{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T05:30:48Z","timestamp":1764307848390,"version":"3.46.0"},"reference-count":55,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Central Core Disease (CCD) is a congenital myopathy predominantly caused by mutations in the gene encoding ryanodine receptor type-1 (RYR1), the intracellular Ca2+ release channel embedded in the skeletal muscle sarcoplasmic reticulum membrane. The I4898T mutation represents one of the most common RYR1 mutations associated with CCD. Unfortunately, there are no approved therapies for CCD or for other myopathies caused by mutations in this gene. This study aims to perform a top-down differential proteomic analysis on soleus muscle samples from wild-type mice (WT) and heterozygous knock-in mice carrying the I4895T (IT) mutation in RyR1, to investigate the pathogenic mechanisms and molecular pathways involved in this myopathy and to shed light on new potential biomarkers useful for future therapies. Proteomic analysis revealed 50 dysregulated protein species, and multivariate analysis showed that IT mice exhibit a distinct proteomic signature compared to WT mice, characterized by alterations in proteins associated with contractile and structural dysfunction, metabolism, and stress response. In particular, a significant increase in myosin fragments was observed in IT mice, likely due to muscle breakdown. In contrast, myotilin was downregulated, suggesting a weakening of the muscle cytoskeletal structure. There was a notable downregulation of proteins involved in glycolysis and the TCA cycle; conversely, there was an increase in proteins related to anaerobic glycolysis, suggesting a shift from aerobic to anaerobic glycolysis. Furthermore, proteins involved in fatty acid beta-oxidation and oxidative phosphorylation were also found to be upregulated in IT mice, indicating an attempt by the muscle to maximize energy production. Finally, we found a significant decrease in PGC1\u03b1, which could serve as potential therapy target and biomarker in CCD.<\/jats:p>","DOI":"10.3390\/ijms262311451","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T14:39:43Z","timestamp":1764167983000},"page":"11451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Insights into Central Core Disease: Proteomic Signatures and Potential Therapeutic Biomarkers in RYR1 I4895T Mice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4078-7250","authenticated-orcid":false,"given":"Lorenza","family":"Vantaggiato","sequence":"first","affiliation":[{"name":"Functional Proteomics Lab., Department of Life Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9561-2426","authenticated-orcid":false,"given":"Enxhi","family":"Shaba","sequence":"additional","affiliation":[{"name":"Functional Proteomics Lab., Department of Life Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4008-3498","authenticated-orcid":false,"given":"Federica","family":"Fiore","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0463-7327","authenticated-orcid":false,"given":"Daniela","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"},{"name":"Program of Molecular Diagnosis of Rare Genetic Diseases, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8573-8631","authenticated-orcid":false,"given":"Vincenzo","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"},{"name":"Program of Molecular Diagnosis of Rare Genetic Diseases, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8951-2106","authenticated-orcid":false,"given":"Luca","family":"Bini","sequence":"additional","affiliation":[{"name":"Functional Proteomics Lab., Department of Life Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0410-8038","authenticated-orcid":false,"given":"Claudia","family":"Landi","sequence":"additional","affiliation":[{"name":"Functional Proteomics Lab., Department of Life Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1152\/physrev.1997.77.3.699","article-title":"Ryanodine Receptors of Striated Muscles: A Complex Channel Capable of Multiple Interactions","volume":"77","author":"Protasi","year":"1997","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev.ph.56.030194.002335","article-title":"Control of Calcium Release in Functioning Skeletal Muscle Fibers","volume":"56","author":"Schneider","year":"1994","journal-title":"Annu. Rev. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e202213115","DOI":"10.1085\/jgp.202213115","article-title":"Mutations in Proteins Involved in E-C Coupling and SOCE and Congenital Myopathies","volume":"154","author":"Rossi","year":"2022","journal-title":"J. Gen. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13395-020-00243-4","article-title":"Ryanodine Receptor 1-Related Disorders: An Historical Perspective and Proposal for a Unified Nomenclature","volume":"10","author":"Lawal","year":"2020","journal-title":"Skelet. Muscle"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/B978-0-444-64074-1.00038-0","article-title":"Malignant Hyperthermia","volume":"Volume 157","author":"Hopkins","year":"2018","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1002\/humu.9442","article-title":"Frequency and Localization of Mutations in the 106 Exons of the RYR1 Gene in 50 Individuals with Malignant Hyperthermia","volume":"27","author":"Galli","year":"2006","journal-title":"Hum. Mutat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1093\/brain\/79.4.610","article-title":"A New Congenital Non-Progressive Myopathy","volume":"79","author":"Magee","year":"1956","journal-title":"Brain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1093\/brain\/awl077","article-title":"Central Core Disease Is Due to RYR1 Mutations in More than 90% of Patients","volume":"129","author":"Wu","year":"2006","journal-title":"Brain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s13311-018-00677-1","article-title":"Ryanodine Receptor 1-Related Myopathies: Diagnostic and Therapeutic Approaches","volume":"15","author":"Lawal","year":"2018","journal-title":"Neurotherapeutics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.bbamcr.2010.11.009","article-title":"Mechanistic Models for Muscle Diseases and Disorders Originating in the Sarcoplasmic Reticulum","volume":"1813","author":"MacLennan","year":"2011","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1750-1172-2-25","article-title":"Central Core Disease","volume":"2","author":"Jungbluth","year":"2007","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_12","first-page":"266","article-title":"Core Myopathies\u2014A Short Review","volume":"39","author":"Topaloglu","year":"2020","journal-title":"Acta Myol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1212\/WNL.0b013e3182900380","article-title":"Severe Congenital RYR1-Associated Myopathy: The Expanding Clinicopathologic and Genetic Spectrum","volume":"80","author":"Santi","year":"2013","journal-title":"Neurology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1093\/brain\/awg244","article-title":"Dominant and Recessive Central Core Disease Associated with RYR1 Mutations and Fetal Akinesia","volume":"126","author":"Romero","year":"2003","journal-title":"Brain"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Iodice, P., Boncompagni, S., Pietrangelo, L., Galli, L., Pierantozzi, E., Rossi, D., Fusella, A., Caulo, M., Kern, H., and Sorrentino, V. (2019). Functional Electrical Stimulation: A Possible Strategy to Improve Muscle Function in Central Core Disease?. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00479"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4214","DOI":"10.1111\/ejn.15728","article-title":"Ryanodine Receptor 1 (RYR1) Mutations in Two Patients with Tubular Aggregate Myopathy","volume":"56","author":"Vattemi","year":"2022","journal-title":"Eur. J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1085\/jgp.201010523","article-title":"Muscle Weakness in Ryr1I4895T\/WT Knock-in Mice as a Result of Reduced Ryanodine Receptor Ca2+ Ion Permeation and Release from the Sarcoplasmic Reticulum","volume":"137","author":"Loy","year":"2011","journal-title":"J. Gen. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"18537","DOI":"10.1073\/pnas.0709312104","article-title":"An Ryr1I4895T Mutation Abolishes Ca2+ Release Channel Function and Delays Development in Homozygous Offspring of a Mutant Mouse Line","volume":"104","author":"Zvaritch","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"21813","DOI":"10.1073\/pnas.0912126106","article-title":"Ca2+ Dysregulation in Ryr1I4895T\/Wt Mice Causes Congenital Myopathy with Progressive Formation of Minicores, Cores, and Nemaline Rods","volume":"106","author":"Zvaritch","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14659","DOI":"10.1038\/ncomms14659","article-title":"A Chemical Chaperone Improves Muscle Function in Mice with a RyR1 Mutation","volume":"8","author":"Lee","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1111\/j.1474-9726.2010.00623.x","article-title":"The I4895T Mutation in the Type 1 Ryanodine Receptor Induces Fiber-Type Specific Alterations in Skeletal Muscle That Mimic Premature Aging","volume":"9","author":"Boncompagni","year":"2010","journal-title":"Aging Cell"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Melka, M., Rotard, L., Benstaali, C., Brocard, J., Giannesini, B., Jouve, F., Pelletier, L., Faur\u00e9, J., Rendu, J., and Jacquemond, V. (2025). Limited Pre-Clinical Relevance of the Heterozygous RYR1-I4895T\/+ Mouse Model Due to Its Mild Phenotype. J. Neuromuscul. Dis.","DOI":"10.1177\/22143602251339354"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1177\/0883073812436605","article-title":"Consensus Statement on Standard of Care for Congenital Myopathies","volume":"27","author":"Wang","year":"2012","journal-title":"J. Child Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jprot.2014.03.015","article-title":"The Proteomics Quantification Dilemma","volume":"107","author":"Jungblut","year":"2014","journal-title":"J. Proteom."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Vantaggiato, L., Landi, C., Shaba, E., Rossi, D., Sorrentino, V., and Bini, L. (2024). Protein Extraction Methods Suitable for Muscle Tissue Proteomic Analysis. Proteomes, 12.","DOI":"10.3390\/proteomes12040027"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Plotkin, D.L., Mattingly, M.L., Anglin, D.A., Michel, J.M., Godwin, J.S., McIntosh, M.C., Bergamasco, J.G.A., Scarpelli, M.C., Angleri, V., and Taylor, L.W. (2024). Skeletal Muscle Myosin Heavy Chain Protein Fragmentation as a Potential Marker of Protein Degradation in Response to Resistance Training and Disuse Atrophy. bioRxiv, 2024.05.24.595789.","DOI":"10.1101\/2024.05.24.595789"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s11357-011-9211-y","article-title":"Sequential Stages in the Age-Dependent Gradual Formation and Accumulation of Tubular Aggregates in Fast Twitch Muscle Fibers: SERCA and Calsequestrin Involvement","volume":"34","author":"Boncompagni","year":"2012","journal-title":"Age"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wadmore, K., Azad, A.J., and Gehmlich, K. (2021). The Role of Z-Disc Proteins in Myopathy and Cardiomyopathy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063058"},{"key":"ref_29","first-page":"1595","article-title":"Myozenin: An \u03b1-Actinin- and \u03b3-Filamin-Binding Protein of Skeletal Muscle Z Lines","volume":"98","author":"Takada","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0304-4165(91)90062-L","article-title":"Tissue Distribution and Developmental Profiles of Immunoreactive \u03b1B Crystallin in the Rat Determined with a Sensitive Immunoassay System","volume":"1074","author":"Kato","year":"1991","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1091\/mbc.e03-12-0893","article-title":"Desmin Aggregate Formation by R120G \u03b1B-Crystallin Is Caused by Altered Filament Interactions and Is Dependent upon Network Status in Cells","volume":"15","author":"Wen","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/00003677-200204000-00009","article-title":"Regulation of Pyruvate Dehydrogenase (PDH) Activity in Human Skeletal Muscle During Exercise","volume":"30","author":"Spriet","year":"2002","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.mito.2014.05.007","article-title":"Comprehensive Review on Lactate Metabolism in Human Health","volume":"17","year":"2014","journal-title":"Mitochondrion"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ni, Y., Hagras, M.A., Konstantopoulou, V., Mayr, J.A., Stuchebrukhov, A.A., and Meierhofer, D. (2019). Mutations in NDUFS1 Cause Metabolic Reprogramming and Disruption of the Electron Transfer. Cells, 8.","DOI":"10.3390\/cells8101149"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/s12276-022-00800-5","article-title":"Cardiac-Specific Overexpression of Ndufs1 Ameliorates Cardiac Dysfunction after Myocardial Infarction by Alleviating Mitochondrial Dysfunction and Apoptosis","volume":"54","author":"Qi","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e13157","DOI":"10.1111\/bpa.13157","article-title":"Mic60 Is Essential to Maintain Mitochondrial Integrity and to Prevent Encephalomyopathy","volume":"33","author":"Dong","year":"2023","journal-title":"Brain Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e15817","DOI":"10.14814\/phy2.15817","article-title":"Acyl-CoA Synthetase Expression in Human Skeletal Muscle Is Reduced in Obesity and Insulin Resistance","volume":"11","author":"Poppelreuther","year":"2023","journal-title":"Physiol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s12672-022-00521-1","article-title":"Acetyl-CoA Synthetase 2(ACSS2): A Review with a Focus on Metabolism and Tumor Development","volume":"13","author":"Ling","year":"2022","journal-title":"Discov. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1515\/BC.2007.052","article-title":"Calcium Signalling in the Regulation of PGC-1\u03b1, PDK4 and HKII mRNA Expression","volume":"388","author":"Kusuhara","year":"2007","journal-title":"Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.bbamcr.2010.03.019","article-title":"Calcineurin Signaling and PGC-1\u03b1 Expression Are Suppressed during Muscle Atrophy Due to Diabetes","volume":"1803","author":"Reddy","year":"2010","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"R849","DOI":"10.1152\/ajpregu.1997.272.3.R849","article-title":"Intracellular Regulation of Protein Degradation during Sepsis Is Different in Fast- and Slow-Twitch Muscle","volume":"272","author":"Tiao","year":"1997","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1096\/fj.06-6604com","article-title":"Rapid Disuse and Denervation Atrophy Involve Transcriptional Changes Similar to Those of Muscle Wasting During Systemic Diseases","volume":"21","author":"Sacheck","year":"2007","journal-title":"FASEB J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.cell.2008.02.042","article-title":"RyR1 S-Nitrosylation Underlies Environmental Heat Stroke and Sudden Death in Y522S RyR1 Knock-in Mice","volume":"133","author":"Durham","year":"2008","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.bbadis.2011.09.014","article-title":"AMPK-Mediated Increase of Glycolysis as an Adaptive Response to Oxidative Stress in Human Cells: Implication of the Cell Survival in Mitochondrial Diseases","volume":"1822","author":"Wu","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/cbf.3497","article-title":"Proteomic Changes in Skeletal Muscle of Aged Rats in Response to Resistance Training","volume":"38","author":"Carvalho","year":"2020","journal-title":"Cell Biochem. Funct."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2018306","DOI":"10.1155\/2018\/2018306","article-title":"Protective Role of Carbonic Anhydrases III and VII in Cellular Defense Mechanisms upon Redox Unbalance","volume":"2018","author":"Monti","year":"2018","journal-title":"Oxidative Med. Cell Longev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1515\/CCLM.2010.179","article-title":"Biochemical Markers of Muscular Damage","volume":"48","author":"Brancaccio","year":"2010","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0009-8981(83)90405-9","article-title":"Carbonic Anhydrase III in Duchenne Muscular Dystrophy","volume":"133","author":"Carter","year":"1983","journal-title":"Clin. Chim. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1080\/14789450.2021.2017776","article-title":"Proteomic Profiling of Carbonic Anhydrase CA3 in Skeletal Muscle","volume":"18","author":"Dowling","year":"2021","journal-title":"Expert Rev. Proteom."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Vantaggiato, L., Cameli, P., Bergantini, L., d\u2019Alessandro, M., Shaba, E., Carleo, A., Di Giuseppe, F., Angelucci, S., Sebastiani, G., and Dotta, F. (2022). Serum Proteomic Profile of Asthmatic Patients After Six Months of Benralizumab and Mepolizumab Treatment. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040761"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/0003-2697(80)90470-4","article-title":"A Simplified Ultrasensitive Silver Stain for Detecting Proteins in Polyacrylamide Gels","volume":"105","author":"Oakley","year":"1980","journal-title":"Anal. Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/(SICI)1522-2683(19990301)20:3<601::AID-ELPS601>3.0.CO;2-6","article-title":"Mass Spectrometric Identification of Proteins from Silver-Stained Polyacrylamide Gel: A Method for the Removal of Silver Ions to Enhance Sensitivity","volume":"20","author":"Gharahdaghi","year":"1999","journal-title":"Electrophoresis"},{"key":"ref_54","first-page":"165","article-title":"Bronchoalveolar Lavage Proteomic Analysis in Pulmonary Fibrosis Associated with Systemic Sclerosis: S100A6 and 14-3-3\u03b5 as Potential Biomarkers","volume":"58","author":"Landi","year":"2019","journal-title":"Rheumatology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","article-title":"The PRIDE Database Resources in 2022: A Hub for Mass Spectrometry-Based Proteomics Evidences","volume":"50","author":"Bai","year":"2022","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11451\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T05:26:47Z","timestamp":1764307607000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":55,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311451"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311451","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,11,26]]}}}