{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T23:49:05Z","timestamp":1783727345005,"version":"3.55.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82027803"],"award-info":[{"award-number":["82027803"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Nanosecond Pulsed Electric Field (nsPEF) is an intense electrical pulse technology with ultra-short duration (nanoseconds), capable of generating electric field intensities up to several kV\/cm. By inducing irreversible electroporation for tumor tissue ablation, nsPEF triggers apoptosis in cancer cells, stimulates anti-tumor immune responses, and enhances exogenous gene transfection. As a primarily non-thermal technique, it offers advantages such as minimal tissue damage, high targeting efficiency, short treatment duration, and compatibility with other therapies. Currently demonstrating broad application potential in cancer treatment. Urothelial Bladder Carcinoma (UBC), accounting for over 90% of bladder cancers, originates from the transitional epithelium of the bladder\u2019s urothelium and represents the most common malignant tumor in the urinary system. Cisplatin (CDDP), a key chemotherapeutic agent for UBC, is particularly effective for recurrent or advanced-stage patients. However, repeated use often leads to drug resistance. This study investigates the cytotoxic effects of nsPEF on UBC cells and its inhibitory mechanisms against drug-resistant UBC. Through sustained gradient concentration induction of CDDP, we successfully established drug-resistant cell lines T24\/CDDP and TCC\/CDDP. After treatment with nsPEF on parental cell lines (T24, TCC) and their drug-resistant variants (T24\/CDDP, TCC\/CDDP), all cells exhibited time-and dose-dependent sensitivity. Western blot analysis revealed that the basal expression of \u03b3-H2AX was significantly reduced in the drug-resistant cells (T24\/CDDP, TCC\/CDDP), while nsPEF treatment significantly upregulated its expression. In vivo experiments further demonstrated that nsPEF exhibited significant antitumor efficacy against tumor-bearing mice from T24\/CDDP. Overall, nsPEF effectively induces apoptosis in T24, TCC, and their drug-resistant variants, with particularly potent effects on drug-resistant UBC cells. This enhanced effect may be attributed to nsPEF-induced more severe DNA damage in drug-resistant cells, as manifested by elevated \u03b3-H2AX expression.. This study provides experimental evidence for applying nsPEF to overcome chemotherapy resistance in UBC.<\/jats:p>","DOI":"10.1371\/journal.pone.0346699","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T17:47:08Z","timestamp":1776361628000},"page":"e0346699","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Physicochemical Synergy Effect of Nanosecond Pulsed Electric Fields (nsPEF) and cisplatin on reversing chemoresistance of bladder cancer"],"prefix":"10.1371","volume":"21","author":[{"given":"Danjing","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4573-9111","authenticated-orcid":true,"given":"Xinhua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqiang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"issue":"3","key":"pone.0346699.ref001","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"6","key":"pone.0346699.ref002","first-page":"285","article-title":"Bladder cancer: a review of diagnosis and management","volume":"92","author":"MC Metts","year":"2000","journal-title":"J Natl Med Assoc"},{"issue":"1","key":"pone.0346699.ref003","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s11701-024-01850-9","article-title":"Systematic review comparing uretero-enteric stricture rates between open cystectomy with ileal conduit, robotic cystectomy with extra-corporeal ileal conduit and robotic cystectomy with intra corporeal ileal conduit formation","volume":"18","author":"DP McNicholas","year":"2024","journal-title":"J Robot Surg"},{"key":"pone.0346699.ref004","article-title":"Bladder cancer: immunotherapy and pelvic lymph node dissection","volume":"12","author":"Z Fan","year":"2024","journal-title":"Vaccines"},{"issue":"1","key":"pone.0346699.ref005","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00345-023-04744-x","article-title":"Radiotherapy in metastatic bladder cancer","volume":"42","author":"S Ashley","year":"2024","journal-title":"World J Urol"},{"issue":"1","key":"pone.0346699.ref006","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.eururo.2020.03.055","article-title":"European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines","volume":"79","author":"JA Witjes","year":"2021","journal-title":"Eur Urol"},{"issue":"2","key":"pone.0346699.ref007","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41568-020-00313-1","article-title":"Advances in bladder cancer biology and therapy","volume":"21","author":"L Tran","year":"2021","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"pone.0346699.ref008","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.eururo.2016.06.040","article-title":"Trends in Bladder Cancer Incidence and Mortality: Success or Disappointment?","volume":"71","author":"M Babjuk","year":"2017","journal-title":"Eur Urol"},{"issue":"21","key":"pone.0346699.ref009","doi-asserted-by":"crossref","first-page":"4602","DOI":"10.1200\/JCO.2005.07.757","article-title":"Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer","volume":"23","author":"H von der Maase","year":"2005","journal-title":"J Clin Oncol"},{"key":"pone.0346699.ref010","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s11864-009-0101-9","article-title":"Systemic therapy of advanced urothelial cancer","volume":"10","author":"U Vaishampayan","year":"2009","journal-title":"Curr Treat Options Oncol"},{"issue":"1","key":"pone.0346699.ref011","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.bbrc.2019.08.131","article-title":"DJ-1 overexpression confers the multidrug resistance phenotype to SGC7901\u00a0cells by upregulating P-gp and Bcl-2","volume":"519","author":"H-Y Liu","year":"2019","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"pone.0346699.ref012","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/med.21510","article-title":"Small-molecule inhibitors of multidrug resistance-associated protein 1 and related processes: A historic approach and recent advances","volume":"39","author":"SM Stefan","year":"2019","journal-title":"Med Res Rev"},{"issue":"12","key":"pone.0346699.ref013","doi-asserted-by":"crossref","first-page":"5108","DOI":"10.1021\/acs.jmedchem.7b01457","article-title":"Inhibit or Evade Multidrug Resistance P-Glycoprotein in Cancer Treatment","volume":"61","author":"D Waghray","year":"2018","journal-title":"J Med Chem"},{"key":"pone.0346699.ref014","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.pharmthera.2016.02.003","article-title":"DNA repair targeted therapy: The past or future of cancer treatment?","volume":"160","author":"NS Gavande","year":"2016","journal-title":"Pharmacol Ther"},{"issue":"1","key":"pone.0346699.ref015","doi-asserted-by":"crossref","first-page":"188577","DOI":"10.1016\/j.bbcan.2021.188577","article-title":"Pathogenesis and therapeutic strategy in platinum resistance lung cancer","volume":"1876","author":"P Lv","year":"2021","journal-title":"Biochim Biophys Acta Rev Cancer"},{"issue":"1","key":"pone.0346699.ref016","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/s41598-018-36527-5","article-title":"Mechanisms and immunogenicity of nsPEF-induced cell death in B16F10 melanoma tumors","volume":"9","author":"A Rossi","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0346699.ref017","first-page":"85","article-title":"Activation of Anti-tumor Immune Response by Ablation of HCC with Nanosecond Pulsed Electric Field","volume":"6","author":"X Xu","year":"2018","journal-title":"J Clin Transl Hepatol"},{"issue":"8","key":"pone.0346699.ref018","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1002\/ijc.27860","article-title":"Nanoelectroablation of human pancreatic carcinoma in a murine xenograft model without recurrence","volume":"132","author":"R Nuccitelli","year":"2013","journal-title":"Int J Cancer"},{"issue":"4","key":"pone.0346699.ref019","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1046\/j.1365-201X.2003.01093.x","article-title":"Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research","volume":"177","author":"J Gehl","year":"2003","journal-title":"Acta Physiol Scand"},{"issue":"1","key":"pone.0346699.ref020","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3390\/cancers12010179","article-title":"Evaluation of Calcium Electroporation for the Treatment of Cutaneous Metastases: A Double Blinded Randomised Controlled Phase II Trial","volume":"12","author":"D \u00c1goston","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"4","key":"pone.0346699.ref021","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1053\/j.tvir.2013.08.002","article-title":"Tumor ablation: common modalities and general practices","volume":"16","author":"EM Knavel","year":"2013","journal-title":"Tech Vasc Interv Radiol"},{"key":"pone.0346699.ref022","doi-asserted-by":"crossref","DOI":"10.3390\/molecules25225406","article-title":"In Vitro Study of Calcium Microsecond Electroporation of Prostate Adenocarcinoma Cells","volume":"25","author":"A Kie\u0142bik","year":"2020","journal-title":"Molecules"},{"issue":"1","key":"pone.0346699.ref023","doi-asserted-by":"crossref","first-page":"15835","DOI":"10.1038\/s41598-021-95180-7","article-title":"Effects of high-frequency nanosecond pulses on prostate cancer cells","volume":"11","author":"A Kie\u0142bik","year":"2021","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0346699.ref024","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.bbrc.2019.08.133","article-title":"Excitation and electroporation by MHz bursts of nanosecond stimuli","volume":"518","author":"AG Pakhomov","year":"2019","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0346699.ref025","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s40425-017-0234-5","article-title":"Nano-Pulse Stimulation is a physical modality that can trigger immunogenic tumor cell death","volume":"5","author":"R Nuccitelli","year":"2017","journal-title":"J Immunother Cancer"},{"key":"pone.0346699.ref026","doi-asserted-by":"crossref","first-page":"108289","DOI":"10.1016\/j.bioelechem.2022.108289","article-title":"Urine protects urothelial cells against killing with nanosecond pulsed electric fields","volume":"149","author":"A Kie\u0142bik","year":"2023","journal-title":"Bioelectrochemistry"},{"issue":"5","key":"pone.0346699.ref027","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1093\/nar\/gkv061","article-title":"Multiple facets of histone variant H2AX: a DNA double-strand-break marker with several biological functions","volume":"43","author":"V Turinetto","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pone.0346699.ref028","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.1038\/s41467-020-16926-x","article-title":"DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner","volume":"11","author":"PL Collins","year":"2020","journal-title":"Nat Commun"},{"issue":"2022","key":"pone.0346699.ref029","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1097\/CM9.0000000000002108","article-title":"Cancer statistics in China and United States, 2022: profiles, trends, and determinants","volume":"135","author":"C Xia","year":"2022","journal-title":"Chin Med J (Engl)"},{"issue":"12","key":"pone.0346699.ref030","doi-asserted-by":"crossref","first-page":"6278","DOI":"10.1172\/JCI139597","article-title":"Urine DNA methylation assay enables early detection and recurrence monitoring for bladder cancer","volume":"130","author":"X Chen","year":"2020","journal-title":"J Clin Invest"},{"issue":"17","key":"pone.0346699.ref031","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1200\/JCO.2000.18.17.3068","article-title":"Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study","volume":"18","author":"H von der Maase","year":"2000","journal-title":"J Clin Oncol"},{"issue":"47","key":"pone.0346699.ref032","doi-asserted-by":"crossref","first-page":"7265","DOI":"10.1038\/sj.onc.1206933","article-title":"Cisplatin: mode of cytotoxic action and molecular basis of resistance","volume":"22","author":"ZH Siddik","year":"2003","journal-title":"Oncogene"},{"issue":"15","key":"pone.0346699.ref033","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1038\/onc.2011.384","article-title":"Molecular mechanisms of cisplatin resistance","volume":"31","author":"L Galluzzi","year":"2012","journal-title":"Oncogene"},{"issue":"4","key":"pone.0346699.ref034","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1007\/s10495-010-0572-y","article-title":"An apoptosis targeted stimulus with nanosecond pulsed electric fields (nsPEFs) in E4 squamous cell carcinoma","volume":"16","author":"W Ren","year":"2011","journal-title":"Apoptosis"},{"issue":"1","key":"pone.0346699.ref035","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.abb.2012.08.004","article-title":"Oxidative effects of nanosecond pulsed electric field exposure in cells and cell-free media","volume":"527","author":"ON Pakhomova","year":"2012","journal-title":"Arch Biochem Biophys"},{"issue":"4","key":"pone.0346699.ref036","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.bbrc.2015.10.072","article-title":"Electrical breakdown in tissue electroporation","volume":"467","author":"E Guenther","year":"2015","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"pone.0346699.ref037","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00232-010-9277-y","article-title":"Life cycle of an electropore: field-dependent and field-independent steps in pore creation and annihilation","volume":"236","author":"ZA Levine","year":"2010","journal-title":"J Membr Biol"},{"issue":"7","key":"pone.0346699.ref038","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3390\/cancers10070217","article-title":"Nano-Pulse Stimulation for the Treatment of Pancreatic Cancer and the Changes in Immune Profile","volume":"10","author":"S Guo","year":"2018","journal-title":"Cancers (Basel)"},{"issue":"2","key":"pone.0346699.ref039","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1002\/ijc.24345","article-title":"A new pulsed electric field therapy for melanoma disrupts the tumor\u2019s blood supply and causes complete remission without recurrence","volume":"125","author":"R Nuccitelli","year":"2009","journal-title":"Int J Cancer"},{"issue":"2","key":"pone.0346699.ref040","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/exd.12303","article-title":"First-in-human trial of nanoelectroablation therapy for basal cell carcinoma: proof of method","volume":"23","author":"R Nuccitelli","year":"2014","journal-title":"Exp Dermatol"},{"issue":"2","key":"pone.0346699.ref041","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bbrc.2009.05.035","article-title":"Lipid nanopores can form a stable, ion channel-like conduction pathway in cell membrane","volume":"385","author":"AG Pakhomov","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0346699.ref042","doi-asserted-by":"crossref","first-page":"107876","DOI":"10.1016\/j.bioelechem.2021.107876","article-title":"Interference targeting of bipolar nanosecond electric pulses for spatially focused electroporation, electrostimulation, and tissue ablation","volume":"141","author":"AG Pakhomov","year":"2021","journal-title":"Bioelectrochemistry"},{"issue":"2","key":"pone.0346699.ref043","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.bbrc.2006.02.181","article-title":"Nanosecond pulsed electric fields cause melanomas to self-destruct","volume":"343","author":"R Nuccitelli","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"issue":"5","key":"pone.0346699.ref044","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/bem.21696","article-title":"Cell permeabilization and inhibition of voltage-gated Ca(2+) and Na(+) channel currents by nanosecond pulsed electric field","volume":"33","author":"V Nesin","year":"2012","journal-title":"Bioelectromagnetics"},{"issue":"2","key":"pone.0346699.ref045","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S0014-4827(03)00224-6","article-title":"Electrotransfection of anchorage-dependent mammalian cells","volume":"288","author":"KJ M\u00fcller","year":"2003","journal-title":"Exp Cell Res"},{"issue":"1","key":"pone.0346699.ref046","doi-asserted-by":"crossref","first-page":"23745","DOI":"10.1038\/s41598-021-03342-4","article-title":"The role of reactive oxygen species in the immunity induced by nano-pulse stimulation","volume":"11","author":"S Guo","year":"2021","journal-title":"Sci Rep"},{"issue":"8","key":"pone.0346699.ref047","article-title":"Synergistic effects of nanosecond pulsed electric fields combined with low concentration of gemcitabine on human oral squamous cell carcinoma in vitro","volume":"7","author":"J Wang","year":"2012","journal-title":"PLoS One"},{"key":"pone.0346699.ref048","doi-asserted-by":"crossref","first-page":"1533033818802305","DOI":"10.1177\/1533033818802305","article-title":"Moderate Heat Application Enhances the Efficacy of Nanosecond Pulse Stimulation for the Treatment of Squamous Cell Carcinoma","volume":"17","author":"CM Edelblute","year":"2018","journal-title":"Technol Cancer Res Treat"},{"issue":"12","key":"pone.0346699.ref049","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1109\/TBME.2019.2900720","article-title":"Enhanced antitumor efficacy achieved through combination of nsPEFs and low-dosage paclitaxel","volume":"66","author":"Y Zhang","year":"2019","journal-title":"IEEE Transactions on Biomedical Engineering"},{"issue":"9","key":"pone.0346699.ref050","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.7150\/ijms.34876","article-title":"Dual-function of Baicalin in nsPEFs-treated Hepatocytes and Hepatocellular Carcinoma cells for Different Death Pathway and Mitochondrial Response","volume":"16","author":"Y Wang","year":"2019","journal-title":"Int J Med Sci"},{"issue":"1","key":"pone.0346699.ref051","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1080\/02656736.2022.2093994","article-title":"Neutrophil membrane-coated nanoparticles for enhanced nanosecond pulsed electric field treatment of pancreatic cancer","volume":"39","author":"J Zhao","year":"2022","journal-title":"Int J Hyperthermia"},{"issue":"1","key":"pone.0346699.ref052","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s13046-019-1280-2","article-title":"A novel method to establish glucocorticoid resistant acute lymphoblastic leukemia cell lines","volume":"38","author":"L Gu","year":"2019","journal-title":"J Exp Clin Cancer Res"},{"issue":"11","key":"pone.0346699.ref053","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ejcsup.2006.08.002","article-title":"Electrochemotherapy \u2013 An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study","volume":"4","author":"M Marty","year":"2006","journal-title":"European Journal of Cancer Supplements"},{"issue":"15","key":"pone.0346699.ref054","first-page":"3450","article-title":"Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice","volume":"55","author":"G Sersa","year":"1995","journal-title":"Cancer Res"},{"issue":"3","key":"pone.0346699.ref055","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.juro.2014.09.039","article-title":"In vitro and in vivo experiments on electrochemotherapy for bladder cancer","volume":"193","author":"JL V\u00e1squez","year":"2015","journal-title":"J Urol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0346699","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T17:47:17Z","timestamp":1776361637000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0346699"}},"subtitle":[],"editor":[{"given":"Olga","family":"Zeni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":55,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0346699","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]}}}