{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T03:13:01Z","timestamp":1783480381175,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lithuanian National Science Foundation","award":["S-PD-22-16"],"award-info":[{"award-number":["S-PD-22-16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Aeruginosins (AERs) are one of the most common classes of cyanobacterial peptides synthesised through a hybrid non-ribosomal peptide synthase\/polyketide synthase pathway. They have been found in Microcystis, Nodularia spumigena, Oscillatoria\/Plantothrix, and Nostoc. The presence of AER in Aphanizomenon isolated from the Curonian Lagoon was reported for the first time in our previous work. Here, the structure of aeruginosin 525 (AER525), isolated from Aphanizomenon sp. KUCC C2, was characterised based on high-resolution mass spectrometry. This new AER variant shows potent activity against thrombin. It also inhibits trypsin and carboxypeptidase A but has no effect on elastase and chymotrypsin. In terms of the N-terminal residue and biological activity, AER525 displaces some similarity to dysinosins, which belongs to the most potent inhibitors of thrombin among AERs. The findings underline the potential of AER525 as a new anticoagulant agent.<\/jats:p>","DOI":"10.3390\/md22110506","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T04:02:54Z","timestamp":1731038574000},"page":"506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Aeruginosin 525 (AER525) from Cyanobacterium Aphanizomenon Sp. (KUCC C2): A New Serine Proteases Inhibitor"],"prefix":"10.3390","volume":"22","author":[{"given":"Donata","family":"Overling\u0117","sequence":"first","affiliation":[{"name":"Marine Research Institute, Klaip\u0117da University, Universiteto av. 17, LT-92294 Klaip\u0117da, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6601-5825","authenticated-orcid":false,"given":"Marta","family":"Ceg\u0142owska","sequence":"additional","affiliation":[{"name":"Institute of Oceanology, Polish Academy of Sciences, Powsta\u0144c\u00f3w Warszawy 55, PL-81712 Sopot, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6732-3646","authenticated-orcid":false,"given":"Robert","family":"Konkel","sequence":"additional","affiliation":[{"name":"Department of Marine Biology and Biotechnology, University of Gda\u0144sk, M. J. Pi\u0142sudskiego 46, PL-81378 Gdynia, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6526-4045","authenticated-orcid":false,"given":"Hanna","family":"Mazur-Marzec","sequence":"additional","affiliation":[{"name":"Department of Marine Biology and Biotechnology, University of Gda\u0144sk, M. J. Pi\u0142sudskiego 46, PL-81378 Gdynia, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"ref_1","first-page":"147","article-title":"Evaluation of Microalgae for Use as Nutraceuticals and Nutritional Supplements","volume":"2","author":"Bishop","year":"2012","journal-title":"J. Nutr. Food Sci."},{"key":"ref_2","unstructured":"Kownacka, J., Busch, S., G\u00f6bel, J., Gromisz, S., H\u00e4llfors, H., H\u00f6glander, H., Huseby, S., Jaanus, A., Jakobsen, H.H., and Johansen, M. (2024, September 17). Cyanobacteria Biomass 1990\u20132020. HELCOM Baltic Sea Environment Fact Sheets. Available online: https:\/\/helcom.fi\/baltic-sea-trends\/environment-fact-sheets\/eutrophication\/."},{"key":"ref_3","unstructured":"Severo, A.S., Mart\u00ednez-Burgos, J.W., and Ordonez, J. (2024). Extracts and Benefits. Insights into Algae-Fundamentals, Culture Techniques and Biotechnological Uses of Microalgae and Cyanobacteria, IntechOpen Limited."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Whitton, B. (2012). The Biotechnology of Cyanobacteria. Ecology of Cyanobacteria II: Their Diversity in Space and Time, Springer.","DOI":"10.1007\/978-94-007-3855-3"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1007\/s10811-024-03214-0","article-title":"The Commercial Potential of Aphanizomenon Flos-Aquae, a Nitrogen-Fixing Edible Cyanobacterium","volume":"36","author":"Scoglio","year":"2024","journal-title":"J. Appl. Phycol."},{"key":"ref_6","first-page":"1867","article-title":"Phylogenetic Comparison of the Cyanobacterial Genera Anabaena and Aphanizomenon","volume":"52","author":"Gugger","year":"2002","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.marpolbul.2015.07.057","article-title":"Increased Risk of Exposure to Microcystins in the Scum of the Filamentous Cyanobacterium Aphanizomenon flos-aquae Accumulated on the Western Shoreline of the Curonian Lagoon","volume":"99","author":"Pilkaityte","year":"2015","journal-title":"Mar. Pollut. Bull."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1021\/np000120k","article-title":"New Anabaenopeptins, Carboxypeptidaze-A Inhibitors from the Cyanobacterium Aphanizomenon flos-aquae","volume":"63","author":"Murakami","year":"2000","journal-title":"J. Nat. Prod."},{"key":"ref_9","unstructured":"Ferreira, F.A.H. (2006). Peptides in Cyanobacteria under Different Environmental Conditions. [Ph.D. Dissertation, Technical University of Berlin]."},{"key":"ref_10","first-page":"381","article-title":"Effects of Klamath Algae Extract on Psychological Disorders and Depression in Menopausal Women: A Pilot Study","volume":"62","author":"Genazzani","year":"2010","journal-title":"Minerva Ginecol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1089\/jmf.2016.0181","article-title":"The Effect of Experimental Supplementation with the Klamath Algae Extract Klamin on Attention-Deficit\/Hyperactivity Disorder","volume":"20","author":"Cremonte","year":"2017","journal-title":"J. Med. Food"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.3109\/14756366.2016.1149478","article-title":"Inhibitory Effects of Aphanizomenon flos-aquae Constituents on Human UDP-Glucose Dehydrogenase Activity","volume":"31","author":"Scoglio","year":"2016","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"927","DOI":"10.3892\/etm.2015.2644","article-title":"Extracellular Polymeric Substance from Aphanizomenon Flos-Aquae Induces Apoptosis via the Mitochondrial Pathway in A431 Human Epidermoid Carcinoma Cells","volume":"10","author":"Xue","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Overling\u0117, D., Toru\u0144ska-Sitarz, A., Ceg\u0142owska, M., Szubert, K., and Mazur-Marzec, H. (2024). Phylogenetic and Molecular Characteristics of Two Aphanizomenon Strains from the Curonian Lagoon, Southeastern Baltic Sea and Their Biological Activities. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-76064-y"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.chembiol.2007.04.006","article-title":"Biosynthesis and Structure of Aeruginoside 126A and 126B, Cyanobacterial Peptide Glycosides Bearing a 2-Carboxy-6-Hydroxyoctahydroindole Moiety","volume":"14","author":"Ishida","year":"2007","journal-title":"Chem. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1002\/anie.200605219","article-title":"Chemistry and Biology of the Aeruginosin Family of Serine Protease Inhibitors","volume":"47","author":"Ersmark","year":"2008","journal-title":"Angew. Chem.-Int. Ed."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/j.1574-6976.2006.00022.x","article-title":"Cyanobacterial Peptides\u2014Nature\u2019s Own Combinatorial Biosynthesis","volume":"30","author":"Welker","year":"2006","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1016\/S0040-4039(00)76848-1","article-title":"Aeruginosin 298-A, a Thrombin and Trypsin Inhibitor from the Blue-Green Alga Microcystis Aeruginosa (NIES-298)","volume":"35","author":"Murakami","year":"1994","journal-title":"Tetrahedron Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"117017","DOI":"10.1016\/j.watres.2021.117017","article-title":"CyanoMetDB, a Comprehensive Public Database of Secondary Metabolites from Cyanobacteria","volume":"196","author":"Jones","year":"2021","journal-title":"Water Res."},{"key":"ref_20","unstructured":"Janssen, E.M.L., Jones, M.R., Pinto, E., D\u00f6rr, F., Torres, M., Rios Jacinavicius, F., Mazur-Marzec, H., Szubert, K., Konkel, R., and Tartaglione, L. (2024). Comprehensive database of secondary metabolites from cyanobacteria (NORMAN-SLE-S75.0.3.0) [Data set]. Zenodo."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Entfellner, E., Baumann, K.B.L., Edwards, C., and Kurmayer, R. (2023). High Structural Diversity of Aeruginosins in Bloom-Forming Cyanobacteria of the Genus Planktothrix as a Consequence of Multiple Recombination Events. Mar. Drugs, 21.","DOI":"10.3390\/md21120638"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1016\/j.peptides.2006.03.014","article-title":"Detection and Identification of Oligopeptides in Microcystis (Cyanobacteria) Colonies: Toward an Understanding of Metabolic Diversity","volume":"27","author":"Welker","year":"2006","journal-title":"Peptides"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1021\/np049968p","article-title":"Dysinosins B-D, Inhibitors of Factor VIIa and Thrombin from the Australian Sponge Lamellodysidea chlorea","volume":"67","author":"Carroll","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_24","first-page":"1","article-title":"Comparative Genomics of Cyanobacterial Symbionts Reveals Distinct, Specialized Metabolism in Tropical Dysideidae Sponges","volume":"10","author":"Schorn","year":"2019","journal-title":"Appl. Environ. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1002\/cbic.201300246","article-title":"Novel Aeruginosin-865 from Nostoc Sp. as a Potent Anti-Inflammatory Agent","volume":"14","author":"Hrouzek","year":"2013","journal-title":"ChemBioChem"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10491","DOI":"10.1021\/ja0625834","article-title":"Total Synthesis and Structural Confirmation of Chlorodysinosin A","volume":"128","author":"Hanessian","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Du, X., Liu, H., Yuan, L., Wang, Y., Ma, Y., Wang, R., Chen, X., Losiewicz, M.D., Guo, H., and Zhang, H. (2019). The Diversity of Cyanobacterial Toxins on Structural Characterization, Distribution and Identification: A Systematic Review. Toxins, 11.","DOI":"10.3390\/toxins11090530"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1021\/cb5004306","article-title":"Pseudoaeruginosins, Nonribosomal Peptides in Nodularia spumigena","volume":"10","author":"Liu","year":"2014","journal-title":"ACS Chem. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10835","DOI":"10.1016\/S0040-4020(99)00597-9","article-title":"Inhibitors of Serine Proteases from a Waterbloom of the Cyanobacterium Microcystis sp.","volume":"55","author":"Banker","year":"1999","journal-title":"Tetrahedron"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Fewer, D.P., Jokela, J., Paukku, E., \u00d6sterholm, J., Wahlsten, M., Permi, P., Aitio, O., Rouhiainen, L., Gomez-Saez, G.V., and Sivonen, K. (2013). New Structural Variants of Aeruginosin Produced by the Toxic Bloom Forming Cyanobacterium Nodularia spumigena. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073618"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.3390\/md13042347","article-title":"New Prenylated Aeruginosin, Microphycin, Anabaenopeptin and Micropeptin Analogues from a Microcystis Bloom Material Collected in Kibbutz Kfar Blum, Israel","volume":"13","author":"Carmeli","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1021\/np4006844","article-title":"Protease Inhibitors from Microcystis Aeruginosa Bloom Material Collected from the Dalton Reservoir, Israel","volume":"76","author":"Adiv","year":"2013","journal-title":"J. Nat. Prod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6817","DOI":"10.1016\/j.tet.2014.07.057","article-title":"Three Aeruginosins and a Microviridin from a Bloom Assembly of Microcystis Spp. Collected from a Fishpond near Kibbutz Lehavot HaBashan, Israel","volume":"70","author":"Vegman","year":"2014","journal-title":"Tetrahedron"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.hal.2014.07.003","article-title":"The Toxicity and Enzyme Activity of a Chlorine and Sulfate Containing Aeruginosin Isolated from a Non-Microcystin-Producing Planktothrix Strain","volume":"39","author":"Kohler","year":"2014","journal-title":"Harmful Algae"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.3390\/md13063892","article-title":"Structural Characterization of New Peptide Variants Produced by Cyanobacteria from the Brazilian Atlantic Coastal Forest Using Liquid Chromatography Coupled to Quadrupole Time-of-Flight Tandem Mass Spectrometry","volume":"13","author":"Sanz","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13340","DOI":"10.1021\/ja020814a","article-title":"Dysinosin A: A Novel Inhibitor of Factor Viia and Thrombin from a New Genus and Species of Australian Sponge of the Family Dysideidae","volume":"124","author":"Carroll","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"145053","DOI":"10.1016\/j.scitotenv.2021.145053","article-title":"Hot Moments and Hotspots of Cyanobacteria Hyperblooms in the Curonian Lagoon (SE Baltic Sea) Revealed via Remote Sensing-Based Retrospective Analysis","volume":"769","author":"Bresciani","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s10533-018-0508-0","article-title":"The Influence of Cyanobacteria Blooms on the Attenuation of Nitrogen Throughputs in a Baltic Coastal Lagoon","volume":"141","author":"Zilius","year":"2018","journal-title":"Biogeochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111500","DOI":"10.1016\/j.marpolbul.2020.111500","article-title":"Are There Concerns Regarding CHAB in Coastal Bathing Waters Affected by Freshwater-Brackish Continuum?","volume":"159","author":"Gyraite","year":"2020","journal-title":"Mar. Pollut. Bull."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pilkaityt\u0117, R., Overling\u0117, D., Gasi\u016bnait\u0117, Z.R., and Mazur-Marzec, H. (2021). Spatial and Temporal Diversity of Cyanometabolites in the Eutrophic Curonian Lagoon (SE Baltic Sea). Water, 13.","DOI":"10.3390\/w13131760"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.algal.2018.08.006","article-title":"Recovery of Lipophilic Products from Wild Cyanobacteria (Aphanizomenon flos-aquae) Isolated from the Curonian Lagoon by Means of Supercritical Carbon Dioxide Extraction","volume":"35","author":"Syrpas","year":"2018","journal-title":"Algal Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1021\/acs.jafc.9b05483","article-title":"Ultrasound-Assisted Extraction and Assessment of Biological Activity of Phycobiliprotein-Rich Aqueous Extracts from Wild Cyanobacteria (Aphanizomenon flos-aquae)","volume":"68","author":"Syrpas","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_43","unstructured":"(2024, October 10). Available online: https:\/\/algaeservice.gamtostyrimai.lt\/wp-content\/uploads\/2021\/07\/AlgaeService_for-LIFE_Mid-term-Report.pdf."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Overling\u0117, D., Toru\u0144ska-sitarz, A., Ceg\u0142owska, M., B\u0142aszczyk, A., Szubert, K., Pilkaityt\u0117, R., and Mazur-marzec, H. (2021). Phytoplankton of the Curonian Lagoon as a New Interesting Source for Bioactive Natural Products. Special Impact on Cyanobacterial Metabolites. Biomolecules, 11.","DOI":"10.3390\/biom11081139"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/j.scitotenv.2017.07.253","article-title":"The Profound Effect of Harmful Cyanobacterial Blooms: From Food-Web and Management Perspectives","volume":"609","year":"2017","journal-title":"Sci. Total Environ."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14501","DOI":"10.1016\/0040-4020(96)00890-3","article-title":"Aeruginosins 102-A and B, New Thrombin Inhibitors from the Cyanobacterium Microcystis Viridis (NIES-102)","volume":"52","author":"Matsuda","year":"1996","journal-title":"Tetrahedron"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10971","DOI":"10.1016\/S0040-4020(99)00621-3","article-title":"Aeruginosins, Protease Inhibitors from the Cyanobacterium Microcystis aeruginosa","volume":"55","author":"Ishida","year":"1999","journal-title":"Tetrahedron"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9427","DOI":"10.1002\/anie.201602755","article-title":"Investigating the Toxicity of the Aeruginosin Chlorosulfopeptides by Chemical Synthesis","volume":"55","author":"Scherer","year":"2016","journal-title":"Angew. Chem.-Int. Ed."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1021\/np3005612","article-title":"Bromine-and Chlorine-Containing Aeruginosins from Microcystis aeruginosa Bloom Material Collected in Kibbutz Geva, Israel","volume":"75","author":"Faigenbaum","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.phytol.2008.10.002","article-title":"Two Novel Biological Active Modified Peptides from the Cyanobacterium Microcystis sp.","volume":"2","author":"Raveh","year":"2009","journal-title":"Phytochem. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1016\/0040-4039(95)00396-T","article-title":"Aeruginosins 98-A and B, Trypsin Inhibitors from the Blue-Green Alga Microcystis aeruginosa (NIES-98)","volume":"36","author":"Murakami","year":"1995","journal-title":"Tetrahedron Lett."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Liu, J., Zhang, M., Huang, Z., Fang, J., Wang, Z., Zou, C., and Qui, X. (2023). Diversity, Biosynthesis and Bioactivity of Aeruginosins, a Family of Cyanobacteria-Derived Nonribosomal Linear Tetrapeptides. Mar. Drugs, 21.","DOI":"10.3390\/md21040217"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1039\/D1OB02454J","article-title":"Discovery of Varlaxins, New Aeruginosin-Type Inhibitors of Human Trypsins","volume":"20","author":"Jokela","year":"2022","journal-title":"Org. Biomol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Faltermann, S., Hutter, S., Christen, V., Hettich, T., and Fent, K. (2016). Anti-Inflammatory Activity of Cyanobacterial Serine Protease Inhibitors Aeruginosin 828A and Cyanopeptolin 1020 in Human Hepatoma Cell Line Huh7 and Effects in Zebrafish (Danio rerio). Toxins, 8.","DOI":"10.3390\/toxins8070219"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.tet.2004.11.016","article-title":"Banyasin A and Banyasides A and B, Three Novel Modified Peptides from a Water Bloom of the Cyanobacterium Nostoc sp.","volume":"61","author":"Pluotno","year":"2005","journal-title":"Tetrahedron"},{"key":"ref_56","unstructured":"Ocampo Bennet, X. (2007). Peptide au Seiner Cyanobakterien Wasserbl\u00fctte (1998) aus dem Wannsee\/Berli: Strukturen and Biologische Wirksamkeit, University of Freiburg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"528","DOI":"10.3390\/md7040528","article-title":"Lyngbyastatins 8\u201310, Elastase Inhibitors with Cyclic Depsipeptide Scaffolds Isolated from the Marine Cyanobacterium Lyngbya semiplena","volume":"7","author":"Kwan","year":"2009","journal-title":"Mar. Drugs"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/22\/11\/506\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:28:27Z","timestamp":1760113707000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/22\/11\/506"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,8]]},"references-count":57,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["md22110506"],"URL":"https:\/\/doi.org\/10.3390\/md22110506","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,8]]}}}