{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:14:19Z","timestamp":1785428059607,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,16]]},"group-title":"Molecular Biology","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico, CNPQ","award":["401737\/2023-3"],"award-info":[{"award-number":["401737\/2023-3"]}]},{"award":["SEI-260003\/001743\/2023"],"award-info":[{"award-number":["SEI-260003\/001743\/2023"]}],"id":[{"id":"https:\/\/ror.org\/03kk0s825","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Instituto Nacional de Entomologia Molecular, INCT-EM","award":["573959\/2008-0"],"award-info":[{"award-number":["573959\/2008-0"]}]},{"name":"Division of Intramural Research of the National Institute of Allergy and Infectious Diseases","award":["Z01 AI001337-01"],"award-info":[{"award-number":["Z01 AI001337-01"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["439669440 TRR319 RMaP TP A01"],"award-info":[{"award-number":["439669440 TRR319 RMaP TP A01"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Epitranscriptomic RNA modifications, particularly N\n                  <jats:sup>6<\/jats:sup>\n                  -methyladenosine (m\u2076A), have emerged as important regulators of host\u2013virus interctions. However, the role of m\u2076A in arbovirus infection within mosquito vectors remains poorly defined. Here, we characterized the m\u2076A RNA methylation machinery in\n                  <jats:italic>Aedes albopictus<\/jats:italic>\n                  C6\/36 cells and examined its contribution to Zika virus (ZIKV) replication. Arbovirus infection did not significantly alter the transcriptional levels or enzymatic activity of the core m\u2076A methyltransferase components METTL3 and METTL14. In contrast, pharmacological inhibition of METTL3 markedly enhanced ZIKV replication, indicating an antiviral role for m\u2076A in mosquito cells. Transcriptome-wide analysis of C6\/36 cells treated with the METTL3 inhibitor STM2457 revealed extensive changes in gene expression, including the pronounced upregulation of multiple serine proteases, particularly members of the CLIP family. Single-nucleotide\u2013resolution mapping of m\u2076A using GLORI-sequencing showed that m\n                  <jats:sup>6<\/jats:sup>\n                  A is absent from Zika virus RNA, but readily detectable in the\n                  <jats:italic>A. albopictus<\/jats:italic>\n                  transcriptome. Data analysis defined key features of the mosquito epitranscriptome and demonstrated that m\u2076A modifications are enriched within the coding regions of serine protease transcripts, supporting their direct regulation by m\u2076A. Functionally, inhibition of serine protease activity using AEBSF resulted in a significant reduction of ZIKV replication. Together, these findings identify m\u2076A RNA methylation as a critical regulator of ZIKV infection in mosquito cells and uncover an epitranscriptomic pathway linking m\u2076A-dependent control of serine proteases to vector\u2013virus interactions.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Author Summary<\/jats:title>\n                  <jats:p>\n                    Mosquito-borne viruses such as Zika virus pose a major threat to global public health. Successful transmission of these viruses depends not only on infection in humans, but also on their ability to replicate efficiently inside mosquito vectors. Chemical modifications of RNA, collectively known as epitranscriptomic marks, have recently emerged as important regulators of gene expression and virus\u2013host interactions. Among these, N\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) is the most abundant internal RNA modification in eukaryotic cells. While m\n                    <jats:sup>6<\/jats:sup>\n                    A has been extensively studied in mammalian systems, its role in mosquito antiviral responses remains poorly understood. In this study, we investigated how m\n                    <jats:sup>6<\/jats:sup>\n                    A RNA methylation influences Zika virus infection in mosquito cells derived from\n                    <jats:italic>Aedes albopictus<\/jats:italic>\n                    . We found that reducing m\n                    <jats:sup>6<\/jats:sup>\n                    A levels enhances viral replication, indicating that this RNA modification restricts infection in mosquito cells. Notably, Zika virus RNA itself does not contain detectable m\n                    <jats:sup>6<\/jats:sup>\n                    A modifications. Instead, m\n                    <jats:sup>6<\/jats:sup>\n                    A regulates the expression of specific mosquito genes, including a group of serine proteases that influence viral replication. Pharmacological inhibition of these proteases significantly impaired virus growth, identifying them as key downstream effectors. Our findings reveal an antiviral role for m\n                    <jats:sup>6<\/jats:sup>\n                    A in mosquito cells and uncover a previously unrecognized epitranscriptomic pathway that shapes mosquito\u2013virus interactions. Understanding how RNA modifications regulate arbovirus infection in vectors may open new avenues for strategies aimed at limiting virus transmission.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.16.711780","type":"posted-content","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:25:12Z","timestamp":1773721512000},"source":"Crossref","is-referenced-by-count":0,"title":["m\n                  <sup>6<\/sup>\n                  A RNA methylation modulates Zika virus infection by regulating serine proteases in\n                  <i>Aedes albopictus<\/i>"],"prefix":"10.64898","author":[{"given":"Anderson de Mendon\u00e7a","family":"Amarante","sequence":"first","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil"},{"name":"Instituto Nacional de Entomologia Molecular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Tirloni","sequence":"additional","affiliation":[{"name":"Tick-Pathogen Transmission Unit, Laboratory of Bacteriology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Hamilton, MT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Koch","sequence":"additional","affiliation":[{"name":"Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Bormann","sequence":"additional","affiliation":[{"name":"Bioinformatics.Expert UG, 12305 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Rosignoli","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, 41125, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9078-7545","authenticated-orcid":false,"given":"Alessandro","family":"Paiardini","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u2018A. Rossi Fanelli \u201c, Sapienza University of Rome, P.Ie Aldo Moro 5, 00185, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dante","family":"Rotili","sequence":"additional","affiliation":[{"name":"Department of Science, \u201cRoma Tre\u201d University, V.le G. Marconi 446, 00146 Rome, Italy"},{"name":"Biostructures and Biosystems National Institute (INBB), Via dei Carpegna 19, 00165, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarcisio","family":"Brito","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil, RJ, 21941-590"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura de Andrade","family":"Tavares","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil, RJ, 21941-590"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Diego de Paula","family":"Li Yasumura","sequence":"additional","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil"},{"name":"Instituto Nacional de Entomologia Molecular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor Coutinho","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Menendez","family":"Kury","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics, Im Neuenheimer Fel 280, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attilio","family":"Pane","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil, RJ, 21941-590"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Lyko","sequence":"additional","affiliation":[{"name":"Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Rosado","family":"Fantappi\u00e9","sequence":"additional","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil"},{"name":"Instituto Nacional de Entomologia Molecular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026032019400894000_2026.03.16.711780v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2025.110606"},{"key":"2026032019400894000_2026.03.16.711780v2.2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.70086"},{"key":"2026032019400894000_2026.03.16.711780v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.10.002"},{"key":"2026032019400894000_2026.03.16.711780v2.4","doi-asserted-by":"publisher","DOI":"10.3390\/epigenomes10010013"},{"key":"2026032019400894000_2026.03.16.711780v2.5","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000935"},{"key":"2026032019400894000_2026.03.16.711780v2.6","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01723-24"},{"key":"2026032019400894000_2026.03.16.711780v2.7","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00658-23"},{"key":"2026032019400894000_2026.03.16.711780v2.8","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.584283"},{"key":"2026032019400894000_2026.03.16.711780v2.9","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3724"},{"key":"2026032019400894000_2026.03.16.711780v2.10","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3785"},{"key":"2026032019400894000_2026.03.16.711780v2.11","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2025.5605"},{"key":"2026032019400894000_2026.03.16.711780v2.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-022-00534-0"},{"key":"2026032019400894000_2026.03.16.711780v2.13","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100616"},{"key":"2026032019400894000_2026.03.16.711780v2.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33085-3"},{"key":"2026032019400894000_2026.03.16.711780v2.15","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021109895"},{"key":"2026032019400894000_2026.03.16.711780v2.16","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06221-y"},{"key":"2026032019400894000_2026.03.16.711780v2.17","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-024-01280-2"},{"key":"2026032019400894000_2026.03.16.711780v2.18","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1401997"},{"key":"2026032019400894000_2026.03.16.711780v2.19","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2025.2544726"},{"key":"2026032019400894000_2026.03.16.711780v2.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.09.015"},{"key":"2026032019400894000_2026.03.16.711780v2.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.11.007"},{"key":"2026032019400894000_2026.03.16.711780v2.22","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03566-8"},{"key":"2026032019400894000_2026.03.16.711780v2.23","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c01626"},{"key":"2026032019400894000_2026.03.16.711780v2.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46278-9"},{"key":"2026032019400894000_2026.03.16.711780v2.25","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi0301s42"},{"key":"2026032019400894000_2026.03.16.711780v2.26","doi-asserted-by":"crossref","unstructured":"Thompson JD , Higgins DG , Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994. Available: https:\/\/academic.oup.com\/nar\/article\/22\/22\/4673\/2400290","DOI":"10.1093\/nar\/22.22.4673"},{"key":"2026032019400894000_2026.03.16.711780v2.27","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-40-3-531"},{"key":"2026032019400894000_2026.03.16.711780v2.28","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1968.17.219"},{"key":"2026032019400894000_2026.03.16.711780v2.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03536-w"},{"key":"2026032019400894000_2026.03.16.711780v2.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2017.11.003"},{"key":"2026032019400894000_2026.03.16.711780v2.31","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"2026032019400894000_2026.03.16.711780v2.32","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762005000600008"},{"key":"2026032019400894000_2026.03.16.711780v2.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107300"},{"key":"2026032019400894000_2026.03.16.711780v2.34","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz436"},{"key":"2026032019400894000_2026.03.16.711780v2.35","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2026032019400894000_2026.03.16.711780v2.36","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"2026032019400894000_2026.03.16.711780v2.37","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026032019400894000_2026.03.16.711780v2.38","unstructured":"J. R. Adrian Alexa . topGO. Bioconductor. 2017."},{"key":"2026032019400894000_2026.03.16.711780v2.39","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583525000034"},{"key":"2026032019400894000_2026.03.16.711780v2.40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh340"},{"key":"2026032019400894000_2026.03.16.711780v2.41","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.13902"},{"key":"2026032019400894000_2026.03.16.711780v2.42","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c00203"},{"key":"2026032019400894000_2026.03.16.711780v2.43","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"2026032019400894000_2026.03.16.711780v2.44","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac452"},{"key":"2026032019400894000_2026.03.16.711780v2.45","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1010"},{"key":"2026032019400894000_2026.03.16.711780v2.46","doi-asserted-by":"publisher","DOI":"10.1101\/2025.07.11.664345"},{"key":"2026032019400894000_2026.03.16.711780v2.47","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-023-00937-1"},{"key":"2026032019400894000_2026.03.16.711780v2.48","doi-asserted-by":"crossref","unstructured":"Dentan C , Tselepis AD , Chapman MJ , Ninio E. Pefabloc , 4-[2-aminoethyl] benzenesulfonyl fluoride, is a new, potent nontoxic and irreversible inhibitor of PAF-degrading acetylhydrolase. Biochim Biophys Acta. 1996.","DOI":"10.1016\/0005-2760(95)00226-X"},{"key":"2026032019400894000_2026.03.16.711780v2.49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1671173"},{"key":"2026032019400894000_2026.03.16.711780v2.50","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01055-25"},{"key":"2026032019400894000_2026.03.16.711780v2.51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1013854"},{"key":"2026032019400894000_2026.03.16.711780v2.52","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02235-13"},{"key":"2026032019400894000_2026.03.16.711780v2.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2017.04.003"},{"key":"2026032019400894000_2026.03.16.711780v2.54","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23168971"},{"key":"2026032019400894000_2026.03.16.711780v2.55","doi-asserted-by":"publisher","DOI":"10.1089\/cell.2016.0041"},{"key":"2026032019400894000_2026.03.16.711780v2.56","doi-asserted-by":"publisher","DOI":"10.3390\/insects16050463"},{"key":"2026032019400894000_2026.03.16.711780v2.57","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-025-03898-5"},{"key":"2026032019400894000_2026.03.16.711780v2.58","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1563240"},{"key":"2026032019400894000_2026.03.16.711780v2.59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00922"},{"key":"2026032019400894000_2026.03.16.711780v2.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.126934"},{"key":"2026032019400894000_2026.03.16.711780v2.61","unstructured":"Jang I-H , Nam H-J , Lee J. CLIP-domain serine proteases in Drosophila innate immunity The molecular organization of clip-SPs. Available: http:\/\/bmbreports.org"},{"key":"2026032019400894000_2026.03.16.711780v2.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.cois.2015.09.003"},{"key":"2026032019400894000_2026.03.16.711780v2.63","doi-asserted-by":"publisher","DOI":"10.1159\/000547814"},{"key":"2026032019400894000_2026.03.16.711780v2.64","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2021"},{"key":"2026032019400894000_2026.03.16.711780v2.65","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00143.2025"},{"key":"2026032019400894000_2026.03.16.711780v2.66","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i12.2106"},{"key":"2026032019400894000_2026.03.16.711780v2.67","doi-asserted-by":"publisher","DOI":"10.7554\/ELIFE.64508"},{"key":"2026032019400894000_2026.03.16.711780v2.68","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-017-0824-3"},{"key":"2026032019400894000_2026.03.16.711780v2.69","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2601-5"},{"key":"2026032019400894000_2026.03.16.711780v2.70","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12827"},{"key":"2026032019400894000_2026.03.16.711780v2.71","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2015.03.014"},{"key":"2026032019400894000_2026.03.16.711780v2.72","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens11030293"},{"key":"2026032019400894000_2026.03.16.711780v2.73","doi-asserted-by":"publisher","DOI":"10.3390\/v14010044"},{"key":"2026032019400894000_2026.03.16.711780v2.74","doi-asserted-by":"publisher","DOI":"10.26508\/LSA.202000786"},{"key":"2026032019400894000_2026.03.16.711780v2.75","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix515"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.16.711780","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T02:40:22Z","timestamp":1774060822000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.16.711780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,16]]},"references-count":75,"URL":"https:\/\/doi.org\/10.64898\/2026.03.16.711780","relation":{},"subject":[],"published":{"date-parts":[[2026,3,16]]},"subtype":"preprint"}}