{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:27:51Z","timestamp":1792106871855,"version":"4.4.0"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero dell\u2019Universit\u00e0 e della Ricerca scientifica e Tecnologica (MURST)","award":["2022BPNY3E"],"award-info":[{"award-number":["2022BPNY3E"]}]},{"name":"Research Projects of National Relevance (PRIN)","award":["2022BPNY3E"],"award-info":[{"award-number":["2022BPNY3E"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sepsis is the leading cause of mortality in patients with burn injuries and it may represent, in these patients, a real diagnostic challenge. Here we studied the profile of miRNAs contained in extracellular vesicles (EVs) (EV-miRNAs) isolated from plasma from burn patients complicated by sepsis at admission and 7 days later. We enrolled 28 burn patients, 18 with (Burn Septic Patients\u2014BSPs) and 10 without (Burn non-Septic Patients\u2014BnSPs) sepsis. Ten healthy subjects (HSs) were used as additional controls. After EV isolation by charge precipitation and miRNA extraction, we proceeded with a two-phase approach. Through a first screening phase, we identified 178 miRNAs differentially expressed in BSPs compared to HSs. Among these, by a validation phase based on qRT-PCR, we found that miR-483-5p, miR-193a-5p, and miR-188-3p were increased in the BSPs compared to the BnSPs and HSs. Upon ROC analysis, all three miRNAs showed a good accuracy in differentiating BSPs from BnSPs, especially miR-483-5p (AUC = 0.955, p-value = 0.001). Moreover, we found 173 miRNAs differentially expressed in BSPs after 7 days from enrollment compared to T0, among whose miR-1-3p, miR-34a-3p, and miR-193a-5p decreased in BSPs after 7 days, in parallel with a decrease in SOFA scores. Finally, the other two miRNAs, miR-34a-3p and miR-193a-5p, positively correlated with the SOFA score. In conclusion, we identified several miRNAs\u2014namely miR-483-5p, miR-193a-5p, and miR-188-3p\u2014with potential clinical utility as diagnostic biomarkers in a heterogeneous population of burn patients at high risk of developing sepsis. Moreover, we found some miRNAs (miR-1-3p, miR-34a-3p, and miR-193a-5p) that vary according to the course of sepsis and others (miR-34a-3p and miR-193a-5p) that are associated with its clinical severity.<\/jats:p>","DOI":"10.3390\/ijms26051844","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T06:39:07Z","timestamp":1740119947000},"page":"1844","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Profiling of miRNAs Contained in Circulating Extracellular Vesicles and Associated with Sepsis Development in Burn Patients: A Proof-of-Concept Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2738-9119","authenticated-orcid":false,"given":"Martina","family":"Schiavello","sequence":"first","affiliation":[{"name":"Department of Medical Science, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7806-7008","authenticated-orcid":false,"given":"Ornella","family":"Bosco","sequence":"additional","affiliation":[{"name":"Department of Medical Science, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2389-8581","authenticated-orcid":false,"given":"Barbara","family":"Vizio","sequence":"additional","affiliation":[{"name":"Department of Medical Science, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Sciarrillo","sequence":"additional","affiliation":[{"name":"Plastic Surgery and Burn Center, Department of General and Specialized Surgery, City of Health and Science, CTO Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0247-8035","authenticated-orcid":false,"given":"Anna","family":"Pensa","sequence":"additional","affiliation":[{"name":"Plastic Surgery and Burn Center, Department of General and Specialized Surgery, City of Health and Science, CTO Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Pivetta","sequence":"additional","affiliation":[{"name":"Department of Medical Science, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7833-9632","authenticated-orcid":false,"given":"Fulvio","family":"Morello","sequence":"additional","affiliation":[{"name":"Department of Medical Science, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Risso","sequence":"additional","affiliation":[{"name":"Plastic Surgery and Burn Center, Department of General and Specialized Surgery, City of Health and Science, CTO Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Montrucchio","sequence":"additional","affiliation":[{"name":"Department of Medical Science, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7137-2141","authenticated-orcid":false,"given":"Filippo","family":"Mariano","sequence":"additional","affiliation":[{"name":"Department of Medical Science, University of Turin, 10126 Turin, Italy"},{"name":"Nephrology, Dialysis and Transplantation Unit, City of Health and Science, CTO Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-1217","authenticated-orcid":false,"given":"Enrico","family":"Lupia","sequence":"additional","affiliation":[{"name":"Department of Medical Science, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1093\/jbcr\/iry022","article-title":"Predictors for Identifying Burn Sepsis and Performance vs. Existing Criteria","volume":"39","author":"Hill","year":"2018","journal-title":"J. Burn. Care Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.jamcollsurg.2008.11.012","article-title":"Causes of Mortality by Autopsy Findings of Combat Casualties and Civilian Patients Admitted to a Burn Unit","volume":"208","author":"Gomez","year":"2009","journal-title":"J. Am. Coll. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.mpaic.2024.06.010","article-title":"Sepsis in 2024: A Review","volume":"25","author":"Wayland","year":"2024","journal-title":"Anaesth. Intensive Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.surg.2018.05.053","article-title":"Sepsis Criteria versus Clinical Diagnosis of Sepsis in Burn Patients: A Validation of Current Sepsis Scores","volume":"164","author":"Yan","year":"2018","journal-title":"Surgery"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1016\/j.burns.2023.05.003","article-title":"Surviving Sepsis After Burn Campaign","volume":"49","author":"Greenhalgh","year":"2023","journal-title":"Burns"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Boehm, D., and Menke, H. (2021). Sepsis in Burns\u2014Lessons Learnt from Developments in the Management of Septic Shock. Medicina, 58.","DOI":"10.3390\/medicina58010026"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1097\/SLA.0000000000005198","article-title":"Biomarkers for the Early Diagnosis of Sepsis in Burns: Systematic Review and Meta-Analysis","volume":"275","author":"Li","year":"2022","journal-title":"Ann. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/j.burns.2017.03.026","article-title":"Procalcitonin for the Early Diagnosis of Sepsis in Burn Patients: A Retrospective Study","volume":"43","author":"Cabral","year":"2017","journal-title":"Burns"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yoon, J., Kym, D., Cho, Y.S., Hur, J., and Yoon, D. (2024). Advanced Biomarker Clustering Analysis Reveals Mortality Predictors in Burn Patients with Sepsis. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-74313-8"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Schiavello, M., Vizio, B., Bosco, O., Pivetta, E., Mariano, F., Montrucchio, G., and Lupia, E. (2023). Extracellular Vesicles: New Players in the Mechanisms of Sepsis- and COVID-19-Related Thromboinflammation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031920"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding Light on the Cell Biology of Extracellular Vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Im, Y., Yoo, H., Ko, R.-E., Lee, J.Y., Park, J., and Jeon, K. (2021). Exosomal CD63 in Critically Ill Patients with Sepsis. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-99777-w"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1669881","DOI":"10.1080\/20013078.2019.1669881","article-title":"Circulating Extracellular Vesicle Content Reveals de Novo DNA Methyltransferase Expression as a Molecular Method to Predict Septic Shock","volume":"8","author":"Dakhlallah","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1097\/SHK.0000000000001938","article-title":"Burn Injury-Induced Extracellular Vesicle Production and Characteristics","volume":"57","author":"Yang","year":"2022","journal-title":"Shock"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"O\u2019Toole, H.J., Lowe, N., Arun, V., Kolesov, A.V., Palmieri, T.L., Tran, N.K., and Carney, R.P. (2024). Plasma-Derived Extracellular Vesicles (EVs) as Biomarkers of Sepsis in Burn Patients via Label-Free Raman Spectroscopy. bioRxiv.","DOI":"10.1101\/2024.05.14.593634"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, Biogenesis, Mechanism, and Function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Antonakos, N., Gilbert, C., Th\u00e9roude, C., Schrijver, I.T., and Roger, T. (2022). Modes of Action and Diagnostic Value of miRNAs in Sepsis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.951798"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1038\/cdd.2016.94","article-title":"Cellular and Viral microRNAs in Sepsis: Mechanisms of Action and Clinical Applications","volume":"23","author":"Giza","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Roderburg, C., Luedde, M., Vargas Cardenas, D., Vucur, M., Scholten, D., Frey, N., Koch, A., Trautwein, C., Tacke, F., and Luedde, T. (2013). Circulating MicroRNA-150 Serum Levels Predict Survival in Patients with Critical Illness and Sepsis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054612"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1097\/CCM.0000000000000131","article-title":"Levels of Circulating miR-133a Are Elevated in Sepsis and Predict Mortality in Critically Ill Patients","volume":"42","author":"Tacke","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1186\/s13054-015-1162-8","article-title":"Plasma Levels of microRNA Are Altered with the Development of Shock in Human Sepsis: An Observational Study","volume":"19","author":"Goodwin","year":"2015","journal-title":"Crit. Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41572-020-0145-5","article-title":"Burn Injury","volume":"6","author":"Jeschke","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"tkaa047","DOI":"10.1093\/burnst\/tkaa047","article-title":"The Pathogenesis and Diagnosis of Sepsis Post Burn Injury","volume":"9","author":"Zhang","year":"2021","journal-title":"Burn. Trauma"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.burns.2024.02.028","article-title":"CytoSorb\u00ae in Burn Patients with Septic Shock and Acute Kidney Injury on Continuous Kidney Replacement Therapy Is Associated with Improved Clinical Outcome and Survival","volume":"50","author":"Mariano","year":"2024","journal-title":"Burns"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"ii33","DOI":"10.1093\/jac\/dkq523","article-title":"Diagnostic and Prognostic Biomarkers of Sepsis in Critical Care","volume":"66","author":"Kibe","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.emc.2016.09.004","article-title":"Ready for Prime Time? Biomarkers in Sepsis","volume":"35","author":"Long","year":"2017","journal-title":"Emerg. Med. Clin. N. Am."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1586\/1744666X.2014.949675","article-title":"Biomarkers of Sepsis and Their Potential Value in Diagnosis, Prognosis and Treatment","volume":"10","author":"Sandquist","year":"2014","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/s12276-024-01186-2","article-title":"Advances in Single-Cell Omics and Multiomics for High-Resolution Molecular Profiling","volume":"56","author":"Lim","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"tkac050","DOI":"10.1093\/burnst\/tkac050","article-title":"Prospective Study and Validation of Early Warning Marker Discovery Based on Integrating Multi-Omics Analysis in Severe Burn Patients with Sepsis","volume":"11","author":"Huang","year":"2023","journal-title":"Burn. Trauma"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1038\/s12276-023-01050-9","article-title":"MicroRNA: Trends in Clinical Trials of Cancer Diagnosis and Therapy Strategies","volume":"55","author":"Kim","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhai, W., Zhao, M., Wei, C., Zhang, G., Qi, Y., Zhao, A., and Sun, L. (2024). Biomarker Profiling to Determine Clinical Impact of microRNAs in Cognitive Disorders. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-58882-2"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2009.09.061","article-title":"MicroRNA Isolation and Stability in Stored RNA Samples","volume":"390","author":"Mraz","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sanz-Rubio, D., Martin-Burriel, I., Gil, A., Cubero, P., Forner, M., Khalyfa, A., and Marin, J.M. (2018). Stability of Circulating Exosomal miRNAs in Healthy Subjects. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-28748-5"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3892\/mco.2020.2193","article-title":"Multiple microRNAs as Biomarkers for Early Breast Cancer Diagnosis","volume":"14","author":"Jang","year":"2021","journal-title":"Mol. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1038\/leu.2014.155","article-title":"Circulating miRNA Markers Show Promise as New Prognosticators for Multiple Myeloma","volume":"28","author":"Rocci","year":"2014","journal-title":"Leukemia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12967-021-03215-4","article-title":"The Role of Exosomal miRNAs in Cancer","volume":"20","author":"Li","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zheng, D., Huo, M., Li, B., Wang, W., Piao, H., Wang, Y., Zhu, Z., Li, D., Wang, T., and Liu, K. (2021). The Role of Exosomes and Exosomal MicroRNA in Cardiovascular Disease. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.616161"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"77","DOI":"10.2131\/jts.45.77","article-title":"High Expression of miR-483-5p Aggravates Sepsis-Induced Acute Lung Injury","volume":"45","author":"Leng","year":"2020","journal-title":"J. Toxicol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, H., Zhang, P., Chen, W., Feng, D., Jia, Y., and Xie, L. (2012). Serum microRNA Signatures Identified by Solexa Sequencing Predict Sepsis Patients\u2019 Mortality: A Prospective Observational Study. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038885"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1111\/jcmm.13162","article-title":"Cellular and Extracellular miRNAs Are Blood-Compartment-Specific Diagnostic Targets in Sepsis","volume":"21","author":"Reithmair","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1158\/1078-0432.CCR-16-0497","article-title":"Genome-Wide miRNA Analysis Identifies miR-188-3p as a Novel Prognostic Marker and Molecular Factor Involved in Colorectal Carcinogenesis","volume":"23","author":"Pichler","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e924394-1","DOI":"10.12659\/MSM.924394","article-title":"miR-188-3p Inhibits Vascular Smooth Muscle Cell Proliferation and Migration by Targeting Fibroblast Growth Factor 1 (FGF1)","volume":"26","author":"Mi","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.biopha.2018.06.063","article-title":"MicroRNA-34a Promotes iNOS Secretion from Pulmonary Macrophages in Septic Suckling Rats through Activating STAT3 Pathway","volume":"105","author":"Cheng","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Abdelaleem, O.O., Mohammed, S.R., El Sayed, H.S., Hussein, S.K., Ali, D.Y., Abdelwahed, M.Y., Gaber, S.N., Hemeda, N.F., and El-Hmid, R.G.A. (2022). Serum miR-34a-5p and miR-199a-3p as New Biomarkers of Neonatal Sepsis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0262339"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"C\u00f3rdova-Rivas, S., Fraire-Soto, I., Mercado-Casas Torres, A., Serv\u00edn-Gonz\u00e1lez, L.S., Granados-L\u00f3pez, A.J., L\u00f3pez-Hern\u00e1ndez, Y., Reyes-Estrada, C.A., Guti\u00e9rrez-Hern\u00e1ndez, R., Casta\u00f1eda-Delgado, J.E., and Ram\u00edrez-Hern\u00e1ndez, L. (2019). 5p and 3p Strands of miR-34 Family Members Have Differential Effects in Cell Proliferation, Migration, and Invasion in Cervical Cancer Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030545"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1097\/00003246-199811000-00016","article-title":"Use of the SOFA Score to Assess the Incidence of Organ Dysfunction\/Failure in Intensive Care Units: Results of a Multicenter, Prospective Study. Working Group on \u201cSepsis-Related Problems\u201d of the European Society of Intensive Care Medicine","volume":"26","author":"Vincent","year":"1998","journal-title":"Crit. Care Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.3892\/ijmm.2016.2759","article-title":"Charge-Based Precipitation of Extracellular Vesicles","volume":"38","author":"Deregibus","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal Information for Studies of Extracellular Vesicles (MISEV2023): From Basic to Advanced Approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1713526","DOI":"10.1080\/20013078.2020.1713526","article-title":"MIFlowCyt-EV: A Framework for Standardized Reporting of Extracellular Vesicle Flow Cytometry Experiments","volume":"9","author":"Welsh","year":"2020","journal-title":"J. Extracell. Vesicles"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/1844\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:39:30Z","timestamp":1760027970000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/1844"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,21]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26051844"],"URL":"https:\/\/doi.org\/10.3390\/ijms26051844","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,21]]}}}