{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:50:19Z","timestamp":1789638619783,"version":"4.0.0"},"reference-count":60,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T00:00:00Z","timestamp":1513123200000},"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>Canine parvovirus type 2c (CPV-2c) emerged in 2000 and is known for causing a more severe disease than other CPV-2 variants in puppies. In 2015, the emerging CPV-2c variant was isolated in Taiwan and it subsequently became the predominant variant. To trace the evolution of Taiwanese CPV-2c, we compared complete VP2 genes of CPV-2c from Taiwan and sequences obtained from GenBank. The evolutionary rate of CPV-2c was estimated to be 4.586 \u00d7 10\u22124 substitutions per site per year (95% highest posterior density (HPD) was 3.284\u20136.076 \u00d7 10\u22124). The time to the most recent common ancestor (TMRCA) dated to 1990 (95% HPD: 1984\u20131996) and 2011 (95% HPD: 2010\u20132013) for the CPV-2c variant and Taiwanese isolates, respectively. The CPV-2c variant isolated from Taiwan was clustered with CPV-2c from China. This phylogenetic clade began to branch off in approximately 2010 (95% HPD was 3.823\u20136.497). Notably, two unique mutations of Taiwanese CPV-2c were found, Q383R and P410L. In summary, this is the first report on the genome evolution of CPV-2c in Taiwan, revealing that this CPV-2c variant shares a common evolutionary origin with strains from China. The demographic history inferred by the Bayesian skyline plot showed that the effective population of CPV-2c increased until 2006 and then slowly declined until 2011.<\/jats:p>","DOI":"10.3390\/ijms18122703","type":"journal-article","created":{"date-parts":[[2017,12,14]],"date-time":"2017-12-14T04:30:55Z","timestamp":1513225855000},"page":"2703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Phylodynamic and Genetic Diversity of Canine Parvovirus Type 2c in Taiwan"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3672-3000","authenticated-orcid":false,"given":"Yung-Cheng","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung 82144, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Yun","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung-Hsing University, Taichung 40227, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jih-Hui","family":"Lin","sequence":"additional","affiliation":[{"name":"Center of Diagnostics and Vaccine Development, Centers for Disease Control, Taipei 11561, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Tang","family":"Chiou","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"},{"name":"Animal Disease Diagnostic Center, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Fu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 20224, Taiwan"},{"name":"Department of Nursing, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0082-2269","authenticated-orcid":false,"given":"Chao-Nan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"},{"name":"Animal Disease Diagnostic Center, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1073\/pnas.0406765102","article-title":"High rate of viral evolution associated with the emergence of carnivore parvovirus","volume":"102","author":"Shackelton","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s11262-005-0034-8","article-title":"Evolution of CPV-2 and implication for antigenic\/genetic characterization","volume":"33","author":"Martella","year":"2006","journal-title":"Virus Genes"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1099\/0022-1317-72-10-2445","article-title":"Fine mapping of canine parvovirus b cell epitopes","volume":"72","author":"Cortes","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6858","DOI":"10.1128\/jvi.66.12.6858-6867.1992","article-title":"Multiple amino acids in the capsid structure of canine parvovirus coordinately determine the canine host range and specific antigenic and hemagglutination properties","volume":"66","author":"Chang","year":"1992","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8915","DOI":"10.1128\/JVI.77.16.8915-8923.2003","article-title":"Residues in the apical domain of the feline and canine transferrin receptors control host-specific binding and cell infection of canine and feline parvoviruses","volume":"77","author":"Palermo","year":"2003","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9214","DOI":"10.1128\/jvi.71.12.9214-9222.1997","article-title":"Canine parvovirus host range is determined by the specific conformation of an additional region of the capsid","volume":"71","author":"Parker","year":"1997","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1099\/0022-1317-82-12-3021","article-title":"Evidence for evolution of canine parvovirus type 2 in Italy","volume":"82","author":"Buonavoglia","year":"2001","journal-title":"J. Gen. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vetmic.2011.09.007","article-title":"Canine parvovirus: A review of epidemiological and diagnostic aspects, with emphasis on type 2c","volume":"155","author":"Decaro","year":"2012","journal-title":"Vet. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jviromet.2007.08.006","article-title":"Specific identification of feline panleukopenia virus and its rapid differentiation from canine parvoviruses using minor groove binder probes","volume":"147","author":"Decaro","year":"2008","journal-title":"J. Virol. Methods"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.3201\/eid1308.070505","article-title":"The study molecular epidemiology of canine parvovirus, europe","volume":"13","author":"Decaro","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jviromet.2005.10.026","article-title":"Characterisation of the canine parvovirus type 2 variants using minor groove binder probe technology","volume":"133","author":"Decaro","year":"2006","journal-title":"J. Virol. Methods"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4044","DOI":"10.1128\/JCM.01300-07","article-title":"Canine parvovirus types 2c and 2b circulating in north american dogs in 2006 and 2007","volume":"45","author":"Kapil","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s11262-008-0314-1","article-title":"Molecular characterization of canine parvovirus-2 variants circulating in tunisia","volume":"38","author":"Touihri","year":"2009","journal-title":"Virus Genes"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s11262-011-0659-8","article-title":"Study of canine parvovirus evolution: Comparative analysis of full-length VP2 gene sequences from argentina and international field strains","volume":"44","author":"Wilda","year":"2012","journal-title":"Virus Genes"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s11262-011-0703-8","article-title":"Characterization of the partial VP2 gene region of canine parvoviruses in domestic cats from turkey","volume":"44","author":"Muz","year":"2012","journal-title":"Virus Genes"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.vetmic.2015.11.037","article-title":"Epidemiological evolution of canine parvovirus in the portuguese domestic dog population","volume":"183","author":"Miranda","year":"2016","journal-title":"Vet. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1099\/jgv.0.000540","article-title":"Canine parvovirus: The worldwide occurrence of antigenic variants","volume":"97","author":"Miranda","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s12985-016-0620-5","article-title":"Identification of a novel canine parvovirus type 2c in Taiwan","volume":"13","author":"Chiang","year":"2016","journal-title":"Virol. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/1743-422X-11-39","article-title":"Genetic characterization of type 2a canine parvoviruses from Taiwan reveals the emergence of an ILE324 mutation in VP2","volume":"11","author":"Lin","year":"2014","journal-title":"Virol. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.virusres.2011.02.015","article-title":"Evolution of canine parvovirus in argentina between years 2003 and 2010: CPV2C has become the predominant variant affecting the domestic dog population","volume":"157","author":"Calderon","year":"2011","journal-title":"Virus Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1136\/vr.138.18.447","article-title":"Antigenic types of canine parvoviruses prevailing in Taiwan","volume":"138","author":"Chang","year":"1996","journal-title":"Vet. Rec."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s11262-005-1791-0","article-title":"Phylogenetic analysis of canine parvovirus VP2 gene in Taiwan","volume":"31","author":"Wang","year":"2005","journal-title":"Virus Genes"},{"key":"ref_23","first-page":"81","article-title":"Genotyping of canine parvovirus type 2 VP2 gene in southern Taiwan in 2011","volume":"39","author":"Chou","year":"2013","journal-title":"Taiwan Vet. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"Mega7: Molecular evolutionary genetics analysis version 7.0 for bigger datasets","volume":"33","author":"Kumar","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Silva, S.P., Silva, L., Rodrigues, E.D.L., Cardoso, J.F., Tavares, F.N., Souza, W.M., Santos, C.M.P., Martins, F.M.S., Jesus, I.S., and Brito, T.C. (2017). Full-length genomic and molecular characterization of canine parvovirus in dogs from north of brazil. Genet. Mol. Res., 16.","DOI":"10.4238\/gmr16039719"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1099\/vir.0.2008\/002055-0","article-title":"Phylogenetic analysis reveals the emergence, evolution and dispersal of carnivore parvoviruses","volume":"89","author":"Hoelzer","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.meegid.2006.03.007","article-title":"Selective regimen shift and demographic growth increase associated with the emergence of high-fitness variants of canine parvovirus","volume":"7","author":"Pereira","year":"2007","journal-title":"Infect. Genet. Evol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nrg2323","article-title":"Rates of evolutionary change in viruses: Patterns and determinants","volume":"9","author":"Duffy","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.vetmic.2013.06.012","article-title":"High local genetic diversity of canine parvovirus from ecuador","volume":"166","author":"Aldaz","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1007\/s00705-004-0367-y","article-title":"A novel antigenic variant of canine parvovirus from a vietnamese dog","volume":"149","author":"Nakamura","year":"2004","journal-title":"Arch. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s11262-010-0466-7","article-title":"Phylogenetic analysis of the VP2 gene of canine parvoviruses circulating in china","volume":"40","author":"Zhang","year":"2010","journal-title":"Virus Genes"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/tbed.12390","article-title":"Typing of canine parvovirus strains circulating in North-East China","volume":"64","author":"Zhao","year":"2015","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00203-015-1093-4","article-title":"Full-length genomic characterizations of two canine parvoviruses prevalent in northwest china","volume":"197","author":"Han","year":"2015","journal-title":"Arch. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/tbed.12078","article-title":"Phylogenetic analysis of canine parvovirus isolates from Sichuan and Gansu provinces of china in 2011","volume":"62","author":"Xu","year":"2015","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s11262-013-1000-5","article-title":"Phylogenetic analysis of canine parvovirus partial VP2 gene in India","volume":"48","author":"Mukhopadhyay","year":"2013","journal-title":"Virus Genes"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.vetmic.2011.09.017","article-title":"Recent spreading of a divergent canine parvovirus type 2a (CPV-2a) strain in a CPV-2c homogenous population","volume":"155","author":"Perez","year":"2012","journal-title":"Vet. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Perez, R., Calleros, L., Marandino, A., Sarute, N., Iraola, G., Grecco, S., Blanc, H., Vignuzzi, M., Isakov, O., and Shomron, N. (2014). Phylogenetic and genome-wide deep-sequencing analyses of canine parvovirus reveal co-infection with field variants and emergence of a recent recombinant strain. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111779"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/prot.340160204","article-title":"Structure determination of feline Panleukopenia virus empty particles","volume":"16","author":"Agbandje","year":"1993","journal-title":"Proteins"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1126\/science.2006420","article-title":"The three-dimensional structure of canine parvovirus and its functional implications","volume":"251","author":"Tsao","year":"1991","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12166","DOI":"10.3390\/ijms150712166","article-title":"First isolation of new canine parvovirus 2a from Tibetan mastiff and global analysis of the full-length VP2 gene of canine parvoviruses 2 in china","volume":"15","author":"Zhong","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e262","DOI":"10.1111\/tbed.12268","article-title":"Phylogenetic analysis of canine parvovirus VP2 gene in china","volume":"63","author":"Yi","year":"2014","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Geng, Y., Guo, D., Li, C., Wang, E., Wei, S., Wang, Z., Yao, S., Zhao, X., Su, M., and Wang, X. (2015). Co-circulation of the rare CPV-2c with unique Gln370Arg substitution, new CPV-2b with unique Thr440Ala substitution and new CPV-2a with high prevalence and variation in Heilongjiang province, northeast china. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137288"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1292\/jvms.70.719","article-title":"Genetic analysis of VP2 gene of canine parvovirus isolates in Korea","volume":"70","author":"Jeoung","year":"2008","journal-title":"J. Vet. Med. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s00705-009-0444-3","article-title":"Molecular insights into the phylogeny of canine parvovirus 2 (CPV-2) with emphasis on Korean isolates: A bayesian approach","volume":"154","author":"Yoon","year":"2009","journal-title":"Arch. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s11262-010-0475-6","article-title":"Sequence analysis of VP2 gene of canine parvovirus isolates in thailand","volume":"41","author":"Phromnoi","year":"2010","journal-title":"Virus Genes"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.rvsc.2012.09.013","article-title":"Analysis of the VP2 protein gene of canine parvovirus strains from affected dogs in japan","volume":"94","author":"Soma","year":"2013","journal-title":"Res. Vet. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mittal, M., Chakravarti, S., Mohapatra, J.K., Chug, P.K., Dubey, R., Narwal, P.S., Kumar, A., Churamani, C.P., and Kanwar, N.S. (2014). Molecular typing of canine parvovirus strains circulating from 2008\u20132012 in an organized kennel in India reveals the possibility of vaccination failure. Infect. Genet. Evol.","DOI":"10.1016\/j.meegid.2014.01.015"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1007\/s00705-014-2068-5","article-title":"Analysis of the full-length VP2 protein of canine parvoviruses circulating in Hungary","volume":"159","author":"Csagola","year":"2014","journal-title":"Arch. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/S1369-5274(03)00083-3","article-title":"Parvovirus host range, cell tropism and evolution","volume":"6","author":"Hueffer","year":"2003","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/1743-422X-10-163","article-title":"Identification of canine parvovirus with the Q370R point mutation in the VP2 gene from a giant panda (Ailuropoda melanoleuca)","volume":"10","author":"Guo","year":"2013","journal-title":"Virol. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1006\/jmbi.2000.3868","article-title":"Host range and variability of calcium binding by surface loops in the capsids of canine and feline parvoviruses","volume":"300","author":"Simpson","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1006\/jmbi.2000.4042","article-title":"T-coffee: A novel method for fast and accurate multiple sequence alignment","volume":"302","author":"Notredame","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/sysbio\/syq010","article-title":"New algorithms and methods to estimate maximum-likelihood phylogenies: Assessing the performance of phyml 3.0","volume":"59","author":"Guindon","year":"2010","journal-title":"Syst. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"vew007","DOI":"10.1093\/ve\/vew007","article-title":"Exploring the temporal structure of heterochronous sequences using tempest (formerly Path-O-Gen)","volume":"2","author":"Rambaut","year":"2016","journal-title":"Virus Evol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1093\/molbev\/mss075","article-title":"Bayesian phylogenetics with beauti and the beast 1.7","volume":"29","author":"Drummond","year":"2012","journal-title":"Mol. Biol. Evol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/molbev\/msj021","article-title":"Choosing appropriate substitution models for the phylogenetic analysis of protein-coding sequences","volume":"23","author":"Shapiro","year":"2006","journal-title":"Mol. Biol. Evol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1093\/molbev\/mss084","article-title":"Improving the accuracy of demographic and molecular clock model comparison while accommodating phylogenetic uncertainty","volume":"29","author":"Baele","year":"2012","journal-title":"Mol. Biol. Evol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1093\/molbev\/mst030","article-title":"Fubar: A fast, unconstrained bayesian approximation for inferring selection","volume":"30","author":"Murrell","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/978-1-59745-251-9_8","article-title":"Detecting signatures of selection from DNA sequences using datamonkey","volume":"537","author":"Poon","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1093\/bioinformatics\/btq429","article-title":"Datamonkey 2010: A suite of phylogenetic analysis tools for evolutionary biology","volume":"26","author":"Delport","year":"2010","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/12\/2703\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:53:53Z","timestamp":1760208833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/12\/2703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,13]]},"references-count":60,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["ijms18122703"],"URL":"https:\/\/doi.org\/10.3390\/ijms18122703","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,13]]}}}