{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T03:43:42Z","timestamp":1771386222359,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health and Welfare","award":["HI22C1650"],"award-info":[{"award-number":["HI22C1650"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoporosis is a common skeletal disease characterized by decreased bone density, leading to bone fragility and fractures, especially in menopausal women. The purpose of this study is to confirm the anti-osteoporosis activity of stem cell extracellular vesicles (EVs) as a material of regenerative medicine. Mesenchymal stem cells have a potential to differentiate into osteocytes, so directly reconstruct bone tissue or facilitate bone regeneration via paracrine effects. Paracrine effects are mediated by functional molecules delivered in EVs released from stem cells. EVs containing high concentrations of growth factors (GFs) and neurotrophic factors (NFs) were attained via hypoxia culture of human amniotic membrane stem cells (AMSCs). From the EVs with a mean diameter of 77 nm, 751 proteins and 15 species of lipids were identified. Sprague-Dawley rats were ovariectomized, and eight weeks later, intravenously injected with EVs at doses of 1 \u00d7 108, 3 \u00d7 108 or 1 \u00d7 109 particles\/100 \u03bcL\/body, weekly for eight weeks. One week after the final administration, the serum and bone parameters related to bone density were analyzed. Serum 17\u03b2-estradiol, alkaline phosphatase, and calcium levels that decreased in ovariectomized rats were restored by EVs in a dose-dependent manner. Bone parameters such as bone mineral density, bone mineral content, bone volume\/tissue volume ratio, trabecular number, trabecular space, and bending strength were also improved by treatment with EVs. Such effects were confirmed by morphological findings of micro-computed tomography. Taken together, it is suggested that AMSC-EVs containing high concentrations of GFs and NFs preserve bone soundness by promoting bone regeneration and inhibiting bone resorption.<\/jats:p>","DOI":"10.3390\/ijms26199503","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"9503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Osteoporosis-Improving Effects of Extracellular Vesicles from Human Amniotic Membrane Stem Cells in Ovariectomized Rats"],"prefix":"10.3390","volume":"26","author":[{"given":"Ka Young","family":"Kim","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3572-5772","authenticated-orcid":false,"given":"Khan-Erdene","family":"Tsolmon","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zolzaya","family":"Bavuu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan Ho","family":"Noh","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea"},{"name":"Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"High-Technology Research Institute, ThanEver Inc., Daejeon 34054, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heon-Sang","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology, Chungbuk National University, Cheongju 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongsun","family":"Park","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9330-7620","authenticated-orcid":false,"given":"Soon-Cheol","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul 02841, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1340-041X","authenticated-orcid":false,"given":"Yun-Bae","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea"},{"name":"Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1007\/s00198-021-05900-y","article-title":"The clinician\u2019s guide to prevention and treatment of osteoporosis","volume":"33","author":"LeBoff","year":"2022","journal-title":"Osteoporos. Int."},{"key":"ref_2","first-page":"e29367","article-title":"Postmenopausal osteoporosis: A literature review","volume":"14","author":"Bhatnagar","year":"2022","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.tem.2012.03.008","article-title":"Estrogen and the skeleton","volume":"23","author":"Khosla","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Cheng, C.H., Chen, L.R., and Chen, K.H. (2022). Osteoporosis due to hormone imbalance: An overview of the effects of estrogen deficiency and glucocorticoid overuse on bone turnover. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031376"},{"key":"ref_5","first-page":"9","article-title":"Primary osteoporosis in postmenopausal women","volume":"1","author":"Ji","year":"2015","journal-title":"Chronic Dis. Transl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.bone.2016.03.016","article-title":"Estrogen receptors alpha and beta in bone","volume":"87","author":"Khalid","year":"2016","journal-title":"Bone"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kim, J.M., Lin, C., Stavre, Z., Greenblatt, M.B., and Shim, J.H. (2020). Osteoblast\u2013osteoclast communication and bone homeostasis. Cells, 9.","DOI":"10.3390\/cells9092073"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"478","DOI":"10.3899\/jrheum.080759","article-title":"Bisphosphonate associated osteonecrosis of the jaw","volume":"36","author":"Khan","year":"2009","journal-title":"J. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.joms.2009.03.050","article-title":"Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure","volume":"68","author":"Lo","year":"2013","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ocl.2013.01.001","article-title":"Bisphosphonate therapy and atypical fractures","volume":"44","author":"Saleh","year":"2013","journal-title":"Orthop. Clin. N. Am."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4731","DOI":"10.1210\/en.2014-1359","article-title":"Influence of early zoledronic acid administration on bone marrow fat in ovariectomized rats","volume":"155","author":"Li","year":"2014","journal-title":"Endocrinology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"893","DOI":"10.4065\/84.10.893","article-title":"Mesenchymal stem cells for bone repair and metabolic bone diseases","volume":"84","author":"Undale","year":"2009","journal-title":"Mayo Clin. Proc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2217\/rme.09.74","article-title":"Stem cell paracrine actions and tissue regeneration","volume":"5","author":"Baraniak","year":"2010","journal-title":"Regen. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Linero, I., and Chaparro, O. (2014). Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS ONE, 9, Erratum in PLoS ONE 2015, 10, e0119262.","DOI":"10.1371\/journal.pone.0119262"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1042\/CS20120226","article-title":"Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury","volume":"124","author":"Chang","year":"2013","journal-title":"Clin. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Yoon, Y.M., and Lee, S.H. (2017). Hypoxic preconditioning promotes the bioactivities of mesenchymal stem cells via the HIF-1\u03b1-GRP78-Akt axis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061320"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.cell.2016.01.043","article-title":"Communication by extracellular vesicles: Where we are and where we need to go","volume":"164","author":"Tkach","year":"2016","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6917","DOI":"10.2147\/IJN.S264498","article-title":"Exosome: A review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications","volume":"22","author":"Zhang","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Seong, H.R., Noh, C.H., Park, S., Cho, S., Hong, S.J., Lee, A.y., Geum, D., Hong, S.C., Park, D., and Kim, T.M. (2023). Intraocular pressure-lowering and retina-protective effects of exosome-rich conditioned media from human amniotic membrane stem cells in a rat model of glaucoma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098073"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Noh, C.H., Park, S., Seong, H.R., Lee, A.-y., Tsolmon, K.E., Geum, D., Hong, S.C., Kim, T.M., Choi, E.K., and Kim, Y.B. (2023). An exosome-rich conditioned medium from human amniotic membrane stem cells facilitates wound healing via increased reepithelization, collagen synthesis, and angiogenesis. Cells, 12.","DOI":"10.20944\/preprints202311.1137.v1"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1002\/jbmr.4413","article-title":"Osteal macrophages support osteoclast-mediated resorption and contribute to bone pathology in a postmenopausal osteoporosis mouse model","volume":"36","author":"Batoon","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"119208","DOI":"10.1016\/j.lfs.2021.119208","article-title":"Extracellular vesicles from GPNMB-modified bone marrow mesenchymal stem cells attenuate bone loss in an ovariectomized rat model","volume":"272","author":"Huang","year":"2021","journal-title":"Life Sci."},{"key":"ref_23","first-page":"207","article-title":"A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis","volume":"10","author":"Cui","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1159\/000527514","article-title":"Effect of human amniotic epithelial stem cell transplantation on preterm premature rupture of fetal membrane using the amniotic pore culture technique in vitro","volume":"87","author":"Kang","year":"2022","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhu, Z., Zhang, X., Hao, H., Xu, H., Shu, J., Hou, Q., and Wang, M. (2022). Exosomes derived from umbilical cord mesenchymal stem cells treat cutaneous nerve damage and promote wound healing. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.913009"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1172\/JCI12939","article-title":"SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury","volume":"107","author":"Bradshaw","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.bbamcr.2010.01.003","article-title":"The tissue inhibitors of metalloproteinases (TIMPs): An ancient family with structural and functional diversity","volume":"1803","author":"Brew","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"160","DOI":"10.4161\/cam.5.2.14401","article-title":"The filamins: Organizers of cell structure and function","volume":"5","author":"Nakamura","year":"2011","journal-title":"Cell Adhes. Migr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10403","DOI":"10.1021\/acs.jmedchem.8b00822","article-title":"Collagen prolyl 4-hydroxylase as a therapeutic target","volume":"61","author":"Vasta","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_30","first-page":"76","article-title":"Localization of type I and III collagen and fibronectin production in injured gastrocnemius muscle","volume":"64","author":"Hurme","year":"1991","journal-title":"Lab. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Shin, K.O., Ha, D.H., Kim, J.O., Crumrine, D.A., Meyer, J.M., Wakefield, J.S., Lee, Y., Kim, B., Kim, S., and Kim, H.K. (2020). Exosomes from human adipose tissue-derived mesenchymal stem cells promote epidermal barrier repair by inducing de novo synthesis of ceramides in atopic dermatitis. Cells, 9.","DOI":"10.3390\/cells9030680"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1002\/sctm.20-0152","article-title":"Human perivascular stem cells prevent bone graft resorption in osteoporotic contexts by inhibiting osteoclast formation","volume":"9","author":"Negri","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lizcano, F., and Guzman, G. (2014). Estrogen deficiency and the origin of obesity during menopause. Biomed. Res. Int., 2014.","DOI":"10.1155\/2014\/757461"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.3390\/nu5051544","article-title":"Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease","volume":"5","author":"Gaggini","year":"2013","journal-title":"Nutrients"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.1016\/j.jhep.2014.12.012","article-title":"NAFLD: A multisystem disease","volume":"62","author":"Byrne","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jnutbio.2016.08.007","article-title":"Soy isoflavones (Glycine max) ameliorate hypertriglyceridemia and hepatic steatosis in high fat-fed ovariectomized Wistar rats (an experimental model of postmenopausal obesity)","volume":"38","author":"Panneerselvam","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_37","first-page":"3298","article-title":"Bone marrow mesenchymal stem cell-derived exosome protects kidney against ischemia reperfusion injury in rats","volume":"94","author":"Wang","year":"2014","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3808674","DOI":"10.1155\/2016\/3808674","article-title":"Hijacking the cellular mail: Exosome mediated differentiation of mesenchymal stem cells","volume":"2016","author":"Narayanan","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"180","DOI":"10.7150\/thno.17133","article-title":"Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model","volume":"7","author":"Tao","year":"2017","journal-title":"Theranostics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1080\/00365510802409703","article-title":"Order of magnitude differences between methods for maintaining physiological 17beta-oestradiol concentrations in ovariectomized rats","volume":"68","author":"Strom","year":"2008","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1080\/0886022X.2019.1625787","article-title":"Potential role of estradiol in ovariectomy-induced derangement of renal endocrine functions","volume":"41","author":"Elsaed","year":"2019","journal-title":"Ren. Fail."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"433","DOI":"10.3340\/jkns.2019.0097","article-title":"Rutin Improves Bone histomorphometric values by reduction of osteoclastic activity in osteoporosis mouse model induced by bilateral ovariectomy","volume":"63","author":"Lee","year":"2020","journal-title":"J. Korean Neurosurg. Soc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0960-0760(03)00360-1","article-title":"Sources of estrogen and their importance","volume":"86","author":"Simpson","year":"2003","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.molmed.2012.12.007","article-title":"Estrogen synthesis and signaling pathways during ageing: From periphery to brain","volume":"19","author":"Cui","year":"2013","journal-title":"Trends Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Hetemaki, N., Mikkola, T.S., Tikkanen, M.J., Wang, F., Hamalainen, E., Turpeinen, U., Haanpaa, M., Vihma, V., and Peltonen, H.S. (2021). Adipose tissue estrogen production and metabolism in premenopausal women. J. Steroid Biochem. Mol. Biol., 209.","DOI":"10.1016\/j.jsbmb.2021.105849"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.bone.2006.08.002","article-title":"Effects of ibandronate on bone quality: Preclinical studies","volume":"40","author":"Bauss","year":"2007","journal-title":"Bone"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/j.1365-2613.2009.00661.x","article-title":"Ovariectomy-associated changes in bone mineral density and bone marrow haematopoiesis in rats","volume":"90","author":"Lei","year":"2009","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_48","first-page":"582","article-title":"Zoledronic acid inhibits osteoclast differentiation and function through the regulation of NF-\u03baB and JNK signalling pathways","volume":"44","author":"Huang","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3892\/mmr.2021.12575","article-title":"Zoledronic acid inhibits osteoclastogenesis and bone resorptive function by suppressing RANKL-mediated NF-\u03baB and JNK and their downstream signalling pathways","volume":"25","author":"Huang","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Wang, B., Zhan, Y., Yan, L., and Hao, D. (2022). How zoledronic acid improves osteoporosis by acting on osteoclasts. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.961941"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1172\/JCI82585","article-title":"Osteoblast-derived VEGF regulates osteoblast differentiation and bone formation during bone repair","volume":"126","author":"Hu","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.12659\/MSM.905703","article-title":"Resveratrol attenuates lipopolysaccharides (LPS)-induced inhibition of osteoblast differentiation in MC3T3-E1 cells","volume":"24","author":"Ma","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ejphar.2015.03.028","article-title":"Animal models for osteoporosis","volume":"759","author":"Komori","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/978-1-4939-8994-2_29","article-title":"Description of ovariectomy protocol in mice","volume":"1916","author":"Souza","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s00774-007-0811-7","article-title":"Correlation among geometric, densitometric, and mechanical properties in mandible and femur of osteoporotic rats","volume":"26","author":"Jiang","year":"2008","journal-title":"J. Bone Miner. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lee, C., Lee, J.H., Han, S.S., Kim, Y.H., Choi, Y.J., Jeon, K.J., and Jung, H.I. (2019). Site-specific and time-course changes of postmenopausal osteoporosis in rat mandible: Comparative study with femur. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-50554-w"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9503\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T04:23:46Z","timestamp":1759292626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,28]]},"references-count":56,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms26199503"],"URL":"https:\/\/doi.org\/10.3390\/ijms26199503","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,28]]}}}