{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T11:38:52Z","timestamp":1789213132902,"version":"build-2803163510"},"reference-count":61,"publisher":"American Chemical Society (ACS)","issue":"23","license":[{"start":{"date-parts":[[2020,11,15]],"date-time":"2020-11-15T00:00:00Z","timestamp":1605398400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,11,15]],"date-time":"2020-11-15T00:00:00Z","timestamp":1605398400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,11,15]],"date-time":"2020-11-15T00:00:00Z","timestamp":1605398400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100007957","name":"Chongqing Municipal Education Commission","doi-asserted-by":"publisher","award":["KJQN201900440"],"award-info":[{"award-number":["KJQN201900440"]}],"id":[{"id":"10.13039\/501100007957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing","doi-asserted-by":"publisher","award":["cstc2020jcyj-msxmX0150"],"award-info":[{"award-number":["cstc2020jcyj-msxmX0150"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21707012"],"award-info":[{"award-number":["21707012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021189","name":"Guangxi Key Laboratory of Theory and Technology for Environmental Pollution Control","doi-asserted-by":"crossref","award":["GKN1901K005"],"award-info":[{"award-number":["GKN1901K005"]}],"id":[{"id":"10.13039\/501100021189","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The prediction and mechanism analysis of hepatotoxicity of contaminants, because of their various phenotypes and complex mechanisms, is still a key problem in environmental research. We applied a toxicological network analysis method to predict the hepatotoxicity of three hexabromocyclododecane (HBCD) diastereoisomers (\u03b1-HBCD, \u03b2-HBCD, and \u03b3-HBCD) and explore their potential mechanisms. First, we collected the hepatotoxicity related genes and found that those genes were significantly localized in the human interactome. Therefore, these genes form a disease module of hepatotoxicity. We also collected targets of \u03b1-, \u03b2-, and \u03b3-HBCD and found that their targets overlap with the hepatotoxicity disease module. Then, we trained a model to predict hepatotoxicity of three HBCD diastereoisomers based on the relationship between the hepatotoxicity disease module and targets of compounds. We found that 593 genes were significantly located in the hepatotoxicity disease module (Z = 11.9, p &amp;lt; 0.001) involved in oxidative stress, cellular immunity, and proliferation, and the accuracy of hepatotoxicity prediction of HBCD was 0.7095 \u00b1 0.0193 and the recall score was 0.8355 \u00b1 0.0352. HBCD mainly affects the core disease module genes to mediate the adenosine monophosphate-activated kinase, p38MAPK, PI3K\/Akt, and TNF\u03b1 pathways to regulate the immune reaction and inflammation. HBCD also induces the secretion of IL6 and STAT3 to lead hepatotoxicity by regulating NR3C1. This approach is transferable to other toxicity research studies of environmental pollutants.<\/jats:p>","DOI":"10.1021\/acs.est.0c03998","type":"journal-article","created":{"date-parts":[[2020,11,15]],"date-time":"2020-11-15T11:47:03Z","timestamp":1605440823000},"page":"15235-15245","source":"Crossref","is-referenced-by-count":43,"title":["Probing the Mechanism of Hepatotoxicity of Hexabromocyclododecanes\nthrough Toxicological Network Analysis"],"prefix":"10.1021","volume":"54","author":[{"given":"Weina","family":"Dai","sequence":"first","affiliation":[{"name":"Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Tang","sequence":"additional","affiliation":[{"name":"Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghua","family":"Dai","sequence":"additional","affiliation":[{"name":"Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]},{"name":"Chongqing Academy of Metrology and Quality Inspection , ,","place":["Chongqing, China, 401123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1953-2299","authenticated-orcid":true,"given":"Da","family":"Shi","sequence":"additional","affiliation":[{"name":"University of California San Diego , , , ,","place":["La Jolla, California, United States, 92093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Mo","sequence":"additional","affiliation":[{"name":"Guilin University of Technology , , ,","place":["Guilin, China, 541004"]},{"name":"Ministry of Natural Resources , , ,","place":["Nanning, China, 530028"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8574-9288","authenticated-orcid":true,"given":"Yonghong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,11,15]]},"reference":[{"key":"2026081418153326400_cit1","doi-asserted-by":"publisher","first-page":"3679","DOI":"10.1021\/es0602492","article-title":"Hexabromocyclododecanes (HBCDs) in the environment\nand humans: a review","volume":"40","author":"Covaci","year":"2006","journal-title":"Environ. 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Technol."},{"key":"2026081418153326400_cit5","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.chemosphere.2016.07.001","article-title":"In vitro study on the biotransformation and cytotoxicity\nof three hexabromocyclododecane diastereoisomers in liver cells","volume":"161","author":"Huang","year":"2016","journal-title":"Chemosphere"},{"key":"2026081418153326400_cit6","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.scitotenv.2013.08.014","article-title":"Hexabromocyclododecane concentrations in Canadian human\nfetal liver and placental tissues","volume":"468\u2013469","author":"Rawn","year":"2014","journal-title":"Sci. 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