{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:13:30Z","timestamp":1785420810937,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jilin Provincial Natural Science Foundation of China","award":["20220101335JC"],"award-info":[{"award-number":["20220101335JC"]}]},{"name":"Jilin Provincial Department of Education","award":["JJKH20230377KJ"],"award-info":[{"award-number":["JJKH20230377KJ"]}]},{"award":["JJKH20230377KJ"],"award-info":[{"award-number":["JJKH20230377KJ"]}],"id":[{"id":"https:\/\/ror.org\/05782e512","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: This study aimed to construct a recombinant Pseudomonas aeruginosa outer membrane vesicle (OMV) vector vaccine delivering pcrV and compare the immunological impacts of OMVs as carriers versus as adjuvants. Methods: The recombinant plasmid pBBRMCS5-pcrV was constructed and transformed into P. aeruginosa. Recombinant OMVs (OMVPcrV) were prepared via ultracentrifugation and characterized in terms of their morphology and particle size by means of transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). After a biosafety evaluation, mice were intramuscularly immunized with PcrV or OMVPcrV, followed by a booster immunization on day 21. On day 42, the mice were challenged subcutaneously and intranasally with PAO1. Bacterial loads in tissues and blood, pulmonary T-cell subsets, and serum antibody levels were assessed. Results: The recombinant plasmid was successfully constructed, and Western blotting confirmed the delivery of PcrV into OMVs. TEM revealed typical spherical nanostructures, and NTA showed a median particle size of 127.4 \u00b1 5.3 nm. Upon subcutaneous challenge, the OMV, OMVPcrV, and OMV + PcrV groups all achieved 100% protection. Both the OMVPcrV and OMV + PcrV groups exhibited increased CD4+ and CD8+ T-cell counts and higher induction levels of specific IgM, IgG1, and IgG2a antibodies. The OMVPcrV group showed superior clearance of respiratory bacterial colonization and reduced inflammatory injury compared with the PBS control group. Conclusions: The constructed vector successfully delivered the PcrV antigen, and the OMVPcrV vaccine induced effective immune responses. Compared with wild-type outer membrane vesicles (OMVs) and the strategy of directly mixing free PcrV antigen with OMVs (OMV + PcrV), the recombinant OMVPcrV vaccine exhibited superior immunoprotective efficacy in terms of bacterial clearance and tissue protection, providing experimental evidence for the development of a Pseudomonas aeruginosa vaccine.<\/jats:p>","DOI":"10.3390\/vaccines14060518","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:33:44Z","timestamp":1781073224000},"page":"518","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Recombinant OMV-Based Vaccine Elicits Potent Protective Immunity Against Pseudomonas aeruginosa"],"prefix":"10.3390","volume":"14","author":[{"given":"Jiannan","family":"Li","sequence":"first","affiliation":[{"name":"College of Life Sciences, Jilin Agricultural University, Changchun 130118, China"},{"name":"Key Laboratory of Jilin Province for Zoonoses Prevention and Control, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyu","family":"Qi","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixian","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Jilin Province for Zoonoses Prevention and Control, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3260-3514","authenticated-orcid":false,"given":"Gejin","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Jilin Province for Zoonoses Prevention and Control, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xulong","family":"Lang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Jilin Province for Zoonoses Prevention and Control, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiancheng","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2144-5725","authenticated-orcid":false,"given":"Lingwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Jilin Province for Zoonoses Prevention and Control, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuran","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Laboratory Animal & Shandong Laboratory Animal Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wood, S.J., Kuzel, T.M., and Shafikhani, S.H. (2023). Pseudomonas aeruginosa: Infections, Animal Modeling, and Therapeutics. Cells, 12.","DOI":"10.3390\/cells12010199"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Liao, C., Huang, X., Wang, Q., Yao, D., and Lu, W. (2022). Virulence Factors of Pseudomonas aeruginosa and Antivirulence Strategies to Combat Its Drug Resistance. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.926758"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1080\/1040841X.2023.2285995","article-title":"Emerging strategies to target virulence in Pseudomonas aeruginosa respiratory infections","volume":"50","author":"Hibbert","year":"2024","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1007\/s40265-021-01635-6","article-title":"The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update","volume":"81","author":"Reynolds","year":"2021","journal-title":"Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.37201\/req\/s01.13.2023","article-title":"Present and future of resistance in Pseudomonas aeruginosa: Implications for treatment","volume":"36","author":"Rua","year":"2023","journal-title":"Rev. Esp. Quim."},{"key":"ref_6","first-page":"1261","article-title":"Research progress of Pseudomonas aeruginosa vaccines","volume":"34","author":"Yang","year":"2021","journal-title":"Chin. J. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sainz-Mej\u00edas, M., Jurado-Mart\u00edn, I., and McClean, S. (2020). Understanding Pseudomonas aeruginosa\u2013Host Interactions: The Ongoing Quest for an Efficacious Vaccine. Cells, 9.","DOI":"10.3390\/cells9122617"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jinf.2017.05.001","article-title":"Predicted vs. observed effectiveness of outer membrane vesicle (OMV) vaccines against meningococcal serogroup B disease: Systematic review","volume":"75","author":"Harder","year":"2017","journal-title":"J. Infect."},{"key":"ref_9","first-page":"413","article-title":"Outer Membrane Vesicle Vaccine Platforms","volume":"117","author":"Micoli","year":"2023","journal-title":"Pathog. Glob. Health"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lieberman, L.A. (2022). Outer membrane vesicles: A bacterial-derived vaccination system. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1029146"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41579-018-0112-2","article-title":"Types and origins of bacterial membrane vesicles","volume":"17","author":"Toyofuku","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12934-025-02653-9","article-title":"Review on bacterial outer membrane vesicles: Structure, vesicle formation, separation and biotechnological applications","volume":"24","author":"Zhao","year":"2025","journal-title":"Microb. Cell Fact."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.vaccine.2003.08.027","article-title":"Stability of mono- and trivalent meningococcal outer membrane vesicle vaccines","volume":"22","author":"Arigita","year":"2004","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tan, K., Li, R., Huang, X., and Liu, Q. (2018). Outer Membrane Vesicles: Current Status and Future Direction of These Novel Vaccine Adjuvants. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00783"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.biotechadv.2017.05.003","article-title":"Bioengineering bacterial outer membrane vesicles as vaccine platform","volume":"35","author":"Gerritzen","year":"2017","journal-title":"Biotechnol. Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e02567-17","DOI":"10.1128\/AEM.02567-17","article-title":"Display of Recombinant Proteins on Bacterial Outer Membrane Vesicles by Using Protein Ligation","volume":"84","author":"Houben","year":"2018","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jmb.2008.03.076","article-title":"Engineered Bacterial Outer Membrane Vesicles with Enhanced Functionality","volume":"380","author":"Kim","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cheng, K., Zhao, R., Li, Y., Qi, Y., Wang, Y., Zhang, Y., Qin, H., Qin, Y., Chen, L., and Li, C. (2021). Bioengineered bacteria-derived outer membrane vesicles as a versatile antigen display platform for tumor vaccination via Plug-and-Display technology. Nat. Commun., 12.","DOI":"10.1038\/s41467-021-22308-8"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8267","DOI":"10.1021\/acs.nanolett.5c01359","article-title":"Synthetic Bacterial Membrane Vesicles as Versatile Antigen-Display Platforms against Respiratory Syncytial Virus","volume":"25","author":"Meng","year":"2025","journal-title":"Nano Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e00330-24","DOI":"10.1128\/msphere.00330-24","article-title":"Delivery of Yersinia pestis antigens via Escherichia coli outer membrane vesicles offered improved protection against plague","volume":"9","author":"Tong","year":"2024","journal-title":"mSphere"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1074\/jbc.M307628200","article-title":"Incorporation of Heterologous Outer Membrane and Periplasmic Proteins into Escherichia coli Outer Membrane Vesicles","volume":"279","author":"Kesty","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1128\/IAI.00950-10","article-title":"Immunization with Salmonella enterica Serovar Typhimurium-Derived Outer Membrane Vesicles Delivering the Pneumococcal Protein PspA Confers Protection against Challenge with Streptococcus pneumoniae","volume":"79","author":"Muralinath","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41392-022-01056-1","article-title":"Pseudomonas aeruginosa: Pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics","volume":"7","author":"Qin","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sundin, C., Saleeb, M., Spjut, S., Qin, L., and Elofsson, M. (2021). Identification of Small Molecules Blocking the Pseudomonas aeruginosa Type III Secretion System Protein PcrV. Biomolecules, 11.","DOI":"10.3390\/biom11010055"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1128\/IAI.00815-08","article-title":"An Engineered Human Antibody Fab Fragment Specific for Pseudomonas aeruginosa PcrV Antigen Has Potent Antibacterial Activity","volume":"77","author":"Baer","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Audia, J.P., Lindsey, A.S., Housley, N.A., Ochoa, C.R., Zhou, C., Toba, M., Oka, M., Annamdevula, N.S., Fitzgerald, M.S., and Frank, D.W. (2013). In the absence of effector proteins, the Pseudomonas aeruginosa type three secretion system needle tip complex contributes to lung injury and systemic inflammatory responses. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081792"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/s41541-023-00672-4","article-title":"Strong immune responses and protection of PcrV and OprF-I mRNA vaccine candidates against Pseudomonas aeruginosa","volume":"8","author":"Wang","year":"2023","journal-title":"npj Vaccines"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1038\/s41598-022-05157-3","article-title":"Vaccination of mice with hybrid protein containing Exotoxin S and PcrV with adjuvants alum and MPL protects Pseudomonas aeruginosa infections","volume":"12","author":"Badmasti","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2109667119","DOI":"10.1073\/pnas.2109667119","article-title":"Remodeling Yersinia pseudotuberculosis to Generate a Highly Immunogenic Outer Membrane Vesicle Vaccine against Pneumonic Plague","volume":"119","author":"Wang","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1016\/S0140-6736(22)02185-7","article-title":"Global mortality associated with 33 bacterial pathogens in 2019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"400","author":"Ikuta","year":"2022","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2580160","DOI":"10.1080\/21505594.2025.2580160","article-title":"Multidrug-resistant Pseudomonas aeruginosa: Pathogenesis, resistance mechanisms, and novel therapeutic strategies","volume":"16","author":"Alharbi","year":"2025","journal-title":"Virulence"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lorusso, A.B., Carrara, J.A., Barroso, C.D.N., Tuon, F.F., and Faoro, H. (2022). Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415779"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/ppul.22890","article-title":"Anti-PcrV antibody in cystic fibrosis: A novel approach targeting Pseudomonas aeruginosa airway infection","volume":"49","author":"Milla","year":"2014","journal-title":"Pediatr. Pulmonol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1080\/21645515.2019.1650999","article-title":"Immunological considerations in the development of Pseudomonas aeruginosa vaccines","volume":"16","author":"Baker","year":"2020","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1086\/341069","article-title":"Generation and Characterization of a Protective Monoclonal Antibody to Pseudomonas aeruginosa PcrV","volume":"186","author":"Frank","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Killough, M., Rodgers, A., and Ingram, R. (2022). Pseudomonas aeruginosa: Recent Advances in Vaccine Development. Vaccines, 10.","DOI":"10.3390\/vaccines10071100"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41522-025-00738-2","article-title":"Immune system dynamics in response to Pseudomonas aeruginosa biofilms","volume":"11","author":"Sahu","year":"2025","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Santamarina-Fern\u00e1ndez, R., Fuentes-Valverde, V., Silva-Rodr\u00edguez, A., Garc\u00eda, P., Moscoso, M., and Bou, G. (2025). Pseudomonas aeruginosa Vaccine Development: Lessons, Challenges, and Future Innovations. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052012"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"126899","DOI":"10.1016\/j.vaccine.2025.126899","article-title":"Development of intimin-enriched outer membrane vesicles (OMVs) as a vaccine to control intestinal carriage of Enterohemorrhagic Escherichia coli","volume":"52","author":"Garling","year":"2025","journal-title":"Vaccine"},{"key":"ref_40","first-page":"809","article-title":"Role of Interleukin-17 in Defense against Pseudomonas aeruginosa Infection in Lungs","volume":"7","author":"Xu","year":"2014","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/j.1600-065X.2008.00703.x","article-title":"Th17 cytokines and mucosal immunity","volume":"226","author":"Dubin","year":"2008","journal-title":"Immunol. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/nri2800","article-title":"Innate IL-17-producing cells: The sentinels of the immune system","volume":"10","author":"Cua","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41577-021-00583-2","article-title":"Mucosal vaccines\u2014Fortifying the frontiers","volume":"22","author":"Lavelle","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1016\/j.vaccine.2015.03.010","article-title":"Salmonella outer membrane vesicles displaying high densities of pneumococcal antigen at the surface offer protection against colonization","volume":"33","author":"Kuipers","year":"2015","journal-title":"Vaccine"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sereme, Y., Villeret, B., Caboche, S., Ikeh, S., Beury, D., Maurier, F., Desterke, C., Born-Bony, M., Xing, Z., and Voulhoux, R. (2025). Mucosal vaccine immunity induced by a new auxotrophic Pseudomonas aeruginosa strain is linked to Th17 and IgA responses. bioRxiv.","DOI":"10.1101\/2025.10.03.679932"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Katseff, A.S., Toumanios, C., Barahim, E., McCormick, A.A., and Arnaboldi, P.M. (2025). PcrV in an Intranasal Adjuvanted Tobacco Mosaic Virus Conjugate Vaccine Mediates Protection from Pseudomonas aeruginosa via an Early Th1\/Th17 Skewed Localized and Systemic Immune Response. Vaccines, 60.","DOI":"10.1016\/j.vaccine.2025.127306"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.1128\/IAI.00635-16","article-title":"Meningococcal Outer Membrane Vesicle Composition-Dependent Activation of the Innate Immune Response","volume":"84","author":"Zariri","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_48","first-page":"3269","article-title":"Adjuvant Activity of Outer Membrane Vesicles from Salmonella minnesota Re595 with Lipopolysaccharides Modified for Attenuating Toxicity","volume":"64","author":"Zhang","year":"2024","journal-title":"Acta Microbiol. Sin."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e00699-21","DOI":"10.1128\/mSphere.00699-21","article-title":"Outer Membrane Vesicles Displaying a Heterologous PcrV-HitA Fusion Antigen Promote Protection against Pulmonary Pseudomonas aeruginosa Infection","volume":"6","author":"Peng","year":"2021","journal-title":"mSphere"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e188105","DOI":"10.1172\/jci.insight.188105","article-title":"STING-Adjuvanted Outer Membrane Vesicle Nanoparticle Vaccine against Pseudomonas aeruginosa","volume":"10","author":"Krishnan","year":"2025","journal-title":"JCI Insight"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/6\/518\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T10:10:19Z","timestamp":1781086219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/6\/518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":50,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["vaccines14060518"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14060518","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]}}}