{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:53:37Z","timestamp":1777949617573,"version":"3.51.4"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Unsymmetrical dimethylhydrazine (UDMH), a highly toxic rocket propellant with known multiorgan effects, requires urgent characterization of its chronic low\u2010dose toxicity. Using an integrated approach including exploratory transcriptomics (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093\/group) and metabolomic (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094\/group) approaches in male Sprague\u2013Dawley rats exposed to high\u2010dose UDMH concentrations (100\u2009ppm (v\/v), 4\u2009h\/day, 5\u2009days\/week for 60\u2009days), we delineated organ\u2010specific injury mechanisms and identified candidate systemic biomarkers. Histopathological assessment revealed significant pulmonary injury (62.5% incidence of focal hemorrhage,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.015; inflammatory focus density: 8.3\u2009\u00b1\u20091.7 foci\/mm\n                    <jats:sup>2<\/jats:sup>\n                    ) and renal injury (tubular basophilia index: 1.8\u2009\u00b1\u20090.4,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Integrated multiomics analysis identified a mechanistically interconnected biomarker triad: (1) hepatic\n                    <jats:italic>Cyp4a1<\/jats:italic>\n                    upregulation (log\n                    <jats:sub>2<\/jats:sub>\n                    FC\u2009=\u20094.7), indicating PPAR\u03b1\u2010mediated adaptive detoxification; (2) elevated serum taurine (1.27\u2010fold,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), reflecting mitochondrial compensatory responses; and (3) increased urinary L\u2010DOPA (3.1\u2010fold, false discovery rate [FDR]\u2009&lt;\u20090.05), signifying neuroendocrine dysregulation. Together, these core biomarkers delineate the pathophysiology of chronic UDMH toxicity, characterized by PPAR\u03b1\u2010driven detoxification intersecting with mitochondrial stress adaptation and catecholaminergic disruption across organ systems. To our knowledge, this is the first integrated multiomics study of chronic UDMH exposure, establishing a mechanistic framework for toxicity and highlighting pulmonary\u2013renal pathology, serum taurine, and hepatic\n                    <jats:italic>Cyp4a1<\/jats:italic>\n                    as key indicators for developing future risk assessment strategies.\n                  <\/jats:p>","DOI":"10.1002\/jat.70008","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T02:34:49Z","timestamp":1764383689000},"page":"1987-2002","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic Low\u2010Dose Unsymmetrical Dimethylhydrazine Exposure in Rats: Multiorgan Mechanisms and Biomarker Identification"],"prefix":"10.1002","volume":"46","author":[{"given":"Fuzhou","family":"Liu","sequence":"first","affiliation":[{"name":"Department of General Medicine PLA Rocket Force Characteristic Medical Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Disease Prevention and Control PLA Rocket Force Characteristic Medical Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keli","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Medicine PLA Rocket Force Characteristic Medical Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Medicine PLA Rocket Force Characteristic Medical Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine PLA Rocket Force Characteristic Medical Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojuan","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of General Medicine PLA Rocket Force Characteristic Medical Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2722-2239","authenticated-orcid":false,"given":"Zengming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Chinese PLA Center for Disease Control and Prevention  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0297811"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2024.110930"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2023.140747"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1289\/EHP14696"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10081207"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-024-03124-3"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-025-04841-5"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.12.013"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-024-01093-6"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25116070"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07185-7"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2025.343728"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.101921"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2022.128708"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242417196"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2023.100948"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2024.142679"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.4c02606"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.add7150"},{"key":"e_1_2_12_21_1","volume-title":"AVMA Guidelines for the Euthanasia of Animals: 2020 Edition","author":"Leary S."},{"key":"e_1_2_12_22_1","volume-title":"Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals","author":"Levels, N.R.C. 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