Biliary Elimination of Cholesterol Can Be Modulated by Hepatocyte Mitochondrial Aquaporin-8 in Mice

Biliary Elimination of Cholesterol Can Be Modulated by Hepatocyte Mitochondrial Aquaporin-8 in Mice | 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 Biliary Elimination of Cholesterol Can Be Modulated by Hepatocyte Mitochondrial Aquaporin-8 in Mice María Celeste Capitani, Alejo M. Capiglioni, Raúl A. Marinelli, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8058626/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Feb, 2026 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Sterol regulatory element-binding protein (SREBP) transcription factors directly or indirectly regulate key genes involved in hepatic cholesterol homeostasis, including biliary elimination. The ATP-binding cassette transporter G5 (ABCG5), located in hepatocyte canalicular plasma membranes, strongly controls the excretion of unesterified cholesterol into bile. Recently, we demonstrated in cultured hepatocytes that mitochondrial aquaporin-8 (mtAQP8), a channel protein capable of conducting H 2 O 2 , is involved in SREBP-controlled cholesterol synthesis. In this study, we evaluated whether hepatic mtAQP8 participates in modulating the biliary elimination of cholesterol. Using C57BL/6 mice, we found that adenovirus-induced mtAQP8 knockdown significantly downregulated the expression of SREBP-2 and, through liver X receptors (LXR), that of ABCG5, which in turn decreased biliary cholesterol excretion. In contrast, mice with adenovirus-mediated mtAQP8 overexpression significantly increased the expressions of SREBP-2, LXR, and ABCG5 and, consequently, the biliary excretion of cholesterol. A mitochondrial-targeted antioxidant, which has been shown to quench mitochondrial H 2 O 2 release, did not affect mtAQP8 expression, but prevented upregulation of SREBP-2, ABCG5, and biliary cholesterol excretion. Our data further support the involvement of mtAQP8 in hepatic cholesterol metabolism, suggesting that it modulates biliary cholesterol elimination through ABCG5 gene expression. Biological sciences/Cell biology Health sciences/Diseases Health sciences/Gastroenterology Biological sciences/Molecular biology Biological sciences/Physiology Biliary cholesterol excretion mitochondrial aquaporin-8 ABCG5 adenovirus hydrogen peroxide Full Text Additional Declarations No competing interests reported. Supplementary Files SUPPLEMENTARYDATA.pdf Cite Share Download PDF Status: Published Journal Publication published 06 Feb, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 15 Dec, 2025 Reviews received at journal 15 Dec, 2025 Reviews received at journal 15 Dec, 2025 Reviewers agreed at journal 06 Dec, 2025 Reviewers agreed at journal 26 Nov, 2025 Reviewers invited by journal 25 Nov, 2025 Editor assigned by journal 25 Nov, 2025 Editor invited by journal 20 Nov, 2025 Submission checks completed at journal 19 Nov, 2025 First submitted to journal 19 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8058626","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":552960437,"identity":"a6d9b91a-0c09-48f4-bf82-00a284941004","order_by":0,"name":"María Celeste Capitani","email":"","orcid":"","institution":"Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario","correspondingAuthor":false,"prefix":"","firstName":"María","middleName":"Celeste","lastName":"Capitani","suffix":""},{"id":552960438,"identity":"ae8ec1dd-cf8e-4ad5-ac46-4dee7f6b3542","order_by":1,"name":"Alejo M. Capiglioni","email":"","orcid":"","institution":"Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario","correspondingAuthor":false,"prefix":"","firstName":"Alejo","middleName":"M.","lastName":"Capiglioni","suffix":""},{"id":552960439,"identity":"d6dd15d3-b889-410f-b3df-26d24b1f7fea","order_by":2,"name":"Raúl A. Marinelli","email":"","orcid":"","institution":"Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario","correspondingAuthor":false,"prefix":"","firstName":"Raúl","middleName":"A.","lastName":"Marinelli","suffix":""},{"id":552960440,"identity":"27fd748b-a5bb-477e-9c61-091a7eb932b0","order_by":3,"name":"Julieta Marrone","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFUlEQVRIiWNgGAWjYBADOTbmgw0QJjORWozZ2BKRtBwgQktiA1sCEhefFt32s88+fNxhk97Hxtz84QODnZw5O/PDxx8YauUMDjA/+4BFi9mZdOOZM8+k5baxMbZJzmBINrZsZjM2OMBwHEiwGc/ApuVAGjMzb9vh3Db5xjZm3n8HEjcc5mGTOMBwLHFmA4MxNoeZnX8G0vI/nY2NsfnzHwawFvYfEC3sn7FquQG25UACUEuDNANECxvQ+zWJ/Qw82G258YyZcWZbsiHYLz1AvxgcZjOWOGNwwJifmacYu8PSmBk+ttnJy7exP/7wAxhiBucPP/xQUVEnx8bevhlXQGMDBoeJTwYwUEei+lEwCkbBKBjGAAAcvFtz2/GJ/gAAAABJRU5ErkJggg==","orcid":"","institution":"Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario","correspondingAuthor":true,"prefix":"","firstName":"Julieta","middleName":"","lastName":"Marrone","suffix":""}],"badges":[],"createdAt":"2025-11-07 15:53:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8058626/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8058626/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-026-39058-6","type":"published","date":"2026-02-06T15:58:31+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":97248687,"identity":"856a6a0a-1916-4994-adaf-950fba61b844","added_by":"auto","created_at":"2025-12-02 13:05:24","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":936499,"visible":true,"origin":"","legend":"","description":"","filename":"paperFINAL2.docx","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/71f5bdacc2672f22210a7c41.docx"},{"id":97248365,"identity":"19fca880-0ff3-40de-894a-6573c2f5c913","added_by":"auto","created_at":"2025-12-02 12:55:25","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":5990,"visible":true,"origin":"","legend":"","description":"","filename":"e5ac03479f124f0faf298aac75709ec4.json","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/89941eec09b59950d7cefcf7.json"},{"id":97158387,"identity":"ec4f6804-16de-43e9-987e-92812f465e68","added_by":"auto","created_at":"2025-12-01 11:56:15","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":866778,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPLEMENTARYDATA.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/cadd0e79c7dfd17da026da74.pdf"},{"id":97158377,"identity":"c55ed607-49c2-48f8-bf65-03634891cf47","added_by":"auto","created_at":"2025-12-01 11:56:15","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":122914,"visible":true,"origin":"","legend":"","description":"","filename":"e5ac03479f124f0faf298aac75709ec41enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/5027bb9e3555aff10baec93b.xml"},{"id":97249067,"identity":"adaa49ed-24fe-44f3-b9cf-a863d14ae331","added_by":"auto","created_at":"2025-12-02 13:10:10","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":727122,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/981b2c533b4ba6df9f7515b7.jpeg"},{"id":97158378,"identity":"9311b8a4-2cb2-4174-82b0-40b16e8f997b","added_by":"auto","created_at":"2025-12-01 11:56:15","extension":"jpeg","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":752054,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/3f7e881e38c2c4abf9e7b6e9.jpeg"},{"id":97248906,"identity":"45808621-bd6d-4b7b-a8a8-35d88616c26e","added_by":"auto","created_at":"2025-12-02 13:08:05","extension":"jpeg","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":634303,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/27cdc8d0e752d81ce0255772.jpeg"},{"id":97249834,"identity":"ad22a1d8-7e51-4dd9-9408-61fc3b8fdbec","added_by":"auto","created_at":"2025-12-02 13:13:31","extension":"jpeg","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":712287,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/8622ad257c06531f47bd8c02.jpeg"},{"id":97248484,"identity":"834bb1db-a91f-4ceb-8cf8-b18d1dc6c9e6","added_by":"auto","created_at":"2025-12-02 13:00:27","extension":"jpeg","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":457548,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/6d32225957d425b935f0e271.jpeg"},{"id":97158395,"identity":"0df8fa0d-51c3-4657-a405-4148b069c209","added_by":"auto","created_at":"2025-12-01 11:56:15","extension":"jpeg","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":624865,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/feb53f2779a7a165ecb5d8ab.jpeg"},{"id":97249960,"identity":"7b9e320b-253a-46c4-8353-2d18c433a8e1","added_by":"auto","created_at":"2025-12-02 13:13:43","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":179239,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/86b83a785f2b9ba4fc38376c.png"},{"id":97249760,"identity":"fe422fa8-3b09-45d1-b8ad-420534aa80ed","added_by":"auto","created_at":"2025-12-02 13:13:21","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":215772,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/6cb6e66c2729103768e9c057.png"},{"id":97158386,"identity":"707e414b-849f-471d-b252-5c8a09442420","added_by":"auto","created_at":"2025-12-01 11:56:15","extension":"png","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":143867,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/a3df23cd337a21528f24646f.png"},{"id":97158383,"identity":"82a251cd-71d9-40d8-b037-51980128fdea","added_by":"auto","created_at":"2025-12-01 11:56:15","extension":"png","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":212869,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/69a09eb1f2b30dfdccd47a79.png"},{"id":97249430,"identity":"4297bff0-9363-4fe5-b2a1-eb3a51f0801d","added_by":"auto","created_at":"2025-12-02 13:12:33","extension":"png","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":107612,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/362ef5b35a7c0589d608b538.png"},{"id":97158391,"identity":"ec230e1e-07bf-42d0-a036-22ef40110403","added_by":"auto","created_at":"2025-12-01 11:56:15","extension":"png","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":148769,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/6b58c920f150d61250f183ef.png"},{"id":97248591,"identity":"25c38b00-820d-436e-8e19-7e8d062e2ffc","added_by":"auto","created_at":"2025-12-02 13:03:51","extension":"xml","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":120488,"visible":true,"origin":"","legend":"","description":"","filename":"e5ac03479f124f0faf298aac75709ec41structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/4d34fb784e12a7732c9de56a.xml"},{"id":97158394,"identity":"da43054c-c3cb-4416-8897-2449961156ea","added_by":"auto","created_at":"2025-12-01 11:56:15","extension":"html","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":135141,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/2cc8d9f487e81bbce5f78847.html"},{"id":102234703,"identity":"fb6c3983-ba46-4553-b16e-9bbfb222f011","added_by":"auto","created_at":"2026-02-09 16:13:02","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":952753,"visible":true,"origin":"","legend":"","description":"","filename":"paperFINAL2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1_covered_57902e7e-4e02-4726-876b-b114f826b202.pdf"},{"id":97158376,"identity":"f6ea5bcb-c768-477d-8e7e-c915da1b0b1d","added_by":"auto","created_at":"2025-12-01 11:56:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":866778,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPLEMENTARYDATA.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8058626/v1/f8bf5f816082f1293745edee.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eBiliary Elimination of Cholesterol Can Be Modulated by Hepatocyte Mitochondrial Aquaporin-8 in Mice\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"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":"Biliary cholesterol excretion, mitochondrial aquaporin-8, ABCG5, adenovirus, hydrogen peroxide","lastPublishedDoi":"10.21203/rs.3.rs-8058626/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8058626/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSterol regulatory element-binding protein (SREBP) transcription factors directly or indirectly regulate key genes involved in hepatic cholesterol homeostasis, including biliary elimination. The ATP-binding cassette transporter G5 (ABCG5), located in hepatocyte canalicular plasma membranes, strongly controls the excretion of unesterified cholesterol into bile. Recently, we demonstrated in cultured hepatocytes that mitochondrial aquaporin-8 (mtAQP8), a channel protein capable of conducting H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e, is involved in SREBP-controlled cholesterol synthesis. In this study, we evaluated whether hepatic mtAQP8 participates in modulating the biliary elimination of cholesterol. Using C57BL/6 mice, we found that adenovirus-induced mtAQP8 knockdown significantly downregulated the expression of SREBP-2 and, through liver X receptors (LXR), that of ABCG5, which in turn decreased biliary cholesterol excretion. In contrast, mice with adenovirus-mediated mtAQP8 overexpression significantly increased the expressions of SREBP-2, LXR, and ABCG5 and, consequently, the biliary excretion of cholesterol. A mitochondrial-targeted antioxidant, which has been shown to quench mitochondrial H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e release, did not affect mtAQP8 expression, but prevented upregulation of SREBP-2, ABCG5, and biliary cholesterol excretion. Our data further support the involvement of mtAQP8 in hepatic cholesterol metabolism, suggesting that it modulates biliary cholesterol elimination through ABCG5 gene expression.\u003c/p\u003e","manuscriptTitle":"Biliary Elimination of Cholesterol Can Be Modulated by Hepatocyte Mitochondrial Aquaporin-8 in Mice","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-01 11:56:10","doi":"10.21203/rs.3.rs-8058626/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-15T14:46:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-15T07:12:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-15T06:20:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"84139117300932262104370493618575003140","date":"2025-12-06T08:44:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"30349739357835042767908778416184288217","date":"2025-11-26T13:00:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-25T14:06:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-25T14:00:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-20T05:17:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-19T18:04:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-11-19T18:01:44+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":"506308fc-75be-4e8d-b89a-3058c28c5b72","owner":[],"postedDate":"December 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":58882095,"name":"Biological sciences/Cell biology"},{"id":58882096,"name":"Health sciences/Diseases"},{"id":58882097,"name":"Health sciences/Gastroenterology"},{"id":58882098,"name":"Biological sciences/Molecular biology"},{"id":58882099,"name":"Biological sciences/Physiology"}],"tags":[],"updatedAt":"2026-02-09T16:08:39+00:00","versionOfRecord":{"articleIdentity":"rs-8058626","link":"https://doi.org/10.1038/s41598-026-39058-6","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-02-06 15:58:31","publishedOnDateReadable":"February 6th, 2026"},"versionCreatedAt":"2025-12-01 11:56:10","video":"","vorDoi":"10.1038/s41598-026-39058-6","vorDoiUrl":"https://doi.org/10.1038/s41598-026-39058-6","workflowStages":[]},"version":"v1","identity":"rs-8058626","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8058626","identity":"rs-8058626","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}