{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:56:06Z","timestamp":1791575766660,"version":"4.3.4"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100020763","name":"Ministry of Emergency Management of the People&apos;s Republic of China","doi-asserted-by":"publisher","award":["YJBZZJJTJU202403"],"award-info":[{"award-number":["YJBZZJJTJU202403"]}],"id":[{"id":"10.13039\/100020763","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Tianjin Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["23JCYBJC01560"],"award-info":[{"award-number":["23JCYBJC01560"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Chemico-Biological Interactions"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.cbi.2026.112356","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:29:04Z","timestamp":1790836144000},"page":"112356","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Integrated network toxicology, machine learning, and multi-omics characterization of 2,4-DTBP neurotoxicity"],"prefix":"10.1016","volume":"440","author":[{"given":"Jinchao","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayab","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinrui","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojun","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cbi.2026.112356_bib1","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.chemosphere.2018.12.068","article-title":"Distribution and fate of synthetic phenolic antioxidants in various wastewater treatment processes in Canada","volume":"219","author":"Lu","year":"2019","journal-title":"Chemosphere"},{"key":"10.1016\/j.cbi.2026.112356_bib2","doi-asserted-by":"crossref","DOI":"10.3390\/toxins12010035","article-title":"Natural sources and bioactivities of 2,4-Di-Tert-Butylphenol and its analogs","volume":"12","author":"Zhao","year":"2020","journal-title":"Toxins"},{"key":"10.1016\/j.cbi.2026.112356_bib3","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhazmat.2024.133987","article-title":"Effects of the plastic additive 2,4-di-tert-butylphenol on intestinal microbiota of zebrafish","volume":"469","author":"Yang","year":"2024","journal-title":"J. Hazard Mater."},{"key":"10.1016\/j.cbi.2026.112356_bib4","doi-asserted-by":"crossref","first-page":"11706","DOI":"10.1021\/acs.est.0c05077","article-title":"Synthetic phenolic antioxidants: a review of environmental occurrence, fate, human exposure, and toxicity","volume":"54","author":"Liu","year":"2020","journal-title":"Environ. Sci. Technol."},{"key":"10.1016\/j.cbi.2026.112356_bib5","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.envpol.2016.11.069","article-title":"Occurrence of synthetic phenolic antioxidants and transformation products in urban and rural indoor dust","volume":"221","author":"Liu","year":"2017","journal-title":"Environ. Pollut."},{"key":"10.1016\/j.cbi.2026.112356_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2024.170054","article-title":"Exposure to environmental levels of 2,4-di-tert-butylphenol affects digestive glands and induces inflammation in Asian clam (Corbicula fluminea)","volume":"915","author":"Zhang","year":"2024","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.cbi.2026.112356_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbamcr.2023.119573","article-title":"Reactive oxygen species and cell signaling. Review","volume":"1871","author":"Averill-Bates","year":"2024","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"10.1016\/j.cbi.2026.112356_bib8","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s00204-023-03562-9","article-title":"Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging","volume":"97","author":"Jomova","year":"2023","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.cbi.2026.112356_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.foodchem.2021.129488","article-title":"Synthetic phenolic antioxidants: metabolism, hazards and mechanism of action","volume":"353","author":"Xu","year":"2021","journal-title":"Food Chem."},{"key":"10.1016\/j.cbi.2026.112356_bib10","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.cbi.2026.112356_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhazmat.2025.138289","article-title":"Ovarian toxicity of 2,6-di-tert-butyl-hydroxytoluene on female ruditapes philippinarum: reproductive endocrine disruption and oxidative stress","volume":"492","author":"Zheng","year":"2025","journal-title":"J. Hazard Mater."},{"key":"10.1016\/j.cbi.2026.112356_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhazmat.2025.138108","article-title":"Long-term exposure to 2,4-di-tert-butylphenol impairs zebrafish fecundity and affects offspring development","volume":"492","author":"Gao","year":"2025","journal-title":"J. Hazard Mater."},{"key":"10.1016\/j.cbi.2026.112356_bib13","doi-asserted-by":"crossref","DOI":"10.1210\/endocr\/bqad021","article-title":"2,4-Di-tert-butylphenol induces adipogenesis in human mesenchymal stem cells by activating retinoid X receptors","volume":"164","author":"Ren","year":"2023","journal-title":"Endocrinology"},{"key":"10.1016\/j.cbi.2026.112356_bib14","doi-asserted-by":"crossref","first-page":"528","DOI":"10.3389\/fncel.2019.00528","article-title":"Traumatic brain injuries: pathophysiology and potential therapeutic targets","volume":"13","author":"Ng","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.cbi.2026.112356_bib15","doi-asserted-by":"crossref","DOI":"10.3389\/ftox.2022.837579","article-title":"Role of environmental toxicants on neurodegenerative disorders","volume":"4","author":"Nabi","year":"2022","journal-title":"Front Toxicol"},{"key":"10.1016\/j.cbi.2026.112356_bib16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s42466-025-00452-6","article-title":"Environmental toxins in neurodegeneration - a narrative review","volume":"7","author":"Kulcs\u00e1rov\u00e1","year":"2025","journal-title":"Neurol Res Pract"},{"key":"10.1016\/j.cbi.2026.112356_bib17","doi-asserted-by":"crossref","DOI":"10.1038\/cddiscovery.2017.13","article-title":"MPP+ induces necrostatin-1- and ferrostatin-1-sensitive necrotic death of neuronal SH-SY5Y cells","volume":"3","author":"Ito","year":"2017","journal-title":"Cell Death Discov."},{"key":"10.1016\/j.cbi.2026.112356_bib18","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.redox.2017.03.007","article-title":"BID links ferroptosis to mitochondrial cell death pathways","volume":"12","author":"Neitemeier","year":"2017","journal-title":"Redox Biol."},{"key":"10.1016\/j.cbi.2026.112356_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2025.118372","article-title":"Downregulated NT-3 and PI3K\/AKT signaling pathway mediates arsenic-induced apoptosis in hippocampal neurons in vivo and in vitro","volume":"299","author":"Cui","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.cbi.2026.112356_bib20","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1007\/s12640-022-00573-9","article-title":"Activation of PI3k\/Akt\/mTOR signaling induces deposition of p-tau to promote aluminum neurotoxicity","volume":"40","author":"Xu","year":"2022","journal-title":"Neurotox. Res."},{"key":"10.1016\/j.cbi.2026.112356_bib21","doi-asserted-by":"crossref","DOI":"10.3390\/cells13060485","article-title":"NF-\u03baB as an inducible regulator of inflammation in the central nervous system","volume":"13","author":"Anilkumar","year":"2024","journal-title":"Cells"},{"key":"10.1016\/j.cbi.2026.112356_bib22","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/1742-2094-8-79","article-title":"Microglial p38\u03b1 MAPK is a key regulator of proinflammatory cytokine up-regulation induced by toll-like receptor (TLR) ligands or beta-amyloid (A\u03b2)","volume":"8","author":"Bachstetter","year":"2011","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.cbi.2026.112356_bib23","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.neuron.2014.06.007","article-title":"Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases","volume":"83","author":"Mei","year":"2014","journal-title":"Neuron"},{"key":"10.1016\/j.cbi.2026.112356_bib24","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21010275","article-title":"On the modulatory roles of Neuregulins\/ErbB signaling on synaptic plasticity","volume":"21","author":"Ledonne","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.cbi.2026.112356_bib25","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1172\/JCI79300","article-title":"Parkin cooperates with GDNF\/RET signaling to prevent dopaminergic neuron degeneration","volume":"125","author":"Meka","year":"2015","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.cbi.2026.112356_bib26","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1002\/mds.28258","article-title":"GDNF\/RET signaling pathway activation eliminates lewy body pathology in midbrain dopamine neurons","volume":"35","author":"Chmielarz","year":"2020","journal-title":"Mov. Disord."},{"key":"10.1016\/j.cbi.2026.112356_bib27","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2014.578","article-title":"Brain ischemia downregulates the neuroprotective GDNF-ret signaling by a calpain-dependent mechanism in cultured hippocampal neurons","volume":"6","author":"Curcio","year":"2015","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.cbi.2026.112356_bib28","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s12974-025-03558-5","article-title":"Soluble CSF1R promotes microglial activation and amyloid clearance in Alzheimer'S disease","volume":"22","author":"Zhang","year":"2025","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.cbi.2026.112356_bib29","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/s41590-025-02195-7","article-title":"Mutations in the human CSF1R gene impact microglia's maintenance of brain white matter integrity","volume":"26","author":"Du","year":"2025","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.cbi.2026.112356_bib30","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/glia.24664","article-title":"Microglial depletion, a new tool in neuroinflammatory disorders: comparison of pharmacological inhibitors of the CSF-1R","volume":"73","author":"Guenoun","year":"2025","journal-title":"Glia"},{"key":"10.1016\/j.cbi.2026.112356_bib31","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/s41419-020-03084-7","article-title":"CSF1R signaling is a regulator of pathogenesis in progressive MS","volume":"11","author":"Hagan","year":"2020","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.cbi.2026.112356_bib32","doi-asserted-by":"crossref","DOI":"10.3390\/ijms18112306","article-title":"The C-C chemokines CCL17 and CCL22 and their receptor CCR4 in CNS autoimmunity","volume":"18","author":"Scheu","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.cbi.2026.112356_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2020.106314","article-title":"The role of chemokines and chemokine receptors in multiple sclerosis","volume":"83","author":"Cui","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.cbi.2026.112356_bib34","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1111\/bph.16196","article-title":"Regulation of the ATP-Binding cassette transporters ABCB1, ABCG2 and ABCC5 by nuclear receptors in porcine blood-brain barrier endothelial cells","volume":"180","author":"Ho","year":"2023","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.cbi.2026.112356_bib35","doi-asserted-by":"crossref","DOI":"10.3390\/ijms262311641","article-title":"Liproxstatin-1 protects SH-SY5Y cells by inhibiting H(2)O(2)-Induced excessive mitophagy and apoptosis","volume":"26","author":"Yan","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.cbi.2026.112356_bib36","article-title":"Targeting molecular mediators of ferroptosis and oxidative stress for neurological disorders","volume":"2022","author":"Li","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.cbi.2026.112356_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.tox.2024.153727","article-title":"Ferroptosis at the crossroads of manganese-induced neurotoxicity: a retrospective study","volume":"502","author":"Liu","year":"2024","journal-title":"Toxicology"},{"key":"10.1016\/j.cbi.2026.112356_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2026.120401","article-title":"Ferrostatin-1 inhibits ferroptosis and alleviates organophosphate nerve agent-induced cognitive deficits by regulating ACSL4\/GPX4 and NCOA4\/FTH1 pathways in the hippocampus of Guinea pigs","volume":"321","author":"Jin","year":"2026","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.cbi.2026.112356_bib39","doi-asserted-by":"crossref","DOI":"10.3390\/biology14091153","article-title":"Therapeutic potential of natural compounds for brain ischemia-reperfusion injury","volume":"14","author":"Yoo","year":"2025","journal-title":"Biology"},{"key":"10.1016\/j.cbi.2026.112356_bib40","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemosphere.2022.136465","article-title":"Environmental concentrations of 2, 4-DTBP cause immunotoxicity in zebrafish (Danio rerio) and May elicit ecological risk to wildlife","volume":"308","author":"Liu","year":"2022","journal-title":"Chemosphere"},{"key":"10.1016\/j.cbi.2026.112356_bib41","doi-asserted-by":"crossref","DOI":"10.3390\/cells13070581","article-title":"NF-\u03baB and JAK\/STAT signaling pathways as crucial regulators of neuroinflammation and Astrocyte modulation in spinal cord injury","volume":"13","author":"Ageeva","year":"2024","journal-title":"Cells"},{"key":"10.1016\/j.cbi.2026.112356_bib42","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/s41392-025-02179-x","article-title":"Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery","volume":"10","author":"Wu","year":"2025","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.cbi.2026.112356_bib43","doi-asserted-by":"crossref","DOI":"10.3390\/cells9122655","article-title":"Ca(2+) dyshomeostasis disrupts neuronal and synaptic function in Alzheimer's Disease","volume":"9","author":"McDaid","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.cbi.2026.112356_bib44","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/s41392-023-01569-3","article-title":"Amino acid metabolism in health and disease","volume":"8","author":"Ling","year":"2023","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.cbi.2026.112356_bib45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.apsb.2024.10.004","article-title":"Oxidative stress and inflammation in the pathogenesis of neurological disorders: mechanisms and implications","volume":"15","author":"Dash","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.cbi.2026.112356_bib46","doi-asserted-by":"crossref","DOI":"10.1111\/jnc.70344","article-title":"Neurons in a dish: a review of in vitro cell models for studying neurogenesis","volume":"170","author":"Vassal","year":"2026","journal-title":"J. Neurochem."}],"container-title":["Chemico-Biological Interactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0009279726004643?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0009279726004643?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:46:56Z","timestamp":1791575216000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0009279726004643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":46,"alternative-id":["S0009279726004643"],"URL":"https:\/\/doi.org\/10.1016\/j.cbi.2026.112356","relation":{},"ISSN":["0009-2797"],"issn-type":[{"value":"0009-2797","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Integrated network toxicology, machine learning, and multi-omics characterization of 2,4-DTBP neurotoxicity","name":"articletitle","label":"Article Title"},{"value":"Chemico-Biological Interactions","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cbi.2026.112356","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"112356"}}