{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:47:06Z","timestamp":1777351626398,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T00:00:00Z","timestamp":1693094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23-25-00157"],"award-info":[{"award-number":["23-25-00157"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bacterial infections represent an unsolved problem today since bacteria can evade antibiotics and suppress the host\u2019s immune response. A family of TRIM proteins is known to play a role in antiviral defense. However, the data on the involvement of the corresponding genes in the antibacterial response are limited. Here, we used RT-qPCR to profile the transcript levels of TRIM genes, as well as interferons and inflammatory genes, in human cell lines (in vitro) and in mice (in vivo) after bacterial infections caused by Pseudomonas aeruginosa and Chlamydia spp. As a result, the genes were identified that are involved in the overall immune response and associated primarily with inflammation in human cells and in mouse organs when infected with both pathogens (TRIM7, 8, 14, 16, 17, 18, 19, 20, 21, 47, 68). TRIMs specific to the infection (TRIM59 for P. aeruginosa, TRIM67 for Chlamydia spp.) were revealed. Our findings can serve as a basis for further, more detailed studies on the mechanisms of the immune response to P. aeruginosa and Chlamydia spp. Studying the interaction between bacterial pathogens and the immune system contributes to the search for new ways to successfully fight bacterial infections.<\/jats:p>","DOI":"10.3390\/ijms241713290","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T01:56:57Z","timestamp":1693187817000},"page":"13290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of Key TRIM Genes Involved in Response to Pseudomonas aeruginosa or Chlamydia spp. Infections in Human Cell Lines and in Mouse Organs"],"prefix":"10.3390","volume":"24","author":[{"given":"Ekaterina","family":"Stepanenko","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, Moscow 123182, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Bondareva","sequence":"additional","affiliation":[{"name":"Laboratory for Chlamydiosis, National Research Center for Epidemiology and Microbiology Named after N. F. Gamaleya, Russian Health Ministry, Moscow 123098, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Sheremet","sequence":"additional","affiliation":[{"name":"Laboratory for Chlamydiosis, National Research Center for Epidemiology and Microbiology Named after N. F. Gamaleya, Russian Health Ministry, Moscow 123098, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Fedina","sequence":"additional","affiliation":[{"name":"Laboratory for Chlamydiosis, National Research Center for Epidemiology and Microbiology Named after N. F. Gamaleya, Russian Health Ministry, Moscow 123098, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexei","family":"Tikhomirov","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, Moscow 123182, Russia"},{"name":"Department of Chemistry and Technology of Biomedical Pharmaceuticals, D. Mendeleev University of Chemical Technology of Russia, Moscow 125047, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3858-4561","authenticated-orcid":false,"given":"Tatiana","family":"Gerasimova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, Moscow 123182, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7281-4714","authenticated-orcid":false,"given":"Daniil","family":"Poberezhniy","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, Moscow 123182, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Makarova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, Moscow 123182, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vyacheslav","family":"Tarantul","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, Moscow 123182, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nailya","family":"Zigangirova","sequence":"additional","affiliation":[{"name":"Laboratory for Chlamydiosis, National Research Center for Epidemiology and Microbiology Named after N. F. Gamaleya, Russian Health Ministry, Moscow 123098, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3985-6466","authenticated-orcid":false,"given":"Valentina","family":"Nenasheva","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, Moscow 123182, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"628275","DOI":"10.3389\/fcimb.2021.628275","article-title":"The Roles of TRIMs in Antiviral Innate Immune Signaling","volume":"15","author":"Shen","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.3390\/v13020279","article-title":"TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense","volume":"13","author":"Wang","year":"2021","journal-title":"Viruses"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.micpath.2017.12.008","article-title":"Gene Expression Profiling of the TRIM Protein Family Reveals Potential Biomarkers for Indicating Tuberculosis Status","volume":"114","author":"Chen","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8971","DOI":"10.1002\/jcb.27153","article-title":"TRIM22 regulates macrophage autophagy and enhances Mycobacterium tuberculosis clearance by targeting the nuclear factor\u2013multiplicity \u03baB\/beclin 1 pathway","volume":"119","author":"Lou","year":"2018","journal-title":"J. Cell Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"34827","DOI":"10.1038\/srep34827","article-title":"The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by Mycobacterium tuberculosis PtpA during mycobacterial infection","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Perelman, S.S., Abrams, M.E., Eitson, J.L., Chen, D., Jimenez, A., Mettlen, M., Schoggins, J.W., and Alto, N.M. (2016). Cell-Based Screen Identifies Human Interferon-Stimulated Regulators of Listeria monocytogenes Infection. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1006102"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"153","DOI":"10.4049\/jimmunol.1901511","article-title":"TRIM14 Is a Key Regulator of the Type I IFN Response during Mycobacterium tuberculosis Infection","volume":"205","author":"Hoffpauir","year":"2020","journal-title":"J. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.4049\/jimmunol.2000048","article-title":"TRIM21 Is Targeted for Chaperone-Mediated Autophagy during Salmonella Typhimurium Infection","volume":"205","author":"Hos","year":"2020","journal-title":"J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kamanova, J., Sun, H., Lara-Tejero, M., and Gal\u00e1n, J.E. (2016). The Salmonella Effector Protein SopA Modulates Innate Immune Responses by Targeting TRIM E3 Ligase Family Members. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005552"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00957-19","DOI":"10.1128\/IAI.00957-19","article-title":"TRIM32 Drives Pathogenesis in Streptococcal Toxic Shock-Like Syndrome and Streptococcus suis Meningitis by Regulating Innate Immune Responses","volume":"88","author":"OuYang","year":"2020","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13054-017-1755-5","article-title":"Treatment of severe hospital-acquired and ventilator-associated pneumonia: A systematic review of inclusion and judgment criteria used in randomized controlled trials","volume":"21","author":"Weiss","year":"2017","journal-title":"Crit Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"a010256","DOI":"10.1101\/cshperspect.a010256","article-title":"Chlamydial intracellular survival strategies","volume":"3","author":"Bastidas","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1128\/IAI.70.6.2741-2751.2002","article-title":"Immunity to murine chlamydial genital infection","volume":"70","author":"Morrison","year":"1978","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.mcp.2014.01.006","article-title":"Chlamydia trachomatis infection increases the expression of inflammatory tumorigenic cytokines and chemokines as well as components of the Toll-like receptor and NF-\u03baB pathways in human prostate epithelial cells","volume":"28","author":"Sellami","year":"2014","journal-title":"Mol. Cell Probes"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"42781","DOI":"10.1038\/srep42781","article-title":"Expression profiling of TRIM protein family in THP1-derived macrophages following TLR stimulation","volume":"7","author":"Jiang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Carthagena, L., Bergamaschi, A., Luna, J.M., David, A., Uchil, P.D., Margottin-Goguet, F., Mothes, W., Hazan, U., Transy, C., and Pancino, G. (2009). Human TRIM gene expression in response to interferons. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004894"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ebenezer, D.L., Fu, P., Krishnan, Y., Maienschein-Cline, M., Hu, H., Jung, S., Madduri, R., Arbieva, Z., Harijith, A., and Natarajan, V. (2019). Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung. BMC Genomics, 20.","DOI":"10.1186\/s12864-019-6367-9"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3389\/fcimb.2019.00192","article-title":"Indoleamine 2,3-Dioxygenase Activity in Chlamydia muridarum and Chlamydia pneumoniae Infected Mouse Lung Tissues","volume":"9","author":"Virok","year":"2019","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16315","DOI":"10.1073\/pnas.0506190102","article-title":"Innate control of adaptive immunity via remodeling of lymph node feed arteriole","volume":"102","author":"Soderberg","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/nm1007-1142b","article-title":"Not so fast: Adaptive suppression of innate immunity","volume":"13","author":"Palm","year":"2007","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s10753-020-01394-8","article-title":"TRIM Proteins in Inflammation: From Expression to Emerging Regulatory Mechanisms","volume":"44","author":"Yang","year":"2021","journal-title":"Inflammation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"02157","DOI":"10.3389\/fimmu.2020.02157","article-title":"To TRIM the Immunity: From Innate to Adaptive Immunity","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1189\/jlb.0811410","article-title":"Toll-like receptors in the host defense against Pseudomonas aeruginosa respiratory infection and cystic fibrosis","volume":"92","author":"McIsaac","year":"2012","journal-title":"J. Leukoc. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Al-Kuhlani, M., Lambert, G., Pal, S., de la Maza, L., and Ojcius, D.M. (2020). Immune response against Chlamydia trachomatis via toll-like receptors is negatively regulated by SIGIRR. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0230718"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/j.micinf.2012.08.004","article-title":"Innate immune responses to Chlamydia pneumoniae infection: Role of TLRs, NLRs, and the inflammasome","volume":"14","author":"Shimada","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/s00018-020-03656-y","article-title":"TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling","volume":"78","author":"Ciesielska","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/nri2413","article-title":"TRIM family proteins and their emerging roles in innate immunity","volume":"8","author":"Ozato","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/eji.200737916","article-title":"Type I interferon-dependent and -independent expression of tripartite motif proteins in immune cells","volume":"38","author":"Rajsbaum","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41392-022-00953-9","article-title":"TRIM47 is a novel endothelial activation factor that aggravates lipopolysaccharide-induced acute lung injury in mice via K63-linked ubiquitination of TRAF2","volume":"7","author":"Qian","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1007\/s10753-016-0491-3","article-title":"Tripartite Motif 8 (TRIM8) Positively Regulates Pro-inflammatory Responses in Pseudomonas aeruginosa-Induced Keratitis Through Promoting K63-Linked Polyubiquitination of TAK1 Protein","volume":"40","author":"Guo","year":"2017","journal-title":"Inflammation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"42","DOI":"10.15252\/embj.201695081","article-title":"Dedicated SNAREs and specialized TRIM cargo receptors mediate secretory autophagy","volume":"36","author":"Kimura","year":"2017","journal-title":"EMBO J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/JPER.19-0222","article-title":"Differential expression of inflammasome regulatory transcripts in periodontal disease","volume":"91","author":"Aral","year":"2020","journal-title":"J. Periodontol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.joen.2020.06.008","article-title":"Dysregulation of Inflammasomes in Human Dental Pulp Cells Exposed to Porphyromonas gingivalis and Fusobacterium nucleatum","volume":"46","author":"Aral","year":"2020","journal-title":"J. Endod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"109522","DOI":"10.1016\/j.cellsig.2019.109522","article-title":"TRIM59 expression is regulated by Sp1 and Nrf1 in LPS-activated macrophages through JNK signaling pathway","volume":"67","author":"An","year":"2020","journal-title":"Cell Signal"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3389\/fimmu.2020.00263","article-title":"TRIM59 Protects Mice From Sepsis by Regulating Inflammation and Phagocytosis in Macrophages","volume":"11","author":"Jin","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"793147","DOI":"10.3389\/fimmu.2022.793147","article-title":"TRIM67 Suppresses TNFalpha-Triggered NF-kB Activation by Competitively Binding Beta-TrCP to IkBa","volume":"13","author":"Fan","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.molimm.2019.01.015","article-title":"E3 ubiquitin ligase tripartite motif 7 positively regulates the TLR4-mediated immune response via its E3 ligase domain in macrophages","volume":"109","author":"Lu","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"109209","DOI":"10.1016\/j.vetmic.2021.109209","article-title":"TRIM21 negatively regulated Corynebacterium pseudotuberculosis-induced inflammation and is critical for the survival of C. pseudotuberculosis infected C57BL6 mice","volume":"261","author":"Tan","year":"2021","journal-title":"Vet. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1165\/rcmb.2017-0236OC","article-title":"Inhibition of Macrophage Complement Receptor CRIg by TRIM72 Polarizes Innate Immunity of the Lung","volume":"58","author":"Nagre","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5810767","DOI":"10.1155\/2018\/5810767","article-title":"Small molecule inhibitor of type three secretion system belonging to a class 2, 4-disubstituted-4H-[1, 3, 4]-thiadiazine-5-ones improves survival and decreases bacterial loads in an airway Pseudomonas aeruginosa infection in mice","volume":"2018","author":"Sheremet","year":"2018","journal-title":"BioMed. Res. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1128\/jcm.6.4.328-331.1977","article-title":"Cultivation of Chlamydia trachomatis in cycloheximide-treated mccoy cells","volume":"6","author":"Ripa","year":"1977","journal-title":"J. Clin. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1128\/jcm.30.11.2911-2916.1992","article-title":"Establishment of a particle-counting method for purified elementary bodies of chlamydiae and evaluation of sensitivities of the IDEIA Chlamydia kit and DNA probe by using the purified elementary bodies","volume":"30","author":"Miyashita","year":"1992","journal-title":"J. Clin. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11B.1.14","DOI":"10.1002\/9780471729259.mc11b01s12","article-title":"Cultivation and laboratory maintenance of Chlamydia pneumoniae","volume":"12","author":"Campbell","year":"2009","journal-title":"Curr. Protoc. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/j.1365-2567.2009.03157.x","article-title":"Differences in innate immune responses correlate with differences in murine susceptibility to Chlamydia muridarum pulmonary infection","volume":"129","author":"Jiang","year":"2010","journal-title":"Immunology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T))","volume":"25","author":"Livak","year":"2001","journal-title":"Method. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/0003-2697(85)90442-7","article-title":"Measurement of protein using bicinchoninic acid","volume":"150","author":"Smith","year":"1985","journal-title":"Anal. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"GigaScience"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1093\/bioinformatics\/btac166","article-title":"Analysing high-throughput sequencing data in Python with HTSeq 2.0","volume":"38","author":"Putri","year":"2022","journal-title":"Bioinformatics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_51","unstructured":"R Core Team (2023). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1124\/mol.116.106716","article-title":"Trim13 Potentiates Toll-Like Receptor 2-Mediated Nuclear Factor \u03baB Activation via K29-Linked Polyubiquitination of Tumor Necrosis Factor Receptor-Associated Factor 6","volume":"91","author":"Huang","year":"2017","journal-title":"Mol. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:39:58Z","timestamp":1760128798000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,27]]},"references-count":52,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241713290"],"URL":"https:\/\/doi.org\/10.3390\/ijms241713290","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,27]]}}}