{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T22:22:05Z","timestamp":1776205325422,"version":"3.50.1"},"reference-count":59,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"crossref","award":["TTK230430100291"],"award-info":[{"award-number":["TTK230430100291"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001323","name":"Poliomyelitis Research Foundation","doi-asserted-by":"crossref","award":["24\/81"],"award-info":[{"award-number":["24\/81"]}],"id":[{"id":"10.13039\/501100001323","id-type":"DOI","asserted-by":"crossref"}]},{"name":"PRF","award":["24\/64"],"award-info":[{"award-number":["24\/64"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High-risk human papillomavirus (HR-HPV) types exhibit an uneven global distribution, with types 35, 51, 56, and 59 being more prevalent in Africa yet not covered by current L1-based vaccines. The genetic diversity of HR-HPV oncoproteins in Africa remains poorly characterized, despite their potential as alternative vaccine targets. This study investigates the genetic diversity of HR-HPV types 16, 18, 35, 51, 56, and 59 to inform vaccine development. We analyzed 14,332 sequences from the NCBI Virus database and 222 HPV reference sequences from the Papillomavirus Episteme (PaVE) database using phylogenetic analysis and variant identification. HPV16 and HPV35 exhibited close evolutionary relatedness, which may indicate shared traits relevant to vaccine design, although functional implications remain to be experimentally validated. A key finding of the study was the discovery of novel non-synonymous mutations, including E148K in HPV35 E6, S63C in HPV16 E7 and S495F in HPV18 L1, as well as known oncogenic variants such as L83V (E6) and N29S (E7) in HPV16. These findings highlight significant intra- and inter-type diversity among African HR-HPVs. This study provides new insights into the genetic diversity and evolutionary relationships of underrepresented HR-HPV types. The findings underscore the need for continued genomic surveillance and support efforts to develop region-specific vaccines that include HPV35, 51, 56, and 59 to address gaps in current vaccine coverage and help reduce the burden of HPV-related cancers in Africa.<\/jats:p>","DOI":"10.3390\/ijms262211056","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:24:58Z","timestamp":1763375098000},"page":"11056","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Diversity of Selected High-Risk HPV Types Prevalent in Africa and Not Covered by Current Vaccines: A Pooled Sequence Data Analysis"],"prefix":"10.3390","volume":"26","author":[{"given":"Babalwa","family":"Nyide","sequence":"first","affiliation":[{"name":"Discipline of Biochemistry, School of Agriculture and Science, University of KwaZulu-Natal, Pietermaritzburg 3209, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda","family":"Thomas","sequence":"additional","affiliation":[{"name":"Tumour Virology, International Centre for Genetic Engineering and Biotechnology (I.C.G.E.B.), 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Banks","sequence":"additional","affiliation":[{"name":"Tumour Virology, International Centre for Genetic Engineering and Biotechnology (I.C.G.E.B.), 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2176-9807","authenticated-orcid":false,"given":"Pamela P.","family":"Mkhize","sequence":"additional","affiliation":[{"name":"Discipline of Biochemistry, School of Agriculture and Science, University of KwaZulu-Natal, Pietermaritzburg 3209, South Africa"},{"name":"Centre for the AIDS Programme of Research in South Africa (CAPRISA), School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nontokozo D.","family":"Matume","sequence":"additional","affiliation":[{"name":"Discipline of Genetics, School of Agriculture and Science, University of KwaZulu-Natal, Pietermaritzburg 3209, South Africa"},{"name":"SAMRC-UNIVEN Antimicrobial Resistance and Global Health Research Unit, HIV\/AIDS & Global Health Research Programme, University of Venda, Thohoyandou 0950, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,15]]},"reference":[{"key":"ref_1","unstructured":"WHO (2025). Global Cancer Observatory, WHO. Available online: https:\/\/gco.iarc.fr\/tomorrow\/en\/dataviz\/isotype?cancers=23&single_unit=50000&types=0."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.canlet.2020.10.034","article-title":"HPV post-infection microenvironment and cervical cancer","volume":"497","author":"Yuan","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.ijid.2021.06.024","article-title":"Prevalence of cervical HPV infection, sexually transmitted infections and associated antimicrobial resistance in women attending cervical cancer screening in Mali","volume":"108","author":"Jary","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.bpobgyn.2017.08.015","article-title":"The natural history of human papillomavirus infection","volume":"47","author":"Brotons","year":"2018","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lagan\u00e0, A.S., Chiantera, V., Gerli, S., Proietti, S., Lepore, E., Unfer, V., Carugno, J., and Favilli, A. (2023). Preventing persistence of HPV infection with natural molecules. Pathogens, 12.","DOI":"10.3390\/pathogens12030416"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Szymonowicz, K.A., and Chen, J. (2020). Biological and clinical aspects of HPV-related cancers. Cancer Biol. Med., 17.","DOI":"10.20892\/j.issn.2095-3941.2020.0370"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e203204","DOI":"10.5327\/DST-2177-8264-20203204","article-title":"The impact of the HPV vaccine on the world: Initial outcomes and challenges","volume":"32","author":"Ribeiro","year":"2020","journal-title":"Braz. J. Sex. Transm. Dis."},{"key":"ref_8","first-page":"17455065211020702","article-title":"Human papillomavirus persistence or clearance after infection in reproductive age. What is the status? Review of the literature and new data of a vaginal gel containing silicate dioxide, citric acid, and selenite","volume":"17","author":"Huber","year":"2021","journal-title":"Women\u2019s Health"},{"key":"ref_9","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"ref_10","unstructured":"WHO (2022). Accelerating the Elimination of Cervical Cancer as a Public Health Problem: Towards Achieving 90\u201370\u201390 Targets by 2030, WHO."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"F55","DOI":"10.1016\/j.vaccine.2012.06.083","article-title":"The biology and life-cycle of human papillomaviruses","volume":"30","author":"Doorbar","year":"2012","journal-title":"Vaccine"},{"key":"ref_12","unstructured":"Bruni, L., Albero, G., Serrano, B., Mena, M., Collado, J.J., G\u00f3mez, D., Mu\u00f1oz, J., Bosch, F., and de Sanjos\u00e9, S. (2023). Human Papillomavirus and Related Diseases in Africa: Summary Report 10 March 2023, IARC Information Centre on HPV and Cancer (HPV Information Centre)."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1345","DOI":"10.1016\/S2214-109X(23)00305-4","article-title":"Global and regional estimates of genital human papillomavirus prevalence among men: A systematic review and meta-analysis","volume":"11","author":"Bruni","year":"2023","journal-title":"Lancet Glob. Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"K1","DOI":"10.1016\/j.vaccine.2008.05.064","article-title":"Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia","volume":"26","author":"Bosch","year":"2008","journal-title":"Vaccine"},{"key":"ref_15","unstructured":"Bruni, L., Albero, G., Serrano, B., Mena, M., Collado, J., G\u00f3mez, D., Mu\u00f1oz, J., Bosch, F., and de Sanjos\u00e9, S. (2023). Human Papillomavirus and Related Diseases in the World: Summary Report 10 March 2023, IARC Information Centre on HPV and Cancer (HPV Information Centre)."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"188","DOI":"10.4103\/ijd.ijd_805_24","article-title":"HPV Vaccines\u2013An Overview","volume":"70","author":"Ghosh","year":"2025","journal-title":"Indian J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, R., Huang, H., Yu, C., Li, X., Wang, Y., and Xie, L. (2024). Current status and future directions for the development of human papillomavirus vaccines. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1362770"},{"key":"ref_18","first-page":"1233","article-title":"HPV vaccination in south Asia: New progress, old challenges","volume":"23","author":"Oncology","year":"2022","journal-title":"Oncology"},{"key":"ref_19","unstructured":"WHO (2024). WHO Adds an HPV Vaccine for Single-Dose Use, WHO. Available online: https:\/\/www.who.int\/news\/item\/04-10-2024-who-adds-an-hpv-vaccine-for-single-dose-use."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gomez, F., Hirbo, J., and Tishkoff, S.A. (2014). Genetic variation and adaptation in Africa: Implications for human evolution and disease. Cold Spring Harb. Perspect. Biol., 6.","DOI":"10.1101\/cshperspect.a008524"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ghattas, M., Dwivedi, G., Lavertu, M., and Alameh, M.-G. (2021). Vaccine technologies and platforms for infectious diseases: Current progress, challenges, and opportunities. Vaccines, 9.","DOI":"10.3390\/vaccines9121490"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41392-024-02083-w","article-title":"Roles of human papillomavirus in cancers: Oncogenic mechanisms and clinical use","volume":"10","author":"Zhang","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7866","DOI":"10.1038\/sj.onc.1204915","article-title":"Mechanisms of cell transformation by papillomavirus E5 proteins","volume":"20","author":"DiMaio","year":"2001","journal-title":"Oncogene"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41417-023-00682-3","article-title":"HPV E6\/E7: Insights into their regulatory role and mechanism in signaling pathways in HPV-associated tumor","volume":"31","author":"Peng","year":"2024","journal-title":"Cancer Gene Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.virol.2005.06.024","article-title":"Worldwide genomic diversity of the human papillomaviruses-53, 56, and 66, a group of high-risk HPVs unrelated to HPV-16 and HPV-18","volume":"340","author":"Prado","year":"2005","journal-title":"Virology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.virol.2003.11.009","article-title":"Genomic diversity of human papillomavirus-16, 18, 31, and 35 isolates in a Mexican population and relationship to European, African, and Native American variants","volume":"319","author":"Kalantari","year":"2004","journal-title":"Virology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13630","DOI":"10.1128\/JVI.79.21.13630-13640.2005","article-title":"Worldwide genomic diversity of the high-risk human papillomavirus types 31, 35, 52, and 58, four close relatives of human papillomavirus type 16","volume":"79","author":"Villa","year":"2005","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/01.qai.0000247226.45375.01","article-title":"Polymorphism of the L1 capsid gene and persistence of human papillomavirus type 52 infection in women at high risk or infected by HIV","volume":"44","author":"Gagnon","year":"2007","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1086\/424854","article-title":"Viral polymorphism in human papillomavirus types 33 and 35 and persistent and transient infection in the genital tract of women","volume":"190","author":"Gagnon","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/jmv.20259","article-title":"Polymorphism of human papillomavirus type 31 isolates infecting the genital tract of HIV\u2014seropositive and HIV\u2014seronegative women at risk for HIV infection","volume":"75","author":"Gagnon","year":"2005","journal-title":"J. Med. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/jmv.21432","article-title":"Genetic variability and phylogeny of the high-risk HPV-31, -33, -35, -52, and -58 in central Brazil","volume":"81","author":"Raiol","year":"2009","journal-title":"J. Med. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chen, Z., Schiffman, M., Herrero, R., DeSalle, R., Anastos, K., Segondy, M., Sahasrabuddhe, V.V., Gravitt, P.E., Hsing, A.W., and Burk, R.D. (2011). Evolution and taxonomic classification of human papillomavirus 16 (HPV16)-related variant genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020183"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ygyno.2017.04.004","article-title":"HPV vaccines\u2013a review of the first decade","volume":"146","author":"Harper","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"749","DOI":"10.2478\/s11756-019-00386-w","article-title":"The possible regions to design Human Papilloma Viruses vaccine in Iranian L1 protein","volume":"75","author":"Dehghani","year":"2020","journal-title":"Biologia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"145533","DOI":"10.1016\/j.gene.2021.145533","article-title":"Worldwide genetic variations in high-risk human papillomaviruses capsid L1 gene and their impact on vaccine efficiency","volume":"782","author":"Oumeslakht","year":"2021","journal-title":"Gene"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Tsakogiannis, D., Nikolaidis, M., Zagouri, F., Zografos, E., Kottaridi, C., Kyriakopoulou, Z., Tzioga, L., Markoulatos, P., Amoutzias, G.D., and Bletsa, G. (2022). Mutation profile of HPV16 L1 and L2 genes in different geographic areas. Viruses, 15.","DOI":"10.3390\/v15010141"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Alsanea, M., Alsaleh, A., Obeid, D., Alhadeq, F., Alahideb, B., and Alhamlan, F. (2022). Genetic variability in the E6, E7, and L1 genes of human papillomavirus types 16 and 18 among women in Saudi Arabia. Viruses, 15.","DOI":"10.3390\/v15010109"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.meegid.2013.05.013","article-title":"Amino acid sequence diversity of the major human papillomavirus capsid protein: Implications for current and next generation vaccines","volume":"18","author":"Ahmed","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_39","first-page":"7131","article-title":"Phylogeny and polymorphism in the long control regions E6, E7, and L1 of HPV Type 56 in women from southwest China","volume":"17","author":"Jing","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Basukala, O., and Banks, L. (2021). The not-so-good, the bad and the ugly: HPV E5, E6 and E7 oncoproteins in the orchestration of carcinogenesis. Viruses, 13.","DOI":"10.3390\/v13101892"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/1476-4598-10-140","article-title":"Papillomavirus E5: The smallest oncoprotein with many functions","volume":"10","author":"Venuti","year":"2011","journal-title":"Mol. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s12985-023-02188-8","article-title":"Genetic variation of E6 and E7 genes of human papillomavirus type 16 from central China","volume":"20","author":"Li","year":"2023","journal-title":"Virol. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1017\/erm.2021.18","article-title":"Genetic variability of the HPV16 early genes and LCR. Present and future perspectives","volume":"23","author":"Bletsa","year":"2021","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13027-015-0010-4","article-title":"Genetic variability in E6 and E7 oncogenes of human papillomavirus Type 16 from Congolese cervical cancer isolates","volume":"10","author":"Boumba","year":"2015","journal-title":"Infect. Agents Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s12985-024-02357-3","article-title":"The polymorphism analysis and therapy vaccine target epitopes screening of HPV-35 E6 E7 among the threaten \u03b1-9 HPV in Sichuan area","volume":"21","author":"He","year":"2024","journal-title":"Virol. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/jmv.21093","article-title":"Isolation and functional analysis of five HPVE6 variants with respect to p53 degradation","volume":"80","author":"Hiller","year":"2008","journal-title":"J. Med. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12985-025-02650-9","article-title":"Genetic variations and carcinogenicity analysis of E6\/E7 oncogenes in HPV31 and HPV35 in Taizhou, China","volume":"22","author":"Yuan","year":"2025","journal-title":"Virol. J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Mboumba Bouassa, R.-S., Avala Ntsigouaye, J., Lemba Tsimba, P.C., Nodjikouambaye, Z.A., Sadjoli, D., Mbeko Simaleko, M., Camengo, S.P., Longo, J.D.D., Gr\u00e9senguet, G., and Veyer, D. (2024). Genetic diversity of HPV35 in Chad and the Central African Republic, two landlocked countries of Central Africa: A cross-sectional study. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0297054"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lou, H., Boland, J.F., Li, H., Burk, R., Yeager, M., Anderson, S.K., Wentzensen, N., Schiffman, M., Mirabello, L., and Dean, M. (2022). HPV16 E7 nucleotide variants found in cancer-free subjects affect E7 protein expression and transformation. Cancers, 14.","DOI":"10.20944\/preprints202111.0134.v1"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1186\/s12985-025-02851-2","article-title":"Genetic variability in HPV 33 and 35 E6 and E7 genes from South African and Mozambican women with different cervical cytology status","volume":"22","author":"Maueia","year":"2025","journal-title":"Virol. J."},{"key":"ref_51","first-page":"65","article-title":"Human papilloma virus: A review study of epidemiology, carcinogenesis, diagnostic methods, and treatment of all HPV-related cancers","volume":"35","author":"Soheili","year":"2021","journal-title":"Med. J. Islam. Repub. Iran"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/S0140-6736(07)61416-0","article-title":"Human papillomavirus and cervical cancer","volume":"370","author":"Schiffman","year":"2007","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e997","DOI":"10.1016\/S2214-109X(23)00203-6","article-title":"Impact of the human papillomavirus vaccine in low-resource settings","volume":"11","author":"Murenzi","year":"2023","journal-title":"Lancet Glob. Health"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"D20","DOI":"10.1093\/nar\/gkae979","article-title":"Database resources of the National Center for Biotechnology Information in 2025","volume":"53","author":"Sayers","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"D499","DOI":"10.1093\/nar\/gkw879","article-title":"The Papillomavirus Episteme: A major update to the papillomavirus sequence database","volume":"45","author":"Li","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Liu, Y., Pan, Y., Gao, W., Ke, Y., and Lu, Z. (2017). Whole-genome analysis of human papillomavirus types 16, 18, and 58 isolated from cervical Precancer and Cancer samples in Chinese women. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-00364-9"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1093\/molbev\/msaa015","article-title":"IQ-TREE 2: New models and efficient methods for phylogenetic inference in the genomic era","volume":"37","author":"Minh","year":"2020","journal-title":"Mol. Biol. Evol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"W78","DOI":"10.1093\/nar\/gkae268","article-title":"Interactive Tree of Life (iTOL) v6: Recent updates to the phylogenetic tree display and annotation tool","volume":"52","author":"Letunic","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_59","unstructured":"DSTI (2025, February 05). Building a Local Vaccine Capability Critical in the Era of Health Challenges, Available online: https:\/\/www.dsti.gov.za\/index.php\/media-room\/latest-news\/4363-building-a-local-vaccine-capability-critical-in-the-era-of-health-challenges."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/11056\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T05:13:13Z","timestamp":1763442793000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/11056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,15]]},"references-count":59,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262211056"],"URL":"https:\/\/doi.org\/10.3390\/ijms262211056","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,15]]}}}