{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T06:27:52Z","timestamp":1787120872805,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dysregulation of neutrophil and consistent vascular calcification(VC) contributes to the pathogenesis and progression of chronic IgA nephropathy(C-IgAN). However, its integrated mechanism in IgAN has not yet been elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We integrated GSVA, CIBERSORT and WGCNA algorithms in C-IgAN patient bulk profiles(GSE35487 and GSE93798) downloaded from GEO database for identified VC and neutrophil (VN)-related shared DEGs. Next, explainable and systemic machine learning algorithms in C-IgAN training and validation bulk profiles identified VN-associated diagnostic model and hub gene. In addition, based on VN-associated shared gene signature, we performed NMF analysis for identification of VN-related molecular subgroups, and then we also investigated the molecular and immune patterns between subgroups. Besides, we also investigated hub gene, VC and neutrophil molecular landscapes at C-IgAN patient single-cell level via advanced analytical frameworks, such as sctenifoldknk and Bayes-prism algorithms. Novelty, deep learning algorithm (DrugRefLector) and molecular docking based on C-IgAN identified optimal therapeutic agent targeting hub gene. Finally,\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays examined the expression pattern of hub gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our study first traced dynamic VN patterns in C-IgAN and identified VN-associated diagnostic and molecular subgroups. Besides,\n                      <jats:italic>CLEC4D<\/jats:italic>\n                      can be considered as neutrophil-distributed hub gene involved in VC and C-IgAN pathogenesis, which also can be considered as a drug target of BRD-K27184429 in C-IgAN.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study first identified VN-related patterns for C-IgAN patients, which provides novel idea into clinical applications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1928397","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:47:51Z","timestamp":1787118471000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding vascular calcification-neutrophil signature in pathogenesis of chronic IgA nephropathy: evidence from artificial intelligence-driven multi-omics and in vitro validation"],"prefix":"10.3389","volume":"17","author":[{"given":"Chunyu","family":"Cao","sequence":"first","affiliation":[{"name":"First Affiliated Hospital of Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencheng","family":"Yan","sequence":"additional","affiliation":[{"name":"First Clinical Medical College of Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Li","sequence":"additional","affiliation":[{"name":"First Clinical Medical College of Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lu","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat. 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