{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:10:05Z","timestamp":1789150205295,"version":"build-2803163510"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Atopic dermatitis (AD) is characterized by a self-reinforcing loop between epidermal barrier dysfunction and type 2-skewed inflammation; yet the most perturbed keratinocyte states and actionable epidermal targets remain incompletely defined. We integrated pharmacogenomic target mining, complementary machine-learning feature selection (LASSO and SVM-RFE), single-cell state\u2013resolved perturbation analyses (Augur and scDist), and structure-based molecular modeling (molecular docking, MD simulation, and MM-PBSA free energy calculation) to prioritize candidate targets of baicalin in AD. CA2 emerged as a convergent epidermal candidate; scRNA-seq analyses localized CA2-associated transcriptional differences to keratinocytes, with the keratinocyte compartment exhibiting the disease-associated strongest separability and transcriptomic distance, accompanied by enrichment of metabolic reprogramming, epithelial junction and barrier remodeling, and proliferative quiescence gene programs. Structure-based evaluation supported a computationally plausible baicalin\u2013CA2 interaction, with an estimated MM-PBSA binding free energy of \u221222.082 kcal\/mol. Collectively, these findings nominate a computationally supported \u201cbaicalin\u2013CA2\u2013Kcs9\u201d axis as a hypothesis-generating framework for epidermal stratification and experimental prioritization in AD.<\/jats:p>","DOI":"10.1371\/journal.pone.0356174","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:38:13Z","timestamp":1789148293000},"page":"e0356174","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A bioinformatic single-cell and structure-informed framework identifies a baicalin\u2013CA2\u2013keratinocyte state axis in atopic dermatitis"],"prefix":"10.1371","volume":"21","author":[{"given":"Boyan","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4395-9664","authenticated-orcid":true,"given":"Jun","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"pone.0356174.ref001","article-title":"Itch, Scratching, and Sleep Mediate the Association between Disease Severity and Quality of Life in Pruritic Dermatoses: A Cross-Sectional Study","author":"MP Pereira","year":"2026","journal-title":"Dermatol Ther (Heidelb)"},{"issue":"12","key":"pone.0356174.ref002","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.3390\/life12122026","article-title":"The 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