{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:08:47Z","timestamp":1788977327978,"version":"build-2803163510"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangxi Science and Technology Department \u2014 Capacity Enhancement of Guangxi Zhuang and Yao Medicine Engineering Technology Research Center","award":["Guike ZY24212016"],"award-info":[{"award-number":["Guike ZY24212016"]}]},{"name":"Guangxi Administration of Traditional Chinese Medicine \u2014 Research and Promotion of Tuina (Massage) Techniques for Treating Obesity","award":["GZSY2025035"],"award-info":[{"award-number":["GZSY2025035"]}]},{"name":"China National Center for the Development of Traditional Chinese Medicine \u2014 Collaborative Clinical Research Project of Chinese and Western Medicine","award":["CXZH2025008"],"award-info":[{"award-number":["CXZH2025008"]}]},{"name":"Innovation Project of Guangxi Graduate Education of GXUCM","award":["YCSY2025058"],"award-info":[{"award-number":["YCSY2025058"]}]},{"DOI":"10.13039\/501100004924","name":"Guangxi Traditional Chinese Medical University","doi-asserted-by":"publisher","award":["2025YJ-32"],"award-info":[{"award-number":["2025YJ-32"]}],"id":[{"id":"10.13039\/501100004924","id-type":"DOI","asserted-by":"publisher"}]}],"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>Perfluorooctanoic acid (PFOA), a pervasive environmental pollutant, has been implicated in hepatic injury and metabolic dysfunction. However, its role as an environmental risk factor in the pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) remains incompletely understood, particularly from a systems biology perspective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study employed an integrative approach combining computational toxicology, multi-omics data analysis, and machine learning. Public databases were utilized to identify PFOA-related targets and MASLD-associated genes. A comprehensive machine learning framework comprising 113 model combinations was applied to transcriptomic datasets (GSE66676, GSE89632, GSE164760) to identify hub genes. Single-cell RNA sequencing (scRNA-seq) analysis delineated cell type-specific expression patterns. Molecular docking and dynamics simulations assessed the binding stability between PFOA and core targets, which was further validated in vitro using an FFA-induced MASLD HepG2 cell model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 17 shared targets between PFOA and NAFLD. Machine learning pinpointed six hub genes (NR4A2, BCL6, CASP1, SHBG, FABP4, IL10) with high diagnostic accuracy (AUC up to 0.996). scRNA-seq revealed distinct expression patterns of these genes across liver cell subtypes in MASLD. Molecular docking and dynamics simulations demonstrated stable binding of PFOA to SHBG and FABP4. In vitro experiments confirmed that PFOA exposure significantly altered the mRNA and protein expression levels of these core genes in the MASLD model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest a potential mechanistic association between PFOA exposure and MASLD pathogenesis, characterized by disruption of lipid metabolism, inflammatory responses, and immune homeostasis. While these results identify biologically plausible pathways, they do not establish epidemiological causation, and further prospective studies with quantified PFOA exposure are required to confirm causality in humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0357970","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:36:30Z","timestamp":1788975390000},"page":"e0357970","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Environmental PFOA exposure and the risk of metabolic dysfunction-associated steatotic liver disease: An integrated computational toxicology and multi-omics study"],"prefix":"10.1371","volume":"21","author":[{"given":"Tianyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Guangxi University of Chinese Medicine","place":["Nanning, Guangxi, China"],"department":["Department of Acupuncture and 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