{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:27:18Z","timestamp":1788276438241,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273674"],"award-info":[{"award-number":["82273674"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Silver nanoparticles (AgNPs) possess potent antimicrobial properties but incur substantial pulmonary toxicity upon inhalation, with the respiratory system as their primary target. Although accumulating evidence implicates lysosomal dysfunction and ferroptosis in AgNPs\u2010associated lung injury, the upstream regulatory mechanisms linking lysosomal damage to iron\u2010dependent lipid peroxidation remain elusive. Using ICR mice (intranasal instillation of 20\u2009nm AgNPs at 0, 5, and 50\u2009mg\/kg bw for 28\u2009days) and BEAS\u20102B cells (20\u2009nm AgNPs at 0, 5, 10, and 20\u2009\u03bcg\/mL for 24\u2009h) as in\u00a0vivo and in\u00a0vitro models, we systematically explored AgNPs\u2010induced ferroptotic lung injury, focusing on transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and repair. AgNPs exposure caused dose\u2010dependent cytotoxicity and pulmonary damage, accompanied by iron dyshomeostasis, labile iron accumulation, glutathione depletion, elevated ROS\/MDA levels, dysregulated ferroptosis\u2010related proteins, and enhanced lipid peroxidation, hallmarks of ferroptosis, all significantly attenuated by iron chelation (deferoxamine, DFO). Mechanistically, AgNPs induced lysosomal injury (reduced LAMP1\/LAMP2, elevated CTSB, impaired membrane integrity, and disrupted luminal pH). Critically, TFEB activation (C1 agonist) mitigated lysosomal damage, restored iron homeostasis, and suppressed ferroptosis, while TFEB knockdown (siRNA) exacerbated these abnormalities. Our findings identify TFEB as a critical protective mediator that facilitates lysosomal repair, counteracts iron dysregulation, and inhibits ferroptosis in AgNPs\u2010exposed lung cells, elucidating AgNPs pulmonary toxicity mechanisms and highlighting TFEB as a potential therapeutic target.<\/jats:p>","DOI":"10.1002\/jat.70234","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:56:56Z","timestamp":1777874216000},"page":"3605-3621","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TFEB Attenuates Silver Nanoparticle\u2010Induced Pulmonary Ferroptosis by Preserving Lysosomal Integrity and Limiting Iron Dysregulation"],"prefix":"10.1002","volume":"46","author":[{"given":"Chenyu","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health Southeast University  Nanjing 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