{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:26:37Z","timestamp":1791516397139,"version":"4.3.4"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Propolis, also known as bee-glue, is a resinous substance produced by honeybees from materials collected from plants they visit. It contains mixtures of wax and bee enzymes and is used by bees as a building material in their hives and by humans for different purposes in traditional healthcare practices. Although the composition of propolis has been shown to depend on its geographic location, climatic zone, and local flora; two largely studied types of propolis: (i) New Zealand and (ii) Brazilian green propolis have been shown to possess Caffeic Acid Phenethyl Ester (CAPE) and Artepillin C (ARC) as the main bioactive constituents, respectively. We have earlier reported that CAPE and ARC possess anticancer activities, mediated by abrogation of mortalin-p53 complex and reactivation of p53 tumor suppressor function. Like CAPE, Artepillin C (ARC) and the supercritical extract of green propolis (GPSE) showed potent anticancer activity. In this study, we recruited low doses of GPSE and ARC (that did not affect either cancer cell proliferation or migration) to investigate their antistress potential using in vitro cell based assays. We report that both GPSE and ARC have the capability to disaggregate metal- and heat-induced aggregated proteins. Metal-induced aggregation of GFP was reduced by fourfold in GPSE- as well as ARC-treated cells. Similarly, whereas heat-induced misfolding of luciferase protein showed 80% loss of activity, the cells treated with either GPSE or ARC showed 60\u201380% recovery. Furthermore, we demonstrate their pro-hypoxia (marked by the upregulation of HIF-1\u03b1) and neuro-differentiation (marked by differentiation morphology and upregulation of expression of GFAP, \u03b2-tubulin III, and MAP2). Both GPSE and ARC also offered significant protection against oxidative stress and, hence, may be useful in the treatment of old age-related brain pathologies.<\/jats:p>","DOI":"10.3390\/molecules27010080","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T21:40:21Z","timestamp":1640295621000},"page":"80","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Molecular Insights into the Antistress Potentials of Brazilian Green Propolis Extract and Its Constituent Artepillin C"],"prefix":"10.3390","volume":"27","author":[{"given":"Ashish","family":"Kaul","sequence":"first","affiliation":[{"name":"AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba 305-8565, Japan"},{"name":"School of Integrative & Global Majors, University of Tsukuba, Tsukuba 305-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0697-7835","authenticated-orcid":false,"given":"Raviprasad","family":"Kuthethur","sequence":"additional","affiliation":[{"name":"AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba 305-8565, Japan"},{"name":"Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education (MAHE), Manipal 576-104, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Ishida","sequence":"additional","affiliation":[{"name":"CycloChem Co., Ltd., 7-4-5 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6563-095X","authenticated-orcid":false,"given":"Keiji","family":"Terao","sequence":"additional","affiliation":[{"name":"CycloChem Co., Ltd., 7-4-5 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8248-5192","authenticated-orcid":false,"given":"Renu","family":"Wadhwa","sequence":"additional","affiliation":[{"name":"AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba 305-8565, Japan"},{"name":"School of Integrative & Global Majors, University of Tsukuba, Tsukuba 305-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil C.","family":"Kaul","sequence":"additional","affiliation":[{"name":"AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba 305-8565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"96414","DOI":"10.1155\/2013\/964149","article-title":"Historical Aspects of Propolis Research in Modern Times","volume":"2013","author":"Kuropatnicki","year":"2013","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.jep.2005.05.004","article-title":"Chemical diversity of propolis and the problem of standardization","volume":"100","author":"Bankova","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1590\/S1678-91992007000400002","article-title":"Propolis: A review of its anti-inflammatory and healing actions","volume":"13","author":"Ramos","year":"2007","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1002\/med.21757","article-title":"Propolis: A useful agent on psychiatric and neurological disorders? A focus on CAPE and pinocembrin components","volume":"41","author":"Luz","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kurek-G\u00f3recka, A., G\u00f3recki, M., Rzepecka-Stojko, A., Balwierz, R., and Stojko, J. (2020). Bee Products in Dermatology and Skin Care. Molecules, 25.","DOI":"10.3390\/molecules25030556"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"779","DOI":"10.2741\/e418","article-title":"Beneficial effects of propolis on human health and neurological diseases","volume":"E4","author":"Farooqui","year":"2012","journal-title":"Front. Biosci. Elite Ed."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"113623","DOI":"10.1016\/j.jep.2020.113623","article-title":"The gastroprotective effect of red propolis extract from Northeastern Brazil and the role of its isolated compounds","volume":"267","author":"Boeing","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153368","DOI":"10.1016\/j.phymed.2020.153368","article-title":"A standardized polyphenol mixture extracted from poplar-type propolis for remission of symptoms of uncomplicated upper respiratory tract infection (URTI): A monocentric, randomized, double-blind, placebo-controlled clinical trial","volume":"80","author":"Esposito","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.biopha.2017.12.069","article-title":"Potential role of propolis in wound healing: Biological properties and therapeutic activities","volume":"98","author":"Oryan","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/j.sjbs.2018.08.013","article-title":"Composition and functional properties of propolis (bee glue): A review","volume":"26","author":"Anjum","year":"2019","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1002\/jsfa.10024","article-title":"Propolis: Types, composition, biological activities, and veterinary product patent prospecting","volume":"100","author":"Santos","year":"2020","journal-title":"J. Sci. Food Agric."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104775","DOI":"10.1016\/j.fitote.2020.104775","article-title":"Artepillin C: A comprehensive review of its chemistry, bioavailability, and pharmacological properties","volume":"147","author":"Shahinozzaman","year":"2020","journal-title":"Fitoterapia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"70","DOI":"10.15430\/JCP.2020.25.2.70","article-title":"Chemopreventive and Chemotherapeutic Effect of Propolis and Its Constituents: A Mini-review","volume":"25","author":"Chiu","year":"2020","journal-title":"J. Cancer Prev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Przyby\u0142ek, I., and Karpi\u0144ski, T.M. (2019). Antibacterial Properties of Propolis. Molecules, 24.","DOI":"10.3390\/molecules24112047"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"344","DOI":"10.5455\/jice.20151012013034","article-title":"Antiviral Properties of Caffeic Acid Phenethyl Ester and Its Potential Application","volume":"4","author":"Erdemli","year":"2015","journal-title":"J. Intercult. Ethnopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1046\/j.1439-0507.2001.00671.x","article-title":"Antifungal activity of propolis on different species of Candida","volume":"44","author":"Ota","year":"2001","journal-title":"Mycoses"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s12275-020-0277-z","article-title":"Anti-inflammatory and anti-oxidative effect of Korean propolis on Helicobacter pylori-induced gastric damage in vitro","volume":"58","author":"Song","year":"2020","journal-title":"J. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1021\/acs.jafc.8b07304","article-title":"Anti-inflammatory and anti-Candida Effects of Brazilian Organic Propolis, a Promising Source of Bioactive Molecules and Functional Food","volume":"68","author":"Nani","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wang, J., Bhargava, P., Yu, Y., Sari, A.N., Zhang, H., Ishii, N., Yan, K., Zhang, Z., Ishida, Y., and Terao, K. (2020). Novel Caffeic Acid Phenethyl Ester-Mortalin Antibody Nanoparticles Offer Enhanced Selective Cytotoxicity to Cancer Cells. Cancers, 12.","DOI":"10.3390\/cancers12092370"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102390","DOI":"10.1016\/j.ctim.2020.102390","article-title":"Bee products and their role in cancer prevention and treatment","volume":"51","year":"2020","journal-title":"Complement. Ther. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100039","DOI":"10.1016\/j.medidd.2020.100039","article-title":"PAK1-blockers: Potential Therapeutics against COVID-19","volume":"6","author":"Maruta","year":"2020","journal-title":"Med. Drug Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"104536","DOI":"10.1016\/j.bioorg.2020.104536","article-title":"Discovery of CAPE derivatives as dual EGFR and CSK inhibitors with anticancer activity in a murine model of hepatocellular carcinoma","volume":"107","author":"Liu","year":"2021","journal-title":"Bioorg. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.7150\/jca.15170","article-title":"Molecular Characterization and Enhancement of Anticancer Activity of Caffeic Acid Phenethyl Ester by \u03b3 Cyclodextrin","volume":"7","author":"Wadhwa","year":"2016","journal-title":"J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sari, A.N., Bhargava, P., Dhanjal, J.K., Putri, J.F., Radhakrishnan, N., Shefrin, S., Ishida, Y., Terao, K., Sundar, D., and Kaul, S.C. (2020). Combination of Withaferin-A and CAPE Provides Superior Anticancer Potency: Bioinformatics and Experimental Evidence to Their Molecular Targets and Mechanism of Action. Cancers, 12.","DOI":"10.3390\/cancers12051160"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s11010-007-9663-7","article-title":"Caffeic acid phenethyl ester induces mitochondria-mediated apoptosis in human myeloid leukemia U937 cells","volume":"310","author":"Jin","year":"2008","journal-title":"Mol. Cell. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1016\/j.bcp.2003.07.014","article-title":"Involvement of tumor suppressor protein p53 and p38 MAPK in caffeic acid phenethyl ester-induced apoptosis of C6 glioma cells","volume":"66","author":"Lee","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"926","DOI":"10.3109\/13880209.2013.865243","article-title":"Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-\u03baB signaling in activated HMC-1 human mast cells","volume":"52","author":"Cho","year":"2014","journal-title":"Pharm. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"735176","DOI":"10.1155\/2013\/735176","article-title":"Inhibition of Inflammatory Response by Artepillin C in Activated RAW264.7 Macrophages","volume":"2013","author":"Szliszka","year":"2013","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.freeradbiomed.2020.06.033","article-title":"Mechanism of synergistic DNA damage induced by caffeic acid phenethyl ester (CAPE) and Cu(II): Competitive binding between CAPE and DNA with Cu(II)\/Cu(I)","volume":"159","author":"Shao","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/bmc.737","article-title":"Stability of caffeic acid phenethyl ester and its fluorinated derivative in rat plasma","volume":"21","author":"Wang","year":"2007","journal-title":"Biomed. Chromatogr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9928","DOI":"10.1021\/jf051962y","article-title":"Absorption and Bioavailability of Artepillin C in Rats after Oral Administration","volume":"53","author":"Konishi","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","first-page":"308249","article-title":"Propolis: A Wonder Bees Product and Its Pharmacological Potentials","volume":"2013","author":"Wagh","year":"2013","journal-title":"Adv. Pharmacol. Sci."},{"key":"ref_33","first-page":"925","article-title":"Anticancer activity of the supercritical extract of Brazilian green propolis and its active component, artepillin\u00ef\u00bf\u00bdC: Bioinformatics and experimental analyses of its mechanisms of action","volume":"52","author":"Bhargava","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zabot, G.L., Vigan\u00f3, J., and Silva, E.K. (2021). Low-Frequency Ultrasound Coupled with High-Pressure Technologies: Impact of Hybridized Techniques on the Recovery of Phytochemical Compounds. Molecules, 26.","DOI":"10.3390\/molecules26175117"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Baldino, L., Scognamiglio, M., and Reverchon, E. (2021). Supercritical CO2 Extraction of Organic Solvents from Flunisolide and Fluticasone Propionate. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13050612"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.supflu.2017.09.008","article-title":"Concentration of Ruta graveolens active compounds using SC-CO2 extraction coupled with fractional separation","volume":"131","author":"Baldino","year":"2018","journal-title":"J. Supercrit. Fluids"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1007\/s12192-018-0915-0","article-title":"Caffeic acid phenethyl ester (CAPE) possesses pro-hypoxia and anti-stress activities: Bioinformatics and experimental evidences","volume":"23","author":"Bhargava","year":"2018","journal-title":"Cell Stress Chaperones"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8078","DOI":"10.1093\/nar\/gkr492","article-title":"MicroRNA-296 is enriched in cancer cells and downregulates p21WAF1 mRNA expression via interaction with its 3\u2032 untranslated region","volume":"39","author":"Yoon","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1186\/s13046-019-1500-9","article-title":"Mortaparib, a novel dual inhibitor of mortalin and PARP1, is a potential drug candidate for ovarian and cervical cancers","volume":"38","author":"Putri","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e22643","DOI":"10.1002\/jbt.22643","article-title":"Understanding the complicated relationship between antioxidants and carcinogenesis","volume":"35","author":"Majumder","year":"2021","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.arr.2012.10.004","article-title":"Oxidative stress and cancer: An overview","volume":"12","author":"Sosa","year":"2013","journal-title":"Ageing Res. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"561925","DOI":"10.3389\/fnagi.2020.561925","article-title":"Identification of Caffeic Acid Phenethyl Ester (CAPE) as a Potent Neurodifferentiating Natural Compound That Improves Cognitive and Physiological Functions in Animal Models of Neurodegenerative Diseases","volume":"12","author":"Konar","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8977","DOI":"10.1111\/jcmm.15531","article-title":"Neuroprotective effects of astaxanthin against oxygen and glucose deprivation damage via the PI3K\/Akt\/GSK3\u03b2\/Nrf2 signalling pathway in vitro","volume":"24","author":"Zhang","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.cmet.2018.05.011","article-title":"Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States","volume":"27","author":"Mattson","year":"2018","journal-title":"Cell Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"105124","DOI":"10.1016\/j.neuint.2021.105124","article-title":"Experimental evidence and mechanism of action of some popular neuro-nutraceutical herbs","volume":"149","author":"Kumar","year":"2021","journal-title":"Neurochem. Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1016\/j.sjbs.2020.11.068","article-title":"Induction of liver fibrosis by CCl4 mediates pathological alterations in the spleen and lymph nodes: The potential therapeutic role of propolis","volume":"28","author":"Sayed","year":"2020","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108334","DOI":"10.1016\/j.neuropharm.2020.108334","article-title":"Caffeic acid phenethyl ester counteracts doxorubicin-induced chemobrain in Sprague-Dawley rats: Emphasis on the modulation of oxidative stress and neuroinflammation","volume":"181","author":"Ali","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Choromanska, A., Saczko, J., and Kulbacka, J. (2020). Caffeic Acid Phenethyl Ester Assisted by Reversible Electroporation\u2014In Vitro Study on Human Melanoma Cells. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12050478"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Spanidi, E., Karapetsas, A., Voulgaridou, G.-P., Letsiou, S., Aligiannis, N., Tsochantaridis, I., Kynigopoulos, S., Lambropoulou, M., Mourtzinos, I., and Pappa, A. (2021). A New Controlled Release System for Propolis Polyphenols and Its Biochemical Activity for Skin Applications. Plants, 10.","DOI":"10.3390\/plants10020420"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1177\/1534735417753545","article-title":"Anticancer Activity in Honeybee Propolis: Functional Insights to the Role of Caffeic Acid Phenethyl Ester and Its Complex With \u03b3-Cyclodextrin","volume":"17","author":"Ishida","year":"2018","journal-title":"Integr. Cancer Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.abb.2004.02.021","article-title":"Antioxidative bioavailability of artepillin C in Brazilian propolis","volume":"424","author":"Shimizu","year":"2004","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7984327","DOI":"10.1155\/2017\/7984327","article-title":"The Neuroprotective Effects of Brazilian Green Propolis on Neurodegenerative Damage in Human Neuronal SH-SY5Y Cells","volume":"2017","author":"Ni","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1080\/02713683.2019.1705493","article-title":"Neuroprotective Effect of Brazilian Green Propolis on Retinal Ganglion Cells in Ischemic Mouse Retina","volume":"45","author":"Park","year":"2020","journal-title":"Curr. Eye Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/1\/80\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:52:22Z","timestamp":1760169142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/1\/80"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,23]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["molecules27010080"],"URL":"https:\/\/doi.org\/10.3390\/molecules27010080","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,23]]}}}