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We therefore built an adverse outcome pathway (AOP)-guided prediction-to-validation strategy\u2500coupling environmental occurrence mining, feature-assisted network toxicology, and zebrafish testing\u2500for 1,3,6-tribromocarbazole (1,3,6-BCZ), one of the most frequently detected congeners. Compiled data from 24 sites on three continents confirmed multimedia contamination (water, 0.3\u20132.69 ng\/L; sediment, 0.09\u20133.45 ng\/g) and framed a multiconcentration design anchored by measured aqueous concentrations (up to 43.60 \u03bcg\/L) and larval body burdens. LASSO\/SVM-RFE prioritization of the chemical\u2013target network nominated estrogen receptor 1 (ESR1) as the candidate molecular initiating event, supported by docking (\u22127.61 kcal\/mol) to a ligand-binding domain conserved between human and zebrafish. Sublethal exposure impaired angiogenic sprouting, enlarged the common cardinal vein, reduced subintestinal vessel area, and produced pericardial edema. Transcriptomics and network prediction converged on 18 shared pathways, notably NF-\u03baB signaling and endothelial junctions; ESR1 expression fell while NF-\u03baB subunits, proinflammatory genes, neutrophil infiltration, and oxidative stress rose. 17\u03b2-Estradiol cotreatment partially reversed these responses, supporting ESR1-associated, NF-\u03baB-linked cardiovascular injury and providing a transferable framework for data-poor halogenated contaminants.<\/jats:p>","DOI":"10.1021\/acs.est.6c08481","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:01:46Z","timestamp":1790395306000},"page":"28431-28444","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism-Driven\nRisk Assessment of 1,3,6-Tribromocarbazole:\nAn Integrated Strategy Implicates ESR1-Associated Cardiovascular Toxicity"],"prefix":"10.1021","volume":"60","author":[{"given":"Jie","family":"Gu","sequence":"first","affiliation":[{"name":"Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment , , ,","place":["Nanjing, China, 210042"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Suzhou Medical College of Soochow University , , ,","place":["Suzhou, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liguo","family":"Guo","sequence":"additional","affiliation":[{"name":"Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment , , ,","place":["Nanjing, China, 210042"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9961-3928","authenticated-orcid":true,"given":"Wenhui","family":"Qiu","sequence":"additional","affiliation":[{"name":"Southern University of Science and Technology , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4332-9781","authenticated-orcid":true,"given":"Lihong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment , , ,","place":["Nanjing, China, 210042"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3639-6126","authenticated-orcid":true,"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu University , , ,","place":["Zhenjiang, China, 212013"]},{"name":"Nanjing University , , ,","place":["Nanjing, China, 210023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3622-1505","authenticated-orcid":true,"given":"Guixiang","family":"Ji","sequence":"additional","affiliation":[{"name":"Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment , , ,","place":["Nanjing, China, 210042"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0478-5306","authenticated-orcid":true,"given":"Xiaowei","family":"Jin","sequence":"additional","affiliation":[{"name":"China National Environmental Monitoring Centre , ,","place":["Beijing, China, 100012"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"issue":"3","key":"2026101310153599500_cit1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1053\/j.arrt.2004.04.002","article-title":"The spectrum of cardiovascular disease in children\nwith predialysis chronic kidney disease","volume":"11","author":"Chavers","year":"2004","journal-title":"Adv.\nChronic Kidney Dis."},{"issue":"5","key":"2026101310153599500_cit2","doi-asserted-by":"publisher","first-page":"427","DOI":"10.26719\/2018.24.5.427","article-title":"Comparative analysis\nof essential\nmedicines for cardiovascular diseases in countries of the WHO Eastern\nMediterranean Region","volume":"24","author":"Mehrtash","year":"2018","journal-title":"East. 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