{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T08:14:27Z","timestamp":1767946467257,"version":"3.49.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Osteoclastogenesis, the differentiation of osteoclasts from monocyte\/macrophage precursors, is essential for physiological bone remodeling but contributes to pathological bone loss in arthritis, osteoporosis, and bone metastasis when dysregulated. CXCL13 is a CXC chemokine well recognized for its role in immune regulation; however, its function in osteoclast biology remains undefined. This study aimed to investigate the effects of CXCL13 on RANKL-induced osteoclastogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>RAW264.7 cells were stimulated with RANKL to induce osteoclastogenesis. Osteoclast formation was evaluated by TRAP and F-actin ring staining, and quantitative real-time PCR (qPCR). GEO bioinformatic analysis revealed gene expression changes during RANKL-induced osteoclastogenesis. Mature osteoclast apoptosis was analyzed by cleaved caspase-3 immunofluorescence staining. MAPK and NF-\u03baB signaling activation was examined by Western blotting and NF-\u03baB luciferase reporter assays. Molecular docking and co-immunoprecipitation were performed to evaluate the interaction between CXCL13 and RANK.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CXCL13 inhibited RANKL-induced osteoclast formation, suppressed osteoclast marker expression, disrupted F-actin ring assembly, and promoted apoptosis in mature osteoclasts. Mechanistically, CXCL13 attenuated MAPK and NF-\u03baB activation and blocked p65 nuclear translocation in a CXCR5-independent manner by competitively interfering with RANKL\u2013RANK binding and downstream RANK\u2013TRAF6 signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings identify CXCL13 as a novel suppressor of osteoclastogenesis by interfering with RANKL\u2013RANK signaling, unveiling an unrecognized regulatory role in osteoclast biology and suggesting potential therapeutic relevance for bone loss disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1729222","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:36:56Z","timestamp":1767940616000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["C-X-C motif chemokine ligand 13 suppresses osteoclast differentiation via interference with RANKL\u2013RANK interaction"],"prefix":"10.3389","volume":"16","author":[{"given":"Trung-Loc","family":"Ho","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun-Tsan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Hao","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le Huynh Hoai","family":"Thuong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Achudhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Chien","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Yuan","family":"Ko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Lin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeng-Hung","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Hsin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/s41413-023-00285-6","article-title":"Interoceptive regulation of skeletal tissue homeostasis and repair","volume":"11","author":"Xiao","year":"2023","journal-title":"Bone Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1365.035","article-title":"Bone remodeling","volume":"1092","author":"Hadjidakis","year":"2006","journal-title":"Ann N Y Acad Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1242\/dev.199908","article-title":"The origins and roles of osteoclasts in bone development, homeostasis and repair","volume":"149","author":"Yahara","year":"2022","journal-title":"Development"},{"key":"B4","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13046-018-1001-2","article-title":"Rankl\/Rank\/Opg system beyond bone remodeling: involvement in breast cancer and clinical perspectives","volume":"38","author":"Infante","year":"2019","journal-title":"J Exp Clin Cancer Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2017.0225","article-title":"Current understanding of rank signaling in osteoclast differentiation and maturation","volume":"40","author":"Park","year":"2017","journal-title":"Mol Cells"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2021.155591","article-title":"Interleukin 19 suppresses Rankl-induced osteoclastogenesis via the inhibition of Nf-Kappab and P38mapk activation and C-Fos expression in Raw264.7 cells","volume":"144","author":"Tsubaki","year":"2021","journal-title":"Cytokine"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202009200","article-title":"A Rank\/Traf6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function","volume":"277","author":"Armstrong","year":"2002","journal-title":"J Biol Chem"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115392","article-title":"Ugonin L inhibits osteoclast formation and promotes osteoclast apoptosis by inhibiting the Mapk and Nf-Kappab pathways","volume":"166","author":"Liu","year":"2023","journal-title":"BioMed Pharmacother"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2817-9","article-title":"Mechanisms involved in normal and pathological osteoclastogenesis","volume":"75","author":"Park-Min","year":"2018","journal-title":"Cell Mol Life Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2015.85","article-title":"Aconine inhibits Rankl-induced osteoclast differentiation in Raw264.7 cells by suppressing Nf-Kappab and Nfatc1 activation and Dc-stamp expression","volume":"37","author":"Zeng","year":"2016","journal-title":"Acta Pharmacol Sin"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112902","article-title":"Niloticin inhibits osteoclastogenesis by blocking Rankl-Rank interaction and suppressing the Akt, Mapk, and Nf-Kappab signaling pathways","volume":"149","author":"Xu","year":"2022","journal-title":"BioMed Pharmacother"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73539","article-title":"Transferrin receptor 1-mediated iron uptake regulates bone mass in mice via osteoclast mitochondria and cytoskeleton","volume":"11","author":"Das","year":"2022","journal-title":"Elife"},{"key":"B13","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/s41392-023-01467-8","article-title":"Targeting strategies for bone diseases: signaling pathways and clinical studies","volume":"8","author":"Xu","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-2023H","article-title":"Bisphosphonates: mode of action and pharmacology","author":"Russell","year":"2007","journal-title":"Pediatrics"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.7.637","article-title":"Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple outcomes of raloxifene evaluation (More) investigators","volume":"282","author":"Ettinger","year":"1999","journal-title":"JAMA"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.253","article-title":"Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American society for bone and mineral research","volume":"25","author":"Shane","year":"2010","journal-title":"J Bone Miner Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/s1074-7613(01)00257-6","article-title":"Cxcl13 is required for B1 cell homing, natural antibody production, and body cavity immunity","volume":"16","author":"Ansel","year":"2002","journal-title":"Immunity"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14020294","article-title":"Potential role of Cxcl13\/Cxcr5 signaling in immune checkpoint inhibitor treatment in cancer","volume":"14","author":"Hsieh","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/978-3-030-62658-7_6","article-title":"Cxcl13 signaling in the tumor microenvironment","volume":"1302","author":"Hussain","year":"2021","journal-title":"Adv Exp Med Biol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1038\/s41419-021-04136-2","article-title":"Cxcl13\/Cxcr5 axis facilitates endothelial progenitor cell homing and angiogenesis during rheumatoid arthritis progression","volume":"12","author":"Tsai","year":"2021","journal-title":"Cell Death Dis"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.04.053","article-title":"Cxcl13\/Cxcr5 signaling axis in cancer","volume":"227","author":"Hussain","year":"2019","journal-title":"Life Sci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.850998","article-title":"Role of the Cxcl13\/Cxcr5 axis in autoimmune diseases","volume":"13","author":"Pan","year":"2022","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-02-140426","article-title":"Altered expression of the receptor-ligand pair Cxcr5\/Cxcl13 in B cells during chronic Hiv-1 infection","volume":"112","author":"Cagigi","year":"2008","journal-title":"Blood"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.09.031","article-title":"Cxcl13-mediated recruitment of intrahepatic Cxcr5(+)Cd8(+) T cells favors viral control in chronic Hbv infection","volume":"72","author":"Li","year":"2020","journal-title":"J Hepatol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/632305","article-title":"Cxcl13 promotes osteogenic differentiation of mesenchymal stem cells by inhibiting Mir-23a expression","volume":"2015","author":"Tian","year":"2015","journal-title":"Stem Cells Int"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.09.058","article-title":"High glucose prevents osteogenic differentiation of mesenchymal stem cells via Lncrna Ak028326\/Cxcl13 pathway","volume":"84","author":"Cao","year":"2016","journal-title":"BioMed Pharmacother"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116037","article-title":"Cxcl13 promotes Tnf-Alpha synthesis in rheumatoid arthritis through activating Erk\/P38 pathway and inhibiting Mir-330-3p generation","volume":"221","author":"Achudhan","year":"2024","journal-title":"Biochem Pharmacol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/onc.2012.24","article-title":"Cxcl13 activation of C-Myc induces rank ligand expression in stromal\/preosteoblast cells in the oral squamous cell carcinoma tumor-bone microenvironment","volume":"32","author":"Sambandam","year":"2013","journal-title":"Oncogene"},{"key":"B29","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s13045-022-01366-5","article-title":"Cxcl13 chemokine is a novel player in multiple myeloma osteolytic microenvironment, M2 macrophage polarization, and tumor progression","volume":"15","author":"Beider","year":"2022","journal-title":"J Hematol Oncol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1051\/bmdcn\/2017070102","article-title":"Kuei-Lu-Er-Xian-Jiao extract enhances Bmp-2 production in osteoblasts","volume":"7","author":"Wu","year":"2017","journal-title":"Biomedicine (Taipei)"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e52807","DOI":"10.3791\/52807","article-title":"Transfecting Raw264.7 cells with a luciferase reporter gene","author":"Cheung","year":"2015","journal-title":"J Vis Exp"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2023.0325-1","article-title":"Usp7 inhibits osteoclastogenesis via dual effects of attenuating Traf6\/Tak1 axis and stimulating sting signaling","volume":"14","author":"Xie","year":"2023","journal-title":"Aging Dis"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.72211","article-title":"Knockout and double knockout of cathepsin K and Mmp9 reveals a novel function of cathepsin K as a regulator of osteoclast gene expression and bone homeostasis","volume":"18","author":"Zhu","year":"2022","journal-title":"Int J Biol Sci"},{"key":"B34","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/s42003-023-04806-1","article-title":"Mechanical stimulation controls osteoclast function through the regulation of Ca(2+)-activated Cl(-) channel anoctamin 1","volume":"6","author":"Sun","year":"2023","journal-title":"Commun Biol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5484.1504","article-title":"Bone resorption by osteoclasts","volume":"289","author":"Teitelbaum","year":"2000","journal-title":"Science"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/nri2062","article-title":"Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems","volume":"7","author":"Takayanagi","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510156200","article-title":"Mcp-1-induced human osteoclast-like cells are tartrate-resistant acid phosphatase, nfatc1, and calcitonin receptor-positive but require receptor activator of nfkappab ligand for bone resorption","volume":"281","author":"Kim","year":"2006","journal-title":"J Biol Chem"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01344-6","article-title":"The Mcp-3\/Ccr3 axis contributes to increased bone mass by affecting osteoblast and osteoclast differentiation","volume":"56","author":"Kim","year":"2024","journal-title":"Exp Mol Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/s41419-019-1448-x","article-title":"Abnormal inhibition of osteoclastogenesis by mesenchymal stem cells through the Mir-4284\/Cxcl5 axis in ankylosing spondylitis","volume":"10","author":"Liu","year":"2019","journal-title":"Cell Death Dis"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1210\/me.2007-0237","article-title":"Nfatc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (Dc-stamp)","volume":"22","author":"Kim","year":"2008","journal-title":"Mol Endocrinol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1002\/mc.1067","article-title":"Inhibition of osteoclast differentiation and bone resorption by cathepsin K antisense oligonucleotides","volume":"32","author":"Ishikawa","year":"2001","journal-title":"Mol Carcinog"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.33.22907","article-title":"Intracellular fragmentation of bone resorption products by reactive oxygen species generated by osteoclastic tartrate-resistant acid phosphatase","volume":"274","author":"Halleen","year":"1999","journal-title":"J Biol Chem"},{"key":"B44","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/s1534-5807(02)00369-6","article-title":"Induction and activation of the transcription factor nfatc1 (Nfat2) integrate Rankl signaling in terminal differentiation of osteoclasts","volume":"3","author":"Takayanagi","year":"2002","journal-title":"Dev Cell"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600858","article-title":"Role of Rankl-induced osteoclast formation and Mmp-dependent matrix degradation in bone destruction by breast cancer metastasis","volume":"88","author":"Ohshiba","year":"2003","journal-title":"Br J Cancer"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0198943","article-title":"Evaluation of phenotypic and functional stability of Raw 264.7 cell line through serial passages","volume":"13","author":"Taciak","year":"2018","journal-title":"PloS One"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1998.13.6.970","article-title":"Osteoclast differentiation requires ascorbic acid","volume":"13","author":"Ragab","year":"1998","journal-title":"J Bone Miner Res"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.bonr.2022.101620","article-title":"Amino acid metabolism in skeletal cells","volume":"17","author":"Devignes","year":"2022","journal-title":"Bone Rep"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0277871","article-title":"Evaluation of culture conditions for osteoclastogenesis in Raw264.7 cells","volume":"17","author":"Cheng","year":"2022","journal-title":"PloS One"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26452","article-title":"Effect of L-caldesmon on osteoclastogenesis in Rankl-induced Raw264.7 cells","volume":"233","author":"Liou","year":"2018","journal-title":"J Cell Physiol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.bcp.2019.05.005","article-title":"Thrombospondin enhances Rankl-dependent osteoclastogenesis and facilitates lung cancer bone metastasis","volume":"166","author":"Wang","year":"2019","journal-title":"Biochem Pharmacol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.4142\/jvs.2013.14.4.405","article-title":"Inhibitory effects of osteoprotegerin on osteoclast formation and function under serum-free conditions","volume":"14","author":"Fu","year":"2013","journal-title":"J Vet Sci"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514552677","article-title":"Osteoprotegerin expressed by osteoclasts: an autoregulator of osteoclastogenesis","volume":"93","author":"Kang","year":"2014","journal-title":"J Dent Res"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.080203","article-title":"Interleukin-4 and interleukin-13 stimulate the osteoclast inhibitor osteoprotegerin by human endothelial cells through the Stat6 pathway","volume":"23","author":"Stein","year":"2008","journal-title":"J Bone Miner Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.6.1271","article-title":"Segregation of Traf6-mediated signaling pathways clarifies its role in osteoclastogenesis","volume":"20","author":"Kobayashi","year":"2001","journal-title":"EMBO J"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.13814","article-title":"Selective regulation of mapk signaling mediates Rankl-dependent osteoclast differentiation","volume":"12","author":"Lee","year":"2016","journal-title":"Int J Biol Sci"},{"key":"B57","doi-asserted-by":"publisher","first-page":"ra54","DOI":"10.1126\/scisignal.2005867","article-title":"The scaffold protein rack1 mediates the Rankl-dependent activation of P38 Mapk in osteoclast precursors","volume":"8","author":"Lin","year":"2015","journal-title":"Sci Signal"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.18632\/aging.206067","article-title":"Caffeic acid derivative Mpmca suppresses osteoclastogenesis and facilitates osteoclast apoptosis: implications for the treatment of bone loss disorders","volume":"16","author":"Thuong","year":"2024","journal-title":"Aging"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01613-4","article-title":"Melatonin interrupts osteoclast functioning and suppresses tumor-secreted Rankl expression: implications for bone metastases","volume":"40","author":"Liu","year":"2021","journal-title":"Oncogene"},{"key":"B60","doi-asserted-by":"publisher","first-page":"5338","DOI":"10.1038\/s41467-022-33006-4","article-title":"Identification of a binding site on soluble Rankl that can be targeted to inhibit soluble Rank-Rankl interactions and treat osteoporosis","volume":"13","author":"Huang","year":"2022","journal-title":"Nat Commun"},{"key":"B61","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3892\/mmr.2021.12575","article-title":"Zoledronic acid inhibits osteoclastogenesis and bone resorptive function by suppressing Rankl\u2212Mediated Nf\u2212Kappab and Jnk and their downstream signalling pathways","volume":"25","author":"Huang","year":"2022","journal-title":"Mol Med Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1729222\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:36:57Z","timestamp":1767940617000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1729222\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,9]]},"references-count":61,"alternative-id":["10.3389\/fimmu.2025.1729222"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1729222","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,9]]},"article-number":"1729222"}}