{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:14:17Z","timestamp":1792275257569,"version":"4.4.0"},"reference-count":46,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,10]],"date-time":"2021-07-10T00:00:00Z","timestamp":1625875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004923","name":"AFM-T\u00e9l\u00e9thon","doi-asserted-by":"publisher","award":["20607"],"award-info":[{"award-number":["20607"]}],"id":[{"id":"10.13039\/501100004923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015565","name":"Consorzio Interuniversitario Biotecnologie","doi-asserted-by":"publisher","award":["BIOS.ROBERTI.CIB.2020"],"award-info":[{"award-number":["BIOS.ROBERTI.CIB.2020"]}],"id":[{"id":"10.13039\/100015565","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005362","name":"Universita degli Studi di Bari Aldo Moro","doi-asserted-by":"publisher","award":["Bruni11906Ricat17_18"],"award-info":[{"award-number":["Bruni11906Ricat17_18"]}],"id":[{"id":"10.13039\/501100005362","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005362","name":"Universita degli Studi di Bari Aldo Moro","doi-asserted-by":"publisher","award":["Bruni11906Ricat15_16"],"award-info":[{"award-number":["Bruni11906Ricat15_16"]}],"id":[{"id":"10.13039\/501100005362","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005362","name":"Universita degli Studi di Bari Aldo Moro","doi-asserted-by":"publisher","award":["Loguercio4523Ricat15_16"],"award-info":[{"award-number":["Loguercio4523Ricat15_16"]}],"id":[{"id":"10.13039\/501100005362","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The m.3243A&gt;G mutation within the mitochondrial mt-tRNALeu(UUR) gene is the most prevalent variant linked to mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome. This pathogenic mutation causes severe impairment of mitochondrial protein synthesis due to alterations of the mutated tRNA, such as reduced aminoacylation and a lack of post-transcriptional modification. In transmitochondrial cybrids, overexpression of human mitochondrial leucyl-tRNA synthetase (LARS2) has proven effective in rescuing the phenotype associated with m.3243A&gt;G substitution. The rescuing activity resides in the carboxy-terminal domain (Cterm) of the enzyme; however, the precise molecular mechanisms underlying this process have not been fully elucidated. To deepen our knowledge on the rescuing mechanisms, we demonstrated the interactions of the Cterm with mutated mt-tRNALeu(UUR) and its precursor in MELAS cybrids. Further, the effect of Cterm expression on mitochondrial functions was evaluated. We found that Cterm ameliorates de novo mitochondrial protein synthesis, whilst it has no effect on mt-tRNALeu(UUR) steady-state levels and aminoacylation. Despite the complete recovery of cell viability and the increase in mitochondrial translation, Cterm-overexpressing cybrids were not able to recover bioenergetic competence. These data suggest that, in our MELAS cell model, the beneficial effect of Cterm may be mediated by factors that are independent of the mitochondrial bioenergetics.<\/jats:p>","DOI":"10.3390\/life11070674","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:23:36Z","timestamp":1626049416000},"page":"674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exploring the Ability of LARS2 Carboxy-Terminal Domain in Rescuing the MELAS Phenotype"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7113-1276","authenticated-orcid":false,"given":"Francesco","family":"Capriglia","sequence":"first","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1736-8966","authenticated-orcid":false,"given":"Francesca","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8035-8368","authenticated-orcid":false,"given":"Giuseppe","family":"Petrosillo","sequence":"additional","affiliation":[{"name":"Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council (CNR), 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Morea","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology (IMBP), National Research Council (CNR), 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6959-691X","authenticated-orcid":false,"given":"Giulia","family":"d\u2019Amati","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palmiro","family":"Cantatore","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Roberti","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy"},{"name":"Consorzio Interuniversitario Biotecnologie (CIB), 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Loguercio Polosa","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy"},{"name":"Consorzio Interuniversitario Biotecnologie (CIB), 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5120-5936","authenticated-orcid":false,"given":"Francesco","family":"Bruni","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16080","DOI":"10.1038\/nrdp.2016.80","article-title":"Mitochondrial Diseases","volume":"2","author":"Gorman","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"835","DOI":"10.2741\/4520","article-title":"Mitochondrial Transcription in Mammalian Cells","volume":"22","author":"Shokolenko","year":"2017","journal-title":"Front. Biosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41580-018-0092-0","article-title":"Mitochondrial Proteins: From Biogenesis to Functional Networks","volume":"20","author":"Pfanner","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Majamaa-Voltti, K., Peuhkurinen, K., Kortelainen, M.-L., Hassinen, I.E., and Majamaa, K. (2002). Cardiac Abnormalities in Patients with Mitochondrial DNA Mutation 3243A>G. BMC Cardiovasc. Disord., 2.","DOI":"10.1186\/1471-2261-2-12"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1016\/j.ijcard.2013.05.062","article-title":"Defining Cardiac Adaptations and Safety of Endurance Training in Patients with m.3243A>G-Related Mitochondrial Disease","volume":"168","author":"Bates","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ymgme.2015.06.004","article-title":"MELAS Syndrome: Clinical Manifestations, Pathogenesis, and Treatment Options","volume":"116","author":"Adesina","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4251","DOI":"10.1074\/jbc.275.6.4251","article-title":"Modification Defect at Anticodon Wobble Nucleotide of Mitochondrial TRNAs Leu (UUR) with Pathogenic Mutations of Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes","volume":"275","author":"Yasukawa","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7127","DOI":"10.1073\/pnas.0500563102","article-title":"Specific Correlation between the Wobble Modification Deficiency in Mutant TRNAs and the Clinical Features of a Human Mitochondrial Disease","volume":"102","author":"Kirino","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","first-page":"480","article-title":"Defects in Mitochondrial Protein Synthesis and Respiratory Chain Activity Segregate with the TRNA(Leu(UUR)) Mutation Associated with Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Strokelike Episodes","volume":"12","author":"King","year":"1992","journal-title":"Mol. Cell. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1093\/hmg\/ddn265","article-title":"The A3243G TRNALeu(UUR) MELAS Mutation Causes Amino Acid Misincorporation and a Combined Respiratory Chain Assembly Defect Partially Suppressed by Overexpression of EFTu and EFG2","volume":"17","author":"Sasarman","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"35494","DOI":"10.1074\/jbc.M111.279810","article-title":"Taurine-Containing Uridine Modifications in TRNA Anticodons Are Required to Decipher Non-Universal Genetic Codes in Ascidian Mitochondria","volume":"286","author":"Suzuki","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1093\/nar\/gkn147","article-title":"Overexpression of Human Mitochondrial Valyl TRNA Synthetase Can Partially Restore Levels of Cognate Mt-TRNAVal Carrying the Pathogenic C25U Mutation","volume":"36","author":"Rorbach","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/emmm.201303202","article-title":"Human Mitochondrial Leucyl TRNA Synthetase Can Suppress Non Cognate Pathogenic Mt-TRNA Mutations","volume":"6","author":"Montanari","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/emmm.201303198","article-title":"The Isolated Carboxy-Terminal Domain of Human Mitochondrial Leucyl-TRNA Synthetase Rescues the Pathological Phenotype of Mitochondrial TRNA Mutations in Human Cells","volume":"6","author":"Perli","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3389\/fgene.2015.00113","article-title":"The Phenotypic Expression of Mitochondrial TRNA-Mutations Can Be Modulated by Either Mitochondrial Leucyl-TRNA Synthetase or the C-Terminal Domain Thereof","volume":"6","author":"Giordano","year":"2015","journal-title":"Front. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1093\/hmg\/ddv619","article-title":"Short Peptides from Leucyl-TRNA Synthetase Rescue Disease-Causing Mitochondrial TRNA Point Mutations","volume":"25","author":"Perli","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7675","DOI":"10.1096\/fj.201903270R","article-title":"Exogenous Peptides Are Able to Penetrate Human Cell and Mitochondrial Membranes, Stabilize Mitochondrial TRNA Structures, and Rescue Severe Mitochondrial Defects","volume":"34","author":"Perli","year":"2020","journal-title":"FASEB J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.cmet.2011.04.002","article-title":"MTERF4 Regulates Translation by Targeting the Methyltransferase NSUN4 to the Mammalian Mitochondrial Ribosome","volume":"13","author":"Park","year":"2011","journal-title":"Cell Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/febs.15342","article-title":"Messenger RNA Delivery to Mitoribosomes\u2014Hints from a Bacterial Toxin","volume":"288","author":"Bruni","year":"2021","journal-title":"FEBS J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e98","DOI":"10.1093\/nar\/gkp1235","article-title":"A Sensitive Non-Radioactive Northern Blot Method to Detect Small RNAs","volume":"38","author":"Kim","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/nprot.2012.058","article-title":"Assessment of Mitochondrial Respiratory Chain Enzymatic Activities on Tissues and Cultured Cells","volume":"7","author":"Spinazzi","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Garin, S., Levi, O., Cohen, B., Golani-Armon, A., and Arava, Y.S. (2020). Localization and RNA Binding of Mitochondrial Aminoacyl TRNA Synthetases. Genes, 11.","DOI":"10.3390\/genes11101185"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/0885-4505(92)90056-5","article-title":"Nonviability of Cells with Oxidative Defects in Galactose Medium: A Screening Test for Affected Patient Fibroblasts","volume":"48","author":"Robinson","year":"1992","journal-title":"Biochem. Med. Metab. Biol."},{"key":"ref_24","first-page":"2236","article-title":"In Vitro Genetic Transfer of Protein Synthesis and Respiration Defects to Mitochondrial DNA-Less Cells with Myopathy-Patient Mitochondria","volume":"11","author":"Chomyn","year":"1991","journal-title":"Mol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19198","DOI":"10.1074\/jbc.M908734199","article-title":"The Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episode Syndrome-Associated Human Mitochondrial TRNA Leu(UUR) Mutation Causes Aminoacylation Deficiency and Concomitant Reduced Association of MRNA with Ribosomes","volume":"275","author":"Chomyn","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1136\/jmg.38.10.665","article-title":"Frequency of Mitochondrial Transfer RNA Mutations and Deletions in 225 Patients Presenting with Respiratory Chain Deficiencies","volume":"38","author":"Jaksch","year":"2001","journal-title":"J. Med. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1096\/fj.10-165340","article-title":"Secondary Coenzyme Q10 Deficiency Triggers Mitochondria Degradation by Mitophagy in MELAS Fibroblasts","volume":"25","author":"Cordero","year":"2011","journal-title":"FASEB J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1016\/j.bbadis.2015.08.027","article-title":"Critical Role of AMP-Activated Protein Kinase in the Balance between Mitophagy and Mitochondrial Biogenesis in MELAS Disease","volume":"1852","author":"Paz","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/348651a0","article-title":"A Mutation in the TRNA Leu(UUR) Gene Associated with the MELAS Subgroup of Mitochondrial Encephalomyopathies","volume":"348","author":"Goto","year":"1990","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/S0006-291X(05)80860-5","article-title":"A Point Mutation in the Mitochondrial TRNALeu(UUR) Gene in Melas (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like Episodes)","volume":"173","author":"Kobayashi","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","first-page":"206","article-title":"The Mitochondrial TRNALeu(UUR) Mutation in MELAS: A Model for Pathogenesis","volume":"1101","author":"Schon","year":"1992","journal-title":"Biochim. Et Biophys. Acta BBA Bioenergy"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1021\/bi026882r","article-title":"The Pathogenic A3243G Mutation in Human Mitochondrial TRNALeu(UUR) Decreases the Efficiency of Aminoacylation","volume":"42","author":"Park","year":"2003","journal-title":"Biochemistry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/jb\/mvaa098","article-title":"Posttranscriptional Modifications in Mitochondrial TRNA and Its Implication in Mitochondrial Translation and Disease","volume":"168","author":"Kazuhito","year":"2020","journal-title":"J. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.mito.2011.08.006","article-title":"Peptides from Aminoacyl-TRNA Synthetases Can Cure the Defects Due to Mutations in Mt TRNA Genes","volume":"11","author":"Francisci","year":"2011","journal-title":"Mitochondrion"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.biochi.2012.02.030","article-title":"Adaptation of Aminoacylation Identity Rules to Mammalian Mitochondria","volume":"94","author":"Fender","year":"2012","journal-title":"Biochimie"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/ana.410400208","article-title":"Mitochondrial DNA and RNA Processing in MELAS","volume":"40","author":"Kaufmann","year":"1996","journal-title":"Ann Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6404","DOI":"10.1093\/nar\/gkl727","article-title":"Molecular Dysfunction Associated with the Human Mitochondrial 3302A>G Mutation in the MTTL1 (Mt-TRNALeu(UUR)) Gene","volume":"34","author":"Helm","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/0925-4439(95)00087-9","article-title":"Assembly of Mitochondrial ATP Synthase in Cultured Human Cells: Implications for Mitochondrial Diseases","volume":"1272","author":"Nijtmans","year":"1995","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.mito.2009.09.006","article-title":"Energetics, Epigenetics, Mitochondrial Genetics","volume":"10","author":"Wallace","year":"2010","journal-title":"Mitochondrion"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1016\/j.bbamcr.2019.06.004","article-title":"The MELAS Mutation m.3243A>G Alters the Expression of Mitochondrial TRNA Fragments","volume":"1866","author":"Meseguer","year":"2019","journal-title":"Biochim. Biophys. Acta BBA Mol. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E4033","DOI":"10.1073\/pnas.1414028111","article-title":"Progressive Increase in MtDNA 3243A>G Heteroplasmy Causes Abrupt Transcriptional Reprogramming","volume":"111","author":"Picard","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s41544-019-0046-5","article-title":"Circular RNA: Functions, Applications and Prospects","volume":"2","author":"Lu","year":"2020","journal-title":"ExRNA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"dev175786","DOI":"10.1242\/dev.175786","article-title":"Transposable Elements, Circular RNAs and Mitochondrial Transcription in Age-Related Genomic Regulation","volume":"147","author":"Bravo","year":"2020","journal-title":"Development"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"643575","DOI":"10.3389\/fmolb.2021.643575","article-title":"MicroRNAs and TRNA-Derived Small Fragments: Key Messengers in Nuclear\u2013Mitochondrial Communication","volume":"8","author":"Meseguer","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/nsmb986","article-title":"The Crystal Structure of Leucyl-TRNA Synthetase Complexed with TRNALeu in the Post-Transfer-Editing Conformation","volume":"12","author":"Tukalo","year":"2005","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14772","DOI":"10.1074\/jbc.M111.322412","article-title":"Yeast Mitochondrial Leucyl-TRNA Synthetase CP1 Domain Has Functionally Diverged to Accommodate RNA Splicing at Expense of Hydrolytic Editing","volume":"287","author":"Sarkar","year":"2012","journal-title":"J. Biol. Chem."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/7\/674\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:28:43Z","timestamp":1760164123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/7\/674"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,10]]},"references-count":46,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["life11070674"],"URL":"https:\/\/doi.org\/10.3390\/life11070674","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,10]]}}}