Microbiological research最新文献

{"title":"Links between oropharyngeal microbiota and IgA nephropathy: A paradigm shift from isolated microbe to microbiome.","authors":"Narongsak Tangon, Sirinart Kumfu, Nipon Chattipakorn, Siriporn C Chattipakorn","doi":"10.1016/j.micres.2024.128005","DOIUrl":"10.1016/j.micres.2024.128005","url":null,"abstract":"<p><p>Immunoglobulin A nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis globally, yet its pathogenesis remains incompletely understood. While much research has focused on the gut microbiome in the development of the disease, emerging evidence suggests that the oropharyngeal microbiota may also be a potential contributor. Studies have revealed significant alterations in oropharyngeal microbial diversity and specific bacterial taxa in IgAN patients, correlating with disease severity and progression. This review aims to comprehensively summarize and discuss the key findings from in vitro, in vivo, and clinical studies into the oropharyngeal bacteria and microbiome alterations in IgAN. Clinical studies have identified associations between certain oropharyngeal bacteria, particularly Cnm⁺Streptococcus mutans, Campylobacter rectus, and Porphyromonas gingivalis with IgAN patients and severe clinical outcomes with. In vitro and in vivo studies further establish a causal relationship between IgAN and oropharyngeal bacteria such as Streptococcus and Haemophilus. Microbiome analyses demonstrate dysbiotic patterns in IgAN patients and identify new potential bacterial genera that have yet to be explored experimentally but may potentially contribute to the disease's pathogenesis. Additionally, the use of these bacterial genera as diagnostic and prognostic biomarkers of IgAN has achieved promising performance. Overall, the evidence highlights the strong connection between oropharyngeal bacteria and IgAN through both causal and non-causal associations. Further investigation into these newly identified bacterial genera and integration of multi-omics data are necessary to uncover mechanisms, validate their role in IgAN, and potentially develop novel diagnostic and therapeutic approaches.</p>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"128005"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reciprocal regulation between bacterial secretion systems and host metabolism: Enhancing bacterial intracellular survival capability.","authors":"Lina Zhan, Jiongchen Ge, Lin Xia, Ying Zhang","doi":"10.1016/j.micres.2024.128025","DOIUrl":"10.1016/j.micres.2024.128025","url":null,"abstract":"<p><p>Secretion systems are intricate nanomachines present on many bacterial cell membranes that deliver various bacterially-encoded effector proteins into eukaryotic or prokaryotic cells. They are pivotal in bacterial invasion, host colonization, and pathogenesis. After infection, bacteria employ these machines to deliver toxic effectors to the cytoplasm of host cells that disrupt their metabolic balance, such as interfering with glucose metabolism, promoting lipid droplets formation, altering amino acid profiles and mitochondrial morphology, and reducing ROS levels, to ensure bacterial intracellular survival. Furthermore, metabolites within host cells can modulate the expression and/or function of bacterial secretion systems. This review summarizes recent advancements in understanding the impact of bacterial secretion systems on host cell metabolism and the feedback regulation of host metabolites on these machines, providing novel perspectives on host-pathogen interactions and mechanisms of bacterial pathogenesis.</p>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"128025"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Root metabolites regulated by FERONIA promote phosphorus-solubilizing rhizobacteria enrichment induced by Arabidopsis thaliana coping with phosphorus deficiency.","authors":"Lingyun Zhang, Xuelei Deng, Jia Xiao, Wei Zhao, Pan Zou, Ruizhe Liao, Keying Xie, Hongdong Liao","doi":"10.1016/j.micres.2024.128030","DOIUrl":"10.1016/j.micres.2024.128030","url":null,"abstract":"<p><p>The recruitment of the phosphorus-solubilizing rhizobacteria plays an important role in response to phosphorus deficiency. Through the treatments of Arabidopsis thaliana (Col-0) and the FERONIA (FER) functional deficient mutants (fer-4 and fer-5) with the soil suspension in various phosphorus conditions, we discovered that FER could promote phosphorus-solubilizing rhizobacteria enrichment to rescue the defective plant during phosphorus deficiency. The amplicon sequencing data reflected that the phosphorus-solubilizing rhizobacterial genus Alcaligenes was significantly enriched of Col-0 than fer-4 in low phosphorus conditions. Metabolomics analysis revealed that there were more α-D-Glucose (α-D-Glc) and L-Leucine (L-Leu) in Col-0 roots than those in fer-4 roots. The alterations of α-D-Glc and L-Leu mediated by FER had high-positive correlations to the enrichment of Alcaligenes. We successfully isolated a phosphorus-solubilizing rhizobacteria strain identified as Alcaligenes faecalis PSB15. The α-D-Glc and L-Leu could promote the strain PSB15 growth on LB agar plates and assist fer-4 in recovering from phosphorus starvation in the low phosphorus (LP) liquid medium vermiculite with tricalcium phosphate (TCP). The α-D-Glc and L-Leu could be considered as promising compounds to enrich beneficial phosphorus-solubilizing rhizobacteria, such as Alcaligenes, and provide a reference for overcoming the plight of phosphorus deficiency in crops in the field of agricultural production in the future.</p>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"128030"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ClpP: Unlocking a novel therapeutic approach of isochlorogenic acid A for methicillin-resistant Staphylococcus aureus-infected osteomyelitis.","authors":"Yueying Wang, Li Wang, Dongbin Guo, Xinyao Liu, Yueshan Xu, Rong Wang, Yun Sun, Quan Liu, Jiyu Guan, Da Liu, Bingmei Wang, Yicheng Zhao, Ming Yan","doi":"10.1016/j.micres.2024.128042","DOIUrl":"10.1016/j.micres.2024.128042","url":null,"abstract":"<p><p>A medical predicament has led to extensive drug resistance in methicillin-resistant Staphylococcus aureus (MRSA), and the complexity of treatment has increased exponentially with the induction of osteomyelitis. In view of the severe situation and the potential of bacterial antivirulence strategies, this study focused on the key virulence factor caseinolytic protease (ClpP) of S. aureus to identify new strategies against MRSA-induced osteomyelitis. As the main protein \"quality control\" system of S. aureus, ClpP is indispensable for coordinating drug resistance, regulating adhesion, and acting on numerous virulence targets. Through fluorescence resonance energy transfer (FRET), we successfully identified isochlorogenic acid A (I-A), a polyphenol derivative, as an efficient inhibitor of ClpP, with an IC₅₀ value of 24.89 μg/mL. Further analysis revealed that I-A can effectively inhibit the expression of virulence factors of MRSA and significantly reduce its adhesion to fibrinogen. Molecular docking revealed the potential binding sites of ClpP and I-A, namely, ILE-81, LYS-109, GLU-156, ARG-157, and GLY-184. At the cellular level, I-A can alleviate the death and increased secretion of inflammatory factors caused by MRSA USA300 in MC3T3-E1 cells. Moreover, it downregulates the activity of ClpP and reduces the response of bacteria to environmental stress. In vivo experiments have confirmed that I-A shows significant efficacy in both rat osteomyelitis models and Galleria mellonella infection models. This study provides new insights into the field of treatment strategies targeting virulence and provides a solid foundation for further exploration of the potential of I-A in combating drug-resistant S. aureus.</p>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"128042"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sorghum rhizosphere bacteriome studies and generation of multistrain beneficial bacterial consortia.","authors":"Chandan Kumar, Alfonso Esposito, Iris Bertani, Samson Musonerimana, Mulissa Jida Midekssa, Kassahun Tesfaye, Devin Coleman Derr, Lara Donaldson, Silvano Piazza, Cristina Bez, Vittorio Venturi","doi":"10.1016/j.micres.2024.128036","DOIUrl":"10.1016/j.micres.2024.128036","url":null,"abstract":"<p><p>The plant rhizosphere microbiome plays a crucial role in plant growth and health. Within this microbiome, bacteria dominate, exhibiting traits that benefit plants, such as facilitating nutrient acquisition, fixing nitrogen, controlling pathogens, and promoting root growth. This study focuses on designing synthetic bacterial consortia using key bacterial strains which have been mapped and then isolated from the sorghum rhizosphere microbiome. A large set of samples of the rhizosphere bacteriome of Sorghum bicolor was generated and analyzed across various genotypes and geographical locations. We assessed the taxonomic composition and structure of the sorghum root-associated bacterial community identifying the most prevalent and keystone taxa. A set of 321 bacterial strains was then isolated, and three multi-strain consortia were designed making use of the bacteriome data generated using culture independent methodology. Subsequently, co-existence and plant-growth promoting ability of three bacterial consortia were tested both in vitro and in planta. Consortia 3 promoted plant growth in growth-chamber conditions while Consortia 1 and 2 performed better in field-plot experiments. Despite these differences, bacterial community profiling confirmed the colonization of the inoculated consortia in the sorghum rhizosphere without significant alterations to the overall bacterial community compared to the non inoculated ones. In summary, this study focused on a method, using root bacteriome data, to design and test bacterial consortia for plant beneficial effects with the aim of translating microbiome knowledge into applications.</p>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"128036"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Function analysis of RNase III in response to oxidative stress in Synechocystis sp. PCC 6803.","authors":"Yihang Zhang, Xinyu Hu, Shanyu Wu, Tianyuan Zhang, Guidan Yang, Zhijie Li, Li Wang, Wenli Chen","doi":"10.1016/j.micres.2024.128045","DOIUrl":"10.1016/j.micres.2024.128045","url":null,"abstract":"<p><p>RNase III, a ubiquitously distributed endonuclease, plays an important role in RNA processing and functions as a global regulator of gene expression. In this study, we explored the role of RNase III in mediating the oxidative stress response in Synechocystis sp. PCC 6803. Phenotypic analysis demonstrated that among the three RNase III-encoding genes (slr0346, slr1646, and slr0954), the deletional mutation of slr0346 significantly impaired the growth of cyanobacteria on BG11 agar plates. However, this growth effect was not observed in liquid culture. In contrast, the deletion of slr1646 and slr0954 did not affect the growth of cyanobacteria under the tested conditions. However, under methyl viologen (MV)-induced oxidative stress, the slr0346 deletion mutant exhibited a slower growth rate compared to the wild-type strain. Transcriptome analysis revealed that five pathways-nitrogen metabolism, ABC transporters, folate biosynthesis, ribosome biogenesis, and oxidative phosphorylation-were implicated in the oxidative stress response. The slr0346 gene suppressed global gene expression, with a particular impact on genes associated with energy metabolism, protein synthesis, and transport. Furthermore, we identified Ssl3432 as an interacting protein that may participate in the oxidative stress response in coordination with Slr0346. Overall, the deletion of slr0346 markedly weakened the ability of Synechocystis sp. PCC 6803 to respond to MV-induced oxidative stress. This study offers valuable insights into the oxidative stress response of Synechocystis sp. PCC 6803 and highlights the role of RNase III in adapting to environmental stress.</p>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"128045"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid-liquid phase separation in microorganisms: Insights into existence, functions, and applications.","authors":"Anas Yusuf, Abdurrahman Usman, Murtala Bindawa Isah, Mei Dang, Xiaoying Zhang","doi":"10.1016/j.micres.2024.128026","DOIUrl":"10.1016/j.micres.2024.128026","url":null,"abstract":"<p><p>Liquid-liquid phase separation (LLPS) is a universal mechanism essential for maintaining cellular integrity and function in microorganisms, facilitating the organization of biomolecules into dynamic compartments. Although extensively studied in mammalian cells, research on LLPS formation and regulation in microorganisms remains limited. This review integrates insights from diverse studies exploring LLPS across microorganisms. We discuss the role of intrinsic disorders in microbial proteins and their relationship with environmental adaptation. Additionally, we examine how microorganisms utilize LLPS to sense changes in environmental parameters, such as temperature, pH, and nutrient levels, enabling them to respond to stresses and regulate cellular processes, such as cell division, protein synthesis, and metabolic flux. We highlight that LLPS is a promising target for synthetic biology and therapeutic intervention against pathogenic microorganisms. We also explore the research landscape of LLPS in microorganisms and address challenges associated with the techniques used in LLPS research. Further research is needed to focus on the detailed molecular regulatory mechanisms of condensates, biotechnological and synthetic biology applications, facilitating improved manipulation of microorganisms, and the identification of novel therapeutic targets.</p>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"128026"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the risk of TB progression: Advances in blood-based biomarker research.","authors":"Zhaodong Li, Yunlong Hu, Fa Zou, Wei Gao, SiWan Feng, Guanghuan Chen, Jing Yang, Wenfei Wang, Chenyan Shi, Yi Cai, Guofang Deng, Xinchun Chen","doi":"10.1016/j.micres.2024.128038","DOIUrl":"10.1016/j.micres.2024.128038","url":null,"abstract":"<p><p>This review addresses the significant advancements in the identification of blood-based prognostic biomarkers for tuberculosis (TB), highlighting the importance of early detection to prevent disease progression. The manuscript discusses various biomarker categories, including transcriptomic, proteomic, metabolomic, immune cell-based, cytokine-based, and antibody response-based markers, emphasizing their potential in predicting TB incidence. Despite promising results, practical application is hindered by high costs, technical complexities, and the need for extensive validation across diverse populations. Transcriptomic biomarkers, such as the Risk16 signature, show high sensitivity and specificity, while proteomic and metabolic markers provide insights into protein-level changes and biochemical alterations linked to TB. Immune cell and cytokine markers offer real-time data on the body's response to infection. The manuscript also explores the role of single-nucleotide polymorphisms in TB susceptibility and the challenges of implementing novel RNA signatures as point-of-care tests in low-resource settings. The review concludes that, while significant progress has been made, further research and development are necessary to refine these biomarkers, improve their practical application, and achieve the World Health Organization's TB elimination goals.</p>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"128038"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism and nanotechnological-based therapeutics for tolerance and resistance of bacterial biofilms.","authors":"Beiliang Miao, Dianhong Wang, Li Yu, Xiangfei Meng, Shiyi Liu, Mengqi Gao, Jiatong Han, Zeliang Chen, Ping Li, Shiwei Liu","doi":"10.1016/j.micres.2024.127987","DOIUrl":"10.1016/j.micres.2024.127987","url":null,"abstract":"<p><p>Bacterial biofilms are one of the most relevant drivers of chronic and recurrent infections and a significant healthcare problem. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure and low drug permeability, leading to tolerance and resistance of biofilms to antibiotics and to host responses. Within a biofilm, microbial cells show increased tolerance to both immune system defense mechanisms and antimicrobials than the same cells in the planktonic state. It is one of the key reasons for the failure of traditional clinical drug to treat infectious diseases. Currently, no drugs are available to attack bacterial biofilms in the clinical setting. The development of novel preventive and therapeutic strategies is urgently needed to allow an effective management of biofilm-associated infections. Based on the properties of nanomaterials and biocompatibility, nanotechnology had the advantages of specific targeting, intelligent delivery and low toxicity, which could realize efficient intervention and precise treatment of biofilm-associated infections. In this paper, the mechanisms of bacterial biofilm resistance to antibiotics and host response tolerance were elaborated. Meanwhile, This paper highlighted multiple strategies of biofilms eradication based on nanotechnology. Nanotechnology can interfere with biofilm formation by destroying mature biofilm, modulating biofilm heterogeneity, inhibiting bacterial metabolism, playing antimicrobial properties, activating immunity and enhancing biofilm penetration, which is an important new anti-biofilm preparation. In addition, we presented the key challenges still faced by nanotechnology in combating bacterial biofilm infections. Utilization of nanotechnology safely and effectively should be further strengthened to confirm the safety aspects of their clinical application.</p>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"127987"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering roles of nine hydrophobins (Hyd1A-F and Hyd2A-C) in the asexual and insect-pathogenic lifecycles of Beauveria bassiana.","authors":"Jian-Ru Feng, Min Li, Sheng-Hua Ying, Ming-Guang Feng","doi":"10.1016/j.micres.2024.128029","DOIUrl":"10.1016/j.micres.2024.128029","url":null,"abstract":"<p><p>Hydrophobins are small amphiphilic proteins that confer filamentous fungal hydrophobicity needed for hyphal growth, development, dispersal and adhesion to host and substrata. In insect-pathogenic Beauveria bassiana, nine hydrophobins (class I Hyd1A-F and class II Hyd2A-C) were proven to localize on the cell walls of aerial hyphae and conidia but accumulate in the vacuoles and vesicles of submerged hyphae and blastospores, respectively. Conidial hydrophobicity, adhesion to insect cuticle, virulence via normal cuticle infection and dispersal potential were significantly more reduced by the hyd1A deletion leading to complete ablation of slender rodlets on conidial coat than the hyd1B deletion, which caused a failure to assemble morphologically irregular rodlets into orderly bundles. Aerial conidiation and submerged blastospore production were compromised in Δhyd2A and Δhyd2C. The deletion of hyd1D stimulated conidial germination and virulence via insect hemocoel colonization, which was accelerated in Δhyd2A but decelerated in Δhyd2B. However, these deletion mutants were unaffected in radial growth on rich/minimal media and responses to osmotic, oxidative, cell wall-perturbing and heat-shock stresses except for an increase in conidial thermotolerance of Δhyd1A or cell sensitivity of Δhyd1B to Congo red-induced stress. None of examined phenotypes was altered in Δhyd1C, Δhyd1E and Δhyd1F. Conclusively, Hyd1A and Hyd1B co-regulate the formation, morphology and orderly assembly of rodlet bundles required for conidial hydrophobicity and infectivity, which are independent of Hyd1C-F and Hyd2A-C in B. bassiana. These results unveil a necessity to distinguish major, minor and dispensable roles among multiple class I/II hydrophobin genes in an ascomycetous pathogen.</p>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"128029"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}