{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T08:07:50Z","timestamp":1771142870756,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"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":["82071023"],"award-info":[{"award-number":["82071023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifaceted inflammatory condition that significantly affects patients clinically. It is vital to comprehend the basic molecular mechanisms and to discover new biomarkers. This research combines multi\u2010omics data, molecular docking, and dynamic simulations to investigate gene functions and possible biomarkers related to CRSwNP. Initially, we discovered 555 differentially expressed genes (DEGs) induced by alpha\u2010toxin (Hla) and 8119 DEGs associated with CRSwNP obtained from the Gene Expression Omnibus (GEO) database. Utilizing GO\/KEGG enrichment analysis, we identified the NF\u2010\u03baB signaling pathway as significant. We identified 16 genes associated with TGF\u2010\u03b2 receptor signaling in epithelial\u2013mesenchymal transition (EMT) through PathCards and subsequently intersected these with the differentially expressed genes from two datasets. This analysis revealed the presence of one gene, PRKCZ. Additionally, single\u2010cell sequencing offered deeper insights into cellular diversity, elucidating the expression patterns of PRKCZ across various cell types. Molecular docking and dynamics simulations established that the proteasome inhibitor MG132 can create a stable complex with PRKCZ. In conclusion, qRT\u2010PCR, Western blot, immunohistochemistry, and fluorescence assays validated that Hla stimulation markedly heightened the levels of inflammatory pathway markers in human nasal mucosal epithelial cells. Importantly, the inhibition of PRKCZ by MG132 resulted in a significant reduction of these marker expression levels, offering a foundation for targeted therapeutic interventions. The current research demonstrates that alpha\u2010toxin from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    promotes EMT in CRSwNP via the NF\u2010\u03baB\/TGF\u2010\u03b2 signaling axis. A significant gene that may serve as a potential therapeutic target is PRKCZ.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70202","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T07:56:46Z","timestamp":1763971006000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Omics and Molecular Dynamics Analysis for Biomarker Discovery in Chronic Rhinosinusitis With Nasal Polyps"],"prefix":"10.1111","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7398-709X","authenticated-orcid":false,"given":"Qian","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Rhinology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinjie","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Rhinology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4389-2163","authenticated-orcid":false,"given":"Shuman","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Rhinology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuelong","family":"Wen","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine Jiangnan University  Wuxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zilong","family":"Chen","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Center The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology  Luoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2483-6465","authenticated-orcid":false,"given":"Dong","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Rhinology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2886-8175","authenticated-orcid":false,"given":"Yulin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Rhinology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003783"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/j100854a047"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.6b00041"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10250"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0080-4"},{"issue":"29","key":"e_1_2_10_7_1","first-page":"1","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens W. J.","year":"2020","journal-title":"Rhinology"},{"key":"e_1_2_10_8_1","first-page":"3","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2012","volume":"23","author":"Fokkens W. J.","year":"2012","journal-title":"Rhinology Supplement"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4193\/Rhino12.000"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000040624"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39104"},{"issue":"5","key":"e_1_2_10_12_1","first-page":"418","article-title":"Scoping Review of Chronic Rhinosinusitis Proteomics","volume":"58","author":"Kao S. S.","year":"2020","journal-title":"Rhinology"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-6-56"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.11.030"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-009-0030-5"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.12.036"},{"issue":"4","key":"e_1_2_10_17_1","first-page":"701","article-title":"Radius of Gyration Is Indicator of Compactness of Protein Structure","volume":"42","author":"Lobanov M.","year":"2008","journal-title":"Molekuliarnaia Biologiia (Mosk)"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/med4.34"},{"key":"e_1_2_10_19_1","first-page":"227","article-title":"The Role of Nasal Endoscopy in the Diagnosis and Medical Management of Chronic Rhinosinusitis","volume":"20","author":"Melroy C. T.","year":"2007","journal-title":"Clinical Allergy and Immunology"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00541-3"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/00034894061150S906"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000588"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S180853"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00432-X"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2262"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.07.013"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v2.i12.873"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116566"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1159\/000524950"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/med4.10"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2023.2232113"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.07.008"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.70202","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.70202","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.70202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T07:49:29Z","timestamp":1771141769000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.70202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/cbdd.70202"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.70202","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-08-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70202"}}