{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T16:18:17Z","timestamp":1775578697864,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"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":["31970127"],"award-info":[{"award-number":["31970127"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Epsilon toxin (ETX), a potential agent of biological and toxic warfare, causes the death of many ruminants and threatens human health. It is crucial to understand the toxic mechanism of such a highly lethal and rapid course toxin. In this study, we detected the effects of ETX on the proteome and phosphoproteome of MDCK cells after 10 min and 30 min. A total of 44 differentially expressed proteins (DEPs) and 588 differentially phosphorylated proteins (DPPs) were screened in the 10 min group, while 73 DEPs and 489 DPPs were screened in the 30 min group. ETX-induced proteins and phosphorylated proteins were mainly located in the nucleus, cytoplasm, and mitochondria, and their enrichment pathways were related to transcription and translation, virus infection, and intercellular junction. Meanwhile, the protein\u2013protein interaction network screened out several hub proteins, including SRSF1\/2\/6\/7\/11, SF3B1\/2, NOP14\/56, ANLN, GTPBP4, THOC2, and RRP1B. Almost all of these proteins were present in the spliceosome pathway, indicating that the spliceosome pathway is involved in ETX-induced cell death. Next, we used RNAi lentiviruses and inhibitors of several key proteins to verify whether these proteins play a critical role. The results confirmed that SRSF1, SF3B2, and THOC2 were the key proteins involved in the cytotoxic effect of ETX. In addition, we found that the common upstream kinase of these key proteins was SRPK1, and a reduction in the level of SRPK1 could also reduce ETX-induced cell death. This result was consistent with the phosphorylated proteomics analysis. In summary, our study demonstrated that ETX induces phosphorylation of SRSF1, SF3B2, THOC2, and SRPK1 proteins on the spliceosome pathway, which inhibits normal splicing of mRNA and leads to cell death.<\/jats:p>","DOI":"10.3390\/toxins16090394","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T10:56:57Z","timestamp":1726484217000},"page":"394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Proteome and Phosphoproteome Profiling Reveal the Toxic Mechanism of Clostridium perfringens Epsilon Toxin in MDCK Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"Nan","family":"Yue","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Huang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100020, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingxin","family":"Dong","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Science, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingshuang","family":"Wang","sequence":"additional","affiliation":[{"name":"Health Bureau of Nanguan District, Changchun 130022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongxue","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songyang","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinglin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Xu","sequence":"additional","affiliation":[{"name":"Academic Affairs Office, Jilin Medical University, Jilin 132013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Kang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5468-2084","authenticated-orcid":false,"given":"Wenwen","family":"Xin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1128\/MMBR.00062-12","article-title":"Toxin plasmids of Clostridium perfringens","volume":"77","author":"Li","year":"2013","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1177\/0300985814540543","article-title":"Comparative neuropathology of ovine enterotoxemia produced by Clostridium perfringens type D wild-type strain CN1020 and its genetically modified derivatives","volume":"52","author":"Garcia","year":"2015","journal-title":"Vet. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"ENEURO.0051-17.2017","DOI":"10.1523\/ENEURO.0051-17.2017","article-title":"Acute Effect of Pore-Forming Clostridium perfringens \u03b5-Toxin on Compound Action Potentials of Optic Nerve of Mouse","volume":"4","author":"Cases","year":"2017","journal-title":"eNeuro"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yao, W., Kang, J., Kang, L., Gao, S., Yang, H., Ji, B., Li, P., Liu, J., Xin, W., and Wang, J. (2016). Immunization with a novel Clostridium perfringens epsilon toxin mutant rETX(Y196E)-C confers strong protection in mice. Sci. Rep., 6.","DOI":"10.1038\/srep24162"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1016\/j.vaccine.2014.03.079","article-title":"Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia","volume":"32","author":"Hall","year":"2014","journal-title":"Vaccine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4589","DOI":"10.1111\/j.1742-4658.2011.08140.x","article-title":"Molecular basis of toxicity of Clostridium perfringens epsilon toxin","volume":"278","author":"Savva","year":"2011","journal-title":"FEBS J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1111\/j.1348-0421.1997.tb01888.x","article-title":"Lambda-toxin of Clostridium perfringens activates the precursor of epsilon-toxin by releasing its N- and C-terminal peptides","volume":"41","author":"Minami","year":"1997","journal-title":"Microbiol. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.3390\/toxins5112138","article-title":"Clostridium perfringens epsilon toxin: A malevolent molecule for animals and man?","volume":"5","author":"Stiles","year":"2013","journal-title":"Toxins"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4602","DOI":"10.1111\/j.1742-4658.2011.08145.x","article-title":"Epsilon toxin: A fascinating pore-forming toxin","volume":"278","author":"Popoff","year":"2011","journal-title":"FEBS J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6480","DOI":"10.1128\/jb.179.20.6480-6487.1997","article-title":"Clostridium perfringens epsilon-toxin acts on MDCK cells by forming a large membrane complex","volume":"179","author":"Petit","year":"1997","journal-title":"J. Bacteriol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1191\/096032700678815710","article-title":"An assessment of the in vitro toxicology of Clostridium perfringens type D epsilon-toxin in human and animal cells","volume":"19","author":"Shortt","year":"2000","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ivie, S.E., Fennessey, C.M., Sheng, J., Rubin, D.H., and McClain, M.S. (2011). Gene-trap mutagenesis identifies mammalian genes contributing to intoxication by Clostridium perfringens \u03b5-toxin. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017787"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"F927","DOI":"10.1152\/ajprenal.00199.2007","article-title":"Pore-forming epsilon toxin causes membrane permeabilization and rapid ATP depletion-mediated cell death in renal collecting duct cells","volume":"293","author":"Chassin","year":"2007","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1080\/21505594.2018.1528842","article-title":"Research articleHemolysis in human erythrocytes by Clostridium perfringens epsilon toxin requires activation of P2 receptors","volume":"9","author":"Gao","year":"2018","journal-title":"Virulence"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.bsheal.2019.09.004","article-title":"Clostridium perfringens epsilon toxin: Toxic effects and mechanisms of action","volume":"1","author":"Xin","year":"2019","journal-title":"Biosaf. Health"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1038\/s41467-019-10645-8","article-title":"The pore structure of Clostridium perfringens epsilon toxin","volume":"10","author":"Savva","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"39463","DOI":"10.1074\/jbc.M206731200","article-title":"Clostridium perfringens epsilon-toxin forms a heptameric pore within the detergent-insoluble microdomains of Madin-Darby canine kidney cells and rat synaptosomes","volume":"277","author":"Miyata","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15736","DOI":"10.1074\/jbc.M010412200","article-title":"Clostridium perfringens epsilon toxin induces a rapid change of cell membrane permeability to ions and forms channels in artificial lipid bilayers","volume":"276","author":"Petit","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.anaerobe.2013.09.009","article-title":"Cellular vacuolation and mitochondrial-associated factors induced by Clostridium perfringens epsilon toxin detected using acoustic flow cytometry","volume":"24","author":"Ferrarezi","year":"2013","journal-title":"Anaerobe"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/cmi.12373","article-title":"Epsilon toxin from Clostridium perfringens acts on oligodendrocytes without forming pores, and causes demyelination","volume":"17","author":"Wioland","year":"2015","journal-title":"Cell Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rashid Rumah, K., Eleso, O., and Fischetti, V.A.J.B. (2019). Human blood exposure to Clostridium perfringens epsilon toxin may shed light on erythrocyte fragility during active multiple sclerosis. bioRivx.","DOI":"10.1101\/789123"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Abou Faycal, C., Gazzeri, S., and Eymin, B. (2019). A VEGF-A\/SOX2\/SRSF2 network controls VEGFR1 pre-mRNA alternative splicing in lung carcinoma cells. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-36728-y"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"He, C., Liu, B., Wang, H.Y., Wu, L., Zhao, G., Huang, C., Liu, Y., Shan, B., and Liu, L. (2022). Inhibition of SRPK1, a key splicing regulator, exhibits antitumor and chemotherapeutic-sensitizing effects on extranodal NK\/T-cell lymphoma cells. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-10158-6"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.anaerobe.2016.06.006","article-title":"New insights into Clostridium perfringens epsilon toxin activation and action on the brain during enterotoxemia","volume":"41","author":"Freedman","year":"2016","journal-title":"Anaerobe"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.anaerobe.2019.05.010","article-title":"Elucidation of protein biomarkers in plasma and urine for epsilon toxin exposure in mouse model","volume":"59","author":"Babele","year":"2019","journal-title":"Anaerobe"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1073\/pnas.74.8.3171","article-title":"Spliced segments at the 5\u2032 terminus of adenovirus 2 late mRNA","volume":"74","author":"Berget","year":"1977","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0092-8674(77)90180-5","article-title":"An amazing sequence arrangement at the 5\u2032 ends of adenovirus 2 messenger RNA","volume":"12","author":"Chow","year":"1977","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1101\/gad.1973010","article-title":"Alternative pre-mRNA splicing regulation in cancer: Pathways and programs unhinged","volume":"24","author":"David","year":"2010","journal-title":"Genes. Dev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/S1672-0229(03)01002-7","article-title":"Advances in the study of SR protein family","volume":"1","author":"Ma","year":"2003","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41392-021-00495-6","article-title":"SRSF1 inhibits autophagy through regulating Bcl-x splicing and interacting with PIK3C3 in lung cancer","volume":"6","author":"Lv","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s13046-021-01978-8","article-title":"Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1","volume":"40","author":"Du","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1158\/2159-8290.CD-22-1013","article-title":"Splicing Factor SRSF1 Promotes Pancreatitis and KRASG12D-Mediated Pancreatic Cancer","volume":"13","author":"Wan","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41375-019-0567-9","article-title":"Altered expression of CSF3R splice variants impacts signal response and is associated with SRSF2 mutations","volume":"34","author":"Lance","year":"2020","journal-title":"Leukemia"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gout, S., Brambilla, E., Boudria, A., Drissi, R., Lantuejoul, S., Gazzeri, S., and Eymin, B. (2012). Abnormal expression of the pre-mRNA splicing regulators SRSF1, SRSF2, SRPK1 and SRPK2 in non small cell lung carcinoma. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046539"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1158\/0008-5472.CAN-16-1919","article-title":"SRSF2 Regulates Alternative Splicing to Drive Hepatocellular Carcinoma Development","volume":"77","author":"Luo","year":"2017","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.7150\/ijbs.58888","article-title":"Splicing factor SRSF2-centric gene regulation","volume":"17","author":"Li","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1136\/gutjnl-2017-314983","article-title":"SRSF6-regulated alternative splicing that promotes tumour progression offers a therapy target for colorectal cancer","volume":"68","author":"Wan","year":"2019","journal-title":"Gut"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12943-020-01299-y","article-title":"LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM","volume":"20","author":"Zhang","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1016\/j.cmet.2021.09.008","article-title":"DRAK2 aggravates nonalcoholic fatty liver disease progression through SRSF6-associated RNA alternative splicing","volume":"33","author":"Li","year":"2021","journal-title":"Cell Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1182\/blood-2011-12-399774","article-title":"Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis","volume":"119","author":"Makishima","year":"2012","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1182\/blood-2012-09-399725","article-title":"Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms","volume":"121","author":"Cazzola","year":"2013","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s00277-013-1915-x","article-title":"Clinical significance of SF3B1 mutations in Korean patients with myelodysplastic syndromes and myelodysplasia\/myeloproliferative neoplasms with ring sideroblasts","volume":"93","author":"Seo","year":"2014","journal-title":"Ann. Hematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/path.4846","article-title":"The many faces of SRPK1","volume":"241","author":"Bullock","year":"2017","journal-title":"J. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13046-021-01877-y","article-title":"SRPK1\/2 and PP1\u03b1 exert opposite functions by modulating SRSF1-guided MKNK2 alternative splicing in colon adenocarcinoma","volume":"40","author":"Liu","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1007\/s11033-018-4545-5","article-title":"Serine arginine protein kinase 1 (SRPK1): A moonlighting protein with theranostic ability in cancer prevention","volume":"46","author":"Patel","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7341","DOI":"10.1111\/jcmm.15315","article-title":"Clostridium perfringens epsilon toxin binds to erythrocyte MAL receptors and triggers phosphatidylserine exposure","volume":"24","author":"Geng","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101074","DOI":"10.1016\/j.isci.2020.101074","article-title":"Landscapes of Protein Posttranslational Modifications of African Trypanosoma Parasites","volume":"23","author":"Zhang","year":"2020","journal-title":"iScience"},{"key":"ref_48","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":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/9\/394\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:56:12Z","timestamp":1760111772000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/9\/394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,14]]},"references-count":48,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["toxins16090394"],"URL":"https:\/\/doi.org\/10.3390\/toxins16090394","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,14]]}}}