{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:11:45Z","timestamp":1788509505787,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T00:00:00Z","timestamp":1639872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the excellent research support project of Kwangwoon University","award":["2021"],"award-info":[{"award-number":["2021"]}]},{"name":"the Basic Science Research Program of the National Research Foundation of Korea","award":["2021R1A2C1004285, 2020R1A2C1004006, 2017R1A6A3A11030955"],"award-info":[{"award-number":["2021R1A2C1004285, 2020R1A2C1004006, 2017R1A6A3A11030955"]}]},{"name":"the Center for Women in Science, Engineering and Technology (WISET) Grant funded by the Ministry of Science and ICT(MSIT) under the Program for Returners into R&amp;D.","award":["2021"],"award-info":[{"award-number":["2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polyurethane foams (PUFs) have attracted attention as biomaterials because of their low adhesion to the wound area and suitability as biodegradable or bioactive materials. The composition of the building blocks for PUFs can be controlled with additives, which provide excellent anti-drug resistance and biocompatibility. Herein, nanosized Cu-BTC (copper(II)-benzene-1,3,5-tricarboxylate) was incorporated into a PUF via the crosslinking reaction of castor oil and chitosan with toluene-2,4-diisocyanate, to enhance therapeutic efficiency through the modification of the surface of PUF. The physical and thermal properties of the nanosized Cu-BTC-incorporated PUF (PUF@Cu-BTC), e.g., swelling ratio, phase transition, thermal gravity loss, and cell morphology, were compared with those of the control PUF. The bactericidal activities of PUF@Cu-BTC and control PUF were evaluated against Pseudomonas aeruginosa, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus. PUF@Cu-BTC exhibited selective and significant antibacterial activity toward the tested bacteria and lower cytotoxicity for mouse embryonic fibroblasts compared with the control PUF at a dose of 2 mg mL\u22121. The Cu(II) ions release test showed that PUF@Cu-BTC was stable in phosphate buffered saline (PBS) for 24 h. The selective bactericidal activity and low cytotoxicity of PUF@Cu-BTC ensure it is a candidate for therapeutic applications for the drug delivery, treatment of skin disease, and wound healing.<\/jats:p>","DOI":"10.3390\/ijms222413622","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:37:27Z","timestamp":1639946247000},"page":"13622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Polyurethane Foam Incorporated with Nanosized Copper-Based Metal-Organic Framework: Its Antibacterial Properties and Biocompatibility"],"prefix":"10.3390","volume":"22","author":[{"given":"Do Nam","family":"Lee","sequence":"first","affiliation":[{"name":"Ingenium College of Liberal Arts (Chemistry), Kwangwoon University, Seoul 01897, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2651-1074","authenticated-orcid":false,"given":"Kihak","family":"Gwon","sequence":"additional","affiliation":[{"name":"Ingenium College of Liberal Arts (Chemistry), Kwangwoon University, Seoul 01897, Korea"},{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55902, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhee","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Chemical Engineering, Hanyang University, Ansan 15588, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Jung","family":"Lee","sequence":"additional","affiliation":[{"name":"Ingenium College of Liberal Arts (Chemistry), Kwangwoon University, Seoul 01897, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc Minh","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Chemical Engineering, Hanyang University, Ansan 15588, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4932-3885","authenticated-orcid":false,"given":"Hyojong","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Chemical Engineering, Hanyang University, Ansan 15588, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.progpolymsci.2012.05.003","article-title":"Elastomeric biomaterials for tissue engineering","volume":"38","author":"Chen","year":"2013","journal-title":"Prog. Polym. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.progpolymsci.2015.02.004","article-title":"Advancing biomaterials of human origin for tissue engineering","volume":"53","author":"Chen","year":"2016","journal-title":"Prog. Polym. Sci."},{"key":"ref_3","unstructured":"Alves, P., Ferreira, P., and Gil, M.H. (2012). Biomedical Polyurethane-Based Materials in: Polyurethane: Properties, Structure and Application, Nova Publishers."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/088532829901400104","article-title":"Biomedical applications of polyurethanes: A review of past promises, present realities, and a vibrant future","volume":"14","author":"Zdrahhala","year":"1999","journal-title":"J. Biomater. Appl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/mabi.201200332","article-title":"Design strategies and applications of tissue bioadhesives","volume":"13","author":"Mehdizadeh","year":"2013","journal-title":"Marcromol. Biosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.eurpolymj.2017.08.022","article-title":"PU foam derived from renewable sources: Perspective on properties enhancement: An overview","volume":"95","author":"Agrawal","year":"2017","journal-title":"Eur. Polym. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00289-015-1514-1","article-title":"Synthesis and characterization of rigid polyurethane foams from algae oil using biobased chain extenders","volume":"73","author":"Pawar","year":"2016","journal-title":"Polym. Bull."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1080\/15583720701834224","article-title":"Polyurethanes from vegetable oils","volume":"48","year":"2008","journal-title":"Polym. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/(SICI)1097-4628(20000711)77:2<467::AID-APP25>3.0.CO;2-F","article-title":"Rigid polyurethane foams based on soybean oil","volume":"77","author":"Guo","year":"2000","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s10965-018-1578-3","article-title":"Polyurethanes from vegetable oils and applications: A review","volume":"25","author":"Sawpan","year":"2018","journal-title":"J. Polym. Res."},{"key":"ref_11","unstructured":"Vermette, P., Griesser, H.J., Laroche, G., and Guidoin, R. (2001). Biomedical Application of Polyurethanes, Landes Bioscience."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0032-3861(99)00135-4","article-title":"Surfactant level influences on structure and properties of flexible slabstock polyurethane foams","volume":"41","author":"Kaushiva","year":"2000","journal-title":"Polymer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.progpolymsci.2006.05.003","article-title":"Structural engineering of polyurethane coatings for high performance applications","volume":"32","author":"Chattopadhyay","year":"2007","journal-title":"Prog. Polym. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/cssc.200800241","article-title":"Novel polymeric materials from vegetable oils and vinyl monomers: Preparation, properties, and applications","volume":"2","author":"Lu","year":"2009","journal-title":"ChemSusChem"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1002\/jbm.820261108","article-title":"Porous polyurethane vascular prostheses with variable compliances","volume":"26","author":"Liu","year":"1992","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_16","first-page":"M354","article-title":"Evaluation of stented polyurethane mitral valve prosthesis","volume":"37","author":"Hoffman","year":"1991","journal-title":"Trans Am. Soc. Artif. Intern. Organs."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.compscitech.2016.02.031","article-title":"Antibacterial and biocompatible properties of polyurethane nanofiber composites with integrated antifouling and bactericidal properties","volume":"127","author":"Shi","year":"2016","journal-title":"Compos. Sci. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.carbpol.2013.10.070","article-title":"Electrospun antibacterial polyurethane-cellulose acetate-zein composite mats for wound dressing","volume":"102","author":"Unnithan","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_19","first-page":"635","article-title":"Electrospun polyurethane\/keratin\/AgNP biocomposite mats for biocompatible antibacterial wound dressings","volume":"4","author":"Wang","year":"2016","journal-title":"J. Mater. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1163\/156856299X00874","article-title":"Bacterial adhesion to functionalized polyurethanes","volume":"10","author":"Flemming","year":"1999","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0142-9612(99)00176-3","article-title":"Bacterial colonization of functionalized polyurethanes","volume":"21","author":"Flemming","year":"2000","journal-title":"Biomaterials"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1128\/AAC.29.5.814","article-title":"Quaternary ammonium compounds efficiently inhibit Plasmodium falciparum growth in vitro by impairment of chlorine transport","volume":"29","author":"Ancelin","year":"1986","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.msec.2015.11.038","article-title":"Guanidine hydrochloride embedded polyurethanes as antimicrobial and absorptive wound dressing membranes with promising cytocompatibility","volume":"59","author":"Sahraro","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1381-5148(00)00038-9","article-title":"A review of chitin and chitosan applications","volume":"46","author":"Majeti","year":"2000","journal-title":"React. Funct. Polym."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1021\/bm034130m","article-title":"Chitosan as antimicrobial agent: Applications and mode of action","volume":"4","author":"Rabea","year":"2003","journal-title":"Biomacromolecules"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.1021\/acs.biomac.7b01058","article-title":"Antimicrobial chitosan and chitosan derivatives: A review of the structure\u2013activity relationship","volume":"18","author":"Sahariah","year":"2017","journal-title":"Biomacromolecules"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/adv.20264","article-title":"Antimicrobial Activity of Novel Aminated Chitosan Derivatives for Biomedical Applications","volume":"31","author":"Soliman","year":"2012","journal-title":"Adv. Polym. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.carbpol.2005.10.028","article-title":"Effect of MW and concentration of chitosan on antibacterial activity of Escherichia Coli","volume":"64","author":"Liu","year":"2006","journal-title":"Carbohydr. Polym."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1126\/science.1083440","article-title":"Hydrogen storage in microporous metal-organic frameworks","volume":"300","author":"Rosi","year":"2003","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11887","DOI":"10.1021\/ja4045289","article-title":"Methane storage in metal\u2013organic frameworks: Current records, surprise findings, and challenges","volume":"135","author":"Peng","year":"2013","journal-title":"J. Am. Chem. Soc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1021\/cr2003272","article-title":"Carbon dioxide capture in metal-organic frameworks","volume":"112","author":"Sumida","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.poly.2018.09.028","article-title":"Investigation of reasons for metal\u2013organic framework\u2019s antibacterial activities","volume":"156","author":"Alavijeh","year":"2018","journal-title":"Polyhedron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.micromeso.2008.07.029","article-title":"Comparison of adsorption isotherms on Cu-BTC metal organic frameworks synthesized from different routes","volume":"117","author":"Chowdhury","year":"2009","journal-title":"Micropor. Mesopor. Mat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.micromeso.2010.09.013","article-title":"High pressure adsorption of hydrogen, nitrogen, carbon dioxide and methane on the metal\u2013organic framework CU-BTC","volume":"138","author":"Glaeser","year":"2011","journal-title":"Micropor. Mesopor. Mat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11165","DOI":"10.1039\/c1cp20168a","article-title":"Effect of air humidity on the removal of carbon tetrachloride from air using Cu-BTC metal-organic framework","volume":"13","author":"Hamad","year":"2011","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.micromeso.2011.11.022","article-title":"Adsorption of CO, CO2 and CH4 on Cu-BTC and MIL-101 metal organic frameworks: Effect of open metal sites and adsorbate polarity","volume":"152","author":"Chowdhury","year":"2012","journal-title":"Micropor. Mesopor. Mat."},{"key":"ref_37","first-page":"207","article-title":"Biological metal\u2013organic frameworks: Structures, host\u2013guest chemistry and bio-applications Coord","volume":"378","author":"Cai","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11922","DOI":"10.1039\/c3ta12497e","article-title":"The effect of water adsorption on the structure of the carboxylate containing metal\u2013organic frameworks Cu-BTC, Mg-MOF-74, and UiO-66","volume":"1","author":"DeCoste","year":"2013","journal-title":"J. Mater. Chem. A"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chen, M., Ye, Q., Jiang, S., Shao, M., Jin, C., and Huang, Z. (2019). Two-step elution recovery of cyanide platinum using functional metal organic resin. Molecules, 24.","DOI":"10.3390\/molecules24152779"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.materresbull.2018.07.025","article-title":"Metal organic framework (MOF) porous octahedral nanocrystals of Cu-BTC: Synthesis, properties and enhanced adsorption properties","volume":"109","author":"Kaura","year":"2019","journal-title":"Mater. Res. Bull."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.snb.2012.10.023","article-title":"Work function based gas sensing with Cu-BTC metal-organic framework for selective aldehyde detection","volume":"187","author":"Davydovskaya","year":"2013","journal-title":"Sens. Actuators B"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.snb.2016.02.008","article-title":"Fabrication of capacitive sensor based on Cu-BTC (MOF-199) nanoporous film for detection of ethanol and methanol vapors","volume":"230","author":"Hosseini","year":"2016","journal-title":"Sensor. Actuat. B-Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kidanemariam, A., Lee, J., and Park, J. (2019). Recent innovation of metal-organic frameworks for carbon dioxide photocatalytic reduction. Polymers, 11.","DOI":"10.3390\/polym11122090"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2000059","DOI":"10.1002\/adsu.202000059","article-title":"Fabricating bioactive 3D metal\u2013organic framework devices","volume":"4","author":"Singh","year":"2020","journal-title":"Adv. Sustain. Syst."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7240","DOI":"10.1038\/ncomms8240","article-title":"Biomimetic mineralization of metal-organic frameworks as protective coatings for biomacromolecules","volume":"6","author":"Liang","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6530","DOI":"10.1021\/jacs.7b01794","article-title":"Shielding against Unfolding by Embedding Enzymes in Metal\u2013Organic Frameworks via a de Novo Approach","volume":"139","author":"Liao","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3386","DOI":"10.1039\/C7CS00058H","article-title":"Enzyme\u2013MOF (metal\u2013organic framework) composites","volume":"46","author":"Lian","year":"2017","journal-title":"Chem. Soc. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ccr.2019.02.009","article-title":"Recent advances in the rational synthesis and sensing applications of metal-organic framework biocomposites","volume":"387","author":"Qiu","year":"2019","journal-title":"Coord. Chem. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1021\/ja2110152","article-title":"Coordination-chemistry control of proton conductivity in the iconic metal\u2212organic framework material HKUST-1","volume":"134","author":"Jeong","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Stachak, P., \u0141ukaszewska, I., Hebda, E., and Pielichowski, K. (2021). Recent Advances in Fabrication of Non-Isocyanate Polyurethane-Based Composite Materials. Materials, 14.","DOI":"10.3390\/ma14133497"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.eurpolymj.2013.04.005","article-title":"Green synthesis of flexible polyurethane foams from liquefied lignin","volume":"49","author":"Cinelli","year":"2013","journal-title":"Eur. Polym. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s10924-012-0538-y","article-title":"Effects of Wood Fiber and Microclay on the Performance of Soy Based Polyurethane Foams","volume":"21","author":"Gu","year":"2013","journal-title":"J. Polym Environ."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.porgcoat.2011.05.006","article-title":"Antimicrobial polyurethane coatings based on ionic liquid quaternary ammonium compounds","volume":"72","author":"Yagci","year":"2011","journal-title":"Prog. Org. Coat."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"586","DOI":"10.3390\/molecules14020586","article-title":"Antimicrobial activity of five herbal extracts against multi drug resistant (MDR) strains of bacteria and fungus of clinical origin","volume":"14","author":"Khan","year":"2009","journal-title":"Molecules"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"109893","DOI":"10.1016\/j.msec.2019.109893","article-title":"Nanocomposite foams based on flexible biobased thermoplastic polyurethane and ZnO nanoparticles as potential wound dressing materials","volume":"104","author":"Dinescu","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1177\/0021998317710707","article-title":"Preparation, characterization, and properties of castor oil-based flexible polyurethane\/Cloisite 30B nanocomposites foam","volume":"52","author":"Panda","year":"2018","journal-title":"J. Compos. Mater."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Wang, R., Zhou, B., Zhu, Y., and Wang, Z. (2019). Preparation and characterization of rigid polyurethane foams with different loadings of lignin-derived polycarboxylic acids. Int. J. Polym. Sci., 3710545.","DOI":"10.1155\/2019\/3710545"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.msec.2018.04.029","article-title":"Improved near infrared-mediated hydrogel formation using diacrylated Pluronic F127-coated upconversion nanoparticles","volume":"90","author":"Gwon","year":"2018","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"101334","DOI":"10.1039\/C6RA18479K","article-title":"Preparation and applications of peptide-based injectable hydrogels","volume":"6","author":"Cheng","year":"2016","journal-title":"RSC Adv."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"20234","DOI":"10.1021\/acsami.0c03187","article-title":"Novel Metal\u2013Organic Framework-Based Photocrosslinked Hydrogel System for Efficient Antibacterial Applications","volume":"12","author":"Gwon","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13622\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:52:09Z","timestamp":1760169129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,19]]},"references-count":60,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222413622"],"URL":"https:\/\/doi.org\/10.3390\/ijms222413622","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,19]]}}}