{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:23:27Z","timestamp":1791897807690,"version":"4.3.4"},"reference-count":56,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010877","name":"Shenzhen Science and Technology Innovation Commission","doi-asserted-by":"publisher","award":["KJZD20240903102714019"],"award-info":[{"award-number":["KJZD20240903102714019"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021M702292"],"award-info":[{"award-number":["2021M702292"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022T150441"],"award-info":[{"award-number":["2022T150441"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104357"],"award-info":[{"award-number":["82104357"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Materials Today Bio"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.mtbio.2025.102278","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T23:51:54Z","timestamp":1756857114000},"page":"102278","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":55,"special_numbering":"C","title":["Carrier-free nanoparticles based on natural products trigger dual \"synergy and attenuation\" for enhanced phototherapy of liver cancer"],"prefix":"10.1016","volume":"35","author":[{"given":"Xiongqin","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunhui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlin","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyue","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbing","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiejie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuguang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2918-7369","authenticated-orcid":false,"given":"Xie-an","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.mtbio.2025.102278_bib1","first-page":"220","article-title":"Carrier-free nanodrugs with efficient drug delivery and release for cancer therapy: from intrinsic physicochemical properties to external modification","volume":"8","author":"Mei","year":"2022","journal-title":"Bioact. Mater."},{"key":"10.1016\/j.mtbio.2025.102278_bib2","doi-asserted-by":"crossref","DOI":"10.1016\/j.giant.2024.100256","article-title":"Carrier-free nanomedicines: mechanisms of formation and biomedical applications","volume":"18","author":"Dong","year":"2024","journal-title":"Giant"},{"key":"10.1016\/j.mtbio.2025.102278_bib3","article-title":"Natural-product-based, carrier-free, noncovalent nanoparticles for tumor chemo-photodynamic combination therapy","author":"Wang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.mtbio.2025.102278_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.actbio.2020.04.052","article-title":"Design of light\/ROS cascade-responsive tumor-recognizing nanotheranostics for spatiotemporally controlled drug release in locoregional photo-chemotherapy","author":"Zuo","year":"2020","journal-title":"Acta Biomater."},{"key":"10.1016\/j.mtbio.2025.102278_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2020.119049","article-title":"Vitamin E-based prodrug self-delivery for nanoformulated irinotecan with synergistic antitumor therapeutics","author":"Ling","year":"2020","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.mtbio.2025.102278_bib6","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.202001128","article-title":"Carrier-free nanoassembly of curcumin-Erlotinib conjugate for cancer targeted therapy","author":"Cheng","year":"2020","journal-title":"Adv. Healthcare Mater."},{"key":"10.1016\/j.mtbio.2025.102278_bib7","article-title":"Enhancing triple negative breast cancer immunotherapy by ICG\u2010templated self\u2010assembly of paclitaxel nanoparticles","author":"Feng","year":"2019","journal-title":"Adv. Funct. Mater."},{"key":"10.1016\/j.mtbio.2025.102278_bib8","doi-asserted-by":"crossref","DOI":"10.1021\/acsnano.5b02513","article-title":"Self-monitoring and self-delivery of photosensitizer-doped nanoparticles for highly effective combination cancer therapy in vitro and in vivo","author":"Zhang","year":"2015","journal-title":"ACS Nano"},{"issue":"1","key":"10.1016\/j.mtbio.2025.102278_bib9","article-title":"Recent advances in self-targeting natural product-based nanomedicines","volume":"23","author":"Liu","year":"2025","journal-title":"J. Nanobiotechnol."},{"issue":"1","key":"10.1016\/j.mtbio.2025.102278_bib10","doi-asserted-by":"crossref","DOI":"10.1186\/s12951-024-02981-9","article-title":"An encounter between metal ions and natural products: natural products-coordinated metal ions for the diagnosis and treatment of tumors","volume":"22","author":"Liu","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"10.1016\/j.mtbio.2025.102278_bib11","first-page":"203","article-title":"Natural-product-based, carrier-free, noncovalent nanoparticles for tumor chemo-photodynamic combination therapy","author":"Wang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.mtbio.2025.102278_bib12","article-title":"Nanomedicine-cum-carrier by Co-assembly of natural small products for synergistic enhanced antitumor with tissues protective actions","author":"Wang","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"10.1016\/j.mtbio.2025.102278_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.jddst.2021.102459","article-title":"An overview on natural product drug formulations from conventional medicines to nanomedicines: past, present and future","author":"Elkordy","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"10.1016\/j.mtbio.2025.102278_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.drup.2020.100704","article-title":"Nanomedicine to target multidrug resistant tumors","author":"Lepeltier","year":"2020","journal-title":"Drug Resist. Updates"},{"key":"10.1016\/j.mtbio.2025.102278_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.nantod.2020.101008","article-title":"Progress, challenges, and future of nanomedicine","author":"Zhang","year":"2020","journal-title":"Nano Today"},{"key":"10.1016\/j.mtbio.2025.102278_bib16","doi-asserted-by":"crossref","DOI":"10.1007\/s10311-021-01276-x","article-title":"Recent strategies in nanodelivery systems for natural products: a review","author":"Vanti","year":"2021","journal-title":"Environ. Chem. Lett."},{"key":"10.1016\/j.mtbio.2025.102278_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.csbj.2021.08.029","article-title":"Co-crystallization and structure determination: an effective direction for anti-SARS-CoV-2 drug discovery","author":"Wang","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"10.1016\/j.mtbio.2025.102278_bib18","article-title":"Immunomodulatory; anti-inflammatory\/antioxidant effects of polyphenols: a comparative review on the parental compounds and their metabolites","author":"Sobhani","year":"2020","journal-title":"Food Rev. Int."},{"key":"10.1016\/j.mtbio.2025.102278_bib19","doi-asserted-by":"crossref","DOI":"10.1080\/00397911.2013.820835","article-title":"Advances in the first total synthesis of natural flavonoids","author":"Wang","year":"2013","journal-title":"Synth. Commun."},{"key":"10.1016\/j.mtbio.2025.102278_bib20","article-title":"Synthesis and anti-hypertensive effects of the twin drug of nicotinic acid and quercetin tetramethyl ether","author":"Wang","year":"2014","journal-title":"Molecules"},{"key":"10.1016\/j.mtbio.2025.102278_bib21","article-title":"Enhanced photothermal therapy through the in situ activation of a temperature and redox dual-sensitive nanoreservoir of triptolide","author":"Liu","year":"2020","journal-title":"Small"},{"key":"10.1016\/j.mtbio.2025.102278_bib22","doi-asserted-by":"crossref","DOI":"10.1186\/s12951-022-01389-7","article-title":"Delivery of triptolide: a combination of traditional Chinese medicine and nanomedicine","author":"Sun","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"10.1016\/j.mtbio.2025.102278_bib23","article-title":"Metformin-mediated immunosuppressive microenvironment remodeling in combination with chemotherapy via a spatial-specific multi-responsive carrier-free self-assembled nanoparticle","author":"Song","year":"2024","journal-title":"Adv. Funct. Mater."},{"key":"10.1016\/j.mtbio.2025.102278_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.jconrel.2023.12.056","article-title":"Ferroptosis boosted oral cancer photodynamic therapy by carrier-free Sorafenib-Ce6 self-assembly nanoparticles","author":"Xu","year":"2024","journal-title":"J. Contr. Release"},{"key":"10.1016\/j.mtbio.2025.102278_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.cej.2024.155709","article-title":"Mechanism of self-assembled celastrol-erianin nanomedicine for treatment of breast cancer","author":"Tian","year":"2024","journal-title":"Chem. Eng. J."},{"issue":"50","key":"10.1016\/j.mtbio.2025.102278_bib26","doi-asserted-by":"crossref","first-page":"43508","DOI":"10.1021\/acsami.7b14755","article-title":"A small molecule nanodrug by self-assembly of dual anticancer drugs and photosensitizer for synergistic near-infrared cancer theranostics","volume":"9","author":"Guo","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"issue":"1\u20133","key":"10.1016\/j.mtbio.2025.102278_bib27","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.tox.2009.03.010","article-title":"Reactive oxygen species accumulation contributes to gambogic acid-induced apoptosis in human hepatoma SMMC-7721 cells","volume":"260","author":"Nie","year":"2009","journal-title":"Toxicology"},{"key":"10.1016\/j.mtbio.2025.102278_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbcan.2020.188381","article-title":"Gambogic acid: a shining natural compound to nanomedicine for cancer therapeutics","author":"Hatami","year":"2020","journal-title":"Biochim. Biophys. Acta Rev. Canc"},{"key":"10.1016\/j.mtbio.2025.102278_bib29","article-title":"Therapeutic potential of gambogic acid, a caged xanthone, to target cancer","author":"Banik","year":"2017","journal-title":"Cancer Lett."},{"key":"10.1016\/j.mtbio.2025.102278_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.cej.2020.127212","article-title":"Tumor-specific carrier-free nanodrugs with GSH depletion and enhanced ROS generation for endogenous synergistic anti-tumor by a chemotherapy-photodynamic therapy","volume":"407","author":"Lan","year":"2021","journal-title":"Chem. Eng. J."},{"key":"10.1016\/j.mtbio.2025.102278_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.freeradbiomed.2013.12.027","article-title":"Gambogic acid induces apoptosis in hepatocellular carcinoma SMMC-7721 cells by targeting cytosolic thioredoxin reductase","author":"Duan","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.mtbio.2025.102278_bib32","doi-asserted-by":"crossref","DOI":"10.18632\/oncotarget.20424","article-title":"Gambogic acid inhibits thioredoxin activity and induces ROS-mediated cell death in castration-resistant prostate cancer","author":"Pan","year":"2017","journal-title":"Oncotarget"},{"issue":"5","key":"10.1016\/j.mtbio.2025.102278_bib33","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1021\/np200029q","article-title":"Gambogic acid, a natural product inhibitor of Hsp90","volume":"74","author":"Davenport","year":"2011","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.mtbio.2025.102278_bib34","doi-asserted-by":"crossref","DOI":"10.2147\/IJN.S277645","article-title":"Gambogic acid as a candidate for cancer therapy: a review","author":"Liu","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"10.1016\/j.mtbio.2025.102278_bib35","article-title":"Simplified gambogic acid prodrug nanoparticles to improve efficiency and reduce toxicity for clinical translation potential","author":"Wang","year":"2024","journal-title":"Adv. Healthcare Mater."},{"key":"10.1016\/j.mtbio.2025.102278_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2010.02.042","article-title":"Glycyrrhetinic acid-modified chitosan\/poly(ethylene glycol) nanoparticles for liver-targeted delivery","author":"Tian","year":"2010","journal-title":"Biomaterials"},{"key":"10.1016\/j.mtbio.2025.102278_bib37","article-title":"Glycyrrhetinic acid functionalized graphene oxide for mitochondria targeting and cancer treatment in vivo","author":"Zhang","year":"2017","journal-title":"Small"},{"key":"10.1016\/j.mtbio.2025.102278_bib38","doi-asserted-by":"crossref","DOI":"10.1021\/acs.molpharmaceut.5b00677","article-title":"Glycyrrhetinic acid mediated drug delivery carriers for hepatocellular carcinoma therapy","author":"Cai","year":"2016","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.mtbio.2025.102278_bib39","article-title":"Glycyrrhetinic acid-decorated and reduction-sensitive micelles to enhance the bioavailability and anti-hepatocellular carcinoma efficacy of tanshinone IIA","author":"Chen","year":"2015","journal-title":"Biomater. Sci."},{"key":"10.1016\/j.mtbio.2025.102278_bib40","article-title":"Acid-sensitive polymeric vector targeting to hepatocarcinoma cells via glycyrrhetinic acid receptor-mediated endocytosis","author":"Yan","year":"2018","journal-title":"Biomater. Adv."},{"key":"10.1016\/j.mtbio.2025.102278_bib41","article-title":"Compound ammonium glycyrrhizin protects hepatocytes from injury induced by lipopolysaccharide\/florfenicol through a mitochondrial pathway","author":"Li","year":"2018","journal-title":"Molecules"},{"key":"10.1016\/j.mtbio.2025.102278_bib42","doi-asserted-by":"crossref","DOI":"10.1039\/D5SC01987G","article-title":"\u201cDual lock-and-key\u201d triggered and endoplasmic reticulum targeting nanophotosensitizers for activatable Type-I photodynamic and photothermal therapies","author":"Zhan","year":"2025","journal-title":"Chem. Sci."},{"key":"10.1016\/j.mtbio.2025.102278_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.mtbio.2025.102047","article-title":"Recent advances in phototherapy-based nanomedicine of lymphoma","author":"Huang","year":"2025","journal-title":"Mater. Today Bio"},{"key":"10.1016\/j.mtbio.2025.102278_bib44","article-title":"Dendritic nanomedicine enhances chemo-immunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells","author":"Li","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.mtbio.2025.102278_bib45","article-title":"Metformin-based nanomedicines for reprogramming tumor immune microenvironment","author":"Liu","year":"2025","journal-title":"Theranostics"},{"key":"10.1016\/j.mtbio.2025.102278_bib46","article-title":"Metabolic targeting of oxidative phosphorylation enhances chemosensitivity in triple-negative breast cancer via a synergistic","author":"Shen","year":"2025","journal-title":"Nanomedicine. Theranostics"},{"key":"10.1016\/j.mtbio.2025.102278_bib47","doi-asserted-by":"crossref","DOI":"10.7150\/thno.112475","article-title":"Nano drug delivery systems for advanced immune checkpoint blockade therapy","author":"Guo","year":"2025","journal-title":"Theranostics"},{"issue":"9","key":"10.1016\/j.mtbio.2025.102278_bib48","article-title":"Machine learning-driven prediction, preparation, and evaluation of functional nanomedicines via drug-drug self-assembly","volume":"12","author":"Zhang","year":"2025","journal-title":"Adv. Sci. (Weinh.)"},{"key":"10.1016\/j.mtbio.2025.102278_bib49","article-title":"Rational design of conjugated small molecules for superior photothermal theranostics in the NIR-II biowindow","author":"Li","year":"2020","journal-title":"Adv. Mater."},{"key":"10.1016\/j.mtbio.2025.102278_bib50","unstructured":"Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al. Gaussian 16 Rev. C.01. Wallingford, CT2016."},{"key":"10.1016\/j.mtbio.2025.102278_bib51","article-title":"Excited-state absorption for zinc phthalocyanine from linear-response time-dependent density functional theory","author":"Wang","year":"2020","journal-title":"RSC Adv."},{"key":"10.1016\/j.mtbio.2025.102278_bib52","doi-asserted-by":"crossref","DOI":"10.3892\/mmr.2017.8026","article-title":"Gambogic acid inhibits spinal cord injury and inflammation through suppressing the p38 and Akt signaling pathways","author":"Fu","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.mtbio.2025.102278_bib53","doi-asserted-by":"crossref","DOI":"10.1016\/j.tox.2009.03.010","article-title":"Reactive oxygen species accumulation contributes to gambogic acid-induced apoptosis in human hepatoma SMMC-7721 cells","author":"Nie","year":"2009","journal-title":"Toxicology"},{"key":"10.1016\/j.mtbio.2025.102278_bib54","doi-asserted-by":"crossref","DOI":"10.1016\/j.freeradbiomed.2024.03.023","article-title":"Unlocking the anticancer activity of gambogic acid: a shift towards ferroptosis via a GSH\/Trx dual antioxidant system","author":"Lan","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.mtbio.2025.102278_bib55","doi-asserted-by":"crossref","DOI":"10.1021\/np200029q","article-title":"Gambogic acid, a natural product inhibitor of Hsp90","author":"Davenport","year":"2011","journal-title":"J. Nat. Prod."},{"issue":"5","key":"10.1016\/j.mtbio.2025.102278_bib56","doi-asserted-by":"crossref","DOI":"10.1016\/j.cclet.2023.108752","article-title":"Multifunctional nano-herb based on tumor microenvironment for enhanced tumor therapy of gambogic acid","volume":"35","author":"Li","year":"2024","journal-title":"Chin. Chem. Lett."}],"container-title":["Materials Today Bio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2590006425008488?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2590006425008488?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T20:40:32Z","timestamp":1772916032000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2590006425008488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":56,"alternative-id":["S2590006425008488"],"URL":"https:\/\/doi.org\/10.1016\/j.mtbio.2025.102278","relation":{},"ISSN":["2590-0064"],"issn-type":[{"value":"2590-0064","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Carrier-free nanoparticles based on natural products trigger dual \"synergy and attenuation\" for enhanced phototherapy of liver cancer","name":"articletitle","label":"Article Title"},{"value":"Materials Today Bio","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mtbio.2025.102278","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"102278"}}