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Here, we present a boron-doped copper single-atom nanomaterial (Cu\/NC-B) designed to achieve a dual functional blockade of the TSLP signaling axis, offering a more comprehensive therapeutic intervention. Therapeutically, Cu\/NC-B significantly alleviated MC903-induced AD-like lesions, showing efficacy comparable to that of crisaborole (CB) with a superior safety profile. Single-cell transcriptomics analysis revealed that Cu\/NC-B selectively targets a previously uncharacterized, highly inflammatory KC subpopulation (KC_Spinous_Tslp), thereby disrupting a critical cellular node in AD pathology. At the molecular level, Cu\/NC-B exerts its effects through two complementary pathways: epigenetic repression of TSLP via nicotinamide adenine dinucleotide (NAD+)-dependent activation of SIRT1\/3 and competitive antagonism of the TSLP receptor (TSLPR). Our work establishes Cu\/NC-B as a dual-action nanotherapeutic capable of concurrently suppressing TSLP transcription and disrupting its receptor engagement, thereby proposing a targeted intervention for AD treatment.<\/jats:p>","DOI":"10.1021\/acsnano.6c08065","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:14:16Z","timestamp":1788354856000},"page":"24797-24817","source":"Crossref","is-referenced-by-count":0,"title":["A Boron-Doped Copper\nSingle-Atom Nanozyme Ameliorates\nAtopic Dermatitis via Dual Regulation of Thymic Stromal Lymphopoietin\nSignaling and Receptor Interaction"],"prefix":"10.1021","volume":"20","author":[{"given":"Pian","family":"Yu","sequence":"first","affiliation":[{"name":"Central South University , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Furong Laboratory , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology , , ,","place":["Changsha, Hunan, China, 410000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihui","family":"Ma","sequence":"additional","affiliation":[{"name":"Central South University , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Furong Laboratory , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology , , ,","place":["Changsha, Hunan, China, 410000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Liu","sequence":"additional","affiliation":[{"name":"Soochow University , , ,","place":["Suzhou, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1605-3225","authenticated-orcid":true,"given":"Ge","family":"Fang","sequence":"additional","affiliation":[{"name":"Soochow University , , ,","place":["Suzhou, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Central South University , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Furong Laboratory , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology , , ,","place":["Changsha, Hunan, China, 410000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongxuan","family":"Yan","sequence":"additional","affiliation":[{"name":"Central South University , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Furong Laboratory , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology , , ,","place":["Changsha, Hunan, China, 410000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Fang","sequence":"additional","affiliation":[{"name":"Central South University , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Furong Laboratory , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology , , ,","place":["Changsha, Hunan, China, 410000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanming","family":"Wang","sequence":"additional","affiliation":[{"name":"Central South University , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Furong Laboratory , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology , , ,","place":["Changsha, Hunan, China, 410000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaozhi","family":"Cao","sequence":"additional","affiliation":[{"name":"Central South University , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Furong Laboratory , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology , , ,","place":["Changsha, Hunan, China, 410000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Central South University , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Furong Laboratory , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology , , ,","place":["Changsha, Hunan, China, 410000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Central South University , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Furong Laboratory , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology , , ,","place":["Changsha, Hunan, China, 410000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0548-2470","authenticated-orcid":true,"given":"Cuicui","family":"Ge","sequence":"additional","affiliation":[{"name":"Soochow University , , ,","place":["Suzhou, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7104-5490","authenticated-orcid":true,"given":"Cong","family":"Peng","sequence":"additional","affiliation":[{"name":"Central South University , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Xiangya Hospital , , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"Furong Laboratory , , ,","place":["Changsha, Hunan, China, 410000"]},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology , , ,","place":["Changsha, Hunan, China, 410000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"issue":"10478","key":"2026091510075791600_cit1","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/S0140-6736(24)02519-4","article-title":"Atopic 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Targeted Ther."},{"key":"2026091510075791600_cit6","doi-asserted-by":"publisher","first-page":"1694066","DOI":"10.3389\/fimmu.2025.1694066","article-title":"Keratinocytes\nas active regulators of cutaneous\nand mucosal immunity: a systematic review across inflammatory epithelial\ndisorders","volume":"16","author":"Klimitz","year":"2025","journal-title":"Front. Immunol."},{"issue":"2","key":"2026091510075791600_cit7","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.cell.2013.08.057","article-title":"The epithelial cell-derived atopic dermatitis cytokine\nTSLP activates neurons to induce itch","volume":"155","author":"Wilson","year":"2013","journal-title":"Cell"},{"issue":"2","key":"2026091510075791600_cit8","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.jaci.2024.06.002","article-title":"Adipose tissue\nremodeling via TSLP-mediated IL-4\/IL-13 signaling: Implications for\natopic dermatitis and skin barrier","volume":"154","author":"Sugita","year":"2024","journal-title":"J. Allergy\nClin. Immunol."},{"issue":"8","key":"2026091510075791600_cit9","doi-asserted-by":"publisher","first-page":"4129","DOI":"10.1007\/s10238-023-01147-5","article-title":"Serum thymic stromal lymphopoietin\n(TSLP) levels in\natopic dermatitis patients: a systematic review and meta-analysis","volume":"23","author":"Garci\u0301a-Reyes","year":"2023","journal-title":"Clin. Exp. Med."},{"issue":"3","key":"2026091510075791600_cit10","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.jaci.2014.09.015","article-title":"Thymic stromal lymphopoietin\nsignaling in CD4(+) T cells is required for TH2 memory","volume":"135","author":"Wang","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026091510075791600_cit11","doi-asserted-by":"publisher","first-page":"14937","DOI":"10.1038\/ncomms14937","article-title":"Structure and antagonism of the receptor complex\nmediated by human TSLP in allergy and asthma","volume":"8","author":"Verstraete","year":"2017","journal-title":"Nat. Commun."},{"key":"2026091510075791600_cit12","doi-asserted-by":"publisher","first-page":"107648","DOI":"10.1016\/j.pharmthera.2020.107648","article-title":"TSLP as druggable\ntarget - a silver-lining\nfor atopic diseases?","volume":"217","author":"Adhikary","year":"2021","journal-title":"Pharmacol. Ther."},{"issue":"7","key":"2026091510075791600_cit13","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1038\/s44321-024-00085-3","article-title":"Disrupting\nTSLP-TSLP receptor interactions via putative\nsmall molecule inhibitors yields a novel and efficient treatment option\nfor atopic diseases","volume":"16","author":"Adhikary","year":"2024","journal-title":"EMBO Mol. Med."},{"issue":"7","key":"2026091510075791600_cit14","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202113943","article-title":"NAD(+)\nhomeostasis in human health and disease","volume":"13","author":"Zapata-Pe\u0301rez","year":"2021","journal-title":"EMBO\nMol. 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Sci."},{"key":"2026091510075791600_cit29","doi-asserted-by":"publisher","first-page":"7697699","DOI":"10.1155\/2023\/7697699","article-title":"The Role of\nTSLP in Atopic Dermatitis: From Pathogenetic Molecule to Therapeutical\nTarget","volume":"2023","author":"Luo","year":"2023","journal-title":"Mediat. Inflamm."},{"issue":"3","key":"2026091510075791600_cit30","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1111\/bjd.12938","article-title":"Quercetagetin inhibits\nmacrophage-derived chemokine in HaCaT human keratinocytes via the\nregulation of signal transducer and activator of transcription 1,\nsuppressor of cytokine signalling 1 and transforming growth factor-\u03b21","volume":"171","author":"Kang","year":"2014","journal-title":"Br. J. Dermatol."},{"issue":"1","key":"2026091510075791600_cit31","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.cell.2008.10.052","article-title":"SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent\ngene expression and organismal life span","volume":"136","author":"Kawahara","year":"2009","journal-title":"Cell"},{"issue":"2","key":"2026091510075791600_cit32","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s41580-020-00313-x","article-title":"NAD(+) metabolism and\nits roles in cellular processes during ageing","volume":"22","author":"Covarrubias","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"2","key":"2026091510075791600_cit33","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1089\/ars.2007.1672","article-title":"NAD+\/NADH\nand NADP+\/NADPH in cellular functions and cell death: regulation and\nbiological consequences","volume":"10","author":"Ying","year":"2008","journal-title":"Antioxid. 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