{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T19:24:25Z","timestamp":1781810665788,"version":"3.54.5"},"reference-count":27,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22206162"],"award-info":[{"award-number":["22206162"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ecotoxicology and Environmental Safety"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.ecoenv.2025.119235","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T19:57:42Z","timestamp":1760731062000},"page":"119235","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Investigating the hepatic developmental toxicity of synthetic phenolic antioxidant 3-BHA: A comprehensive network-based approach combined with human embryonic stem cell-derived hepatocyte models"],"prefix":"10.1016","volume":"305","author":[{"given":"Nadire","family":"Nijiati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mulati","family":"Julaiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilixiati","family":"Wubuli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ecoenv.2025.119235_bib1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.tiv.2007.07.013","article-title":"First steps in establishing a developmental toxicity test method based on human embryonic stem cells","volume":"22","author":"Adler","year":"2008","journal-title":"Toxicol. Vitr."},{"key":"10.1016\/j.ecoenv.2025.119235_bib2","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1016\/S0043-1354(02)00084-2","article-title":"Identification of organic compounds migrating from polyethylene pipelines into drinking water","volume":"36","author":"Brocca","year":"2002","journal-title":"Water Res."},{"key":"10.1016\/j.ecoenv.2025.119235_bib3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.plaphy.2013.05.009","article-title":"Plant phenolics: recent advances on their biosynthesis, genetics, and ecophysiology","volume":"72","author":"Cheynier","year":"2013","journal-title":"Plant Physiol. Biochem."},{"key":"10.1016\/j.ecoenv.2025.119235_bib4","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1016\/j.tiv.2007.06.014","article-title":"An in vitro embryotoxicity assay based on the disturbance of the differentiation of murine embryonic stem cells into endothelial cells. Ii. testing of compounds","volume":"21","author":"Festag","year":"2007","journal-title":"Toxicol. Vitr."},{"key":"10.1016\/j.ecoenv.2025.119235_bib5","doi-asserted-by":"crossref","first-page":"W32","DOI":"10.1093\/nar\/gku293","article-title":"SwissTargetPrediction: a web server for target prediction of bioactive small molecules","volume":"42","author":"Gfeller","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ecoenv.2025.119235_bib6","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1089\/dna.2009.0906","article-title":"In vitro study of calf thymus DNA interaction with butylated hydroxyanisole","volume":"28","author":"Kashanian","year":"2009","journal-title":"DNA Cell Biol."},{"key":"10.1016\/j.ecoenv.2025.119235_bib7","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.trre.2008.04.002","article-title":"Alternative sources of pluripotency: science, ethics, and stem cells","volume":"22","author":"Kastenberg","year":"2008","journal-title":"Transpl. Rev. (Orlando)"},{"key":"10.1016\/j.ecoenv.2025.119235_bib8","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.polymdegradstab.2017.07.012","article-title":"Natural antioxidants as stabilizers for polymers","volume":"145","author":"Kirschweng","year":"2017","journal-title":"Polym. Degrad. Stab."},{"key":"10.1016\/j.ecoenv.2025.119235_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.tice.2019.101312","article-title":"Down-regulation of SOX17, GATA4 and FoxA2 promotes differentiation potential of hepatocytes from human hematopoietic stem cells","volume":"62","author":"Kumar","year":"2020","journal-title":"Tissue Cell"},{"key":"10.1016\/j.ecoenv.2025.119235_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.fsi.2023.108906","article-title":"Synthetic phenolic antioxidants evoked hepatoxicity in grass carp through modulating the ROS-PI3K\/mTOR\/AKT pathway: Apoptosis-autophagy crosstalk","volume":"139","author":"Li","year":"2023","journal-title":"Fish. Shellfish Immun."},{"key":"10.1016\/j.ecoenv.2025.119235_bib11","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.devcel.2022.01.004","article-title":"Temporal analyses of postnatal liver development and maturation by single-cell transcriptomics","volume":"57","author":"Liang","year":"2022","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ecoenv.2025.119235_bib12","first-page":"16","article-title":"Endocrine disrupting effects of butylated hydroxyanisole (BHA - E320)","volume":"86","author":"Pop","year":"2013","journal-title":"Clujul Med."},{"key":"10.1016\/j.ecoenv.2025.119235_bib13","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0165-1218(92)90014-Q","article-title":"Evaluation of genotoxicity of tert.-butylhydroquinone in an hepatocyte-mediated assay with V79 Chinese hamster lung cells and in strain D7 of saccharomyces cerevisiae","volume":"280","author":"Rogers","year":"1992","journal-title":"Mutat. Res."},{"key":"10.1016\/j.ecoenv.2025.119235_bib14","doi-asserted-by":"crossref","first-page":"9516","DOI":"10.1021\/jf8035758","article-title":"Study of the migration of photoinitiators used in printed food-packaging materials into food simulants","volume":"57","author":"Sanches-Silva","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.ecoenv.2025.119235_bib15","doi-asserted-by":"crossref","first-page":"3204","DOI":"10.1021\/acs.est.1c07182","article-title":"3--Butyl-4-hydroxyanisole impairs hepatic lipid metabolism in Male mice fed with a High-Fat diet","volume":"56","author":"Sun","year":"2022","journal-title":"Environ. Sci. Technol."},{"key":"10.1016\/j.ecoenv.2025.119235_bib16","doi-asserted-by":"crossref","first-page":"D380","DOI":"10.1093\/nar\/gkv1277","article-title":"STITCH 5: augmenting protein-chemical interaction networks with tissue and affinity data","volume":"44","author":"Szklarczyk","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ecoenv.2025.119235_bib17","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ecoenv.2025.119235_bib18","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.ecoenv.2025.119235_bib19","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/mt.2011.234","article-title":"Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4\u03b1 transduction","volume":"20","author":"Takayama","year":"2012","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ecoenv.2025.119235_bib20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbi.2005.12.009","article-title":"Free radicals, metals and antioxidants in oxidative stress-induced cancer","volume":"160","author":"Valko","year":"2006","journal-title":"Chem. Biol. Inter."},{"key":"10.1016\/j.ecoenv.2025.119235_bib21","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1089\/dna.2012.1946","article-title":"Cytotoxicity and DNA fragmentation properties of butylated hydroxyanisole","volume":"32","author":"Vandghanooni","year":"2013","journal-title":"DNA Cell Biol."},{"issue":"693","key":"10.1016\/j.ecoenv.2025.119235_bib22","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ecoenv.2025.119235_bib23","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1021\/acs.est.5b04826","article-title":"Synthetic phenolic antioxidants and their metabolites in indoor dust from homes and microenvironments","volume":"50","author":"Wang","year":"2016","journal-title":"Environ. Sci. Technol."},{"key":"10.1016\/j.ecoenv.2025.119235_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2023.114979","article-title":"3-tert-Butyl-4-hydroxyanisole perturbs renal lipid metabolism by targeting androgen receptor-regulated lipogenesis","volume":"258","author":"Wang","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.ecoenv.2025.119235_bib25","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202101506RRR","article-title":"FOXA1\/2 depletion drives global reprogramming of differentiation state and metabolism in a human liver cell line and inhibits differentiation of human stem cell-derived hepatic progenitor cells","volume":"37","author":"Warren","year":"2023","journal-title":"Faseb J."},{"key":"10.1016\/j.ecoenv.2025.119235_bib26","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1021\/acs.est.7b05057","article-title":"Synthetic phenolic antioxidants cause perturbation in steroidogenesis in vitro and in vivo","volume":"52","author":"Yang","year":"2018","journal-title":"Environ. Sci. Technol."},{"key":"10.1016\/j.ecoenv.2025.119235_bib27","doi-asserted-by":"crossref","first-page":"4074","DOI":"10.3748\/wjg.v25.i30.4074","article-title":"Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases","volume":"25","author":"Yeh","year":"2019","journal-title":"World J. Gastroenterol."}],"container-title":["Ecotoxicology and Environmental Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0147651325015805?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0147651325015805?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T12:49:50Z","timestamp":1773838190000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0147651325015805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":27,"alternative-id":["S0147651325015805"],"URL":"https:\/\/doi.org\/10.1016\/j.ecoenv.2025.119235","relation":{},"ISSN":["0147-6513"],"issn-type":[{"value":"0147-6513","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Investigating the hepatic developmental toxicity of synthetic phenolic antioxidant 3-BHA: A comprehensive network-based approach combined with human embryonic stem cell-derived hepatocyte models","name":"articletitle","label":"Article Title"},{"value":"Ecotoxicology and Environmental Safety","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ecoenv.2025.119235","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"119235"}}