{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T08:14:04Z","timestamp":1771661644701,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"INP 026\/2022\u2014program E022"},{"name":"SNI-CONAHCYT"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurotoxicity is a major obstacle in the effectiveness of Cisplatin in cancer chemotherapy. In this process, oxidative stress and inflammation are considered to be the main mechanisms involved in brain and lung toxicity. The aim of the present work was to study the influence of the amount of protein on some oxidative parameters in the brain and lungs of rats treated with Cisplatin (CP) and N-Acetylcysteine (NAC) as neuroprotectors. Four groups of Wistar rats, each containing six animals, were fed with a protein diet at 7% for 15 days. Thereafter, the groups were given either a unique dose of CP\u00ae 5 mg\/kg or NAC\u00ae 5 mg\/kg as follows: group 1 (control), NaCl 0.9% vehicle; group 2, CP; group 3, NAC; and group 4, NAC + CP. The animals were sacrificed immediately after the treatments. Blood samples were collected upon sacrifice and used to measure blood triglycerides and glucose. The brain and lungs of each animal were obtained and used to assay lipid peroxidation (TBARS), glutathione (GSH), serotonin metabolite (5-HIAA), catalase, and the activity of Ca+2, and Mg+2 ATPase using validated methods. TBARS, H2O2, and GSH were found to be significantly decreased in the cortex and cerebellum\/medulla oblongata of the groups treated with CP and NAC. The total ATPase showed a significant increase in the lung and cerebellum\/medulla oblongata, while 5-HIAA showed the same tendency in the cortex of the same group of animals. The increase in 5-HIAA and ATPase during NAC and CP administration resulted in brain protection. This effect could be even more powerful when membrane fluidity is increased, thus proving the efficacy of combined NAC and CP drug therapy, which appears to be a promising strategy for future chemotherapy in malnourished patients.<\/jats:p>","DOI":"10.3390\/ijms25116239","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T11:50:09Z","timestamp":1717588209000},"page":"6239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["N-Acetylcysteine Attenuates Cisplatin Toxicity in the Cerebrum and Lung of Young Rats with Artificially Induced Protein Deficiency"],"prefix":"10.3390","volume":"25","author":[{"given":"David","family":"Calder\u00f3n Guzm\u00e1n","sequence":"first","affiliation":[{"name":"Laboratory of Neurosciences, Instituto Nacional de Pediatria (INP), Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0041-3190","authenticated-orcid":false,"given":"Norma","family":"Osnaya Brizuela","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosciences, Instituto Nacional de Pediatria (INP), Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maribel","family":"Ort\u00edz Herrera","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Bacteriology, Instituto Nacional de Pediatria INP, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armando","family":"Valenzuela Peraza","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosciences, Instituto Nacional de Pediatria (INP), Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norma","family":"Labra Ru\u00edz","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosciences, Instituto Nacional de Pediatria (INP), Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1405-1728","authenticated-orcid":false,"given":"Hugo","family":"Ju\u00e1rez Olgu\u00edn","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Instituto Nacional de Pediatr\u00eda, Avenida Im\u00e1n N\u00b0 1, 3rd piso Colonia Cuicuilco, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3891-8055","authenticated-orcid":false,"given":"Daniel","family":"Santamaria del Angel","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosciences, Instituto Nacional de Pediatria (INP), Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerardo","family":"Barrag\u00e1n Mej\u00eda","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Bacteriology, Instituto Nacional de Pediatria INP, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"146","DOI":"10.15430\/JCP.2019.24.3.146","article-title":"Effect of the interaction between selenium and zinc on DNA repair in association with cancer prevention","volume":"24","author":"Yildiz","year":"2019","journal-title":"J. Cancer Prev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"iii1","DOI":"10.1093\/neuonc\/noab200","article-title":"CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2014\u20132018","volume":"23","author":"Ostrom","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1007\/BF00963999","article-title":"A neurochemical study of developmental impairment of the brain caused by the administration of cytosine arabinoside during the fetal or neonatal period of rats","volume":"8","author":"Matsutani","year":"1983","journal-title":"Neurochem. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41388-019-1006-0","article-title":"Neurotransmitters: Emerging targets in cancer","volume":"39","author":"Jiang","year":"2020","journal-title":"Oncogene"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Aljanabi, R., Alsous, L., Sabbah, D.A., Gul, H.I., Gul, M., and Bardaweel, S.K. (2021). Monoamine Oxidase (MAO) as a Potential Target for Anticancer Drug Design and Development. Molecules, 26.","DOI":"10.3390\/molecules26196019"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1023\/A:1010624823158","article-title":"Role of ceramide during cisplatin-induced apoptosis in C6 glioma cells","volume":"52","author":"Noda","year":"2002","journal-title":"J. Neurooncol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Afsar, T., Razak, S., and Almajwal, A. (2022). Reversal of cisplatin triggered neurotoxicity by Acacia hydaspica ethyl acetate fraction via regulating brain acetylcholinesterase activity, DNA damage, and pro-inflammatory cytokines in the rodent model. BMC Complement. Med. Ther., 22.","DOI":"10.1186\/s12906-022-03657-3"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"124","DOI":"10.31768\/2312-8852.2017.39(2):124-130","article-title":"Determination of cisplatin in human blood plasma and urine using liquid chromatography-mass spectrometry for oncological patients with a variety of fatty tissue mass for prediction of toxicity","volume":"39","author":"Hasnere","year":"2017","journal-title":"Exp. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1021\/acs.chemrev.8b00493","article-title":"Intracellular Catalysis with Selected Metal Complexes and Metallic Nanoparticles: Advances toward the Development of Catalytic Metallodrugs","volume":"119","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tamamouna, V., Pavlou, E., Neophytou, C.M., Papageorgis, P., and Costeas, P. (2022). Regulation of metastatic tumor dormancy and emerging opportunities for therapeutic intervention. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232213931"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ejphar.2014.07.025","article-title":"Cisplatin in cancer therapy: Molecular mechanisms of action","volume":"5","author":"Dasari","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cocetta, V., Ragazzi, E., and Montopoli, M. (2019). Mitochondrial Involvement in Cisplatin Resistance. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143384"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1007\/s11255-019-02113-5","article-title":"Intervention of mitochondrial activity attenuates cisplatin-induced acute kidney injury","volume":"51","author":"Yang","year":"2019","journal-title":"Int. Urol. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.msec.2018.11.039","article-title":"Enhanced treatment effect of nanoparticles containing cisplatin and a GSH-reactive probe compound","volume":"96","author":"Zhu","year":"2019","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_15","first-page":"110","article-title":"Metabolic syndrome in cancer patients during chemotherapy treatment [S\u00edndrome metab\u00f3lico en pacientes con c\u00e1ncer durante el tratamiento con quimioterapia]","volume":"65","year":"2008","journal-title":"Bol. Med. Hosp. Infant Mex."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.cmet.2020.01.005","article-title":"Glucose Starvation Blocks Translation at Multiple Levels","volume":"31","author":"Zhang","year":"2020","journal-title":"Cell Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12987-017-0075-0","article-title":"Dose escalation study of intravenous and intra-arterial N-acetylcysteine for the prevention of oto- and nephrotoxicity of cisplatin with a contrast-induced nephropathy model in patients with renal insufficiency","volume":"14","author":"Heltai","year":"2017","journal-title":"Fluids Barriers CNS"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1002\/(SICI)1097-0215(19980209)75:4<578::AID-IJC14>3.0.CO;2-5","article-title":"Enhancement of doxorubicin cytotoxicity by polyunsaturated fatty acids in the human breast tumor cell line MDA-MB-231: Relationship to lipid peroxidation","volume":"75","author":"Germain","year":"1998","journal-title":"Int. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2152607","DOI":"10.1080\/13510002.2022.2152607","article-title":"Glutathione metabolism rewiring protects renal tubule cells against cisplatin-induced apoptosis and ferroptosis","volume":"28","author":"Dong","year":"2023","journal-title":"Redox Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1073\/pnas.87.4.1620","article-title":"Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxides","volume":"87","author":"Beckman","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0968-0004(90)90206-Q","article-title":"The measurement and mechanism of lipid peroxidation in biological systems","volume":"15","author":"Gutteridge","year":"1990","journal-title":"Trends Biochem. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0892-0362(99)00069-0","article-title":"Age-related changes in reactive oxygen species production in rat brain homogenates","volume":"22","author":"Driver","year":"2000","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"13411","DOI":"10.1021\/la302705f","article-title":"Mapping the mechanical properties of cholesterol-containing supported lipid bilayers with nanoscale spatial resolution","volume":"28","author":"Molchanoff","year":"2012","journal-title":"Langmuir"},{"key":"ref_24","first-page":"700","article-title":"Membrane alterations and fluidity changes in cerebral cortex during ammonia intoxication","volume":"335","author":"Swapna","year":"2005","journal-title":"Neuro Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.ijdevneu.2005.06.003","article-title":"Methionine alters Na+, K+ ATPase activity, lipid peroxidation and nonenzymatic antioxidant defenses in rat hippocampus","volume":"23","author":"Stefanello","year":"2005","journal-title":"Int. J. Dev. Neurosc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.2298\/ABS1304371G","article-title":"Effect of an antiviral and vitamins A,C,D on dopamine and some oxidative stress markers in rat brain exposed to ozone","volume":"65","author":"Calderon","year":"2013","journal-title":"Arch. Biol. Sci. Belgrade"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0188-4409(01)00345-9","article-title":"Effect of nutritional status and ozone exposure on rat brain serotonin","volume":"33","year":"2002","journal-title":"Arch. Med. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1002\/lary.24235","article-title":"Cochlear pharmacokinetics of cisplatin: An in vivo study in the guinea pig","volume":"123","author":"Hellberg","year":"2013","journal-title":"Laryngoscope"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/0091-3057(80)90254-3","article-title":"A rapid method for the regional dissection of the rat brain","volume":"13","author":"Heffner","year":"1980","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0009-8981(77)90472-7","article-title":"Quantitative determination of 5-hydroxyindole- 3-acetic acid in body fluids by HPLC","volume":"79","author":"Beck","year":"1977","journal-title":"Clin. Chim. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Peraza, A.V., Guzm\u00e1n, D.C., Brizuela, N.O., Herrera, M.O., Olgu\u00edn, H.J., Silva, M.L., Tapia, B.J., and Mej\u00eda, G.B. (2018). Riboflavin and pyridoxine restore dopamine levels and reduce oxidative stress in brain of rats. BMC Neurosci., 19.","DOI":"10.1186\/s12868-018-0474-4"},{"key":"ref_32","first-page":"214","article-title":"A fluorometric method for determination of oxidized and reduced glutathione in tissue","volume":"4","author":"Hissin","year":"1974","journal-title":"Anal. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hadwan, M.H. (2018). Simple spectrophotometric assay for measuring catalase activity in biological tissues. BMC Biochem., 19.","DOI":"10.1186\/s12858-018-0097-5"},{"key":"ref_34","first-page":"1491","article-title":"Oleic acid protects against oxidative stress exacerbated by cytarabine and doxorubicin in rat brain","volume":"16","year":"2016","journal-title":"Mini-Revi Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0021-9258(18)84756-1","article-title":"The colorimetric determination of phosphorus","volume":"66","author":"Fiske","year":"1972","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"R43","DOI":"10.1530\/EJE-13-0586","article-title":"Endocrine side effects of anti-cancer drugs: Effects of anti-cancer targeted therapies on lipid and glucose metabolism","volume":"170","author":"Walter","year":"2014","journal-title":"Eur. J. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1055\/s-2007-997833","article-title":"Reduced nutritional status enhances ototoxicity","volume":"74","author":"Lautermann","year":"1995","journal-title":"Laryngorhinootologie"},{"key":"ref_38","first-page":"1055","article-title":"ABT737 reverses cisplatin resistance by targeting glucose metabolism of human ovarian cancer cells","volume":"53","author":"Xu","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.nbd.2014.08.004","article-title":"Folate deficiency-induced oxidative stress contributes to neuropathy in young and aged zebrafish. Iimplication in neural tube defects and Alzheimer\u2019s diseases","volume":"71","author":"Kao","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"108391","DOI":"10.1016\/j.reprotox.2023.108391","article-title":"Melatonin alleviates cisplatin-induced mice spermatogenesis defects","volume":"119","author":"Peng","year":"2023","journal-title":"Reprod. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1007\/BF03401922","article-title":"Na+, K(+)-ATPase phosphorylation in the choroid plexus: Synergistic regulation by serotonin\/protein kinase C and isoproterenol\/cAMP-PK\/PP-1 pathways","volume":"4","author":"Fisone","year":"1998","journal-title":"Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1080\/14756366.2018.1445735","article-title":"Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na+\/K+-ATPase","volume":"33","author":"Kubala","year":"2018","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1097\/WNR.0000000000000792","article-title":"L-Borneol induces transient opening of the blood-brain barrier and enhances the therapeutic effect of cisplatin","volume":"28","author":"Yin","year":"2017","journal-title":"Neuroreport"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"114010","DOI":"10.1016\/j.expneurol.2022.114010","article-title":"Cisplatin toxicity in the developing brain displays an absolute requirement for caspase-3","volume":"351","author":"Hui","year":"2022","journal-title":"Exp. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Genovese, I., Carinci, M., Modesti, L., Aguiari, G., Pinton, P., and Giorgi, C. (2021). Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094770"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"F608","DOI":"10.1152\/ajprenal.00554.2020","article-title":"The novel STING antagonist H151 ameliorates cisplatin-induced acute kidney injury and mitochondrial dysfunction","volume":"320","author":"Gong","year":"2021","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_47","first-page":"2446","article-title":"Relationships between the mitochondrial permeability transition and oxidative stress during ara-C toxicity","volume":"57","author":"Backway","year":"1977","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3233\/JAD-2005-7206","article-title":"N-acteyl cysteine alleviates oxidative damage to central nervous system of ApoE-deficient mice following folate and vitamin E-deficiency","volume":"7","author":"Tchantchou","year":"2005","journal-title":"J. Alzheimers Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00280-007-0597-2","article-title":"Effect of N-acetylcysteine route of administration on chemoprotection against cisplatin- induced toxicity in rat models","volume":"62","author":"Dickey","year":"2007","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0955-2863(02)00218-8","article-title":"Dietary supplementation with cysteine prodrugs selectively restores tissue glutathione levels and redox status in protein- malnourished mice","volume":"13","author":"Li","year":"2002","journal-title":"J. Nutr. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.bbabio.2017.01.012","article-title":"Mitochondria and cancer chemoresistance","volume":"1858","author":"Guerra","year":"2017","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"112369","DOI":"10.1016\/j.yexcr.2020.112369","article-title":"PGC1\u03b1 regulates mitochondrial oxidative phosphorylation involved in cisplatin resistance in ovarian cancer cells via nucleo-mitochondrial transcriptional feedback","volume":"398","author":"Shen","year":"2021","journal-title":"Exp. Cell Res."},{"key":"ref_53","first-page":"963520","article-title":"ROS and brain diseases: The good, the bad, and the ugly","volume":"2013","author":"Mitran","year":"2013","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ali, R., Aouida, M., Sulaiman, A.A., Madhusudan, S., and Ramotar, D. (2022). \u00bfCan Cisplatin Therapy Be Improved? Pathways That Can Be Targeted. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137241"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/s41419-023-06195-z","article-title":"Pyruvate kinase M2 regulates mitochondrial homeostasis in cisplatin-induced acute kidney injury","volume":"14","author":"Xie","year":"2023","journal-title":"Cell Death Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/11\/6239\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:54:20Z","timestamp":1760108060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/11\/6239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,5]]},"references-count":55,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["ijms25116239"],"URL":"https:\/\/doi.org\/10.3390\/ijms25116239","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,5]]}}}