{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T15:26:10Z","timestamp":1787412370658,"version":"build-2736575974"},"reference-count":67,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82241086"],"award-info":[{"award-number":["82241086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473674"],"award-info":[{"award-number":["82473674"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U24A20772"],"award-info":[{"award-number":["U24A20772"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014761","name":"Natural Science Foundation of Qingdao Municipality","doi-asserted-by":"publisher","award":["24-4-4-zrjj-157-jch"],"award-info":[{"award-number":["24-4-4-zrjj-157-jch"]}],"id":[{"id":"10.13039\/501100014761","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Key Laboratory of Environment and Population Health, China CDC","doi-asserted-by":"publisher","award":["2025-CKL-01"],"award-info":[{"award-number":["2025-CKL-01"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Volatile organic compounds (VOCs) are prevalent indoor pollutants, posing significant health risks. However, current toxicological data focus predominantly on individual compounds, leaving a critical gap in understanding how exposure to mixed VOCs alters the plasma proteome and impacts health risk prediction. Herein, we investigated VOCs-induced hematological disturbances using a whole-body inhalation exposure model with C57BL\/6J mice (n = 3) exposed to decoration-derived VOCs for 8 weeks. By integrating plasma proteomics with machine learning, we demonstrated that VOCs exposure significantly disrupts hemostatic homeostasis, primarily by perturbing the complement and coagulation cascades. Network enrichment and correlation analyses further identified a network of suppressed pathways (e.g., platelet activation and focal adhesion) and activated pathways (e.g., necroptosis and IL-17 signaling pathway) that collectively drive this dysregulation. Critically, we identified downregulated von Willebrand factor (VWF) and cell division control protein 42 (CDC42) as a robust biomarker signature, as evidenced by correlation coefficients (r) of 0.91 and 0.90 with complement and coagulation cascades, respectively. Leveraging these biomarkers, we developed a highly accurate health risk scoring model. This study provides the first comprehensive molecular portrait of VOCs-induced hematological disturbances and presents a novel proteomics-driven framework for the early prediction and intervention of VOCs-related health effects.<\/jats:p>","DOI":"10.1021\/envhealth.5c00641","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T08:18:58Z","timestamp":1773908338000},"page":"1625-1636","source":"Crossref","is-referenced-by-count":0,"title":["Indoor VOCs Exposure\nDisrupts Hemostatic Balance:\nPlasma Proteomics Identifies Complement and Coagulation Cascade Dysregulation\nas a Critical Signature"],"prefix":"10.1021","volume":"4","author":[{"given":"Yurong","family":"Cui","sequence":"first","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Miao","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duxing","family":"Li","sequence":"additional","affiliation":[{"name":"ZaoZhuang Center for Disease Control and Prevention , ,","place":["Zaozhuang, China, 277101"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Qiu","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peijie","family":"Sun","sequence":"additional","affiliation":[{"name":"National Institute of Environmental Health , , ,","place":["Beijing, China, 100021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuebin","family":"Lv","sequence":"additional","affiliation":[{"name":"National Institute of Environmental Health , , ,","place":["Beijing, China, 100021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Sun","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijiao","family":"Li","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3962-0261","authenticated-orcid":true,"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hebei Medical University , , ,","place":["Shijiazhuang, China, 050017"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6526-8046","authenticated-orcid":true,"given":"Xiaoting","family":"Jin","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"2026082211090742100_cit1","unstructured":"The Institute for Health Metrics and Evaluation.\n          .  Air Pollution. https:\/\/www.healthdata.org\/research-analysis\/health-topics\/air-pollution."},{"issue":"10440","key":"2026082211090742100_cit2","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1016\/s0140-6736(24)00933-4","article-title":"Global burden and strength of evidence for\n88 risk factors in 204\ncountries and 811 subnational locations, 1990\u20132021: a systematic\nanalysis for the Global Burden of Disease Study 2021","volume":"403","year":"2024","journal-title":"Lancet"},{"key":"2026082211090742100_cit3","doi-asserted-by":"publisher","first-page":"111631","DOI":"10.1016\/j.envres.2021.111631","article-title":"Indoor PM2.5,\nVOCs and asthma outcomes: A systematic review in adults and their\nhome environments","volume":"202","author":"Paterson","year":"2021","journal-title":"Environ. Res."},{"key":"2026082211090742100_cit4","unstructured":"Joint Research Centre.\n          .  Indoor air pollution: new EU research reveals\nhigher risks than previously thought. 2005. https:\/\/cordis.europa.eu\/article\/id\/95197-indoor-air-pollution-new-eu-research-reveals-higher-risks-than-previously-thought."},{"key":"2026082211090742100_cit5","doi-asserted-by":"publisher","first-page":"173254","DOI":"10.1016\/j.scitotenv.2024.173254","article-title":"Interior decorative volatile organic compounds\nexposure induces sleep\ndisorders through aberrant branched chain amino acid transaminase\n2 mediated glutamatergic signaling resulting from a neuroinflammatory\ncascade","volume":"934","author":"Zheng","year":"2024","journal-title":"Sci. Total Environ."},{"issue":"5","key":"2026082211090742100_cit6","doi-asserted-by":"publisher","first-page":"344","DOI":"10.3390\/toxics13050344","article-title":"Volatile Organic Compounds in Indoor\nAir: Sampling, Determination, Sources, Health Risk, and Regulatory\nInsights","volume":"13","author":"Horvat","year":"2025","journal-title":"Toxics"},{"key":"2026082211090742100_cit7","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.envres.2014.12.005","article-title":"Gaseous chemical compounds in indoor and outdoor air\nof 602 houses throughout Japan in winter and summer","volume":"137","author":"Uchiyama","year":"2015","journal-title":"Environ. Res."},{"key":"2026082211090742100_cit8","doi-asserted-by":"publisher","first-page":"107611","DOI":"10.1016\/j.envint.2022.107611","article-title":"A review of\nindoor Gaseous organic compounds and human chemical Exposure: Insights\nfrom Real-time measurements","volume":"170","author":"You","year":"2022","journal-title":"Environ. Int."},{"issue":"10","key":"2026082211090742100_cit9","doi-asserted-by":"publisher","first-page":"6740","DOI":"10.1021\/acs.est.0c08304","article-title":"High-Resolution\nExposure Assessment for Volatile Organic Compounds in Two California\nResidences","volume":"55","author":"Lunderberg","year":"2021","journal-title":"Environ. Sci. Technol."},{"issue":"9","key":"2026082211090742100_cit10","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1021\/envhealth.5c00016","article-title":"Ex Vivo Biosensor Strategy Reveals\nthe Vascular Toxic Effects of\nVolatile Organic Compounds Derived from Indoor Renovation","volume":"3","author":"Yang","year":"2025","journal-title":"Environ. Health."},{"issue":"8","key":"2026082211090742100_cit11","doi-asserted-by":"publisher","first-page":"87004","DOI":"10.1289\/EHP6404","article-title":"Quantitative\nMeta-Analysis of the Relation between Occupational Benzene Exposure\nand Biomarkers of Cytogenetic Damage","volume":"128","author":"Scholten","year":"2020","journal-title":"Environ.\nHealth Perspect."},{"issue":"5","key":"2026082211090742100_cit12","doi-asserted-by":"publisher","DOI":"10.1111\/ina.13038","article-title":"Health effects of exposure\nto indoor volatile organic compounds from\n1980 to 2017: A systematic review and meta-analysis","volume":"32","author":"Liu","year":"2022","journal-title":"Indoor Air"},{"issue":"4","key":"2026082211090742100_cit13","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202512663","article-title":"Interior Decorative VOCs Elevate T Cell-Mediated Obstructive\nLung Disease Risks via Osteogenesis-Driven Lymphoid-Biased Hematopoiesis","volume":"13","author":"Yu","year":"2026","journal-title":"Adv. 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Environ. Health B Crit. Rev."},{"issue":"3","key":"2026082211090742100_cit19","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1093\/carcin\/bgh353","article-title":"Ultrafine\nparticulate matter and high-level benzene urban air pollution in relation\nto oxidative DNA damage","volume":"26","author":"Avogbe","year":"2005","journal-title":"Carcinogenesis"},{"issue":"9","key":"2026082211090742100_cit20","doi-asserted-by":"publisher","first-page":"5261","DOI":"10.1021\/es505316f","article-title":"New Look at BTEX: Are Ambient Levels\na Problem?","volume":"49","author":"Bolden","year":"2015","journal-title":"Environ. Sci. Technol."},{"key":"2026082211090742100_cit21","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3389\/fpubh.2020.00014","article-title":"Environmental\nand Health Impacts of Air Pollution: A Review","volume":"8","author":"Manisalidis","year":"2020","journal-title":"Front. 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Total Environ."},{"issue":"2","key":"2026082211090742100_cit24","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1007\/s12094-024-03616-z","article-title":"Integrating\nplasma proteome with genome reveals novel protein biomarkers\nin colorectal cancer","volume":"27","author":"Ye","year":"2025","journal-title":"Clin. Transl. Oncol."},{"issue":"12","key":"2026082211090742100_cit25","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1038\/s41588-021-00978-w","article-title":"Large-scale integration of the plasma proteome with genetics and\ndisease","volume":"53","author":"Ferkingstad","year":"2021","journal-title":"Nat. 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Proteome Res."},{"key":"2026082211090742100_cit31","doi-asserted-by":"publisher","first-page":"118708","DOI":"10.1016\/j.envpol.2021.118708","article-title":"GCN5-mediated\nPKM2 acetylation participates in benzene-induced hematotoxicity through\nregulating glycolysis and inflammation via p-Stat3\/IL17A axis","volume":"295","author":"Zhang","year":"2022","journal-title":"Environ. Pollut."},{"key":"2026082211090742100_cit32","doi-asserted-by":"publisher","first-page":"108601","DOI":"10.1016\/j.envint.2024.108601","article-title":"Exposure\nto per- and polyfluoroalkyl substances\nand high-throughput proteomics in Hispanic youth","volume":"186","author":"Chen","year":"2024","journal-title":"Environ. Int."},{"issue":"7","key":"2026082211090742100_cit33","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1021\/envhealth.5c00014","article-title":"Evaluating\nthe Vascular Risk of PFCs: An Integrated\nXGBoost-Driven Structure-Activity Prediction and Experimental Validation\nStudy","volume":"3","author":"Miao","year":"2025","journal-title":"Environ. Health."},{"key":"2026082211090742100_cit34","doi-asserted-by":"publisher","first-page":"1197275","DOI":"10.3389\/fimmu.2023.1197275","article-title":"Identification\nof potential\nferroptosis-associated biomarkers in rheumatoid arthritis","volume":"14","author":"He","year":"2023","journal-title":"Front. Immunol."},{"key":"2026082211090742100_cit35","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene\nset variation analysis\nfor microarray and RNA-seq data","volume":"14","author":"Ha\u0308nzelmann","year":"2013","journal-title":"BMC Bioinf."},{"key":"2026082211090742100_cit36","doi-asserted-by":"publisher","first-page":"973799","DOI":"10.3389\/fimmu.2022.973799","article-title":"Revealing the novel autophagy-related genes\nfor ligamentum flavum hypertrophy in patients and mice model","volume":"13","author":"Li","year":"2022","journal-title":"Front. Immunol."},{"issue":"11","key":"2026082211090742100_cit37","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1021\/envhealth.4c00052","article-title":"Lung Single-Cell Transcriptomics\nOffers Insights into the Pulmonary\nInterstitial Toxicity Caused by Silica Nanoparticles","volume":"2","author":"Li","year":"2024","journal-title":"Environ. 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Environ. Saf."},{"key":"2026082211090742100_cit41","doi-asserted-by":"publisher","first-page":"135630","DOI":"10.1016\/j.jhazmat.2024.135630","article-title":"Identifying high-risk\nvolatile organic compounds in residences of Chinese megacities: A\ncomprehensive health-risk assessment","volume":"479","author":"Ji","year":"2024","journal-title":"J. Hazard.\nMater."},{"issue":"2","key":"2026082211090742100_cit42","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.toxlet.2006.11.008","article-title":"Effect of\nlong-term exposure to low-level\ntoluene on airway inflammatory response in mice","volume":"168","author":"Fujimaki","year":"2007","journal-title":"Toxicol. Lett."},{"issue":"19","key":"2026082211090742100_cit43","doi-asserted-by":"publisher","first-page":"10014","DOI":"10.3390\/ijerph181910014","article-title":"Factors Affecting\nAdverse Health Effects of Gasoline Station Workers","volume":"18","author":"Tongsantia","year":"2021","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"2026082211090742100_cit44","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.envres.2018.05.029","article-title":"The role of B7 costimulation in benzene immunotoxicity\nand its potential association with cancer risk","volume":"166","author":"Sauer","year":"2018","journal-title":"Environ. Res."},{"issue":"3","key":"2026082211090742100_cit45","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.3390\/ijms25031566","article-title":"The Lectin\nPathway of the Complement System-Activation,\nRegulation, Disease Connections and Interplay with Other (Proteolytic)\nSystems","volume":"25","author":"Dobo\u0301","year":"2024","journal-title":"Int. J. Mol. Sci."},{"issue":"2","key":"2026082211090742100_cit46","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1124\/pharmrev.120.000072","article-title":"Therapeutic Targeting of the Complement\nSystem: From Rare Diseases to Pandemics","volume":"73","author":"Garred","year":"2021","journal-title":"Pharmacol.\nRev."},{"issue":"16","key":"2026082211090742100_cit47","doi-asserted-by":"publisher","first-page":"12563","DOI":"10.3390\/ijms241612563","article-title":"The Crossroads of the\nCoagulation System and the Immune System: Interactions and Connections","volume":"24","author":"Wilhelm","year":"2023","journal-title":"Int. J. Mol. Sci."},{"issue":"5","key":"2026082211090742100_cit48","doi-asserted-by":"publisher","first-page":"305","DOI":"10.2500\/aap.2024.45.240050","article-title":"Immunodeficiency: Complement disorders","volume":"45","author":"McMurray","year":"2024","journal-title":"Allergy Asthma Proc."},{"issue":"S27","key":"2026082211090742100_cit49","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1111\/pai.13635","article-title":"Inherited defects in\nthe complement system","volume":"33","author":"Leonardi","year":"2022","journal-title":"Pediatr. Allergy Immunol."},{"issue":"5","key":"2026082211090742100_cit50","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1111\/bjh.17172","article-title":"Disseminated\nintravascular coagulation:\nepidemiology, biomarkers, and management","volume":"192","author":"Adelborg","year":"2021","journal-title":"Br.\nJ. Hamaetol."},{"issue":"8","key":"2026082211090742100_cit51","doi-asserted-by":"publisher","first-page":"4200","DOI":"10.3390\/ijms22084200","article-title":"Platelets\nand the Antiphospholipid Syndrome","volume":"22","author":"Huang","year":"2021","journal-title":"Int. J. 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