{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:13:11Z","timestamp":1787029991234,"version":"build-2736575974"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Kent core fund and in part by a Wellcome Trust project","award":["GR074359"],"award-info":[{"award-number":["GR074359"]}]},{"name":"University of Kent core fund and in part by a Wellcome Trust project","award":["28\/B14085"],"award-info":[{"award-number":["28\/B14085"]}]},{"name":"University of Kent core fund and in part by a Wellcome Trust project","award":["BB\/D523078\/1"],"award-info":[{"award-number":["BB\/D523078\/1"]}]},{"name":"Biotechnology and Biological Science Research Council Core Support","award":["GR074359"],"award-info":[{"award-number":["GR074359"]}]},{"name":"Biotechnology and Biological Science Research Council Core Support","award":["28\/B14085"],"award-info":[{"award-number":["28\/B14085"]}]},{"name":"Biotechnology and Biological Science Research Council Core Support","award":["BB\/D523078\/1"],"award-info":[{"award-number":["BB\/D523078\/1"]}]},{"name":"University of Kent PhD studentships","award":["GR074359"],"award-info":[{"award-number":["GR074359"]}]},{"name":"University of Kent PhD studentships","award":["28\/B14085"],"award-info":[{"award-number":["28\/B14085"]}]},{"name":"University of Kent PhD studentships","award":["BB\/D523078\/1"],"award-info":[{"award-number":["BB\/D523078\/1"]}]},{"name":"Basic Research Program at HSE University, Moscow","award":["GR074359"],"award-info":[{"award-number":["GR074359"]}]},{"name":"Basic Research Program at HSE University, Moscow","award":["28\/B14085"],"award-info":[{"award-number":["28\/B14085"]}]},{"name":"Basic Research Program at HSE University, Moscow","award":["BB\/D523078\/1"],"award-info":[{"award-number":["BB\/D523078\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>\u03b1-Latrotoxin (\u03b1LTX) causes exhaustive release of neurotransmitters from nerve terminals in the absence of extracellular Ca2+ (Ca2+e). To investigate the mechanisms underlying this effect, we loaded mouse neuromuscular junctions with BAPTA-AM. This membrane-permeable Ca2+-chelator demonstrates that Ca2+e-independent effects of \u03b1LTX require an increase in cytosolic Ca2+ (Ca2+cyt). We also show that thapsigargin, which depletes Ca2+ stores, induces neurotransmitter release, but inhibits the effect of \u03b1LTX. We then studied \u03b1LTX\u2019s effects on Ca2+cyt using neuroblastoma cells expressing signaling-capable or signaling-incapable variants of latrophilin-1, a G protein-coupled receptor of \u03b1LTX. Our results demonstrate that \u03b1LTX acts as a cation ionophore and a latrophilin agonist. In model cells at 0 Ca2+e, \u03b1LTX forms membrane pores and allows the influx of Na+; this reverses the Na+-Ca2+ exchanger, leading to the release of stored Ca2+ and inhibition of its extrusion. Concurrently, \u03b1LTX stimulates latrophilin signaling, which depletes a Ca2+ store and induces transient opening of Ca2+ channels in the plasmalemma that are sensitive to inhibitors of store-operated Ca2+ entry. These results indicate that Ca2+ release from intracellular stores and that Ca2+ influx through latrophilin-activated store-operated Ca2+ channels contributes to \u03b1LTX actions and may be involved in physiological control of neurotransmitter release at nerve terminals.<\/jats:p>","DOI":"10.3390\/toxins17020073","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T08:53:41Z","timestamp":1738832021000},"page":"73","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["\u03b1-Latrotoxin Actions in the Absence of Extracellular Ca2+ Require Release of Stored Ca2+"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2171-6716","authenticated-orcid":false,"given":"Jennifer K.","family":"Blackburn","sequence":"first","affiliation":[{"name":"Medway School of Pharmacy, University of Kent, Chatham ME4 4TB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quazi Sufia","family":"Islam","sequence":"additional","affiliation":[{"name":"Medway School of Pharmacy, University of Kent, Chatham ME4 4TB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ouafa","family":"Benlaouer","sequence":"additional","affiliation":[{"name":"Medway School of Pharmacy, University of Kent, Chatham ME4 4TB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana A.","family":"Tonevitskaya","sequence":"additional","affiliation":[{"name":"Faculty of Biology and Biotechnology, HSE University, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelina","family":"Petitto","sequence":"additional","affiliation":[{"name":"Medway School of Pharmacy, University of Kent, Chatham ME4 4TB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5712-8297","authenticated-orcid":false,"given":"Yuri A.","family":"Ushkaryov","sequence":"additional","affiliation":[{"name":"Medway School of Pharmacy, University of Kent, Chatham ME4 4TB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.1471-4159.2009.06329.x","article-title":"Penelope\u2019s Web: Using \u03b1-Latrotoxin to Untangle the Mysteries of Exocytosis","volume":"111","author":"Silva","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5055","DOI":"10.3390\/toxins7124862","article-title":"Recent Advances in Research on Widow Spider Venoms and Toxins","volume":"7","author":"Yan","year":"2015","journal-title":"Toxins"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/225701a0","article-title":"Effects of Black Widow Spider Venom on the Frog Neuromuscular Junction","volume":"225","author":"Longenecker","year":"1970","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1126\/science.948756","article-title":"Black Widow Spider Venom: Effect of Purified Toxin on Lipid Bilayer Membranes","volume":"193","author":"Finkelstein","year":"1976","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0163-7258(89)90024-7","article-title":"\u03b1-Latrotoxin and Related Toxins","volume":"42","author":"Rosenthal","year":"1989","journal-title":"Pharmacol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/225703a0","article-title":"Effects of Black Widow Spider Venom on the Frog Neuromuscular Junction. Effects on the Fine Structure of the Frog Neuromuscular Junction","volume":"225","author":"Clark","year":"1970","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1126\/science.1621094","article-title":"Neurexins: Synaptic Cell Surface Proteins Related to the \u03b1-Latrotoxin Receptor and Laminin","volume":"257","author":"Ushkaryov","year":"1992","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23239","DOI":"10.1074\/jbc.271.38.23239","article-title":"Isolation and Biochemical Characterization of a Ca2+-Independent \u03b1-Latrotoxin-Binding Protein","volume":"271","author":"Davletov","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/S0896-6273(00)80332-3","article-title":"\u03b1-Latrotoxin Stimulates Exocytosis by the Interaction with a Neuronal G-Protein-Coupled Receptor","volume":"18","author":"Krasnoperov","year":"1997","journal-title":"Neuron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1124\/pr.114.009647","article-title":"International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein-Coupled Receptors","volume":"67","author":"Hamann","year":"2015","journal-title":"Pharmacol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s10517-009-0600-5","article-title":"Activation of \u03b1-Latrotoxin Receptors in Neuromuscular Synapses Leads to a Prolonged Splash Acetylcholine Release","volume":"147","author":"Lelyanova","year":"2009","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8639","DOI":"10.1523\/JNEUROSCI.0898-09.2009","article-title":"\u03b1-Latrotoxin Stimulates a Novel Pathway of Ca2+-Dependent Synaptic Exocytosis Independent of the Classical Synaptic Fusion Machinery","volume":"29","author":"Liu","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rohou, A., Morris, E.P., Makarova, J., Tonevitsky, A.G., and Ushkaryov, Y.A. (2024). \u03b1-Latrotoxin Tetramers Spontaneously Form Two-Dimensional Crystals in Solution and Coordinated Multi-Pore Assemblies in Biological Membranes. Toxins, 16.","DOI":"10.3390\/toxins16060248"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/71247","article-title":"Structure of \u03b1-Latrotoxin Oligomers Reveals That Divalent Cation-Dependent Tetramers Form Membrane Pores","volume":"7","author":"Orlova","year":"2000","journal-title":"Nat. Struct. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0005-2736(86)90482-7","article-title":"Channels Produced by Spider Venoms in Bilayer Lipid Membrane: Mechanisms of Ion Transport and Toxic Action","volume":"862","author":"Mironov","year":"1986","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8551","DOI":"10.1038\/s41467-024-52635-5","article-title":"Structural Basis of \u03b1-Latrotoxin Transition to a Cation-Selective Pore","volume":"15","author":"Klink","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1111\/j.1471-4159.1990.tb05793.x","article-title":"\u03b1-Latrotoxin Releases Both Vesicular and Cytoplasmic Glutamate from Isolated Nerve Terminals","volume":"55","author":"McMahon","year":"1990","journal-title":"J. Neurochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.1093\/emboj\/17.14.3909","article-title":"Vesicle Exocytosis Stimulated by \u03b1-Latrotoxin Is Mediated by Latrophilin and Requires Both External and Stored Ca2+","volume":"17","author":"Davletov","year":"1998","journal-title":"EMBO J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"31058","DOI":"10.1074\/jbc.M210395200","article-title":"Mutant \u03b1-Latrotoxin (LTXN4C) Does Not Form Pores and Causes Secretion by Receptor Stimulation. This Action Does Not Require Neurexins","volume":"278","author":"Volynski","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4044","DOI":"10.1523\/JNEUROSCI.23-10-04044.2003","article-title":"The \u03b1-Latrotoxin Mutant LTXN4C Enhances Spontaneous and Evoked Transmitter Release in CA3 Pyramidal Neurons","volume":"23","author":"Capogna","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6188","DOI":"10.1093\/emboj\/17.21.6188","article-title":"\u03b1-Latrotoxin Action Probed with Recombinant Toxin: Receptors Recruit \u03b1-Latrotoxin but Do Not Transduce an Exocytotic Signal","volume":"17","author":"Ichtchenko","year":"1998","journal-title":"EMBO J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/S0026-895X(25)09589-6","article-title":"Mode of Action of \u03b1-Latrotoxin: Role of Divalent Cations in Ca2+-Dependent and Ca2+-Independent Effects Mediated by the Toxin","volume":"38","author":"Rosenthal","year":"1990","journal-title":"Mol. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.cub.2005.05.055","article-title":"STIM Is a Ca2+ Sensor Essential for the Ca2+-Store-Depletion-Triggered Ca2+ Influx","volume":"15","author":"Liou","year":"2005","journal-title":"Curr. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/ncb1454","article-title":"STIM1 Carboxyl-Terminus Activates Native SOC, Icrac and TRPC1 Channels","volume":"8","author":"Huang","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1146\/annurev-biochem-061609-165311","article-title":"STIM Proteins and the Endoplasmic Reticulum-Plasma Membrane Junctions","volume":"80","author":"Carrasco","year":"2011","journal-title":"Annu. Rev. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kodakandla, G., Akimzhanov, A.M., and Boehning, D. (2023). Regulatory Mechanisms Controlling Store-Operated Calcium Entry. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1330259"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Rubaiy, H.N. (2023). ORAI Calcium Channels: Regulation, Function, Pharmacology, and Therapeutic Targets. Pharmaceuticals, 16.","DOI":"10.3390\/ph16020162"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1152\/physrev.00020.2014","article-title":"Store-Operated Calcium Channels","volume":"95","author":"Prakriya","year":"2015","journal-title":"Physiol Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ceca.2009.04.001","article-title":"Intracellular Ca2+stores Modulate SOCCs and NMDA Receptors via Tyrosine Kinases in Rat Hippocampal Neurons","volume":"46","author":"Koss","year":"2009","journal-title":"Cell Calcium"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1124\/pr.110.003814","article-title":"Endoplasmic Reticulum Ca2+ Handling in Excitable Cells in Health and Disease","volume":"63","author":"Stutzmann","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8685","DOI":"10.1523\/JNEUROSCI.20-23-08685.2000","article-title":"\u03b1-Latrotoxin Releases Calcium in Frog Motor Nerve Terminals","volume":"20","author":"Tsang","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.jocn.2006.07.013","article-title":"The Role of the Na+\/Ca2+ Exchanger (NCX) in Neurons Following Ischaemia","volume":"14","author":"Jeffs","year":"2007","journal-title":"J. Clin. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Matuz-Mares, D., Gonz\u00e1lez-Andrade, M., Araiza-Villanueva, M.G., Vilchis-Landeros, M.M., and V\u00e1zquez-Meza, H. (2022). Mitochondrial Calcium: Effects of Its Imbalance in Disease. Antioxidants, 11.","DOI":"10.3390\/antiox11050801"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/35036035","article-title":"The Versatility and Universality of Calcium Signalling","volume":"1","author":"Berridge","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1073\/pnas.0908099107","article-title":"NCLX Is an Essential Component of Mitochondrial Na+\/Ca2+ Exchange","volume":"107","author":"Palty","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1007\/s00424-017-1989-8","article-title":"Na+\/Ca2+ Exchangers and Orai Channels Jointly Refill Endoplasmic Reticulum (ER) Ca2+ via ER Nanojunctions in Vascular Endothelial Cells","volume":"469","author":"Shrestha","year":"2017","journal-title":"Pflugers Arch. Eur. J. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/112_2015_23","article-title":"Towards Understanding the Role of the Na+-Ca2+ Exchanger Isoform 3","volume":"168","author":"Michel","year":"2015","journal-title":"Rev. Physiol. Biochem. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.yjmcc.2013.03.012","article-title":"NCLX: The Mitochondrial Sodium Calcium Exchanger","volume":"59","author":"Boyman","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1093\/brain\/awg254","article-title":"Calpain Inhibitors Protect against Axonal Degeneration in a Model of Anti-Ganglioside Antibody-Mediated Motor Nerve Terminal Injury","volume":"126","author":"Humphreys","year":"2003","journal-title":"Brain"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.brainres.2006.03.055","article-title":"Rab3A Deletion Selectively Reduces Spontaneous Neurotransmitter Release at the Mouse Neuromuscular Synapse","volume":"1089","author":"Sons","year":"2006","journal-title":"Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1083\/jcb.87.1.297","article-title":"Ca2+-Dependent Recycling of Synaptic Vesicles at the Frog Neuromuscular Junction","volume":"87","author":"Ceccarelli","year":"1980","journal-title":"J. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/0306-4522(90)90323-V","article-title":"Neurotransmutter Release and Synaptic Vesicle Recycling","volume":"35","author":"Valtorta","year":"1990","journal-title":"Neuroscience"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1085\/jgp.201812298","article-title":"Unraveling the Mechanisms of Calcium-Dependent Secretion","volume":"151","author":"Anantharam","year":"2019","journal-title":"J. Gen. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"44695","DOI":"10.1074\/jbc.M108088200","article-title":"\u03b1-Latrotoxin, Acting via Two Ca2+-Dependent Pathways, Triggers Exocytosis of Two Pools of Synaptic Vesicles","volume":"276","author":"Ashton","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1111\/j.1471-4159.1993.tb03592.x","article-title":"Detection of Intracellular Free Na+ Concentration of Synaptosomes by a Fluorescent Indicator, Na(+)-Binding Benzofuran Isophthalate: The Effect of Veratridine, Ouabain, and \u03b1-Latrotoxin","volume":"61","author":"Deri","year":"1993","journal-title":"J. Neurochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1085\/jgp.20028551","article-title":"Separation and Characterization of Currents through Store-Operated CRAC Channels and Mg2+-Inhibited Cation (MIC) Channels","volume":"119","author":"Prakriya","year":"2002","journal-title":"J. Gen. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3432","DOI":"10.1111\/bph.12691","article-title":"The TRPC Channel Blocker SKF 96365 Inhibits Glioblastoma Cell Growth by Enhancing Reverse Mode of the Na+\/Ca2+ Exchanger and Increasing Intracellular Ca2+","volume":"171","author":"Song","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/j.1469-7793.1997.481bj.x","article-title":"Drastic Facilitation by \u03b1-Latrotoxin of Bovine Chromaffin Cell Exocytosis without Measurable Enhancement of Ca2+ Entry or [Ca2+]I","volume":"502","author":"Michelena","year":"1997","journal-title":"J. Physiol"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"44769","DOI":"10.1074\/jbc.M302511200","article-title":"Sustained Ca2+ Transfer across Mitochondria Is Essential for Mitochondrial Ca2+ Buffering, Store-Operated Ca2+ Entry, and Ca2+ Store Refilling","volume":"278","author":"Malli","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.bbabio.2006.04.017","article-title":"The Regulatory Role of Mitochondria in Capacitative Calcium Entry","volume":"1757","author":"Brutkowski","year":"2006","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0300-9084(00)00199-1","article-title":"Tetramerisation of \u03b1-Latrotoxin by Divalent Cations Is Responsible for Toxin-Induced Non-Vesicular Release and Contributes to the Ca2+-Dependent Vesicular Exocytosis from Synaptosomes","volume":"82","author":"Ashton","year":"2000","journal-title":"Biochimie"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0014-5793(98)01624-X","article-title":"Functional Expression of \u03b1-Latrotoxin in Baculovirus System","volume":"442","author":"Volynski","year":"1999","journal-title":"FEBS Lett."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/17\/2\/73\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:28:05Z","timestamp":1760027285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/17\/2\/73"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,6]]},"references-count":52,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["toxins17020073"],"URL":"https:\/\/doi.org\/10.3390\/toxins17020073","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,6]]}}}