{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T12:32:09Z","timestamp":1771504329768,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC2310800"],"award-info":[{"award-number":["2024YFC2310800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Technological Innovation and Application Development Foundation of Chongqing","award":["CSTB2024TIAD-STX0043"],"award-info":[{"award-number":["CSTB2024TIAD-STX0043"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202396"],"award-info":[{"award-number":["82202396"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Objectives: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) merges multidrug resistance with hypervirulence, posing unprecedented therapeutic challenges. This study aimed to evaluate the efficacy of a recombinant fusion protein vaccine, KPC-Pal, designed to target both the carbapenemase KPC-2 and the virulence-associated peptidoglycan-associated lipoprotein Pal. Methods: The KPC-Pal fusion protein was constructed, expressed, and purified. Its protective efficacy was systematically assessed in a murine pneumonia model by measuring antigen-specific antibodies, cytokine profiles, and memory cell populations. The synergistic effect with the antibiotic meropenem was evaluated both in vitro and in vivo. Furthermore, the interaction with innate immune signaling via TLR2 was investigated. Results: Immunization with KPC-Pal conferred superior protection, resulting in significantly higher survival rates and reduced bacterial burdens in the lungs compared to immunization with either KPC-2 or Pal alone. It induced a robust Th2-biased humoral response and a mixed Th1\/Th2\/Th17 cellular immune profile, along with enhanced formation of tissue-resident memory T cells. Antibodies generated against KPC-Pal enhanced the efficacy of meropenem in vitro and in animal models, demonstrating a synergistic effect. While Pal alone strongly activated TLR2-driven inflammatory pathways, the KPC-Pal fusion selectively modulated MAPK signaling, mitigating excessive cytokine production. Additionally, KPC-Pal vaccination elicited cross-reactive antibodies against KPC-3 and KPC-33 variants. Conclusions: KPC-Pal functions as both an antigen and a self-adjuvant, offering a promising dual-target strategy for combating K. pneumoniae infections.<\/jats:p>","DOI":"10.3390\/vaccines14020190","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T11:44:27Z","timestamp":1771501467000},"page":"190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vaccination with Carbapenemase KPC-2 and Virulence Factor Pal Provided Robust Protection Against Klebsiella pneumoniae Lung Infection"],"prefix":"10.3390","volume":"14","author":[{"given":"Shichun","family":"Jiang","sequence":"first","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Yuan","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0670-383X","authenticated-orcid":false,"given":"Yuanda","family":"Tang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingwen","family":"Liao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhifu","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqian","family":"Yu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China"},{"name":"Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China"},{"name":"School of Laboratory Medicine, North Sichuan Medical College, Nanchong 637000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Disease Prevention and Control, The Fourth Medical Centre of the Chinese PLA General Hospital, Beijing 100089, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Gou","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiming","family":"Jing","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongxue","family":"Xu","sequence":"additional","affiliation":[{"name":"Beijing Minhai Biotechnology Co., Ltd., Beijing 102600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quanming","family":"Zou","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9622-5834","authenticated-orcid":false,"given":"Jinyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S1473-3099(18)30605-4","article-title":"Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: A population-level modelling analysis","volume":"19","author":"Cassini","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"ofz029","DOI":"10.1093\/ofid\/ofz029","article-title":"Bacteremic Community-Acquired Pneumonia in Ethiopian Children: Etiology, Antibiotic Resistance, Risk Factors, and Clinical Outcome","volume":"6","author":"Negash","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4161\/viru.22718","article-title":"Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: A new and dangerous breed","volume":"4","author":"Shon","year":"2013","journal-title":"Virulence"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/cid\/cir202","article-title":"Carbapenem-resistant Enterobacteriaceae: Epidemiology and prevention","volume":"53","author":"Gupta","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/CMR.00001-19","article-title":"Hypervirulent Klebsiella pneumoniae","volume":"32","author":"Russo","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.cmi.2017.08.030","article-title":"Management of KPC-producing Klebsiella pneumoniae infections","volume":"24","author":"Bassetti","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/d41586-017-08323-0","article-title":"Deploy vaccines to fight superbugs","volume":"552","author":"Rappuoli","year":"2017","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1177\/1073110518782912","article-title":"Antibiotic Pipeline Coordinators","volume":"46","author":"Baraldi","year":"2018","journal-title":"J. Law. Med. Ethics"},{"key":"ref_10","unstructured":"(2022). 10. Global mortality associated with 33 bacterial pathogens in 2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 400, 2221\u20132248."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1176","DOI":"10.1016\/S2214-109X(17)30364-9","article-title":"Vaccination to reduce antimicrobial resistance","volume":"5","author":"Ginsburg","year":"2017","journal-title":"Lancet Glob. Health"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1016\/j.vaccine.2017.06.003","article-title":"The complexity and cost of vaccine manufacturing\u2014An overview","volume":"35","author":"Plotkin","year":"2017","journal-title":"Vaccine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41579-020-00506-3","article-title":"The role of vaccines in combatting antimicrobial resistance","volume":"19","author":"Micoli","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1128\/CVI.00290-09","article-title":"Vaccines: The fourth century","volume":"16","author":"Plotkin","year":"2009","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/cmdc.201200487","article-title":"Modern subunit vaccines: Development, components, and research opportunities","volume":"8","author":"Moyle","year":"2013","journal-title":"ChemMedChem"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1016\/j.vaccine.2011.11.027","article-title":"Development of immunization trials against Klebsiella pneumoniae","volume":"30","author":"Ahmad","year":"2012","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18655","DOI":"10.1073\/pnas.1907833116","article-title":"A promising bioconjugate vaccine against hypervirulent Klebsiella pneumoniae","volume":"116","author":"Feldman","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1099\/mic.0.050336-0","article-title":"The role of Klebsiella pneumoniae rmpA in capsular polysaccharide synthesis and virulence revisited","volume":"157","author":"Hsu","year":"2011","journal-title":"Microbiology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107380","DOI":"10.1016\/j.compbiolchem.2020.107380","article-title":"Identification of novel vaccine candidates against carbapenem resistant Klebsiella pneumoniae: A systematic reverse proteomic approach","volume":"89","author":"Mehmood","year":"2020","journal-title":"Comput. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"La Guidara, C., Adamo, R., Sala, C., and Micoli, F. (2024). Vaccines and Monoclonal Antibodies as Alternative Strategies to Antibiotics to Fight Antimicrobial Resistance. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105487"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1038\/s41467-017-02223-7","article-title":"Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae","volume":"8","author":"Pennini","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41577-020-00479-7","article-title":"A guide to vaccinology: From basic principles to new developments","volume":"21","author":"Pollard","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"126217","DOI":"10.1016\/j.vaccine.2024.126217","article-title":"Vaccination with a trivalent Klebsiella pneumoniae vaccine confers protection in a murine model of pneumonia","volume":"42","author":"Chen","year":"2024","journal-title":"Vaccine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S1473-3099(13)70190-7","article-title":"Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases","volume":"13","author":"Poirel","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1128\/CMR.00001-07","article-title":"Carbapenemases: The versatile beta-lactamases","volume":"20","author":"Queenan","year":"2007","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"000759-v3","DOI":"10.1099\/acmi.0.000759.v3","article-title":"Cell division cycle fluctuation of Pal concentration in Escherichia coli","volume":"6","author":"Mertens","year":"2024","journal-title":"Access Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1080\/21505594.2020.1804275","article-title":"The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge","volume":"11","author":"Dyke","year":"2020","journal-title":"Virulence"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.4049\/jimmunol.1001647","article-title":"Bacterial lipoprotein TLR2 agonists broadly modulate endothelial function and coagulation pathways in vitro and in vivo","volume":"186","author":"Shin","year":"2011","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1038\/35074106","article-title":"The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5","volume":"410","author":"Hayashi","year":"2001","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"31312","DOI":"10.1038\/s41598-025-17044-8","article-title":"Exploring mutational possibilities of KPC variants to reach high level resistance to cefiderocol","volume":"15","author":"Hanna","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/s41467-020-15083-5","article-title":"The lipoprotein Pal stabilises the bacterial outer membrane during constriction by a mobilisation-and-capture mechanism","volume":"11","author":"Szczepaniak","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Colleselli, K., Stierschneider, A., and Wiesner, C. (2023). An Update on Toll-like Receptor 2, Its Function and Dimerization in Pro- and Anti-Inflammatory Processes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512464"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1128\/MMBR.00078-15","article-title":"Klebsiella pneumoniae: Going on the Offense with a Strong Defense","volume":"80","author":"Paczosa","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1093\/femsre\/fux013","article-title":"Klebsiella pneumoniae: A major worldwide source and shuttle for antibiotic resistance","volume":"41","author":"Kondratyeva","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1128\/CMR.05035-11","article-title":"Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: An evolving crisis of global dimensions","volume":"25","author":"Tzouvelekis","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1016\/j.drudis.2021.02.014","article-title":"Challenges and opportunities in the discovery, development, and commercialization of pathogen-targeted antibiotics","volume":"26","author":"Altarac","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"262ra155","DOI":"10.1126\/scitranslmed.3009655","article-title":"A multifunctional bispecific antibody protects against Pseudomonas aeruginosa","volume":"6","author":"DiGiandomenico","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1128\/CMR.00037-09","article-title":"Three decades of beta-lactamase inhibitors","volume":"23","author":"Drawz","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"110590","DOI":"10.1016\/j.ygeno.2023.110590","article-title":"Peptidoglycan-associated lipoprotein contributes to the virulence of Acinetobacter baumannii and serves as a vaccine candidate","volume":"115","author":"Zeng","year":"2023","journal-title":"Genomics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/s41590-018-0106-2","article-title":"Cross-specificity of protective human antibodies against Klebsiella pneumoniae LPS O-antigen","volume":"19","author":"Rollenske","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1002\/eji.200939722","article-title":"Heterogeneity of CD4+ memory T cells: Functional modules for tailored immunity","volume":"39","author":"Sallusto","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mackel, J.J., Morffy Smith, C., Wasbotten, R.K., Twentyman, J., and Rosen, D.A. (2022). Classical and \u03b3\u03b4 T cells are each independently sufficient to establish protection against a classical strain of Klebsiella pneumoniae. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.974175"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"eaas9673","DOI":"10.1126\/sciimmunol.aas9673","article-title":"Location, location, location: Tissue resident memory T cells in mice and humans","volume":"4","author":"Szabo","year":"2019","journal-title":"Sci. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4943","DOI":"10.1128\/AAC.00296-11","article-title":"Carbapenems: Past, present, and future","volume":"55","author":"Endimiani","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nrd.2017.23","article-title":"Different drugs for bad bugs: Antivirulence strategies in the age of antibiotic resistance","volume":"16","author":"Dickey","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1007\/s00203-024-04107-z","article-title":"Respiratory tract infections: An update on the complexity of bacterial diversity, therapeutic interventions and breakthroughs","volume":"206","author":"Panickar","year":"2024","journal-title":"Arch. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/nm.3409","article-title":"Key roles of adjuvants in modern vaccines","volume":"19","author":"Reed","year":"2013","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1086\/427815","article-title":"Bacterial peptidoglycan-associated lipoprotein: A naturally occurring toll-like receptor 2 agonist that is shed into serum and has synergy with lipopolysaccharide","volume":"191","author":"Liang","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"127839","DOI":"10.1016\/j.micres.2024.127839","article-title":"Hypervirulent and carbapenem-resistant Klebsiella pneumoniae: A global public health threat","volume":"288","author":"Lei","year":"2024","journal-title":"Microbiol. Res."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/2\/190\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T11:51:21Z","timestamp":1771501881000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/2\/190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":49,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["vaccines14020190"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14020190","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]}}}