Microbial Cell最新文献

{"title":"A novel antibacterial strategy: histone and antimicrobial peptide synergy.","authors":"Leora Duong,&nbsp;Steven P Gross,&nbsp;Albert Siryaporn","doi":"10.15698/mic2020.11.736","DOIUrl":"https://doi.org/10.15698/mic2020.11.736","url":null,"abstract":"<p><p>The rate at which antibiotics are discovered and developed has stagnated; meanwhile, antibacterial resistance continually increases and leads to a plethora of untreatable and deadly infections worldwide. Therefore, there is a critical need to develop new antimicrobial strategies to combat this alarming reality. One approach is to understand natural antimicrobial defense mechanisms that higher-level organisms employ in order to kill bacteria, potentially leading to novel antibiotic therapeutic approaches. Mammalian histones have long been reported to have antibiotic activity, with the first observation of their antibacterial properties reported in 1942. However, there have been doubts about whether histones could truly have any such role in the animal, predominantly based on two issues: they are found in the nucleus (so are not in a position to encounter bacteria), and their antibiotic activity <i>in vitro</i> has been relatively weak in physiological conditions. More recent studies have addressed both sets of concerns. Histones are released from cells as part of neutrophil extracellular traps (NETs) and are thus able to encounter extracellular bacteria. Histones are also present intracellularly in the cytoplasm attached to lipid droplets, positioning them to encounter cytosolic bacteria. Our recent work (Doolin et al., 2020, Nat Commun), which is discussed here, shows that histones have synergistic antimicrobial activities when they are paired with antimicrobial peptides (AMPs), which form pores in bacterial membranes and co-localize with histones in NETs. The work demonstrates that histones enhance AMP-mediated pores, impair bacterial membrane recovery, depolarize the bacterial proton gradient, and enter the bacterial cytoplasm, where they restructure the chromosome and inhibit transcription. Here, we examine potential mechanisms that are responsible for these outcomes.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 11","pages":"309-311"},"PeriodicalIF":4.6,"publicationDate":"2020-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38575631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erythrocyte phospho-signalling is dynamically altered during infection with <i>Plasmodium falciparum</i>.","authors":"Jack D Adderley,&nbsp;Christian Doerig","doi":"10.15698/mic2020.10.733","DOIUrl":"https://doi.org/10.15698/mic2020.10.733","url":null,"abstract":"<p><p>It is well established that intracellular pathogens mobilise signalling pathways to manipulate gene expression of their host cell to promote their own survival. Surprisingly, there is evidence that specific host signalling molecules are likewise activated in a-nucleated erythrocytes in response to infection with malaria parasites. In this paper (Adderley <i>et al.</i>, Nature Communications 2020), we report the system-wide assessment of host erythrocyte signalling during the course of infection with <i>Plasmodium falciparum</i>. This was achieved through the use of antibody microarrays containing >800 antibodies directed against human signalling proteins, which enabled us to interrogate the status of host erythrocyte signalling pathways at the ring, trophozoite and schizont stages of parasite development. This not only confirmed the pre-existing fragmentary data on the activation of a host erythrocyte PAK-MEK pathway, but also identified dynamic changes to many additional signalling elements, with trophozoite-infected erythrocytes displaying the largest mobilisation of host cell signalling. This study generated a comprehensive dataset on the modulation of host erythrocyte signalling during infection with <i>P. falciparum</i>, and provides the proof of principle that human protein kinases activated by <i>Plasmodium</i> infection represent attractive targets for antimalarial intervention.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 10","pages":"286-288"},"PeriodicalIF":4.6,"publicationDate":"2020-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38454379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novobiocin inhibits membrane synthesis and vacuole formation of <i>Enterococcus faecalis</i> protoplasts.","authors":"Rintaro Tsuchikado,&nbsp;Satoshi Kami,&nbsp;Sawako Takahashi,&nbsp;Hiromi Nishida","doi":"10.15698/mic2020.11.735","DOIUrl":"https://doi.org/10.15698/mic2020.11.735","url":null,"abstract":"<p><p>We demonstrate that plasma membrane biosynthesis and vacuole formation require DNA replication in <i>Enterococcus faecalis</i> protoplasts. The replication inhibitor novobiocin inhibited not only DNA replication but also cell enlargement (plasma membrane biosynthesis) and vacuole formation during the enlargement of the <i>E. faecalis</i> protoplasts. After novobiocin treatment prior to vacuole formation, the cell size of <i>E. faecalis</i> protoplasts was limited to 6 μm in diameter and the cells lacked vacuoles. When novobiocin was added after vacuole formation, <i>E. faecalis</i> protoplasts grew with vacuole enlargement; after novobiocin removal, protoplasts were enlarged again. Although cell size distribution of the protoplasts was similar following the 24 h and 48 h novobiocin treatments, after 72 h of novobiocin treatment there was a greater number of smaller sized protoplasts, suggesting that extended novobiocin treatment may inhibit the re-enlargement of <i>E. faecalis</i> protoplasts after novobiocin removal. Our findings demonstrate that novobiocin can control the enlargement of <i>E. faecalis</i> protoplasts due to inhibition of DNA replication.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 11","pages":"300-308"},"PeriodicalIF":4.6,"publicationDate":"2020-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38568210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variants of the human <i>RAD52</i> gene confer defects in ionizing radiation resistance and homologous recombination repair in budding yeast.","authors":"Alissa D Clear,&nbsp;Glenn M Manthey,&nbsp;Olivia Lewis,&nbsp;Isabelle Y Lopez,&nbsp;Rossana Rico,&nbsp;Shannon Owens,&nbsp;M Cristina Negritto,&nbsp;Elise W Wolf,&nbsp;Jason Xu,&nbsp;Nikola Kenjić,&nbsp;J Jefferson P Perry,&nbsp;Aaron W Adamson,&nbsp;Susan L Neuhausen,&nbsp;Adam M Bailis","doi":"10.15698/mic2020.10.732","DOIUrl":"https://doi.org/10.15698/mic2020.10.732","url":null,"abstract":"<p><p>RAD52 is a structurally and functionally conserved component of the DNA double-strand break (DSB) repair apparatus from budding yeast to humans. We recently showed that expressing the human gene, <i>HsRAD52</i> in <i>rad52</i> mutant budding yeast cells can suppress both their ionizing radiation (IR) sensitivity and homologous recombination repair (HRR) defects. Intriguingly, we observed that <i>HsRAD52</i> supports DSB repair by a mechanism of HRR that conserves genome structure and is independent of the canonical HR machinery. In this study we report that naturally occurring variants of <i>HsRAD52</i>, one of which suppresses the pathogenicity of <i>BRCA2</i> mutations, were unable to suppress the IR sensitivity and HRR defects of <i>rad52</i> mutant yeast cells, but fully suppressed a defect in DSB repair by single-strand annealing (SSA). This failure to suppress both IR sensitivity and the HRR defect correlated with an inability of HsRAD52 protein to associate with and drive an interaction between genomic sequences during DSB repair by HRR. These results suggest that HsRAD52 supports multiple, distinct DSB repair apparatuses in budding yeast cells and help further define its mechanism of action in HRR. They also imply that disruption of HsRAD52-dependent HRR in BRCA2-defective human cells may contribute to protection against tumorigenesis and provide a target for killing BRCA2-defective cancers.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 10","pages":"270-285"},"PeriodicalIF":4.6,"publicationDate":"2020-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38454380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic analysis of nuclear gene function in respiratory growth and expression of the mitochondrial genome in <i>S. cerevisiae</i>.","authors":"Maria Stenger,&nbsp;Duc Tung Le,&nbsp;Till Klecker,&nbsp;Benedikt Westermann","doi":"10.15698/mic2020.09.729","DOIUrl":"https://doi.org/10.15698/mic2020.09.729","url":null,"abstract":"<p><p>The production of metabolic energy in form of ATP by oxidative phosphorylation depends on the coordinated action of hundreds of nuclear-encoded mitochondrial proteins and a handful of proteins encoded by the mitochondrial genome (mtDNA). We used the yeast <i>Saccharomyces cerevisiae</i> as a model system to systematically identify the genes contributing to this process. Integration of genome-wide high-throughput growth assays with previously published large data sets allowed us to define with high confidence a set of 254 nuclear genes that are indispensable for respiratory growth. Next, we induced loss of mtDNA in the yeast deletion collection by growth on ethidium bromide-containing medium and identified twelve genes that are essential for viability in the absence of mtDNA (i.e. <i>petite</i>-negative). Replenishment of mtDNA by cytoduction showed that respiratory-deficient phenotypes are highly variable in many yeast mutants. Using a mitochondrial genome carrying a selectable marker, <i>ARG8</i> ^<i>m</i> , we screened for mutants that are specifically defective in maintenance of mtDNA and mitochondrial protein synthesis. We found that up to 176 nuclear genes are required for expression of mitochondria-encoded proteins during fermentative growth. Taken together, our data provide a comprehensive picture of the molecular processes that are required for respiratory metabolism in a simple eukaryotic cell.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":" ","pages":"234-249"},"PeriodicalIF":4.6,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38358967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From the Uncharacterized Protein Family 0016 to the GDT1 family: Molecular insights into a newly-characterized family of cation secondary transporters.","authors":"Louise Thines,&nbsp;Jiri Stribny,&nbsp;Pierre Morsomme","doi":"10.15698/mic2020.08.725","DOIUrl":"https://doi.org/10.15698/mic2020.08.725","url":null,"abstract":"<p><p>The Uncharacterized Protein Family 0016 (UPF0016) gathers poorly studied membrane proteins well conserved through evolution that possess one or two copies of the consensus motif Glu-x-Gly-Asp-(Arg/Lys)-(Ser/Thr). Members are found in many eukaryotes, bacteria and archaea. The interest for this protein family arose in 2012 when its human member TMEM165 was linked to the occurrence of Congenital Disorders of Glycosylation (CDGs) when harbouring specific mutations. Study of the UPF0016 family is undergone through the characterization of the bacterium <i>Vibrio cholerae</i> (MneA), cyanobacterium <i>Synechocystis</i> (SynPAM71), yeast <i>Saccharomyces cerevisiae</i> (Gdt1p), plant <i>Arabidopsis thaliana</i> (PAM71 and CMT1), and human (TMEM165) members. These proteins have all been identified as transporters of cations, more precisely of Mn²⁺, with an extra reported function in Ca²⁺ and/or H⁺ transport for some of them. Apart from glycosylation in humans, the UPF0016 members are required for lactation in humans, photosynthesis in plants and cyanobacteria, Ca²⁺ signaling in yeast, and Mn²⁺ homeostasis in the five aforementioned species. The requirement of the UPF0016 members for key physiological processes most likely derives from their transport activity at the Golgi membrane in human and yeast, the chloroplasts membranes in plants, the thylakoid and plasma membranes in cyanobacteria, and the cell membrane in bacteria. In the light of these studies on various UPF0016 members, this family is not considered as uncharacterized anymore and has been renamed the Gdt1 family according to the name of its <i>S. cerevisiae</i> member. This review aims at assembling and confronting the current knowledge in order to identify shared and distinct features in terms of transported molecules, mode of action, structure, etc., as well as to better understand their corresponding physiological roles.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 8","pages":"202-214"},"PeriodicalIF":4.6,"publicationDate":"2020-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38219353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A broad-spectrum antibiotic adjuvant SLAP-S25: one stone many birds.","authors":"Meirong Song,&nbsp;Kui Zhu","doi":"10.15698/mic2020.08.726","DOIUrl":"https://doi.org/10.15698/mic2020.08.726","url":null,"abstract":"<p><p>The rapid emergence of antibiotic resistance has caused serious threat to global health. The worldwide search for novel classes of antibiotics to combat multidrug-resistant (MDR) bacteria is barren since about half a century ago. One of the promising strategies to combat the MDR pathogens is the combinational therapy. For instance, trimethoprim and clavulanic acid are routinely used to enhance the efficacies of sulfonamides and β-lactam antibiotics in clinic, respectively. Nevertheless, such adjuvants are specific for certain classes of antibiotics. We hypothesized that the combinational treatments with antibiotic adjuvants targeting the bacterial membrane may potentiate other antibiotics against MDR Gram-negative pathogens. In our recent publication (Song <i>et al.</i>, doi: 10.1038/s41564-020-0723-z), we demonstrate a short linear antibacterial peptide SLAP-S25, which potentiates multiple antibiotics with different modes of action against Gram-negative bacteria. The mechanism studies show that SLAP-S25 targets both lipopolysaccharide (LPS) in the outer membrane and phosphatidylglycerol (PG) in the inner membrane of <i>Escherichia coli</i>. The impaired bacterial membrane caused by SLAP-S25 promotes the intracellular accumulation of antibiotics in bacteria. Our results indicate that the bacterial membranes are promising targets for the discovery of new antibiotics or antibiotic adjuvants to combat MDR bacteria associated infections.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 8","pages":"215-217"},"PeriodicalIF":4.6,"publicationDate":"2020-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38219354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins.","authors":"Mehdi Kabani","doi":"10.15698/mic2020.07.724","DOIUrl":"https://doi.org/10.15698/mic2020.07.724","url":null,"abstract":"<p><p>Infectious proteins or prions are non-native conformations of proteins that are the causative agents of devastating neurodegenerative diseases in humans and heritable traits in filamentous fungi and yeasts. Prion proteins form highly ordered self-perpetuating fibrillar aggregates that traffic vertically and horizontally from cell to cell. The spreading of these infectious entities relies on different mechanisms, among which the extracellular vesicles (EV)-mediated traffic. The prion form of the yeast <i>Saccharomyces cerevisiae</i> Sup35p translation terminator causes the [<i>PSI</i> ⁺] nonsense suppression phenotype. This fascinating biological model helped us shape our understanding of the mechanisms of formation, propagation and elimination of infectious protein aggregates. We discovered that Sup35p is exported via EV, both in its soluble and aggregated infectious states. We recently reported that high amounts of Sup35p prion particles are exported to the yeast periplasm via periplasmic vesicles (PV) in glucose-starved cells. EV and PV are different in terms of size and protein content, and their export is inversely regulated by glucose availability in the growth medium. We believe these are important observations that should make us revise our current view on the way yeast prions propagate. Hence, I propose several hypotheses as to the significance of these observations for the transmission of yeast prions. I also discuss how yeast could be used as a powerful tractable biological model to investigate the molecular mechanisms of vesicle-mediated export of pathological protein aggregates implicated in neurodegenerative diseases.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 7","pages":"199-201"},"PeriodicalIF":4.6,"publicationDate":"2020-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38147028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Cdc42 for polarized growth in budding yeast.","authors":"Kristi E Miller,&nbsp;Pil Jung Kang,&nbsp;Hay-Oak Park","doi":"10.15698/mic2020.07.722","DOIUrl":"https://doi.org/10.15698/mic2020.07.722","url":null,"abstract":"<p><p>The Rho GTPase Cdc42 is a central regulator of cell polarity in diverse cell types. The activity of Cdc42 is dynamically controlled in time and space to enable distinct polarization events, which generally occur along a single axis in response to spatial cues. Our understanding of the mechanisms underlying Cdc42 polarization has benefited largely from studies of the budding yeast <i>Saccharomyces cerevisiae</i>, a genetically tractable model organism. In budding yeast, Cdc42 activation occurs in two temporal steps in the G1 phase of the cell cycle to establish a proper growth site. Here, we review findings in budding yeast that reveal an intricate crosstalk among polarity proteins for biphasic Cdc42 regulation. The first step of Cdc42 activation may determine the axis of cell polarity, while the second step ensures robust Cdc42 polarization for growth. Biphasic Cdc42 polarization is likely to ensure the proper timing of events including the assembly and recognition of spatial landmarks and stepwise assembly of a new ring of septins, cytoskeletal GTP-binding proteins, at the incipient bud site. Biphasic activation of GTPases has also been observed in mammalian cells, suggesting that biphasic activation could be a general mechanism for signal-responsive cell polarization. Cdc42 activity is necessary for polarity establishment during normal cell division and development, but its activity has also been implicated in the promotion of aging. We also discuss negative polarity signaling and emerging concepts of Cdc42 signaling in cellular aging.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 7","pages":"175-189"},"PeriodicalIF":4.6,"publicationDate":"2020-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38147027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yeast-based assays for the functional characterization of cancer-associated variants of human DNA repair genes.","authors":"Tiziana Cervelli,&nbsp;Samuele Lodovichi,&nbsp;Francesca Bellè,&nbsp;Alvaro Galli","doi":"10.15698/mic2020.07.721","DOIUrl":"https://doi.org/10.15698/mic2020.07.721","url":null,"abstract":"<p><p>Technological advances are continuously revealing new genetic variants that are often difficult to interpret. As one of the most genetically tractable model organisms, yeast can have a central role in determining the consequences of human genetic variation. DNA repair gene mutations are associated with many types of cancers, therefore the evaluation of the functional impact of these mutations is crucial for risk assessment and for determining therapeutic strategies. Owing to the evolutionary conservation of DNA repair pathways between human cells and the yeast <i>Saccharomyces cerevisiae</i>, several functional assays have been developed. Here, we describe assays for variants of human genes belonging to the major DNA repair pathways divided in functional assays for human genes with yeast orthologues and human genes lacking a yeast orthologue. Human genes with orthologues can be studied by introducing the correspondent human mutations directly in the yeast gene or expressing the human gene carrying the mutations; while the only possible approach for human genes without a yeast orthologue is the heterologous expression. The common principle of these approaches is that the mutated gene determines a phenotypic alteration that can vary according to the gene studied and the domain of the protein. Here, we show how the versatility of yeast can help in classifying cancer-associated variants.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 7","pages":"162-174"},"PeriodicalIF":4.6,"publicationDate":"2020-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38147025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}