{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:10:56Z","timestamp":1790028656653,"version":"4.0.1"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Da Tong Key Research Project of Science and Technology Planning","award":["2024025"],"award-info":[{"award-number":["2024025"]}]},{"name":"Da Tong Key Research Project of Science and Technology Planning","award":["81902306"],"award-info":[{"award-number":["81902306"]}]},{"name":"Da Tong Key Research Project of Science and Technology Planning","award":["82174406"],"award-info":[{"award-number":["82174406"]}]},{"name":"Da Tong Key Research Project of Science and Technology Planning","award":["2024QN012"],"award-info":[{"award-number":["2024QN012"]}]},{"name":"National Natural Science Foundation of China","award":["2024025"],"award-info":[{"award-number":["2024025"]}]},{"name":"National Natural Science Foundation of China","award":["81902306"],"award-info":[{"award-number":["81902306"]}]},{"name":"National Natural Science Foundation of China","award":["82174406"],"award-info":[{"award-number":["82174406"]}]},{"name":"National Natural Science Foundation of China","award":["2024QN012"],"award-info":[{"award-number":["2024QN012"]}]},{"name":"Shanghai Municipal Health Commission Traditional Chinese Medicine Research Project","award":["2024025"],"award-info":[{"award-number":["2024025"]}]},{"name":"Shanghai Municipal Health Commission Traditional Chinese Medicine Research Project","award":["81902306"],"award-info":[{"award-number":["81902306"]}]},{"name":"Shanghai Municipal Health Commission Traditional Chinese Medicine Research Project","award":["82174406"],"award-info":[{"award-number":["82174406"]}]},{"name":"Shanghai Municipal Health Commission Traditional Chinese Medicine Research Project","award":["2024QN012"],"award-info":[{"award-number":["2024QN012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is a debilitating joint disorder characterized by cartilage degradation and disruption of chondrocyte homeostasis. Although retinoic acid (RA) has been used in OA models, its precise targets are not clear. A translational framework was employed, integrating RNA-sequencing results, network pharmacology prediction, computational ligand-receptor molecular docking, and biological experimental validation, to systematically elucidate RA\u2019s disease-modifying targets in OA pathogenesis. RNA-sequencing of RA-treated chondrocytes revealed 656 differentially expressed genes (DEGs). Protein\u2013protein interaction (PPI) network analysis and functional enrichment [Gene Ontology (GO)\/Kyoto Encyclopedia of Genes and Genomes (KEGG)] highlighted key pathways, including extracellular matrix (ECM) reorganization and PI3K-Akt-mediated mechanotransduction and others. Network pharmacology analysis identified 42 shared targets between RA and OA. PPI analysis and functional enrichment (GO\/KEGG) highlighted pathways including the renin\u2013angiotensin system and the neuroactive ligand\u2013receptor interaction, among others. Molecular docking ranked candidate targets by binding affinity of RA in descending order as MAPK14 (p38\u03b1), PTGER3 (PGE2 receptor), CA2 (CA2), and others. Five intersecting targets CA2, ACE, PTGS1 (COX-1), PGR, and EDNRA (ETAR) were identified by integrating RNA-sequencing (RNA-seq) results and network pharmacology predictions. These interactions were experimentally validated via western blot, RT-qPCR and immunofluorescence. RA increased the expression of MMP13, CA2 and ACE, and decreased the expression of COL2A1 in chondrocytes. siRNA-mediated knockdown of both CA2 (human CA2 homolog) and ACE (human ACE homolog) inhibit cartilage degradation through downregulating MMP13 and upregulating COL2A1. This study not only elucidates potential molecular mechanisms by which RA modulates chondrocyte catabolism but also offers a valuable reference for the development of novel OA therapeutics.<\/jats:p>","DOI":"10.3390\/ijms26125519","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T09:13:01Z","timestamp":1749460381000},"page":"5519","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Study of Retinoic Acid-Induced Osteoarthritis: Integrating RNA-Sequencing, Network Pharmacology, Molecular Docking, and Experimental Validation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4354-7367","authenticated-orcid":false,"given":"Tao","family":"Lu","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Shanxi Datong University, Datong 037009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0157-456X","authenticated-orcid":false,"given":"Zi-Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Datong Key Laboratory of Smart Medicine and Health Care for Elderly Chronic Diseases, Shanxi Datong University, Datong 037009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang-Shuo","family":"Ge","sequence":"additional","affiliation":[{"name":"Institute of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai-Yu","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Shanxi Datong University, Datong 037009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7154-9208","authenticated-orcid":false,"given":"Qing-Ao","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Shanxi Datong University, Datong 037009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4056-142X","authenticated-orcid":false,"given":"Dao-Fang","family":"Ding","sequence":"additional","affiliation":[{"name":"Institute of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/S0140-6736(20)32230-3","article-title":"Osteoarthritis in 2020 and beyond: A Lancet Commission","volume":"396","author":"Hunter","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zheng, L., Lu, Z., Xu, G., Niu, X., and Zhao, J. (2024). Dual-targeted disease-modifying therapies for osteoarthritis. Lancet, 403.","DOI":"10.1016\/S0140-6736(24)00475-6"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.joca.2024.02.009","article-title":"A missed opportunity: A scoping review of the effect of sex and age on osteoarthritis using large animal models","volume":"32","author":"Stewart","year":"2024","journal-title":"Osteoarthr. Cartil."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.joca.2024.02.003","article-title":"Obesity and body mass index: Past and future considerations in osteoarthritis research","volume":"32","author":"Godziuk","year":"2024","journal-title":"Osteoarthr. Cartil."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100390","DOI":"10.1016\/j.ocarto.2023.100390","article-title":"Joint biomarker response to mechanical stimuli in osteoarthritis\u2014A scoping review","volume":"5","author":"Hamrouni","year":"2023","journal-title":"Osteoarthr. Cart. Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.berh.2015.04.015","article-title":"HIP osteoarthritis and work","volume":"29","author":"Harris","year":"2015","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.1097\/MS9.0000000000000973","article-title":"Dynamic interaction of obesity, age, MCP-1 Level, and ACE-1 gene with the severity of knee osteoarthritis: A cross-sectional study","volume":"85","author":"Mustari","year":"2023","journal-title":"Ann. Med. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Oliveira, L.M., Teixeira, F., and Sato, M.N. (2018). Impact of Retinoic Acid on Immune Cells and Inflammatory Diseases. Mediat. Inflamm., 2018.","DOI":"10.1155\/2018\/3067126"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Jakaria, M., Belaidi, A.A., Bush, A.I., and Ayton, S. (2023). Vitamin A metabolites inhibit ferroptosis. Biomed. Pharmacother., 164.","DOI":"10.1016\/j.biopha.2023.114930"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/347558a0","article-title":"The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus","volume":"347","author":"Chomienne","year":"1990","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1126\/science.2218500","article-title":"Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17","volume":"249","author":"Borrow","year":"1990","journal-title":"Science"},{"key":"ref_13","first-page":"118","article-title":"Retinoid teratogenesis: Toxicokinetics and structure-specificity","volume":"16","author":"Nau","year":"1994","journal-title":"Arch. Toxicol. Suppl."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s002040050368","article-title":"Effects of all-trans-retinoyl-beta-D-glucuronide and all-trans-retinoic acid on chondrogenesis and retinoid metabolism in mouse limb bud mesenchymal cells in vitro","volume":"71","author":"Sass","year":"1997","journal-title":"Arch. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/S0190-9622(84)80329-1","article-title":"Isotretinoin therapy is associated with early skeletal radiographic changes","volume":"10","author":"Ellis","year":"1984","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gerber, L.H., Helfgott, R.K., Gross, E.G., Hicks, J.E., Ellenberg, S.S., and Peck, G.L. (1984). Vertebral abnormalities associated with synthetic retinoid use. J. Am. Acad. Dermatol., 10.","DOI":"10.1016\/S0190-9622(84)70097-1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.gene.2013.05.069","article-title":"A current review of molecular mechanisms regarding osteoarthritis and pain","volume":"527","author":"Lee","year":"2013","journal-title":"Gene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"50","DOI":"10.2460\/ajvr.77.1.50","article-title":"Production of serum amyloid A in equine articular chondrocytes and fibroblast-like synoviocytes treated with proinflammatory cytokines and its effects on the two cell types in culture","volume":"77","author":"Jacobsen","year":"2016","journal-title":"Am. J. Vet. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.joca.2020.01.007","article-title":"Macrophages regulate the progression of osteoarthritis","volume":"28","author":"Zhang","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"W422","DOI":"10.1093\/nar\/gkae236","article-title":"ADMETlab 3.0: An updated comprehensive online ADMET prediction platform enhanced with broader coverage, improved performance, API functionality and decision support","volume":"52","author":"Fu","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1083\/jcb.106.1.171","article-title":"Alterations in chondrocyte cytoskeletal architecture during phenotypic modulation by retinoic acid and dihydrocytochalasin B-induced reexpression","volume":"106","author":"Brown","year":"1988","journal-title":"J. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.bbrc.2005.12.100","article-title":"All-trans retinoic acid inhibited chondrogenesis of mouse embryonic palate mesenchymal cells by down-regulation of TGF-beta\/Smad signaling","volume":"340","author":"Yu","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.bone.2017.08.010","article-title":"Retinoid roles and action in skeletal development and growth provide the rationale for an ongoing heterotopic ossification prevention trial","volume":"109","author":"Pacifici","year":"2018","journal-title":"Bone"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Feneck, E., and Logan, M. (2020). The Role of Retinoic Acid in Establishing the Early Limb Bud. Biomolecules, 10.","DOI":"10.3390\/biom10020312"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.stemcr.2019.07.012","article-title":"Simple and Robust Differentiation of Human Pluripotent Stem Cells toward Chondrocytes by Two Small-Molecule Compounds","volume":"13","author":"Kawata","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mancini, F.E., Humphreys, P., Woods, S., Bates, N., Cuvertino, S., O\u2019Flaherty, J., Biant, L., Domingos, M., and Kimber, S.J. (2024). Effect of a retinoic acid analogue on BMP-driven pluripotent stem cell chondrogenesis. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-52362-3"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/0012-1606(87)90409-X","article-title":"Retinoic acid rapidly reduces cartilage matrix synthesis by altering gene transcription in chondrocytes","volume":"123","author":"Horton","year":"1987","journal-title":"Dev. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0945-053X(99)00024-4","article-title":"Effects of culture conditions and exposure to catabolic stimulators (IL-1 and retinoic acid) on the expression of matrix metalloproteinases (MMPs) and disintegrin metalloproteinases (ADAMs) by articular cartilage chondrocytes","volume":"18","author":"Flannery","year":"1999","journal-title":"Matrix Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/art.34453","article-title":"Osteoarthritis: A disease of the joint as an organ","volume":"64","author":"Loeser","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Horvath, E., Solyom, A., Szekely, J., Nagy, E.E., and Popoviciu, H. (2023). Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216468"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"723","DOI":"10.2147\/JIR.S348491","article-title":"p38MAPK Signaling Pathway in Osteoarthritis: Pathological and Therapeutic Aspects","volume":"15","author":"Li","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/hr.2015.18","article-title":"Continuous infusion of angiotensin II modulates hypertrophic differentiation and apoptosis of chondrocytes in cartilage formation in a fracture model mouse","volume":"38","author":"Kawahata","year":"2015","journal-title":"Hypertens. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1006\/excr.1998.4071","article-title":"Carbonic anhydrase II plays a major role in osteoclast differentiation and bone resorption by effecting the steady state intracellular pH and Ca2+","volume":"242","author":"Lehenkari","year":"1998","journal-title":"Exp. Cell Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Natua, S., Dhamdhere, S.G., Mutnuru, S.A., and Shukla, S. (2022). Interplay within tumor microenvironment orchestrates neoplastic RNA metabolism and transcriptome diversity. Wiley Interdiscip. Rev.-RNA, 13.","DOI":"10.1002\/wrna.1676"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gao, P., Gao, P., Zhao, J., Shan, S., Luo, W., Slivano, O.J., Zhang, W., Tabuchi, A., LeMaire, S.A., and Maegdefessel, L. (2021). MKL1 cooperates with p38MAPK to promote vascular senescence, inflammation, and abdominal aortic aneurysm. Redox Biol., 41.","DOI":"10.1016\/j.redox.2021.101903"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12771","DOI":"10.1002\/jcp.27897","article-title":"Naproxen attenuates osteoarthritis progression through inhibiting the expression of prostaglandinl-endoperoxide synthase 1","volume":"234","author":"Wang","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Dai, C., Jia, J., Kot, A., Liu, X., Liu, L., Jiang, M., Lane, N.E., Wise, B.L., and Yao, W. (2020). Selective inhibition of progesterone receptor in osteochondral progenitor cells, but not in mature chondrocytes, modulated subchondral bone structures. Bone, 132.","DOI":"10.1016\/j.bone.2019.115196"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.joca.2020.01.001","article-title":"RNA-seq analysis of chondrocyte transcriptome reveals genetic heterogeneity in LG\/J and SM\/J murine strains","volume":"28","author":"Duan","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3928\/19404921-20200312-01","article-title":"Genetic Predictors of Knee Pain in Persons with Mild to Moderate Osteoarthritis","volume":"13","author":"Schutte","year":"2020","journal-title":"Res. Gerontol. Nurs."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1002\/jor.22099","article-title":"Transforming growth factor-alpha induces endothelin receptor A expression in osteoarthritis","volume":"30","author":"Usmani","year":"2012","journal-title":"J. Orthop. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chen, G., Hu, S., Lai, Z., and Qiu, B. (2019). Association between ACE gene I\/D polymorphism and knee osteoarthritis in a Chinese population. Biosci. Rep., 39.","DOI":"10.1042\/BSR20181713"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mustari, M.N., Massi, M.N., Usman, M.A., Bukhari, A., Idris, I., Zainuddin, A., Adnan, E., Bakri, S., Hatta, M., and Rasyid, H. (2024). Association between angiotensin-converting enzyme (ACE) gene I\/D polymorphism with the risk of knee OA: A systematic review, meta-analysis, and meta-regression. F1000Research, 13.","DOI":"10.12688\/f1000research.140233.1"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/bdrb.21110","article-title":"Excessive retinoic acid impaired proliferation and differentiation of human fetal palatal chondrocytes (hFPCs)","volume":"101","author":"Li","year":"2014","journal-title":"Birth Defects Res. B Dev. Reprod. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"D1388","DOI":"10.1093\/nar\/gkaa971","article-title":"PubChem in 2021: New data content and improved web interfaces","volume":"49","author":"Kim","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"W357","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cpbi.5","article-title":"The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses","volume":"54","author":"Stelzer","year":"2016","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Tang, D., Chen, M., Huang, X., Zhang, G., Zeng, L., Zhang, G., Wu, S., and Wang, Y. (2023). SRplot: A free online platform for data visualization and graphing. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0294236"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"O\u2019Boyle, N.M., Banck, M., James, C.A., Morley, C., Vandermeersch, T., and Hutchison, G.R. (2011). Open Babel: An open chemical toolbox. J. Cheminform., 3.","DOI":"10.1186\/1758-2946-3-33"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"The UniProt Consortium (2023). Uniprot UniProt: The Universal Protein Knowledgebase in 2023. Nucleic Acids Res., 51, D523\u2013D531.","DOI":"10.1093\/nar\/gkac1052"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10822-007-9114-2","article-title":"Surflex-Dock 2.1: Robust performance from ligand energetic modeling, ring flexibility, and knowledge-based search","volume":"21","author":"Jain","year":"2007","journal-title":"J. Comput.-Aided Mol. Des."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5519\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:48:55Z","timestamp":1760032135000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":53,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125519"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125519","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]}}}