{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:25:01Z","timestamp":1772252701281,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,12]],"date-time":"2023-02-12T00:00:00Z","timestamp":1676160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japanese Ministry of Education, Culture, Sports, Science, and Technology, Japan (Kasumigaseki, Chiyoda-ku, Tokyo)","award":["20K18750"],"award-info":[{"award-number":["20K18750"]}]},{"name":"Japanese Ministry of Education, Culture, Sports, Science, and Technology, Japan (Kasumigaseki, Chiyoda-ku, Tokyo)","award":["21BA100275"],"award-info":[{"award-number":["21BA100275"]}]},{"name":"AnGes Inc., and Hosokawa Micron Corporation","award":["20K18750"],"award-info":[{"award-number":["20K18750"]}]},{"name":"AnGes Inc., and Hosokawa Micron Corporation","award":["21BA100275"],"award-info":[{"award-number":["21BA100275"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Residual ridge resorption combined with dimensional loss resulting from tooth extraction has a prolonged correlation with early excessive inflammation. Nuclear factor-kappa B (NF-\u03baB) decoy oligodeoxynucleotides (ODNs) are double-stranded DNA sequences capable of downregulating the expression of downstream genes of the NF-\u03baB pathway, which is recognized for regulating prototypical proinflammatory signals, physiological bone metabolism, pathologic bone destruction, and bone regeneration. The aim of this study was to investigate the therapeutic effect of NF-\u03baB decoy ODNs on the extraction sockets of Wistar\/ST rats when delivered by poly(lactic-co-glycolic acid) (PLGA) nanospheres. Microcomputed tomography and trabecular bone analysis following treatment with NF-\u03baB decoy ODN-loaded PLGA nanospheres (PLGA-NfDs) demonstrated inhibition of vertical alveolar bone loss with increased bone volume, smoother trabecular bone surface, thicker trabecular bone, larger trabecular number and separation, and fewer bone porosities. Histomorphometric and reverse transcription\u2013quantitative polymerase chain reaction analysis revealed reduced tartrate-resistant acid phosphatase-expressing osteoclasts, interleukin-1\u03b2, tumor necrosis factor-\u03b1, receptor activator of NF-\u03baB ligand, turnover rate, and increased transforming growth factor-\u03b21 immunopositive reactions and relative gene expression. These data demonstrate that local NF-\u03baB decoy ODN transfection via PLGA-NfD can be used to effectively suppress inflammation in a tooth-extraction socket during the healing process, with the potential to accelerate new bone formation.<\/jats:p>","DOI":"10.3390\/ijms24043699","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T03:28:46Z","timestamp":1676258926000},"page":"3699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["NF-\u03baB Decoy ODN-Loaded Poly(Lactic-co-glycolic Acid) Nanospheres Inhibit Alveolar Ridge Resorption"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4710-032X","authenticated-orcid":false,"given":"Albert chun-shuo","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4973-8762","authenticated-orcid":false,"given":"Yuji","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duantawan","family":"Rintanalert","sequence":"additional","affiliation":[{"name":"Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan"},{"name":"Department of Orthodontics, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kasumi","family":"Hatano-sato","sequence":"additional","affiliation":[{"name":"Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Oishi","sequence":"additional","affiliation":[{"name":"Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Hosomichi","sequence":"additional","affiliation":[{"name":"Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Risa","family":"Usumi-fujita","sequence":"additional","affiliation":[{"name":"Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3754-6723","authenticated-orcid":false,"given":"Hiroyuki","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan"},{"name":"Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Tsujimoto","sequence":"additional","affiliation":[{"name":"Pharmaceutical\/Beauty Science Research Center, Material Business Division, Hosokawa Micron Corporation, Osaka 573-1132, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiko","family":"Sasai","sequence":"additional","affiliation":[{"name":"Pharmaceutical\/Beauty Science Research Center, Material Business Division, Hosokawa Micron Corporation, Osaka 573-1132, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayaka","family":"Ochi","sequence":"additional","affiliation":[{"name":"Pharmaceutical\/Beauty Science Research Center, Material Business Division, Hosokawa Micron Corporation, Osaka 573-1132, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajime","family":"Watanabe","sequence":"additional","affiliation":[{"name":"AnGes Inc., Tokyo 108-0014, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8043-660X","authenticated-orcid":false,"given":"Takashi","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151030","DOI":"10.1155\/2012\/151030","article-title":"Postextraction Alveolar Ridge Preservation: Biological Basis and Treatments","volume":"2012","author":"Pagni","year":"2012","journal-title":"Int. J. Dent."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1097\/00008505-200009020-00011","article-title":"Postextraction Ridge Preservation Using a Synthetic Alloplast","volume":"9","author":"Ashman","year":"2000","journal-title":"Implant. Dent."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1758736012456543","DOI":"10.1177\/1758736012456543","article-title":"Alveolar Ridge Resorption after Tooth Extraction: A Consequence of a Fundamental Principle of Bone Physiology","volume":"3","author":"Hansson","year":"2012","journal-title":"J. Dent. Biomech."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/prd.12082","article-title":"Alveolar Socket Healing: What Can We Learn?","volume":"68","author":"Silva","year":"2015","journal-title":"Periodontology 2000"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1177\/0022034514541127","article-title":"Effect of Alveolar Ridge Preservation after Tooth Extraction: A Systematic Review and Meta-Analysis","volume":"93","author":"Elangovan","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/jcpe.13390","article-title":"Post-Extraction Dimensional Changes: A Systematic Review and Meta-Analysis","volume":"48","author":"Stuhr","year":"2021","journal-title":"J. Clin. Periodontol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u039aB Signaling in Inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_8","first-page":"71","article-title":"Application of Decoy Oligonucleotides as Novel Therapeutic Strategy: A Contemporary Overview","volume":"10","author":"Akhter","year":"2013","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/bs.apcsb.2016.11.002","article-title":"NF-\u039aB as a Therapeutic Target in Inflammatory-Associated Bone Diseases","volume":"107","author":"Lin","year":"2017","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.actbio.2016.05.038","article-title":"NF-\u039aB Decoy Oligodeoxynucleotide Mitigates Wear Particle-Associated Bone Loss in the Murine Continuous Infusion Model","volume":"41","author":"Lin","year":"2016","journal-title":"Acta. Biomater."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.phrs.2009.03.012","article-title":"Oligonucleotide Decoy to NF-\u039aB Slowly Released from PLGA Microspheres Reduces Chronic Inflammation in Rat","volume":"60","author":"Maiuri","year":"2009","journal-title":"Pharmacol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6454","DOI":"10.1073\/pnas.86.17.6454","article-title":"Mechanism of Oligonucleotide Uptake by Cells: Involvement of Specific Receptors?","volume":"86","author":"Yakubov","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","unstructured":"Naito, M., Yokoyama, T., Hosokawa, K., and Nogi, K. (2018). Nanoparticle Technology Handbook, Elsevier. [3rd ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/j.1834-7819.1963.tb02649.x","article-title":"A study of the dimensional changes occurring in the maxilla after tooth extraction Part I. Normal healing","volume":"8","author":"Johnson","year":"1963","journal-title":"Aust. Dent. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.archoralbio.2012.12.013","article-title":"Alveolar Ridge Reduction after Tooth Extraction in Adolescents: An Animal Study","volume":"58","author":"Sun","year":"2013","journal-title":"Arch. Oral Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1563\/0-727.1","article-title":"Dimensional Stability of the Alveolar Ridge after Implantation of a Bioabsorbable Bone Graft Substitute: A Radiographic and Histomorphometric Study in Rats","volume":"31","author":"Hile","year":"2005","journal-title":"J. Oral Implantol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/12_2011_139","article-title":"Development and Modification of Decoy Oligodeoxynucleotides for Clinical Application","volume":"Volume 249","author":"Murakami","year":"2011","journal-title":"Nucleic Acid Drugs. Advances in Polymer Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1080\/10717544.2017.1370511","article-title":"Suppression of Chronic Inflammation with Engineered Nanomaterials Delivering Nuclear Factor \u039aB Transcription Factor Decoy Oligodeoxynucleotides","volume":"24","author":"Farahmand","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/jcpe.13057","article-title":"Effect of Alveolar Ridge Preservation Interventions Following Tooth Extraction: A Systematic Review and Meta-Analysis","volume":"46","author":"Chambrone","year":"2019","journal-title":"J. Clin. Periodontol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"979","DOI":"10.11607\/jomi.6399","article-title":"Systematic Review and Meta-Analysis of Hard Tissue Outcomes of Alveolar Ridge Preservation","volume":"33","author":"Bassir","year":"2018","journal-title":"Int. J. Oral Maxillofac. Implants"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/etp.12016","article-title":"Wound Healing of Extraction Sockets","volume":"25","author":"Farina","year":"2011","journal-title":"Endod. Topics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R59","DOI":"10.1172\/JCI10763","article-title":"Functional Human T-Cell Immunity and Osteoprotegerin Ligand Control Alveolar Bone Destruction in Periodontal Infection","volume":"106","author":"Teng","year":"2000","journal-title":"J. Clin. Invest."},{"key":"ref_23","first-page":"115","article-title":"Birth and Death of Bone Cells: Basic Regulatory Mechanisms and Implications for the Pathogenesis and Treatment of Osteoporosis","volume":"21","author":"Manolagas","year":"2000","journal-title":"Endocr. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1034\/j.1601-0825.2002.01829.x","article-title":"Regulatory Mechanisms of Osteoblast and Osteoclast Differentiation","volume":"8","author":"Katagiri","year":"2002","journal-title":"Oral Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"158","DOI":"10.5051\/jpis.2012.42.5.158","article-title":"Changes in Periodontium after Extraction of a Periodontally-Involved Tooth in Rats","volume":"42","author":"Kim","year":"2012","journal-title":"J. Periodont. Implant. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/S0006-2952(03)00470-2","article-title":"Decoy Oligodeoxynucleotides Targeting NF-KappaB Transcription Factors: Induction of Apoptosis in Human Primary Osteoclasts","volume":"66","author":"Penolazzi","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/sj.gt.3302711","article-title":"NF\u03baB Decoy Oligodeoxynucleotides Ameliorates Osteoporosis through Inhibition of Activation and Differentiation of Osteoclasts","volume":"13","author":"Shimizu","year":"2006","journal-title":"Gene Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"27091","DOI":"10.1074\/jbc.273.42.27091","article-title":"Transforming Growth Factor-\u03b2 Stimulates the Production of Osteoprotegerin\/Osteoclastogenesis Inhibitory Factor by Bone Marrow Stromal Cells","volume":"273","author":"Takai","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/jcp.20036","article-title":"Roles of Stromal Cell RANKL, OPG, and M-CSF Expression in Biphasic TGF-\u03b2 Regulation of Osteoclast Differentiation","volume":"200","author":"Karst","year":"2004","journal-title":"J. Cell Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5940","DOI":"10.4049\/jimmunol.172.10.5940","article-title":"Curcumin (Diferuloylmethane) Inhibits Receptor Activator of NF-\u039aB Ligand-Induced NF-\u039aB Activation in Osteoclast Precursors and Suppresses Osteoclastogenesis","volume":"172","author":"Bharti","year":"2004","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nm1054","article-title":"Selective Inhibition of NF-\u039aB Blocks Osteoclastogenesis and Prevents Inflammatory Bone Destruction in Vivo","volume":"10","author":"Jimi","year":"2004","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Deng, F., Chen, X., Liao, Z., Yan, Z., Wang, Z., Deng, Y., Zhang, Q., Zhang, Z., Ye, J., and Qiao, M. (2014). A Simplified and Versatile System for the Simultaneous Expression of Multiple SiRNAs in Mammalian Cells Using Gibson DNA Assembly. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113064"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.coph.2003.10.008","article-title":"Molecular Therapy to Inhibit NF\u03baB Activation by Transcription Factor Decoy Oligonucleotides","volume":"4","author":"Morishita","year":"2004","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1161\/01.RES.0000023200.19316.D5","article-title":"Inhibitory Effects of Novel AP-1 Decoy Oligodeoxynucleotides on Vascular Smooth Muscle Cell Proliferation In Vitro and Neointimal Formation In Vivo","volume":"90","author":"Ahn","year":"2002","journal-title":"Circ. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/S0006-291X(03)01455-4","article-title":"Inhibitory Effects of Novel E2F Decoy Oligodeoxynucleotides on Mesangial Cell Proliferation by Coexpression of E2F\/DP","volume":"308","author":"Park","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.biomaterials.2010.09.034","article-title":"Oral Nuclear Factor-\u039aB Decoy Oligonucleotides Delivery System with Chitosan Modified Poly(d,l-Lactide-Co-Glycolide) Nanospheres for Inflammatory Bowel Disease","volume":"32","author":"Tahara","year":"2011","journal-title":"Biomaterials"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.jconrel.2021.08.010","article-title":"Recent Trends of NF\u03baB Decoy Oligodeoxynucleotide-Based Nanotherapeutics in Lung Diseases","volume":"337","author":"Mehta","year":"2021","journal-title":"J. Control Release"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/jgm.724","article-title":"Enhanced Intracellular Uptake and Inhibition of NF-\u039aB Activation by Decoy Oligonucleotide Released from PLGA Microspheres","volume":"7","author":"Maiuri","year":"2005","journal-title":"J. Gene Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yamaguchi, H., Ishida, Y., Hosomichi, J., Suzuki, J., Hatano, K., Usumi-Fujita, R., Shimizu, Y., Kaneko, S., and Ono, T. (2017). Ultrasound Microbubble-Mediated Transfection of NF-\u039aB Decoy Oligodeoxynucleotide into Gingival Tissues Inhibits Periodontitis in Rats in Vivo. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186264"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/JPER.21-0134","article-title":"Nuclear Factor-Kappa B Decoy Oligodeoxynucleotide-Loaded Poly Lactic-Co-Glycolic Acid Nanospheres Promote Periodontal Tissue Healing after Tooth Replantation in Rats","volume":"93","author":"Li","year":"2022","journal-title":"J. Periodontol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41368-020-00107-z","article-title":"Titanium Mesh for Bone Augmentation in Oral Implantology: Current Application and Progress","volume":"12","author":"Xie","year":"2020","journal-title":"Int. J. Oral Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jobcr.2016.03.001","article-title":"Clinical Use of the Resorbable Bioscaffold Poly Lactic Co-Glycolic Acid (PLGA) in Post-Extraction Socket for Maintaining the Alveolar Height: A Prospective Study","volume":"6","author":"Hoda","year":"2016","journal-title":"J. Oral Biol. Craniofacial Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/01495739708936692","article-title":"Quantification of Bone Microarchitecture with the Structure Model Index","volume":"1","author":"Hildebrand","year":"1997","journal-title":"Comput. Methods Biomech. Biomed. Engin."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1472-6750-12-5","article-title":"An Improved Method for Isolation of RNA from Bone","volume":"12","author":"Carter","year":"2012","journal-title":"BMC Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3699\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:32:38Z","timestamp":1760121158000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,12]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043699"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043699","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.08.30.505814","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,12]]}}}