1\u0026times;MIC, and 2\u0026times;MIC. The plate was incubated statically at 35 ℃ for 24 hours. After incubation, the supernatant was carefully removed, and the adhered biofilms were gently rinsed with physiological saline. Biofilms were stained with 12.5 g/L crystal violet for 10 minutes, followed by another gentle wash with phosphate-buffered saline (PBS) and air-drying. Subsequently, 0.2 mL of 95% ethanol was added to each well and incubated for 30 minutes to solubilize the bound dye. A volume of 100 \u0026micro;L of the dissolved crystal violet solution from each well was transferred to a new 96-well plate, and the absorbance was measured at 595 nm using a microplate reader (Perlong, Beijing, China).\u003c/p\u003e\u003cp\u003eThe percentage of biofilm inhibition was calculated using the formula:\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ewhere C represents the mean absorbance of the control wells (without CPM) and T represents the mean absorbance of the treated wells.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eBiofilm destruction assay\u003c/h3\u003e\n\u003cp\u003eThis experiment evaluated the ability of CPM to disrupt pre-formed biofilms, following a previously described method with minor modifications(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), Biofilms were cultivated in 96-well plates under static conditions at 35 ℃ for 72 hours. The pre-formed biofilms were then treated with various concentrations of CPM and incubated overnight. After treatment, biofilms were fixed with 75% ethanol and stained with 12.5 g/L crystal violet for 10 minutes to assess antibiofilm activity. Control biofilms were maintained without CPM treatment.\u003c/p\u003e\n\u003ch3\u003eDouble-disk synergy test\u003c/h3\u003e\n\u003cp\u003eThe assay was performed based on previously described methods(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e) with minor modifications. Mueller-Hinton agar plates (Detgerm, China) were inoculated with bacterial suspensions of clinical isolated and control strains, adjusted to the 0.5 McFarland turbidity standard. Two 6-mm diameter wells were punched into the agar using a sterile borer. A volume of 80 \u0026micro;L of CPM at a concentration of 125 mg/mL was added into each well. To evaluate synergistic interactions, antibiotic disks containing erythromycin(Ery) (Oxoid, UK), clindamycin(DA) (Oxoid, UK), penicillin(P) (Oxoid, UK), clindamycin(CLI) (Taikang, China), or compound sulfamethoxazole(SXT) (Oxoid, UK) were placed on the inoculated plates at a distance of 15\u0026ndash;20 mm (center to center) from the CPM wells. Following 16\u0026ndash;20 hours of incubation at 35℃, plates were examined for synergistic effects, which were indicated by an elongation or enlargement of the inhibition zone between the antibiotic disk and the CPM well.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eCheckerboard synergy assay\u003c/h2\u003e\u003cp\u003eSynergistic interactions between CPM and erythromycin were evaluated using a checkerboard method adapted from a previous study(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) with minor modifications. Briefly, 96-well plates were prepared by adding 100 \u0026micro;L of bacterial suspension (1\u0026times;10⁶ CFU/mL), 50 \u0026micro;L of serially diluted CPM extract, and 50 \u0026micro;L of varying concentrations of erythromycin. The plates were incubated at 37\u0026deg;C for 24 hours, after which the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined as previously described. The fractional inhibitory concentration index (FICI) and fractional bactericidal concentration index (FBCI) were calculated as follows: FICI = (MIC of drug A in combination / MIC of drug A alone) + (MIC of drug B in combination / MIC of drug B alone); FBCI = (MBC of drug A in combination / MBC of drug A alone) + (MBC of drug B in combination / MBC of drug B alone). FIC indices (FICI) and FBCI were interpreted as follows: \u0026le; 0.5, synergy; \u0026gt;0.5-\u0026le;1.0, additive; \u0026gt;1.0-\u0026le;2.0, indifference; and \u0026gt;\u0026thinsp;2.0, antagonism.\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003eAntimicrobial susceptibility and CPM activity\u003c/h2\u003e\n \u003cp\u003eThe antimicrobial susceptibility profiles of seven non-duplicate SA clinical isolates and the reference strain ATCC25923 were determined using the VITEK-2 Compact System, as summarized in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. All seven clinical isolates obtained from sputum, bronchoalveolar lavage fluid, blood, secretions, and ascites were resistant to penicillin. Among them, four (57%) were identified as MRSA, four (57%) were resistant to Ery, and two (28.6%) exhibited a positive D-test. In the evaluation of CPM anti-SA activity, the MIC and MBC values for all clinical isolates were between 3125 \u0026micro;g/mL and 6250 \u0026micro;g/mL, respectively. In comparison, the reference strain ATCC25923 showed slightly lower values, with an MIC of 1562.5 \u0026micro;g/mL and an MBC of 3125 \u0026micro;g/mL (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). These results indicated that CPM exhibited consistent inhibitory activity against both methicillin-sensitive and methicillin-resistant SA strains. This observation supported the hypothesis that CPM might act through multiple mechanisms a characteristic that might also contribute to the low propensity of traditional Chinese medicine to induce bacterial resistance(\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1. The Drug susceptibility test results of eight SA strains:\u0026nbsp;\u003c/strong\u003eD-Test: Erythromycin-Induced Clindamycin Resistance Test; P: Penicillin; VA: Vancomycin; GM: Gentamycin; Ery: Erythromycin; LEV: Levofloxacin; MXF: Moxifloxacin; DA: Clindamycin; SXT: Compound sulfamethoxazole; RA: Rifampicin; LZN: Linezolid; TGC: Tigecycline; OX: Oxacillin; Cefoxitin screen test:Cefoxitin Disk Screen Test for Detection of Methicillin-Resistant Staphylococcus aureus. 1-7 represent clinical isolates and 8 represents ATCC25923.\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003cimg width=\"516\" height=\"169\" 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awL3wzJc+J7HVo7+dVgkZ5IWII5TaAvHHvk9zitL+2bD/nuf+/T/APxNJ/ben79n2n5sZ2+U+cev3aAL1FUv7ZsP+e5/79P/APE0f2zYf89z/wB+n/8AiaALtFUv7ZsP+e5/79P/APE0f2zYf89z/wB+n/8AiaAF1LrZf9fkf8mq5WPqGr2LGzxOeLuMn90/TB9qt/2zYf8APc/9+n/+JoAu0VS/tmw/57n/AL9P/wDE0f2zYf8APc/9+n/+JoAu1R1mxbUdOa3SKzly6kx3aF42APIIHQ+h7Uv9s2H/AD3P/fp//iaRta09VLNcEKBkkxPgD/vmgA0bS49G01bODIjV2ZVySEDHO0Z5wO1XqpDWbAjIuCQf+mT/APxNH9s2H/Pc/wDfp/8A4mgC7RVL+2bD/nuf+/T/APxNH9s2H/Pc/wDfp/8A4mgC7VPS/wDj2l/6+Zv/AEY1J/bNh/z3P/fp/wD4mqmm6vYrbygzkf6RMf8AVP8A89G9qANiiqX9s2H/AD3P/fp//iaP7ZsP+e5/79P/APE0AXaKpf2zYf8APc/9+n/+Jo/tmw/57n/v0/8A8TQBk2nhWS28SHUTcoYxczXIwpEjeYoXYx6FRjI/CujqiNb08uVFz8wAJHlPkA9P4fY0v9s2H/Pc/wDfp/8A4mgC7RVL+2bD/nuf+/T/APxNH9s2H/Pc/wDfp/8A4mgC7VO7/wCQlpv/AF0k/wDRbUn9s2H/AD3P/fp//iaqXWr2J1DTyJzhZJM/un/55t7UAbFFUv7ZsP8Anuf+/T//ABNH9s2H/Pc/9+n/APiaALtFUv7ZsP8Anuf+/T//ABNH9s2H/Pc/9+n/APiaAJr2KW4sZ4YJBHJIhRXP8OeM1JDElvBHDEu2ONQij0AGBVR9b06NSz3O1R1JicAfpS/2xY/892/78yf/ABNAF2iqX9s2H/Pc/wDfp/8A4mj+2bD/AJ7n/v0//wATQBdpyffX61Q/tmw/57n/AL9P/wDE0qazYb1/fnr/AM8ZP/iaAE0X/kC2v+5/U1drF0fV7JNHtVacghOf3T+p9qu/2zYf89z/AN+n/wDiaALtFUv7ZsP+e5/79P8A/E0f2zYf89z/AN+n/wDiaALw61zei+GJ9L16fUZLmJjMjrL5YIM5L7lZh0BUccda1v7ZsP8Anuf+/T//ABNINb09mYC5yV4YCJ+O/Py0AXqKpf2zYf8APc/9+n/+Jo/tmw/57n/v0/8A8TQBdoql/bNh/wA9z/36f/4mj+2bD/nuf+/T/wDxNAGNrPPjSx/7B03/AKNjoqHUbyC68ZWRgkLBdOmB+Rl/5ax+oFFAi94N/wCQRdf9hG6/9Gmt6uf8HC6Ok3fk2FxMv9o3XzoYwP8AWn1YGt7Zf/8AQJvP++ov/i6BjqKbsv8A/oE3n/fUX/xdGy//AOgTef8AfUX/AMXQA6im7L//AKBN5/31F/8AF0bL/wD6BN5/31F/8XQA6im7L/8A6BN5/wB9Rf8AxdGy/wD+gTef99Rf/F0AOopuy/8A+gTef99Rf/F0bL//AKBN5/31F/8AF0AOopuy/wD+gTef99Rf/F0bL/8A6BN5/wB9Rf8AxdAFTWf+QLe/9cW/lV8s2TyfzrO1lL7+xb3dpd2o8lsktFgcf79XSt/n/kE3n/fUX/xdAGFJ4kuLLxSdOvkiFrNGzW0yZDM6gEocnGcHjFZ9t4t1aeGzdo7NGudVbTiu1zsxn5s7uenSt6bQpLi4SafSNQlkjnFxGXliPluBgFfn6Y7ewqmng9Y1iVdN1gCG5N2n+kxcTHq33qEJ+Qul63qGuWs97YR262yzNFDHKW3yBTgsSOF74GD9a3gx3DDHr61lwaFJazSvbaTqMKSyebJCk0YjZz1O3fxnvjitALf5B/sm8/76i/8Ai6AOdv8AWbnQ/CkN5b+UxFyY2EoJGGmYZ4I6ZzTrXxcFsbm6vtjQLd/ZbWe3ztus91BPGCCDzjipo9Il1nQobe50zUDEk7yfupY0yyyMRzv7GnN4SjYzY0fUkE063JCTxqFmXpIo3/K3rjrQA+LxTaTz+TGlz5n2b7TtZdh24J6Eg9semcVnTeOUmhgewhky8tqHE4/5Zzk4IweoxWxLokk95HdT6RqEssalVLzRkDK7Sfv9SCazo/BFvEoVNI1YAeVj/SY+PKz5f8fbNAxZPGMT2drPZW80wuLxLQBmVSpPXPPBGOh79a1bVm/tbUeT/wAse/8AsmqZ8MKw50bUC/2hLnzPOj3eYgwpzv8ATirFqL06tqGNLuyf3WRui4+U/wC3QITXr2/sdKkuNNSKa4Q8RS5w/sMEYNZK+Lp7640FdOEJh1T5ZHk3MY227iAAR0xg1vXFne3Ij3abqCeW4kHlyRDJHTPz8is1fCiRPaNBo+pQfZJXmhEU8QCu/wB4/f564+lAzM0/xjfXqWMHlW/22/upoY8bhHGkX3mPOST2AxXT2z3n7wXflcMNjRE/MMdSD0Oc8c1lw+E0t7aOGPSNTxFMbiKQ3Ee+Jz94q2/jPcdDWpBbXsCFRpl+5JyWkkiZif8AvugRFcMf7X0/k/cm7+y1zsPi/UH1h7BY7SaZNRNp5Ee5ZGjAyZQSSOM8it65F7/a9gDpd2DsmwN0XPC/7dUj4QjZpHOlar5j3P2vzPtEYdJf7ynfxkYBHTijqMH8Z6epvcG4ZLTcHkVPlJVgrc9sE98cZPQUl54ysrEr5sV0QbdLkFApGxnCDv6kfhVqHQJLZLlINL1OOO5kMzotxGFDnGWA38Zxz2qpceDLe5hiibRNRRIoRAojnjXKB94B+fn5hmheYDNO8XCa+ezvEKzm9ltofK+6wQqMnJ6/NnA7Amnxay+taNczeQ8KxXywLuYHdsmUZ496lj8KrG7N/ZGpPuuPtTK88ZBkyDuxv9QKJ9Ll0zTJkttJvY0mu0mYNJGwDtKpOPn4yaEI2yxz1P51zcPiW8j1690u9jhDrGZLJ03Dz8NtIOT1Bx07V0G2/wA/8gm7/wC+ov8A4us5vD7vcRXEmlai88LSNFK0sRaMuMNg7/8A9VIZhad4x1G7j0KWZLRI9T88ybVcmNYsk4+bnIFa+javqWtabBqUUVultcPlImZt6xbsbi3TdgE4x+NR2vg9LM2Bg0vVgLAubdTcxEJu+9/Hzn3q5ZaFJpwCWmlalHAHLrbiePy1JOThd/HPbpTEaRZsHk9PWuZvdbuNF0TQWjeBYrloreR5gxEYKZ3cEdMV0RS/wf8AiU3n/fUX/wAXWPDo0uqaTpDT6bqJ+ypHNCYpYlG8KMN9/n8fWgZWtfGQTR4bzUoWVrieSK3Fvki4RcnzFBOQCB0NW5PFtnGL4hbhvsUPnyjaAdm0NkAkHoe/cEdqSLwlHAEEGkanEIrg3MIS4jHkueuz5/lBzyOlTXHh37XNNJcaNfytNC8DbpozhGxuA+fjOBQBnT+NF+1WyW0MhjN15E+9csAYvNBTB5OOxqwvixLh9J+x28sqajK0atvX5Qq7ievP/wBY96RPBscciuulatuWUTA/aY87wmwH7/8Ad4qxH4aEUkEiaLfiSCdrhH82LJdhhifn5yKBFvT2Pnahyf8Aj6Pf/YSqfifVr/RtLN5YxRTmMlpI5N2SgBJKkHqADVjT1vTPqGNLuyftRzhouPkT/bqa4sbu5eNpNMv8RknaskQVsjBDDfyME/nQxmNL4nuLjW7K1077O1pdWklws8gZiSqg4ABHHIH51X0jxbfauukwJHbpeX9u907EN5cUattwBnLMSPUCtCPwmsD2rW+k6pD9khaCERzxAIjfeH3+/rS2/hVbS3s4rfSdTjNluFvKJ4/MjVuq7t/Kn0OaBampbPdGNvtYjWQMQPLJIZex56H2qEljrygNgmzYAn/roKmht72GMIul3zdyXkiYk+pO+qrLe/28o/sy8DG0YABos/fHP36BmFo3jC+1LUbW2KWsrSTzRTxw7g8CRnAkOSRgntV1fG+myWstyn2gwxuqiQphWDMVB3E4AyD1x29afB4QjtjA0Wk6oJLeZpopPtEe9Wb7wzv6HuOlTxeGzBpz2MWlamlqzMwiE8e1N2SQBv6cnigCKfxba29+LOSK6EheBM4GAZs7O/sc1X0LxgNSW3huYyt5MJGCx8KQrsvGTk/d564yKnm8IxTXEU39i6jG0QhCiOeNR+6/1fG/nGTT7Twstl9n8rR9RYW8hliWSeNgrHOT9/8A2j+dAEVjrD65o+l6gYWgE14pVCwPALAHj6VvbmPAY5rF/syXSLLT7O10q9jgju1KK8kbYzuOAd/vWvsv/wDoFXg/4FF/8XQI5iHxbegavbXUMC31onm2wUsEmjwfmOTnjac1FB4yvVNjNeJbi2n0t9Rl8tW3KF/gGWx+NbD+GvMO59J1JpfIe384zRb/AC3OWGd/1/M1Hb+FFtpraRNK1Rvs1ubWNJJ4mXyj1QjfyKWv9fP/AIAybSr/AFS/srO9kS1WG5USGNWbdEhGRz0Y9M8CrmpMf7KvOT/x7yd/9k1XsNGn02OOO20zUxDEMRRPPGyRj0AL/wA84qXUlvhpV5u0u7A8iTJLRcfKf9umIydb8QT6LcaTF51rDb3aOJJrgMRFsTdngjg9KSDxisOlafPqtvNDd3iNIIIgX+QHG8d8EEHHXmrs+hyalJY3VzpWoM9qn7sLLEE+ZcNkb+cjjntUdr4VFkbU2+larGbQv5BFzHmNW+8g+f7p9KEMSfxdZwQX8pW4ZbGQRzBQMglto4Jz1Oeeo5FU5/GyR30ISGT7KDdJPlcyK0IGduDgg5q/c+GFuxdfaNF1BzdIEkYzR52htwAO/jB5qKLwgkM6TJperCRHkkB+1R/ekxvP3++BQBJF4lFxqmm2lvBI8d7DJMJd64VVIHGDz17dqu6Wx+zS8n/j5m7/APTRqrW3hwWk9rNBot8klqJFjIliGQ5y2RvwcnmptLW++zS7dLu2/wBJm6NF/wA9G/26BFLxPrt5oENvdxRRzWocfaQ27eiZALLg44z0xVK/8V3seq6hb2a2zW9rpzX0cj7iZdpIxwQMEg81t3ulXGoArc6VftG0bxNGJIgrKwwcjfVB/CKO7sNK1RN9oLIqlxEB5I/gxv8A/r0hkGl+JL7Vrq1s4Ut0maxjvbiRgxVQ/wB1FXOSfUk1v2z3LQKboIk3O4RsSvXjBPtisyLw0bc2zwaVqcU1tD5EcyTxB/L7Ix3/ADAds1pxwXsUaouk3uFGOXiJ/MvVMSKu+QapfmNgHFtEVLZIzmTrWB4e8Z3WrSWpmW2aJ7V7i6MO4G02k43ZJyGxxW4Ib2XVb6P+zb1S1vEDteIMBmTnO+qlt4Phs/sph0bUgbaNokJnjyY26o3z/MvJ4PrSGNj8bafLaR3CrdCOSVY0LJgNuXcpyTjkDGM5zxT5/FsEd9LYrHOLhJmtwWA2bxH5gzznGKk/4RnOlJpraVqjWaDasbXEZAX+7y/SmTeFEnvzeHR9SSYv5nyTxhd2zZnG/wDu8UPyAraV4zjvtOSSWGT7ULIXckaEBcbS3y5OccYz0zxVuz1GTVIdCvnjMJuA0mzdnGYmPWktvCkdrHCiaLqDpBE0MayTRttRhtIHz+nFPWxuNOk0i0g0u9EUJdIw8kbHAjYAZ30CNaRpPLbY2GwcFskZ965D/hNb1NC1WWa3gXVNPbJhBbY0e0MH65wR+tdW8V+8bL/Zd6u4YyrxAj6fPWVP4VS5inSXR9RJuLdbaWQTRB3jU5Ck7/8AOBSGZtz4xu9NuLw3yQvBa6dHenylYM7OcBOSQBk9a3rKXVHED3YtdkibpPKLAxnGQBk/N9ePpVRfCy/aJZpdJ1KczW4tZFmmiZXiHRSN/b1q3Z6ZdWKIsenao6ouxBLPG+xfQfP/ADzTEhdaY/2Ndcn7o7/7QrJ8S+J7jRdZW282zihktZLhXnD/AHlOAnB7k1pa0t6NHud2l3ajaOS0XHzD/bpl/wCHjqWofa7rSNQkfymg2GWLYY2+8pXf3/pSYyuniqOJrC3v4J4b66hSWSBBv8ncdoz7Z/IdaB4vs2thOiXLIbpbTgDIdiQMjPHI5zzyOKltPDTWM9vNBpeqiW3i8hHNzGSY852N8/IB6elNk8LrIkofRtRLSSxzNJ58e/dH9w539qYjNHjuI3UcpiddPe0afcwxIrCbyiDztC55z2rWs/EBu/EMenxW8mxrRboylhwGbAGM+1VrbwdHaNG0GlaqpjjaJf8ASYzhWbeR9/n5ueauWOgf2fdwXFtot9G8MAtlxLHjywcgEb+ec0IGS6Kx/sW15P3PX3NZ+u6/daJqViWSJtOmkWO4kOQ8O44DdcYz7Vc0Vb06Na7dLu2GzqGiweT/ALdGoaJJqiTJe6TqEkU0XlPF5sQQjOem/rkdaBmBqHjHUbZteeGK18rTIopow4cmVXPcgjHrWnZa5e6lqt1Y2ot1NjHGbiWQNh5HXcFUA8ADuSfpRdeEUvHvml0rVcXyolwq3EQDKv3Vxv4A9qsjQJEuvtMWmapFOY1ikkjniVpVXpv+fkj160IDRgedreM3ACTFRvVGyAe4B7isu5u5rKHXbqDaZIAJFD5KnbCpwcH2rTWK+RQq6TeAAYHzxf8AxdZv2O6v5NXtZdMvvLmZUkEckSsAYlBGd/cfzpPyBeZlaR4zlu0muLsQNZQWCXc89vu/cOeTEwJOTjnitCLxdZy/ZRsuVa5kaJA6gfMMd84OQwIxnv6U1PB8KDA0XUSDbfZHBnjxLFjAV/n+bA6HqMVYk8PvNawW0+l6pNFBt2CS4jbO0grn5+cYHvVdRGde+N4YoLtbaGb7TCtztEoGwtAAWBwc4ORint4zhXSr25EMrz2Vss0sYIAyVU8ZOcfNwcc4OKkm8GwzzzTNo+phpjKXC3EYH70ASYG/jOBUp8KxvDJHJouoSLJbm1O+aMkRnGQDv46D8qXQfUztQme48VaXLIhRn0uVipOcZkj9KKNSilt/F2nRSWtxCI9MlVfOZWLASR9wxooEdN8Of+Reuv8AsI3X/o1q6uuI8BPqQ0O6FrDaPH/aN1gyTMp/1rdgprpvM1n/AJ9rD/wIf/4igDRorO8zWf8An2sP/Ah//iKPM1n/AJ9rD/wIf/4igDL8QX95Z39xJbXbxpbWDXIi2qUdlboeM8jjg1qm8lui9ulvd27MCBcFFKrx1HP9KoXWlXd7eJdXOn6fJKihQTdS4wDkArtweeeRV7zNZ/59rD/wIf8A+IoAyrLV5tP0gXN5cyXTz3LwRLLtUKVdxyVXptX0PI96uf8ACQ5+wsto6pdBSWlbZtJONoyME98HGR0zUSaVdx2QtUsbEQiQyAC8lyrE5JDbcg5J6HuaWTTLyWaOV7GwLxqqr/pcuCFORkbcHB55zQvMC7p97eXOoX0NxbxRwwSBI2SUsW+UHkYGOvrWjWMltqMd5JdJZ6eJpQA7faZOccdNmM8Dn2qx5ms/8+1h/wCBD/8AxFAGjRWd5ms/8+1h/wCBD/8AxFHmaz/z7WH/AIEP/wDEUAGv/wDIv6h/17v/ACNaNc/rkmrnQr7fb2AXyHyRO5PQ/wCxV/zNZ/59rD/wIf8A+IoA0a5C6u9abxNe22nS3EohltyqMsfkpG3MgY4DdAcYyc4re8zWf+faw/8AAh//AIiq0NnfW93NdQ6dpaXE3+tkWZwz/U7OaANqis7zNZ/59rD/AMCH/wDiKPM1n/n2sP8AwIf/AOIoATw//wAghP8ArpL/AOjGrSrntCfVhpSbLexK+ZLyZ3H/AC0b/YrQ8zWf+faw/wDAh/8A4igDL8TXV9Bq2nw2M92BPFNmK2WMksoBU/OPU881t6Ybw6XanUhGt6Yl88R/dD4+bHtms+Wzvp7yK7m07S3uIRiOVpnLJ64OzirPmaz/AM+1h/4EP/8AEUAaNZlj/wAh3VP+2P8A6Cad5ms/8+1h/wCBD/8AxFZ1m+rf21qWLex3futw898D5T/sUAdFWP4ibUo4LaTSJ1S5EwHlSAeXMMElWOMjOOCOh9an8zWf+faw/wDAh/8A4ioLm21C8MRubDTJTE2+MtO52t6j5OtAEXh7Vv7Yu72VZZ1EexHtJQoNtJzuU4Gc8DuQc5HBrdrKVdUSWSRLLTVkkxvYTOC2OBk7Oak8zWf+faw/8CH/APiKAEvP+Q/pv/XOb+S1pVzt0+rf25p+bex3bJsDz3x0XP8ABWj5ms/8+1h/4EP/APEUASax5v8AY921vO9vMsTMkiAEqQMjggg1iabrF7cazaadqUjW+oQozTRRgeVcpj5ZUyM4z1Gcg8HsTpXEep3cDwXFlpskTjDI07kMPf5KRINRjMRWw0wGFdkZ858oPQHZwOB+VCA16ztd/wCQZ/23g/8ARqUeZrP/AD7WH/gQ/wD8RVDWpNWOnfPb2AHnw9J3P/LVcfwUAdBSEZBGSPcVn+ZrP/PtYf8AgQ//AMRR5ms/8+1h/wCBD/8AxFAHOyaxqVgrWeo3UgSe6MdjfoqgtiTb5MgxgPjODj5h7jnshwKxYrC8gtzBFpmlLCX8woJWxuznONnXIzmrXmaz/wA+1h/4EP8A/EUdANBvun6VR0L/AJAGnf8AXtH/AOgimGTWMH/RtP8A/Ah//iKpaLJq/wDYdhst7Ar9njwTO4ONo/2KAN+uZ1TU77R9YuZpZHm0fyk8/ao8y0Lbh5i4HzIMcg5I69MitXzNZ/59rD/wIf8A+IqutrfpdS3K6fpgnmULI/nPlwOx+TmgC3osrz6LZzSTtO0kSuZTj5sjOeABV6suIarBEkUVnpyRoAqqs7gKB0AGyn+ZrP8Az7WH/gQ//wARQwDSv+PnVP8Ar7/9ppWjXPaY+rfaNS229iT9q5zO/Xy0/wBitDzNZ/59rD/wIf8A+IoAqeIJtUtbizm0lhKwZvMtHwFnUKSQGxlW9DnHrT/DmpJq8V3dwXMs0Jn2okqhTDhVLIRgEEMSCDzxSzW2oXFxDPNYaY80JJjdp3JTPXHyU+NdUhLmKy01DI299szjc3TJ+Tk8CgDVrMb/AJGiP/rzb/0Nad5ms/8APtYf+BD/APxFZzPq3/CSJ/o9jv8Asjcee+Mb1/2KAOirN8Qfaho8z2Fyba5XBjk2BhnOMMD1Hr3pfM1n/n2sP/Ah/wD4iobu31G+gMF3YaZNESCUedyDj/gFAFPR9Yn1HWzbXTSW15bQMLqz4KbsgLIpxkqwJwc9sHkGujrKEeprKJRZaaJAmwP5z529cZ2dKk8zWf8An2sP/Ah//iKAG6z10/8A6/I/5GtOud1d9WzY77exH+lpjE79cH/YrR8zWf8An2sP/Ah//iKAL8il42UOyFhjcuMj3Ga46z1rUVOn6fqty8dzNKrW9zGqhbuPPKkEYDgdQMZHI7gdAzau6FWtdPKsMEG4fkf98VBDZXsEEUEWm6UsULb40ErYRvUfJweTQBtVS1n/AJAl/wD9e8n/AKCaj8zWf+faw/8AAh//AIiqeryav/Y17ut7AL9nkyRO+cbT/sUAbFr/AMekP+4v8qlrJtpNY+yxYt7DGwY/0h/T/cqXzNZ/59rD/wACH/8AiKAMLU9X1DRbnUmu7h20pm2R3QVd9lIUBG7jBQk4BI4PXg5HT2W77FAZHZ3MalmbGScdTjisxbK9Q3BXTdK/0n/X/vW/edvm+TmrCtrCqFW108ADAAuH4/8AHKOgGlWfov8Ax6T/APX3cf8Ao1qTzNZ/59rD/wACH/8AiKoaRJq/2WbZb2BH2qfOZ36+a2f4KAOgrnvEtzd29/pUdrPdolxJIkkdssZZsRswxvHqBWh5ms/8+1h/4EP/APEVWns766uYbi407S5JoDmJ2mclD7HZxQBc0U37aPanV1Rb4xjzgnTd+HH5VerO8zWf+faw/wDAh/8A4ijzNZ/59rD/AMCH/wDiKAFt/wDkYL7/AK94P/Qpa0K5+CTV/wC3bzFvYbvs8OR574xukx/B9av+ZrP/AD7WH/gQ/wD8RQBX8WXVxZeGry5s5nhniUMrIFJ6gYwQR3p2gtqTC8/tAS+SJv8ARTPtEpTaM7tvH3t2O+MZpLy11DULcwXmn6XPCSCUkmdlP4bKlQ6vGiolrp4VRgAXD8D/AL4oA06zdQ/5C2k/9dZP/RbUvmaz/wA+1h/4EP8A/EVn376t/ammbrex3ea+3E78/u2/2KAOhqvfq7WE4jleF9hKyIAWU46jIIqt5ms/8+1h/wCBD/8AxFRzLqtxC8U1npzxuNrK07kEen3KGBkaZrV9Pf6bp2qTNBqH3z5SgR3sWwneuQcYIAKgggn0IrrKx47bUIlgWPT9LUQDEWJm/d8Y4+Tjip/M1n/n2sP/AAIf/wCIoAb4i/5AV19B/wChCtOud159WOiXO+3sQuBkidyeo/2K0fM1n/n2sP8AwIf/AOIoA0a4u71nUdLW8gv7qT7NLM0dnfKqho3B4ik4xz/C2Oeh5xno/M1n/n2sP/Ah/wD4iqsdheRQyxJpmkiOZt8iea2Hb1I2cmgDaUbVAJJwMZPU0tZ3maz/AM+1h/4EP/8AEUeZrP8Az7WH/gQ//wARQAnh3/kA2n+5/U1pVzugyasNEtdlvYldvBM7g9T/ALFaPmaz/wA+1h/4EP8A/EUAZmr6hqOk609wrPcaWsKtcwqgMkAJI8xMDJAxypzxyOmDp6BObrRbec3LXQlBZZjj51JODwAMYxUAttQW8a7FhpguGXY0vnPuK+mdnSpIV1S3iWKGy02ONeFRJnAH0GygDUrO0/8A5Cmq/wDXZP8A0UlHmaz/AM+1h/4EP/8AEVn2D6t/aWp7bexz5ybszvx+7T/YoA6GsbxC2pxCzl0eVTOJSGt5MbJ12sSpOMqfl4PY9cirHmaz/wA+1h/4EP8A/EVBPbahdSQyT2GmSPC26NmnclD6j5KAI/DuqjWJb24jmnMauqeRKoVrd9o3IQBkEE9ya3KykXVI3keOy01XkOXYTOCxxjJ+TngAVJ5ms/8APtYf+BD/APxFAHKeL/8AkedO/wCwdP8A+jI6Kr+JWvG8b2H2yO3Rv7Om2+VIzZ/eR9cgUUAbPw5/5F66/wCwjdf+jWrq64fwFa3suh3TQah5Kf2jdfJ5Ct/y1bua6X7Dqf8A0Fv/ACWX/GgDTorM+w6n/wBBb/yWX/Gj7Dqf/QW/8ll/xoA06KzPsOp/9Bb/AMll/wAaiuI7y0QPc67FCpOAZIUUE+nJoAz0s5rrxXePbOiCCeFpJPPYsF2AlAnTB9/yrqKxUtLlbqRI9YgFwQHkVbdN5HYnnOKmS11GVFePWFZGGQy26kEfnQBqUVmfYdT/AOgt/wCSy/40fYdT/wCgt/5LL/jQBp0VmfYdT/6C3/ksv+NH2HU/+gt/5LL/AI0AO1//AJF/UP8Ar3f+RrRrntcs9RXQr4vqm5RA+R9mXng+9XvsOp/9Bb/yWX/GgBmpC9N2P7N+0edtGS2PI6/xZ5z/ALvNYVte3FvrQlvZ2S4juZ/tgy3lpbBCUOOy524PXk+9a9x4fmvJBJdXVvM4GN0lkjHHpUkdteK/2eLWYg6KD5a26ZVe3GeBQBQWGR/HS3cd2l3CYzG0Ku6mzwuQSA21g2f4hnkYPFdPWOyXa3S2za7ELhhuWIwpvI9QM5xUv2HU/wDoLf8Aksv+NAC+H/8AkEJ/10l/9GNWlXO6HZ6i2loU1TaPMl4+zL/z0b3q/wDYdT/6C3/ksv8AjQBzPjHe+v8AlWgaS4OmyttSd1ZCHTDqq/eZRuIHBODzXXaVcRXWl20sF0LtDGo8/wD56EDBJ9D7VTmivbfb5+uRx7jhd8CDJ9Bk1ILLUiARq4IPcWy/40LYGadZlj/yHdU/7Y/+gmj7Dqf/AEFv/JZf8ayraz1k+Jb5Y9UhEAjjMjG2Bcvg4A5wBik2Jux0N7j7HLnzvu/8sfv/AIe9c3fPqCfZBqjsmlPcASs7BZQuxseYUwAN23p7ZrWl0y/niaObU0kjYYZWtUII+lV7bRpLKcpa39tBKy5Kx2kasV/wpjM4zTaj4LWzudVWxvmRA8soO7BJKBuQQWUckEHr3re0FZF0KyWaEwSCIBo97Pg/VvmP481CYL5ZlhbWoxKwJVDAm4gdwM0/7Dqf/QW/8ll/xoAW8/5D+m/9c5v5LWlXO3VnqI1vTwdUyxSXB+zLx933q/8AYdT/AOgt/wCSy/40AHiNkXw3qTSPsAtnIYMVIO04wR3zisDwbOUv3jnmMJntYWhtvNaRJQF+aVWbuScFR0289c1v/YdT/wCgsP8AwGX/ABqOGK8uc+RrkUu04OyBGx+RoQGvWdrv/IM/7bwf+jUpv2HU/wDoLf8Aksv+NZ3iCz1ZNHkaLU0eUPH5avbqFL+Yu3Jz0zih6CbsrnSVkXo1D+0D/ZvnBuN/n48j8P4s/wC7xTorHV/KTztXQyYG7ZaqFz7ZPSqt1oDSs1xd3dq7AZaSWzjPA9SaBmZo9/LBqUUt1O6vtnGoh2JVH80LEMdBwSBjqKuaXBKvjK+uftaX0MyMNys4NqVIHlldxU565wG4PrWj9lv1i8z+2UEYXdu+zpjHrnPSiO11CWNZItZV0YZVlt0II9jmgDUb7p+lUdC/5AGnf9e0f/oIqM2Op4P/ABNv/JZf8apaLZak2h2BXVNqm3jwPsy8fKPegDoK8/8AFDMfEeoLayvGyW1u8k0cz77X533SLGPvYXbkemOtdb9h1P8A6C3/AJLL/jUUsd5A6LNrkUbP90PAgLfTnmgDUgmjuIElhkWSNwCrqchh61JWZ9h1P/oLf+Sy/wCNH2HU/wDoLf8Aksv+NADtK/4+dU/6+/8A2mlT6j/x5vj7TnIx9n+/nPbPH58VhaZZ6ydW1QDVIRaiYYItgXZ9iZzzgADFaE+lXt1EYrjUY5Yz1R7RCD+FK9xJ3MbVZNQRrddYlaOyZZirRttfeFHlhyvG772AOCQKXV3n1PwpbW0mpRWuoKIxcI+5fNlCBjESpDDOQflOa07XSZrR3is9Rt4X4Z0itUB9iQDU3kXxnMP9tR+aF3FPITdj1xnpTGXrDd/Z9tviMLeUuYyxYocDjJ649aqN/wAjRH/15t/6GtH2HU/+gt/5LL/jWe1nqP8AwkaL/anzfZGO77MvTevHWgDo6wPG7rH4Q1By5RljyhDlTuzxgjmrn2HU/wDoLf8Aksv+NBstSUEnVwAOSTbL/jQBmeFJfLvtTt5ZjHIZBJFZ+YZFjj2gB0c/eVuvHAPGK6asiCK9uU32+txyr/eSBGH6GpPsOp/9Bb/yWX/GgA1nrp//AF+R/wAjWnXMa/Z6wtvam31OJrj7VGIhLbgLn1ODnpmtRbHVNo3auCcc4tVH9aVxX1sQXH9pi9lOmCXbu+f7Vjyjx/B/F/Ssrw3fmK7i824kMctrEtx5rEkXhYgrz0brkD0FX59B2yNdXF5aBwdxlezjBz65NW5ba/gjaSXWUjjUZLNboAPxzTWg2ZvhmCWLWtTla6W/iuMSLdI74Xk/uipYqMccrjjqK2tZ/wCQJf8A/XvJ/wCgmoFs9SZQy6uCCMgi2Xn9aq6tZakNHvS2q5AgkyPsy8/KfegDZtf+PSH/AHF/lUtZFvZakbaIjVcDYP8Al2X0+tSfYdT/AOgt/wCSy/40AcfqE3l+KdRkinaGCC9t2luUmdjbrtBYbOm1j8pPQbskcV6CrK6BkYMrDIIOQRWU8V5HMsT65EsrDKoYEDEewzUn2HU/+gt/5LL/AI0dANOs/Rf+PSf/AK+7j/0a1M+w6n/0Fv8AyWX/ABqjpFnqLWsu3VMD7TOD/oy9fNb3oA1NU3/Zl8r7V5m8bfsxG7PvnjH1rltZl1WMsuoSFJBZyNZeQSN1xuG0HHBfpx0wTW9caPeXkfl3N/FMgOdslojDPrUcenTaaqxRapb2yyPhVW2RNzH0GeTQBn+KC2p2NsLW/i82GRmez3On2p04ZAyEMCCT0yM4yMV1a/dHGOOlZFzHd2cfmXWuxQpnG6SFFGfTJNS/YtT/AOgsP/AZf8aAH2//ACMF9/17wf8AoUtaFc9DZ6iddvANU+YW8OT9mXn5pPer32HU/wDoLf8Aksv+NAFDxu8ceiRM7hW+1wBcymMHMihgSO23dn2zR4PlYWt5bTzMLmO5dmtXYsbZT91Qx5ZcchunzdulXntdQiRnk1hVRRks1ugAH502K3vp4w8OtJIh6MkCEfmDQgNas3UP+QtpP/XWT/0W1J9h1P8A6C3/AJLL/jVC+s9RGp6YDqmSZXwfsy8fu296AOirnL86ykF42lCfYI5CBdYJLYOPLx83XGN3FaH2HU/+gt/5LL/jVVfDrpP563Nss27d5gsk3Z9c+tAFTw/fRRXFyiXTGzkWLyGkYtmXYWlwT6AAkeuaf4OtprVb5Zblb5XlEiXqu5E+Rk/KWIUj/Z45HAq/DBfXCF4dajkUEjKQIRkdRwabCl3ctIsGuxStE21wkKMUPocHg0dQJfEX/ICuvoP/AEIVp1zmvWeorotyX1TcuBkfZl55HvWh9h1P/oLf+Sy/40Aaded2lwsPiKScXLQWcWqyK9ys7OMbBtiZeiozE4bplccZrsfsOp/9Bb/yWX/GojHeCfyDrkXnYz5fkJux9M0LcOhr0tZn2HU/+gt/5LL/AI0fYdT/AOgt/wCSy/40AL4d/wCQDaf7n9TTtV83ZF9m+1+dk7fIK46fxbuMf5FY/hyz1ltIQy6pCse5hCEtgTsycFjnqfar9zot1eqq3V9DOFOQJLNGx+dJaoSd9TD1GbVEvXW7kA1BVt/sKwlgjkyEScdztxuz0FWteb+0r/S7mxvo50ikD/YQ7oZgX2lwVYH5cHggrwc1pR6dc2ESRx6pDbxlsKq2yKCT2HPU1N9h1P8A6C3/AJLL/jTGadZ2n/8AIU1X/rsn/opKb9h1P/oLf+Sy/wCNULGz1E6jqYGqYImTJ+zLz+7T3oA6KsLxYM2NoFQSObuMLGZjGJOvy5HrVr7Dqf8A0Fv/ACWX/Gormyu1i8y61aIRxkNuktkwp7HJPFAEvht/M8P2b+d525M7sk4yT8uTz8v3eeeK06yYbK+MeYNWj2Ek5S2TBPfoaf8AYdT/AOgt/wCSy/40Act4v/5HnTv+wdP/AOjI6KreJIbmHxtYC5u/PJ06bB8oJj95H6UUAbXw5/5F66/7CN1/6Naurrh/AWmR3Oh3UjT3aH+0boYjuHQf61uwNdP/AGLF/wA/Wof+Bcn+NAGjRWd/YsX/AD9ah/4Fyf40f2LF/wA/Wof+Bcn+NAGjVLWNNj1fS57OTA8xfkYjOxxyrD3BAP4VH/YsX/P1qH/gXJ/jVa8tLGwWM3N9qCmRtkardSszt1wFByTgHpQBSVtTuNISS4sTDqV+ywSYTesKDgliOx+Yj/eHpU3hKK606C60m5tnjis5mFtIEIjeJvmCrkk/Lkrz2Aphn0hXt1fUtRQ3Ext4908w/e4zsOfun2OKsGDTxqq6b9v1A3hi87yxcynCZxknOBzxzQBuUVnf2LF/z9ah/wCBcn+NH9ixf8/Wof8AgXJ/jQBo0Vnf2LF/z9ah/wCBcn+NH9ixf8/Wof8AgXJ/jQAa/wD8i/qH/Xu/8jWjXP65o8UehXzC6vyRA5wbuQjofer/APYsX/P1qH/gXJ/jQBT11ohcRiXUoI12c2k0vlrJz1JHPtzke1ZFhaXMF7DcJZPiC4numkgwyywshCIh43dVGP8AY+ldBLpVrBGZJr69jQdWe9cAfjmqkC6XdXf2aHUr55SDjF1Lg4AJAOcEgEEjrzQgI49LJ8ZHU7dblSV2XIuIwU27flMbHkHPUA4PORmujrBMenDVRpv27UjdlN5RZ5iFHuw+UHjoTmrv9ixf8/Wof+Bcn+NACeH/APkEJ/10l/8ARjVpVzuh6PFJpSMbq/H7yXpdyD/lo3vWj/YsX/P1qH/gXJ/jQBleLLCe5lhuLNJ/tEMUiqREJopA2MxvGecNgfMCMY61vWKyLp9us0SwyiJQ8aHKoccgHuBWVew6fp7olzfairMrOFW4lY7VxuYgE4AyOenNWY9It5YlkjvL9kcBlP2uTkH8aEBqVmWP/Id1T/tj/wCgmnf2LF/z9ah/4Fyf41nWejxNrWpL9qvsL5X/AC9Sf3T70AdFWFcxvH40t7pbSVkWwljaVI8jJdGC59cK3+TVz+xYv+frUP8AwLk/xqlcpploxSXUr3zAQPLS7ld8noNoJOf8DQBQuLG8utaMq2syme5trmKZgB5MaKN6N6H7wx33/WutrCmh06DTP7Qk1G++ybQ4kW6lbIPTAByc56CprXTba8to7iG71Ly5F3LuuJUOPcEgj8aAJbz/AJD+m/8AXOb+S1pVzt1o8Q1zT1+1X+GSb/l6kz0X3rR/sWL/AJ+tQ/8AAuT/ABoAt3aeZZzoUaTdGw2K2C3HQHtXPeFbG7sLueGSJ2tEgjSKaeIRzDGf3bEcOFHRsDr3rUfSLeNGd7y+VFBLMbyQAD161VsYdP1EkW19qLEIJMNcTLlTnDDOMg4ODQtwN2s7Xf8AkGf9t4P/AEalH9ixf8/Wof8AgXJ/jVDWtHiTTtwur8/v4RzdyH/lqvvQB0FZ+vRefoF/EITMZLd1EYXcWJU4GPrSf2LF/wA/Wof+Bcn+NRT6baWsRkuL+8iQfxPeuB/OkwRnTx3M/hmxtEs7jfDHbSyoyYDKjLvj6/ewp47/AI1o+Hbaa2s7gzI0azXUs0UTDBjRmyBjt647ZqC1i029uHgt9Rv3kUE4+1SgEA4JBJwcHg46Gkhj06fU5tPivtSa5hXdIBPNtXpxv+7nkcZzVXEbrfdP0qjoX/IA07/r2j/9BFMOixYP+lah/wCBcn+NUtF0eJ9DsGN1fgm3jOBdyAfdHvSGb9cn4q066mv/ALVYQSST+QIvLeISwXC7idjDqhHXeCOvfGK2/wCxYv8An61D/wAC5P8AGqN4mm2E3lXOoagrhPMYC4mbaucbmx0GeOaAN5clRuGDjkUtZ39ixf8AP1qH/gXJ/jR/YsX/AD9ah/4Fyf40AGlf8fOqf9ff/tNK0a57TNHia41LN1f/AC3WOLuT/nmnvWh/YsX/AD9ah/4Fyf40AUMPa+LtRvBZTtGbCIb44v8AWsrOSoPc4Zf8iqkGnXh19WMEisuoPdNckcGExbQmfXJA2/7Oat3J0m0JEuqXm4HBVLuVyOMnIBPQDJ9BT76HTtNsRd3WoagICQFZLmVyxPTAUkn8BQgN2sxv+Roj/wCvNv8A0NaSLSYJokkS61Ha6hhm6lBwfYnIqi2jxf8ACSIn2q+x9kY5+1SZ++vvQB0VUtZtlvNGu7d4pZlliZDHE+12BGOD2NR/2LF/z9ah/wCBcn+NRXGm2lpbSXFxfX0cMalndryTCgdT1oYIq+Fre9t2vVvF3pvURXLwCGWYBcfOo4JHA3ADPpxXQVi2dpZX3mCC81LdGQHV7iZGXIyMhsHpVn+xYv8An61D/wAC5P8AGgEN1nrp/wD1+R/yNadc7q2jxIbHF1fHN2g5upD2PvWj/YsX/P1qH/gXJ/jQBW8YWz3nhTUIIrdriV48JGqbiW7YFR6yZbs2jJaXDw2txHNMhT/WIVYcDuVJUke1T3Gn2dqoa41C8jDHA3XrjJ9BzzUNlDp2os62uoX8hQAn/SpRkHOGGTyDg8jjigCz4ctJ7LQreG5UpIC7bCc7FLEqv4AgfhU+s/8AIEv/APr3k/8AQTWdZx6df3dxbW19qTyWx2yfv5goPoGPB6dicUuraNEmjXrC6vzi3kPN3IR90+9AGxa/8ekP+4v8qlrJttGiNrEftV/yg/5e5PT61L/YsX/P1qH/AIFyf40AYes6fdjxB9rsbeSRpJIRJFNGHhmVSDvDdY2XJ56HHQ11tYEy6bb3ZtpNQ1ASgqGAuJiFLHCgkcAntmr39ixf8/Wof+Bcn+NHQDRrP0X/AI9J/wDr7uP/AEa1J/YsX/P1qH/gXJ/jVDSNHie1mJur8YuZxxdyDpK3vQBo6yQLA5vxY5YfvSQAf9nn19sGuTurF703Js7eG5Wazkto5LaXzQs7EEOxPK9jkk429a6n+xYR1u7/AP8AAuT/ABqhM+kQNtfVbwnODsu5GC4xkkg8AZGSeBmgCDxDp7aza2qCO9W8tnYwMYg0TOvGZFOQVPYnnGcYNdOM4GcZ74rC1KPTtJijkvL/AFJRI+xAk80jMevCrk1c/sWL/n61D/wLk/xoAdb/APIwX3/XvB/6FLWhXPwaPEddvF+1X+BbwnP2uTP3pPer/wDYsX/P1qH/AIFyf40AN8Q2Y1DRprZknYOU/wBQwDrhgdwzwcYzg9cYqv4XjvYrGcX8SBzOxWUQ+S064Hzsn8LcY98ZwM0+7sLOxtmnub6/SJcAn7XIeScAAA8kkgYpLSys76Nnt7zUSEbYwa5lUq3oQTkHkUIDZrN1D/kLaT/11k/9FtS/2LF/z9ah/wCBcn+NZ9/o8S6ppi/ar/5pX63cn/PNvegDoa5HVkFy15BFqNrd3ModIUln2NA5BACgfKSD7A+9bv8AYsX/AD9ah/4Fyf41Bc2VjaY+06ldxZ6b71xn9aTApaJHNa3VzL9huYLe4SKNIwgBRkjO5iM8Z4UHuQO3NS+E9KOlRXSRCYWkjh4ftKATA4+YMcZbnoW569sVLY21hqKO1rf6g4QgMDcyqRkZHBOcEHIPemadHp2qiY2V9qUiwvsZjPMqk+xOAw9xkVXUC34i/wCQFdfQf+hCtOud17R4o9FuWF1fEgDrdSEdR71o/wBixf8AP1qH/gXJ/jSA0a5KTTruHxULi1t5Hhmuw80U8YZFwuPOjkHKnAA2nOeeB1rc/sWL/n61D/wLk/xqjt037YbX+0NQ80SCI4uJiu8jO3d0zjnGaOodDforO/sWL/n61D/wLk/xo/sWL/n61D/wLk/xoATw7/yAbT/c/qa0q53QdHik0S1Y3V8CV7XUgHU+9aB0aFQS13fgDkk3kn+NAFXxVA01pZGO2kneO+gl/dx7igVwWb24Brcrni2kCZIhqt4zOQoKXcrKCTgZYHAyeBnqeKffR6dp09vDc32pCW4bbEiTzOSeOu3OByOTxQBvVnaf/wAhTVf+uyf+iko/sWL/AJ+tQ/8AAuT/ABrPsNHibUtTX7Vf/LMnS7k/55p70AdDWR4lsjfadGii5DpMsiSW4UtEy5IbaeGHqvfNTf2LF/z9ah/4Fyf41XvLKysIlkub3UFDMEUC6lYsx6AAHJP0oAf4aS6j0ZFvoIoZt7nEabA4LEhimTtJ6kZ4JrWrItdPtL2ATW97qDxklc/apRyDgjBPqDU39ixf8/Wof+Bcn+NAHKeL/wDkedO/7B0//oyOiq/iWzW08b2CpLcPu06Y/vZmfH7yPpk8UUAbHw6YDw9dZIH/ABMbrv8A9NWrqt6/3h+dcX4A0uwutCupLiytpZDqN0CzxKx/1rdyK6j+w9L/AOgbZf8AfhP8KALm9f7w/Ojev94fnVP+w9L/AOgbZf8AfhP8KP7D0v8A6Btl/wB+E/woAub1/vD86x9Y0+4m1bTtUsmiklsvMRoJG2h0cDJB5ww2jt0yKuf2Hpf/AEDbL/vwn+FZ+tQaVo1mlw2i2sytKkRCxRrguwUElsDGSKAM6Tw/eXltLBeYZbq6kmLG6LtbKVwm3PUqfm4x0qzpWmajb6/DfX/2aR3szFczRyYzIWB4Uj7oAx1povfDcMRfULLTrNhuIVkjfcoIBYbc8AnH1rQtbbw/euFtrOwkYxLMNtuv3G+63TocUIDW3r/eH50b1/vD86p/2Hpf/QNsv+/Cf4Uf2Hpf/QNsv+/Cf4UAXN6/3h+dG9f7w/Oqf9h6X/0DbL/vwn+FH9h6X/0DbL/vwn+FAEevsv8Awj9/8w/4937+xrQ3r/eH51h67oumJoN+y6dZqwgcgiBQRx9K0P7D0v8A6Btl/wB+E/woAo6zDE97FOsd41wi/I8UXmxjnup4z7jB96oWuk38dxHPiB1huJr2PcxjaR5FI2MMHbgseeegrak0bS442f8Asq0faM7Vt0JP04rLvLjw7aWT3B0+0JQqrRtbojJkgZbcBtXJ5Y8UbAWU0lT4l/tNYI7WQArLLHLk3SlcAOuAOD0JyeOOtbW9f7w/Osqw07Sr+yiuRpFtEJBna9umRz7DBHoe4qz/AGHpf/QNsv8Avwn+FAEOgMv9kJ8w/wBZL3/6aNWlvX+8PzrC0LRtMfSUZ9Os2PmS8mBT/wAtG9q0f7D0v/oG2X/fhP8ACgDN8S6TLqhiktlVZ4VbybiOcxSxOcdDggr6qQQeOK2bQPFZwR3EqSTLGokdRtDMByQO3Nc9q8+laRdvC/h+GZY7Z7t5EiiAEaEBuDjkZHHetW20rR7q2ini02z8uVA65t1BwRkcYoQM0d6/3h+dZtiy/wBu6p8w/wCWXf8A2TU39h6X/wBA2y/78J/hWbZaNph1vUlOnWZVfKwPIXA+U+1AGxe+VJZTJIJHRkIKxE7yPbHOa5yOyuPOtGsY5dllL5qQ3UIh35VkI3jqcNnkZ461u/2Hpf8A0DbL/vwn+FVLi20O0n8u5021iUgEStar5f03YwPxxQBTi0Vk8OrpN5Y2t/Au0kNNtDEksxHHG0kY5z9MVs6XbGw0y3tZbgzvEgUyO2ScepPJ+prHs5dEvtXmsItHty0JIZ/IjwCMdR1AOeCRg9q1v7D0v/oG2X/fhP8ACgCG8Zf7f035h/q5u/staW9f7w/OsK70bTBrunKNOswpSbI8hcHhfatH+w9L/wCgbZf9+E/woAsXH7y2lRfLZmQgB+VJx39qxPDmkXOkXM6mQRWBRVitfOMojfJ3FCRlU6YXJ/CrWo6fpWn6dcXZ0i0lEEZkKLAgJAGTjIx0qlpD6PqlzJbHRILedIY7ja8EbAo+dpyueeDweaEB0W9f7w/Os/XWX+zPvD/Xwd/+mqVJ/Yel/wDQNsv+/Cf4Vn63oumJp2V06zB8+EZEC/8APVfagDc3r/eH51h6nHGuqfaoYr03IUASJB50ePoen/ASK0P7D0v/AKBtl/34T/Co59I0qCFpP7Jtn2jO2O2UsfoMc0AZGm6PfWMtrIRBILJJUizIVMvmyKxLcHbtA6c5NXbDSUt9fuNRjgjs/NDLKsUuRcnIKyMuAAwAPPXnFVb668O2dqky6fZSFpBFtMMcexiCRv3Y29MDPU4HetO20rSrm1inGk20YkQNsktlDLkdCMcGgDQZ12n5h09apaE6/wBgaf8AMP8Aj2j7/wCyKU6Hpe0/8S2y/wC/Cf4VS0TRdMfQrBm06zLG2jJJgXJO0e1AG1vX+8PzrnfEWjXOo3aXNgY4btIwkV0kxR05JIdcEOnT5T79Ota39h6X/wBA2y/78J/hWDql7o+k3V1HceH4mhtIo5pZkhiICOSoIHU8qeOv1oA6lWAUbnUnHJpd6/3h+dUhomlEZ/s2y/8AAdf8KX+w9L/6Btl/34T/AAoAi0pl+06p8w/4+/X/AKZpU2qJDcadLHMs0kbDBWAneee2OaztL0XTGuNSDadZkLd4GYF4Hlp7VPdWehWbBZbCy8xhlY0tlZ2+igZoYGSbG8lmils1O23jlhSK6hEHEgHOQMHBUdAOCasXOifaNBt9JuLK3uY7YJFFK05Vl2oAJRgZVgc9Dn37UWs2h3V8luNHgQSO8SSPbxgNIoyyeuQM/kfSn3I0ey1BLe60SCOKRXZZzbxlfkXc2QOQMZ5x/SgDbtVMFpDFJN5roiq0jHlyByT9apMy/wDCTx/MP+PNu/8AtrVLw+NH8Q6YL6DRrWKF2IjLRwtvA7/KTj6HkY5FObRtM/4SVE/s6z2/ZGOPIXGd6+1DA3d6/wB4fnVbUoReabcW4SCXzUKeXN9xs9mx2pn9h6X/ANA2y/78J/hVbULHRdM064vbjTbTybeMyPttlJwBk4GKGCIvDmnXOli6jmnY2pZfs0Mk3nNEoHI3kZIz0Bzj19Nrev8AeH51i6Za6VqUJkGjWsa4BVjFGyOCMgqy5BFXv7D0v/oG2X/fhP8AChgiHWWXOn/MP+PxO/sa0t6/3h+dYWr6Npimw26dZjN2gOIF5GD7VffR9IiRnk0+xRFGSzQoAB+VAGbewIupTS20d6s0nyvJ9n82MjGOCeV/Age1M0fSr3T7m3lkW3Y29rHYgLLjcikkydOvTC/XmnTyaGjRpb6PDcPK+yLZaoqyNgnAZgAeATnpxU0VvpN3pcV7Y6NbXIlGVQQRqfcHPAxgj60LQNxdF0lNPv7q6jhjskuAN9tFLuQvkkyYwACc84HOOavay6/2Jf8AzD/j3k7/AOya5+HU9Aub/TbO30WB5r+HzwrQxIYk9SGIJ6Hhc9K1NX0XTF0a+ZdOswRbyEEQLx8p9qANO1dfskPzD7i9/apd6/3h+dZ1tomlm1iJ02yyUH/LBfT6VL/Yel/9A2y/78J/hQBkarot1c62t9YNHbT7owbhJiN8YILLLHjD98dxnqK6Pev94fnXOyvoqazJpsejW8s0So0myCPKhzgEKeSB3I6Vrf2Hpf8A0DbL/vwn+FHQC5vX+8PzrP0Zl+yTfMP+Pq47/wDTVqk/sPS/+gbZf9+E/wAKoaPoumPazFtOsyRdTjmBeglb2oAu6zFBc2BjnS4lTcDtt8lsj2HUex4rn59JvL8T+TgJPaPYkXEXkNGrHO8AcNjnpjtXRf2Hpf8A0DbL/vwn+FUjBoSXDQTadawyA4USWqqH/wB04wfoOaAINX0ltWtoYJrSESwswguluCJLcjG11IGckDJGfbkV0AZQAC4J9c1z+iNouuRyPBo9siJghmhjIOc8HGcMMcqeRxWp/Yel/wDQNsv+/Cf4UARwMv8AwkF78w/494O/+1LWhvX+8PzrEg0XTDr16p06z2i3hIHkLgfNJ7Vf/sPS/wDoG2X/AH4T/CgBNYtE1LTJbVooJ1kwGjmYhWGQTyOQfQ9jiq3h2zu9OsZIr25aUGUmESS+Y8aYGFZ8DceDyecYGTiotYttL0m0Sf8AsS2n3ypFtSGMEF2Cg844yRSaRDo2rxTsmkW0UlvO1vLG8CfK64zgjII5HIoQG5vX+8PzrO1Bl/tbSvmH+tk7/wDTNql/sPS/+gbZf9+E/wAKzr/RtMXVNLA06zAaV8gQLz+7b2oA3d6/3h+dcxfWCzve29ot7C14Hikkkt/MT5hjIY8gd+uPatiXSdGt4mkmsLCONerPCgA/HFZVzPocLKsOixzs4ZlC2iruVRliNwGcZH1JFICfTbK+true6nhti9ykcLxrNwqxo2D05yzdOMDH0qXw9pKaQlx5USWkM7B1tI5NyQnHO30z6Dj86juodJi0tb+20W2u4Wi84eXDGPkxnPOO3aqlteaDea5FpltpFs8jW63DsYYl8pWGRlT8xPToDjIzVdQ6Gr4hZf7CuvmHQd/9oVpb1/vD86wtf0bTE0S5ZNOs1YAYIgUHqPatH+w9L/6Btl/34T/CkBc3r/eH51zkui3Q8SLf2jR2weYNcNHMdk8YGMPGRjf6MMY4+la/9h6X/wBA2y/78J/hWTFJos+rT2MOjW8jW8qxSssEfyMV3Aleu3B+9jGaOodDot6/3h+dG9f7w/Oqf9h6X/0DbL/vwn+FH9h6X/0DbL/vwn+FAEPh5l/sG0+Yfc9fc0a3Db3NvEJo7mXa+5fs678HHdehH1BFVNA0bTH0O1Z9Os2YryTApJ5PtUtxBoNvIYv7PtJJV+8kVsrFfrgfL+OKTAy30e81BrjLAQ3ggSRpU8l4hE5bhOc5Bx25q9qGlvq1zZzzWkNvdwEMt3HcEvDhslRwNwYDkHjn2pNMOianKY00i2iZoluIt9un7yJiQGGPp0PPT1qpe3+h6ZFfPf6HDB9kiWb5oIsSKzFVwegOR0OMdaewHVb1/vD86ztPZf7U1X5h/rk7/wDTJKjsNN0y+sIbk6PaQ+agfY0UTEA9OVyD+BNQWGi6Y2paoDp1mQsyAAwLx+7T2oA3N6/3h+dZuvWC6rp4tzDDOu8MVaQxsMZwUYcqwOMGpv7D0v8A6Btl/wB+E/wqpqFlpNhFGx0mzkeWQRxoIY13MQTjJ4HQ0ATaDb3VlpSQ6hc+fMGYhmYMwUk7QzADcQMAnHNaO9f7w/Os220nTLi2SVtHtoWYZMclum5fY4qb+w9L/wCgbZf9+E/woA5DxcQfHOnYIP8AxLp//RkdFQ+J7K1s/G9gtrbQwhtOmJEcYXP7yP0ooAt+AtYsLPRLqK4ukjkGo3RKnP8Az1aul/4SLSv+f2L9ax/hz/yL1z/2Ebr/ANGtXV0AZn/CRaV/z+xfrR/wkWlf8/sX61p0UAZn/CRaV/z+xfrWbr19p2sWCW0epW0YE0creZEZA2xgwGMjqQPwrpaym1G6HilNOCQfZmtTcFjnfwwXHp3oAw4rizs7+K+Oo2bpbxTBbW2tSm7ftJ2kt1JXv69qn8NX2maZpzB7sI0rlxHIctCmfkjyOPlHFPHiG+bXbrTx9kUxXKwoDHIS4ZA+Sw4BAJ47496s2Or391F5LraJfx3jQTR/NtCDncO/KlSO3zYoQFv/AISLSv8An9i/Wj/hItK/5/Yv1rTooAzP+Ei0r/n9i/Wj/hItK/5/Yv1rTooA57XNf0yTQr5FvIyxgcAc+hq5H4n0eZA8WowSIejI2QfxFS6+ceH9Q/693H/jpq5BBFawJDBGscUahVRRgADtS1uLW5mXHiDTWt5Fivow5UhcNt5+uDj8qwnlsbuFo3nt7aTcrGdpzcGXawOxwQCUPcZFdNql/Jp8du8cSyCW4jhbL42hmC5HHPXpxVuWRYYXkf7qKWP0FPzH5GHpGo6RpWmxWaahGyx5xwQBkk4A7KM4A7ACrn/CRaV/z+xfrUOi61LqMwjuYY4mltku4gjE4jckAN/tDHbjmtmgDnNC1/TI9KRWvIwfMl9f+ejVof8ACRaV/wA/sX60ugHOkJn/AJ6y/wDoxq0qAOO1qHSNc1RLi51O3ESW7QoojO9GLKwcNnGQVHGMdc1sWev2UVpGl5qdvNOow0iRlA3vtycfnUfiLX30SW2BSOOCXduuZ9wiRhjajMPu7sn5jxxWzA7SQRuwAZlBIU5AOOx70LYCh/wkWlf8/sX61n2ev6YutakxvI9reVg8/wB010dZlkf+J5qn0i/9BNAB/wAJFpX/AD+xfrWVqWqWNzdZ3w3UG0Dy5LoomfdNvP45rSXVpbiYwxRJbNnA+1nax57KOv596gu9emtNQeERxvBamBLmQkhi0p2jaPbgnPrQBm2I0u11n+0H1SItlyqhCGAfH7st/Ei4+UYGK3P+Ei0r/n9i/WtGQsI2MYDOAdoJwCfrWL/bV7NoVrf29tCpliMshkclI8DOOOTnpnFAEF1r+mHXNPcXke1Umyee4WtD/hItK/5/Yv1pjyvNqukSPG0TSQys0bdVJCHB+la1AGHqesabf6ZdWseowxNPE0e9lLBcjGccZ6+tZuhnTdClH2fVbbyJI1E0IhIDSKAu9Tn5cgDI5HHGK6uZ2jgkdIzIyqSEB5Y46VjeG9ffXFk3iBXjVfMiUsskLnOUdGGQR69D2oQMs/8ACRaV/wA/sX61Q1vxDpR0w/6dEAJoWJJIAAkUk/lXRVmeIY0m0d4pVDxySxI6noVMigj8jQ/ITvbQRPEukSIHS/hZSMhlOQfxqG91/T5bORIL1PMIwNrlD/31g4/KthVVECoAqqMAAYAFYuj69LqV1GssKRxXMLT25DEtsVgp3e/Knj1x2oGY0x069hCPLZ2xDh38xzcrcjawKyZAJAzkc8HFbWnatpOn6db2g1FZRDGEDuSS2B3q1rF7d2UHmWkMbhVZ3eViFXA4XjnJ6Cqw1if+1YIJVSCGQKMSRuW3lc7d33Qfb2oAnPiLSsH/AE2L9apaLr+mR6HYI15GGW3jBHPXaK3z901R0L/kAaf/ANe0f/oIoAj/AOEi0r/n9i/Wue1O30vU9Ymv31a2jk8qNbdhCS0DoxYNknDAljkY5H512lc/rniKTSdTgtjHDHHLHlJrglY5JM48sOBhW7/N1zxR1AtQ+IdPWFBPqEDygfMyKVBPsOcfnT/+Ei0r/n9i/WtOigDm9M8R6Ql7qUbahAJGud4Td823y0GcdcZpup6tp9xOrw/ZpHC4E4uWhkX2BC5x+laWlQx/2jq1wI1Ez3IRnxyVEaYH4ZNM1nV57CZIbSGOSXyZLh/MYgBExkDHc7gBS9RK/Uw7dbGGRZRrMStHJJcRK6eZ5c0i4Yk8bgMtgYHWpzfE6zJef8JDZeSUKRwmzJKcf3t3TOCeBnGMiumt7hbqziuIgSssYkUd8EZFY41jURFciW1iSZEidAu59pc42MByWA549R0p7MY3TdQ0jTxcP9tt/NuZfNlMaFFLYAyBzjgCmNr+mf8ACSI/2yPb9kYZ5671rY0u7N9p8czOjOSQ2xWUAgkEYbkEYwQagY/8VPGP+nNv/Q1oAT/hItK/5/Yv1qK613Tp7WSOLUo4XYYWQLu2n1wRg1sVW1G5ls9OuLiC3e5lijZ0hT70hA4AoYI5/Q5NH0WS8eK/t1W6kD+TChjiQgYyq5OCepx19K1v+Ei0r/n9i/Wo/D2tf21bSSrJbSKjBd0JIIOOQyN8yEehrXoYI5vWvEWlBbJ2v4VRLpGZmOAo55Jq5ceINJmtXVbm2nDrwjn5X9icHin69FHPFZQzIskUl3GGRhkHGTz+IFatIWtzjBPaS3EMqXcNk1s/mQjz2njBwVI2EDAwx6Edqe0kFvov9nadr9tAgCgPJbFzjkvnDDO4n2xXRXF/JBrFnZ+UpjuVkPmb+VKgHGMe/XNLq+of2Xpk115fmMmAqZxuZiFAz9SKYzCFxYTiyW/1WznW1ZJFKWxjYSL3Xk7V9vTjNXNW8QaW+jXqreRkm3kAHP8AdNX9Kv5bxbmO5RFuLWYwyeWSVJwGBGfZhTtZ/wCQJf8A/XvJ/wCgmgCrbeIdLFrEDexZCD19Kk/4SLSv+f2L9avWvNrD/uL/ACqWgDkdWGlatexTyapbr5UqSRuIj5sO3BIRwQQGxznI5rb/AOEi0r/n9i/WqV94ils/EKac0cMKvs8lpyVFxk/MEb7uVH8J5NdBR0AzP+Ei0r/n9i/WqOka/piWswa8jBN1Oe/QytXQ1maZL5OnXMhV5NlzcHagyx/etwBQAf8ACRaV/wA/sX61jy6lZS37SStBMm/KSSXZPlj1VNuAR+fvWvb6jPfyhYhDb4PKSnMuP9zjH5mq9rr0lxqqQtCi20001vEwY7y8eckjpg4bH09+AChoL6Xozyu2qwyvJGkbMqFPM25+d+TlznluM4FbH/CRaV/z+xfrUus30mmaTcXkUSytCu7Yz7cjvzg1BqWoXtpcx+TbI8G6NSWb5pCzYIUDuo5Oe1AFODX9MGu3jm8j2tbwgHns0n+NXv8AhItK/wCf2L9afAf+Kgvf+veD/wBClrQoA5rX7zTda09bVdSto186ORvMjLhgjBsYyOpA/CjRrzTdHjlto9Ugey3FoIvLIaIHkru/iGc4yMj1Na+tX0umaTPdwW73EkYB8tAScZAJwOTgZOBycVHoWqDV9P8AtKS20qFyqyW7llYADqDypzkFTyMUIBP+Ei0r/n9i/WqF/r+mNqmmMLyPCyuT14/dtXRVm6gf+JtpX/XWT/0W1AFe+13Sp7R4/NtrnP8AyylOFb8cGsQyWs8qzDUUs5I0eNAZmuF2OMNgEAg8KRyRx0rpL3VDa3PkLbtkgHzpTsi57buefwqG61G7t1tIYzbTXV5IViPIjUBSxJ6k8D9aQGPdzQnS4rDT9es7eCIqqiS0MuY1UAIfmGeRkn8PrZW80+W9tbi+1O1me0+aJlhKPuKbWycng5JwMduuK29Kv11TS7e8RdgmQNtznae4/Oqo1S5ebVIY7RXlsyoiVZP9buXIzkDFMCjr2v6ZJolyqXkZYgYHPqK0P+Ei0r/n9i/WqV5eXF14d1D7SkavDJ5YeInZIAV5Gee5H1BroKAMz/hItK/5/Yv1rEuhpV3rVvqEmqQB7eXzEdYisoXH+r3g8p6gg111c+PEUv8AwkraXJHDCd4EaTEo8ybcmRD91sHjaORgmjqHQu/8JFpX/P7F+tH/AAkWlf8AP7F+tadFAHOaDr+mR6Jao95GGC8jn1NVr3UbGa6kaH7Ogc4aaK7MbOP9pduD+Oa1NIuDbeGLebypZiqfciXczc9hU1pfT30oKNbxID80ZYtJj3HG39aAMPT2sNPlikTWoHeGJLZC0J/1KknaefvHj5vbpSWV41u909x4h0+4adgebEqMeh+fJGOB0x71p6Tr0mo3cSyQpHDdRyS2xDEttRgp3e5yDx64q9q19Jp1rHNHEsgaaONgz7cBmC5HBzjPSgCjpup6LpenxWdveRCOIEAYwOTngdhz0qGw1/TF1LU2N5HhpkI68/u0q7c6hewapFEtqhtnlWIHd87ZXJcey9DmpNPP/Ez1Uf8ATZP/AEUlADf+Ei0r/n9i/WqeqaxYXlqIoruykBb95FcIWSRcHjpxzg59q36oaxfvp1msqKuC4VpHBKRDn5mxzjt+PpQBR0zV9NsdOht5NRjkaMYzljjngDPOB059Ktf8JFpX/P7F+tW7GaS4sopZfK3uuSYn3ofcHuKsUAedeJNQtb7xvYNazLIF06YNjt+8joqz4v8A+R507/sHT/8AoyKigCTwFqLW2h3UYsbyYf2jdHfGilf9a3qa6X+2H/6Beo/9+1/+KrH+HP8AyL11/wBhG6/9GtXV0AZn9sP/ANAvUf8Av2v/AMVR/bD/APQL1H/v2v8A8VWnRQBmf2w//QL1H/v2v/xVZl5F9r1I3ywa5BN5Jg/crGAFJycZzzkda6auXh1y7sdZvrK+cTrM5/s4lQpLDAaI464LAg+hPpQAy3s1tZpnii19RM6vIn7vDFQFHPXooHBq5G0EWsTammkakLqaJYnOxcEAkjjd156+gFc//bevWmiabq0uoLcJPG63UJhVRFyR5wIXOxOCQe1aUdxrC661gNQurqNYLd/PjhgCguXDMwxnadoxj86ANr+2H/6Beo/9+1/+Ko/th/8AoF6j/wB+1/8Aiq06KAMz+2H/AOgXqP8A37X/AOKo/th/+gXqP/ftf/iq06KAOe1zVnfQr5TpuoLmBxkxrgcH/aq9/bD/APQL1H/v2v8A8VTtf/5F/UP+vd/5GnarezWUUZgSFmdsfvZAmBjtnqfbI+tAGbqs8upwRRraanb+XKku5YY2yVOQOT6irC6jLvn82x1OWOXGI2iTCDGCBg5OevNRXWpSWWmXl608ktzBbvIsDxeWvA646kdOcmrGjXVy93e2d3N57WxjIl2Bdwdc4wOODn8MUAUNKVdLYstjqspEawR+ZGn7uJc7VGDz1PJ5PFaX9sP/ANAvUf8Av2v/AMVTNRfUFv4fss6BSyBYQgO8bv3hYnoAuMEHr60yxvLkay8F28+2YSPAD5ZQqrAH7o3AjI6k5zRuGxW0PVXTS0UabqDfvJeRGv8Az0b/AGqv/wBsP/0C9R/79r/8VS+H/wDkEJ/10l/9GNWlQBz+oONRB32Orx7o2ibywgDKeoIJI/HrVm21BbS2it4NI1BIokCIojXhQMAfepuu3V3aujRSyQ2wQmSaKJZDG3Yup52Yzkjn6VsKQyggggjOR3oAzf7Yf/oF6j/37X/4qs+z1VxrWpN/Zt+d3lceWvHyn/aro6zLH/kO6p9Iv/QTQBRlMTqRFpmpwg9VWNCh/wCAFiv6VBLbpNdrObDVFU+V50SxRhZTGcoTzxg+nXirialcXTv50q20KkjdbgTce7fw/io7896rXesXUOoTeRNm2s2tUKFQxnErYJJ68AjGO4Oc0AXI9SuEtmja01N5DuxK0MeRknHAIHHT8KzIobmDTLOzhGrKLXO1zbQnd6ZGcZHaulvfP+xy/ZHjSbb8rSfdX3NYctxqosNySzSATOySIIkkkiC5BIYY656AZGOmaAGzanIur6bu0/UWZIpQS0a5bhefvVpf2w//AEC9R/79r/8AFVF56XWpaNPGzMksEjqzDBIKoeRWxQBlS6oZoXifS9S2upU4RQcH/gVUrLy7K8kuxp2rS3DxrF5kqoSEBJC5zzyepyfet24Mi20ph2eaEJTecLuxxn2rO0O6nnM8d1NMZo9u6GeJUeMkeq8MpxwR70AP/th/+gXqP/ftf/iqo6zqzvp4B03UF/fw8mNf+eq/7VdDWdrv/IM/7bwf+jUoAb/bD/8AQL1H/v2v/wAVWPbWv2Iuba21eMhDHAfKjPkKW3ELk88+ueAK2tUv57Rokt0hJkzku+COnReN3X1H41RvtRlstLnnjunku8xxhZY9ix73C7tuO2fU9OtACalc3N6YTDBqlsYyT8sEbAnscMTyO1ROHlvYppbbWJI43WXyWRCpdV2g9eB3wOM81p6LdTzreQ3L+a9rctD5hUKXGFYEgcZ+bHHpUdw+orrMQinQwmQZhCjAi2/MzHqDu6YOPbrQA86w+D/xK9R/79r/APFVS0XVnTQ7Bf7N1BsW8YyI1wflH+1U2kXly93Pb30kxmMQmQP5ZXYSRwUHr2JParehf8gDTv8Ar2j/APQRQBH/AGw//QL1H/v2v/xVZ2pJFqokW40/VxHKgjljULtkUEnBBPv1GD710lYuq3l1bajH++kgtPkHmJEsi7i3Ik7qCMAEccnNAE66uyqFGlagABgDy1/+Ko/th/8AoF6j/wB+1/8Aiq06KAOd03VnW41L/iW6gd11niNeP3af7VN1QDVGRzY6rBIqPEXjjTLRvjcvJ74HPbFaOmtsl1ZuOLonk4/5ZpVWHUJ7td91P9li/wCncCRf+/nP8lNADoL6S3DoljqflEKsUflR4iAGMDnJ9ec1RgF3FbPE/wDbLMWVkcQxKVYHOTg/NnvnrUzaxdrrBxIPsyX62Pk7RyDGG3k9c5P0wK2dQM4tCbeZIGBG6RxnamfmI7ZxnGeKPMPIzdPuzp9qIV07U5CWZ3do0y7MSWPDY6moG1V/+EjR/wCzb/8A49GG3y1z99efvU25vdUttNhnnknCxLJLM0SxK5jDfKxVgedvJAxz6dK0chvE0RHQ2TEf99rQAv8AbD/9AvUf+/a//FVFc6h9rtpIJNM1MK4wSiqpH0Ibitiq2oNcJYTNZhTcBf3YYgAn8aAMixdLCe5nTTdUknuSpllkRCzBRhRwQOBV3+2H/wCgXqP/AH7X/wCKpdFuXubeXzZ5pJEk2lZ4hHJHwDtYDg+uRwQRWlQBzmraq7mx/wCJbfjF2h5jXng8ferQ/th/+gXqP/ftf/iqNZ66f/1+R/yNGpX9xb3McFusWHXJYtucfRMjP5/hQBRuppbnVbO9Fpqkf2YMBGIYyH3dcknPYdKW4lN5pktleWOqzLITl/LRWHzZXGDjjjH05p17fy29tEtvdyPPc3UduzyIAYdxOSFIGOAcZz261e0S7lvNPLXB3SxzSQs4GN+xyu7HvigCjp1y1hFIDYanNLNIZZZHiQF2IA6BsDgAfhRq2rO2j3q/2ZqAzBIMmNcD5T/tVK8upJqrATpJCBIzRKo2xpt+Q5PO4ntnGM9Kqx3U8ui6vb3rztcw25ZhJ5eMMhwQUAHY/lQBct9XcW0Q/szUDhB/yzX0/wB6pP7Yf/oF6j/37X/4qr1r/wAekP8AuL/KpaAOavYodQlLXGnau0bOkjw4XYxXBXgnjkDpjPetL+2H/wCgXqP/AH7X/wCKqC6vLuHXESWZ4bVpFWMrErxvkcqx+8rZ6Hp071tUAZn9sP8A9AvUf+/a/wDxVUNM1LdYzxvpd9Ij3M+4GJSDmRuPvV0VZWnymDSruVQpKXFwwDNtB/et1POPrQBTdl3IY9O1NQrAhGjR169gzHH4YqulusV7JcRWerJlpJIk8uMiKSQfM4yeT7Hjk+tX7e9muirXdwbdSQAsKgoTnp5nIP6VWstYvJtYi8yRTb3F1cWywhR+78vOGz1ydpzn1H4gDtSml1HR5LFrXVEMiBHmEMZY+pxnGT9KZNLeS3cM4TVl8tVVlFvFhsHkjJ4z0OK19UM62ymC4Fuob95JtDMFweFBBGScdRWTLfalax2U180qIqR/afJEeNzNjkEE+mcYxzjNHUB0OrONdvG/s3UObeEY8tcj5pP9qr39sP8A9AvUf+/a/wDxVPt/+Rgvv+veD/0KWtCgDGur83cBifTdUUZDBo1VWBByOd3tUOnSx6Ys3k6ZqbvPIZZZHRNzsQBk4IHQAcDtWnqr3Mdg7WQJmyOFxuxnnbu43YzjPGaZo9wbmwDtcPOwdlLSReW6kH7rL2I6frQBH/bD/wDQL1H/AL9r/wDFVQvtWdtT0xv7N1AbZX4Ma8/u2/2q6Ks3UP8AkLaT/wBdZP8A0W1AFae5jnkMh0rUklIx5kahW/EhufxqnLGXhjCWepxzQymWKZLeIMpK7TkZwcgkcj+VaN9qFyl99mgESptBLg+ZJ/37yDj3GfpVe5vJg1ja2d7Jvu52R53Qbo9sZbAUgAHgcEetABYXB05EhhsdU+zxxLGkTRJgEZy2c5JPf6VWxcC51GZI9WRr0KPlgi/dYGBjn09a2NDvn1LRbS7lULJLGCwAwM9Dj2qiZdVSe6/0hZQIXJCKoWJ937sKTjJ28ndnnHrQwRQvrue28O3MMtrqMucYZoI0CjIwAFPTitn+2H/6Beo/9+1/+KrOuLmWfw3qMdw0zXEEgjk83ZkH5SMFQARgg9O9dJQBmf2w/wD0C9R/79r/APFVmyxQz3kc8unau4jn+0LEwUoJAMBhzkY9AcV0tYqXd2uveVczPFE7sIl8tWilXbwA45VwQSQeuOKAJ/7Yf/oF6j/37X/4qj+2H/6Beo/9+1/+KrTooA5rRtQEmgW0MulX0qFOQYlIPP8AvVKJAk8cken6phCCFeNJAPoWYkfgam0y4e18KQTRrGzqnAkk2KTu7tg4/Kn2l1JcSxtdXLxlm+SNIwqN7b+d34GgDLt7X7Izm2ttXjIRo7f91Gfs6s25guTzyB1zwAKt6tPLqdmsC2mp2+JEk3rDGxJVgwHJ9QKZoWsXl7d2zXEgeK9glmWMIB5OxwoGepyG5z3H4Vo6014kCtaXAhADZwgZ3bHyKoIxyev9KOgdTOM10dTF0ItVCcAxfZ4sYA6ZzkAnk06x1Z11HU2/s3UDumTgRrx+7T/ap73t9b6lam8aRIXMcTiLyynmMO4ILYzxnI7e9XdP/wCQpqv/AF2T/wBFJQA3+2H/AOgXqP8A37X/AOKqve3891GghtNVt3RtwZI0OeCMEE4I5rbqhrEt1FaK1mJCd48zygpk2YOdobgnpx6Z70AU7C8/s+zjto9M1IqmeTGnJJyejYHJqx/bD/8AQL1H/v2v/wAVVjS5/tOmwymf7QWXmTy9hbnHK9j6j1q3QB514kuzdeNrBja3EG3TphiVQM/vI+mCaKs+L/8AkedO/wCwdP8A+jI6KAJfAMt+uh3Qt7W3kj/tG6wz3BQ/61uwQ/zrp/P1X/nxs/8AwLb/AON1ifDn/kXrr/sI3X/o1q6ugDP8/Vf+fGz/APAtv/jdHn6r/wA+Nn/4Ft/8brQooAz/AD9V/wCfGz/8C2/+N1STTpo2Zl0bT9zSGXJu2JDkEFh+74OCRxW7WB4xljh0mBpLgwZvLddwmMeQZFDDII42k59qAI7bQhZpIlvoenRrLEYXAu3wUPJX/V9Kfp+kPpUvmWGi6fA+wR5S7f7o6L/q+grKXVjZ6vf22l3Ul1ZyxxR24abcFuWLbljdjzhAGIyQD6ZxWp4Q1F5rOfTLyZ3v9NlMMglcNIydY2YgnJKkZPqDQBo+fqv/AD42f/gW3/xujz9V/wCfGz/8C2/+N1oUUAZ/n6r/AM+Nn/4Ft/8AG6PP1X/nxs//AALb/wCN1oUUAYGuz6odBvg9laBfIfJF2xI4/wCudXml1R1Ktp9kQeoN23/xujX/APkX9Q/693/kaXVpLpIE+ySGM7vmIhMnGOnGcfXB+lAFVbS7USKul2QjkUq8YvH2MD1+Xy8fpUdvp1zaoiw6bbrtkEuf7QkJLAbRk7MkAcYPHA9KgnuvK0XULmzWV72K2kZZjKJcEDPHofbA6VPoNysd1e24uTLaq8QgeSXeWZowzKCTz649zQDHT2N5cXoupLGLzRt+7qUqqdpyMqEwefai1sLqzuWng0u0WRgR/wAfzkKCdxCgphcnk46ml1SPzNUi2XzxzBoiF83asShvmyM/MXHy4Oah0qcDXmCyJOLlZnDJLITHtkAwVY4744A+6RzQgF0KbUxpSbLK0I8yXk3TD/lo3/TOtDz9V/58bP8A8C2/+N03w/8A8ghP+ukv/oxq0qAMO8sbu/kWS4022LBSmVv5F3KeqnCDIOOhq2JtUUACwswBwALtv/jdY3i+WSG7gMbSD/RpSXW5aMQ/NGBKQPvbdxOPTNdRGCI1BbccDLevvQgKPn6r/wA+Nn/4Ft/8brOsptT/ALb1IiytC37rI+1Nx8p/6Z10NZlj/wAh3VP+2P8A6CaAI54L25bdJpllvHRxdsrD6MI81DJp9zNdRXMml2jTRhQGN8/zbfu7hs+YgkkZzjNbtYN7OsN662oaCcnJPm53+/lgMT+IFAEjWl69jJZtp9uYZCSw/tCTPJyfm2Z6+9V30eeSERyadC4DMd7alKX+YYYbtmcEDGM4qlrd1dJ5LyTybobXzJgrmBkO7HmKmSGIwfkJ9PWuuHIFAHPTvqMes6aiWFmoSOVUVbpsYwv/AEz4rS8/Vf8Anxs//Atv/jdNvP8AkP6b/wBc5v5LWlQBmStqU8LxS6fZtG6lWU3bcg8Ef6uoLK1vbAN5Gn22WABZ7+RzgdBlkJwPStK//wCQfcZJX903IOCOPWsHwbLLLDP5rupVIR5LztKclN3mZPZsjj/ZPvQBrefqv/PjZ/8AgW3/AMbqhrU+qHTvmsrQDz4el0x/5ar/ANM636ztd/5Bn/beD/0alACO+pyoVk06ydT1DXTEH/yHVY2N00EsJ0uzMMo2vEb19n4DZgfhW3VLVDEtruniMig5GHCbT67iRigChb2V3amIw6dbKYmZgf7QkO5m+8W+T5j9c0jWF41+bs2EPmlgxH9pS7CQMDK7MdPaoVvLkWV5Ibp1t1t3KuqGQoccESEDP0wfrUvhiSXN5BOSJImTKCczIMrnKueeeuD0/GgB1lY3Wnbza6ZaIWUJzfO21RnCjKcKMngcUmiz6oNCsAtlaFfs0eCbtgSNo/6Z1uN90/SqOhf8gDTv+vaP/wBBFACefqv/AD42f/gW3/xuqdzYXV3c+fNptqXwqti/kCuASQGATBwT3rcrkvEUkqeIY1ikkjDRwgyi4ZVgJlI3FBw2fu/iM0dQ6G75+q/8+Nn/AOBbf/G6PP1X/nxs/wDwLb/43WhRQBz+mT6oLjUttlaE/auc3TDB8tP+mdWJre9nfe2mWayf89EvHVvzEeal00kS6sV+8Lo44z/yzSs+OZnlCam8twx6Ip8of9+zjP5tQBObC5a/+2nS7Pz+u77a+Ccbd2NmN2OM9cUslleyaelm1hD5KY241GUMMHI+bZn9az3vJx4hYiaQTLqKW6wbyF8gw7idvQ85OfbGa3NSkhn00P8AazHCzKd8Tf6wZHygj+9049aOgdTNfR5pY40l0y3cICMtqMpLAncQx2ZYE84ORQZtT/4SRD9itN32RuPtTYxvXv5dUb5mtdNiMl5HK1tHLP5TXMm5lDjCBlIyQMLk557GtvOfE0RwRmybg/760ASefqv/AD42f/gW3/xuorldQvLZ4LjTrN4pBhl+2MMj8I61azfETFPDuoMrsjLA7BlcqQQOOR0oBEVpDf2SOsNhbZdtzs987sx6ckoSeABU/n6r/wA+Nn/4Ft/8bqp4Zd3t7zzCybbhkFu0xlMOABjceTn7w9mFbdAHPavNqZNhusrQf6WmMXTHJwf+mdXpW1GdCk2m2MiH+Frokf8AoujWeun/APX5H/I1HrE11HMnlzNHb7fnwhGT/wBdMHb+X40ARPY3cls9u2m2xiYhtv2+T5SDkFfk+Ug88Yp1taXloYjBptqnlIY1Av5MYJycjZgnPc81Tvp0XT4fs3mwxz3kUVzN5u4lCcH5wT1OBnIxntWh4euvO05Y5JvMYSSrEWfLPGshVW9TxjmgCt/Zlz9olmbToHMu4uj6jKyHcMH5SmOnHSobm0u9P0TUVg062USQPvY3ruxAQgclOw6CnygRarNOupNiMSmXfL8uNvCBR/d+8SBn8zUFpJt0bWbXcsnlW+/zUldw26MnHzkkEf1BwKEBq20+q/ZYsWNpjYP+XtvT/rnUnn6r/wA+Nn/4Ft/8bq3a/wDHpD/uL/KpaAMN7C6kvTdNptqZSwc/6fJtZgMAldmCR64q55+q/wDPjZ/+Bbf/ABus27l8vxCrvO0kYmjjAiuCrQMRwrR9GVs5z159uOioAz/P1X/nxs//AALb/wCN1R0efVBazbbK0I+1T9bthz5rZ/5Z1vVlae0i6VdmE4kFxcbTs3c+a3bIz9M0ARvbXryiUaZZpIDnfHeOhP1Ij5/Gov7Nn+0zXA0q0EswYMRfSD7wAYgBOCcDJGDxTbWXzLhUvzLczZGBv2AH18o7T/6F9ap2N/N/bqPJcvve6uo7iNpPljiQfIdvQYwvPfd70AaNzaX11bwwyWMIWEgoU1GVWBAwPmCZP41F/ZU5eFjpdsTEFAzqEh3bTld3yfNgkkZzzV7VzFLaQl7hljZwQscm0z5BwoYEEDocg9vSsSeR7VbKSS8jvJLZIA6ieQNIXcrkYIDfiDnb2o6gX4J9U/t68IsrTd9nhyPtbY+9J/0zq95+q/8APjZ/+Bbf/G6Lf/kYL7/r3g/9ClrQoAybuPUL2Aw3GnWjJkNxeupBByCCI8g5FFrHqFnD5cGn2gUksSb12LE9SSY8k0eJyw0OUoWDeZEBtlMZOZFGNw6Zzik8Mu8mkb5HYkyyfu2cu0OGI8sseSVxigCfz9V/58bP/wAC2/8AjdZ9/Nqf9qaXmytAfNfAF03P7tv+mddBWbqH/IW0n/rrJ/6LagBs39oXCbZtMsJF9Guif/adVpdPup7YQSadblFbeh/tCTchxj5W2ZHGeh7mn6pNdJd489o7XAyqqUyf+umCPw+X61UvZIiumwxmW2s7m5YTv52C2I2YfOCeCQOc9sUAXbeC+tXDQabaJiNYgovX2hVzgBdmB169arLpE4EytpsEiTBlZJNSldcMcnAKYHPpV3w7ePd6JZtcyBrloFdwT8xB6MR74rMfbC17Mupkx+TKsjyTHDsWGCAPuhB8uVx19qHuCE1OC9svD93HFYWyq53uxvXdmYkcklMk9O9bHn6r/wA+Nn/4Ft/8brGL/wDFNapbnaxt5vLMiyO6v905G4kjrgjPUGupoAz/AD9V/wCfGz/8C2/+N1TSwuo7w3S6ba+YXMmDfyFQ5GCwXZgHHGcVuVzsUuzxHmSdplkmeNHinPyELny3j6YGCQw9s+4Bpefqv/PjZ/8AgW3/AMbo8/Vf+fGz/wDAtv8A43WhRQBz+gTamNDtQllaFdnBN0w7n/pnU4tr1ZxNHplnG4OSY7x13fUCPn8an8O/8gG0/wBz+prG1S8uE124xPIssElottEHKq6u+H46NkZHtt7UAW10mZDOU0q1TzwQ22/kXAJ3ELhPlyeTjHNS3tpfah5ZnsYQY87TFqMsZGRg/dQVev5IptLmZLwQR4IM8bA7cHnB9e1c/cps0/y/tyAebLNHHNcyZVVUHYWVgeM55PGe+KAL4024W6S4Gl2nmJtI/wBOkxkDaGI2YJA4yeaSwn1T+0tUxZWhPnJkG6bj92n/AEzrXsZvtGn282xo/MiV9jHJXIBwTVbT/wDkKar/ANdk/wDRSUMBfP1X/nxs/wDwLb/43Ve8hv76NEn0+2+Rt6Ml86MrYIyCEB7mtisvXt7WkKRzRozSgCN5TGJuCdm8cqe/4UAFuNRtIFhg06zWNeg+2Mf18vk1J5+q/wDPjZ/+Bbf/ABunaLMk+kW7oZiMEfvn3uCCQQW78jr3q9QB534me6fxvYfaoIYj/Z020Ryl8/vI/VRiirHi/wD5HnTv+wdP/wCjI6KAJPAUF++h3Rt72GKP+0br5Wt9x/1rd9wrp/suq/8AQSt//AQ//F1i/Dn/AJF66/7CN1/6NauroAzvsuq/9BK3/wDAQ/8AxdH2XVf+glb/APgIf/i60aKAM77Lqv8A0Erf/wABD/8AF1FJBfl1jk1Oz3Nyqta8n6DfWtXI63YXI8QG8s7eSdneBHgmh3RyBWzuSQcxsuSTng46UAagFyEJGr6ftjOCfswwp/774oja5eXbHrWnmRjjC24yf/H656/02FNcOq2+kXElhJcJFeWYtmzO6523ATHIUn8evUDOxYadar4qvdumiOJbeAwyG22puUuTtbHUbh/kUAaX2XVf+glb/wDgIf8A4uj7Lqv/AEErf/wEP/xdaNFAGd9l1X/oJW//AICH/wCLo+y6r/0Erf8A8BD/APF1o0UAc/rltqg0K/LahbkC3fj7LjPynjO+rNpb689pG15f2aXBXLpHakqp9AS/NTa//wAi/qH/AF7v/I1o0raitrcyBa3zXLEajZGdVwcWnzAH/gecUyDTbkxILe80/wAtHLJsshhW5yRh+D1rI1CG2uptRTTBIt+kNyqAIwd3YfNliOBnhRnr06Cr+gyw29zdvDG8NlcSxR26CFlG8R/NxjgcYycDINNDZPNpU8l3HLPdac1z/wAs3exBfjngl88VLHpt/FLJLHeWaSSffdbLBb6nfzWTrVvK2uT/ALp2uJfsv2KTYSF2yEyYP8OByfUYrrKAOd0O21M6UhTUIAvmS8G1z/y0b/brR+y6r/0Erf8A8BD/APF0nh//AJBCf9dJf/RjVpUAYtxYXRkV7q/sC7Axq0lmMkHqoy/f0qdbPVEUKmoWyqowALPAA/77rP8AE6x+fG5TzJRCwWGWAyRTAkfJkcq/TB/nXQoSY1JUqSBwe1AFD7Lqv/QSt/8AwEP/AMXWdZ22pnWtSA1CAMPKyfsvX5T/ALddFWZY/wDId1T/ALY/+gmgB32XVf8AoJW//gIf/i6hNve20mDqdlG8rdPsmC5/775NXr+GSeykjhZ1dhgGN9jDnscHH5VmWAayuUSS2VXc4MkkZDn/AIGNwb8xQBLNpt9O6NNeWUjRHcheyyUPqMvxUiQ6nKgePVLV1PRltcg/+P1g3ied/wAJNBZRyF2kidkRCC6gL5mPUkBhxWx4cUCO+khQpaSXTNbrsKjbtUEgdgWDGgCtdW2p/wBuaeDqEBYpNg/ZenC/7daP2XVf+glb/wDgIf8A4ukvP+Q/pv8A1zm/ktaVAGY9lqciMj6hasjDBVrPII/77qG2sboDdaX9gMKI8xWY4A6Lw/QelaV8FawuA4kKmNgRF98jH8Pv6VkeGdqm5WNI2QbALhIDCZODwy/3l7keo6UAXfsuq/8AQSt//AQ//F1Q1q21Madl9QgI8+HgWv8A01X/AG66Cs7Xf+QZ/wBt4P8A0alAB9l1X/oJW/8A4CH/AOLqOWx1GRQZb+0YKdw3WecH1+/WrWHfWc32953jkniJBVH/AHsa8f3Bgj8moAnjj1CeMtHqto6ZxlbXI/8AQ6ZBYXlpi3t76xhzlhGlmFz6nAeqmuXEEmi2kssarsvISoRGbbtkGTjAIwM544qpPBK3iZiInN01/FLFLsOPs4iAbDdhncMep96EBuG11XB/4mVv/wCAh/8Ai6paLbaodDsCmowBfs8eAbXOBtH+3W833T9Ko6F/yANO/wCvaP8A9BFADfsuq/8AQSt//AQ//F1Vn064ab/SL3TjLMuz57IbnA5xy/I9q265rXFjXV45BF58u2MeRLAWWQByQY3H3XHJPbpn1oA0/suq/wDQSt//AAEP/wAXS/ZdV/6CVv8A+Ah/+LrRooA57TLbUzcalt1CAYuuc2vU+Wn+3V2Sw1KZCkt9aup6q1nkf+h0/Sv+PnVP+vv/ANppUupwS3FmUgeVW3A5ikCNge+P04+ooApNaXa3iM+oWAuSu1SbMbyvXA+fOKSTS7o2nkS3dgbZB/q2sRsUDnpvwKXTCbW4WBraONnyCxjKO2PfkN/31WIAkmn36QRsbePV1lnjEbcxblLHGORwScehoA2k0i5MMKpc6eYozviC2A2qeuV+fj8Krtban/wkiD+0IN/2RufsvGN6/wC3Vzw3G8eltlSkTTyvApXbtjLkrx2GOg9Ke3/I0R/9ebf+hrQA77Lqv/QSt/8AwEP/AMXUc1hqM0LRz31o8TD5lezypHuC9atUtZSOTSLlZvO8sphvJXc4HsO/0oAq29nekGW21Cyw+MvHaD5sDA5D84HFTfZdV/6CVv8A+Ah/+LqDw4c2twBHCFE3E0MRiWf5R8209D2PbIrYoA53VrbUwbHdqEB/0tMYtehwf9utH7Lqv/QSt/8AwEP/AMXTdZ66f/1+R/yNadAGPJp14I5fMvbEJIP3u6yGGH+18/P40Q2V4RHLBf2JAXZG6WY4X0B39OOntUFxZzRXsk8sT3CliV80ecij2AwV/wC+T9aZrFxA8mhTyKA32sFSiswVdjA844GSOuKEDJ00qdL1pY7rTluiMs62ID4PcnfnmodQ06+tdDvlhu7SOPyJGKR2W0H5Tno9U7G3lXxKuYZBdLe3Ek0hQ/NAy4T5uhH3AB/sn0roNZ/5Al//ANe8n/oJoArW1tqv2WLGo2+Ng/5dPb/fqX7Lqv8A0Erf/wABD/8AF1ctf+PSH/cX+VS0AYrWN19tR3v7D7Vj5WNmN+Pb581Z+y6r/wBBK3/8BD/8XWXeLGviZWSPzpGmj3RSwEkcD95HIOgA6g8cHpnnpaAM77Lqv/QSt/8AwEP/AMXVDSLbUzazbdQgA+0z5za9/NbP8ddBWfov/HpP/wBfdx/6NagCOSw1GYAS31o4ByN1nnB/77qE2Vy11Ipv9PNxIm1wbMbmX0Pz5Iq3q1tNdW6LA0ww2WEUgQkY6HPUe2R9ag0xxC7W7W8UI2knETRsceo5B69QxoAjudMuJLYJdXmntBH0ElkCq447vgU4aRdgwlbmxBhGIiLEfux/s/Px+FYVr5DaNp5MTNp9vqMxnj8psBCZNhKkZK5Knp3BrovDkU8Hh+zjuQyyLH91uqjPyg/QYFAFKC21P+3bwDUIN32eHJ+y/wC1Jj+Or/2XVf8AoJW//gIf/i6W3/5GC+/694P/AEKWtCgDJubC+mgYXV9ZPEPmIks8qMc55eiCzvwpe31Cz2yHeWSz4Ynvw/P1qTXkjk0pxK0qLvQ744/M2ncMEr3XPUemab4fOdL/ANRFEPMfHlIUSTn76qeQD1xQA/7Lqv8A0Erf/wABD/8AF1n39tqY1TTAdQgJMr7T9l6fu2/266Gs3UP+QtpP/XWT/wBFtQAfZdV/6CVv/wCAh/8Ai6rzabdLbSLPeWAgY5cPZDaT6nL49K2q502s1pO0txC1xySGnBmCjPZl5Uf8B/HigC5HZ35YTx6hZ7nUAOtnyy9QM7+nJqGHSJo5pjBc6aspGJdliAxB5w2H7+9Mv5oT4k0OVlxI6yDcqkgBl4GcdM+uKo+HreWPVYA0TpcRR3AvnZCN7NKCmW/iyMkegoAsaxYX1roE8cd5apCoGEjs9oHzDp89an2XVf8AoJW//gIf/i6b4i/5AV19B/6EK06AM77Lqv8A0Erf/wABD/8AF1WWwulvmdb7TxdlfmYWY8wj3+fOK2q5qBY4/FB8qLzWaZy4lgIkhO376ydCh4GD68dMUAan2XVf+glb/wDgIf8A4uj7Lqv/AEErf/wEP/xdaNFAHO6DbamdEtSmoQBdvANrnuf9urradqDzJK97ZtLHnY5sssueuDv4p/h3/kA2n+5/U0msWk1yIvKMxRc7ljkADfVTjcPxFAFcWNxIj2Yv9PZeS8P2MEcnJJXf6006RLFaiJrnTUtw+4KbEBN3rjfjNT2UsQt54JreGKNYyXURMmR3ypH8ia5tFjk0DRHngkls47WWJ08pjtlKgJlcZz94DjqfegDqPsuq/wDQSt//AAEP/wAXVCwttTOpamBqEAImTcfsvX92n+3WtpSTxaRZpdEm4WBBIT/e2jP61Dp//IU1X/rsn/opKGCD7Lqv/QSt/wDwEP8A8XUN1ZXsluwvL+yaEct5tmCv45fFa9ZPiFY2soTLI0e2YFX8nzUU4P317r2+uOlADo7TUljURajaiMABQtpxjtj56f8AZdV/6CVv/wCAh/8Ai6dohzo9v/o6W/yn92gIUcnkA8gHqAfWr9AHnfiWK6j8b2AurmOYnTpsFItmP3kfuc0VY8X/API86d/2Dp//AEZHRQBJ4C037Tod1J9svIv+JjdDbHLtX/Wt2xXS/wBi/wDUR1H/AL//AP1qx/hz/wAi9df9hG6/9GtXV0AZn9i/9RHUf+//AP8AWo/sX/qI6j/3/wD/AK1adFAGZ/Yv/UR1H/v/AP8A1qq6hb2ulwrLearqMcbuIwRIzZYnAHAPU8Vu1jeKLO7v9Ljgso2eT7TDISsgQqqSKxIJ7/LxQAy0t7S+tXuLbWL54kLK588jYR1BBGQR6Gn2djb39nFdWmrX0sEyh45FuOGB6HpWbbaTqlrZz6asIK3F0XlvxKpeRDyWZT/FgBSBxjp6Ve8NWF9pJvbK4QNZrO0trNuUEq/zMpUD5cMWx7EUAWv7F/6iOo/9/wD/AOtR/Yv/AFEdR/7/AP8A9atOigDM/sX/AKiOo/8Af/8A+tR/Yv8A1EdR/wC//wD9atOigDntc0jy9Cvm+36gcQOcGfg8H2q9/Yv/AFEdR/7/AP8A9an6/wA+H9Q/693/AJGrzrvjZeOQRzQBizW1rDIYjquoPKP+WccxdvyA4pDBZi/FkdXvxckZ8vzz6ZxnGM45x1xzSxWF3pabLNAIh0WHBX/vhjx+DVWfS7w6ywELeS9+l954YYCiIKUIznORj0wetAF2506K0gaafUtSVFxkiUseTjoBk0tvpsd1AssWo6nsbpulKn8iAamvTLd6SrNYyszFGktzIFcDIzyDgkDtnn1pdEhuLfTVS5Dq29yiO25kQsSqk5OSBgdTQBm6HpHmaWjfb9QH7yXgT/8ATRvar/8AYv8A1EdR/wC//wD9al0DjSE/66S/+jGrSoAwr2C007b9q1bUI8jP+tJwO5OBwPc8Va/sYf8AQR1H/v8A/wD1qr67b3Mk8clnbz/aFjYRzwuow2fuOrcFD1PXGK2U3bF343Y5x0zQBnf2L/1EdR/7/wD/ANas+z0jdrWpL9v1AbfK58/r8p9q6Osyx/5Duqf9sv8A0E0AMm0yK3jMk+q30aD+JrnA/lVcxWi20lw+qakkCYG9pGAYngbeOfw65q3qOmNc3Ud1EsXnRrtViSrjvwwyPTgg1Tvra/urWFnjeR7S6in8tgoMiqeQCDgnuMgdBQBYttOhu7dJ7fVL+SJxlWE/X9KiS2tpL1rRNT1MzJ94b22jjP3tuO/rU2hxXNpAIZ7eRfOea4LblKx7pCwQ85zhu3HB5qCK0u/+EiWZLaWBBJIZZfO3JKhXCjbng5wenGDzzQBFdaRjW9PX7fqHzJLz5/I+77Vf/sX/AKiOo/8Af/8A+tS3f/If03/rnN/Ja0qAMt9IVELvqWoKqjJJuMAD8qr2dta6h5n2bVdRcxkBgZSpGeRwQOvrWtdoZLOZBEsxaNh5bHAfjoT71naFFdQ+csyXCW4CiFLlleROu4bgTlRxgk560ASf2L/1EdR/7/8A/wBaqOs6Rs08N9v1A/v4Rgz/APTVfauhrO1wZ03j/nvB/wCjUoAb/Yv/AFEdR/7/AP8A9aqr29ss3lLquoyS5wUimLkfXA4/Gti5gFzaywsFIkUqQwyOfUZFZdvaXmnFI4VxACBtiIZQP91sEfgxoAjjgs5b57OPWL5rhAdyCc9sZGcYyMjI7ZFSXdjDZQ+bcalqQUkKNsjMST7AE1RttMvbbU1Y2zNHbXNzdCRWX98JAdqDnr83OcD5RzzWpqqPc2MBaxlmUuGkhSXa6jaemCASDgYzQAyPSkmgWWPUdS2su4ZmKnH0IyKq6Lo+/Q7Bvt+oDNvGcCfgfKPatLSYbmDR7eK9YvcLHhyW3HPoT3I6Z70mhf8AIA07/r2j/wDQRQBH/Yv/AFEdR/7/AP8A9aqtzDZ2c6Q3Gr6gjvjA84kDJwMkDAyeBmt2sPVbe7OprNY28yzbUUTI6+W43HKyKewGSCBnnigCz/Yv/UR1H/v/AP8A1qP7F/6iOo/9/wD/AOtWnRQBzum6RvuNS/0/UBtuscT9f3ae1W59PgtU33GrXsa9AXucZ/SptK/4+dU/6+//AGmlMvdMd7/7ZbrH520LuBKPgds8gj2IoAqSR2kNqbibVNTji3bVLyMCx9hjJ/LsatRaVHPEksWp37xuAystxkEHoRxVa7hvpGsLtoJZns7hmaLCK7KY2XI52kgt7cZq1oNvcafpttYXETboYVLS7gVLEnKjnPH0xQBXgtre5uZIItT1RnjyGy7BeDg4Yrg8+hqBtI/4qNE+36h/x6Mc+fz99faptNtbpNaaU20ttFskE26bekrFwUKjPYZ7Drjmrbf8jPH/ANebf+hrQAn9i/8AUR1H/v8A/wD1qZNpcdvC0sup36RoMsxn4A/Ktaqmpxedps8YtvtO5ceTv27/AGB7H3oAoWdnb38bPbapqLBW2MDKVKn0IIyOoqf+xf8AqI6j/wB//wD61LoqXUdvKtz52zzP3P2gqZduB94rwec4PXGM1pUAc5q2kbDY/wCn6gc3aDmfpwfatD+xf+ojqP8A3/8A/rUus/e0/wD6/E/katX1ot9ZyW7qjK4wRIpZTz3AI/nQBlLb20k4ii1TUZXzg+XMWC/UgYH40W0Fnd3MsFvrF88sX31E59cHHHODxx0PFT2sN7ZyxxYbyM4wpDqB+OGH/j1Zmk6ff6bJAZLORxYW80Q2Ov8ApBeQMCuT6Lk5xyaAL15aW9giNcanqYDnaoV2ck4z0UE1Hqmkj+xLyQahqBH2d2AM3X5T7VY1+CW4hjEdnLcDD/6qby2RiPlPUd++eKkvEmj8LTpcvvnWyYSN/ebZyfzoAjt9GzbRH+0NR5Qf8t/b6VJ/Yv8A1EdR/wC//wD9ar1r/wAekP8AuL/KpaAMKWGzhvEtZNX1ATOQoHnHGT0BOMAn0NWv7F/6iOo/9/8A/wCtVa4t7sa75trbzR7pE8yQOphmQAZLKTkMOgIHYdq3KAMz+xf+ojqP/f8A/wDrVR0jSN9rKft+oDFzOOJ/SVvauhrP0Yf6JN/19XH/AKNagCtcWNvaAG41a+jz0BuOT9BjmoJ1srW3Sa51XUoUckL5kjAnHJOMZxjnPYVZuNMlS+lvLVUEknLMh2OcDHOcq35D61T1O11Cdre6W2ad1gnt2jO1CC+3a3XGPlwTnvnFAGgNGDAEajqBB5BE/wD9aq1pbW98XFvqeqNs6kuyj8CVGenar2mRy21nHZyRvm2ijjEpIxKQoyRznr6gVR0O1uobyV3t5bWAworRPN5gaUE7mXk8YwM8Z9OKfUOhFDpGddvF+36hxbwnPn8/ek9qvf2L/wBRHUf+/wD/APWp8H/IwXv/AF7wf+hS1oUgMi406K1haWfU9QVF6nzifoAAOT7U20sYL6ATW2qag8ZJGfOIwQcEEEZBzVvWITPp7ILd7j5lOyOTY4wR8ynIwR1HPak0dbpbDF7vL722GTbvKZ+Xdt43Y9KAI/7F/wCojqP/AH//APrVQvtI26npi/b9QO6V+TP0/dt7V0VZuof8hbSv+usn/otqAEOjAAk6jqAA6nz/AP61Vora2nm8uDVNRlPdo5iyj6tjFaOpWK6haGF1jYbg2JFJGR06EY+tU4re+UNauXEToyBgQ6rwcYPDDt1B+tAEVlBaagZPsmr30vlnDYnP4HpyDg8jg4ou7a3snjWfU9UDSZ2hHZ+mP7qnHUVW0W0vrF45prKQGCzgsvLV1+cqx3OOfugHPPPXirPiG1ubnAtbWV5PKZYZo59nlSEjBIyOB1zz0xjmgEQa9pHl6Lct9v1A4A4M/uPatD+xf+ojqP8A3/8A/rUeIAf7AuQeTtGfzFadAGZ/Yv8A1EdR/wC//wD9aqohszfCzGr6h55JAXzjgkDJGcYzjnGc1u1hw291HrxeC3mgieVmmy6tDIu3hwOqvnHAwOuaALP9i/8AUR1H/v8A/wD1qP7F/wCojqP/AH//APrVp0UAc5oOkeZolq32/UBlegn46n2qzcWdtakCfVr5WPRfPyx+gAyaseHuNBtP9z+pqB9Mntbma4s1QNKxZjEdrMT6hsqT054oAhmSztvJ+06tqMLTfcWSUg9cZIxwMkcn1FW20cIpZtR1AADJPn//AFqytY02/vJJJEgMhvLE2hPyoYW3Z3EZPGD2J+6K3maaW0uUFu4dQyIHcAS8cEEZwD0559qOgGfZ2kF/GZLfUtUKg4yzsn/oSjNQWOkbtR1Nft+oDbMnIn6/u09qs6DbXED3TSQzW9u+zyoZZN5UgfOc5OATjv2z3qxp/wDyFNV/67J/6KShgN/sX/qI6j/3/wD/AK1Q3VhDZxeZPqeoqpOBiYsSfQADJ/Ctms3W4GntYwtvPMVkDZgkCSR8H5lJIye2O4JoAittOhu7dJ7fVL+SKQZVhP1H5VJ/Yv8A1EdR/wC//wD9arGli5GnQi9/4+MHccAE88ZxxnGM44zmrdAHnXiSz+yeNrBftFxNu06Y5lk3Y/eR9KKs+L/+R507/sHT/wDoyKigCTwFpGn3eh3UtxZwSyHUboFmQE/61q6f/hHtJ/6B1t/37Fcz4B1awtNDuori9t4pBqN0SryAH/WtXT/2/pP/AEErT/v8v+NACf8ACPaT/wBA62/79ij/AIR7Sf8AoHW3/fsUv9v6T/0ErT/v8v8AjR/b+k/9BK0/7/L/AI0AJ/wj2k/9A62/79iqDWejjXF0v+x0MjQmfzfLTYFBx65zkjtWh/b+k/8AQStP+/y/41i3l5E2vf2jZazpSYtjbhJTu6sGzww9OlAC350iwvYbY+HnleeXyYfLjj/eEDJIBYHaB1OMCm2c/h/ULKO5tNJWQtOLeSIxIrwOTjDgn+Wcg5GarwyGLVZ79tf0iad1WKOSQcxRjGVUBsckEk9+PQUsVrpYnsLs61ZxXduVE5hcBLmNSSqsCeoPIPUc9jQgOh/4R7Sf+gdbf9+xR/wj2k/9A62/79il/t/Sf+glaf8Af5f8aP7f0n/oJWn/AH+X/GgBP+Ee0n/oHW3/AH7FH/CPaT/0Drb/AL9il/t/Sf8AoJWn/f5f8aP7f0n/AKCVp/3+X/GgDP1zQdLTQb9lsLcEW74IQZHynkVYs/CukWdpHAtlFIEGN8o3M3uSe9Qa7rulvoN8qajaljA4AEq88Vf/ALf0n/oJWn/f5f8AGlbW4rK9yhqVnoumBd+kJMSjSFYolOFXBY8kDjI46ntVpNE0aSBZlsLby2XeCYwOMZqnq2sW9yiR2l9pckRz5qTXOzd6DgHI9RU663YTJPDc6jp4iZQqeXMM4K/NnPTnOPan0GV9Mg0LVGYRaXHGfLWVPMiUeZG2drj2OD1wfatH/hHtJ/6B1t/37FY2iTWOnzLJdatp7tDax2kRjmHzIhJ3NnoTkcDpjrW1/b+k/wDQStP+/wAv+NAGboWg6XJpSM9hbk+ZLyUH/PRq0f8AhHtJ/wCgdbf9+xWfoWuaXHpSK+oWoPmS8GVf+ejVo/2/pP8A0ErT/v8AL/jQBQvrPR7KZYV0dLiUoZCkMSkhAQCcEjPXoMmro8P6SR/yDrb/AL9isrW7yy1IosOoaWVVTtd59skL9nRhzx6cZ9a1U17SlRQ2p2jEDBPmrz+tAC/8I9pP/QOtv+/YrItvDOky+Jr6ZrOP9zHGixgYTkEk7e57Vsf2/pP/AEErT/v8v+NZ1lrmlrrepMdQtQreVg+avPymk1cTSZebQNIRSx0+2wBk/uxVLTrXRdRkdF0hImEaSqJYlG9GztYYJ9DwcEelXm1/S9h2alZ7scZmGM1l2WsLCJHmvdG8+RkLut0W3DPzdhjA+6PzpjH6jFoOmTCKXTI3byzLJ5cQPlRggF29sntk9eOK0f8AhH9J/wCgfbf9+xWLrT2Oo3Mklvq+nqtzam0nEko4QtncuOp5YYOOo54rbXXtJVQBqVpgDH+uX/GgDOu9B0sa5p6iwt9rJNkbBzwtaP8Awj2k/wDQOtv+/YrPu9c0s65p7DULUqqTZPmrxwtaP9v6T/0ErT/v8v8AjQBFPomjW8Ek0thbCONS7HyxwAMmoLDTdKvlY/2MsIABBkjXDgjIIIJBqxPr2mtbyLDqdkshUhC0qkA44yM9KztGvdP09pzJf6bCku0iCC4zGrDO5hnGM+gGOKANT/hHtJ/6B1t/37FZniHw5pb6NLGtlDEZHjj3xoAy7pFGQfXmtT+39J/6CVp/3+X/ABrP1rXdLfTsLqFqT58JwJV/56rQ1cTV1YuQ+GdIghSJdPgKoAAWXcT9SeTVHUYND02TbJpKOFTzJGjhUiNM4yc9eewya0v7f0n/AKCVp/3+X/GszU9YguJ4hb32kyW64ZlmuduWzwcAHIHXGRzQMu3GjaLaW0txPY2qRRIXdjGOABkmq+nWWi6kJAulRwyRFd0csShgGGVPGeo/rSXep6fqWmX1ndanYIs6vEjRzAkIRgE57+1RaRfWVrPdXV7qmnm4uBGpEUwKhUXA69yST+OKANI+H9Jwf+Jdbf8AfsVS0XQdLfQrBm0+2LNbxkkxjk7RV46/pO0/8TK0/wC/y/41S0XXdLTQrBW1G1DC2jBBlXg7RQBd/wCEe0n/AKB1t/37FULmz0e3vPsyaOszgK0nlRKfLViQCQSCRwegOMVof2/pP/QStP8Av8v+NY+q3dlfXsckWo6YoTaY5zNtlhIOWxj7wIxwSB65oA1/+Ee0n/oHW3/fsUf8I9pP/QOtv+/Ypf7f0n/oJWn/AH+X/Gj+39J/6CVp/wB/l/xoAyNM8MaS2rarcmzjJ88RBCPkUBEPC9MnPJrRuNG0a1tpZ5dPt9kSF2xFk4AyeKq6ZrulrcakW1C1Aa6yMyryPLSrlxr+n/Z5Ps2pWPnbTs3zDbu7Zx2pWtsJJIq6fYaNfmZRpMcMkLBXSSNcjIBByCRyDUV1FoNpfC2fTImI2ebIsS7Yt7bU3fUjtn3xSWGsRW6ASXukBnmDSlbosWXby2cD5s44xgCq2otp93qEzx6tYC2uzAZw0w3L5Tbht9c8DnGMZ5pjNz/hHtJ/6B1t/wB+xWc2g6X/AMJIifYLfb9kY42DrvWtL+39J/6CVp/3+X/Gs5tc0v8A4SVH/tC12/ZGGfNXGd60AaH/AAj2k/8AQOtv+/YqC80nRbG0kuZ9PtxHGMtiMVY/t/Sf+glaf9/l/wAar3ut6fNZSx2+paf5rLhfNkDIfYjPSgBLPSNLuo2Z9GS3ZW2lZY1yeAcggkEc9jVj/hHtJ/6B1t/37FZ+jahpunwSo+o2EaNJujgjuNyRDA4UnHGcnGABnitH+39J/wCglaf9/l/xoAyPEHhrSp7a1g+xxxCW6jUvENrAcng9umPxrVXw7pKqFGnW2AMDKA1Q1fXNLc2G3ULU4u0JxKvAwa0f7f0n/oJWn/f5f8aVtbisr3M26t9EtLwW7aSjANGryLCu1C5wue5yfQHHerN9peiadZS3VxYW4ijGTiIEnsAB6k8VVu9Ygm1KJ1vtJe1jKkeZc4ZTnltoGCcdOaNQ1Cy1TRprWfVNPinZtyMkwZQVfcmc/QZ/GmMsWGm6NfxSMulxRPE5jkjkjXcjDscZHQg8HvTdX0DS00a9ZdPtgwt5CCIxx8ppmk6jp9oLqW51Ow8+6nMziOYFV+UKACcZ4Uc4FSavrulvo18q6jaljbyAASrz8poAmtvD+lG1iJ0+2yUH/LMelS/8I9pP/QOtv+/YqO21/ShaxA6jaZCD/lqvpUv9v6T/ANBK0/7/AC/40AZ7WejjUDapo6y7GVJJEiUrGWGRkZzjHfGKv/8ACPaT/wBA62/79isi6u7O41mO6XUdLRY3UrOs22UIPvIQOGBOep4z0zWx/b+k/wDQStP+/wAv+NACf8I9pP8A0Drb/v2KytD8L6Sv224NojtLdSja4yqBXKgKOgHGfxrW/t/Sf+glaf8Af5f8aoaPrulpazBtRtQTdTnmVehlbFKwrJ6k95pOjWNo9xLpsBVMcJECTk4AH4mmWGm6PfxSMulRRPFIYpI5I1yrD6ZB6joakvNfsjaSCy1KwFwR8hkmAUfln+VVbDWbe3SKOS90lE3OZdlyWPPQ5IGSTnOcUxjXi0FNT+xnTIyRIImlES7FkK7ghPXJHtjketaX/CPaT/0Drb/v2Kw5WsH1ZpRq1h9ke7S8YGYbw6oF2jtg4Bz9Rit3+39J/wCglaf9/l/xo6AZ8Gg6WdevFNhb7RbwkDyx3aT/AAq//wAI9pP/AEDrb/v2Kowa7pY168Y6ja7TbwgHzV5w0n+NX/7f0n/oJWn/AH+X/GgCtfaXo1hbGaTTbdhuVFVY1yzMcAc8dT3pbTR9KuoPMbSI4GyVMcsShgQcdsgj3FM1LWNOurJ4ob/TXLEbknkBR1zyD9RmmaRqWnWFiIZdUszh2KoLjcI1J4UE8kCgC7/wj2k/9A62/wC/YrJ1nwxpNzeaXA1nHGrXBZjENhYKjHBI7HvWv/b+k/8AQStP+/y/41nX+u6W2qaWw1C1IWVyT5q8fu2pNXE0nozQ/wCEe0n/AKB1t/37FZz2+iR6itodJTmQQ+b5K7A5XcF9enfGPetL+39J/wCglaf9/l/xrMfWIX1dZXvtJa2Q/u2Nz86DbyQuMbieM56Uxlm/03RdOtvOl02BtzrGiJGCzsxwFH1JosdL0XULUTxabAo3MrK8QDIykgg+4INVb/ULPUNNtxJqenJewSxzgLPmMupzjPXB5Gcd6m0jUdMsLNkl1OyaWWWSaTZMNoZ2LEDPYZx+FAEev6DpceiXLJYW4YAYIQeorR/4R7Sf+gdbf9+xWfr+uaXJolyqahasxAwBKPUVo/2/pP8A0ErT/v8AL/jQAn/CPaT/ANA62/79iqEVno8981vFo6squY2mESlFcDJB5yPrjFaH9v6T/wBBK0/7/L/jWOt3ZnXBeNqOlxhXOZYp8PLHjAR16HB5znsOKANf/hHtJ/6B1t/37FH/AAj2k/8AQOtv+/Ypf7f0n/oJWn/f5f8AGj+39J/6CVp/3+X/ABoAzdA0HS5NDtWewtyxXklB6mtH/hHtJ/6B1t/37FZ+ga5pceh2qvqFqrBeQZV9TWj/AG/pP/QStP8Av8v+NAGbqVvommPtk0lJNqebIY4VIRM4LHOM9egyfatD/hH9J/6B1t/37FZ2qaxBcSxrbX2kyW45ZZrnbls8ZAByB1xxzWl/b+lf9BK0/wC/q/40AH/CPaT/ANA62/79is+w0HS21LU1NhbkLMgA2Dj92laP9v6T/wBBK0/7/L/jWfYa7pa6lqhOoWoDTIQfNXn92lAF/wD4R7Sf+gdbf9+xVW+0zR7GOMnS4JHlcRxoqKCzEE4ycDoD1NW/7f0n/oJWn/f5f8ao6tqunXtoIo73S5lLDzIriUbXXB7jODnBBx2oAsW2i6Tc26S/2VFFuGdkkQDL7EVL/wAI9pP/AEDrb/v2Kq6Zq2nWenQwT6taSOgwW88HvwMk5OBxk8nFW/7f0n/oJWn/AH+X/GgDivEun2tj43sFtbeOENp0xYIuM/vI6KXxNf2t743sGtbmKYLp0wYxuGx+8j9KKANn4c/8i9df9hG6/wDRrV1dcP4C1JbbQ7qM2t5J/wATG6O6OEsv+tbvXTf20v8Az46h/wCAzUAaVFZv9tL/AM+Oof8AgM1H9tL/AM+Oof8AgM1AGlWHealq0OrxWcNrZsJ0keIvKwJCbeuF4J3fhirX9tL/AM+Oof8AgM1UZ7iOfVra/MGrK9ujosa23yMGxnPGf4R37UAMbxQxtZdQSK3TTo7g24kmmKtIQ+xiOMAZBAB647ZFT22t3mpG6m02ziltbedoBvlKvKynDEDGAAcjnrjtWc9jZHz447fWYrW4nFxJbJB8hfcGJGRlcsMkAgfnViFYLW5nktYdZhiuJTNLAkHyFz1I4yM98EZoQHS0Vm/20v8Az46h/wCAzUf20v8Az46h/wCAzUAaVFZv9tL/AM+Oof8AgM1H9tL/AM+Oof8AgM1ADtf/AORf1D/r3f8Akamv79dPiWR4ppAxx+7TOPcnoB7msjXNYWTQr5fsWoDMDjJt2wODVmfUYLkKJdP1ElTlSIHUg+xHIoAfJqslvp1xqM4g+zQxNJsifexwM43cD+fWpNK1KW8kube6iSK5tyu9UfcuGXcCDge4/CsqRbeZLiKa01KSK4iaJ91p8+CMfeAz+eaLKR7NzLjU3nkkVppDZf6xVXaFx27HI759aANi51B7fVbK08kMlyH/AHm/7pUZxjHOahtNSupdTNtcWgiRkd0IfLKFbb8wxgbuowexqjeXLXWqWN2kWoxralj5f2InfuGDz24pLG6ntbuWWb+0Z0kJOz7DtOSeMnvgcCgDR8P/APIIT/rpL/6MatKud0PV1j0tF+xX5/eS8i3P/PRq0P7aX/nx1D/wGagBmratLYXMEEMcO6UEq08hjVyP4A2CNx7ZrUHSud1SY6kpQR6nHC8ZjliNnvVwe/PRvQ1fTWERFUWOo4UY5t2NAGpWZY/8h3VP+2X/AKCaX+2l/wCfHUP/AAGas6z1dV1rUm+xX53eVx9nPHymgC8mrvdTtDawiNwcf6UfLPXsnUj8qhu9ee1v2g8lHhtzClzLu2kNKdq7Rz04Jye9QTPbyIVis9TjHXZ9mLpn/dbIH4YqvNDDNeLN9n1NUbyvPiW0O2UxnKH256+uBQB1EhZY2KKGcAkKTjJ9M1jHW7qbRbW/trNP30RmfzJMJEAM4JA6noOKWLVZUtmR4dRklJbbIbMjGSccD04HvisuJLiDSrOyik1EfZuN7afkP/dyM9qANd5jPqukStG0ZkhlYo3VchDg1r1zU2q7dX03daag7JFKCxtiCxwvOK0/7aX/AJ8dQ/8AAZqAL08hht5JFjaQopYIvVsDoPeqOjalJqcDyuLcoCNrQyFvqrAgFSPQ1HNqwlgkjFpqcZdSodbc5XPce9VNOuPsc0880GozzzBQz/Y9mQucZA6nk8/T0oA6Gs7Xf+QZ/wBt4P8A0alJ/bS/8+Oof+AzVQ1nWFk08L9i1Afv4Tzbt/z1WgDU1DUl08JuhlkL5wVX5V/3mPC/jVa51Wez02W+lSCRflWKOF925mIUZbp1I7Uy4v4Lkqz2GpB1ztdIHVh+IqhNHBPb3EEltqRWYLhxaYdWB3A5A5wQDyKANrSr976KdZo1jnt5jDKqNlcgA5B9CCDQ1+660lgYfke3aYS7+pDAEY/4EOc1lWM7WTBgmpuzyPLcZs8eczAAf7oGBjHpSy3Lya3FfrFqKpHC0Pk/YichiDnd9VFAF7TtSurq5lgurQQFYllG19xXdn5W44YYzxnrUuhf8gDTv+vaP/0EVl6bdT2XmfaBqNyGH/PjsOe7EjqTx+VP0XWFTQ7BfsWoHFvGMi3bB+UUAdBWVfatLbarDZxRw5cKw86QoZMnBCcYJA5I9xT/AO2l/wCfHUP/AAGaszUZP7Rl+ePU1t2274fseRlTkFSeVPv7UAdLRWb/AG0v/PjqH/gM1H9tL/z46h/4DNQAaY22fVScnF2TwMn/AFaUyDVZb99lpEkJHX7Sdrj/ALZjn8yKpadqyCfUw1jfkPckkfZz/wA8060k7QOgWK01NAOiPbGRB+DdPwIoAstr7LqvkeSv2ZbkWbS7vm80pv4GPu8gdc5NaV/cvZ6fcXEcYlaKMuELbd2BnGe1c+0cLan9q+z6mIzMLgw/ZTgyhNgbPXpjj1GaszX0k+kSWckeotNJEY2nNlycjBO0cUdAW5Ne6zdQ2EN3b2ayRtAJ3LPjrj5FwOWOeO3FTE58Tx/9ebf+hrWQzXX2aziik1FPs0ezJ0/O4jgNjPBxU51df+Ejjf7FqH/Howx9nOfvrQwOjqvf3LWVjNcLE0pjUsEXqaq/20v/AD46h/4DNUN1qn2i1kijt9UgdhgSJbHKn1GaALWlXsl/Z+dJ9nYFsI9vJvRx69OO4x7VerA066WxE7Pa6hLLPJ5kjCzKAnAHAHsB9au/20v/AD46h/4DNQAms9dP/wCvxP5GpNQ1RbGRIzDIzOMhz8sY9i54H86y9W1dXNj/AKFfjbdoebc+hqzcXsFw+9rHU0kA2h44XU4/Dr+NAEt3qdxZ2iSOkEktxMkMCIx2hmPVm9ByeB2qzpd8dRshMyCORXeKRQcgMrFTg9xkVhypFLbtGLfUVcSpNFItlgo6nIJxgN+XT86n0+4/s9Y0SLU3jAcyK1p/rJGbcXz25J46c0AaB1OUaleWgtSxgt1nQq4JlzuG3HY5X9apyX9zd6Rq8V1brE8MDcoxZTujJxyByO/4VA08p1a5vUXUU863ECoLHOzGSGz3OWNQPdy2mg38U6X8+6Bwp+xFAvynJPqSeSTQB01r/wAekP8AuL/KpayLfWVFtEPsOocIP+XZvSpf7aX/AJ8dQ/8AAZqAGSatMNcFgkcIAxkSSFXdSMlkGMMB0Izng/jq1zdzIbq+SWSPUzAsqzLCbPO1lHG1uoBxyPr61pf20v8Az46h/wCAzUAaVZmlyiHTrmQq7BLm4O1FLMf3rdAOppf7aX/nx1D/AMBmrJ0jXrS4hvbP7HfSvHczCZBathdzsQCenQilcLo1bbUptQf/AEZIolB+YTNmQD/cHT8TUFrr7XGqLAYAtvLNLBFJv+Znj+9kY6HDY57e9V5JITIjJa6nhCCFktjIB9M8j8DVdIY4r17iKLVFAaWWFPsmRFJIPmb374B9TTA3dYv30vS57xIRMYV3FN+3I784qDUdSurO4QR2gkgzGrMXwXLttwgxyR1OccVR1O5bUtGksTFqMbyoEeb7GST6nHTmmTXN1LeQThtQURqqsv8AZ+cnPzEHPGRx3xR1A1YP+Rgvf+veD/0KWtCufh1hRrt432HUPmt4Rj7O2eGkq9/bS/8APjqH/gM1AE2qXp07T5LhU37SBznCgnG44ycDqfYU7TrmS7skmlEO5s4MMm9GGeCD6GqF5qbXFuUhg1O3k3BhItqTjBzgg9QehqLTbuPTrYxCz1B2d2kYi0KjcxycAdBQBvVm6h/yFtK/66yf+i2o/tpf+fHUP/AZqz77V1bU9Mb7FqA2yv1tzz+7agDRvdWFrci3ELlyAQ8h8uP6bz1PsM1Hd6jd2q2sIS3lu7uQpEAxVFAUsSTyTwOw7ioJ7u3ncv8AYdUjkYYLxwsCfqOh/EVTkVWhiEUOoRTwSmWGVLHG0lSpyvQ5BPp29KAN7TL9NT023vI1KrMgbaTnae4/Oqo1adpdTiSyLyWZUIquCZdwyO3FVNPul02OOCG31M20cSxpG1qeCM5bPUk5/SqweZbrUp4zqSNehQuLH/VYGAQc88UMEWL69mvPD2oi4iRJIZPKJjYsj4KnIJA9cfUGugrkr29kt/DlzBNDfSnja32MxqoyOMD/ADzW3/bS/wDPjqH/AIDNQBpVkwatLPrUtmI4VWIkMrSES4xkOFxgqTxwak/tpf8Anx1D/wABmrN8wvqSXM0epyRxSNJFG1nyhIwRu67eTxQB0lFZv9tL/wA+Oof+AzUf20v/AD46h/4DNQBDo9wLXwxbzNHLIFTO2JC7HnsB1qe0v5r9w0IgSEH5gz73x9Bwv4k1laPqUMmgW0M2n37rt5/0dsHmpfOiW5jmW21M7DnEtqXP4MfmH50AT6Vr7ajdxo0Cxw3Mby2zb8syowU7hjgnII68Gruq376dbRzJCJQ00cTDft2hmC56c4JHFYFtbrZM5tl1RCkbx22bPPkKzbm6/e5A69hVvV7ptTslgjh1G3IkSTf9jL52sGAwfcCgC7c6ndW+pxQizBt3lWIOX+ZiVyWUY6DHOafp/wDyFNV/67J/6KSs1rq4OqC6/wCJiIuAYvsHOAOQG7Ank06x1dV1HU2+xagd0ydLduP3aUAdDVDV9QOm2iygJhnCF5CQkec/MxAOB2+pFM/tpf8Anx1D/wABmqtfak9zEggi1K3dW3ZFoWDDBGCD1HP6UAalnLJPZxSzIiO65IR96/ge4qesTT72LTrGO2jstRZUzz9lI5JyeBwBz07VZ/tpf+fHUP8AwGagDlfF/wDyPOnf9g6f/wBGRUVW8SXgu/G1gwguItunTDEsZXP7yPpRQBtfDn/kXrr/ALCN1/6Naurrh/AVxfx6HdLb2Mcsf9o3XzNcbT/rW7bTXTfa9V/6BkP/AIFf/Y0AaVFZv2vVf+gZD/4Ff/Y0fa9V/wCgZD/4Ff8A2NAGlWT4h1SbTYLNLYL5t5dx2qyOMrHuz8xHfpwPUipPteq/9AyH/wACv/sahu/t19bPb3Wj28sL/eRrrIP/AI7QBQubvVvtt/pMGoQpcQ2qXcN3JCCq5LApIOmPlzkY4z6czeFNTvtailu7yRYtmIWstg3xSADcWPv1A9CD34Y2lO1u8LaHCUd1dyb5tzkdNzYycehNTQ2tzb6nPqEWiwrd3ChZZBeH5wOmRtxxQgN6is37Xqv/AEDIf/Ar/wCxo+16r/0DIf8AwK/+xoA0qKzfteq/9AyH/wACv/saPteq/wDQMh/8Cv8A7GgBdf8A+Rf1D/r3f+Rp+p3stlHGYIo5HdtuHkCY46gH730FZuuXWpnQr4PpsQUwPki66cH/AGauPPqUqFJNJgdT1DXIIP8A47QBXudUey069vXufNnt4GkFsYvKHAz0PzY6c5qfR7y5kub2zvJFmktihEqpt3B1zjHsc/hiq4t7sLJGNIj8mRCjwm8JjIPX5duKjtrG7tEUQ6aQRIJSx1BizkDaAxxyAMDB44FAFvUZdRjvofsskXllkCxbcmQFv3hY/wAIC4II70yxvLr+2pILx5gsokaBGRApVWAOCDnIBHXrmoJ7S/uL5bprF1cbRtTUWVTtORkBcf40WlndWV008OkoHIYAG9JVAx3NtG3AyeTQgL3h/wD5BCf9dJf/AEY1aVc7od1qY0pAmmxFfMl5N1/00b/ZrQ+16r/0DIf/AAK/+xoAg128vLN42ikMFttJecQ+aEbtvHUJ15H5itgHKg5ByOorBvbW81CRXm0wBgpQ7L8qGU9VOF5FXFutUVQq6XCABgAXXT/x2gDTrMsf+Q7qn/bH/wBBNL9r1X/oGQ/+BX/2NZ1ndamNa1IjTYix8rI+1dPlP+zQBqahP5MqeXcyJKRxEsXmBh6lRz+oqqddaKxnluUgikRgiZmXDMRxu/ufiegpLlb+7YGfS0ZQPufbSFP1AXn8ak8zUVgMMelQxIQR+7uguPpheKAJfD9+2p6FZ3UksUsskYMjRfdLd8fjWda6zdy6wgdk+yzXc1osQXlfLUndn3Knj3FPsbW+06OFINObbDGY0V9QZhgnPIK8njgnmkjsrmLUWvU0eMTMS3/H6doYgAsF24BIABNPqLoXrz/kP6b/ANc5v5LWlXO3V1qZ1zTydNiDBJsD7V1+7/s1ofa9V/6BkP8A4Ff/AGNIZcvGdLKdo22usbFWxnBxWP4W1K71OCV7iRpY1WPDvD5TByuXXHoMrg4796szTanPBJE+mRhXUqdt3g4PvtqrY2t5pzM1tpagtGkbbr4nIUYBOV64wM+woA36ztd/5Bn/AG3g/wDRqUn2vVf+gZD/AOBX/wBjVDWbrUzp4D6bEB58PIuv+mq/7NAG9MQIXLOYxtOXBxt96yF1SeGSMKRcwuwXzJV8jAJHIJ4br0AqZ7nVXRl/s2MZGMi7wR/47UEEV5bOXj0eEyHrI93uc/8AAiuaAEg14XHio6ek1t5Cwv8ALuBkaRWUHjPAAJ+uDVnWLu4hksbW1cRSXk5j80ru2AIzEgdz8uPxqnPa31xffa309hKImhGzUCoCt14C9enPXgU65gvbu0igl0wEREGNxfEOpAwCG25zjPPuaOgF3Rr59S0W3upVCyOpDgdMgkHHtxS6F/yANO/69o//AEEVXt31C0tUt4NJhSKNQqqLvoB/wGq+i3WpjQ7AJpsRUW8eD9qxkbR/s0Ab9c3rWq31prsVtazN+8SMxw+TuV2LkEM/8I2g9+3fpWl9r1X/AKBkP/gV/wDY1Qu7G7vrh5p9My7oqfLfkBdrblIwvBB5zR1A6Gis37Xqv/QMi/8AAr/7Gj7Xqv8A0DIf/Ar/AOxoAXSv+PnVP+vv/wBppRfXDQXH7m4k83bnyBD5gI9eOR9c1n6ZdamLjUtumxHN1z/pXQ+Wn+zU08d9dSh59KjkAxhGvTs+u3bg/jQBHf8AiGS20Oe4P2WG6y0cIeYMm4LnLEdPXb17d61tOuReabbXAdX82JWLL0JI5xWfcDULiyktTpcaROpQiO72kA+hC8Uy0j1Cy2+Vp+QkSxAPflhhc44K4zz169KAItH1m7vL63M5Qw3qTvHGq4MPluFAz3yDk+9Xm/5GiP8A682/9DWqdrZ3VldyXEGkRq77sA3pKpuO5to24GTycd6Y11qf/CRof7Ni3/ZGGPtXbev+zQB0VUdbuJrTRL24t32TRQs6Nt3YIGeneo/teq/9AyH/AMCv/sagvf7Rv7OW1m0xPKlUo2282nB9wtAD/D97cX1tPJM7SxLMUikeLy3YAAHK9sNuHQdK1qxLSO/snmaHS0HnuHcG9yC2AM/d4zgZ9as/a9V/6BkP/gV/9jQAms9dP/6/I/5Grt0yrbOzymFQOXGMr+dYerXWpk2O7TYhi7Qj/Supwf8AZq7LPqksTIdORQ3GUvMEfQ7aAGQ6ncLdQxMBNFIwXzZB5LdOyn734Adaj0vXhqWv3lsk9s1ukSNCqMC5+Zgxbn2GB/jTrdLy1JMOjW6serm6yx+pK5NQS2V7Ndz3LWDrJPEIm2aiygKDkYwvB5PI9TQBY1u/u4bq2tLKRInljlmMjru4QDjHuWH4A0+e7+3+EZbsrtM9iZNvpuTOP1qvqFtd6miLc6ShKZ2sl6VYAjBGQucEcEUmpz6jHod3GNLhSNbZ1AF0PlG09BtoA2rX/j0h/wBxf5VLWTb3eqC2ixpkWNg/5evb/dqT7Xqv/QMh/wDAr/7GgDNudVvo/FX2KKZmQvEFhMHyFSCXJfsQBkD9K6SudlsLqa8e5fTP3rSRyZF+RtZAQMfLxwSD6gmtD7Xqv/QMh/8AAr/7GgDSrO0UAWtwQACbufJA6/vGH9KT7Xqv/QMh/wDAr/7GqOkXWpi1l26bER9pnz/pXfzWz/DQBoa5fS6dpUk8AUy7kjTd0BZwoJ+mc03Rrue5S7iuWEktrcNAZAu3eMBgceuGx+FQ3Zv721kt7nSIXikGGU3f/wBjUFta3tp5Xk6bgxszkm/J3s3Ut8vzH69KAJrm9ubfXYhK8yWTusS7UQqXKkgE53de44rZrn2s7p9QF4dJTzdwfH207S4G0Nt24zjjNXvteq/9AyH/AMCv/saAHW//ACMF9/17wf8AoUtaFc/Ddan/AG7eEabFuNvDkfaunzSf7NXvteq/9AyH/wACv/saAJtVkuYrB3skLygjhQC23PJUHgnGcCm6Pctdaesj3Anbcyl/KMbDB6Mp6MOhqpd/2he25hm0tNuQwKXpUgg5BBC5HIotBqFlD5cOlx4LFmZrzczMepJK8mgDZrN1D/kLaT/11k/9FtR9r1X/AKBkP/gV/wDY1n391qZ1PTCdNiBEr7R9q6/u2/2aAL17qNzHfG2hjjCBQTL/AKxhn/pmOfxqtc304+xWtneh5byZkadkB8sKhYgLxzwOD6mppzfXKgT6NbyAdN1yDj6fLVaazvLi3EMmmkhH8yN/7QbfGcY+VtuRwSPxNAGlot+2p6Na3cihXljBYDpnoce1UPtGrJcXSl45MQu22NARE+f3YBPUleSD0x6GnW0d9ZsvkaWiIsSxLGL07FVc4wu3GeevU1VXS7nE6yac8scwYNHJqLMo3HJwMcHPehghbi6luPDWoR3LytcQSCOQSKqlT8pH3eCMEHPvXSVymox3tjoF3GmmqA53ySPeb2ZiRySV56AfhWz9r1X/AKBkP/gV/wDY0AaVYsd7djX/ACLmUwxMzCKMxZSVduQVcdGz1B7ZwO9WPteq/wDQMh/8Cv8A7GqKWd2l6boaWC28yBDfEoHIwWC7cA4/nQB0FFZv2vVf+gZD/wCBX/2NH2vVf+gZD/4Ff/Y0AV9MuWtPCsEyIjsqcK8gjBO7+8eBUlrdy3E0f2m68hiflhWPaG9txzu/CqehXOpDQ7VV02Jl2dTdDnk/7NTLDexyiSHSY4SDkiO82q31AXBoAh0TWbu+vLc3DIYr2GWaNFXHk7HC4z3yGH4g1oa1JexW6tZypEAG3MU3szY+VVXvk1mppc8RnMWlCMzArlNQZdgJ3EJgfLk8nFTX8Goah5RksXjMWdph1AoeRg9Fo6B1Fe+voNStTeGSKCTy42WNEZPMYdCSd2M8ZHtVzT/+Qpqv/XZP/RSVnDT7gXiXP9kqXQq2DfEqWUbQxG3kgcZNLYXWpjUdTI02IkzJkfaun7tP9mgDoaoaxNdQWataLITvAkMSB3VOclVPU5xx6Z60z7Xqv/QMh/8AAr/7Gq96uoX0aLLpqqUbejR3xRlOCMghfQmgC/pk5udOglM6Tll/1qIUDf8AAT0PtVusi2bULO3WGHSogi9M3eSSTkknbySal+16r/0DIf8AwK/+xoA5Xxf/AMjzp3/YOn/9GR0VW8Sy3UvjawN1bJARp02Asu/P7yP2GKKANn4dZ/4R26x1/tG7/wDRrU3Qbs32lQ3t5qFwuq+axmtVlxtYMf3Pl9AMDHTJ655rn7Ia9oX2q10/VrRbc3UsoWSx3EFnJPO8etTDUfEwmMo1TTRIRgv/AGZyR9fMoAlk8SXeu2dpvvLCGCe9hRkik3PhlYtG4DDBBA7gnuB3t23ibUH07Fk1kD9jWaISBj5ThwnkOS2Sx6A9cg8Gs03viNvvajpZ+bdzpff1/wBZ1pft/iT5v+JnpnzNub/iWdT6/wCs60AWLzxPd3M2mvDe2kEs2fMwp3wYniVo2XfjIBwT7HGAadB4wubebUFEum+Xb3IyAzEvuuDGeS3HGD6e2Kp/a/EIYt/aGlbj1P8AZfJ/8iUn2rxBkn7fpWT1/wCJUOf/ACJQgZ2Gqa3NYa5a2qojQTKOg3MWJOARkEA44OCM9cVkQeLrm7sbSe1vtKc3VxDCUw263Lhsow3feBA9CeeBWWdT8Ts6udV04sv3SdN5H0/eUw33iQ9dS0w/Nv8A+QZ/F6/6zr70AXj46vU85pP7OREk8iTMoD2z7yu6RSeFOOrY5I6jmp7PxhfPdwR3UulndcwQMsDlwwkQnIbPqBjjp+dZZ1HxKxfOp6afM4fOmfe+v7zmm/bPEW7d/aOl7uDn+y+eOn/LShAdB4g1660bWZ3+0R/ZktImETqAFLSlGctnoowT2+nWoIPFGoT+XC72W6aF/LmtSJkLhXIPDccKD0I6jdWU2p+J3OX1XTmOCvOm54PUf6ykXUfEylSuqaaCg2qRpnQeg/eUdA6nTC4kuvh95886zyyWG55FGNxKc9zXRV5ncXviWexltm1awWKRChC6djgjt+8qf+2PFX/QYsP/AAXH/wCOUMEei1zssktv4gWKWe4NvdXI8v8AeMAkipkp/usOcdMqfWuc/tjxV/0GLD/wXH/45US33iNGZk1LS1Zn3sRpmCWxjJ/edcd6A6HpVFedf2x4q/6DFh/4Lj/8co/tjxV/0GLD/wAFx/8AjlAHZ+H/APkEJ/10l/8ARjVpV5paX/ie0txFFrFjtDM3On9yST/y09TU39seKv8AoMWH/guP/wAcoA6bxHNLZuLxZplgjgZZ0RyBsYgbxjoVODkc4zW5Eu2FFyThQMk5J/HvXnD3/iSSUyPqWmNIUKbzpmTtPVc+Z09qlGr+KgMDWLD/AMFx/wDjlAHotZlj/wAh3VP+2P8A6Ca43+2PFX/QYsP/AAXH/wCOVDFf+J4rqeZdYsd823d/xL/QYH/LSgD0usjxI0i6bH5Jl3m5hXbFKYywLgEbgRjINcj/AGx4q/6DFh/4Lj/8cqOe/wDElyqrcanpkqqwYB9M3AMOh5k6igDu9IhuoNPVL1i0m5iAX3lFJJVS38RAwM1erzr+2PFX/QYsP/Bcf/jlH9seKv8AoMWH/guP/wAcoA7O8/5D+m/9c5v5LWlXmkl/4nku4Z21ix3xBgv/ABL+OcZ/5ae1Tf2x4q/6DFh/4Lj/APHKAO+vs/YLjDMp8tsFTgjjsayPC8d99kWe6aUQywRFElnMzFsZZ8noDkcZ7dq5Z9U8USxskmrac6MMMrabkEehHmUkWp+J4Ilih1XTo40G1UTTcBR6AeZQB6RWdrv/ACDP+28H/o1K4v8AtjxV/wBBiw/8Fx/+OVDdah4nuofLk1ix271bjT+6sGH/AC09QKAPS6K86/tjxV/0GLD/AMFx/wDjlH9seKv+gxYf+C4//HKAOg0qO/l1y4kWSYW0V3KrtJcF1dccIqHOME5zx0966WvNob/xJb7/ACNS0yLzGLvs0zbuY9ScScn3qT+2PFX/AEGLD/wXH/45QB6I33T9Ko6F/wAgDTv+vaP/ANBFcT/a/ir/AKDFh/4Lj/8AHKitdR8UWtpDBFrFjsiRUXOnnOAMD/lpQB6VXNavHf3HiAw2Ekyv9mR1YXBSOI7z8xTo3A6Yrn/7Y8Vf9Biw/wDBcf8A45UYv/EguTcDUtME5XYZf7M+Yr1xnzM49qAPSaK86/tjxV/0GLD/AMFx/wDjlH9seKv+gxYf+C4//HKAO00r/j51T/r7/wDaaVo15pBqHieB52TWLHM0nmNnT++0D/np6AVN/bHir/oMWH/guP8A8coA6vxGZcaesAnZnudpjinMJcbHOCwI9Afwq/pcVzBpsEd9IJLhVw7Zzk/Xv9e9cDLf+JJ2jabUtMkaJt0ZfTMlD6j95wak/tjxV/0GLD/wXH/45QB6LWY3/I0R/wDXm3/oa1xv9seKv+gxYf8AguP/AMcqE3/ic3wuf7YsfMEZj/5B/GCQf+entQB6XWd4gd4/D1+8TujrA7KyMVYEDIwR0ri/7Y8Vf9Biw/8ABcf/AI5TJtR8TXMLRT6ppssTjDI+mblYe4MlAHa6JBeQxzm73rG7gwxSTGVkGBnLHrk5OOcVp15yureKVUKur6eFAwANO4H/AJEpf7Y8Vf8AQYsP/Bcf/jlAI7LWeun/APX5H/I1p15pc3/ie4MPmaxY/upBIuNP7j/tp71N/bHir/oMWH/guP8A8coA9Frm/Dkd/Jcee7zfZgZkYy3Bl80iQhSFOduACPfNc9/bHir/AKDFh/4Lj/8AHKjgv/ElrF5dvqemQx5J2x6ZtGTyTgSUAek1S1n/AJAl/wD9e8n/AKCa4f8AtjxV/wBBiw/8Fx/+OVHc6l4oubWWGTWLHZIhRsaec4Iwf+WlAHolr/x6Q/7i/wAqlrzhNW8VJGqjWLDCgAf8S4//ABynf2x4q/6DFh/4Lj/8coA6CaO/n8UXC2skwSNoHLm5IjRedw8vocgY6d810tebJf8AiSOeSZNS0xZZcb5F0zDPjpk+ZzipP7Y8Vf8AQYsP/Bcf/jlAHotZ+i/8ek//AF93H/o1q4r+2PFX/QYsP/Bcf/jlRW2oeJ7aNkj1ixw0juc6d3Zix/5aepoA9KrD8RSy2nl3kUkwjgjkaeONiA8fAY4Hdc7gevB9a5b+2PFX/QYsP/Bcf/jlRvqHiSSUSvqemNIqlQ50zJAPUZ8zoaAPQrIAWMGHZx5a4ZmLE8dcnrU9ecrq3ilVCrq+ngAYAGndP/IlL/bHir/oMWH/AILj/wDHKAO1t/8AkYL7/r3g/wDQpa0K81XUPE63cs41ix8yRFRv+JdxhSxH/LT/AGjUv9seKv8AoMWH/guP/wAcoA7bWYpZtOKW87wTF02SIxGG3DGfUeo9Kj0C6F7YPcfvQzzPvSRyxjYHDLz0AIIwOK4qXUfEtwoWbVNNkUMGAfTMgEdD/rOtOXVfFCZ2atp65OTjTcZPr/rKAPRqzdQ/5C2k/wDXWT/0W1cZ/bHir/oMWH/guP8A8cqGa/8AE808Er6xY7oWLJjT+5Uj/np6GgD0uo5uYJOSPlPQ4PT1rz7+2PFX/QYsP/Bcf/jlI+q+KZEKPq+nsrDBB03II/7+UAdP4fllN1La3U00k9rCi7nckSI2Sr46E44J65U1v15tFqPiWEKItT02MKoQBdMxhR0H+s6VJ/bHir/oMWH/AILj/wDHKAOy8Rf8gK6+g/8AQhWnXml5f+J7u1eCXWLHY4wcafz1/wCulTf2x4q/6DFh/wCC4/8AxygD0WudSWSHxClvNPO0NzcNJDmRsKyqd0fX7uMMAeODXOf2x4q/6DFh/wCC4/8AxyokvvEcRJj1LTEJcyErpmMseC3+s6+9AdD0qivOv7Y8Vf8AQYsP/Bcf/jlH9seKv+gxYf8AguP/AMcoA7Pw7/yAbT/c/qa0q80s7/xPaWscEWsWOxBgZ0/n/wBGVN/bHir/AKDFh/4Lj/8AHKAOk8RTS2dwboTzrbCERTokhAUM2BIMdCDjJHYn0rfUbVA54GOTmvN2vvEbytI+paY0jLsZjpmSV9CfM6e1S/2x4q/6DFh/4Lj/APHKAPRaztP/AOQpqv8A12T/ANFJXF/2x4q/6DFh/wCC4/8AxyoYdQ8TwzzyJrFjumYM+dP7hQP+enoBQB6XWZriXDW0LWcjrPHKHRVbAkwCdjeoOMfrXG/2x4q/6DFh/wCC4/8AxymSaj4lmZGl1TTXMbbkLaZnafUfvODQB3Ghzx3WkQXELyPHNl1MjFmwSeDnnjpitCvOU1XxRGu1NW09V9BpuB/6Mpf7Y8Vf9Biw/wDBcf8A45QBZ8X/API86d/2Dp//AEZHRVK1sdU1nX0vNU1KCVobV4kEVp5eAzITn5zn7tFAH//Z\" alt=\"image\"\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2. The results of CPM and Ery:\u0026nbsp;\u003c/strong\u003eMIC (minimum inhibitory concentration) , MBC (minimum bactericidal concentration) and synergistic effect in eight SA strains: CPM:Caulis Polygoni Multiflori; Ery: erythromycin; FIC:fractional inhibitory concentration index; FBC:fractional bactericidal concentration index. 1-7 represent clinical isolates and 8 represents ATCC25923.\u003c/p\u003e\n \u003cp\u003e\u003cimg width=\"343\" height=\"219\" 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\" alt=\"image\"\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eTime kill assay\u003c/h2\u003e\n \u003cp\u003eIn this experiment, bacterial counts were determined by real-time PCR rather than by plating on nutrient agar. As shown in the results(Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e), a slight increase in the growth curve was observed at 1/2\u0026times;MIC, indicating that bacterial proliferative capacity was restored when the drug concentration fell below the MIC level. This sub-inhibitory concentration environment was insufficient to control the infection and may instead facilitate bacterial survival and regrowth. At 1\u0026times;MIC, the bacterial growth curve plateaued, representing a critical pharmacological threshold. This indicates that the CPM concentration achieved a net inhibitory effect on the bacterial population, effectively preventing the majority of bacteria from dividing and growing, though without substantially reducing the total viable count. This pattern provides strong evidence that CPM acted as a typical time-dependent antibacterial agent. The marked decline in the curve at 2\u0026times;MIC clearly demonstrates that CPM not only inhibits bacterial growth but also exerts potent direct bactericidal activity. When the concentration was merely doubled, the effect shifted from \u0026quot;inhibition\u0026quot; to \u0026quot;rapid killing,\u0026quot; indicating a steep concentration-effect relationship beyond the MIC. These results strongly suggested that in clinical applications, it was essential not only to maintain T\u0026thinsp;\u0026gt;\u0026thinsp;MIC but also to consider increasing the dosing frequency or prolonging intravenous infusion duration to ensure rapid and effective pathogen clearance.\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003eCPM could inhibit Fibrinogen-Binding\u003c/h2\u003e\n \u003cp\u003eThe 96-well plates were pre-coated with rabbit fibrinogen, followed by the addition of bacterial suspensions and incubation at 35℃ for 2 hours. After removing non-adherent cells by washing, the quantity of bacteria attached to fibrinogen was assessed by crystal violet staining. As expected, CPM inhibited bacterial binding to fibrinogen in a dose-dependent manner(Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The inhibition rates ranged from 60.7% to 82.23% in the 2\u0026times;MIC group, from 23.15% to 49.14% in the 1\u0026times;MIC group, and from 1.81% to 23.20% in the 1/2\u0026times;MIC group. Since bacterial adhesion represents the initial step in the formation of infectious foci and subsequent biofilms, these results demonstrated that CPM effectively blocked this critical process in a concentration-dependent manner. This suggests that CPM can disarm bacteria by preventing their attachment to host tissues or medical device surfaces, thereby suppressing the development of infections at their origin.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003eCPM inhibited bacterial aggregation and reduced the diameter of bacterial particles\u003c/h2\u003e\n \u003cp\u003eOvernight bacterial cultures were adjusted to 1.0 McFarland turbidity and co-incubated with different concentrations of CPM. In the 1\u0026times;MIC and 2\u0026times;MIC groups, the bacterial suspensions became visibly clearer to the naked eye, with higher drug concentrations resulting in greater clarity. These observations were consistent with the spectrophotometric measurements(Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA and B). Unexpectedly, although the turbidity of the 1/2\u0026times;MIC group showed no obvious visual difference from the control group, its OD600 values were higher than those of the control, a result contrary to expectations. This discrepancy may be attributed to the failure of the drug to effectively induce bacterial aggregation at this concentration, combined with potential background interference. Surprisingly, particle size analysis revealed a significant reduction in bacterial particle diameter following CPM treatment(Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eC). Higher drug concentrations resulted in smaller particle sizes. At 2\u0026times;MIC, no bacterial particles were detected in the supernatants, likely because the particle count fell below the instrument\u0026apos;s detection limit. This absence may be explained by extensive bacterial aggregation and subsequent precipitation at the bottom of the tube under high drug concentrations.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003eCPM inhibited biofilm formation\u003c/h2\u003e\n \u003cp\u003eIn this experiment, three concentrations of CPM were selected. The crystal violet staining method was employed to quantify total biofilm biomass by binding to extracellular polysaccharides, proteins, and nucleic acids within the biofilm matrix. The results demonstrated a dose-dependent lightening of color: lower concentrations corresponded to lower inhibition rates. The inhibition rates ranged from 57.95% to 78.45% in the 2\u0026times;MIC group, from 30.12% to 54.54% in the 1\u0026times;MIC group, and from 17.36% to 31.68% in the 1/2\u0026times;MIC group(Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). These findings clearly illustrated the inhibitory effect of the drug on biofilm formation: at low concentrations, the drug likely interfered with initial bacterial adhesion; as the concentration increased, it further suppressed the secretion of extracellular polymeric substances and the maturation of microcolonies. Finally, at high concentrations, it nearly completely impeded the structural development of biofilms. As expected, the inhibition rates were not correlated with the intrinsic drug susceptibility of the bacteria. This suggests that the drug not only exhibited conventional bactericidal activity against planktonic bacteria but also possessed a crucial capacity to disrupt the collective lifestyle of bacterial communities. Most importantly, no significant difference was observed in the inhibitory effect of the same CPM concentration on biofilm formation across different bacterial strains.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n \u003ch2\u003eCPM could not destroy biofilm\u003c/h2\u003e\n \u003cp\u003eIn the biofilm disruption assay, after pre-formed biofilms were co-incubated with CPM at concentrations ranging from 1/2\u0026times;MIC to 2\u0026times;MIC, no significant reduction in biofilm biomass was observed compared with the control group(Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). A slight increase in staining was even detected in some cases, possibly due to nonspecific binding of the drug to the biofilm matrix. The data indicated that CPM did not exhibit a significant disruptive effect on pre-established biofilms, which represented a notable finding. It is likely that the drug only inhibited the growth of metabolically active bacteria in the outer layer of the biofilm, without effectively killing the internal persister cells or degrading the extracellular polymeric matrix. Consequently, no significant change was observed in the total biomass as measured by crystal violet staining. These results clearly demonstrated that the conventional drug susceptibility concentration (MIC) determined for planktonic bacteria is often inadequate against mature biofilms, underscoring the considerable challenge in treating biofilm-associated infections.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\n \u003ch2\u003eSynergistic effect between CPM and Ery\u003c/h2\u003e\n \u003cp\u003eIn these experiments, the double-disk synergy test was employed to evaluate the synergistic effects between CPM and commonly used clinical antibiotics, including penicillin, erythromycin, clindamycin, and compound sulfamethoxazole. Since the active components of Chinese herbal medicine are mostly large molecules such as polysaccharides(\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e), alkaloids(\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e), and flavonoids(\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e), their ability to diffuse in agar medium is relatively limited. Therefore, when performing synergy testing, the distance between the two drug disks was appropriately reduced. CPM exhibited varying degrees of synergy with three of the antibiotics P, Eyr, and DA but not with SXT, and the effects were not observed in all strains. The highest synergy rate was 50% (4/8) between CPM and Ery. Synergy between CPM and P was detected in two strains, and between CPM and DA in one strain(Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e). Subsequently, the synergistic interaction between Ery and CPM was confirmed using the checkerboard dilution method. Surprisingly, CPM and Ery showed synergistic or additive effects in all 8 tested strains. All fractional bactericidal concentrations (FBCs) and fractional inhibitory concentrations (FICs) were below 0.5, except for the FIC of strain ATCC25923(Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The discrepancy between the results of the two methods may be attributed to the inadequate diffusion of active components in the agar medium.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eSA is one of the most common pathogens in clinical infections, causing conditions ranging from respiratory tract and superficial skin infections to more invasive diseases such as cellulitis, folliculitis, and subcutaneous abscesses(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), MRSA in particular, exhibits resistance to multiple antibiotics and poses a major challenge in clinical practice(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). According to the most recent data from the Chinese Bacterial Resistance Surveillance Network, the detection rate of MRSA was as high as 28.7%(\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Some MRSA strains have been reported to exhibit resistance to vancomycin and other last-resort antibiotics(\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e).These findings indicate that SA infection has become a serious public health threat and a global problem complicating anti-infective therapy(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). The World Health Organization has listed MRSA as a high-priority pathogen requiring the development of new antibiotics(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). In recent years, there has been growing interest in exploring novel antibacterial agents or combination therapies as alternatives to conventional antibiotics(\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). Concurrently, research on the antibacterial properties of traditional Chinese medicine has increased. For example, crude ragweed extract(\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e), and myricetin(\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e)have been reported to act as effective inhibitors of SA infection. The antibacterial mechanisms include inhibition of SA alpha-hemolysin(\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e), and alteration of bacterial surface hydrophobicity(\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e), etc.\u003c/p\u003e\u003cp\u003eCPM has been reported to exhibit antibacterial activity(\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e), however, over the past decade, no further studies have addressed its antibacterial properties or underlying mechanisms. Therefore, this study conducted a preliminary investigation into the antibacterial activity and mechanism of the water extract of CPM. Clinical isolates along with the standard strain ATCC25923 were selected for the experiments. The results demonstrated that CPM exhibited substantial inhibitory activity against all eight bacterial strains, with MIC values ranging from 1562.5 to 3125 \u0026micro;g/mL and MBC values from 3125 to 6250 \u0026micro;g/mL. The antibacterial activity showed no significant correlation with bacterial resistance profiles, indicating that CPM possesses consistent antibacterial activity against SA. The time-kill curve assay is a powerful phenotypic method that transforms the static activity of antibiotics into a dynamic process(\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). Its major value lies in dynamically and quantitatively assessing the rate and extent of killing of a specific pathogen by an antibiotic over a defined period. In this experiment, SA load was quantified using both real-time PCR (for bacterial DNA copies) and culture-based enumeration on nutrient agar plates. These data were used to generate standard curves. The results showed that, compared with the control group, both the 1/2\u0026times;MIC and 1\u0026times;MIC concentrations significantly inhibited bacterial proliferation. However, the difference between the proliferation curves of these two treatment groups was less pronounced than expected. In the 2\u0026times;MIC group, no viable bacteria were detected after 2 hours of exposure, and no regrowth was observed within 24 hours, indicating a strong bactericidal effect at this concentration. These findings further confirmed the efficacy of CPM against both standard and clinical isolates of SA.\u003c/p\u003e\u003cp\u003eAt infection sites, microorganisms typically exist in two phenotypic states: planktonic (free-living) and biofilm (sessile/attached/aggregated)(\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e). Planktonic microorganisms can attach to suitable surfaces and develop into biofilm aggregates. Within biofilms, microorganisms adapt to enhance their survival under specific environmental conditions(\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e). The densely packed polymeric matrix acts as a physical barrier, impairing wound healing and prolonging the inflammatory phase(\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e), Meanwhile, biofilm-embedded microorganisms enhance their tolerance to antibiotics and host immune defenses through mechanisms such as plasmid-mediated sharing of resistance genes(\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFibrin is a major component of blood clots and wound healing matrices. By adhering to fibrin, bacteria achieve initial colonization the \"first step\" in establishing infection foci and subsequent biofilm formation. The results of this experiment demonstrated that CPM dose-dependently inhibited this binding process, thereby preventing bacterial anchoring to host tissues and blocking the formation of infection foci at their origin. This reflects an anti-virulence strategy: even without directly killing the bacteria, reducing their pathogenicity may assist the host in clearing the infection.\u003c/p\u003e\u003cp\u003eThe bacterial aggregation constitutes the initial key step in biofilm formation. Thus, the core significance of aggregation inhibition assays lies in directly evaluating a drug\u0026rsquo;s ability to interfere with this critical pathogenic process, beyond mere bactericidal activity. A drug that inhibits aggregation holds potential to prevent early biofilm formation, offering considerable promise for preventing medical device-related infections and certain chronic infections caused by SA. In this study, we found that compared with the control group, CPM significantly promoted the aggregation of SA, particularly at 2\u0026times;MIC, where the aggregation rate reached 76.69%\u0026ndash;95.07%. Surprisingly, no significant aggregation was observed in the 1/2\u0026times;MIC group, and the OD value was higher than that of the control. However, visual inspection revealed no marked difference in turbidity between this group and the control. This may indicate that at this concentration, CPM did not effectively inhibit bacterial proliferation but instead increased the detection background. Unexpectedly, after co-incubation with CPM, bacterial particle size decreased significantly, with higher CPM concentrations leading to smaller particles. As is well known, SA typically exists as grape-like clusters during growth. The addition of CPM appeared to disperse bacterial cells prior to reducing their size. Subsequent staining with DMAO/PI (Beyotime, China) showed that CPM treated cells were poorly stained by both DMAO and PI (data not shown), suggesting that the reduction in particle size was not solely due to improved dispersion. Instead, CPM may have altered the cell wall or membrane structure, leading to bacterial contraction or transformation from regular rod/spherical shapes into smaller, denser, irregular forms. However, further experimental validation is required to confirm this hypothesis.\u003c/p\u003e\u003cp\u003eThe extracellular polymeric substance (EPS) of biofilms functions as a robust \"fortress\" that effectively limits antibiotic penetration. To evaluate whether CPM can inhibit biofilm formation, we employed crystal violet staining. This method quantifies total biofilm biomass by binding to extracellular polysaccharides, proteins, and nucleic acids within the biofilm matrix. A darker color in the well indicates greater biofilm accumulation, while lighter staining reflects reduced biofilm formation. The dose-dependent decrease in color intensity observed in our results clearly illustrated the inhibitory process of CPM on biofilm development: at lower concentrations, the drug likely interfered with initial bacterial adhesion; with increasing concentration, it further suppressed the secretion of extracellular polymers and the maturation of microcolonies; at high concentrations, it substantially blocked the structural development of most biofilms. These findings indicated that CPM not only exhibited conventional bactericidal activity against planktonic bacteria but also interfered with the collective survival mode of bacteria. CPM dose-dependently inhibited biofilm formation, suggesting its potential to inhibit the protective barrier of bacteria and thereby expose them to attacks from both the drug and the host immune system. This provides new therapeutic strategies and drug candidates for addressing stubborn biofilm-associated infections. It should be noted that crystal violet staining is an endpoint total biomass assay that cannot distinguish whether the drug directly kills adherent bacteria or merely inhibits EPS production without affecting bacterial viability. Therefore, a comprehensive evaluation of the anti-biofilm mechanism of CPM requires integration with additional experimental approaches. Once a biofilm is established, it can enhance the tolerance of SA to antibiotics(\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e). We therefore evaluated whether CPM could disrupt pre-formed biofilms. Unfortunately, even at 2\u0026times;MIC, CPM showed no disruptive effect on mature biofilms. This is likely because the active components in traditional Chinese medicine are mostly large molecules with limited penetration into the deep layers of biofilms. Thus, even when the nominal concentration reached 2\u0026times;MIC, the actual drug concentration inside the biofilm may have been far below the minimum biofilm eradication concentration (MBEC), insufficient to induce a qualitative disruptive effect.\u003c/p\u003e\u003cp\u003eAs combination therapy is a common clinical strategy for drug-resistant bacterial infections, we also assessed whether CPM could synergize with conventional antibiotics. Observation of inhibition zone morphology revealed that CPM and Ery showed clear synergy in four SA strains, whereas no significant synergy was observed between CPM and SXT in any of the eight strains. In the checkerboard dilution assay, we unexpectedly found that CPM and Ery exhibited varying degrees of synergistic or additive effects across all eight strains. This discrepancy may be attributed to the limited diffusion of active components from CPM in solid media. Nevertheless, this does not preclude the potential of developing CPM and Ery as a topical combination for treating wound infections caused by SA.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, CPM exhibited potent inhibitory and bactericidal activity against SA, including MRSA. It effectively inhibited biofilm formation by blocking the binding of SA to fibrin and promoting bacterial aggregation. However, CPM did not disrupt pre-formed biofilms. Notably, CPM demonstrated strong synergy with erythromycin, particularly in broth dilution assays, highlighting its potential as a promising topical agent for the treatment of MRSA-related skin and wound infections. However, the specific molecular mechanisms underlying its anti-staphylococcal activity and synergistic effects with erythromycin require further investigation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eThe determination of bacterial particle size was assisted by Professor Yao Shujuan from Liaocheng University, and we would like to express our sincere gratitude.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYinguang\u003c/strong\u003e \u003cstrong\u003eCao\u0026nbsp;\u003c/strong\u003eis responsible for experimental design,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eZhihui\u003c/strong\u003e \u003cstrong\u003eLi\u0026nbsp;\u003c/strong\u003eand \u003cstrong\u003eWenlong\u003c/strong\u003e \u003cstrong\u003eWang\u0026nbsp;\u003c/strong\u003eare responsible for\u0026nbsp;experimental design and biofilm related experiments,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYan\u003c/strong\u003e \u003cstrong\u003eWang\u0026nbsp;\u003c/strong\u003eand \u003cstrong\u003eZhiqing\u003c/strong\u003e \u003cstrong\u003eYou\u0026nbsp;\u003c/strong\u003eare responsible for isolation, collection, preservation, and activation of bacterial strains,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMin\u003c/strong\u003e \u003cstrong\u003eFeng\u0026nbsp;\u003c/strong\u003eand \u003cstrong\u003eJuanjuan\u003c/strong\u003e \u003cstrong\u003eFu\u0026nbsp;\u003c/strong\u003eare responsible for preparation of CPM and synergism assay.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u0026nbsp;\u003c/strong\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eShandong Provincial Natural Science Foundation (ZR2017MH099).\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTouaitia, R. et al. 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Health\u003c/em\u003e. \u003cb\u003e18\u003c/b\u003e, 7602 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePictures.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Caulis Polygoni Multiflori, antibacterial activity, synergistic effect, MRSA","lastPublishedDoi":"10.21203/rs.3.rs-8026576/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8026576/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eStaphylococcus aureus(SA), particularly methicillin-resistant staphylococcus aureus (MRSA), represents a major clinical challenge due to its ability to form biofilms, which contribute to treatment failure and recurrent infections. This study evaluated the antibacterial and anti-biofilm activity of the water extract of Caulis Polygoni Multiflori (CPM) against clinical and standard strains of SA. CPM exhibited consistent bacteriostatic and bactericidal effects, with time-kill assays confirming rapid elimination of planktonic bacteria at 2\u0026times;MIC. Mechanistically, CPM dose-dependently inhibited bacterial adhesion to fibrin and suppressed biofilm formation, though it did not disrupt pre-formed biofilms, likely due to poor penetration into the biofilm matrix. In combination studies, CPM showed clear synergistic or additive effects with erythromycin in broth microdilution assays, but not in disk diffusion tests, possibly reflecting limited diffusion of CPM components in solid media. Importantly, CPM's activity was independent of bacterial resistance profiles. These findings indicate that CPM acts through both direct bactericidal activity and anti-virulence mechanisms, and represents a promising candidate for topical combination therapy against MRSA skin and wound infections. Further studies are needed to elucidate its molecular mechanisms.\u003c/p\u003e","manuscriptTitle":"Bi-functional Caulis polygoni multiflori inhibits Staphylococcus aureus and potentiates the activity of erythromycin in vitro","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-26 08:08:04","doi":"10.21203/rs.3.rs-8026576/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-01T11:22:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-29T16:08:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-29T12:43:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-28T11:57:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-27T06:47:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"118577688331551037884334226777837055944","date":"2025-11-24T06:36:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"141355086047644746867303527797014335663","date":"2025-11-23T06:31:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"201475691338523814365599617729486296981","date":"2025-11-20T11:10:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"264948150064550623512953672626633938834","date":"2025-11-20T06:02:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"321297314426784493615976055840344985785","date":"2025-11-20T04:44:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"108815447373532667013086038414030230266","date":"2025-11-20T00:49:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"286415330104963176317363378252665270455","date":"2025-11-18T08:36:10+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-18T00:40:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-18T00:36:28+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-12T06:18:40+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-09T02:21:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-11-09T02:17:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d3ccd9b9-77e3-4977-a523-c8814c84e96b","owner":[],"postedDate":"November 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":58487137,"name":"Biological sciences/Biotechnology"},{"id":58487138,"name":"Biological sciences/Microbiology"}],"tags":[],"updatedAt":"2026-02-16T16:00:33+00:00","versionOfRecord":{"articleIdentity":"rs-8026576","link":"https://doi.org/10.1038/s41598-026-40228-9","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-02-15 15:57:16","publishedOnDateReadable":"February 15th, 2026"},"versionCreatedAt":"2025-11-26 08:08:04","video":"","vorDoi":"10.1038/s41598-026-40228-9","vorDoiUrl":"https://doi.org/10.1038/s41598-026-40228-9","workflowStages":[]},"version":"v1","identity":"rs-8026576","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8026576","identity":"rs-8026576","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}