{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:59:09Z","timestamp":1790405949449,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82205220"],"award-info":[{"award-number":["82205220"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Grilled food toxicants 4\u2010hydroxynonenal (4\u2010HNE), benzo[a]pyrene (BaP), and 2\u2010amino\u20101\u2010methyl\u20106\u2010phenylimidazo[4,5\u2010b]pyridine (PhIP) pose health risks, including non\u2010alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). However, their synergistic molecular mechanisms in driving NASH to NASH\u2010HCC progression remain unclear. We employed network toxicology (CTD, GeneCards), bioinformatics analysis of the GSE164760 dataset, machine learning (LASSO, SVM\u2010RFE, Random Forest), SHAP interpretability analysis, immune infiltration profiling (CIBERSORT), miRNA\u2010TF\u2010mRNA network construction, and molecular docking to identify core genes and elucidate mechanisms. Toxicity prediction confirmed significant hepatotoxicity for all three compounds. Intersection analysis identified 8 key genes (InterGenes) enriched in oxidant detoxification, fatty acid metabolism, and chemical carcinogenesis pathways. Machine learning refined this to 6 CoreGenes (\n                    <jats:italic>GSTA1, EPHX1, CYP2E1, GPX3, ALB, TF<\/jats:italic>\n                    ). SHAP analysis revealed that high expression of ALB, TF, GSTA1 and CYP2E1, together with low expression of GPX3 and EPHX1, correlated with increased progression risk. A CoreGenes\u2010based diagnostic nomogram achieved exceptional performance (AUC\u2009=\u20090.967). Immune infiltration analysis revealed significant shifts in regulatory T cells and M2 macrophages during progression. Molecular docking confirmed strong binding affinities between the toxicants and CoreGenes proteins (e.g., BaP\u2010GSTA1: \u221210.7\u2009kcal\/mol). Functional enrichment implicated dysregulated fatty acid metabolism, PPAR, and TGF\u2010beta signaling. This study identifies GSTA1, EPHX1, CYP2E1, GPX3, ALB, and TF as pivotal biomarkers and mediators through which 4\u2010HNE, BaP, and PhIP synergistically promote NASH\u2010HCC progression via oxidative stress, metabolic dysfunction and remodeling of the immune microenvironment. The CoreGenes signature and multi\u2010gene model provide a powerful tool for risk assessment and early intervention.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.72303","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:55:32Z","timestamp":1788238532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic Analysis Reveals Core Genes and Mechanisms Linking Grilled Food Toxicants (4\u2010\n                    <scp>HNE<\/scp>\n                    ,\n                    <scp>BaP<\/scp>\n                    ,\n                    <scp>PhIP<\/scp>\n                    ) to\n                    <scp>NASH<\/scp>\n                    \u2010\n                    <scp>HCC<\/scp>\n                    Progression"],"prefix":"10.1002","volume":"14","author":[{"given":"Bingbing","family":"Qin","sequence":"first","affiliation":[{"name":"Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Zhang","sequence":"additional","affiliation":[{"name":"Artemisinin Research Center Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"},{"name":"School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine  Guangzhou Guangdong 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Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3569-6189","authenticated-orcid":false,"given":"Ying","family":"Tang","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"},{"name":"Institute of Tumor Guangzhou University of Chinese Medicine  Guangzhou Guangdong 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