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We applied integrated proteomic, phosphoproteomic, acetylomic, and lactylomic analyses to kidney tissues from a mouse model of CaOx nephrolithiasis followed by bioinformatic analysis and experimental validation. We identified 658 differentially expressed proteins, 735 differential phosphorylation sites, 335 differential acetylation sites, and 113 differential lactylation sites. Functional enrichment indicated immune activation, fibrotic remodeling, and alterations in PI3K-Akt, NOD-like receptor, p53, and Toll-like receptor signaling together with changes in fatty acid degradation, the tricarboxylic acid cycle, and glycolysis. Kinase activity prediction suggested the relative activation of multiple cyclin-dependent kinases. Proteins associated with ferroptosis, autophagy, necroptosis, and pyroptosis, including ACSL4, BNIP3, RIPK3, and GSDMD, showed coordinated abundance and modification changes. Several candidate sites, including MTOR_S1849, GCLM_K94, GCLM_S59, and GSS_K172, were also dysregulated. These data provide a multiomics resource for CaOx nephrolithiasis and identify candidate PTM events and regulatory pathways for future mechanistic validation.<\/jats:p>","DOI":"10.1021\/acs.jproteome.6c00230","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T15:02:41Z","timestamp":1786460561000},"page":"4688-4703","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive\nLandscape of Post-Translational Modification\nAlterations in Nephrolithiasis Revealing Activation of Multiple Cell\nDeath Pathways"],"prefix":"10.1021","volume":"25","author":[{"given":"Yining","family":"Dong","sequence":"first","affiliation":[{"name":"Shandong University , , , ,","place":["Jinan, Shandong, China, 250031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8869-7239","authenticated-orcid":true,"given":"Mengya","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Jinan, Shandong, China, 250012"]},{"name":"University of Health and Rehabilitation Sciences , , , ,","place":["Qingdao, Shandong, China, 266109"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"The Second Qilu Hospital of Shandong University , , , ,","place":["Jinan, Shandong, China, 250033"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianchao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Jinan, Shandong, China, 250031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Jinan, Shandong, China, 250031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9350-2880","authenticated-orcid":true,"given":"Xiaolu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Jinan, Shandong, China, 250012"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Ni","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Jinan, Shandong, China, 250031"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"issue":"3","key":"2026090409125309000_cit1","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.advnut.2023.03.002","article-title":"Kidney stone prevention","volume":"14","author":"Peerapen","year":"2023","journal-title":"Adv.\nNutr."},{"issue":"4","key":"2026090409125309000_cit2","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/s41581-021-00513-4","article-title":"The genetics\nof\nkidney stone disease and nephrocalcinosis","volume":"18","author":"Singh","year":"2022","journal-title":"Nat.\nRev. 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