{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:13:17Z","timestamp":1788437597175,"version":"build-2803163510"},"reference-count":52,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"T?rkiye Bilimsel ve Teknolojik Arastirma Kurumu","doi-asserted-by":"publisher","award":["KBAG118Z860"],"award-info":[{"award-number":["KBAG118Z860"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Apalutamide (APA) is a recently FDA-approved androgen receptor inhibitor for the treatment of nonmetastatic castration-resistant prostate cancer. Herein, we report a pH-responsive, dual-acting nanocarrier system based on zeolitic imidazolate framework-8 (ZIF-8) to enhance the therapeutic efficacy of APA. APA was successfully encapsulated into ZIF-8 nanoparticles with an encapsulation efficiency of 69.4% and a drug loading capacity of 47.8% (APA@ZIF-8). The structural and physicochemical properties of ZIF-8 and APA@ZIF-8 were comprehensively characterized using FTIR, SEM, STEM, DLS, EDX, PXRD, TGA, and BET analyses. Drug release studies demonstrated a pronounced pH-dependent behavior, with a faster release at pH 5.0 (93% over 120 h) compared to pH 7.4 (62% over 120 h), indicating suitability for the acidic tumor microenvironment. Biocompatibility assessments, including hemolysis and serum protein binding assays, confirmed the hemocompatible nature of both ZIF-8 and APA@ZIF-8 nanoparticles. The biological effects of APA, ZIF-8, and APA@ZIF-8 were evaluated through cell viability, cell cycle progression, reactive oxygen species generation, apoptosis, and androgen receptor transcriptional activity in prostate cancer and healthy cell lines. The results reveal that the pH-triggered biodegradation of ZIF-8 leads to zinc ion release, which, together with APA, contributes to enhanced cytotoxic effects in prostate cancer cells, highlighting the potential of APA@ZIF-8 as a zinc-enhanced dual cytotoxic nanotherapeutic platform.<\/jats:p>","DOI":"10.1021\/acsomega.6c01591","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:01:49Z","timestamp":1786975309000},"page":"50818-50830","source":"Crossref","is-referenced-by-count":0,"title":["pH-Responsive Apalutamide-Loaded ZIF-8 Nanoparticles\nfor Zinc-Enhanced Dual Cytotoxicity in Prostate Cancer"],"prefix":"10.1021","volume":"11","author":[{"given":"Derya","family":"Mete","sequence":"first","affiliation":[{"name":"I\u0307zmir Institute of Technology , , ,","place":["I\u0307zmir, Turkey, 35430"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0282-4428","authenticated-orcid":true,"given":"Gu\u0308ls\u0327ah","family":"S\u0327anl\u0131-Mohamed","sequence":"additional","affiliation":[{"name":"I\u0307zmir Institute of Technology , , ,","place":["I\u0307zmir, Turkey, 35430"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"issue":"1","key":"2026090307175874800_cit1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21387","article-title":"Cancer Statistics,\n2017","volume":"67","author":"Siegel","year":"2017","journal-title":"CA Cancer J. Clin."},{"issue":"1","key":"2026090307175874800_cit2","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer Statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. Clin."},{"issue":"6","key":"2026090307175874800_cit3","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1038\/aja.2011.83","article-title":"Androgen Deprivation\nTherapy through Bilateral Orchiectomy: Increased Metabolic Risks","volume":"13","author":"Bo","year":"2011","journal-title":"Asian J. Androl."},{"issue":"1","key":"2026090307175874800_cit4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1056\/NEJMoa1903307","article-title":"Apalutamide for Metastatic, Castration-Sensitive\nProstate Cancer","volume":"381","author":"Chi","year":"2019","journal-title":"N. Engl. J. Med."},{"issue":"6","key":"2026090307175874800_cit5","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s40265-018-0900-z","article-title":"Apalutamide:\nFirst Global Approval","volume":"78","author":"Al-Salama","year":"2018","journal-title":"Drugs"},{"issue":"4","key":"2026090307175874800_cit6","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1056\/NEJMoa1704174","article-title":"Abiraterone plus\nPrednisone in Metastatic, Castration-Sensitive Prostate Cancer","volume":"377","author":"Fizazi","year":"2017","journal-title":"N. Engl. J. Med."},{"issue":"11","key":"2026090307175874800_cit7","doi-asserted-by":"publisher","DOI":"10.3390\/ph18111697","article-title":"Recent Advances in\nAndrogen Receptor Pathway Inhibitors for Castration-Sensitive Prostate\nCancer","volume":"18","author":"Lancia","year":"2025","journal-title":"Pharmaceuticals"},{"issue":"1","key":"2026090307175874800_cit8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1359-6454(99)00285-2","article-title":"Nanostructured\nMaterials: Basic Concepts and Microstructure","volume":"48","author":"Gleiter","year":"2000","journal-title":"Acta Mater."},{"issue":"2","key":"2026090307175874800_cit9","doi-asserted-by":"publisher","DOI":"10.3390\/nano12020277","article-title":"Biomedical Applications\nof Metal\u2013Organic Frameworks for Disease Diagnosis and Drug\nDelivery: A Review","volume":"12","author":"Al Sharabati","year":"2022","journal-title":"Nanomaterials"},{"key":"2026090307175874800_cit10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2021.214064","article-title":"Classification and\nRole of Modulators on Crystal Engineering of Metal\nOrganic Frameworks (MOFs)","volume":"444","author":"Jiang","year":"2021","journal-title":"Coord. Chem. Rev."},{"key":"2026090307175874800_cit11","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2019.05.019","article-title":"Regeneration, Degradation,\nand Toxicity Effect of MOFs: Opportunities\nand Challenges","volume":"176","author":"Kumar","year":"2019","journal-title":"Environ. Res."},{"issue":"1","key":"2026090307175874800_cit12","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03252-x","article-title":"Metal\u2013Organic\nFramework-Based Smart Stimuli-Responsive Drug Delivery Systems for\nCancer Therapy: Advances, Challenges, and Future Perspectives","volume":"23","author":"Guo","year":"2025","journal-title":"J. Nanobiotechnology"},{"key":"2026090307175874800_cit13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2021.214064","article-title":"Classification and\nrole of Modulators on Crystal Engineering of Metal\nOrganic Frameworks (MOFs)","volume":"444","author":"Jiang","year":"2021","journal-title":"Coord. Chem. Rev."},{"issue":"2","key":"2026090307175874800_cit14","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s11705-020-1927-8","article-title":"Zeolitic Imidazolate\nFramework-8 (ZIF-8) for Drug Delivery: A Critical Review","volume":"15","author":"Feng","year":"2021","journal-title":"Front. Chem. Sci. Eng."},{"issue":"36","key":"2026090307175874800_cit15","doi-asserted-by":"publisher","first-page":"7210","DOI":"10.1039\/C8SC02305K","article-title":"An \u201cAll-in-One\u201d\nAntitumor and Anti-Recurrence\/Metastasis Nanomedicine with Multi-Drug\nCo-Loading and Burst Drug Release for Multi-Modality Therapy","volume":"9","author":"Yang","year":"2018","journal-title":"Chem. Sci."},{"issue":"42","key":"2026090307175874800_cit16","doi-asserted-by":"publisher","first-page":"5377","DOI":"10.1039\/C8CC02708K","article-title":"One-Pot Synthesis\nof a Metal\u2013Organic Framework-Based Drug Carrier for Intelligent\nGlucose-Responsive Insulin Delivery","volume":"54","author":"Duan","year":"2018","journal-title":"Chem. Commun."},{"issue":"40","key":"2026090307175874800_cit17","doi-asserted-by":"publisher","first-page":"22181","DOI":"10.1021\/acsami.5b04315","article-title":"One-Step Synthesis of Nanoscale Zeolitic\nImidazolate Frameworks with High Curcumin Loading for Treatment of\nCervical Cancer","volume":"7","author":"Zheng","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"issue":"10","key":"2026090307175874800_cit18","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1021\/acsbiomaterials.7b00435","article-title":"ZnO\u2013DOX@ZIF-8\nCore\u2013Shell Nanoparticles for PH-Responsive Drug Delivery","volume":"3","author":"Zheng","year":"2017","journal-title":"ACS Biomater. Sci. Eng."},{"issue":"9","key":"2026090307175874800_cit19","doi-asserted-by":"publisher","first-page":"5016","DOI":"10.1021\/am301365h","article-title":"CAF@ZIF-8: One-Step Encapsulation\nof Caffeine in MOF","volume":"4","author":"Lie\u0301dana","year":"2012","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"2026090307175874800_cit20","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.jddst.2017.07.004","article-title":"Synthesis\nand Characterization of ZIF-8 Nanoparticles for Controlled Release\nof 6-Mercaptopurine Drug","volume":"41","author":"Kaur","year":"2017","journal-title":"J. Drug Delivery Sci.\nTechnol."},{"issue":"3","key":"2026090307175874800_cit21","doi-asserted-by":"publisher","first-page":"2812","DOI":"10.1021\/nn406590q","article-title":"Optimized Metal\u2013Organic-Framework Nanospheres\nfor Drug Delivery: Evaluation of Small-Molecule Encapsulation","volume":"8","author":"Zhuang","year":"2014","journal-title":"ACS Nano"},{"issue":"23","key":"2026090307175874800_cit22","doi-asserted-by":"publisher","first-page":"6906","DOI":"10.1039\/c2dt30357d","article-title":"Zeolitic\nImidazolate Framework-8 as Efficient PH-Sensitive Drug Delivery Vehicle","volume":"41","author":"Sun","year":"2012","journal-title":"Dalton Trans."},{"issue":"3","key":"2026090307175874800_cit23","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1021\/jacs.5b11720","article-title":"One-Pot Synthesis of\nMetal\u2013Organic\nFrameworks with Encapsulated Target Molecules and Their Applications\nfor Controlled Drug Delivery","volume":"138","author":"Zheng","year":"2016","journal-title":"J. Am. Chem. Soc."},{"issue":"7","key":"2026090307175874800_cit24","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15071874","article-title":"Development of Novel Paclitaxel-Loaded\nZIF-8 Metal-Organic Framework Nanoparticles Modified with Peptide\nDimers and an Evaluation of Its Inhibitory Effect against Prostate\nCancer Cells","volume":"15","author":"Zhao","year":"2023","journal-title":"Pharmaceutics"},{"key":"2026090307175874800_cit25","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2021.115557","article-title":"Simulation of Adsorption\nand Release of Doxepin onto ZIF-8 Including in Vitro Cellular Toxicity\nand Viability","volume":"329","author":"Dou","year":"2021","journal-title":"J. Mol. Liq."},{"issue":"7","key":"2026090307175874800_cit26","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1039\/c0cc05002d","article-title":"Rapid Synthesis of\nZeolitic Imidazolate Framework-8 (ZIF-8) Nanocrystals in an Aqueous\nSystem","volume":"47","author":"Pan","year":"2011","journal-title":"Chem. Commun."},{"issue":"12","key":"2026090307175874800_cit27","doi-asserted-by":"publisher","first-page":"3758","DOI":"10.1039\/D4TB02289K","article-title":"Functionalized ZIF-8\nas a Versatile Platform for Drug Delivery and\nCancer Therapy: Strategies, Challenges and Prospects","volume":"13","author":"Gao","year":"2025","journal-title":"J. Mater. Chem. B"},{"issue":"11","key":"2026090307175874800_cit28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0165956","article-title":"Zinc Intake\nand Risk of Prostate\nCancer: Case-Control Study and Meta-Analysis","volume":"11","author":"Mahmoud","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"2026090307175874800_cit29","doi-asserted-by":"publisher","DOI":"10.1038\/srep36772","article-title":"Analysis of Zinc-Exporters Expression\nin Prostate Cancer","volume":"6","author":"Singh","year":"2016","journal-title":"Sci. Rep."},{"issue":"1","key":"2026090307175874800_cit30","doi-asserted-by":"publisher","first-page":"994","DOI":"10.3390\/cancers3010994","article-title":"Role of P53\nin Cell Death and Human Cancers","volume":"3","author":"Ozaki","year":"2011","journal-title":"Cancers"},{"issue":"46","key":"2026090307175874800_cit31","doi-asserted-by":"publisher","first-page":"28875","DOI":"10.1074\/jbc.272.46.28875","article-title":"Zinc Inhibition of Mitochondrial\nAconitase and Its Importance in Citrate Metabolism of Prostate Epithelial\nCells","volume":"272","author":"Costello","year":"1997","journal-title":"J. Biol. Chem."},{"issue":"5","key":"2026090307175874800_cit32","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054822","article-title":"Zinc: From Biological Functions to\nTherapeutic Potential","volume":"24","author":"Costa","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"2026090307175874800_cit33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biomaterials.2014.12.045","article-title":"Implications\nof Protein Corona on Physico-Chemical and Biological Properties of\nMagnetic Nanoparticles","volume":"46","author":"Yallapu","year":"2015","journal-title":"Biomaterials"},{"issue":"1\u20132","key":"2026090307175874800_cit34","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A Rapid\nand Sensitive Method for the Quantitation of Microgram Quantities\nof Protein Utilizing the Principle of Protein-Dye Binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"issue":"1\u20132","key":"2026090307175874800_cit35","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S0009-8981(99)00246-6","article-title":"A Microtiter\nPlate Assay for Superoxide Dismutase Using\na Water-Soluble Tetrazolium Salt (WST-1)","volume":"293","author":"Peskin","year":"2000","journal-title":"Clin.\nChim. Acta"},{"key":"2026090307175874800_cit36","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/978-1-60761-756-3_16","article-title":"Measurement\nof Mitochondrial ROS Production","volume-title":"Protein\nMisfolding and Cellular Stress in Disease and Aging","author":"Starkov","year":"2010"},{"key":"2026090307175874800_cit37","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/B978-0-12-816505-8.00007-2","article-title":"Multifunctional\nNanocrystals for Cancer Therapy: A Potential Nanocarrier","volume-title":"Nanomaterials for Drug Delivery and Therapy","author":"Joseph","year":"2019"},{"issue":"8","key":"2026090307175874800_cit38","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1089\/ars.2014.5952","article-title":"Molecular Strategies\nfor Targeting Antioxidants to\nMitochondria: Therapeutic Implications","volume":"22","author":"Apostolova","year":"2015","journal-title":"Antioxid.\nRedox Signal."},{"issue":"27","key":"2026090307175874800_cit39","doi-asserted-by":"publisher","first-page":"10186","DOI":"10.1073\/pnas.0602439103","article-title":"Exceptional Chemical and Thermal Stability of Zeolitic\nImidazolate Frameworks","volume":"103","author":"Park","year":"2006","journal-title":"Proc. Natl. Acad. Sci.\nU.S.A."},{"issue":"8","key":"2026090307175874800_cit40","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1021\/cm900166h","article-title":"Rapid Room-Temperature Synthesis and Characterization\nof Nanocrystals of a Prototypical Zeolitic Imidazolate Framework","volume":"21","author":"Cravillon","year":"2009","journal-title":"Chem. Mater."},{"issue":"21","key":"2026090307175874800_cit41","doi-asserted-by":"publisher","first-page":"4493","DOI":"10.1039\/C3CE42485E","article-title":"Controlling\nZIF-8 Nano- and Microcrystal Formation\nand Reactivity through Zinc Salt Variations","volume":"16","author":"Schejn","year":"2014","journal-title":"CrystEngComm"},{"issue":"111","key":"2026090307175874800_cit42","doi-asserted-by":"publisher","first-page":"109608","DOI":"10.1039\/C6RA23870J","article-title":"Fast Adsorption of\nMethyl Blue on Zeolitic Imidazolate Framework-8 and Its Adsorption\nMechanism","volume":"6","author":"Feng","year":"2016","journal-title":"RSC Adv."},{"key":"2026090307175874800_cit43","doi-asserted-by":"publisher","DOI":"10.1590\/s2175-97902022e20954","article-title":"A Novel Second-Generation Platinum\nDerivative and Evaluation of Its Anti-Cancer Potential","volume":"58","author":"Yilmaz","year":"2022","journal-title":"Braz. J. Pharm. Sci."},{"issue":"1","key":"2026090307175874800_cit44","doi-asserted-by":"publisher","first-page":"199","DOI":"10.25177\/JPS.4.1.RA.10640","article-title":"Cytotoxic Potentials\nof the Culture Extract of the\nEndophytic Aspergillus Niger Strain Karmal\u0131 Isolated from Punica\nGranatum against SKOV3 and A549 Cancer Cell Lines","volume":"4","author":"Diorio","year":"2020","journal-title":"SDRP J. Plant Sci."},{"key":"2026090307175874800_cit45","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.msec.2018.05.051","article-title":"Hydrophilic\nZIF-8 Decorated GO Nanosheets\nImprove Biocompatibility and Separation Performance of Polyethersulfone\nHollow Fiber Membranes: A Potential Membrane Material for Bioartificial\nLiver Application","volume":"91","author":"Modi","year":"2018","journal-title":"Mater. Sci. Eng. C"},{"issue":"1","key":"2026090307175874800_cit46","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-02007-w","article-title":"ZIF-8 Induced\nHydroxyapatite-like\nCrystals Enabled Superior Osteogenic Ability of MEW Printing PCL Scaffolds","volume":"21","author":"Wang","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"2026090307175874800_cit47","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/978-3-319-16555-4_10","article-title":"How Nanoparticles\nInteract with Cancer Cells","volume-title":"Nanotechnology-Based\nPrecision Tools for the Detection and Treatment of Cancer","author":"Syed","year":"2015"},{"issue":"8","key":"2026090307175874800_cit48","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21082991","article-title":"Growth Modulatory Role\nof Zinc in Prostate Cancer and Application to Cancer Therapeutics","volume":"21","author":"To","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"33","key":"2026090307175874800_cit49","doi-asserted-by":"publisher","first-page":"24373","DOI":"10.1074\/jbc.M611376200","article-title":"Zinc Irreversibly\nDamages Major Enzymes of Energy Production and Antioxidant Defense\nPrior to Mitochondrial Permeability Transition","volume":"282","author":"Gazaryan","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2026090307175874800_cit50","doi-asserted-by":"publisher","DOI":"10.1177\/1758835920978134","article-title":"Next-Generation Androgen\nReceptor Inhibitors in Non-Metastatic\nCastration-Resistant Prostate Cancer","volume":"12","author":"Lavaud","year":"2020","journal-title":"Ther.\nAdv. Med. Oncol."},{"key":"2026090307175874800_cit51","unstructured":"Mete, D.\n          \n          Synthesis, Characterization\nand Investigation of Cytotoxic Effects of Drug Loaded ZIF-8 Metal-Organic\nFrameworks, Ph.D., Doctoral dissertation; Izmir Institute of Technology: Izmir, 2021."},{"issue":"4","key":"2026090307175874800_cit52","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1097\/CAD.0000000000000592","article-title":"Comparison of the Effect of the Antiandrogen Apalutamide\n(ARN-509) versus Bicalutamide on the Androgen Receptor Pathway in\nProstate Cancer Cell Lines","volume":"29","author":"Koukourakis","year":"2018","journal-title":"Anticancer Drugs"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c01591","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/34\/50818\/66627705\/acsomega.6c01591.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/34\/50818\/66627705\/acsomega.6c01591.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:18:04Z","timestamp":1788434284000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/34\/50818\/5260805\/pH-Responsive-Apalutamide-Loaded-ZIF-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":52,"journal-issue":{"issue":"34","published-online":{"date-parts":[[2026,8,17]]},"published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c01591","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]}}}