{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:50:07Z","timestamp":1791521407680,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2020-02527"],"award-info":[{"award-number":["2020-02527"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2020-02527"],"award-info":[{"award-number":["2020-02527"]}],"id":[{"id":"https:\/\/ror.org\/03zttf063","id-type":"ROR","asserted-by":"publisher"}]},{"name":"ALF-agreement","award":["ALFGBG-965555"],"award-info":[{"award-number":["ALFGBG-965555"]}]},{"DOI":"10.13039\/501100007949","name":"Swedish Rheumatism Association","doi-asserted-by":"publisher","award":["R-981624"],"award-info":[{"award-number":["R-981624"]}],"id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R-981624"],"award-info":[{"award-number":["R-981624"]}],"id":[{"id":"https:\/\/ror.org\/00zps9v98","id-type":"ROR","asserted-by":"publisher"}]},{"name":"SciLifeLab","id":[{"id":"https:\/\/ror.org\/04ev03g22","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/04ev03g22","id-type":"ROR","asserted-by":"publisher"}]},{"name":"BioMS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Knee osteoarthritis (OA) is highly prevalent in women and is characterized by structural joint alterations and synovial inflammatory processes that contribute to pain and impaired mobility. In a previous study, we identified a positive correlation between progesterone levels and pain intensity in postmenopausal women. However, the role of progesterone in synovial inflammation remains poorly understood. Therefore, this study aimed to characterize sex-specific differences in synovial tissue between postmenopausal women and age-matched men and to investigate the association between progesterone levels and the identified molecular profile. Whole blood and synovial tissue were collected from women and men with knee OA to assess plasma progesterone concentrations and the proteomic profiles of synovial tissue and isolated primary fibroblast-like synoviocytes (FLSs). The expression and localization of progesterone receptors were evaluated using RNAscope and immunofluorescence. FLS stimulated with physiological concentrations of progesterone were used for de novo protein synthesis assays. Quantitative proteomics of synovial tissue revealed enrichment of protein synthesis-related pathways in women compared to age-matched men, and isolated FLS from women with knee OA exhibited a pro-inflammatory and pro-fibrotic proteomic profile. Stratification by plasma progesterone levels identified two distinct patient groups, where lower progesterone levels were associated with pro-inflammatory signatures. The RNAscope analysis demonstrated increased transcriptional activity in synovial tissue from women with knee OA, localized to CD90+ sublining FLS. However, progesterone receptor expression at both the RNA and protein levels showed no sex-specific differences. Moreover, physiological concentrations of progesterone inhibited de novo protein synthesis in FLS isolated from men with knee OA. These findings underscore the hormonal context-dependent modulatory effects of progesterone on synovial inflammation and fibroblast activity. The study further highlights the importance of incorporating sex-specific hormonal profiles into OA patient stratification to support more precise and targeted therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms27198899","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:13:02Z","timestamp":1791367982000},"page":"8899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Progesterone Modulates Protein Synthesis in Osteoarthritic Fibroblast-like Synoviocytes"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3631-0348","authenticated-orcid":false,"given":"Fadi","family":"Askar","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Institute of Neuroscience and Physiology, University of Gothenburg, 41390 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6707-159X","authenticated-orcid":false,"given":"Georgios","family":"Chatziagorou","sequence":"additional","affiliation":[{"name":"SportsMed, Carlanderska Hospital, 40545 Gothenburg, Sweden"},{"name":"Department of Orthopedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Sofia","family":"W\u00fcstenhagen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41346 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Alessia","family":"Capraro","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Neuroscience and Physiology, University of Gothenburg, 41390 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Bj\u00f6rn","family":"Andersson","sequence":"additional","affiliation":[{"name":"Bioinformatics and Data Centre, Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6223-8845","authenticated-orcid":false,"given":"Evelin","family":"Berger","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility, SciLifeLab, Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Daniela","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sahlgrenska University Hospital, University of Gothenburg, 41345 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Luminita","family":"Labusca","sequence":"additional","affiliation":[{"name":"National Institute of Research and Development in Technical Physics, 700050 Iasi, Romania"},{"name":"Orthopedics and Trauma Clinic, County Emergency Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1865-3494","authenticated-orcid":false,"given":"Carmen","family":"Corciulo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Neuroscience and Physiology, University of Gothenburg, 41390 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Paskins, Z., Sanders, T., and Hassell, A.B. (2013). What influences patients with osteoarthritis to consult their GP about their symptoms? A narrative review. BMC Fam. Pract., 14.","DOI":"10.1186\/1471-2296-14-195"},{"key":"ref_2","unstructured":"GBD 2021 Osteoarthritis Collaborators (2023). Global, regional, and national burden of osteoarthritis, 1990-2020 and projections to 2050: A systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol., 5, e508\u2013e522."},{"key":"ref_3","first-page":"75","article-title":"Structural correlates of pain in osteoarthritis","volume":"35","author":"Neogi","year":"2017","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1080\/03008207.2025.2531414","article-title":"Pain mechanisms in osteoarthritis: Recent discoveries and opportunities ahead","volume":"66","author":"Hoffman","year":"2025","journal-title":"Connect. Tissue Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Damerau, A., Rosenow, E., Alkhoury, D., Buttgereit, F., and Gaber, T. (2024). Fibrotic pathways and fibroblast-like synoviocyte phenotypes in osteoarthritis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1385006"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41584-022-00749-9","article-title":"Synovial inflammation in osteoarthritis progression","volume":"18","author":"Coras","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pattappa, G., Karlsson, N.G., Steinecker-Frohnwieser, B., Mobasheri, A., Bernotiene, E., Zaucke, F., Roesch, G., Uzieliene, I., Meulenbelt, I., and Rios, J.L. (2025). Towards stratification in osteoarthritis: A review of the scientific terminology used in published basic research. BMC Rheumatol., 9.","DOI":"10.1186\/s41927-025-00557-0"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"iv34","DOI":"10.1093\/rheumatology\/kex417","article-title":"Is osteoarthritis one disease or a collection of many?","volume":"57","author":"Deveza","year":"2018","journal-title":"Rheumatology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Smith, L.C., Ramar, M., Riley, G.L., Mathias, C.B., and Lee, J.-Y. (2025). Steroid hormone regulation of immunometabolism and inflammation. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1654034"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100587","DOI":"10.1016\/j.eclinm.2020.100587","article-title":"Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies","volume":"29\u201330","author":"Cui","year":"2020","journal-title":"EClinicalMedicine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.joca.2018.04.016","article-title":"Gender-related differences observed among immune cells in synovial fluid in knee osteoarthritis","volume":"26","author":"Kriegova","year":"2018","journal-title":"Osteoarthr. Cartil."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100330","DOI":"10.1016\/j.endmts.2026.100330","article-title":"Association of progesterone levels with pain intensity in postmenopausal women with knee osteoarthritis","volume":"22","author":"Askar","year":"2026","journal-title":"Endocr. Metab. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101393","DOI":"10.1016\/j.molmet.2021.101393","article-title":"Impacts of essential amino acids on energy balance","volume":"57","author":"Xiao","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"112272","DOI":"10.1016\/j.jbiomech.2024.112272","article-title":"Synovium friction properties are influenced by proteoglycan content","volume":"174","author":"Gangi","year":"2024","journal-title":"J. Biomech."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1111\/febs.14984","article-title":"Bone and connective tissue disorders caused by defects in glycosaminoglycan biosynthesis: A panoramic view","volume":"286","author":"Paganini","year":"2019","journal-title":"FEBS J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/nrm934","article-title":"Furin at the cutting edge: From protein traffic to embryogenesis and disease","volume":"3","author":"Thomas","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"jcs244749","DOI":"10.1242\/jcs.244749","article-title":"Histone variants at a glance","volume":"134","author":"Talbert","year":"2021","journal-title":"J. Cell Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12822","DOI":"10.1074\/jbc.RA120.012601","article-title":"The tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor complex","volume":"295","author":"Koo","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11601","DOI":"10.1038\/s41598-017-11397-5","article-title":"IL-37 is associated with osteoarthritis disease activity and suppresses proinflammatory cytokines production in synovial cells","volume":"7","author":"Ding","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.joca.2024.04.002","article-title":"Sex differences in osteoarthritis prevalence, pain perception, physical function and therapeutics","volume":"32","author":"Segal","year":"2024","journal-title":"Osteoarthr. Cartil."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/s41590-019-0378-1","article-title":"Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry","volume":"20","author":"Zhang","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s12951-024-02444-1","article-title":"Macrophage-derived mir-100-5p orchestrates synovial proliferation and inflammation in rheumatoid arthritis through mTOR signaling","volume":"22","author":"Liu","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1016\/j.celrep.2018.04.044","article-title":"mTOR Senses Environmental Cues to Shape the Fibroblast-like Synoviocyte Response to Inflammation","volume":"23","author":"Karonitsch","year":"2018","journal-title":"Cell Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bobkova, T., Bobkov, A., and Li, Y. (2025). Pharmacological Inhibition of the PI3K\/AKT\/mTOR Pathway in Rheumatoid Arthritis Synoviocytes: A Systematic Review and Meta-Analysis (Preclinical). Pharmaceuticals, 18.","DOI":"10.3390\/ph18081152"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Barker, B.E., Hanlon, M.M., Marzaioli, V., Smith, C.M., Cunningham, C.C., Fletcher, J.M., Veale, D.J., Fearon, U., and Canavan, M. (2023). The mammalian target of rapamycin contributes to synovial fibroblast pathogenicity in rheumatoid arthritis. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1029021"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11709","DOI":"10.1038\/s41598-023-37732-7","article-title":"Characteristic impairment of progesterone response in cultured cervical fibroblasts obtained from patients with refractory cervical insufficiency","volume":"13","author":"Sugita","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fedotcheva, T.A., Fedotcheva, N.I., and Shimanovsky, N.L. (2022). Progesterone as an Anti-Inflammatory Drug and Immunomodulator: New Aspects in Hormonal Regulation of the Inflammation. Biomolecules, 12.","DOI":"10.3390\/biom12091299"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"351","DOI":"10.4103\/tcmj.tcmj_127_25","article-title":"Ovulation: A consequence of acute inflammation cultivated by E2-induced reactive oxygen species and triggered by progesterone withdrawal","volume":"37","author":"Chen","year":"2025","journal-title":"Tzu Chi Med. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.lfs.2011.12.024","article-title":"Anti-inflammatory effect of proteoglycan and progesterone on human uterine cervical fibroblasts","volume":"90","author":"Fukuyama","year":"2012","journal-title":"Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Li, Y., Adur, M.K., Kannan, A., Davila, J., Zhao, Y., Nowak, R.A., Bagchi, M.K., Bagchi, I.C., and Li, Q. (2016). Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165347"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1042\/bj2750645","article-title":"Hormonal regulation of collagenolysis in uterine cervical fibroblasts. Modulation of synthesis of procollagenase, prostromelysin and tissue inhibitor of metalloproteinases (TIMP) by progesterone and oestradiol-17 beta","volume":"275","author":"Sato","year":"1991","journal-title":"Biochem. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0014-5793(94)80250-5","article-title":"Progesterone increases the production of tissue inhibitor of metalloproteinases-2 in rabbit uterine cervical fibroblasts","volume":"341","author":"Imada","year":"1994","journal-title":"FEBS Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"106199","DOI":"10.1016\/j.jsbmb.2022.106199","article-title":"Regulation of progesterone receptor expression in endometriosis, endometrial cancer, and breast cancer by estrogen, polymorphisms, transcription factors, epigenetic alterations, and ubiquitin-proteasome system","volume":"227","author":"Pu","year":"2023","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s10815-008-9230-5","article-title":"The effect of estradiol on the expression of estrogen, progesterone, androgen, and prolactin receptors in human peritoneal fibroblasts","volume":"25","author":"Detti","year":"2008","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1177\/1933719111419246","article-title":"Interleukin 1beta regulates progesterone metabolism in human cervical fibroblasts","volume":"19","author":"Roberson","year":"2012","journal-title":"Reprod. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1177\/1933719106298191","article-title":"Interleukin 1beta and progesterone stimulate activin a expression and secretion from cultured human endometrial stromal cells","volume":"14","author":"Florio","year":"2007","journal-title":"Reprod. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.joca.2021.09.007","article-title":"A tool for evaluating novel osteoarthritis therapies using multivariate analyses of human cartilage-synovium explant co-culture","volume":"30","author":"Chan","year":"2022","journal-title":"Osteoarthr. Cartil."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.joca.2025.08.012","article-title":"From fat to flame: Multi-omic insights into how adipose-joint crosstalk stokes the fires of osteoarthritis","volume":"34","author":"Wijesinghe","year":"2026","journal-title":"Osteoarthr. Cartil."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lee, A.A., and Den Hartigh, L.J. (2025). Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1682231"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhang, Y.-H., He, M., Wang, Y., and Liao, A.-H. (2017). Modulators of the Balance between M1 and M2 Macrophages during Pregnancy. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00120"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00256-020-03551-4","article-title":"Reliability of three radiographic classification systems for knee osteoarthritis among observers of different experience levels","volume":"50","author":"Wing","year":"2021","journal-title":"Skelet. Radiol."},{"key":"ref_42","first-page":"5","article-title":"The bicinchoninic acid (BCA) assay for protein quantitation","volume":"32","author":"Walker","year":"1994","journal-title":"Methods Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_44","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."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkad1025","article-title":"The Reactome Pathway Knowledgebase 2024","volume":"52","author":"Milacic","year":"2024","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8899\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:18:41Z","timestamp":1791519521000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8899"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":45,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198899"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198899","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]}}}