{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:59:50Z","timestamp":1790791190958,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Environmental nanoplastic exposure is increasingly recognized as a contributor to metabolic dysfunction, yet its impact on susceptibility to diet\u2010induced metabolic dysfunction\u2010associated fatty liver disease (MAFLD) during development remains unclear. Here, we show that polystyrene nanoplastics (PS\u2010NPs) exacerbate high\u2010fat diet (HFD)\u2010induced hepatic steatosis in an age\u2010dependent manner. In juvenile, but not adult, mice, PS\u2010NPs augmented HFD\u2010driven dyslipidemia, hepatomegaly, and hepatic lipid accumulation without altering energy intake. Mechanistic analyses revealed disruption of the hepatic circadian\u2010mitochondrial axis, including altered clock gene programs, impaired AMP\u2010activated protein kinase (AMPK) signaling, mitochondrial dysfunction, and suppressed oxidative metabolism. In hepatocytes, PS\u2010NPs potentiated free\u2010fatty\u2010acid\u2010induced circadian misalignment, mitochondrial impairment, oxidative stress, and lipid accumulation. AMPK activation by AICAR alleviated steatosis and mitochondrial defects, whereas circadian modulation by SR9009 improved mitochondrial function and hepatocellular injury, highlighting distinct protective mechanisms. Collectively, these findings define early life as a critical window of vulnerability to combined environmental and dietary stressors and introduce the concept of chronotoxicity, the capacity of environmental exposures, such as PS\u2010NPs, to perturb circadian timing and temporal metabolic organization\u2010linking nanoplastic exposure to pediatric MAFLD.<\/jats:p>","DOI":"10.1002\/advs.77840","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Developmental Environmental Chronotoxicity by Polystyrene Nanoplastics Exacerbates High\u2010Fat Diet\u2010Induced Pediatric MAFLD Through Circadian Disruption and Mitochondrial Dysfunction"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7094-9398","authenticated-orcid":false,"given":"Peihao","family":"Xu","sequence":"first","affiliation":[{"name":"School of Medical Technology and Information Engineering The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)  Hangzhou Zhejiang China"},{"name":"Joint Medical Research Laboratory for Collaborative Prevention and Treatment of Severe Infections with Integrated Chinese and Western Medicine and Translational Medicine Zhejiang Chinese Medical University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Information Engineering The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)  Hangzhou Zhejiang China"},{"name":"Joint 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