ACS Infectious Diseases最新文献

{"title":"Synthesis of a Phosphoethanolamine Cellulose Mimetic and Evaluation of Its Unanticipated Biofilm Modulating Properties.","authors":"C Elizabeth Adams, Sabrina K Spicer, Jennifer A Gaddy, Steven D Townsend","doi":"10.1021/acsinfecdis.4c00267","DOIUrl":"10.1021/acsinfecdis.4c00267","url":null,"abstract":"<p><p>When coordinating and adhering to a surface, microorganisms produce a biofilm matrix consisting of extracellular DNA, lipids, proteins, and polysaccharides that are intrinsic to the survival of bacterial communities. Indeed, bacteria produce a variety of structurally diverse polysaccharides that play integral roles in the emergence and maintenance of biofilms by providing structural rigidity, adhesion, and protection from environmental stressors. While the roles that polysaccharides play in biofilm dynamics have been described for several bacterial species, the difficulty in isolating homogeneous material has resulted in few structures being elucidated. Recently, Cegelski and co-workers discovered that uropathogenic <i>Escherichia coli</i> (UPEC) secrete a chemically modified cellulose called phosphoethanolamine cellulose (pEtN cellulose) that plays a vital role in biofilm assembly. However, limited chemical tools exist to further examine the functional role of this polysaccharide across bacterial species. To address this critical need, we hypothesized that we could design and synthesize an unnatural glycopolymer to mimic the structure of pEtN cellulose. Herein, we describe the synthesis and evaluation of a pEtN cellulose glycomimetic which was generated using ring-opening metathesis polymerization. Surprisingly, the synthetic polymers behave counter to native pEtN cellulose in that the synthetic polymers repress biofilm formation in <i>E. coli</i> laboratory strain 11775T and UPEC strain 700415 with longer glycopolymers displaying greater repression. To evaluate the mechanism of action, changes in biofilm and cell morphology were visualized using high resolution field-emission gun scanning electron microscopy which further revealed changes in cell surface appendages. Our results suggest synthetic pEtN cellulose glycopolymers act as an antiadhesive and inhibit biofilm formation across <i>E. coli</i> strains, highlighting a potential new inroad to the development of bioinspired, biofilm-modulating materials.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3245-3255"},"PeriodicalIF":4.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pilot-Scale Screening of Clinically Approved Drugs to Identify Uridine Insertion/Deletion RNA Editing Inhibitors in <i>Trypanosoma brucei</i>.","authors":"Mojtaba Rostamighadi, Arezou Kamelshahroudi, Vanessa Pitsitikas, Kenneth A Jacobson, Reza Salavati","doi":"10.1021/acsinfecdis.4c00394","DOIUrl":"10.1021/acsinfecdis.4c00394","url":null,"abstract":"<p><p>RNA editing pathway is a validated target in kinetoplastid parasites (<i>Trypanosoma brucei</i>, <i>Trypanosoma cruzi</i>, and <i>Leishmania</i> spp.) that cause severe diseases in humans and livestock. An essential large protein complex, the editosome, mediates uridine insertion and deletion in RNA editing through a stepwise process. This study details the discovery of editosome inhibitors by screening a library of widely used human drugs using our previously developed <i>in vitro</i> biochemical Ribozyme Insertion Deletion Editing (RIDE) assay. Subsequent studies on the mode of action of the identified hits and hit expansion efforts unveiled compounds that interfere with RNA-editosome interactions and novel ligase inhibitors with IC₅₀ values in the low micromolar range. Docking studies on the ligase demonstrated similar binding characteristics for ATP and our novel epigallocatechin gallate inhibitor. The inhibitors demonstrated potent trypanocidal activity and are promising candidates for drug repurposing due to their lack of cytotoxic effects. Further studies are necessary to validate these targets using more definitive gene-editing techniques and to enhance the safety profile.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3289-3303"},"PeriodicalIF":4.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant Flavonoids with Antimicrobial Activity against Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA).","authors":"Shengnan Xu, Ayue Kang, Yue Tian, Xinhui Li, Shangshang Qin, Ruige Yang, Yong Guo","doi":"10.1021/acsinfecdis.4c00292","DOIUrl":"10.1021/acsinfecdis.4c00292","url":null,"abstract":"<p><p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) has become a serious threat to human public health and global economic development, and there is an urgent need to develop new antimicrobial agents. Flavonoids are the largest group of plant secondary metabolites, and the anti-<i>S. aureus</i> and anti-MRSA activities of flavonoids have now been widely reported. The aim of this Review is to describe plant-derived flavonoid active ingredients and their effects and mechanisms of inhibitory activity against MRSA in order to provide insights for screening novel antimicrobial agents. Here, 85 plant-derived flavonoids (14 flavones, 21 flavonols, 26 flavanones, 9 isoflavones, 12 chalcones, and 3 other classes) with anti-MRSA activity are reviewed. Among these flavonoids, flavones and isoflavones generally showed the most significant anti-MRSA activity (MICs: 1-8 μg/mL). The results of the present Review display that most of the flavonoids with excellent anti-MRSA activity were derived from <i>Morus alba</i> L. and <i>Paulownia tomentosa</i> (Thunb.) Steud. The antibacterial mechanism of flavonoids against MRSA is mainly achieved by disruption of membrane structures, inhibition of efflux pumps, and inhibition of β-lactamases and bacterial virulence factors. We hope this Review can provide insights into the development of novel antimicrobials based on natural products for treating MRSA infections.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3086-3097"},"PeriodicalIF":4.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venom: A Promising Avenue for Antimicrobial Therapeutics.","authors":"Ramkamal Samat, Samya Sen, Moumita Jash, Satyajit Ghosh, Shubham Garg, Jayita Sarkar, Surajit Ghosh","doi":"10.1021/acsinfecdis.4c00314","DOIUrl":"10.1021/acsinfecdis.4c00314","url":null,"abstract":"<p><p>Venom in medicine is well documented in the chronicles of ancient Greece and the Roman Empire and persisted into the Renaissance and even into the modern era. Venoms were not always associated with detrimental consequences. Since ancient times, the curative capacity of venom has been recognized, portraying venom as a metaphor for pharmacy and medicine. Venom proteins and peptides' antimicrobial potential has not undergone systematic exploration despite the huge literature on natural antimicrobials. In light of the escalating challenge of antimicrobial resistance and the diminishing effectiveness of antibiotics, there is a pressing need for innovative antimicrobials capable of effectively addressing illnesses caused by multidrug-resistant microorganisms. This review adds to our understanding of the effectiveness of different venom components against a host of pathogenic microorganisms. The aim is to illuminate the various antimicrobials present in venom and venom peptides, thereby emphasizing the unexplored medicinal potential for antimicrobial properties. We have presented a concise summary of the molecular examination of the venom peptides' functioning processes, as well as the current clinical and preclinical progress of venom antimicrobial peptides.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3098-3125"},"PeriodicalIF":4.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6-Methoxyldihydrochelerythrine Chloride Inhibiting Intra and Extracellular Drug-Resistant Bacteria.","authors":"Li-Yu Bai, Zhao-Jie Wang, Qing-Yu Lu, Huan Huang, Yan-Yan Zhu, Yun-Li Zhao, Xiao-Dong Luo","doi":"10.1021/acsinfecdis.4c00571","DOIUrl":"10.1021/acsinfecdis.4c00571","url":null,"abstract":"<p><p>Vancomycin-resistant enterococcus (VRE) is a major nosocomial pathogen that exhibits enhanced infectivity due to its robust virulence and biofilm-forming capabilities. In this study, 6-methoxyldihydrochelerythrine chloride (6-MDC) inhibited the growth of exponential-phase VRE and restored VRE's sensitivity to vancomycin. 6-MDC predominantly suppressed the <i>de novo</i> biosynthetic pathway of pyrimidine and purine in VRE by the RNA-Seq analysis, resulting in obstructed DNA synthesis, which subsequently weakened bacterial virulence and impeded intracellular survival. Furthermore, 6-MDC inhibited biofilm formation, eradicated established biofilms, reduced virulence, and enhanced the host immune response to prevent intracellular survival and replication of VRE. Finally, 6-MDC reduced the VRE load in peritoneal fluid and cells significantly in a murine peritoneal infection model. This paper provides insight into the potential antimicrobial target of benzophenanthridine alkaloids for the first time.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3430-3439"},"PeriodicalIF":4.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Administration of Bedaquiline-Loaded Fucosylated Liposomes Provides Anti-Tubercular Activity while Reducing the Potential for Systemic Side Effects.","authors":"Franziska Marwitz, Gabriela Hädrich, Natalja Redinger, Karen F W Besecke, Feng Li, Nadine Aboutara, Simone Thomsen, Michaela Cohrs, Paul Robert Neumann, Henrike Lucas, Julia Kollan, Constantin Hozsa, Robert K Gieseler, Dominik Schwudke, Marcus Furch, Ulrich Schaible, Lea Ann Dailey","doi":"10.1021/acsinfecdis.4c00192","DOIUrl":"10.1021/acsinfecdis.4c00192","url":null,"abstract":"<p><p>Liposomal formulations of antibiotics for inhalation offer the potential for the delivery of high drug doses, controlled drug release kinetics in the lung, and an excellent safety profile. In this study, we evaluated the <i>in vivo</i> performance of a liposomal formulation for the poorly soluble, antituberculosis agent, bedaquiline. Bedaquiline was encapsulated within monodisperse liposomes of ∼70 nm at a relatively high drug concentration (∼3.6 mg/mL). Formulations with or without fucose residues, which bind to C-type lectin receptors and mediate a preferential binding to macrophage mannose receptor, were prepared, and efficacy was assessed in an <i>in vivo</i> C3HeB/FeJ mouse model of tuberculosis infection (H37Rv strain). Seven intranasal instillations of 5 mg/kg bedaquiline formulations administered every second day resulted in a significant reduction in lung burden (∼0.4-0.6 Δlog₁₀ CFU), although no differences between fucosylated and nonfucosylated formulations were observed. A pharmacokinetic study in healthy, noninfected Balb/c mice demonstrated that intranasal administration of a single dose of 2.5 mg/kg bedaquiline liposomal formulation (fucosylated) improved the lung bioavailability 6-fold compared to intravenous administration of the same formulation at the same dose. Importantly, intranasal administration reduced systemic concentrations of the primary metabolite, <i>N</i>-desmethyl-bedaquiline (M2), compared with both intravenous and oral administration. This is a clinically relevant finding as the M2 metabolite is associated with a higher risk of QT-prolongation in predisposed patients. The results clearly demonstrate that a bedaquiline liposomal inhalation suspension may show enhanced antitubercular activity in the lung while reducing systemic side effects, thus meriting further nonclinical investigation.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3222-3232"},"PeriodicalIF":4.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141969940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and Biosynthesis of Persiathiacins: Unusual Polyglycosylated Thiopeptides Active Against Multidrug Resistant Tuberculosis.","authors":"Yousef Dashti, Fatemeh Mohammadipanah, Yu Zhang, Pietra M Cerqueira Diaz, Anthony Vocat, Daniel Zabala, Christopher D Fage, Isolda Romero-Canelon, Boyke Bunk, Cathrin Spröer, Lona M Alkhalaf, Jörg Overmann, Stewart T Cole, Gregory L Challis","doi":"10.1021/acsinfecdis.4c00502","DOIUrl":"10.1021/acsinfecdis.4c00502","url":null,"abstract":"<p><p>Thiopeptides are ribosomally biosynthesized and post-translationally modified peptides (RiPPs) that potently inhibit the growth of Gram-positive bacteria by targeting multiple steps in protein biosynthesis. The poor pharmacological properties of thiopeptides, particularly their low aqueous solubility, has hindered their development into clinically useful antibiotics. Antimicrobial activity screens of a library of Actinomycetota extracts led to discovery of the novel polyglycosylated thiopeptides persiathiacins A and B from <i>Actinokineospora</i> sp. UTMC 2448. Persiathiacin A is active against methicillin-resistant <i>Staphylococcus aureus</i> and several <i>Mycobacterium tuberculosis</i> strains, including drug-resistant and multidrug-resistant clinical isolates, and does not significantly affect the growth of ovarian cancer cells at concentrations up to 400 μM. Polyglycosylated thiopeptides are extremely rare and nothing is known about their biosynthesis. Sequencing and analysis of the <i>Actinokineospora</i> sp. UTMC 2448 genome enabled identification of the putative persiathiacin biosynthetic gene cluster (BGC). A cytochrome P450 encoded by this gene cluster catalyzes the hydroxylation of nosiheptide in vitro and in vivo, consistent with the proposal that the cluster directs persiathiacin biosynthesis. Several genes in the cluster encode homologues of enzymes known to catalyze the assembly and attachment of deoxysugars during the biosynthesis of other classes of glycosylated natural products. One of these encodes a glycosyl transferase that was shown to catalyze attachment of a D-glucose residue to nosiheptide in vitro. The discovery of the persiathiacins and their BGC thus provides the basis for the development of biosynthetic engineering approaches to the creation of novel (poly)glycosylated thiopeptide derivatives with enhanced pharmacological properties.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3378-3391"},"PeriodicalIF":4.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Self-Adjuvanted Lipopeptide Vaccines Elicit High Antibody Titers and Strong Cellular Responses against SARS-CoV-2.","authors":"Joshua W C Maxwell, Skye Stockdale, Erica L Stewart, Caroline L Ashley, Lachlan J Smith, Megan Steain, James A Triccas, Scott N Byrne, Warwick J Britton, Anneliese S Ashhurst, Richard J Payne","doi":"10.1021/acsinfecdis.4c00544","DOIUrl":"10.1021/acsinfecdis.4c00544","url":null,"abstract":"<p><p>Despite concerted efforts to tackle the COVID-19 pandemic, the persistent transmission of SARS-CoV-2 demands continued research into novel vaccination strategies to combat the virus. In light of this, intranasally administered peptide vaccines, particularly those conjugated to an immune adjuvant to afford so-called \"self-adjuvanted vaccines\", remain underexplored. Here, we describe the synthesis and immunological evaluation of self-adjuvanting peptide vaccines derived from epitopes of the spike glycoprotein of SARS-CoV-2 covalently fused to the potent adjuvant, Pam₂Cys, that targets toll-like receptor 2 (TLR2). When administered intranasally, these vaccines elicited a strong antigen-specific CD4⁺ and CD8⁺ T-cell response in the lungs as well as high titers of IgG and IgA specific to the native spike protein of SARS-CoV-2. Unfortunately, serum and lung fluid from mice immunized with these vaccines failed to inhibit viral entry in spike-expressing pseudovirus assays. Following this, we designed and synthesized fusion vaccines composed of the T-cell epitope discovered in this work, covalently fused to epitopes of the receptor-binding domain of the spike protein reported to be neutralizing. While antibodies elicited against these fusion vaccines were not neutralizing, the T-cell epitope retained its ability to stimulate strong antigen-specific CD4⁺ lymphocyte responses within the lungs. Given the Spike_(883-909) region is still completely conserved in SARS-CoV-2 variants of concern and variants of interest, we envision the self-adjuvanting vaccine platform reported here may inform future vaccine efforts.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3419-3429"},"PeriodicalIF":4.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mechanism of pH-Induced Protrusion Configuration Switching in Piscine Betanodavirus Implies a Novel Antiviral Strategy.","authors":"Petra Štěrbová, Chun-Hsiung Wang, Kathleen J D Carillo, Yuan-Chao Lou, Takayuki Kato, Keiichi Namba, Der-Lii M Tzou, Wei-Hau Chang","doi":"10.1021/acsinfecdis.4c00407","DOIUrl":"10.1021/acsinfecdis.4c00407","url":null,"abstract":"<p><p>Many viruses contain surface spikes or protrusions that are essential for virus entry. These surface structures can thereby be targeted by antiviral drugs to treat viral infections. Nervous necrosis virus (NNV), a simple nonenveloped virus in the genus of betanodavirus, infects fish and damages aquaculture worldwide. NNV has 60 conspicuous surface protrusions, each comprising three protrusion domains (P-domain) of its capsid protein. NNV uses protrusions to bind to common receptors of sialic acids on the host cell surface to initiate its entry via the endocytic pathway. However, structural alterations of NNV in response to acidic conditions encountered during this pathway remain unknown, while detailed interactions of protrusions with receptors are unclear. Here, we used cryo-EM to discover that Grouper NNV protrusions undergo low-pH-induced compaction and resting. NMR and molecular dynamics (MD) simulations were employed to probe the atomic details. A solution structure of the P-domain at pH 7.0 revealed a long flexible loop (amino acids 311-330) and a pocket outlined by this loop. Molecular docking analysis showed that the N-terminal moiety of sialic acid inserted into this pocket to interact with conserved residues inside. MD simulations demonstrated that part of this loop converted to a β-strand under acidic conditions, allowing for P-domain trimerization and compaction. Additionally, a low-pH-favored conformation is attained for the linker connecting the P-domain to the NNV shell, conferring resting protrusions. Our findings uncover novel pH-dependent conformational switching mechanisms underlying NNV protrusion dynamics potentially utilized for facilitating NNV entry, providing new structural insights into complex NNV-host interactions with the identification of putative druggable hotspots on the protrusion.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3304-3319"},"PeriodicalIF":4.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infectious Disease Research Laboratories in Africa Are Not Using AI Yet─Large Language Models May Facilitate Adoption.","authors":"Gemma Turon, Dhanshree Arora, Miquel Duran-Frigola","doi":"10.1021/acsinfecdis.4c00585","DOIUrl":"10.1021/acsinfecdis.4c00585","url":null,"abstract":"","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3083-3085"},"PeriodicalIF":4.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}