{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:59:01Z","timestamp":1785218341688,"version":"3.55.0"},"reference-count":64,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":["82200311"],"award-info":[{"award-number":["82200311"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The occurrence and development of atherosclerosis (AS) are closely related to disorders of lipid metabolism and dysfunction of autophagy. However, the key regulatory genes and immune microenvironment characteristics require further exploration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study integrated the bulk transcriptome and single\u2010cell RNA sequencing data, and utilized bioinformatics methods to screen the differentially expressed genes (DEGs) of AS. The weighted gene co\u2010expression network analysis (WGCNA) was used to identify the key gene modules related to lipid metabolism and autophagy. The core regulatory genes were further screened based on the machine learning algorithm (LASSO regression). The enrichment scores of 28 immune cell subtypes were calculated by ssGSEA, and the correlation between the immune infiltration characteristics and the expression levels of the three core genes (PRKCB, NLRC4, and TNFSF10) was analyzed by Spearman correlation analysis. The single\u2010cell transcriptome data analysis was performed to determine the cell subtype distribution characteristics of the core genes and to compare the expression differences in lipid metabolism\u2010autophagy\u2010related gene expression across distinct cell subtypes. In addition, we screened potential drugs targeting the key genes from the public drug database, and simulated the binding mode of approved drugs with the active site of PRKCB by molecular docking technology. Ultimately, the expression of target factors in mouse aortic tissues was determined by quantitative real\u2010time PCR (RT\u2010qPCR), Western blotting, and immunohistochemical (IHC) analysis. Concurrently, the levels of TNFSF10 in mouse plasma were confirmed through enzyme\u2010linked immunosorbent assay (ELISA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>Three lipid metabolism\u2010autophagy core regulatory genes, PRKCB, NLRC4, and TNFSF10, were identified. These genes were significantly associated with the immune microenvironment of AS plaques and exhibited different cell subpopulation distribution patterns. The macrophage subpopulations showed higher lipid metabolism\u2010autophagy regulatory activity. Molecular docking revealed that the anti\u2010atherosclerotic drugs quercetin and atenolol can stably bind to the active site of PRKCB (with docking energies of \u20108.3\u2009kcal\/mol and \u20106.2\u2009kcal\/mol, respectively), a finding that identifies PRKCB as a candidate target worthy of further attention. Experimental evidence confirmed that the expression of these three key factors was significantly elevated in atherosclerotic plaque tissue, and the levels of TNFSF10 in the plasma of atherosclerotic mice were also significantly higher than those in the control group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies PRKCB, NLRC4, and TNFSF10 as key hub genes that link lipid metabolism and autophagy in AS, and highlights their potential as diagnostic biomarkers and therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cbf.70221","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T09:32:06Z","timestamp":1782984726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of PRKCB, NLRC4, and TNFSF10 as Key Regulators of the Lipid Metabolism\u2010Autophagy Network in Atherosclerosis"],"prefix":"10.1002","volume":"44","author":[{"given":"Min","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Rui Jin Hospital Shanghai Jiao Tong University School of Medicine Shanghai P.R. 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