{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:13:39Z","timestamp":1783955619551,"version":"3.55.0"},"reference-count":95,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA028435"],"award-info":[{"award-number":["AA028435"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA024337"],"award-info":[{"award-number":["AA024337"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA030424"],"award-info":[{"award-number":["AA030424"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The impairment of neural crest cells (NCCs) plays a pivotal role in the pathogenesis of fetal alcohol spectrum disorders (FASD). Epigenetic regulators mediate ethanol-induced disruptions in NCC development and represent promising targets for nutritional interventions. Here, we developed a biologically informed machine learning framework to predict nutritional supplements that modulate five key epigenetic regulators (miR-34a, DNMT3a, HDAC, miR-125b, and miR-135a) and mitigate ethanol\u2019s adverse effects on NCCs. The optimized models demonstrated robust predictive performance and identified a number of nutritional supplements that could attenuate ethanol-induced NCC impairment, including resveratrol, vitamin B12, emodin, quercetin, and broccoli sprout-derived compounds. Our optimized models also revealed structural features that are critical for mitigating ethanol-induced NCC impairment through specific epigenetic mechanisms. These findings support predictive modeling as a tool to prioritize nutritional supplements for further investigation and the development of dietary strategies to prevent or reduce the risk of FASD.<\/jats:p>","DOI":"10.3390\/ijms27010295","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T05:28:19Z","timestamp":1766986099000},"page":"295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Biologically Informed Machine Learning Prioritizes Dietary Supplements That Protect Neural Crest Cells from Ethanol-Induced Epigenetic Dysregulation and Developmental Impairment"],"prefix":"10.3390","volume":"27","author":[{"given":"Xiaoqing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Health Sciences Center, University of Louisville, Louisville, KY 40292, USA"},{"name":"Alcohol Research Center, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Health Sciences Center, University of Louisville, Louisville, KY 40292, USA"},{"name":"Alcohol Research Center, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6963-6267","authenticated-orcid":false,"given":"Shuoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjia","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Health Sciences Center, University of Louisville, Louisville, KY 40292, USA"},{"name":"Alcohol Research Center, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Health Sciences Center, University of Louisville, Louisville, KY 40292, USA"},{"name":"Alcohol Research Center, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenke","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Structural and Cellular Biology, School of Medicine, Tulane University, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang-ge","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40292, USA"},{"name":"Robley Rex Veterans Affairs Medical Center, Louisville, KY 40292, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Wu","sequence":"additional","affiliation":[{"name":"Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7953-9700","authenticated-orcid":false,"given":"Shao-yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Health Sciences Center, University of Louisville, Louisville, KY 40292, USA"},{"name":"Alcohol Research Center, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106855","DOI":"10.1016\/j.phrs.2023.106855","article-title":"Neural crest cells and fetal alcohol spectrum disorders: Mechanisms and potential targets for prevention","volume":"194","author":"Chen","year":"2023","journal-title":"Pharmacol. 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