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The aryl hydrocarbon receptor (AhR), a contaminant sensor linked to tryptophan metabolites, is regulated by IL4I. However, how PM2.5 stimulation via IL4I1 influences AhR activation and CRS pathogenesis remains unclear. This study explored the IL4I1-AhR pathway in CRS using patient tissues, HNEpCs, and murine models. Methods included IHC, qRT-PCR, and WB under PM2.5 exposure, with further investigation into downstream effects on CYP1B1 and epithelial\u2013mesenchymal transition (EMT). Significant upregulation of IL4I1, AhR, and CYP1B1 was observed in CRS tissues, with higher expression levels in CRS patients. Exposure to PM2.5 activated the IL4I1-AhR pathway, leading to decreased E-cadherin, increased N-cadherin and vimentin, and impaired nasal mucosal barrier function. In vitro experiments demonstrated that PM2.5-induced EMT in HNEpCs was mediated by IL4I1-dependent AhR activation. CH223191 reduced cell migration and EMT, while IL4I1 knockdown attenuated AhR activation and EMT marker expression. Murine models further confirmed that PM2.5 exacerbated nasal polyp formation and tissue remodeling via the IL4I1-AhR pathway. This study underscores the critical role of the IL4I1-AhR signaling pathway in PM2.5-induced nasal mucosal barrier dysfunction and EMT in CRS. IL4I1, as an upstream regulator of AhR, promotes EMT and nasal mucosal barrier disruption.<\/jats:p>","DOI":"10.3390\/toxics13060488","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T04:42:25Z","timestamp":1749530545000},"page":"488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PM2.5 Induced Nasal Mucosal Barrier Dysfunction and Epithelial\u2013Mesenchymal Transition to Promote Chronic Rhinosinusitis Through IL4I1-AhR Signaling Pathway"],"prefix":"10.3390","volume":"13","author":[{"given":"Yue","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Upper Airway Inflammation and Tumor Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Upper Airway Inflammation and Tumor Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panhui","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Upper Airway Inflammation and Tumor Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Upper Airway Inflammation and Tumor Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longlan","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Upper Airway Inflammation and Tumor Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Upper Airway Inflammation and Tumor Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6749-1674","authenticated-orcid":false,"given":"Tao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Upper Airway Inflammation and Tumor Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Upper Airway Inflammation and Tumor Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"ref_1","first-page":"287","article-title":"EPOS2020\/EUFOREA expert opinion on defining disease states and therapeutic goals in CRSwNP","volume":"62","author":"Fokkens","year":"2024","journal-title":"Rhinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11882-015-0540-2","article-title":"The Etiology and Pathogenesis of Chronic Rhinosinusitis: A Review of Current Hypotheses","volume":"15","author":"Lam","year":"2015","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109658","DOI":"10.1016\/j.intimp.2022.109658","article-title":"Ferroptosis is involved in PM2.5-induced acute nasal epithelial injury via AMPK-mediated autophagy","volume":"115","author":"Gu","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.jaci.2019.11.040","article-title":"Long-term air pollution exposure is associated with increased severity of rhinitis in 2 European cohorts","volume":"145","author":"Burte","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1900913","DOI":"10.1183\/13993003.00913-2019","article-title":"Early life exposure to air pollution and incidence of childhood asthma, allergic rhinitis and eczema","volume":"55","author":"To","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12199-021-00969-7","article-title":"Early childhood traffic-related air pollution and risk of allergic rhinitis at 2\u20134 years of age modification by family stress and male gender: A case-control study in Shenyang, China","volume":"26","author":"Hao","year":"2021","journal-title":"Environ. Health Prev. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4936","DOI":"10.1016\/S0021-9258(17)33205-2","article-title":"Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase","volume":"251","author":"Poland","year":"1976","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41419-018-1286-2","article-title":"Tetrandrine enhances the ubiquitination and degradation of Syk through an AhR-c-src-c-Cbl pathway and consequently inhibits osteoclastogenesis and bone destruction in arthritis","volume":"10","author":"Jia","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Manni, G., Mondanelli, G., Scalisi, G., Pallotta, M.T., Nardi, D., Padiglioni, E., Romani, R., Talesa, V.N., Puccetti, P., and Fallarino, F. (2020). Pharmacologic Induction of Endotoxin Tolerance in Dendritic Cells by L-Kynurenine. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00292"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e15677","DOI":"10.15252\/emmm.202215677","article-title":"The AhR-SRC axis as a therapeutic vulnerability in BRAFi-resistant melanoma","volume":"14","author":"Paris","year":"2022","journal-title":"EMBO Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/s41577-019-0125-8","article-title":"The aryl hydrocarbon receptor: An environmental sensor integrating immune responses in health and disease","volume":"19","author":"Rothhammer","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Vogel, C., Van Winkle, L.S., Esser, C., and Haarmann-Stemmann, T. (2020). The aryl hydrocarbon receptor as a target of environmental stressors\u2014Implications for pollution mediated stress and inflammatory responses. Redox Biol., 34.","DOI":"10.1016\/j.redox.2020.101530"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1021\/acs.chemrestox.9b00476","article-title":"The Ah Receptor: Adaptive Metabolism, Ligand Diversity, and the Xenokine Model","volume":"33","author":"Avilla","year":"2020","journal-title":"Chem. Res. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1002\/eji.200535503","article-title":"IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: A potential role in psoriasis","volume":"36","author":"Wolk","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/nrc3846","article-title":"Aryl hydrocarbon receptor ligands in cancer: Friend and foe","volume":"14","author":"Murray","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cope, E.K., Goldberg, A.N., Pletcher, S.D., and Lynch, S.V. (2017). Compositionally and functionally distinct sinus microbiota in chronic rhinosinusitis patients have immunological and clinically divergent consequences. Microbiome, 5.","DOI":"10.1186\/s40168-017-0266-6"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.jaci.2017.06.013","article-title":"Functional role of kynurenine and aryl hydrocarbon receptor axis in chronic rhinosinusitis with nasal polyps","volume":"141","author":"Wang","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/j.cell.2020.07.038","article-title":"IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression","volume":"182","author":"Sadik","year":"2020","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1093\/biolre\/ioae089","article-title":"Male infertility and perfluoroalkyl and poly-fluoroalkyl substances: Evidence for alterations in phosphorylation of proteins and fertility-related functional attributes in bull spermatozoadagger","volume":"111","author":"Kumaresan","year":"2024","journal-title":"Biol. Reprod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"114439","DOI":"10.1016\/j.intimp.2025.114439","article-title":"Macrophage-mediated activation of the IL4I1\/AhR axis is a key player in allergic rhinitis","volume":"152","author":"Liu","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/sj.gene.6363716","article-title":"IL-TIF\/IL-22: Genomic organization and mapping of the human and mouse genes","volume":"1","author":"Dumoutier","year":"2000","journal-title":"Genes Immun."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wang, J., Zhao, Y., Zhang, X., Tu, W., Wan, R., Shen, Y., Zhang, Y., Zhang, Y., Trivedi, R., and Gao, P. (2022). Type II alveolar epithelial cell aryl hydrocarbon receptor protects against allergic airway inflammation through controlling cell autophagy. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.964575"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/exd.12148","article-title":"Role of the aryl hydrocarbon receptor in tobacco smoke extract-induced matrix metalloproteinase-1 expression","volume":"22","author":"Ono","year":"2013","journal-title":"Exp. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1093\/toxsci\/kfs024","article-title":"Aryl hydrocarbon receptor (AhR) regulates silica-induced inflammation but not fibrosis","volume":"126","author":"Beamer","year":"2012","journal-title":"Toxicol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1111\/all.15240","article-title":"Altiner S.; Ozdey U.; Ogulur I.; Mitamura Y.; et al. Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease","volume":"77","author":"Celebi","year":"2022","journal-title":"Allergy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s41577-021-00538-7","article-title":"Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions?","volume":"21","author":"Akdis","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"56","DOI":"10.4168\/aair.2020.12.1.56","article-title":"Particulate Matter 2.5 Causes Deficiency in Barrier Integrity in Human Nasal Epithelial Cells","volume":"12","author":"Xian","year":"2020","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zou, Q.Y., Hong, S.L., Kang, H.Y., Ke, X., Wang, X., Li, J., and Shen, Y. (2020). Effect of di-(2-ethylhexyl) phthalate (DEHP) on allergic rhinitis. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-71517-6"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nm1710","article-title":"IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia","volume":"14","author":"Aujla","year":"2008","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2500\/ajra.2016.30.4311","article-title":"Increased expression of the aryl hydrocarbon receptor in allergic nasal mucosa, contributing to chemokine secretion in nasal epithelium","volume":"30","author":"Kim","year":"2016","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/s41572-020-00218-1","article-title":"Adult chronic rhinosinusitis","volume":"6","author":"Bachert","year":"2020","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3217","DOI":"10.1111\/all.15384","article-title":"The role of hypoxia in the pathophysiology of chronic rhinosinusitis","volume":"77","author":"Zhong","year":"2022","journal-title":"Allergy"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Shen, Y., Zhang, Z.H., Hu, D., Ke, X., Gu, Z., Zou, Q.Y., Hu, G.H., Song, S.H., Kang, H.Y., and Hong, S.L. (2018). The airway inflammation induced by nasal inoculation of PM2.5 and the treatment of bacterial lysates in rats. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-28156-9"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1159\/000481510","article-title":"Differential Expression of the Aryl Hydrocarbon Receptor and Transforming Growth Factor Beta 1 in Chronic Rhinosinusitis with Nasal Polyps with Allergic Rhinitis","volume":"79","author":"Chen","year":"2017","journal-title":"ORL J. Otorhinolaryngol. Relat. Spec."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41590-020-00850-9","article-title":"IL-2 regulates tumor-reactive CD8(+) T cell exhaustion by activating the aryl hydrocarbon receptor","volume":"22","author":"Liu","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1016\/j.apsb.2021.03.009","article-title":"Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT\/GSK3beta\/IL-8 signaling pathway","volume":"11","author":"Zhao","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1111\/febs.17109","article-title":"Targeting of neuroblastoma cells through Kynurenine-AHR pathway inhibition","volume":"291","author":"Dos","year":"2024","journal-title":"FEBS J."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kado, S.Y., Bein, K., Castaneda, A.R., Pouraryan, A.A., Garrity, N., Ishihara, Y., Rossi, A., Haarmann-Stemmann, T., Sweeney, C.A., and Vogel, F.A. (2023). Regulation of IDO2 by the Aryl Hydrocarbon Receptor (AhR) in Breast Cancer. Cells, 12.","DOI":"10.3390\/cells12101433"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s12035-024-04263-9","article-title":"Ido2 Deficiency Exacerbates Motor Impairment and Reduces Aryl Hydrocarbon Receptor Activity through Decreased Kynurenine in a Chronic Demyelinating Mouse Model","volume":"62","author":"Kunisawa","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Badawy, A.A. (2023). The kynurenine pathway of tryptophan metabolism: A neglected therapeutic target of COVID-19 pathophysiology and immunotherapy. Biosci. Rep., 43.","DOI":"10.1042\/BSR20230595"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1016\/j.jaci.2015.10.033","article-title":"The mannose receptor negatively modulates the Toll-like receptor 4-aryl hydrocarbon receptor-indoleamine 2,3-dioxygenase axis in dendritic cells affecting T helper cell polarization","volume":"137","author":"Salazar","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zhang, J., Lin, B., Zhang, Y., Hu, X., Liu, T., Liu, E.H., and Liu, S. (2024). Baitouweng decoction alleviates ulcerative colitis by regulating tryptophan metabolism through DOPA decarboxylase promotion. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1423307"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10678","DOI":"10.1021\/acs.jafc.0c03735","article-title":"Endogenous Indole Pyruvate Pathway for Tryptophan Metabolism Mediated by IL4I1","volume":"68","author":"Zhang","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Luo, J.M., Zhang, T.T., He, Y.Y., Luo, H.N., Hong, Y.Q., and Yang, Z.M. (2023). Human Chorionic Gonadotropin-Stimulated Interleukin-4-Induced-1 (IL4I1) Promotes Human Decidualization via Aryl Hydrocarbon Receptor. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043163"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e355","DOI":"10.1002\/mco2.355","article-title":"Thymol targeting interleukin 4 induced 1 expression reshapes the immune microenvironment to sensitize the immunotherapy in lung adenocarcinoma","volume":"4","author":"Li","year":"2023","journal-title":"MedComm"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"101128","DOI":"10.1016\/j.xcrm.2023.101128","article-title":"Mechanical confinement promotes heat resistance of hepatocellular carcinoma via SP1\/IL4I1\/AHR axis","volume":"4","author":"Zhang","year":"2023","journal-title":"Cell Rep. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, T., Jiang, B., Fu, B., Shang, C., Feng, H., Chen, T., and Jiang, Y. (2024). PM2.5 Induces Cardiomyoblast Senescence via AhR-Mediated Oxidative Stress. Antioxidants, 13.","DOI":"10.3390\/antiox13070786"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e145185","DOI":"10.1172\/jci.insight.145185","article-title":"Particulate matter causes skin barrier dysfunction","volume":"6","author":"Kim","year":"2021","journal-title":"JCI Insight"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"37014","DOI":"10.1289\/EHP11580","article-title":"Multidimensional Analysis of Lung Lymph Nodes in a Mouse Model of Allergic Lung Inflammation following PM2.5 and Indeno[1,2,3-cd]pyrene Exposure","volume":"131","author":"Liu","year":"2023","journal-title":"Environ. Health Perspect."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.jaci.2019.10.008","article-title":"Particulate matter of 2.5 mum or less in diameter disturbs the balance of T(H)17\/regulatory T cells by targeting glutamate oxaloacetate transaminase 1 and hypoxia-inducible factor 1alpha in an asthma model","volume":"145","author":"Sun","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"105939","DOI":"10.1016\/j.intimp.2019.105939","article-title":"Hydrogen ameliorates lung injury in a rat model of subacute exposure to concentrated ambient PM2.5 via Aryl hydrocarbon receptor","volume":"77","author":"Feng","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.jaci.2024.04.019","article-title":"ALOX15(+) M2 macrophages contribute to epithelial remodeling in eosinophilic chronic rhinosinusitis with nasal polyps","volume":"154","author":"Liu","year":"2024","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.molimm.2024.09.004","article-title":"Piezo1 regulates TGF-beta1 induced epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps","volume":"175","author":"Shu","year":"2024","journal-title":"Mol. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s11010-018-3323-y","article-title":"Promoting epithelial-to-mesenchymal transition by D-kynurenine via activating aryl hydrocarbon receptor","volume":"448","author":"Duan","year":"2018","journal-title":"Mol. Cell. Biochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"134560","DOI":"10.1016\/j.jhazmat.2024.134560","article-title":"Benzo[a]pyrene evokes epithelial-mesenchymal transition and pulmonary fibrosis through AhR-mediated Nrf2-p62 signaling","volume":"473","author":"Li","year":"2024","journal-title":"J. Hazard. Mater."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Huang, Q., Chi, Y., Deng, J., Liu, Y., Lu, Y., Chen, J., and Dong, S. (2017). Fine particulate matter 2.5 exerted its toxicological effect by regulating a new layer, long non-coding RNA. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-09818-6"}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/13\/6\/488\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:49:10Z","timestamp":1760032150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/13\/6\/488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,10]]},"references-count":56,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["toxics13060488"],"URL":"https:\/\/doi.org\/10.3390\/toxics13060488","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,10]]}}}