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Here, by integrating environmentally simulated polyethylene terephthalate (PET)-NPs with an aerosol inhalation model that mirrors real-world human exposure (0.1, 1, and 10 mg\/m3), we demonstrate that chronic NP inhalation translocated to the brain and induced demyelination, neuroinflammation, and cognitive deficits. The most pronounced effects were observed at the highest exposure dose (10 mg\/m3), which is relevant to the occupational settings. Mechanistically, NP exposure triggered astrocytic CXCL12 release, leading to CXCR4-dependent microglial activation and cytokine network dysregulation. In vitro, blockade of CXCR4 with AMD3100 attenuated NP-induced microglial migration and oligodendrocytic myelin basic protein reduction. Our study thus definitively links realistic airborne NP exposure to the key neuropathological features of demyelinating disorders and pinpoints a modifiable molecular pathway that could inform exposure-based preventive strategies. These findings underscore the need for further assessment of airborne NP risks, particularly in occupational settings.<\/jats:p>","DOI":"10.1021\/acs.est.6c03987","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:02:06Z","timestamp":1791180126000},"page":"29285-29298","source":"Crossref","is-referenced-by-count":0,"title":["Inhalation\nof Environmentally Simulated PET Nanoplastics\nInduces Demyelinating Disorders via the CXCL12\/CXCR4 Axis"],"prefix":"10.1021","volume":"60","author":[{"given":"Shuang","family":"Liu","sequence":"first","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Hangzhou, China, 310024"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingcun","family":"Dong","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6207-799X","authenticated-orcid":true,"given":"Qingqing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyang","family":"Fu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Hangzhou, China, 310024"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Gao","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyu","family":"Weng","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6213-4720","authenticated-orcid":true,"given":"Ligang","family":"Hu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Hangzhou, China, 310024"]},{"name":"Jianghan University , , ,","place":["Wuhan, China, 430056"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2846-6614","authenticated-orcid":true,"given":"Chunyang","family":"Liao","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Hangzhou, China, 310024"]},{"name":"Jianghan University , , ,","place":["Wuhan, China, 430056"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6335-3917","authenticated-orcid":true,"given":"Guibin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Hangzhou, China, 310024"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"2026102007521268000_cit1","volume-title":"Drowning\nin plastics: Marine litter and plastic waste vital graphics","author":"U. 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Pollut."},{"key":"2026102007521268000_cit7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2024.134054","article-title":"Neurotoxicities\ninduced by micro\/nanoplastics: A review focusing on the risks of neurological\ndiseases","volume":"469","author":"Liu","year":"2024","journal-title":"J. Hazard. Mater."},{"key":"2026102007521268000_cit8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2024.153799","article-title":"The effects of micro- and nanoplastics\non the central nervous system: A new threat to humanity?","volume":"504","author":"Zheng","year":"2024","journal-title":"Toxicol."},{"key":"2026102007521268000_cit9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2022.128459","article-title":"Brain single-nucleus transcriptomics highlights that polystyrene\nnanoplastics potentially induce Parkinson\u2019s disease-like neurodegeneration\nby causing energy metabolism disorders in mice","volume":"430","author":"Liang","year":"2022","journal-title":"J. Hazard. 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Fibre Toxicol."},{"key":"2026102007521268000_cit27","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107390","article-title":"Polyethylene microplastics\nimpede the innate immune response by disrupting the extracellular\nmatrix and signaling transduction","volume":"26","author":"Huang","year":"2023","journal-title":"iScience"},{"key":"2026102007521268000_cit28","doi-asserted-by":"publisher","first-page":"17274","DOI":"10.1039\/D5NR00638D","article-title":"Type-dependent\neffects\nof nanoplastics on microglial activation and CXCR2-mediated chemotactic\nmigration","volume":"17","author":"Koo","year":"2025","journal-title":"Nanoscale"},{"key":"2026102007521268000_cit29","doi-asserted-by":"publisher","first-page":"16790","DOI":"10.1021\/acsnano.4c02335","article-title":"Realistic\nnanoplastics induced pulmonary damage via the crosstalk of ferritinophagy\nand mitochondrial dysfunction","volume":"18","author":"Ji","year":"2024","journal-title":"ACS Nano"},{"key":"2026102007521268000_cit30","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1007\/s11869-022-01272-2","article-title":"Atmospheric\nmicro (nano) plastics:\nfuture growing concerns for human health","volume":"16","author":"Bhat","year":"2023","journal-title":"Air\nQual. Atmos. Hlth."},{"key":"2026102007521268000_cit31","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.scitotenv.2019.04.110","article-title":"Source and potential risk assessment of suspended atmospheric microplastics\nin Shanghai","volume":"675","author":"Liu","year":"2019","journal-title":"Sci. Total Environ."},{"key":"2026102007521268000_cit32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2020.124004","article-title":"Estimation\nof the mass of microplastics ingested -\na pivotal first step towards human health risk assessment","volume":"404","author":"Senathirajah","year":"2021","journal-title":"J. Hazard. Mater."},{"issue":"1","key":"2026102007521268000_cit33","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/0027-5107(94)90020-5","article-title":"Cytogenetic Analysis of Lymphocytes\nfrom Fiberglass-Reinforced Plastics Workers Occupationally Exposed\nto Styrene","volume":"310","author":"Van Hummelen","year":"1994","journal-title":"Mutat. 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Environ."},{"key":"2026102007521268000_cit48","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2022.128874","article-title":"The distinct toxicity effects between\ncommercial and realistic polystyrene microplastics on microbiome and\nhistopathology of gut in zebrafish","volume":"434","author":"Guo","year":"2022","journal-title":"J. Hazard.\nMater."},{"key":"2026102007521268000_cit49","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.fct.2019.04.040","article-title":"Dibutyl phthalate\nimpairs neural progenitor cell proliferation and hippocampal neurogenesis","volume":"129","author":"Lee","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"2026102007521268000_cit50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2022.129593","article-title":"A new source\nof representative secondary PET nanoplastics. Obtention, characterization,\nand hazard evaluation","volume":"439","author":"Villacorta","year":"2022","journal-title":"J. Hazard. 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