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Reactive oxygen species (ROS) accumulation plays a key role in AD's disease progression. Therefore, a novel single\u2010atom catalyst is designed with isolated Cu\n                    <jats:sub>1<\/jats:sub>\n                    \u2010N\n                    <jats:sub>4<\/jats:sub>\n                    sites anchored on carbon support (Cu\n                    <jats:sub>1<\/jats:sub>\n                    \u2010N\n                    <jats:sub>4<\/jats:sub>\n                    ISAC), featuring triple antioxidant enzyme\u2010mimicking activities, for efficient AD cascade catalytic therapy (CCT). The excellent superoxide dismutase (SOD)\u2010, glutathione peroxidase (GPx)\u2010, and ascorbate peroxidase (APx)\u2010like activities of Cu\n                    <jats:sub>1<\/jats:sub>\n                    \u2010N\n                    <jats:sub>4<\/jats:sub>\n                    ISACs enable the sequential conversion of O\n                    <jats:sub>2<\/jats:sub>\n                    \u2022\n                    <jats:sup>\u2212<\/jats:sup>\n                    to H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    and then to harmless H\n                    <jats:sub>2<\/jats:sub>\n                    O, thereby protecting keratinocytes from oxidative stress damage. Notably, two novel experimental methods are developed to directly prove the SOD\u2010GPx and SOD\u2010APx cascade catalytic activities for the first time. In vivo experiments show that Cu\n                    <jats:sub>1<\/jats:sub>\n                    \u2010N\n                    <jats:sub>4<\/jats:sub>\n                    ISACs are more potent than a recommended typical medicine (halcinonide solution). Additionally, RNA sequencing and bioinformatic analysis reveal that Cu\n                    <jats:sub>1<\/jats:sub>\n                    \u2010N\n                    <jats:sub>4<\/jats:sub>\n                    ISACs reduce inflammation and inhibit ROS production by activating PPAR signaling, which is aberrantly reduced in AD. Therefore, the synthesized catalytic medicine offers an alternative to alleviate AD and has the potential to serve as PPAR agonists for treating similar diseases.\n                  <\/jats:p>","DOI":"10.1002\/smll.202407365","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T03:43:46Z","timestamp":1728013426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Single\u2010Atom Catalysts with Isolated Cu\n                    <sub>1<\/sub>\n                    \u2010N\n                    <sub>4<\/sub>\n                    Sites for Atopic Dermatitis Cascade Catalytic Therapy via Activating PPAR Signaling"],"prefix":"10.1002","volume":"20","author":[{"given":"Le","family":"Kuai","sequence":"first","affiliation":[{"name":"Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Institute of Dermatology Shanghai University of Traditional 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