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It systematically reveals the temporal heterogeneity of pollutant-induced liver damage. The findings indicate that pollutants not only directly damage hepatocytes but also modulate key cells in the immune microenvironment, such as hepatic stellate cells (HSCs) and Kupffer cells, thereby amplifying inflammatory and fibrotic responses, ultimately accelerating the progression of HCC. Mechanistically, in the early stage (NAFLD), pollutants primarily cause hepatocyte injury through oxidative stress and lipid metabolism dysregulation. During the fibrosis stage, pollutants promote liver fibrosis by inducing extracellular matrix accumulation, while in the HCC stage, they drive tumorigenesis via activation of the Wnt\/\u03b2-catenin pathway and p53 inactivation. Through multi-omics analyses, this study identifies critical pathogenic molecules and signaling pathways regulated by pollutants, providing new insights into their pathogenic mechanisms, potential biomarkers, and therapeutic targets. These findings offer valuable guidance for the development of diagnostic and therapeutic strategies for liver diseases and the formulation of environmental health risk prevention measures.<\/jats:p>","DOI":"10.3390\/toxics13030163","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T12:01:17Z","timestamp":1740484877000},"page":"163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pollutants in Microenvironmental Cellular Interactions During Liver Inflammation Cancer Transition and the Application of Multi-Omics Analysis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7583-8281","authenticated-orcid":false,"given":"Yulun","family":"Jian","sequence":"first","affiliation":[{"name":"School of Public Health, Center for Single-Cell Omics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Center for Single-Cell Omics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Public Health, Center for Single-Cell Omics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2828-8096","authenticated-orcid":false,"given":"Wei","family":"Mu","sequence":"additional","affiliation":[{"name":"School of Public Health, Center for Single-Cell Omics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ejim.2021.10.035","article-title":"Drug-induced liver injury: Pathogenesis, epidemiology, clinical features, and practical management","volume":"97","year":"2022","journal-title":"Eur. 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