{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:49:58Z","timestamp":1791409798322,"version":"4.3.3"},"reference-count":56,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.bioorg.2026.110433","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:54:54Z","timestamp":1787673294000},"page":"110433","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Design, synthesis, and biological evaluation of secondary amine-containing flavonoids with anti-osteosarcoma activity associated with modulation of AKT signaling and EMT-related gene expression"],"prefix":"10.1016","volume":"181","author":[{"given":"Isabela","family":"Santos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9lio M.T.","family":"Albuquerque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Miguel P.","family":"Ferreira de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduarda","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.bioorg.2026.110433_bb0005","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/clinchem\/hvad202","article-title":"Epidemiology of Cancer","volume":"70","author":"Schwartz","year":"2024","journal-title":"Clin. Chem."},{"issue":"1","key":"10.1016\/j.bioorg.2026.110433_bb0010","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41572-022-00409-y","article-title":"Osteosarcoma","volume":"8","author":"Beird","year":"2022","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.bioorg.2026.110433_bb0015","doi-asserted-by":"crossref","DOI":"10.1016\/j.anndiagpath.2020.151654","article-title":"Osteosarcoma: a comprehensive review of management and treatment strategies","volume":"49","author":"Jafari","year":"2020","journal-title":"Ann. Diagn. Pathol."},{"key":"10.1016\/j.bioorg.2026.110433_bb0020","article-title":"European standard clinical practice recommendations for children and adolescents with primary and recurrent osteosarcoma","volume":"2","author":"van Ewijk","year":"2023","journal-title":"EJC Paediatr. Oncol."},{"issue":"11","key":"10.1016\/j.bioorg.2026.110433_bb0025","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1002\/cncr.34163","article-title":"Osteosarcoma: a surveillance, epidemiology, and end results program-based analysis from 1975 to 2017","volume":"128","author":"Cole","year":"2022","journal-title":"Cancer"},{"issue":"3","key":"10.1016\/j.bioorg.2026.110433_bb0030","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1039\/C5NP00121H","article-title":"The use of isolated natural products as scaffolds for the generation of chemically diverse screening libraries for drug discovery","volume":"33","author":"Barnes","year":"2016","journal-title":"Nat. Prod. Rep."},{"key":"10.1016\/j.bioorg.2026.110433_bb0035","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbpa.2018.12.007","article-title":"Natural product derived privileged scaffolds in drug discovery","volume":"52","author":"Davison","year":"2019","journal-title":"Curr. Opin. Chem. Biol."},{"issue":"10","key":"10.1016\/j.bioorg.2026.110433_bb0040","article-title":"Biosynthesis investigations of terpenoid, alkaloid, and flavonoid antimicrobial agents derived from medicinal plants","volume":"11","author":"Huang","year":"2022","journal-title":"Antibiotics (Basel, Switzerland)"},{"issue":"15","key":"10.1016\/j.bioorg.2026.110433_bb0045","doi-asserted-by":"crossref","DOI":"10.3390\/nu16152550","article-title":"Polyphenols: secondary metabolites with a biological impression","volume":"16","author":"Bolat","year":"2024","journal-title":"Nutrients"},{"issue":"5","key":"10.1016\/j.bioorg.2026.110433_bb0050","doi-asserted-by":"crossref","DOI":"10.1002\/fsn3.70191","article-title":"Organic functional groups and their substitution sites in natural flavonoids: a review on their contributions to antioxidant, anti-inflammatory, and analgesic capabilities","volume":"13","author":"An","year":"2025","journal-title":"Food Sci. Nutr."},{"key":"10.1016\/j.bioorg.2026.110433_bb0055","series-title":"Key Heterocycle Cores for Designing Multitargeting Molecules","first-page":"133","article-title":"Chapter 4 - Flavone: An Important Scaffold for Medicinal Chemistry","author":"Singh","year":"2018"},{"key":"10.1016\/j.bioorg.2026.110433_bb0060","doi-asserted-by":"crossref","DOI":"10.1016\/j.foodchem.2022.132531","article-title":"Plant flavonoids: classification, distribution, biosynthesis, and antioxidant activity","volume":"383","author":"Shen","year":"2022","journal-title":"Food Chem."},{"issue":"9","key":"10.1016\/j.bioorg.2026.110433_bb0065","doi-asserted-by":"crossref","first-page":"4578","DOI":"10.1021\/acs.joc.7b00124","article-title":"Optimization of the synthesis of flavone\u2013amino acid and flavone\u2013dipeptide hybrids via Buchwald\u2013Hartwig reaction","volume":"82","author":"Pajt\u00e1s","year":"2017","journal-title":"J. Organomet. Chem."},{"issue":"8","key":"10.1016\/j.bioorg.2026.110433_bb0070","doi-asserted-by":"crossref","DOI":"10.3390\/ma14081984","article-title":"Recent developments in effective antioxidants: the structure and antioxidant properties","volume":"14","author":"Parcheta","year":"2021","journal-title":"Materials"},{"issue":"17","key":"10.1016\/j.bioorg.2026.110433_bb0075","doi-asserted-by":"crossref","DOI":"10.3390\/molecules26175377","article-title":"Plant flavonoids: chemical characteristics and biological activity","volume":"26","author":"Dias","year":"2021","journal-title":"Molecules"},{"issue":"14","key":"10.1016\/j.bioorg.2026.110433_bb0080","doi-asserted-by":"crossref","first-page":"11622","DOI":"10.1021\/acs.jmedchem.4c01122","article-title":"An update on the nitrogen heterocycle compositions and properties of U.S. FDA-approved pharmaceuticals (2013\u22122023)","volume":"67","author":"Marshall","year":"2024","journal-title":"J. Med. Chem."},{"issue":"34","key":"10.1016\/j.bioorg.2026.110433_bb0085","doi-asserted-by":"crossref","first-page":"23505","DOI":"10.18632\/oncotarget.25239","article-title":"The cyclin-dependent kinase inhibitor flavopiridol (alvocidib) inhibits metastasis of human osteosarcoma cells","volume":"9","author":"Zocchi","year":"2018","journal-title":"Oncotarget"},{"key":"10.1016\/j.bioorg.2026.110433_bb0090","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2025.178432","article-title":"Robinetin inhibits osteosarcoma proliferation and migration, acting via the slug\/twist signaling axis","volume":"1011","author":"Santos","year":"2026","journal-title":"Eur. J. Pharmacol."},{"issue":"9","key":"10.1016\/j.bioorg.2026.110433_bb0095","doi-asserted-by":"crossref","DOI":"10.3390\/antiox12091744","article-title":"Gossypetin is a novel modulator of inflammatory cytokine production and a suppressor of osteosarcoma cell growth","volume":"12","author":"Proen\u00e7a","year":"2023","journal-title":"Antioxidants"},{"issue":"6","key":"10.1016\/j.bioorg.2026.110433_bb0100","doi-asserted-by":"crossref","first-page":"21966","DOI":"10.1002\/med.21966","article-title":"The role of flavonoids in the regulation of epithelial-mesenchymal transition in cancer: a review on targeting signaling pathways and metastasis","volume":"43","author":"Proen\u00e7a","year":"2023","journal-title":"Med. Res. Rev."},{"key":"10.1016\/j.bioorg.2026.110433_bb0105","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2023.1219211","article-title":"Functional role of MicroRNA\/PI3K\/AKT axis in osteosarcoma","volume":"13","author":"Xiang","year":"2023","journal-title":"Front. Oncol."},{"issue":"1","key":"10.1016\/j.bioorg.2026.110433_bb0110","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41413-024-00395-9","article-title":"Targeting AKT as a promising strategy for SOX2-positive, chemoresistant osteosarcoma","volume":"13","author":"Liu","year":"2025","journal-title":"Bone Res."},{"issue":"1","key":"10.1016\/j.bioorg.2026.110433_bb0115","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s13045-022-01347-8","article-title":"The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis","volume":"15","author":"Huang","year":"2022","journal-title":"J. Hematol. Oncol."},{"issue":"10","key":"10.1016\/j.bioorg.2026.110433_bb0120","doi-asserted-by":"crossref","first-page":"8824","DOI":"10.3390\/ijms24108824","article-title":"Multi-faceted role of Luteolin in cancer metastasis: EMT, angiogenesis, ECM degradation and apoptosis","volume":"24","author":"Rocchetti","year":"2023","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.bioorg.2026.110433_bb0125","doi-asserted-by":"crossref","first-page":"98","DOI":"10.38212\/2224-6614.3090","article-title":"Quercetin blocks the aggressive phenotype of triple-negative breast cancer by inhibiting IGF1\/IGF1R-mediated EMT program","volume":"29","author":"Chen","year":"2021","journal-title":"J. Food Drug Anal."},{"issue":"6","key":"10.1016\/j.bioorg.2026.110433_bb0130","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1002\/ijc.22820","article-title":"Cyclin-dependent kinase inhibitor, flavopiridol, induces apoptosis and inhibits tumor growth in drug-resistant osteosarcoma and Ewing\u2019s family tumor cells","volume":"121","author":"Li","year":"2007","journal-title":"Int. J. Cancer"},{"issue":"2","key":"10.1016\/j.bioorg.2026.110433_bb0135","doi-asserted-by":"crossref","DOI":"10.3390\/molecules30020346","article-title":"Mechanistic insights into the anticancer potential of methoxyflavones analogs: a review","volume":"30","author":"Aidiel","year":"2025","journal-title":"Molecules"},{"issue":"2","key":"10.1016\/j.bioorg.2026.110433_bb0140","doi-asserted-by":"crossref","first-page":"C62","DOI":"10.1016\/S0022-328X(00)82974-5","article-title":"Purification of laboratory chemicals: by D.D. Perrin, W.L.F. Armarego, and D.R. Perrin. Pergamon, Oxford, second edition, 1980, x + 568 pages, \u00a332.00 $72.00","volume":"213","author":"Eaborn","year":"1981","journal-title":"J. Organomet. Chem."},{"key":"10.1016\/j.bioorg.2026.110433_bb0145","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ejmech.2016.04.057","article-title":"New polyhydroxylated flavon-3-ols and 3-hydroxy-2-styrylchromones: synthesis and ROS\/RNS scavenging activities","volume":"119","author":"Sousa","year":"2016","journal-title":"Eur. J. Med. Chem."},{"issue":"1","key":"10.1016\/j.bioorg.2026.110433_bb0150","first-page":"98","article-title":"A greener approach to Buchwald-Hartwig coupling. A sustainable Pd\/C-catalyzed Csp2\u2013N bond formation under microwave irradiation and bio-based solvent","volume":"7","author":"Brufani","year":"2026","journal-title":"Green Synt. Catal."},{"issue":"51","key":"10.1016\/j.bioorg.2026.110433_bb0155","doi-asserted-by":"crossref","first-page":"50446","DOI":"10.1021\/acsomega.4c07563","article-title":"Microwave-assisted Buchwald-Hartwig double amination: a rapid and promising approach for the synthesis of TADF compounds","volume":"9","author":"Mohd Jamel","year":"2024","journal-title":"ACS Omega"},{"issue":"22","key":"10.1016\/j.bioorg.2026.110433_bb0160","doi-asserted-by":"crossref","first-page":"8880","DOI":"10.1021\/jo801808r","article-title":"Sequential and selective Buchwald-Hartwig amination reactions for the controlled functionalization of 6-bromo-2-chloroquinoline: synthesis of ligands for the Tec Src homology 3 domain","volume":"73","author":"Smith","year":"2008","journal-title":"J. Organomet. Chem."},{"issue":"1","key":"10.1016\/j.bioorg.2026.110433_bb0165","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12858-019-0108-1","article-title":"Application of WST-8 based colorimetric NAD(P)H detection for quantitative dehydrogenase assays","volume":"20","author":"Chamchoy","year":"2019","journal-title":"BMC Biochem."},{"key":"10.1016\/j.bioorg.2026.110433_bb0170","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/978-1-61779-080-5_34","article-title":"Analysis of drug interactions","volume":"731","author":"Bijnsdorp","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.bioorg.2026.110433_bb0175","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.synres.2018.04.001","article-title":"The combination index (CI\u00a0<\u00a01) as the definition of synergism and of synergy claims","volume":"7","author":"Chou","year":"2018","journal-title":"Synergy"},{"key":"10.1016\/j.bioorg.2026.110433_bb0180","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-13-134","article-title":"Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction","volume":"13","author":"Ye","year":"2012","journal-title":"BMC Bioinformatics"},{"issue":"3","key":"10.1016\/j.bioorg.2026.110433_bb0185","first-page":"71","article-title":"An improvement of the 2^(\u2212delta delta CT) method for quantitative real-time polymerase chain reaction data analysis","volume":"3","author":"Rao","year":"2013","journal-title":"Biostat Bioinforma Biomath"},{"issue":"6","key":"10.1016\/j.bioorg.2026.110433_bb0190","first-page":"3743","article-title":"Characterization of osteosarcoma cell lines MG-63, Saos-2 and U-2 OS in comparison to human osteoblasts","volume":"24","author":"Pautke","year":"2004","journal-title":"Anticancer Res."},{"key":"10.1016\/j.bioorg.2026.110433_bb0195","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmg.2024.104941","article-title":"From biology to personalized medicine: recent knowledge in osteosarcoma","volume":"69","author":"Mohr","year":"2024","journal-title":"Eur. J. Med. Genet."},{"issue":"3","key":"10.1016\/j.bioorg.2026.110433_bb0200","doi-asserted-by":"crossref","first-page":"614","DOI":"10.7150\/jca.19614","article-title":"The role of cancer-associated fibroblast MRC-5 in pancreatic cancer","volume":"9","author":"Ding","year":"2018","journal-title":"J. Cancer"},{"issue":"1","key":"10.1016\/j.bioorg.2026.110433_bb0205","doi-asserted-by":"crossref","DOI":"10.1186\/s12885-017-3047-5","article-title":"Lung cells support osteosarcoma cell migration and survival","volume":"17","author":"Yu","year":"2017","journal-title":"BMC Cancer"},{"issue":"4","key":"10.1016\/j.bioorg.2026.110433_bb0210","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.bioorg.2026.110433_bb0215","series-title":"Cell Signaling Pathways and Their Therapeutic Implication in Cancers","first-page":"1","article-title":"An introduction to cell signalling pathways and their dysregulation in cancer","author":"Talath","year":"2025"},{"issue":"14","key":"10.1016\/j.bioorg.2026.110433_bb0220","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241411367","article-title":"Deciphering the signaling mechanisms of osteosarcoma tumorigenesis","volume":"24","author":"Nirala","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.bioorg.2026.110433_bb0225","doi-asserted-by":"crossref","DOI":"10.1016\/j.prp.2023.154902","article-title":"New emerging targets in osteosarcoma therapy: PTEN and PI3K\/Akt crosstalk in carcinogenesis","volume":"251","author":"Sadrkhanloo","year":"2023","journal-title":"Pathol. Res. Pract."},{"issue":"3","key":"10.1016\/j.bioorg.2026.110433_bb0230","doi-asserted-by":"crossref","DOI":"10.3390\/ph19030499","article-title":"Myricetin inhibits osteosarcoma cell viability and modulates EMT-related genes associated with the SNAI1\/MMP-9 axis","volume":"19","author":"Santos","year":"2026","journal-title":"Pharmaceuticals"},{"issue":"3","key":"10.1016\/j.bioorg.2026.110433_bb0235","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.bmc.2014.12.027","article-title":"Natural antitubulin agents: importance of 3,4,5-trimethoxyphenyl fragment","volume":"23","author":"Negi","year":"2015","journal-title":"Bioorg. Med. Chem."},{"issue":"1","key":"10.1016\/j.bioorg.2026.110433_bb0240","first-page":"1313","article-title":"Novel pyrrolizines bearing 3,4,5-trimethoxyphenyl moiety: design, synthesis, molecular docking, and biological evaluation as potential multi-target cytotoxic agents","volume":"36","author":"Shawky","year":"2021","journal-title":"J. Enzyme Inhib. Med. Chem."},{"issue":"22","key":"10.1016\/j.bioorg.2026.110433_bb0245","doi-asserted-by":"crossref","DOI":"10.3390\/molecules28227530","article-title":"The pharmacological implications of flavopiridol: an updated overview","volume":"28","author":"Joshi","year":"2023","journal-title":"Molecules"},{"key":"10.1016\/j.bioorg.2026.110433_bb0250","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.108839","article-title":"Quercetin suppresses the proliferation and metastasis of metastatic osteosarcoma cells by inhibiting parathyroid hormone receptor 1","volume":"114","author":"Li","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.bioorg.2026.110433_bb0255","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.2147\/IJN.S170862","article-title":"Quercetin and doxorubicin co-delivery using mesoporous silica nanoparticles enhance the efficacy of gastric carcinoma chemotherapy","volume":"13","author":"Fang","year":"2018","journal-title":"Int. J. Nanomedicine"},{"issue":"4","key":"10.1016\/j.bioorg.2026.110433_bb0260","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.molonc.2012.04.002","article-title":"Co-administration phenoxodiol with doxorubicin synergistically inhibit the activity of sphingosine kinase-1 (SphK1), a potential oncogene of osteosarcoma, to suppress osteosarcoma cell growth both in vivo and in vitro","volume":"6","author":"Yao","year":"2012","journal-title":"Mol. Oncol."},{"issue":"9","key":"10.1016\/j.bioorg.2026.110433_bb0265","doi-asserted-by":"crossref","first-page":"5215","DOI":"10.1021\/cr200060g","article-title":"The methylation effect in medicinal chemistry","volume":"111","author":"Barreiro","year":"2011","journal-title":"Chem. Rev."},{"issue":"8","key":"10.1016\/j.bioorg.2026.110433_bb0270","doi-asserted-by":"crossref","DOI":"10.3390\/ph16081157","article-title":"The magic methyl and its tricks in drug discovery and development","volume":"16","author":"Pinheiro","year":"2023","journal-title":"Pharmaceuticals (Basel)"},{"issue":"23","key":"10.1016\/j.bioorg.2026.110433_bb0275","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21239311","article-title":"Methylation: an ineluctable biochemical and physiological process essential to the transmission of life","volume":"21","author":"Menezo","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"19","key":"10.1016\/j.bioorg.2026.110433_bb0280","doi-asserted-by":"crossref","first-page":"17191","DOI":"10.1021\/acs.jmedchem.4c01043","article-title":"Toward the design of allosteric effectors: gaining comprehensive control of drug properties and actions","volume":"67","author":"Tee","year":"2024","journal-title":"J. Med. Chem."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206826009697?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206826009697?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:59:33Z","timestamp":1791406773000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206826009697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":56,"alternative-id":["S0045206826009697"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2026.110433","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design, synthesis, and biological evaluation of secondary amine-containing flavonoids with anti-osteosarcoma activity associated with modulation of AKT signaling and EMT-related gene expression","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2026.110433","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"110433"}}