{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:22:49Z","timestamp":1789474969962,"version":"build-2803163510"},"reference-count":42,"publisher":"American Chemical Society (ACS)","issue":"5","license":[{"start":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T00:00:00Z","timestamp":1585785600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T00:00:00Z","timestamp":1585785600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T00:00:00Z","timestamp":1585785600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100004586","name":"Funda??o Carlos Chagas Filho de Amparo ? Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The polyene amphotericin B (AMB) exerts a powerful and broad antifungal activity. AMB acts by (i) binding to ergosterol, leading to pore formation at the fungal plasma membrane with subsequent ion leakage, and (ii) inducing the intracellular accumulation of reactive oxygen species (ROS). Herein, we have deciphered the AMB resistance mechanisms in clinical isolates of Candida haemulonii complex (C. haemulonii, C. duobushaemulonii, C. haemulonii var. vulnera) in comparison to other clinically relevant non-albicans Candida species. Membrane gas chromatography\u2013mass spectrometry analysis revealed that the vast majority of sterols were composed of ergosterol pathway intermediates, evidencing the absence of AMB target. Supporting this data, C. haemulonii species complex demonstrated poor membrane permeability after AMB treatment. Regarding the oxidative burst, AMB induced the formation of ROS in all species tested; however, this phenomenon was slightly seen in C. haemulonii complex isolates. Our results indicated that these isolates displayed altered respiratory status, as revealed by their poor growth in nonfermented carbon sources, low consumption of oxygen, and derisive mitochondrial membrane potential. The use of specific inhibitors of mitochondrial respiratory chain (complex I\u2013IV) revealed no effects on the yeast growth, highlighting the metabolic shift to fermentative pathway in C. haemulonii strains. Also, C. haemulonii complex proved to be highly resistant to oxidative burst agents, which can be correlated with a high activity of antioxidant enzymes. Our data demonstrated primary evidence suggesting that ergosterol content, mitochondrial function, and fungal redox homeostasis are involved in AMB fungicidal effects and might explain the resistance presented in this multidrug-resistant, emergent, and opportunistic fungal complex.<\/jats:p>","DOI":"10.1021\/acsinfecdis.0c00117","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T13:35:13Z","timestamp":1585834513000},"page":"1273-1282","source":"Crossref","is-referenced-by-count":43,"title":["Unmasking the Amphotericin B Resistance Mechanisms\nin\n                    <i>Candida haemulonii<\/i>\n                    Species Complex"],"prefix":"10.1021","volume":"6","author":[{"given":"Laura\nN.","family":"Silva","sequence":"first","affiliation":[{"name":"Instituto de Microbiologia Paulo de Go\u0301es, Universidade Federal do Rio de Janeiro , , Bloco E - Subsolo sala 05 , ,","place":["Rio de Janeiro, Brazil, 21941-902"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone S. C.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Instituto de Microbiologia Paulo de Go\u0301es, Universidade Federal do Rio de Janeiro , , Bloco E - Subsolo sala 05 , ,","place":["Rio de Janeiro, Brazil, 21941-902"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas B.","family":"Magalha\u0303es","sequence":"additional","affiliation":[{"name":"Instituto de Microbiologia Paulo de Go\u0301es, Universidade Federal do Rio de Janeiro , , Bloco E - Subsolo sala 05 , ,","place":["Rio de Janeiro, Brazil, 21941-902"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valter V.","family":"Andrade Neto","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz , , Av. Brasil, 4365 - Fundac\u0327a\u0303o Oswaldo Cruz , ,","place":["Rio de Janeiro, Brazil, 21040-360"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo C.","family":"Torres-Santos","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz , , Av. Brasil, 4365 - Fundac\u0327a\u0303o Oswaldo Cruz , ,","place":["Rio de Janeiro, Brazil, 21040-360"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana D. C.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro , , Av. Athos da Silveira Ramos, 149 - Bloco A, 5\u00b0 Andar , ,","place":["Rio de Janeiro, Brazil, 21941-909"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos D.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro , , Av. Athos da Silveira Ramos, 149 - Bloco A, 5\u00b0 Andar , ,","place":["Rio de Janeiro, Brazil, 21941-909"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta H.","family":"Branquinha","sequence":"additional","affiliation":[{"name":"Instituto de Microbiologia Paulo de Go\u0301es, Universidade Federal do Rio de Janeiro , , Bloco E - Subsolo sala 05 , ,","place":["Rio de Janeiro, Brazil, 21941-902"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-8592","authenticated-orcid":true,"given":"Andre\u0301 L. S.","family":"Santos","sequence":"additional","affiliation":[{"name":"Instituto de Microbiologia Paulo de Go\u0301es, Universidade Federal do Rio de Janeiro , , Bloco E - Subsolo sala 05 , ,","place":["Rio de Janeiro, Brazil, 21941-902"]},{"name":"Universidade Federal do Rio de Janeiro , , Av. Athos da Silveira Ramos, 149 - Bloco A, 5\u00b0 Andar , ,","place":["Rio de Janeiro, Brazil, 21941-909"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,4,2]]},"reference":[{"issue":"5","key":"2026081806115936800_cit1","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/nchembio.1496","article-title":"Amphotericin\nforms an extramembranous\nand fungicidal sterol sponge","volume":"10","author":"Anderson","year":"2014","journal-title":"Nat. Chem. Biol."},{"issue":"17","key":"2026081806115936800_cit2","doi-asserted-by":"publisher","first-page":"6733","DOI":"10.1073\/pnas.1015023108","article-title":"Synthesis-enabled\nfunctional group deletions reveal key underpinnings of amphotericin\nB ion channel and antifungal activities","volume":"108","author":"Palacios","year":"2011","journal-title":"Proc.\nNatl. Acad. Sci. U. S. A."},{"issue":"1","key":"2026081806115936800_cit3","doi-asserted-by":"publisher","first-page":"17029","DOI":"10.1038\/s41598-019-53517-3","article-title":"Modes of\nthe antibiotic activity of amphotericin B\nagainst Candida albicans","volume":"9","author":"Grela","year":"2019","journal-title":"Sci.\nRep."},{"issue":"45","key":"2026081806115936800_cit4","doi-asserted-by":"publisher","first-page":"13804","DOI":"10.1021\/ja075739o","article-title":"A post-PKS\noxidation of the Amphotericin\nB skeleton predicted to be critical for channel formation is not required\nfor potent antifungal activity","volume":"129","author":"Palacios","year":"2007","journal-title":"J. Am. Chem.\nSoc."},{"issue":"7","key":"2026081806115936800_cit5","doi-asserted-by":"publisher","first-page":"2234","DOI":"10.1073\/pnas.1117280109","article-title":"Amphotericin primarily kills yeast\nby simply binding ergosterol","volume":"109","author":"Gray","year":"2012","journal-title":"Proc. Natl. Acad.\nSci. U. S. A."},{"issue":"8","key":"2026081806115936800_cit6","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/j.bbagen.2011.04.012","article-title":"Amphotericin\nB induces trehalose synthesis and simultaneously activates an antioxidant\nenzymatic response in Candida albicans","volume":"1810","author":"Gonzalez-Parraga","year":"2011","journal-title":"Biochim. Biophys. Acta, Gen. Subj."},{"issue":"4\u20135","key":"2026081806115936800_cit7","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.ijmm.2017.03.005","article-title":"ROS formation\nis a differential contributory factor\nto the fungicidal action of Amphotericin B and Micafungin in Candida albicans","volume":"307","author":"Guirao-Abad","year":"2017","journal-title":"Int. J. Med. Microbiol."},{"issue":"11","key":"2026081806115936800_cit8","doi-asserted-by":"publisher","first-page":"6627","DOI":"10.1128\/AAC.03570-14","article-title":"The production of reactive\noxygen species is a universal action mechanism of Amphotericin B against\npathogenic yeasts and contributes to the fungicidal effect of this\ndrug","volume":"58","author":"Mesa-Arango","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"issue":"1","key":"2026081806115936800_cit9","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1093\/infdis\/154.1.76","article-title":"Amphotericin B-induced oxidative\ndamage and killing of Candida albicans","volume":"154","author":"Sokol-Anderson","year":"1986","journal-title":"J. Infect. Dis."},{"issue":"5","key":"2026081806115936800_cit10","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.micinf.2011.01.015","article-title":"Amphotericin B mediates killing in Cryptococcus\nneoformans through the induction of a strong\noxidative burst","volume":"13","author":"Sangalli-Leite","year":"2011","journal-title":"Microbes Infect."},{"issue":"2","key":"2026081806115936800_cit11","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.celrep.2012.12.021","article-title":"Fungicidal\ndrugs induce a common\noxidative-damage cellular death pathway","volume":"3","author":"Belenky","year":"2013","journal-title":"Cell\nRep."},{"issue":"18","key":"2026081806115936800_cit12","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1089\/ars.2014.6220","article-title":"Amphotericin\nB resistance in Aspergillus terreus is overpowered\nby coapplication of pro-oxidants","volume":"23","author":"Blatzer","year":"2015","journal-title":"Antioxid.\nRedox Signaling"},{"issue":"11","key":"2026081806115936800_cit13","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00978-17","article-title":"Induction of\nmitochondrial reactive oxygen species production by itraconazole,\nterbinafine, and Amphotericin B as a mode of action against Aspergillus fumigatus","volume":"61","author":"Shekhova","year":"2017","journal-title":"Antimicrob.\nAgents Chemother."},{"issue":"10","key":"2026081806115936800_cit14","doi-asserted-by":"publisher","first-page":"e00670","DOI":"10.1128\/AAC.00670-17","article-title":"Oxidative stress response tips the\nbalance in Aspergillus terreus Amphotericin B resistance","volume":"61","author":"Jukic","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"issue":"16","key":"2026081806115936800_cit15","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1002\/(SICI)1097-0061(199812)14:16&lt;1511::AID-YEA356&gt;3.0.CO;2-S","article-title":"Oxidative\nstress responses of the yeast Saccharomyces cerevisiae","volume":"14","author":"Jamieson","year":"1998","journal-title":"Yeast"},{"issue":"4","key":"2026081806115936800_cit16","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s00203-003-0530-y","article-title":"Disruption of mitochondrial\nfunction in Candida\nalbicans leads to reduced cellular ergosterol levels and\nelevated growth in the presence of amphotericin B","volume":"179","author":"Geraghty","year":"2003","journal-title":"Arch. Microbiol."},{"issue":"28","key":"2026081806115936800_cit17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2174\/1568026619666191025152412","article-title":"New\nand promising chemotherapeutics for emerging infections\ninvolving drug-resistant non-albicans Candida species","volume":"19","author":"Silva","year":"2019","journal-title":"Curr. Top. Med. Chem."},{"issue":"1","key":"2026081806115936800_cit18","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/jac\/dku321","article-title":"Candida haemulonii complex: species\nidentification and antifungal susceptibility profiles of clinical\nisolates from Brazil","volume":"70","author":"Ramos","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"issue":"7","key":"2026081806115936800_cit19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/femsyr\/foy082","article-title":"Virulence of Candida haemulonii complex\nin Galleria mellonella and efficacy of\nclassical antifungal drugs: a comparative study with other clinically\nrelevant non-albicans Candida species","volume":"18","author":"Silva","year":"2018","journal-title":"FEMS Yeast Res."},{"issue":"1","key":"2026081806115936800_cit20","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S0005-2728(03)00110-5","article-title":"Rhodamine 123 as a\nprobe of mitochondrial membrane potential: evaluation of proton flux\nthrough F0 during ATP synthesis","volume":"1606","author":"Baracca","year":"2003","journal-title":"Biochim. Biophys.\nActa, Bioenerg."},{"issue":"2","key":"2026081806115936800_cit21","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/S0005-2728(00)00251-6","article-title":"Fungal respiration:\na fusion of standard\nand alternative components","volume":"1504","author":"Joseph-Horne","year":"2001","journal-title":"Biochim. Biophys.\nActa, Bioenerg."},{"issue":"4","key":"2026081806115936800_cit22","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1093\/jac\/dkp273","article-title":"The alternative oxidase of Candida albicans causes\nreduced fluconazole susceptibility","volume":"64","author":"Yan","year":"2009","journal-title":"J. Antimicrob.\nChemother."},{"issue":"22","key":"2026081806115936800_cit23","doi-asserted-by":"publisher","first-page":"13399","DOI":"10.1074\/jbc.270.22.13399","article-title":"Superoxide radical\nand iron modulate aconitase activity in mammalian cells","volume":"270","author":"Gardner","year":"1995","journal-title":"J. Biol. Chem."},{"issue":"10","key":"2026081806115936800_cit24","doi-asserted-by":"publisher","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in\nredox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr.\nBiol."},{"issue":"10","key":"2026081806115936800_cit25","doi-asserted-by":"publisher","first-page":"4769","DOI":"10.1128\/AAC.00477-13","article-title":"Candida\ntropicalis antifungal cross-resistance is related to different\nazole target (Erg11p) modifications","volume":"57","author":"Forastiero","year":"2013","journal-title":"Antimicrob.\nAgents Chemother."},{"issue":"12","key":"2026081806115936800_cit26","doi-asserted-by":"publisher","first-page":"2708","DOI":"10.1128\/AAC.39.12.2708","article-title":"Deletion of the Candida glabrata ERG3\nand ERG11 genes: effect on cell viability, cell growth, sterol\ncomposition, and antifungal susceptibility","volume":"39","author":"Geber","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026081806115936800_cit27","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/978-1-59745-180-2_25","article-title":"Amphotericin B:\npolyene resistance mechanisms","volume-title":"Antimicrobial\nDrug Resistance: Mechanisms of Drug Resistance","author":"O\u2019Shaughnessy","year":"2009"},{"key":"2026081806115936800_cit28","doi-asserted-by":"publisher","first-page":"286","DOI":"10.3389\/fmicb.2012.00286","article-title":"It only takes one to do many jobs:\nAmphotericin B as antifungal and immunomodulatory drug","volume":"3","author":"Mesa-Arango","year":"2012","journal-title":"Front. Microbiol."},{"issue":"8","key":"2026081806115936800_cit29","doi-asserted-by":"publisher","first-page":"2404","DOI":"10.1128\/AAC.47.8.2404-2412.2003","article-title":"Candida\nalbicans mutations in the ergosterol biosynthetic pathway\nand resistance to several antifungal agents","volume":"47","author":"Sanglard","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"issue":"8","key":"2026081806115936800_cit30","doi-asserted-by":"publisher","first-page":"4223","DOI":"10.1128\/AAC.06253-11","article-title":"Facultative sterol\nuptake in an ergosterol-deficient clinical isolate of Candida\nglabrata harboring a missense mutation in ERG11 and exhibiting\ncross-resistance to azoles and amphotericin B","volume":"56","author":"Hull","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"issue":"2","key":"2026081806115936800_cit31","doi-asserted-by":"publisher","first-page":"e01900-18","DOI":"10.1128\/AAC.01900-18","article-title":"ERG6 and ERG2\nare major\ntargets conferring reduced susceptibility to Amphotericin B in clinical Candida glabrata isolates in Kuwait","volume":"63","author":"Ahmad","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026081806115936800_cit32","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1146\/annurev.mi.49.100195.000523","article-title":"Physiological implications of sterol biosynthesis in\nyeast","volume":"49","author":"Parks","year":"1995","journal-title":"Annu. Rev. Microbiol."},{"issue":"3","key":"2026081806115936800_cit33","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1080\/02681219680000381","article-title":"Amphotericin B resistant\nisolates of Cryptococcus neoformans without alteration\nin sterol biosynthesis","volume":"34","author":"Joseph-Horne","year":"1996","journal-title":"Med. Mycol."},{"issue":"3","key":"2026081806115936800_cit34","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/0031-9422(96)00037-4","article-title":"Nonsterol related resistance\nin Ustilago maydis to the polyene antifungals, amphotericin\nB and nystatin","volume":"42","author":"Joseph-Horne","year":"1996","journal-title":"Phytochemistry"},{"issue":"8","key":"2026081806115936800_cit35","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1139\/o59-099","article-title":"A rapid method of\ntotal lipid extraction and purification","volume":"37","author":"Bligh","year":"1959","journal-title":"Can.\nJ. Biochem. Physiol."},{"issue":"11","key":"2026081806115936800_cit36","doi-asserted-by":"publisher","first-page":"6844","DOI":"10.1128\/AAC.01545-16","article-title":"Antileishmanial activity of Ezetimibe:\ninhibition of sterol biosynthesis, in vitro synergy with azoles, and\nefficacy in experimental cutaneous leishmaniasis","volume":"60","author":"Andrade-Neto","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"issue":"6","key":"2026081806115936800_cit37","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1002\/jcb.25803","article-title":"Oxidative\nstress and amyloid toxicity:\ninsights from yeast","volume":"118","author":"Franc\u0327a","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"2026081806115936800_cit38","unstructured":"CLSI\n           (2008) Reference Method for Broth Dilution\nAntifungal Susceptibility Testing of Yeasts: Third Informational Supplement\nM27-S3, Clinical and Laboratory Standards\nInstitute."},{"issue":"5","key":"2026081806115936800_cit39","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1128\/EC.00011-08","article-title":"High resistance\nto oxidative stress in the fungal pathogen Candida glabrata is mediated\nby a single catalase, Cta1p, and is controlled by the transcription\nfactors Yap1p, Skn7p, Msn2p, and Msn4p","volume":"7","author":"Cuellar-Cruz","year":"2008","journal-title":"Eukaryotic\nCell"},{"issue":"1","key":"2026081806115936800_cit40","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement\nwith the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"2026081806115936800_cit41","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","article-title":"Catalase in vitro","volume":"105","author":"Aebi","year":"1984","journal-title":"Methods Enzymol."},{"key":"2026081806115936800_cit42","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1186\/s12906-017-1773-5","article-title":"Membrane of Candida albicans as a\ntarget of berberine","volume":"17","author":"Zoric\u0301","year":"2017","journal-title":"BMC Complementary Altern.\nMed."}],"container-title":["ACS Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsinfecdis.0c00117","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/6\/5\/1273\/12720968\/id0c00117.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/6\/5\/1273\/12720968\/id0c00117.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T10:55:08Z","timestamp":1787050508000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article\/6\/5\/1273\/1292446\/Unmasking-the-Amphotericin-B-Resistance-Mechanisms"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,2]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,4,2]]},"published-print":{"date-parts":[[2020,5,8]]}},"URL":"https:\/\/doi.org\/10.1021\/acsinfecdis.0c00117","relation":{},"ISSN":["2373-8227"],"issn-type":[{"value":"2373-8227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,2]]}}}