JACS Au最新文献

{"title":"Molecular Basis of Siglec-7 Recognition by Neisseria meningitidis Serogroup Y CPS: Implications for Immune Evasion","authors":"Cristina Di Carluccio,&nbsp;Tania Gerpe Amor,&nbsp;Maria Pia Lenza,&nbsp;Alessandro Antonio Masi,&nbsp;Celeste Abreu,&nbsp;Viviana Longo,&nbsp;Francesco Albano,&nbsp;Ferran Nieto-Fabregat,&nbsp;Paola Salvatore,&nbsp;Geppino Falco,&nbsp;Darielys Santana-Medero,&nbsp;Marco Fragai,&nbsp;Yvette van Kooyk,&nbsp;Antonio Molinaro,&nbsp;Yury Valdes-Balbin,&nbsp;Ondřej Vaněk,&nbsp;Vicente Verez-Bencomo,&nbsp;Roberta Marchetti,&nbsp;Fabrizio Chiodo and Alba Silipo*,&nbsp;","doi":"10.1021/jacsau.5c0021410.1021/jacsau.5c00214","DOIUrl":"https://doi.org/10.1021/jacsau.5c00214https://doi.org/10.1021/jacsau.5c00214","url":null,"abstract":"<p >Siglecs, sialic-acid-binding immunoglobulin-like lectins, are key immune cell receptors that recognize sialic acid residues on cell surfaces. Pathogens and tumor cells exploit Siglecs to evade immune responses and modulate immunity, contributing significantly to infectious disease and cancer pathogenesis. Siglec-7, primarily expressed on natural killer (NK) cells, functions as an inhibitory receptor, tightly regulating the immune activity. This study investigates the interaction between Siglec-7 and the capsular polysaccharide (CPS) of <i>Neisseria meningitidis</i> serogroup Y (Men-Y), a bacterium whose sialylated CPS is critical for virulence. We demonstrate that Men-Y CPS binds to inhibitory Siglec-7, potentially dampening immune recognition. We employed a multifaceted approach, combining biochemical and biophysical techniques to dissect this interaction. Enzyme-linked immunosorbent assays (ELISAs) and fluorescence titrations quantified the binding specificity and affinity. Ligand- and protein-based nuclear magnetic resonance (NMR) spectroscopy, coupled with computational modeling, provides detailed molecular insights. We highlight the critical influence of the Men-Y CPS conformation and sialic acid presentation on Siglec-7 binding. The specific arrangement of α-2,6-linked sialic acids on the CPS is crucial for Siglec-7 binding, demonstrating the importance of the CPS 3D structure. Preliminary immunological assays using stimulated U937 cells (a promonocytic cell line) further support the immunomodulatory role of Siglec-7 mediated by Men-Y CPS. These results offer valuable insights into the development of targeted therapeutic strategies against bacterial infections.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2257–2269 2257–2269"},"PeriodicalIF":8.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multistep Cascade Catalyzed by a Single-Chiral Lewis Acid: Efficient Asymmetric Synthesis of Macrocyclic Chiral Dilactones and Dilactams","authors":"Bai-Lin Wang,&nbsp;Jie-Qiang Yu,&nbsp;Qian Zhang* and Xing-Wang Wang*,&nbsp;","doi":"10.1021/jacsau.5c0006910.1021/jacsau.5c00069","DOIUrl":"https://doi.org/10.1021/jacsau.5c00069https://doi.org/10.1021/jacsau.5c00069","url":null,"abstract":"<p >A Cu(II)-catalyzed asymmetric cascade process was successfully developed by the dimerization of β,γ-unsaturated α-keto tryptophol esters or β,γ-unsaturated α-keto tryptamino amides under mild reaction conditions, furnishing the corresponding macrocyclic dilactones and dilactams in good yields with excellent regio-, diastereo-, and enantioselectivities. The transformation involved a four-step cascade of double Friedel–Crafts alkylation and double <i>N</i>-hemiketalization, providing efficient access to a variety of macrocyclic dilactone and dilactam scaffolds bearing four new stereocenters in a one-pot and highly atom-economic fashion. The resultant chiral macrocyclic compounds were further applied as ligands in the copper-catalyzed asymmetric Friedel–Crafts alkylation reactions and also tested as multifunctional chiral host molecules in binding with quinine and quinidine.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2159–2171 2159–2171"},"PeriodicalIF":8.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multistep Cascade Catalyzed by a Single-Chiral Lewis Acid: Efficient Asymmetric Synthesis of Macrocyclic Chiral Dilactones and Dilactams.","authors":"Bai-Lin Wang, Jie-Qiang Yu, Qian Zhang, Xing-Wang Wang","doi":"10.1021/jacsau.5c00069","DOIUrl":"10.1021/jacsau.5c00069","url":null,"abstract":"<p><p>A Cu-(II)-catalyzed asymmetric cascade process was successfully developed by the dimerization of β,γ-unsaturated α-keto tryptophol esters or β,γ-unsaturated α-keto tryptamino amides under mild reaction conditions, furnishing the corresponding macrocyclic dilactones and dilactams in good yields with excellent regio-, diastereo-, and enantioselectivities. The transformation involved a four-step cascade of double Friedel-Crafts alkylation and double <i>N</i>-hemiketalization, providing efficient access to a variety of macrocyclic dilactone and dilactam scaffolds bearing four new stereocenters in a one-pot and highly atom-economic fashion. The resultant chiral macrocyclic compounds were further applied as ligands in the copper-catalyzed asymmetric Friedel-Crafts alkylation reactions and also tested as multifunctional chiral host molecules in binding with quinine and quinidine.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2159-2171"},"PeriodicalIF":8.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Basis of Siglec‑7 Recognition by Neisseria meningitidis Serogroup Y CPS: Implications for Immune Evasion.","authors":"Cristina Di Carluccio, Tania Gerpe Amor, Maria Pia Lenza, Alessandro Antonio Masi, Celeste Abreu, Viviana Longo, Francesco Albano, Ferran Nieto-Fabregat, Paola Salvatore, Geppino Falco, Darielys Santana-Medero, Marco Fragai, Yvette van Kooyk, Antonio Molinaro, Yury Valdes-Balbin, Ondřej Vaněk, Vicente Verez-Bencomo, Roberta Marchetti, Fabrizio Chiodo, Alba Silipo","doi":"10.1021/jacsau.5c00214","DOIUrl":"10.1021/jacsau.5c00214","url":null,"abstract":"<p><p>Siglecs, sialic-acid-binding immunoglobulin-like lectins, are key immune cell receptors that recognize sialic acid residues on cell surfaces. Pathogens and tumor cells exploit Siglecs to evade immune responses and modulate immunity, contributing significantly to infectious disease and cancer pathogenesis. Siglec-7, primarily expressed on natural killer (NK) cells, functions as an inhibitory receptor, tightly regulating the immune activity. This study investigates the interaction between Siglec-7 and the capsular polysaccharide (CPS) of Neisseria meningitidis serogroup Y (Men-Y), a bacterium whose sialylated CPS is critical for virulence. We demonstrate that Men-Y CPS binds to inhibitory Siglec-7, potentially dampening immune recognition. We employed a multifaceted approach, combining biochemical and biophysical techniques to dissect this interaction. Enzyme-linked immunosorbent assays (ELISAs) and fluorescence titrations quantified the binding specificity and affinity. Ligand- and protein-based nuclear magnetic resonance (NMR) spectroscopy, coupled with computational modeling, provides detailed molecular insights. We highlight the critical influence of the Men-Y CPS conformation and sialic acid presentation on Siglec-7 binding. The specific arrangement of α-2,6-linked sialic acids on the CPS is crucial for Siglec-7 binding, demonstrating the importance of the CPS 3D structure. Preliminary immunological assays using stimulated U937 cells (a promonocytic cell line) further support the immunomodulatory role of Siglec-7 mediated by Men-Y CPS. These results offer valuable insights into the development of targeted therapeutic strategies against bacterial infections.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2257-2269"},"PeriodicalIF":8.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monophosphoryl Lipid A–2,4-Dinitrophenylamine Conjugates Are Potent Adjuvants for Carbohydrate and Protein Vaccines","authors":"Jiatong Guo,&nbsp;Rajendra Rohokale,&nbsp;Sayan Kundu and Zhongwu Guo*,&nbsp;","doi":"10.1021/jacsau.5c0018710.1021/jacsau.5c00187","DOIUrl":"https://doi.org/10.1021/jacsau.5c00187https://doi.org/10.1021/jacsau.5c00187","url":null,"abstract":"<p >Adjuvants are essential for effective vaccine formulation, but currently only a few adjuvants with limited efficacies and application scopes are available. To address this issue, we explored covalent conjugates of monophosphoryl lipid A (MPLA) and 2,4-dinitrophenylamine (DNPA) as a new type of adjuvant. Immunological studies in mice prove that MPLA–DNPA conjugates can help a model vaccine induce robust IgG antibody and adaptive immune responses against carbohydrate and protein antigens and are much more potent adjuvants than alum─the positive control─and the MPLA + DNPA mixture. Detailed profiling and comparison of the cytokines/chemokines elicited by various adjuvants suggest that the MPLA–DNPA conjugates can activate macrophages, monocytes, dendritic, T, T helper, and other immune cells to promote cellular immunity against vaccines. The results suggest a synergistic effect of covalently linked MPLA and DNPA, which act via interacting with the Toll-like receptor and recruiting endogenous anti-DNPA antibodies, respectively. Moreover, the linker between MPLA and DNPA shows a major impact on this synergistic effect, especially for the carbohydrate antigen. Eventually, the MPLA–DNPA conjugate with a longer linker containing a triazole moiety is identified as a promising adjuvant for both carbohydrate and protein vaccines worthy of further research and development.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2210–2222 2210–2222"},"PeriodicalIF":8.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monophosphoryl Lipid A-2,4-Dinitrophenylamine Conjugates Are Potent Adjuvants for Carbohydrate and Protein Vaccines.","authors":"Jiatong Guo, Rajendra Rohokale, Sayan Kundu, Zhongwu Guo","doi":"10.1021/jacsau.5c00187","DOIUrl":"10.1021/jacsau.5c00187","url":null,"abstract":"<p><p>Adjuvants are essential for effective vaccine formulation, but currently only a few adjuvants with limited efficacies and application scopes are available. To address this issue, we explored covalent conjugates of monophosphoryl lipid A (MPLA) and 2,4-dinitrophenylamine (DNPA) as a new type of adjuvant. Immunological studies in mice prove that MPLA-DNPA conjugates can help a model vaccine induce robust IgG antibody and adaptive immune responses against carbohydrate and protein antigens and are much more potent adjuvants than alumthe positive controland the MPLA + DNPA mixture. Detailed profiling and comparison of the cytokines/chemokines elicited by various adjuvants suggest that the MPLA-DNPA conjugates can activate macrophages, monocytes, dendritic, T, T helper, and other immune cells to promote cellular immunity against vaccines. The results suggest a synergistic effect of covalently linked MPLA and DNPA, which act via interacting with the Toll-like receptor and recruiting endogenous anti-DNPA antibodies, respectively. Moreover, the linker between MPLA and DNPA shows a major impact on this synergistic effect, especially for the carbohydrate antigen. Eventually, the MPLA-DNPA conjugate with a longer linker containing a triazole moiety is identified as a promising adjuvant for both carbohydrate and protein vaccines worthy of further research and development.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2210-2222"},"PeriodicalIF":8.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrochemical Conversions of Sulfenamides into Sulfonimidoyl- and Sulfondiimidoyl Fluorides.","authors":"Bin Zhao, Ding-Bo Zeng, Xinglei He, Jing-Heng Li, Yuqi Lin, Ke-Yin Ye","doi":"10.1021/jacsau.5c00374","DOIUrl":"10.1021/jacsau.5c00374","url":null,"abstract":"<p><p>The invention of versatile linkage agents provides the chemical basis for SuFEx chemistry. Sulfonimidoyl fluorides and sulfondiimidoyl fluorides are aza-isosteres of sulfonyl fluorides with diverse reactivity through the fine-tuning of <i>N</i>-substituents. However, limited synthetic approaches impede their wide applications in SuFEx chemistry. Herein, we develop a straightforward electrochemical strategy for sulfonimidoyl- and sulfondiimidoyl fluorides through sequential oxidations of the readily available sulfenamides via sulfinamide and iminosulfinamide intermediates, respectively. The previously rarely investigated (bis)-sulfondiimidoyl fluorides are now easily accessible and readily participate in SuFEx chemistry with diverse oxygen and nitrogen nucleophiles, macrocyclization, and polymerization.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2359-2367"},"PeriodicalIF":8.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrochemical Conversions of Sulfenamides into Sulfonimidoyl- and Sulfondiimidoyl Fluorides","authors":"Bin Zhao,&nbsp;Ding-Bo Zeng,&nbsp;Xinglei He,&nbsp;Jing-Heng Li,&nbsp;Yuqi Lin* and Ke-Yin Ye*,&nbsp;","doi":"10.1021/jacsau.5c0037410.1021/jacsau.5c00374","DOIUrl":"https://doi.org/10.1021/jacsau.5c00374https://doi.org/10.1021/jacsau.5c00374","url":null,"abstract":"<p >The invention of versatile linkage agents provides the chemical basis for SuFEx chemistry. Sulfonimidoyl fluorides and sulfondiimidoyl fluorides are aza-isosteres of sulfonyl fluorides with diverse reactivity through the fine-tuning of <i>N</i>-substituents. However, limited synthetic approaches impede their wide applications in SuFEx chemistry. Herein, we develop a straightforward electrochemical strategy for sulfonimidoyl- and sulfondiimidoyl fluorides through sequential oxidations of the readily available sulfenamides via sulfinamide and iminosulfinamide intermediates, respectively. The previously rarely investigated (bis)sulfondiimidoyl fluorides are now easily accessible and readily participate in SuFEx chemistry with diverse oxygen and nitrogen nucleophiles, macrocyclization, and polymerization.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2359–2367 2359–2367"},"PeriodicalIF":8.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluorinated Hexosome Carriers for Enhanced Solubility of Drugs","authors":"Tiffany Guitton-Spassky,&nbsp;Boris Schade,&nbsp;Christian Zoister,&nbsp;Eleonora Veronese,&nbsp;Marta Rosati,&nbsp;Francesca Baldelli Bombelli,&nbsp;Gabriella Cavallo,&nbsp;Andreas F. Thünemann,&nbsp;Hassan Ghermezcheshme,&nbsp;Hesam Makki,&nbsp;Roland R. Netz,&nbsp;Kai Ludwig,&nbsp;Pierangelo Metrangolo*,&nbsp;Abhishek Kumar Singh* and Rainer Haag*,&nbsp;","doi":"10.1021/jacsau.5c0019810.1021/jacsau.5c00198","DOIUrl":"https://doi.org/10.1021/jacsau.5c00198https://doi.org/10.1021/jacsau.5c00198","url":null,"abstract":"<p >Designing nanomaterials for drug encapsulation is a crucial, yet challenging, aspect for pharmaceutical development. An important step is synthesizing amphiphiles that form stable supramolecular systems for efficient drug loading. In the case of fluorinated drugs, these have superior properties and also a tendency toward reduced water solubility. For the first time, we report here fluorinated hexosome carriers made from nonionic dendritic amphiphiles, capable of encapsulating the fluorinated drug Leflunomide with high efficiency (62 ± 3%) and increasing its solubility by 12-fold. We synthesized amphiphiles with varying tail groups (fluorinated/alkylated), and their supramolecular self-assembly was investigated using cryogenic transmission electron microscopy and small-angle X-ray scattering. Furthermore, Leflunomide and its equivalent nonfluorinated counterpart were encapsulated within fluorinated and nonfluorinated assemblies. Self-assembly and encapsulation mechanisms were well supported by coarse-grained molecular simulations, yielding a fundamental understanding of the new systems.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2223–2236 2223–2236"},"PeriodicalIF":8.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluorinated Hexosome Carriers for Enhanced Solubility of Drugs.","authors":"Tiffany Guitton-Spassky, Boris Schade, Christian Zoister, Eleonora Veronese, Marta Rosati, Francesca Baldelli Bombelli, Gabriella Cavallo, Andreas F Thünemann, Hassan Ghermezcheshme, Hesam Makki, Roland R Netz, Kai Ludwig, Pierangelo Metrangolo, Abhishek Kumar Singh, Rainer Haag","doi":"10.1021/jacsau.5c00198","DOIUrl":"10.1021/jacsau.5c00198","url":null,"abstract":"<p><p>Designing nanomaterials for drug encapsulation is a crucial, yet challenging, aspect for pharmaceutical development. An important step is synthesizing amphiphiles that form stable supramolecular systems for efficient drug loading. In the case of fluorinated drugs, these have superior properties and also a tendency toward reduced water solubility. For the first time, we report here fluorinated hexosome carriers made from nonionic dendritic amphiphiles, capable of encapsulating the fluorinated drug Leflunomide with high efficiency (62 ± 3%) and increasing its solubility by 12-fold. We synthesized amphiphiles with varying tail groups (fluorinated/alkylated), and their supramolecular self-assembly was investigated using cryogenic transmission electron microscopy and small-angle X-ray scattering. Furthermore, Leflunomide and its equivalent nonfluorinated counterpart were encapsulated within fluorinated and nonfluorinated assemblies. Self-assembly and encapsulation mechanisms were well supported by coarse-grained molecular simulations, yielding a fundamental understanding of the new systems.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2223-2236"},"PeriodicalIF":8.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}