Pub Date : 2024-01-23DOI: 10.1038/s41579-024-01013-5
Andrea Du Toit
This study reports that antibodies that target the fusion peptide on the HIV envelope provide protection to rhesus macaques against mucosal simian-HIV challenge.
这项研究报告称，针对艾滋病病毒包膜上的融合肽的抗体可保护猕猴免受粘膜猿类艾滋病病毒的挑战。
{"title":"Targeting the HIV-1 Env fusion protein","authors":"Andrea Du Toit","doi":"10.1038/s41579-024-01013-5","DOIUrl":"10.1038/s41579-024-01013-5","url":null,"abstract":"This study reports that antibodies that target the fusion peptide on the HIV envelope provide protection to rhesus macaques against mucosal simian-HIV challenge.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":null,"pages":null},"PeriodicalIF":88.1,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542038","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}
Pub Date : 2024-01-22DOI: 10.1038/s41579-023-01007-9
Ethan M. Jones, John P. Marken, Pamela A. Silver
Microorganisms are a promising means to address many societal sustainability challenges owing to their ability to thrive in diverse environments and interface with the microscale chemical world via diverse metabolic capacities. Synthetic biology can engineer microorganisms by rewiring their regulatory networks or introducing new functionalities, enhancing their utility for target applications. In this Review, we provide a broad, high-level overview of various research efforts addressing sustainability challenges through synthetic biology, emphasizing foundational microbiological research questions that can accelerate the development of these efforts. We introduce an organizational framework that categorizes these efforts along three domains — factory, farm and field — that are defined by the extent to which the engineered microorganisms interface with the natural external environment. Different application areas within the same domain share many fundamental challenges, highlighting productive opportunities for cross-disciplinary collaborations between researchers working in historically disparate fields. In this Review, Jones, Marken and Silver develop a conceptual framework for synthetic microbiology organized into three domains — factory, farm and field — to explore the utility of synthetic microbiology in addressing sustainability challenges, and examine several examples of microbial engineering applications relevant to each domain.
{"title":"Synthetic microbiology in sustainability applications","authors":"Ethan M. Jones, John P. Marken, Pamela A. Silver","doi":"10.1038/s41579-023-01007-9","DOIUrl":"10.1038/s41579-023-01007-9","url":null,"abstract":"Microorganisms are a promising means to address many societal sustainability challenges owing to their ability to thrive in diverse environments and interface with the microscale chemical world via diverse metabolic capacities. Synthetic biology can engineer microorganisms by rewiring their regulatory networks or introducing new functionalities, enhancing their utility for target applications. In this Review, we provide a broad, high-level overview of various research efforts addressing sustainability challenges through synthetic biology, emphasizing foundational microbiological research questions that can accelerate the development of these efforts. We introduce an organizational framework that categorizes these efforts along three domains — factory, farm and field — that are defined by the extent to which the engineered microorganisms interface with the natural external environment. Different application areas within the same domain share many fundamental challenges, highlighting productive opportunities for cross-disciplinary collaborations between researchers working in historically disparate fields. In this Review, Jones, Marken and Silver develop a conceptual framework for synthetic microbiology organized into three domains — factory, farm and field — to explore the utility of synthetic microbiology in addressing sustainability challenges, and examine several examples of microbial engineering applications relevant to each domain.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":null,"pages":null},"PeriodicalIF":88.1,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521503","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":"Genus-wide research provides insights into pathogen evolution","authors":"Stephanie McGimpsey, Mathew A. Beale","doi":"10.1038/s41579-024-01009-1","DOIUrl":"10.1038/s41579-024-01009-1","url":null,"abstract":"This Genome Watch article highlights how studying pathogens in the context of their phylogenetic neighbours can provide insights into their evolution.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":null,"pages":null},"PeriodicalIF":88.1,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521501","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}
Pub Date : 2024-01-19DOI: 10.1038/s41579-024-01012-6
Andrea Du Toit
This study describes Bdellovibrio bacteriovorus trimeric fibre proteins with diverse adhesive tips that enable the identification of a broad range of prey.
{"title":"Bdellovibrio bacteriovorus finds its prey","authors":"Andrea Du Toit","doi":"10.1038/s41579-024-01012-6","DOIUrl":"10.1038/s41579-024-01012-6","url":null,"abstract":"This study describes Bdellovibrio bacteriovorus trimeric fibre proteins with diverse adhesive tips that enable the identification of a broad range of prey.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":null,"pages":null},"PeriodicalIF":88.1,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139502430","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}
Pub Date : 2024-01-18DOI: 10.1038/s41579-024-01011-7
Agustina Taglialegna
In this study, Knödlseder et al. explore the potential of an engineered Cutibacterium acnes strain as a microbiome-based therapy for skin conditions.
在这项研究中，Knödlseder 等人探索了痤疮杆菌工程菌株作为基于微生物的皮肤病疗法的潜力。
{"title":"Cutibacterium improves skin condition","authors":"Agustina Taglialegna","doi":"10.1038/s41579-024-01011-7","DOIUrl":"10.1038/s41579-024-01011-7","url":null,"abstract":"In this study, Knödlseder et al. explore the potential of an engineered Cutibacterium acnes strain as a microbiome-based therapy for skin conditions.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":null,"pages":null},"PeriodicalIF":88.1,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139489394","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}
Pub Date : 2024-01-15DOI: 10.1038/s41579-023-01003-z
Silvio Steiner, Annika Kratzel, G. Tuba Barut, Reto M. Lang, Etori Aguiar Moreira, Lisa Thomann, Jenna N. Kelly, Volker Thiel
The zoonotic emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing coronavirus disease 2019 (COVID-19) pandemic have profoundly affected our society. The rapid spread and continuous evolution of new SARS-CoV-2 variants continue to threaten global public health. Recent scientific advances have dissected many of the molecular and cellular mechanisms involved in coronavirus infections, and large-scale screens have uncovered novel host-cell factors that are vitally important for the virus life cycle. In this Review, we provide an updated summary of the SARS-CoV-2 life cycle, gene function and virus–host interactions, including recent landmark findings on general aspects of coronavirus biology and newly discovered host factors necessary for virus replication. In this Review, Thiel and colleagues summarize our emerging knowledge of the SARS-CoV-2 intracellular life cycle and the molecular functions of the viral proteins, as well as their interaction with the host cell.
{"title":"SARS-CoV-2 biology and host interactions","authors":"Silvio Steiner, Annika Kratzel, G. Tuba Barut, Reto M. Lang, Etori Aguiar Moreira, Lisa Thomann, Jenna N. Kelly, Volker Thiel","doi":"10.1038/s41579-023-01003-z","DOIUrl":"10.1038/s41579-023-01003-z","url":null,"abstract":"The zoonotic emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing coronavirus disease 2019 (COVID-19) pandemic have profoundly affected our society. The rapid spread and continuous evolution of new SARS-CoV-2 variants continue to threaten global public health. Recent scientific advances have dissected many of the molecular and cellular mechanisms involved in coronavirus infections, and large-scale screens have uncovered novel host-cell factors that are vitally important for the virus life cycle. In this Review, we provide an updated summary of the SARS-CoV-2 life cycle, gene function and virus–host interactions, including recent landmark findings on general aspects of coronavirus biology and newly discovered host factors necessary for virus replication. In this Review, Thiel and colleagues summarize our emerging knowledge of the SARS-CoV-2 intracellular life cycle and the molecular functions of the viral proteins, as well as their interaction with the host cell.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":null,"pages":null},"PeriodicalIF":88.1,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139468664","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}
Pub Date : 2024-01-08DOI: 10.1038/s41579-023-00999-8
Charles Roussin-Léveillée, David Mackey, Gayani Ekanayake, Reid Gohmann, Peter Moffett
The plant extracellular space, referred to as the apoplast, is inhabited by a variety of microorganisms. Reflecting the crucial nature of this compartment, both plants and microorganisms seek to control, exploit and respond to its composition. Upon sensing the apoplastic environment, pathogens activate virulence programmes, including the delivery of effectors with well-established roles in suppressing plant immunity. We posit that another key and foundational role of effectors is niche establishment — specifically, the manipulation of plant physiological processes to enrich the apoplast in water and nutritive metabolites. Facets of plant immunity counteract niche establishment by restricting water, nutrients and signals for virulence activation. The complex competition to control and, in the case of pathogens, exploit the apoplast provides remarkable insights into the nature of virulence, host susceptibility, host defence and, ultimately, the origin of phytopathogenesis. This novel framework focuses on the ecology of a microbial niche and highlights areas of future research on plant–microorganism interactions. In this Review, Roussin-Léveillée, Mackey and colleagues examine microorganism interaction with and manipulation of the plant apoplast. Effector-driven extracellular niche establishment is conceptualized as foundational to plant pathogenesis and frames the discussion of the complex interplay between pathogen virulence, host immunity and the physiological dynamics shaping plant–microorganism interactions.
{"title":"Extracellular niche establishment by plant pathogens","authors":"Charles Roussin-Léveillée, David Mackey, Gayani Ekanayake, Reid Gohmann, Peter Moffett","doi":"10.1038/s41579-023-00999-8","DOIUrl":"10.1038/s41579-023-00999-8","url":null,"abstract":"The plant extracellular space, referred to as the apoplast, is inhabited by a variety of microorganisms. Reflecting the crucial nature of this compartment, both plants and microorganisms seek to control, exploit and respond to its composition. Upon sensing the apoplastic environment, pathogens activate virulence programmes, including the delivery of effectors with well-established roles in suppressing plant immunity. We posit that another key and foundational role of effectors is niche establishment — specifically, the manipulation of plant physiological processes to enrich the apoplast in water and nutritive metabolites. Facets of plant immunity counteract niche establishment by restricting water, nutrients and signals for virulence activation. The complex competition to control and, in the case of pathogens, exploit the apoplast provides remarkable insights into the nature of virulence, host susceptibility, host defence and, ultimately, the origin of phytopathogenesis. This novel framework focuses on the ecology of a microbial niche and highlights areas of future research on plant–microorganism interactions. In this Review, Roussin-Léveillée, Mackey and colleagues examine microorganism interaction with and manipulation of the plant apoplast. Effector-driven extracellular niche establishment is conceptualized as foundational to plant pathogenesis and frames the discussion of the complex interplay between pathogen virulence, host immunity and the physiological dynamics shaping plant–microorganism interactions.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":null,"pages":null},"PeriodicalIF":88.1,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139400489","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}
Pub Date : 2023-12-19DOI: 10.1038/s41579-023-01001-1
Eric A. Meyerowitz, Jake Scott, Aaron Richterman, Victoria Male, Muge Cevik
The clinical implications of COVID-19 have changed since SARS-CoV-2 first emerged in humans. The current high levels of population immunity, due to prior infection and/or vaccination, have been associated with a vastly decreased overall risk of severe disease. Some people, particularly those with immunocompromising conditions, remain at risk for severe outcomes. Through the course of the pandemic, variants with somewhat different symptom profiles from the original SARS-CoV-2 virus have emerged. The management of COVID-19 has also changed since 2020, with the increasing availability of evidence-based treatments in two main classes: antivirals and immunomodulators. Selecting the appropriate treatment(s) for patients with COVID-19 requires a deep understanding of the evidence and an awareness of the limitations of applying data that have been largely based on immune-naive populations to patients today who most likely have vaccine-derived and/or infection-derived immunity. In this Review, we provide a summary of the clinical manifestations and approaches to caring for adult patients with COVID-19 in the era of vaccine availability and the dominance of the Omicron subvariants, with a focus on the management of COVID-19 in different patient groups, including immunocompromised, pregnant, vaccinated and unvaccinated patients. In this Review, Meyerowitz et al. examine the clinical presentations of COVID-19 in the era of widespread population immunity and explore current approaches to managing COVID-19 across different patient groups.
{"title":"Clinical course and management of COVID-19 in the era of widespread population immunity","authors":"Eric A. Meyerowitz, Jake Scott, Aaron Richterman, Victoria Male, Muge Cevik","doi":"10.1038/s41579-023-01001-1","DOIUrl":"10.1038/s41579-023-01001-1","url":null,"abstract":"The clinical implications of COVID-19 have changed since SARS-CoV-2 first emerged in humans. The current high levels of population immunity, due to prior infection and/or vaccination, have been associated with a vastly decreased overall risk of severe disease. Some people, particularly those with immunocompromising conditions, remain at risk for severe outcomes. Through the course of the pandemic, variants with somewhat different symptom profiles from the original SARS-CoV-2 virus have emerged. The management of COVID-19 has also changed since 2020, with the increasing availability of evidence-based treatments in two main classes: antivirals and immunomodulators. Selecting the appropriate treatment(s) for patients with COVID-19 requires a deep understanding of the evidence and an awareness of the limitations of applying data that have been largely based on immune-naive populations to patients today who most likely have vaccine-derived and/or infection-derived immunity. In this Review, we provide a summary of the clinical manifestations and approaches to caring for adult patients with COVID-19 in the era of vaccine availability and the dominance of the Omicron subvariants, with a focus on the management of COVID-19 in different patient groups, including immunocompromised, pregnant, vaccinated and unvaccinated patients. In this Review, Meyerowitz et al. examine the clinical presentations of COVID-19 in the era of widespread population immunity and explore current approaches to managing COVID-19 across different patient groups.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":null,"pages":null},"PeriodicalIF":88.1,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138740589","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}
Pub Date : 2023-12-18DOI: 10.1038/s41579-023-00998-9
Karina Ratiner, Dragos Ciocan, Suhaib K. Abdeen, Eran Elinav
Inter-individual human variability, driven by various genetic and environmental factors, complicates the ability to develop effective population-based early disease detection, treatment and prognostic assessment. The microbiome, consisting of diverse microorganism communities including viruses, bacteria, fungi and eukaryotes colonizing human body surfaces, has recently been identified as a contributor to inter-individual variation, through its person-specific signatures. As such, the microbiome may modulate disease manifestations, even among individuals with similar genetic disease susceptibility risks. Information stored within microbiomes may therefore enable early detection and prognostic assessment of disease in at-risk populations, whereas microbiome modulation may constitute an effective and safe treatment tailored to the individual. In this Review, we explore recent advances in the application of microbiome data in precision medicine across a growing number of human diseases. We also discuss the challenges, limitations and prospects of analysing microbiome data for personalized patient care. In this study, Ratiner et al. examine the advantages, challenges and future perspectives of utilizing microbiome data in personalized medicine for optimal patient care.
{"title":"Utilization of the microbiome in personalized medicine","authors":"Karina Ratiner, Dragos Ciocan, Suhaib K. Abdeen, Eran Elinav","doi":"10.1038/s41579-023-00998-9","DOIUrl":"10.1038/s41579-023-00998-9","url":null,"abstract":"Inter-individual human variability, driven by various genetic and environmental factors, complicates the ability to develop effective population-based early disease detection, treatment and prognostic assessment. The microbiome, consisting of diverse microorganism communities including viruses, bacteria, fungi and eukaryotes colonizing human body surfaces, has recently been identified as a contributor to inter-individual variation, through its person-specific signatures. As such, the microbiome may modulate disease manifestations, even among individuals with similar genetic disease susceptibility risks. Information stored within microbiomes may therefore enable early detection and prognostic assessment of disease in at-risk populations, whereas microbiome modulation may constitute an effective and safe treatment tailored to the individual. In this Review, we explore recent advances in the application of microbiome data in precision medicine across a growing number of human diseases. We also discuss the challenges, limitations and prospects of analysing microbiome data for personalized patient care. In this study, Ratiner et al. examine the advantages, challenges and future perspectives of utilizing microbiome data in personalized medicine for optimal patient care.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":null,"pages":null},"PeriodicalIF":88.1,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138714041","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}
Pub Date : 2023-12-15DOI: 10.1038/s41579-023-00995-y
Alagie Jassey, William T. Jackson
Autophagy is a constitutive cellular process of degradation required to maintain homeostasis and turn over spent organelles and aggregated proteins. For some viruses, the process can be antiviral, degrading viral proteins or virions themselves. For many other viruses, the induction of the autophagic process provides a benefit and promotes viral replication. In this Review, we survey the roles that the autophagic pathway plays in the replication of viruses. Most viruses that benefit from autophagic induction block autophagic degradation, which is a ‘bend, but don’t break’ strategy initiating but limiting a potentially antiviral response. In almost all cases, it is other effects of the redirected autophagic machinery that benefit these viruses. This rapid mechanism to generate small double-membraned vesicles can be usurped to shape membranes for viral genome replication and virion maturation. However, data suggest that autophagic maintenance of cellular homeostasis is crucial for the initiation of infection, as viruses have evolved to replicate in normal, healthy cells. Inhibition of autophagic degradation is important once infection has initiated. Although true degradative autophagy is probably a negative for most viruses, initiating nondegradative autophagic membranes benefits a wide variety of viruses. In this Review, Jassey and Jackson explore the intricate relationship between viruses and the autophagic pathway, highlighting how viruses either exploit or manipulate the autophagy pathway to influence their replication and survival within host cells.
{"title":"Viruses and autophagy: bend, but don’t break","authors":"Alagie Jassey, William T. Jackson","doi":"10.1038/s41579-023-00995-y","DOIUrl":"10.1038/s41579-023-00995-y","url":null,"abstract":"Autophagy is a constitutive cellular process of degradation required to maintain homeostasis and turn over spent organelles and aggregated proteins. For some viruses, the process can be antiviral, degrading viral proteins or virions themselves. For many other viruses, the induction of the autophagic process provides a benefit and promotes viral replication. In this Review, we survey the roles that the autophagic pathway plays in the replication of viruses. Most viruses that benefit from autophagic induction block autophagic degradation, which is a ‘bend, but don’t break’ strategy initiating but limiting a potentially antiviral response. In almost all cases, it is other effects of the redirected autophagic machinery that benefit these viruses. This rapid mechanism to generate small double-membraned vesicles can be usurped to shape membranes for viral genome replication and virion maturation. However, data suggest that autophagic maintenance of cellular homeostasis is crucial for the initiation of infection, as viruses have evolved to replicate in normal, healthy cells. Inhibition of autophagic degradation is important once infection has initiated. Although true degradative autophagy is probably a negative for most viruses, initiating nondegradative autophagic membranes benefits a wide variety of viruses. In this Review, Jassey and Jackson explore the intricate relationship between viruses and the autophagic pathway, highlighting how viruses either exploit or manipulate the autophagy pathway to influence their replication and survival within host cells.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":null,"pages":null},"PeriodicalIF":88.1,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138657528","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}
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