{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:25:40Z","timestamp":1760300740096,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Marine life has proved to be an invaluable source of new compounds with significant bioactivities, such as xanthones. This review summarizes the advances made in the study of marine-derived xanthones from 2010 to 2021, from isolation towards synthesis, highlighting their biological activities. Most of these compounds were isolated from marine-derived fungi, found in marine sediments, and associated with other aquatic organisms (sponge and jellyfish). Once isolated, xanthones have been assessed for different bioactivities, such as antibacterial, antifungal, and cytotoxic properties. In the latter case, promising results have been demonstrated. Considering the significant bioactivities showed by xanthones, efforts have been made to synthesize these compounds, like yicathins B and C and the secalonic acid D, through total synthesis.<\/jats:p>","DOI":"10.3390\/md20060347","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T08:41:33Z","timestamp":1653468093000},"page":"347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Marine-Derived Xanthone from 2010 to 2021: Isolation, Bioactivities and Total Synthesis"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7254-5996","authenticated-orcid":false,"given":"Ana C. S.","family":"Ver\u00edssimo","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4249-7089","authenticated-orcid":false,"given":"Diana C. G. A.","family":"Pinto","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-8286","authenticated-orcid":false,"given":"Artur M. S.","family":"Silva","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/07388551.2021.1940087","article-title":"Marine and terrestrial endophytic fungi: A mine of bioactive xanthone compounds, recent progress, limitations, and novel applications","volume":"42","author":"Khattab","year":"2022","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pinto, M.M.M., Palmeira, A., Fernandes, C., Resende, D.I.S.P., Sousa, E., Cidade, H., Tiritan, M.E., Correia-da-Silva, M., and Cravo, S. (2021). From natural products to new synthetic small molecules: A journey through the world of xanthones. Molecules, 26.","DOI":"10.3390\/molecules26020431"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4481","DOI":"10.2174\/09298673113209990144","article-title":"Xanthones as potential antioxidants","volume":"20","author":"Panda","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"621459","DOI":"10.1155\/2013\/621459","article-title":"Naturally occurring xanthones: Chemistry and biology","volume":"2013","author":"Negi","year":"2013","journal-title":"J. Appl. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.1021\/cr100446h","article-title":"Xanthones from fungi, lichens, and bacteria: The natural products and their synthesis","volume":"112","author":"Masters","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Resende, D., Pereira-Terra, P., In\u00e1cio, \u00c2., Costa, P., Pinto, E., Sousa, E., and Pinto, M. (2018). Lichen xanthones as models for new antifungal agents. Molecules, 23.","DOI":"10.3390\/molecules23102617"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S0031-9422(00)00303-4","article-title":"Tetraoxygenated naturally occurring xanthones","volume":"55","author":"Peres","year":"2000","journal-title":"Phytochemistry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1080\/07388551.2020.1721426","article-title":"Current status and perspectives of xanthones production using cultured plant biocatalyst models aided by in-silico tools for its optimization","volume":"40","author":"Khattab","year":"2020","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.2174\/092986709788682056","article-title":"Naturally occurring xanthones; latest investigations: Isolation, structure elucidation and chemosystematic significance","volume":"16","author":"Zayed","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Loureiro, D.R.P., Soares, J.X., Costa, J.C., Magalh\u00e3es, \u00c1.F., Azevedo, C.M.G., Pinto, M.M.M., and Afonso, C.M.M. (2019). Structures, activities and drug-likeness of anti-Infective xanthone derivatives isolated from the marine environment: A review. Molecules, 24.","DOI":"10.3390\/molecules24020243"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pinto, M.M.M., Castanheiro, R.A.P., and Kijjoa, A. (2014). Xanthones from marine-derived microorganisms: Isolation, structure elucidation and biological activities. Encyclopedia of Analytical Chemistry, John Wiley & Sons, Ltd.","DOI":"10.1002\/9780470027318.a9927"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s12272-010-0207-4","article-title":"Bioactive metabolites from the sponge-derived fungus Aspergillus versicolor","volume":"33","author":"Lee","year":"2010","journal-title":"Arch. Pharm. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1080\/14786419.2017.1416376","article-title":"Penicillixanthone A, a marine-derived dual-coreceptor antagonist as anti-HIV-1 agent","volume":"33","author":"Tan","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhu, A., Zhang, X.-W., Zhang, M., Li, W., Ma, Z.-Y., Zhu, H.-J., and Cao, F. (2018). Aspergixanthones I\u2013K, new anti-vibrio prenylxanthones from the marine-derived fungus Aspergillus sp. ZA-01. Mar. Drugs, 16.","DOI":"10.3390\/md16090312"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1016\/j.tet.2016.03.073","article-title":"Xanthones and sesquiterpene derivatives from a marine-derived fungus Scopulariopsis sp.","volume":"72","author":"Elnaggar","year":"2016","journal-title":"Tetrahedron"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fitote.2018.11.015","article-title":"Antibacterial anthraquinone dimers from marine derived fungus Aspergillus sp.","volume":"133","author":"Li","year":"2019","journal-title":"Fitoterapia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10621","DOI":"10.1038\/s41598-018-28996-5","article-title":"Absolute configurations of 14,15-hydroxylated prenylxanthones from a marine-derived Aspergillus sp. fungus by chiroptical methods","volume":"8","author":"Zhu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_18","first-page":"1934578X2110550","article-title":"Three new metabolites from the marine-derived fungus Aspergillus sp. WHUF03110","volume":"16","author":"Lv","year":"2021","journal-title":"Nat. Prod. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.3390\/md10112571","article-title":"Four new antibacterial xanthones from the marine-derived Actinomycetes Streptomyces caelestis","volume":"10","author":"Liu","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/14786419.2021.1915309","article-title":"New aromatic polyketides from the marine-derived fungus Pseudopithomyces maydicus PSU-AMF350 and their antimicrobial activity","volume":"36","author":"Ningsih","year":"2022","journal-title":"Nat. Prod. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1021\/acs.jnatprod.0c00684","article-title":"Monacycliones G\u2013K and ent-gephyromycin A, angucycline derivatives from the marine-derived Streptomyces sp. HDN15129","volume":"83","author":"Chang","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1080\/14786419.2018.1487966","article-title":"Emerixanthone E, a new xanthone derivative from deep sea fungus Emericella sp SCSIO 05240","volume":"33","author":"Fredimoses","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.ejmech.2018.02.041","article-title":"Structure-based discovery of cytotoxic dimeric tetrahydroxanthones as potential topoisomerase I inhibitors from a marine-derived fungus","volume":"148","author":"Wu","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3389\/fchem.2018.00282","article-title":"Structurally diverse polyketides from the mangrove-derived fungus Diaporthe sp. SCSIO 41011 with their anti-influenza A virus activities","volume":"6","author":"Luo","year":"2018","journal-title":"Front. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liu, H., Chen, S., Liu, W., Liu, Y., Huang, X., and She, Z. (2016). Polyketides with immunosuppressive activities from mangrove endophytic fungus Penicillium sp. ZJ-SY2 Hongju. Mar. Drugs, 14.","DOI":"10.3390\/md14120217"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7452","DOI":"10.1002\/chem.201600430","article-title":"Engyodontochones, antibiotic polyketides from the marine fungus Engyodontium album strain LF069","volume":"22","author":"Wu","year":"2016","journal-title":"Chem.-Eur. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1021\/acs.jnatprod.5b00636","article-title":"Versixanthones A\u2013F, cytotoxic xanthone\u2013chromanone dimers from the marine-derived fungus Aspergillus versicolor HDN1009","volume":"78","author":"Wu","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1021\/acs.jnatprod.5b00578","article-title":"Varioxiranols A\u2013G and 19-O-methyl-22-methoxypre-shamixanthone, PKS and hybrid PKS-derived metabolites from a sponge-associated Emericella variecolor fungus","volume":"78","author":"Wu","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_29","first-page":"161","article-title":"Study on aromatic polyketide metabolite with antibacterial activity from the marine-derived Actinomadura sp. FIM95-F26","volume":"40","author":"Jang","year":"2015","journal-title":"Chin. J. Antibiot."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4939","DOI":"10.1016\/j.bmcl.2014.09.040","article-title":"New antibacterial xanthone from the marine sponge-derived Micrococcus sp. EG45","volume":"24","author":"Eltamany","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/14786419.2013.843177","article-title":"Three new polyketides from marine-derived fungus Penicillium citrinum SCSGAF 0167","volume":"28","author":"Sun","year":"2014","journal-title":"Nat. Prod. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1007\/s10600-013-0572-6","article-title":"A new xanthone derivative from the marine fungus Phomopsis sp. (No. SK7RN3G1)","volume":"49","author":"Yang","year":"2013","journal-title":"Chem. Nat. Compd."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1007\/s10600-011-9939-8","article-title":"A new xanthone derivative from the co-culture broth of two marine fungi (strain No. E33 and K38)","volume":"47","author":"Li","year":"2011","journal-title":"Chem. Nat. Compd."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1002\/hlca.201200596","article-title":"New cytotoxic metabolites from the marine-derived fungus Penicillium sp. ZLN29","volume":"96","author":"Gao","year":"2013","journal-title":"Helv. Chim. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Li, H.-L., Li, X.-M., Liu, H., Meng, L.-H., and Wang, B.-G. (2016). Two New diphenylketones and a new xanthone from Talaromyces islandicus EN-501, an endophytic fungus derived from the marine red alga Laurencia okamurai. Mar. Drugs, 14.","DOI":"10.3390\/md14120223"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1080\/14786419.2019.1597355","article-title":"One new xanthenone from the marine-derived fungus Aspergillus versicolor MF160003","volume":"34","author":"Song","year":"2020","journal-title":"Nat. Prod. Res."},{"key":"ref_37","first-page":"219","article-title":"Antioxidant xanthones and anthraquinones isolated from a marine-derived fungus Aspergillus versicolor","volume":"16","author":"Wu","year":"2018","journal-title":"Chin. J. Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1080\/14786419.2017.1289205","article-title":"New metabolites from the sponge-derived fungus Aspergillus sydowii J05B-7F-4","volume":"31","author":"Liu","year":"2017","journal-title":"Nat. Prod. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1080\/10286020.2016.1231673","article-title":"Aspergchromones A and B, two new polyketides from the marine sponge-associated fungus Aspergillus sp. SCSIO XWS03F03","volume":"19","author":"Wang","year":"2017","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/ja.2010.92","article-title":"New xanthoquinodin-like compounds, JBIR-97, -98 and -99, obtained from marine sponge-derived fungus Tritirachium sp. SpB081112MEf2","volume":"63","author":"Ueda","year":"2010","journal-title":"J. Antibiot."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1021\/acsmedchemlett.8b00368","article-title":"Marine natural products in medicinal chemistry","volume":"9","year":"2018","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1039\/B800164M","article-title":"Molecules derived from the extremes of life","volume":"26","author":"Wilson","year":"2009","journal-title":"Nat. Prod. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1080\/14786419.2015.1008472","article-title":"New compound with DNA Topo I inhibitory activity purified from Penicillium oxalicum HSY05","volume":"29","author":"Liu","year":"2015","journal-title":"Nat. Prod. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1080\/13543776.2019.1598972","article-title":"Marine natural products as source of new drugs: A patent review (2015\u20132018)","volume":"29","author":"Shinde","year":"2019","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.drudis.2008.07.004","article-title":"Natural products in drug discovery","volume":"13","author":"Harvey","year":"2008","journal-title":"Drug Discov. Today"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s12272-012-0309-2","article-title":"Tetrahydroanthraquinone and xanthone derivatives from the marine-derived fungus Trichoderma aureoviride PSU-F95","volume":"35","author":"Khamthong","year":"2012","journal-title":"Arch. Pharm. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s10600-012-0378-y","article-title":"A new sulfo-xanthone from the marine-derived fungus Penicillium sacculum","volume":"48","author":"Liu","year":"2012","journal-title":"Chem. Nat. Compd."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/mrc.3903","article-title":"Three new xanthone derivatives from an algicolous isolate of Aspergillus wentii","volume":"51","author":"Sun","year":"2013","journal-title":"Magn. Reson. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Liu, F., Lin, X., Zhou, X., Chen, M., Huang, X., Yang, B., and Tao, H. (2017). Xanthones and quinolones derivatives produced by the deep-sea-derived fungus Penicillium sp. SCSIO Ind16F01. Molecules, 22.","DOI":"10.3390\/molecules22121999"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Soares, J.X., Loureiro, D.R.P., Dias, A.L., Reis, S., Pinto, M.M.M., and Afonso, C.M.M. (2022). Bioactive marine xanthones: A review. Mar. Drugs, 20.","DOI":"10.3390\/md20010058"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/cmdc.201900735","article-title":"Yicathins B and C and analogues: Total synthesis, lipophilicity and biological activities","volume":"15","author":"Loureiro","year":"2020","journal-title":"ChemMedChem"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1021\/np500736b","article-title":"Pentacyclic antibiotics from a tidal mud flat-derived actinomycete","volume":"78","author":"Moon","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1007\/s12272-017-0890-5","article-title":"Anti-inflammatory effects of secondary metabolites isolated from the marine-derived fungal strain Penicillium sp. SF-5629","volume":"40","author":"Ngan","year":"2017","journal-title":"Arch. Pharm. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41429-018-0104-5","article-title":"Isolation of 4,4\u2032-bond secalonic acid D from the marine-derived fungus Penicillium oxalicum with inhibitory property against hepatocellular carcinoma","volume":"72","author":"Chen","year":"2019","journal-title":"J. Antibiot."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1002\/vjch.202000067","article-title":"Secondary metabolites from a marine sponge-associated fungus Xenomyrothecium sp. IMBC-FP2.11","volume":"58","author":"Quang","year":"2020","journal-title":"Vietnam J. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"796","DOI":"10.3109\/13880209.2010.548817","article-title":"Secalonic acid D as a novel DNA topoisomerase I inhibitor from marine lichen-derived fungus Gliocladium sp. T31","volume":"49","author":"Hong","year":"2011","journal-title":"Pharm. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1016\/j.bcp.2013.04.003","article-title":"Secalonic acid D reduced the percentage of side populations by down-regulating the expression of ABCG2","volume":"85","author":"Hu","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_58","first-page":"2624","article-title":"4,4\u2019-Bond secalonic acid D targets SP cells and inhibits metastasis in hepatocellular carcinoma","volume":"21","author":"Chen","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S0021-9673(01)86247-6","article-title":"The separation and detection of several mycotoxins by thin-layer chromatography","volume":"45","author":"Steyn","year":"1969","journal-title":"J. Chromatogr. A"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/BF02977469","article-title":"Secalonic acid D; A cytotoxic constituent from marine lichen-derived fungusGliocladium sp. T31","volume":"29","author":"Ren","year":"2006","journal-title":"Arch. Pharm. Res."},{"key":"ref_61","first-page":"900","article-title":"5-Di-(2\u2019-tetrahydropyranyl)secalonic acid D as a new antibiotic derivative with anticancer activity","volume":"71","author":"Iwaguchi","year":"1980","journal-title":"Gan"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s11418-020-01390-0","article-title":"Secalonic acid D as a selective cytotoxic substance on the cancer cells adapted to nutrient starvation","volume":"74","author":"Tang","year":"2020","journal-title":"J. Nat. Med."},{"key":"ref_63","first-page":"387","article-title":"The cell toxicity effect of secalonic acid D on GH3 cells and the related mechanisms","volume":"23","author":"Liao","year":"2010","journal-title":"Oncol. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1002\/anie.201311260","article-title":"Total syntheses of secalonic acids A and D","volume":"53","author":"Qin","year":"2014","journal-title":"Angew. Chemie Int. Ed."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1021\/ja110698n","article-title":"Vinylogous addition of siloxyfurans to benzopyryliums: A concise approach to the tetrahydroxanthone natural products","volume":"133","author":"Qin","year":"2011","journal-title":"J. Am. Chem. Soc."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/6\/347\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:18:27Z","timestamp":1760138307000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/6\/347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,25]]},"references-count":65,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["md20060347"],"URL":"https:\/\/doi.org\/10.3390\/md20060347","relation":{},"ISSN":["1660-3397"],"issn-type":[{"type":"electronic","value":"1660-3397"}],"subject":[],"published":{"date-parts":[[2022,5,25]]}}}