{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T08:11:20Z","timestamp":1776759080736,"version":"3.51.2"},"reference-count":63,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970471"],"award-info":[{"award-number":["31970471"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Drosophila spermatogenesis involves the renewal of germline stem cells, meiosis of spermatocytes, and morphological transformation of spermatids into mature sperm. We previously demonstrated that Ocnus (ocn) plays an essential role in spermatogenesis. The ValRS-m (Valyl-tRNA synthetase, mitochondrial) gene was down-regulated in ocn RNAi testes. Here, we found that ValRS-m-knockdown induced complete sterility in male flies. The depletion of ValRS-m blocked mitochondrial behavior and ATP synthesis, thus inhibiting the transition from spermatogonia to spermatocytes, and eventually, inducing the accumulation of spermatogonia during spermatogenesis. To understand the intrinsic reason for this, we further conducted transcriptome-sequencing analysis for control and ValRS-m-knockdown testes. The differentially expressed genes (DEGs) between these two groups were selected with a fold change of \u22652 or \u22641\/2. Compared with the control group, 4725 genes were down-regulated (dDEGs) and 2985 genes were up-regulated (uDEGs) in the ValRS-m RNAi group. The dDEGs were mainly concentrated in the glycolytic pathway and pyruvate metabolic pathway, and the uDEGs were primarily related to ribosomal biogenesis. A total of 28 DEGs associated with mitochondria and 6 meiosis-related genes were verified to be suppressed when ValRS-m was deficient. Overall, these results suggest that ValRS-m plays a wide and vital role in mitochondrial behavior and spermatogonia differentiation in Drosophila.<\/jats:p>","DOI":"10.3390\/ijms25137489","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T14:40:50Z","timestamp":1720449650000},"page":"7489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Deficiency of ValRS-m Causes Male Infertility in Drosophila melanogaster"],"prefix":"10.3390","volume":"25","author":[{"given":"Xin","family":"Duan","sequence":"first","affiliation":[{"name":"School of Life Sciences, Central China Normal University, Wuhan 430079, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haolin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Central China Normal University, Wuhan 430079, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhixian","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Central China Normal University, Wuhan 430079, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Su","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Shanghai Normal University, Shanghai 200234, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1823-373X","authenticated-orcid":false,"given":"Yufeng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Central China Normal University, Wuhan 430079, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Shanghai Normal University, Shanghai 200234, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sucato, A., Butt\u00e0, M., Bosco, L., Di Gregorio, L., Perino, A., and Capra, G. (2023). Human Papillomavirus and Male Infertility: What Do We Know?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417562"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.4161\/spmg.21798","article-title":"Drosophila spermiogenesis: Big things come from little packages","volume":"2","author":"Fabian","year":"2012","journal-title":"Spermatogenesis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1083\/jcb.201507035","article-title":"Titration of mitochondrial fusion rescues Mff-deficient cardiomyopathy","volume":"211","author":"Chen","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ymeth.2014.04.020","article-title":"Investigating spermatogenesis in Drosophila melanogaster","volume":"68","author":"Demarco","year":"2014","journal-title":"Methods"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/s41419-021-03783-9","article-title":"CG6015 controls spermatogonia transit-amplifying divisions by epidermal growth factor receptor signaling in Drosophila testes","volume":"12","author":"Yu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4161\/spmg.21775","article-title":"Transcriptional regulation during Drosophila spermatogenesis","volume":"2","author":"Lim","year":"2012","journal-title":"Spermatogenesis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"dev184259","DOI":"10.1242\/dev.184259","article-title":"Single-cyst transcriptome analysis of Drosophila male germline stem cell lineage","volume":"147","author":"Shi","year":"2020","journal-title":"Development"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2664","DOI":"10.1242\/dev.134759","article-title":"Drosophila dany is essential for transcriptional control and nuclear architecture in spermatocytes","volume":"143","author":"Trost","year":"2016","journal-title":"Development"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13072-018-0183-3","article-title":"Genome-wide analysis of gene regulation mechanisms during Drosophila spermatogenesis","volume":"11","author":"Laktionov","year":"2018","journal-title":"Epigenetics Chromatin"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1530\/REP-09-0083","article-title":"Molecular mechanisms of gene regulation during Drosophila spermatogenesis","volume":"139","year":"2010","journal-title":"Reproduction"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e2306073120","DOI":"10.1073\/pnas.2306073120","article-title":"Milton assembles large mitochondrial clusters, mitoballs, to sustain spermatogenesis","volume":"120","author":"Li","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1093\/humupd\/dmq002","article-title":"Mitochondrial DNA transmission, replication and inheritance: A journey from the gamete through the embryo and into offspring and embryonic stem cells","volume":"16","author":"Jiang","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0092-8674(00)80319-0","article-title":"Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase","volume":"90","author":"Hales","year":"1997","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/8904_2018_89","article-title":"Mitochondrial Encephalopathy: First Portuguese Report of a VARS2 Causative Variant","volume":"42","author":"Pereira","year":"2018","journal-title":"JIMD Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s40246-017-0130-6","article-title":"Correction to: Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism","volume":"11","author":"Alsemari","year":"2017","journal-title":"Hum. Genom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1080\/03009734.2019.1670297","article-title":"A novel VARS2 gene variant in a patient with epileptic encephalopathy","volume":"124","author":"Ruzman","year":"2019","journal-title":"Upsala J. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12881-019-0798-7","article-title":"VARS2-linked mitochondrial encephalopathy: Two case reports enlarging the clinical phenotype","volume":"20","author":"Begliuomini","year":"2019","journal-title":"BMC Med. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/imb.12393","article-title":"Ocnus is essential for male germ cell development in Drosophila melanogaster","volume":"27","author":"Zheng","year":"2018","journal-title":"Insect Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3178","DOI":"10.1016\/j.celrep.2017.11.060","article-title":"The Germline Linker Histone dBigH1 and the Translational Regulator Bam Form a Repressor Loop Essential for Male Germ Stem Cell Differentiation","volume":"21","author":"Carbonell","year":"2017","journal-title":"Cell Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/s41419-019-1527-z","article-title":"Srlp is crucial for the self-renewal and differentiation of germline stem cells via RpL6 signals in Drosophila testes","volume":"10","author":"Yu","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Xu, D., Pan, J., Fang, Y., Zhao, L., and Su, Y. (2024). RpS25 is required for sperm elongation and individualization during Drosophila spermatogenesis. Biochem. Biophys. Res. Commun., 702.","DOI":"10.1016\/j.bbrc.2024.149633"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19695","DOI":"10.1038\/s41598-019-55728-0","article-title":"Mitochondrial fission regulates germ cell differentiation by suppressing ROS-mediated activation of Epidermal Growth Factor Signaling in the Drosophila larval testis","volume":"9","author":"Demarco","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Joubert, F., and Puff, N. (2021). Mitochondrial Cristae Architecture and Functions: Lessons from Minimal Model Systems. Membranes, 11.","DOI":"10.3390\/membranes11070465"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.cell.2013.08.032","article-title":"Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency","volume":"155","author":"Cogliati","year":"2013","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Maaroufi, H.O., Pauchova, L., Lin, Y.H., Wu, B.C., Rouhova, L., Kucerova, L., Vieira, L.C., Renner, M., Sehadova, H., and Hradilova, M. (2022). Mutation in Drosophila concentrative nucleoside transporter 1 alters spermatid maturation and mating behavior. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.945572"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chen, M.Y., Duan, X., Wang, Q., Ran, M.J., Ai, H., Zheng, Y., and Wang, Y.F. (2023). Cytochrome c1-like is required for mitochondrial morphogenesis and individualization during spermatogenesis in Drosophila melanogaster. J. Exp. Biol., 226.","DOI":"10.1242\/jeb.245277"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1093\/hmg\/ddab107","article-title":"RNA kinase CLP1\/Cbc regulates meiosis initiation in spermatogenesis","volume":"30","author":"Wu","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Parisi, M., Nuttall, R., Edwards, P., Minor, J., Naiman, D., L\u00fc, J., Doctolero, M., Vainer, M., Chan, C., and Malley, J. (2004). A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults. Genome Biol., 5.","DOI":"10.1186\/gb-2004-5-6-r40"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1242\/dev.056572","article-title":"Sequential changes at differentiation gene promoters as they become active in a stem cell lineage","volume":"138","author":"Chen","year":"2011","journal-title":"Development"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.stem.2012.08.012","article-title":"A self-limiting switch based on translational control regulates the transition from proliferation to differentiation in an adult stem cell lineage","volume":"11","author":"Insco","year":"2012","journal-title":"Cell Stem Cell"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Parrott, B.B., Chiang, Y., Hudson, A., Sarkar, A., Guichet, A., and Schulz, C. (2011). Nucleoporin98-96 function is required for transit amplification divisions in the germ line of Drosophila melanogaster. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025087"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1101\/gad.349689.122","article-title":"Developmentally regulated alternate 3\u2019 end cleavage of nascent transcripts controls dynamic changes in protein expression in an adult stem cell lineage","volume":"36","author":"Berry","year":"2022","journal-title":"Genes. Dev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1756-8722-6-19","article-title":"Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers","volume":"6","author":"Li","year":"2013","journal-title":"J. Hematol. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Costa, J., Braga, P.C., Rebelo, I., Oliveira, P.F., and Alves, M.G. (2023). Mitochondria Quality Control and Male Fertility. Biology, 12.","DOI":"10.3390\/biology12060827"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s10495-016-1295-5","article-title":"Mitochondrial dynamics during cell cycling","volume":"21","author":"Horbay","year":"2016","journal-title":"Apoptosis"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Madan, S., Uttekar, B., Chowdhary, S., and Rikhy, R. (2021). Mitochondria lead the way: Mitochondrial dynamics and function in cellular movements in development and disease. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.781933"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1093\/molehr\/gaz055","article-title":"The spatio-temporal dynamics of mitochondrial membrane potential during oocyte maturation","volume":"25","author":"Liu","year":"2019","journal-title":"Mol. Hum. Reprod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e62885","DOI":"10.7554\/eLife.62885","article-title":"ATP activation of peritubular cells drives testicular sperm transport","volume":"10","author":"Fleck","year":"2021","journal-title":"eLife"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/nrm2275","article-title":"Functions and dysfunctions of mitochondrial dynamics","volume":"8","author":"Detmer","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s00709-012-0434-2","article-title":"Drosophila male-sterile mutation emmenthal specifically affects the mitochondrial morphogenesis","volume":"250","author":"Dorogova","year":"2013","journal-title":"Protoplasma"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1101\/gad.1516607","article-title":"Discovery of tMAC: A Drosophila testis-specific meiotic arrest complex paralogous to Myb-Muv, B","volume":"21","author":"Beall","year":"2007","journal-title":"Genes. Dev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1111\/cas.13251","article-title":"Cytochrome c1 in ductal carcinoma in situ of breast associated with proliferation and comedo necrosis","volume":"108","author":"Chishiki","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1146\/annurev.physiol.66.032102.150251","article-title":"The cytochrome bc1 complex: Function in the context of structure","volume":"66","author":"Crofts","year":"2004","journal-title":"Annu. Rev. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, J.V., and Megraw, T.L. (2014). Spermitin: A novel mitochondrial protein in Drosophila spermatids. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108802"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15500","DOI":"10.1038\/ncomms15500","article-title":"Loss of Parkinson\u2019s disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c","volume":"8","author":"Meng","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12860-017-0132-1","article-title":"Testis-specific ATP synthase peripheral stalk subunits required for tissue-specific mitochondrial morphogenesis in Drosophila","volume":"18","author":"Sawyer","year":"2017","journal-title":"BMC Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1186\/1479-7364-4-5-327","article-title":"The other lives of ribosomal proteins","volume":"4","author":"Bhavsar","year":"2010","journal-title":"Hum. Genom."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/j.dnarep.2007.04.009","article-title":"Translocation of human ribosomal protein S3 to sites of DNA damage is dependant on ERK-mediated phosphorylation following genotoxic stress","volume":"6","author":"Yadavilli","year":"2007","journal-title":"DNA Repair"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fang, Y., Zhang, F., Zhan, Y., Lu, M., Xu, D., Wang, J., Li, Q., Zhao, L., and Su, Y. (2023).  RpS3 Is Required for Spermatogenesis of Drosophila melanogaster. Cells, 12.","DOI":"10.3390\/cells12040573"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"498","DOI":"10.15252\/emmm.201606660","article-title":"Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutations","volume":"9","author":"Ajore","year":"2017","journal-title":"EMBO Mol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/jez.b.23040","article-title":"Knockdown of RpL36 in testes impairs spermatogenesis in Drosophila melanogaster","volume":"336","author":"Fang","year":"2021","journal-title":"J. Exp. Zool."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Laurinyecz, B., Vedelek, V., Kov\u00e1cs, A.L., Szilasi, K., Lipinszki, Z., Slez\u00e1k, C., Darula, Z., Juh\u00e1sz, G., and Sinka, R. (2019). Sperm-Leucylaminopeptidases are required for male fertility as structural components of mitochondrial paracrystalline material in Drosophila melanogaster sperm. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1007987"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Vedelek, V., Laurinyecz, B., Kov\u00e1cs, A.L., Juh\u00e1sz, G., and Sinka, R. (2016). Testis-Specific Bb8 Is Essential in the Development of Spermatid Mitochondria. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161289"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/BF02715797","article-title":"The Hsp60C gene in the 25F cytogenetic region in Drosophila melanogaster is essential for tracheal development and fertility","volume":"84","author":"Sarkar","year":"2005","journal-title":"J. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1387\/ijdb.072522bs","article-title":"Mammalian sperm metabolism: Oxygen and sugar, friend and foe","volume":"52","author":"Storey","year":"2008","journal-title":"Int. J. Dev. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.cell.2019.07.029","article-title":"Sex Differences in intestinal carbohydrate metabolism promote food intake and sperm maturation","volume":"178","author":"Hudry","year":"2019","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"206","DOI":"10.3390\/cells9010206","article-title":"The Drosophila citrate lyase is required for cell division during spermatogenesis","volume":"9","author":"Morciano","year":"2020","journal-title":"Cells"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-cellbio-100913-013344","article-title":"Genetics of gonadal stem cell renewal","volume":"31","author":"Greenspan","year":"2015","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_59","first-page":"341","article-title":"The negative effect of silica nanoparticles on adipogenic differentiation of human mesenchymal stem cells","volume":"81","author":"Yang","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Li, B., and Dewey, C.N. (2011). RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-323"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Xu, J., Du, R., Wang, Y., and Chen, J. (2023). RNA-sequencing reveals the involvement of sesquiterpene biosynthesis genes and transcription factors during an early response to mechanical wounding of Aquilaria sinensis. Genes, 14.","DOI":"10.3390\/genes14020464"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W316","DOI":"10.1093\/nar\/gkr483","article-title":"KOBAS 2.0: A web server for annotation and identification of enriched pathways and diseases","volume":"39","author":"Xie","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7489\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:11:44Z","timestamp":1760109104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7489"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,8]]},"references-count":63,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25137489"],"URL":"https:\/\/doi.org\/10.3390\/ijms25137489","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,8]]}}}