{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T09:48:56Z","timestamp":1762076936287,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology, Taiwan","award":["MOST 107-2314-B-006-063-MY3","MOST 107-2321-B-006-002","MOHW109-TDU-B-212-114006","MOHW110-TDU-B-212-124006","NHRI-110A1-MRCO-03212101"],"award-info":[{"award-number":["MOST 107-2314-B-006-063-MY3","MOST 107-2321-B-006-002","MOHW109-TDU-B-212-114006","MOHW110-TDU-B-212-124006","NHRI-110A1-MRCO-03212101"]}]},{"name":"Ministry of Health and Welfare, Taiwan","award":["MOST 107-2314-B-006-063-MY3","MOST 107-2321-B-006-002","MOHW109-TDU-B-212-114006","MOHW110-TDU-B-212-124006","NHRI-110A1-MRCO-03212101"],"award-info":[{"award-number":["MOST 107-2314-B-006-063-MY3","MOST 107-2321-B-006-002","MOHW109-TDU-B-212-114006","MOHW110-TDU-B-212-124006","NHRI-110A1-MRCO-03212101"]}]},{"name":"National Health Research Institute, Taiwan","award":["MOST 107-2314-B-006-063-MY3","MOST 107-2321-B-006-002","MOHW109-TDU-B-212-114006","MOHW110-TDU-B-212-124006","NHRI-110A1-MRCO-03212101"],"award-info":[{"award-number":["MOST 107-2314-B-006-063-MY3","MOST 107-2321-B-006-002","MOHW109-TDU-B-212-114006","MOHW110-TDU-B-212-124006","NHRI-110A1-MRCO-03212101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hematopoietic stem and progenitor cells (HSPCs) mobilization is the movement of HSPCs from the bone marrow to the peripheral blood or tissue induced by stress. HSPC mobilization is a well-known response to protect the host during infection through urgent differentiation of HSPCs to immune cells. Dengue virus (DENV) infection is known to cause stress in infected humans and the mobilizing capacity of HSPCs during DENV infection in affected patients has not been fully investigated. Here, we investigated whether DENV infection can induce HSPC mobilization and if the mobilized HSPCs are permissive to DENV infection. White blood cells (WBCs) were collected from dengue patients (DENV+) and healthy donors and analyzed by flow cytometry and plaque assay. Elevated HSPCs levels were found in the WBCs of the DENV+ group when compared to the healthy group. Mobilization of HSPCs and homing markers (skin and gut) expression decreased as the patients proceeded from dengue without symptoms (DWoWS) to severe dengue (SD). Mobilizing HSPCs were not only permissive to DENV infection, but infectious DENV could be recovered after coculture. Our results highlight the need for further investigation into HSPC mobilization or alterations of hematopoiesis during viral infections such as DENV in order to develop appropriate countermeasures.<\/jats:p>","DOI":"10.3390\/ijms232214330","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T02:52:21Z","timestamp":1668999141000},"page":"14330","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mobilization of Hematopoietic Stem and Progenitor Cells during Dengue Virus Infection"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0182-3768","authenticated-orcid":false,"given":"Irwin","family":"Puc","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu-Chuan","family":"Ho","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Wen","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Public Health, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"},{"name":"Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sia-Seng","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Cin","family":"Fong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ju","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng-Hsuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-Hsuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 350401, Taiwan"},{"name":"National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Zhunan 350401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan 701401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guey-Chuen","family":"Perng","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"},{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2226-8916","authenticated-orcid":false,"given":"Jih-Jin","family":"Tsai","sequence":"additional","affiliation":[{"name":"Tropical Medicine Center, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan"},{"name":"Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan"},{"name":"School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.mib.2008.06.004","article-title":"Structural proteomics of dengue virus","volume":"11","author":"Perera","year":"2008","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_2","unstructured":"WHO (2012). Global Strategy for Dengue Prevention and Control, 2012\u20132020, WHO."},{"key":"ref_3","first-page":"19839","article-title":"Dengue viruses\u2014An overview","volume":"3","author":"Lundkvist","year":"2013","journal-title":"Infect. Ecol. Epidemiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nri3660","article-title":"Emergency granulopoiesis","volume":"14","author":"Manz","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1182\/blood-2012-11-466268","article-title":"Staphylococcus aureus recognition by hematopoietic stem and progenitor cells via TLR2\/MyD88\/PGE2 stimulates granulopoiesis in wounds","volume":"122","author":"Granick","year":"2013","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1007\/s12026-009-8109-6","article-title":"Hematopoietic stem and progenitor cells: Their mobilization and homing to bone marrow and peripheral tissue","volume":"44","author":"Schulz","year":"2009","journal-title":"Immunol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"28082","DOI":"10.1038\/srep28082","article-title":"Mobilisation and dysfunction of haematopoietic stem\/progenitor cells after Listonella anguillarum infection in ayu, Plecoglossus altivelis","volume":"6","author":"Lu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1016\/j.ajpath.2013.02.027","article-title":"Inflammatory and Innate Immune Responses in Dengue Infection: Protection versus Disease Induction","volume":"182","author":"Costa","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.chom.2014.05.004","article-title":"Infection Mobilizes Hematopoietic Stem Cells through Cooperative NOD-like Receptor and Toll-like Receptor Signaling","volume":"15","author":"Burberry","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s12272-019-01123-2","article-title":"Role of stem cell mobilization in the treatment of ischemic diseases","volume":"42","author":"Kwon","year":"2019","journal-title":"Arch. Pharmacal Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.4103\/1673-5374.235012","article-title":"The impact of hypoxic-ischemic brain injury on stem cell mobilization, migration, adhesion, and proliferation","volume":"13","author":"Peeples","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/s41375-019-0436-6","article-title":"NLRP3 inflammasome couples purinergic signaling with activation of the complement cascade for the optimal release of cells from bone marrow","volume":"33","author":"Ratajczak","year":"2019","journal-title":"Leukemia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0301-472X(02)00883-4","article-title":"Current understanding of stem cell mobilization: The roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells","volume":"30","author":"Lapidot","year":"2002","journal-title":"Exp. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.4049\/jimmunol.1400176","article-title":"IL-33\u2013Induced Hematopoietic Stem and Progenitor Cell Mobilization Depends upon CCR2","volume":"193","author":"Kim","year":"2014","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.stemcr.2018.05.016","article-title":"ICAM-1 Deficiency in the Bone Marrow Niche Impairs Quiescence and Repopulation of Hematopoietic Stem Cells","volume":"11","author":"Liu","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1186\/1471-2334-10-356","article-title":"Acute dengue virus 2 infection in Gabonese patients is associated with an early innate immune response, including strong interferon alpha production","volume":"10","author":"Becquart","year":"2010","journal-title":"BMC Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8403937","DOI":"10.1155\/2018\/8403937","article-title":"Serum Cytokine Profiles in Patients with Dengue Fever at the Acute Infection Phase","volume":"2018","author":"Huang","year":"2018","journal-title":"Dis. Markers"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Patro, A.R.K., Mohanty, S., Prusty, B.K., Singh, D.K., Gaikwad, S., Saswat, T., Chattopadhyay, S., Das, B.K., Tripathy, R., and Ravindran, B. (2019). Cytokine Signature Associated with Disease Severity in Dengue. Viruses, 11.","DOI":"10.3390\/v11010034"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1097\/MOH.0000000000000149","article-title":"Regulation of stress-induced hematopoiesis","volume":"22","author":"Zhao","year":"2015","journal-title":"Curr. Opin. Hematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/j.1574-695X.2008.00399.x","article-title":"Dengue 2 virus inhibits in vitro megakaryocytic colony formation and induces apoptosis in thrombopoietin-inducible megakaryocytic differentiation from cord blood CD34+ cells","volume":"53","author":"Basu","year":"2008","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1111\/trf.15416","article-title":"Identification and characterization of permissive cells to dengue virus infection in human hematopoietic stem and progenitor cells","volume":"59","author":"Hsu","year":"2019","journal-title":"Transfusion"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jcyt.2012.11.006","article-title":"Analysis of chemotactic molecules in bone marrow-derived mesenchymal stem cells and the skin: Ccl27-Ccr10 axis as a basis for targeting to cutaneous tissues","volume":"15","author":"Alexeev","year":"2013","journal-title":"Cytotherapy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2810","DOI":"10.1634\/stemcells.2006-0264","article-title":"CTACK\/CCL27 Accelerates Skin Regeneration via Accumulation of Bone Marrow-Derived Keratinocytes","volume":"24","author":"Inokuma","year":"2006","journal-title":"Stem Cells"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1053\/j.gastro.2015.10.046","article-title":"Leukocyte Trafficking to the Small Intestine and Colon","volume":"150","author":"Habtezion","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"836","DOI":"10.2174\/156652409789105525","article-title":"Role of beta7 integrins in intestinal lymphocyte homing and retention","volume":"9","author":"Gorfu","year":"2009","journal-title":"Curr. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Correa, A.R.V., Berbel, A.C.E.R., Papa, M.P., De Morais, A.T.S., Pe\u00e7anha, L.M.T., and De Arruda, L.B. (2015). Dengue Virus Directly Stimulates Polyclonal B Cell Activation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143391"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jviromet.2013.09.009","article-title":"Development of a FACS-based assay for evaluating antiviral potency of compound in dengue infected peripheral blood mononuclear cells","volume":"196","author":"Fu","year":"2014","journal-title":"J. Virol. Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1126\/science.1219179","article-title":"A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells","volume":"336","author":"Schulz","year":"2012","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nri1779","article-title":"Bone-marrow haematopoietic-stem-cell niches","volume":"6","author":"Wilson","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1634\/stemcells.2007-0461","article-title":"Vaccinia Virus Infection Modulates the Hematopoietic Cell Compartments in the Bone Marrow","volume":"26","author":"Singh","year":"2008","journal-title":"Stem Cells"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"364","DOI":"10.3389\/fimmu.2016.00364","article-title":"Impact of Viral Infections on Hematopoiesis: From Beneficial to Detrimental Effects on Bone Marrow Output","volume":"7","author":"Pascutti","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1038\/s41598-019-39772-4","article-title":"Mobilization of Stem and Progenitor Cells in Septic Shock Patients","volume":"9","author":"Skirecki","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.exphem.2006.09.015","article-title":"Novel Anti-Inflammatory Function of Human Galectin-1: Inhibition of Hematopoietic Progenitor Cell Mobilization","volume":"35","author":"Kiss","year":"2007","journal-title":"Exp. Hematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jbior.2018.09.003","article-title":"Galectins as regulators of cell survival in the leukemia niche","volume":"71","author":"Ruvolo","year":"2019","journal-title":"Adv. Biol. Regul."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Liu, K.T., Liu, Y.H., Chen, Y.H., Lin, C.Y., Huang, C.H., Yen, M.C., and Kuo, P.L. (2016). Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060832"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Vogt, M.B., Lahon, A., Arya, R.P., Clinton, J.L.S., and Rico-Hesse, R. (2019). Dengue viruses infect human megakaryocytes, with probable clinical consequences. PLoS Neglected Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007837"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11648","DOI":"10.1128\/JVI.01156-13","article-title":"Inhibition of Megakaryocyte Development in the Bone Marrow Underlies Dengue Virus-Induced Thrombocytopenia in Humanized Mice","volume":"87","author":"Sridharan","year":"2013","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"165107","DOI":"10.1155\/2012\/165107","article-title":"Hematopoietic Stem and Progenitor Cells as Effectors in Innate Immunity","volume":"2012","author":"Granick","year":"2012","journal-title":"Bone Marrow Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Puc, I., Ho, T.-C., Yen, K.-L., Vats, A., Tsai, J.-J., Chen, P.-L., Chien, Y.-W., Lo, Y.-C., and Perng, G. (2021). Cytokine Signature of Dengue Patients at Different Severity of the Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062879"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1086\/516486","article-title":"Dengue Virus Inhibits Human Hematopoietic Progenitor Growth In Vitro","volume":"175","author":"Murgue","year":"1997","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1097\/01.aids.0000242817.88086.8c","article-title":"Impaired in-vitro growth of megakaryocytic colonies derived from CD34 cells of HIV-1-infected patients with active viral replication","volume":"20","author":"Costantini","year":"2006","journal-title":"AIDS"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1002\/JLB.MR0718-261RR","article-title":"Megakaryocytes as immune cells","volume":"105","author":"Cunin","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1182\/blood-2009-04-214916","article-title":"Dysfunctional expansion of hematopoietic stem cells and block of myeloid differentiation in lethal sepsis","volume":"114","author":"Rodriguez","year":"2009","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1007\/s12015-010-9212-8","article-title":"The Ins and Outs of Hematopoietic Stem Cells: Studies to Improve Transplantation Outcomes","volume":"7","author":"Turner","year":"2011","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4530","DOI":"10.1182\/blood-2011-06-318220","article-title":"How I treat patients who mobilize hematopoietic stem cells poorly","volume":"118","author":"To","year":"2011","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e01220","DOI":"10.1016\/j.idcr.2021.e01220","article-title":"Dengue virus transmission from donor to recipient during haploidentical stem cell transplantation","volume":"25","author":"Yadav","year":"2021","journal-title":"IDCases"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.3201\/eid2008.140508","article-title":"Dengue Virus Transmission by Blood Stem Cell Donor after Travel to Sri Lanka; Germany, 2013","volume":"20","author":"Punzel","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1038\/bmt.2017.152","article-title":"Dengue encephalitis in allogenic hematopoietic stem cell transplantation recipient","volume":"52","author":"Barroso","year":"2017","journal-title":"Bone Marrow Transplant."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1186\/s12879-016-1668-y","article-title":"Serotype influences on dengue severity: A cross-sectional study on 485 confirmed dengue cases in Vit\u00f3ria, Brazil","volume":"16","author":"Vicente","year":"2016","journal-title":"BMC Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12985-022-01773-7","article-title":"Circulation of genotypes of dengue virus serotype 2 in Guangzhou over a period of 20 years","volume":"19","author":"Jiang","year":"2022","journal-title":"Virol. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1089\/vim.2008.0007","article-title":"Guidelines for Plaque-Reduction Neutralization Testing of Human Antibodies to Dengue Viruses","volume":"21","author":"Roehrig","year":"2008","journal-title":"Viral Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14330\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:21:19Z","timestamp":1760145679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,18]]},"references-count":51,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232214330"],"URL":"https:\/\/doi.org\/10.3390\/ijms232214330","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,11,18]]}}}