{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T18:12:06Z","timestamp":1778177526366,"version":"3.51.4"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"publisher","award":["2021GXNSFAA220110"],"award-info":[{"award-number":["2021GXNSFAA220110"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81760604"],"award-info":[{"award-number":["81760604"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005198","name":"Chinese Foundation for Hepatitis Prevention and Control","doi-asserted-by":"publisher","award":["XCGY202302"],"award-info":[{"award-number":["XCGY202302"]}],"id":[{"id":"10.13039\/501100005198","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open project project project of Guangxi Key Laboratory of Viral Hepatitis Prevention and Control","award":["GXCDCKL202301"],"award-info":[{"award-number":["GXCDCKL202301"]}]},{"name":"Sub-project of Guangxi Horizontal Research project of hepatitis B Prevention and Control","award":["QT02201906"],"award-info":[{"award-number":["QT02201906"]}]},{"name":"Sub-project of Guangxi hepatitis B Prevention and Control","award":["QT02201907"],"award-info":[{"award-number":["QT02201907"]}]},{"name":"High-Level Public Health Talent Cultivation Innovation Team of Guangxi University of Chinese Medicine","award":["2022A009"],"award-info":[{"award-number":["2022A009"]}]},{"name":"Guangxi School of Xinglin Top Talent Project of Guangxi University of Traditional Chinese Medicine","award":["2022C010"],"award-info":[{"award-number":["2022C010"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Residual mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains a significant clinical challenge despite standard immunoprophylaxis. Identifying molecular markers is crucial for improved prevention and diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a case-control study using the Guangxi Liuzhou HBV MTCT registry. Peripheral blood RNA sequencing (Illumina HiSeq) was performed on infants from HBsAg-positive mothers: cases (HBsAg-positive, n\u2009=\u20096) and controls (HBsAg-negative, n\u2009=\u200910). All infants receive HBIG and the first dose of hepatitis B vaccine within 24 hours after birth, followed by completion of the three-dose vaccination series. Differentially expressed miRNAs (DEMs; adj-p\u2009&lt;\u20090.05, |log2FC|\u2009&gt;\u20091) were identified. Target genes were predicted (miRanda\/RNAhybrid) and functionally analyzed (GO\/KEGG enrichment, PPI network). HBV-associated target genes were identified by cross-referencing GeneCards\/NCBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RNA-seq identified 62 DEMs (19 upregulated, 43 downregulated). Target prediction yielded 5,014 genes. Functional enrichment highlighted key pathways and processes. PPI analysis pinpointed highly connected genes. Integration with HBV databases revealed 3 key target genes potentially modulated by 4 specific DEMs (hsa-miR-6747-3p, hsa-miR-4772-3p upregulated; hsa-miR-4676-5p, hsa-miR-485-5p downregulated).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies dysregulation of 4 key miRNAs and their association with 3 HBV-linked target genes as potential contributors to residual HBV MTCT. These findings provide novel insights into the molecular mechanisms underlying HBV MTCT and suggest potential targets for intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0348899","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T17:25:44Z","timestamp":1778174744000},"page":"e0348899","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and functional analysis of key miRNAs and target genes associated with failure of HBV mother-to-child transmission prevention"],"prefix":"10.1371","volume":"21","author":[{"given":"Quan","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiong","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peipei","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinli","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haichen","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongjian","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3098-3023","authenticated-orcid":true,"given":"Hai","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"pone.0348899.ref001","unstructured":"World Health Organization. Hepatitis B. Fact sheet; 2025 [cited 2025 Dec 25]. Available from: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-b"},{"issue":"1","key":"pone.0348899.ref002","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1186\/s12889-024-20462-4","article-title":"Global, regional, and national total burden related to hepatitis B in children and adolescents from 1990 to 2021","volume":"24","author":"J Li","year":"2024","journal-title":"BMC Public Health"},{"issue":"1","key":"pone.0348899.ref003","doi-asserted-by":"crossref","first-page":"66","DOI":"10.21037\/hbsn-2024-754","article-title":"2024 latest report on hepatitis B virus epidemiology in China: current status, changing trajectory, and challenges","volume":"14","author":"R Yan","year":"2025","journal-title":"Hepatobiliary Surg Nutr"},{"issue":"7","key":"pone.0348899.ref004","first-page":"599","article-title":"Epidemiology, achievements, and challenges in the elimination of hepatitis B in China","volume":"13","author":"Y Deng","year":"2025","journal-title":"J Clin 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Hepatol"},{"issue":"5","key":"pone.0348899.ref017","first-page":"769","article-title":"Guidelines for prevention and treatment of chronic hepatitis B","volume":"9","author":"G Wang","year":"2021","journal-title":"J Clin Transl Hepatol"},{"issue":"1","key":"pone.0348899.ref018","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s13059-016-1047-4","article-title":"Erratum to: A survey of best practices for RNA-seq data analysis","volume":"17","author":"A Conesa","year":"2016","journal-title":"Genome Biol"},{"issue":"12","key":"pone.0348899.ref019","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"issue":"6","key":"pone.0348899.ref020","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1016\/j.cell.2006.07.031","article-title":"A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes","volume":"126","author":"KC Miranda","year":"2006","journal-title":"Cell"},{"issue":"10","key":"pone.0348899.ref021","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1261\/rna.5248604","article-title":"Fast and effective prediction of microRNA\/target duplexes","volume":"10","author":"M Rehmsmeier","year":"2004","journal-title":"RNA"},{"issue":"9","key":"pone.0348899.ref022","article-title":"Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways","volume":"12","author":"L Chen","year":"2017","journal-title":"PLoS One"},{"key":"pone.0348899.ref023","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: new perspectives on genomes, pathways, diseases and drugs","volume":"45","author":"M Kanehisa","year":"2017","journal-title":"Nucleic Acids Res"},{"issue":"10","key":"pone.0348899.ref024","article-title":"Management algorithm for interrupting mother-to-child transmission of hepatitis B virus","volume":"17","author":"J Hou","year":"2019","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"9","key":"pone.0348899.ref025","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1097\/INF.0000000000000315","article-title":"Immunoprophylaxis failure against vertical transmission of hepatitis B virus in the Chinese population: a hospital-based study and a meta-analysis","volume":"33","author":"X Lin","year":"2014","journal-title":"Pediatr Infect Dis J"},{"key":"pone.0348899.ref026","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jhep.2014.10.004","article-title":"miR-122--a key factor and therapeutic target in liver disease","volume":"62","author":"S Bandiera","year":"2015","journal-title":"J Hepatol"},{"key":"pone.0348899.ref027","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.molimm.2017.08.021","article-title":"Both Notch1 and its ligands in B cells promote antibody production","volume":"91","author":"G Zhu","year":"2017","journal-title":"Mol Immunol"},{"issue":"12","key":"pone.0348899.ref028","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/s41423-019-0318-x","article-title":"Jagged1-mediated myeloid Notch1 signaling activates HSF1\/Snail and controls NLRP3 inflammasome activation in liver inflammatory injury","volume":"17","author":"Y Jin","year":"2020","journal-title":"Cell Mol Immunol"},{"issue":"8","key":"pone.0348899.ref029","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1158\/1535-7163.MCT-17-0001","article-title":"Notch inhibitor PF-03084014 inhibits hepatocellular carcinoma growth and metastasis via suppression of cancer stemness due to reduced activation of Notch1-Stat3","volume":"16","author":"CX Wu","year":"2017","journal-title":"Mol Cancer Ther"},{"issue":"1","key":"pone.0348899.ref030","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s12964-022-00901-8","article-title":"Macrophage Notch1 inhibits TAK1 function and RIPK3-mediated hepatocyte necroptosis through activation of \u03b2-catenin signaling in liver ischemia and reperfusion injury","volume":"20","author":"D Xu","year":"2022","journal-title":"Cell Commun Signal"},{"issue":"43","key":"pone.0348899.ref031","doi-asserted-by":"crossref","first-page":"17081","DOI":"10.1073\/pnas.0704126104","article-title":"The EGF receptor is required for efficient liver regeneration","volume":"104","author":"A Natarajan","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"pone.0348899.ref032","doi-asserted-by":"crossref","first-page":"119359","DOI":"10.1016\/j.bbamcr.2022.119359","article-title":"Control of cell metabolism by the epidermal growth factor receptor","volume":"1869","author":"LA Orofiamma","year":"2022","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"issue":"1","key":"pone.0348899.ref033","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12929-025-01119-9","article-title":"EGF receptor in organ development, tissue homeostasis and regeneration","volume":"32","author":"C Tito","year":"2025","journal-title":"J Biomed Sci"},{"key":"pone.0348899.ref034","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4939-7219-7_1","article-title":"ErbB receptors and cancer","volume":"1652","author":"Z Wang","year":"2017","journal-title":"Methods Mol Biol"},{"issue":"3","key":"pone.0348899.ref035","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1002\/path.6002","article-title":"Lack of EGFR catalytic activity in hepatocytes improves liver regeneration following DDC-induced cholestatic injury by promoting a pro-restorative inflammatory response","volume":"258","author":"N Lazcanoiturburu","year":"2022","journal-title":"J 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