{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T16:39:08Z","timestamp":1774370348582,"version":"3.50.1"},"reference-count":66,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>MicroRNAs (miRNAs) play versatile roles in multiple biological processes. However, little is known about miRNA\u2019s involvement in flavivirus persistent infection. Here, we used an miRNA array analysis of Japanese encephalitis virus (JEV)-infected cells to search for persistent infection-associated miRNAs in comparison to acute infection. Among all differentially expressed miRNAs, the miR-125b-5p is the most significantly increased one. The high level of miR-125b-5p in persistently JEV-infected cells was confirmed by Northern analysis and real-time quantitative polymerase chain reaction. As soon as the cells established a persistent infection, a significantly high expression of miR-125b-5p was readily observed. Transfecting excess quantities of a miR-125b-5p mimic into acutely infected cells reduced genome replication and virus titers. Host targets of miR125b-5p were analyzed by target prediction algorithms, and six candidates were confirmed by a dual-luciferase reporter assay. These genes were upregulated in the acutely infected cells and sharply declined in the persistently infected cells. The transfection of the miR125b-5p mimic reduced the expression levels of Stat3, Map2k7, and Triap1. Our studies indicated that miR-125b-5p targets both viral and host sequences, suggesting its role in coordinating viral replication and host antiviral responses. This is the first report to characterize the potential roles of miR-125b-5p in persistent JEV infections.<\/jats:p>","DOI":"10.3390\/ijms22084218","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T11:21:38Z","timestamp":1618831298000},"page":"4218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Differential miRNA Expression Profiling Reveals Correlation of miR125b-5p with Persistent Infection of Japanese Encephalitis Virus"],"prefix":"10.3390","volume":"22","author":[{"given":"Chih-Wei","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Life Science, National Dong Hwa University, Hualien 97401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuen-Nan","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Life Science, National Dong Hwa University, Hualien 97401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Shiuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Life Science, National Dong Hwa University, Hualien 97401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2528-2211","authenticated-orcid":false,"given":"Ruey-Yi","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Life Science, National Dong Hwa University, Hualien 97401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.micinf.2011.01.002","article-title":"Japanese encephalitis virus: From genome to infectome","volume":"13","author":"Unni","year":"2011","journal-title":"Microbes Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.12688\/f1000research.19693.1","article-title":"Recent advances in understanding Japanese encephalitis","volume":"8","author":"Banerjee","year":"2019","journal-title":"F1000Research"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.coviro.2017.03.001","article-title":"Within host RNA virus persistence: Mechanisms and consequences","volume":"23","author":"Randall","year":"2017","journal-title":"Curr. Opin. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/2049-632X.12178","article-title":"The role of viral persistence in flavivirus biology","volume":"71","author":"Mlera","year":"2014","journal-title":"Pathog. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/s1016-8478(23)12908-6","article-title":"Characterization of homologous defective interfering RNA during persistent infection of Vero cells with Japanese encephalitis virus","volume":"21","author":"Yoon","year":"2006","journal-title":"Mol. Cells"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.virusres.2006.10.013","article-title":"Defective interfering RNAs of Japanese encephalitis virus found in mosquito cells and correlation with persistent infection","volume":"124","author":"Tsai","year":"2007","journal-title":"Virus Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1002\/jmv.23665","article-title":"Integrative effect of defective interfering RNA accumulation and helper virus attenuation is responsible for the persistent infection of Japanese encephalitis virus in BHK-21 cells","volume":"85","author":"Park","year":"2013","journal-title":"J. Med Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/ncb0309-228","article-title":"Many roads to maturity: MicroRNA biogenesis pathways and their regulation","volume":"11","author":"Winter","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ejca.2010.11.005","article-title":"MicroRNA regulation of core apoptosis pathways in cancer","volume":"47","author":"Lima","year":"2011","journal-title":"Eur. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2006.08.028","article-title":"microRNAs as oncogenes and tumor suppressors","volume":"302","author":"Zhang","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.bbadis.2011.02.002","article-title":"MicroRNAs and the cell cycle","volume":"1812","author":"Bueno","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.stem.2010.06.012","article-title":"MicroRNAs as regulators of differentiation and cell fate decisions","volume":"7","author":"Ivey","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.3748\/wjg.v19.i20.2985","article-title":"Role of microRNAs in the immune system, inflammation and cancer","volume":"19","author":"Raisch","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.3389\/fimmu.2019.03079","article-title":"The interplay between viral-derived miRNAs and host immunity during infection","volume":"10","author":"Mishra","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1159\/000354455","article-title":"miRNAs: Biogenesis, origin and evolution, functions on virus-host interaction","volume":"32","author":"Zhuo","year":"2013","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1101\/gad.259077.115","article-title":"Viral noncoding RNAs: More surprises","volume":"29","author":"Tycowski","year":"2015","journal-title":"Genes Dev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.chom.2008.05.002","article-title":"Viral and cellular microRNAs as determinants of viral pathogenesis and immunity","volume":"3","author":"Gottwein","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Vojtechova, Z., and Tachezy, R. (2018). The role of miRNAs in virus-mediated oncogenesis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041217"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.molmed.2016.11.003","article-title":"MicroRNA regulation of RNA virus replication and pathogenesis","volume":"23","author":"Trobaugh","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s12985-016-0541-3","article-title":"A glance at subgenomic flavivirus RNAs and microRNAs in flavivirus infections","volume":"13","author":"Bavia","year":"2016","journal-title":"Virol. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1073\/pnas.1320123111","article-title":"MicroRNA-like viral small RNA from Dengue virus 2 autoregulates its replication in mosquito cells","volume":"111","author":"Hussain","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1093\/nar\/gkr848","article-title":"West Nile virus encodes a microRNA-like small RNA in the 3\u2019 untranslated region which up-regulates GATA4 mRNA and facilitates virus replication in mosquito cells","volume":"40","author":"Hussain","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4780","DOI":"10.1128\/JVI.02586-15","article-title":"MicroRNA-19b-3p modulates japanese encephalitis virus-mediated inflammation via targeting RNF11","volume":"90","author":"Ashraf","year":"2016","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4798","DOI":"10.1128\/JVI.02979-13","article-title":"MicroRNA 155 regulates Japanese encephalitis virus-induced inflammatory response by targeting Src homology 2-containing inositol phosphatase 1","volume":"88","author":"Thounaojam","year":"2014","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"22581","DOI":"10.1038\/srep22581","article-title":"Transcriptional regulation of miR-15b by c-Rel and CREB in Japanese encephalitis virus infection","volume":"6","author":"Zhu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/jnc.12609","article-title":"MicroRNA-29b modulates Japanese encephalitis virus-induced microglia activation by targeting tumor necrosis factor alpha-induced protein 3","volume":"129","author":"Thounaojam","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s12985-016-0562-y","article-title":"miR-124 attenuates Japanese encephalitis virus replication by targeting DNM2","volume":"13","author":"Yang","year":"2016","journal-title":"Virol. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1128\/JVI.03242-15","article-title":"MicroRNA-33a-5p modulates Japanese encephalitis virus replication by targeting eukaryotic translation elongation factor 1A1","volume":"90","author":"Chen","year":"2016","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.2147\/NDT.S113236","article-title":"miR-370 mimic inhibits replication of Japanese encephalitis virus in glioblastoma cells","volume":"12","author":"Li","year":"2016","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s10528-020-10009-8","article-title":"Regulation of apoptosis and inflammatory response in interleukin-1beta-induced nucleus pulposus cells by miR-125b-5p via targeting TRIAP1","volume":"59","author":"Jie","year":"2021","journal-title":"Biochem. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.bbrc.2018.08.172","article-title":"miR-125b-5p inhibits breast cancer cell proliferation, migration and invasion by targeting KIAA1522","volume":"504","author":"Li","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.bbrc.2017.07.135","article-title":"MicroRNA-125b-5p modulates the inflammatory state of macrophages via targeting B7-H4","volume":"491","author":"Diao","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.mce.2017.02.023","article-title":"STAT3 activation in infection and infection-associated cancer","volume":"451","author":"Lu","year":"2017","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1010428317719869","DOI":"10.1177\/1010428317719869","article-title":"The relationship between microRNAs and the STAT3-related signaling pathway in cancer","volume":"39","author":"Zhang","year":"2017","journal-title":"Tumor Biol."},{"key":"ref_35","first-page":"2639","article-title":"miR-125b inhibited epithelial-mesenchymal transition of triple-negative breast cancer by targeting MAP2K7","volume":"9","author":"Hong","year":"2016","journal-title":"Onco. Targets Ther."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Huang, Y., Liu, H., Li, S., Tang, Y., Wei, B., Yu, H., and Wang, C. (2014). MAVS-MKK7-JNK2 defines a novel apoptotic signaling pathway during viral infection. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004020"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ibmb.2019.04.008","article-title":"Small RNA responses of Culex mosquitoes and cell lines during acute and persistent virus infection","volume":"109","author":"Ruckert","year":"2019","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sempere, R.N., and Arias, A. (2019). Establishment of a cell culture model of persistent flaviviral infection: Usutu virus shows sustained replication during passages and resistance to extinction by antiviral nucleosides. Viruses, 11.","DOI":"10.3390\/v11060560"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virol.2019.02.018","article-title":"Mosquito cells persistently infected with dengue virus produce viral particles with host-dependent replication","volume":"531","author":"Jaworski","year":"2019","journal-title":"Virology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.virusres.2017.03.005","article-title":"Analysis of the miRNA profile in C6\/36 cells persistently infected with dengue virus type 2","volume":"232","author":"Marchat","year":"2017","journal-title":"Virus Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nbt1385","article-title":"Direct multiplexed measurement of gene expression with color-coded probe pairs","volume":"26","author":"Geiss","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1756-8722-6-6","article-title":"Diverse functions of miR-125 family in different cell contexts","volume":"6","author":"Sun","year":"2013","journal-title":"J. Hematol. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"365273","DOI":"10.1155\/2015\/365273","article-title":"miR-125b suppresses proliferation and invasion by targeting MCL1 in gastric cancer","volume":"2015","author":"Wu","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1038\/bjc.2013.672","article-title":"MiR-125b acts as an oncogene in glioblastoma cells and inhibits cell apoptosis through p53 and p38MAPK-independent pathways","volume":"109","author":"Wu","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1101\/gad.1767609","article-title":"MicroRNA-125b is a novel negative regulator of p53","volume":"23","author":"Le","year":"2009","journal-title":"Genes Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.biopha.2017.08.072","article-title":"MiR125b-5p protects endothelial cells from apoptosis under oxidative stress","volume":"95","author":"Wei","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.3892\/or.2017.5475","article-title":"Upregulation of microRNA-125b-5p is involved in the pathogenesis of osteoarthritis by downregulating SYVN1","volume":"37","author":"Ge","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1124\/mol.111.076794","article-title":"Camptothecin induces apoptosis in cancer cells via microRNA-125b-mediated mitochondrial pathways","volume":"81","author":"Zeng","year":"2012","journal-title":"Mol. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Le, M.T., Shyh-Chang, N., Khaw, S.L., Chin, L., Teh, C., Tay, J., O\u2018Day, E., Korzh, V., Yang, H., and Lal, A. (2011). Conserved regulation of p53 network dosage by microRNA-125b occurs through evolving miRNA-target gene pairs. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002242"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4338","DOI":"10.1182\/blood-2010-06-289058","article-title":"Enforced expression of miR-125b affects myelopoiesis by targeting multiple signaling pathways","volume":"117","author":"Surdziel","year":"2011","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"21496","DOI":"10.1074\/jbc.M109.083337","article-title":"MicroRNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) expression","volume":"285","author":"Zhou","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4034","DOI":"10.1073\/pnas.0510928103","article-title":"MicroRNAs direct rapid deadenylation of mRNA","volume":"103","author":"Wu","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1158\/0008-5472.CAN-06-3071","article-title":"Protein phosphatase-1alpha regulates centrosome splitting through Nek2","volume":"67","author":"Mi","year":"2007","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.15252\/embj.201387576","article-title":"MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer\u2018s disease","volume":"33","author":"Benito","year":"2014","journal-title":"EMBO J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"36109","DOI":"10.1074\/jbc.M205109200","article-title":"The direct binding of the catalytic subunit of protein phosphatase 1 to the PKR protein kinase is necessary but not sufficient for inactivation and disruption of enzyme dimer formation","volume":"277","author":"Tan","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1530\/ERC-12-0194","article-title":"p42\/p44 MAPK-mediated Stat3Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth","volume":"20","author":"Tkach","year":"2013","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"919","DOI":"10.7150\/jca.33696","article-title":"miR-125b-5p\/STAT3 pathway regulated by mTORC1 plays a critical role in promoting cell proliferation and tumor growth","volume":"11","author":"Zhang","year":"2020","journal-title":"J. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.1038\/onc.2008.120","article-title":"Multiple facets of junD gene expression are atypical among AP-1 family members","volume":"27","author":"Hernandez","year":"2008","journal-title":"Oncogene"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S0161-5890(02)00252-3","article-title":"The Bcl-2 protein family: Sensors and checkpoints for life-or-death decisions","volume":"39","author":"Borner","year":"2003","journal-title":"Mol. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"415","DOI":"10.3892\/or.2015.3988","article-title":"Apoptosis inhibitor TRIAP1 is a novel effector of drug resistance","volume":"34","author":"Adams","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/jvh.12522","article-title":"The expression of miR-125b-5p is increased in the serum of patients with chronic hepatitis B infection and inhibits the detection of hepatitis B virus surface antigen","volume":"23","author":"Ninomiya","year":"2016","journal-title":"J. Viral Hepat."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.1007\/s00705-014-2208-y","article-title":"miR-125b inhibits hepatitis B virus expression in vitro through targeting of the SCNN1A gene","volume":"159","author":"Zhang","year":"2014","journal-title":"Arch. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1080\/15476286.2017.1293770","article-title":"MicroRNA-125b-5p mediates post-transcriptional regulation of hepatitis B virus replication via the LIN28B\/let-7 axis","volume":"14","author":"Deng","year":"2017","journal-title":"RNA Biol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Wang, D., Cao, L., Xu, Z., Fang, L., Zhong, Y., Chen, Q., Luo, R., Chen, H., Li, K., and Xiao, S. (2013). MiR-125b reduces porcine reproductive and respiratory syndrome virus replication by negatively regulating the NF-kappaB pathway. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055838"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"24149","DOI":"10.1038\/srep24149","article-title":"Elevated expression of circulating miR876\u20135p is a specific response to severe EV71 infections","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1746-4811-3-12","article-title":"Protocol: A highly sensitive RT-PCR method for detection and quantification of microRNAs","volume":"3","author":"Wu","year":"2007","journal-title":"Plant. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/4218\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:49:44Z","timestamp":1760161784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/4218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,19]]},"references-count":66,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22084218"],"URL":"https:\/\/doi.org\/10.3390\/ijms22084218","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,19]]}}}