Dear Editor,The occurrence of concentrated pneumonia cases in Wuhan city,Hubei province of China was first reported on December 30,2019 by the Wuhan Municipal Health Commission(WHO,2020).The pneumonia cases were found...Dear Editor,The occurrence of concentrated pneumonia cases in Wuhan city,Hubei province of China was first reported on December 30,2019 by the Wuhan Municipal Health Commission(WHO,2020).The pneumonia cases were found to be linked to a large seafood and animal market in Wuhan,and measures for sanitation and disinfection were taken swiftly by the local government agency.The Centers for Disease Control and Prevention(CDC)and Chinese health authorities later determined and announced that a novel coronavirus(CoV),denoted as 2019-nCoV,had caused the pneumonia outbreak in Wuhan city(CDC,2020).Scientists from multiple groups had obtained the virus samples from hospitalized patients(Normile,2020).The isolated viruses were morphologically identical when observed under electron microscopy.展开更多
CRISPR/Cas9 genome targeting systems have been applied to a variety of species. However, most CRISPR/Cas9 systems reported for plants can only modify one or a few target sites. Here, we report a robust CRISPR/Cas9 vec...CRISPR/Cas9 genome targeting systems have been applied to a variety of species. However, most CRISPR/Cas9 systems reported for plants can only modify one or a few target sites. Here, we report a robust CRISPR/Cas9 vector system, utilizing a plant codon optimized Cas9 gene, for convenient and high- efficiency multiplex genome editing in monocot and dicot plants. We designed PCR-based procedures to rapidly generate multiple sgRNA expression cassettes, which can be assembled into the binary CRISPR/ Cas9 vectors in one round of cloning by Golden Gate ligation or Gibson Assembly. With this system, we edi- ted 46 target sites in rice with an average 85.4% rate of mutation, mostly in biallelic and homozygous status. We reasoned that about 16% of the homozygous mutations in rice were generated through the non-homol- ogous end-joining mechanism followed by homologous recombination-based repair. We also obtained uni- form biallelic, heterozygous, homozygous, and chimeric mutations in Arabidopsis T1 plants. The targeted mutations in both rice and Arabidopsis were heritable. We provide examples of loss-of-function gene mu- tations in To rice and T1Arabidopsis plants by simultaneous targeting of multiple （up to eight） members of a gene family, multiple genes in a biosynthetic pathway, or multiple sites in a single gene. This system has provided a versatile toolbox for studying functions of multiple genes and gene families in plants for basic research and genetic improvement.展开更多
The huge land areas in China provide highly diverse habitats for macrofungi.Of these macrofungi,many are directly related to people’s daily life and have been utilized by ancient Chinese for at least 6800 years.In th...The huge land areas in China provide highly diverse habitats for macrofungi.Of these macrofungi,many are directly related to people’s daily life and have been utilized by ancient Chinese for at least 6800 years.In this study,we evaluate the current known resource diversity of Chinese macrofungi.A total of 1662 taxa are summarized,and all species names and their authorities have been checked and corrected according to authentic mycological databases.Among the 1662 taxa,1020,692,and 480 are considered to be edible,medicinal and poisonous mushrooms,respectively.A few of edible macrofungi in China are commonly used for commercial production.All known medicinal functions are labeled for medicinal species.The most common medicinal functions possessed by Chinese macrofungi are antitumor or anticancer,followed by antioxidant and antimicrobial.A total of 277 Chinese macrofungi are edible simultaneously with certain medicinal functions and without known toxicity.These species could be treated as“Gold Mushrooms”.Contrarily,193 edible and/or medicinal species are also recognized as poisonous mushrooms.To avoid poisoning caused by these species,ingestion either in a proper way or in small amounts is important.However,the mycotoxins metabolized by these poisonous species could be a huge wealth of natural products yet to be explored.How to utilize these Chinese macrofungal resources is a critical to benefit humans worldwide.展开更多
The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,an...The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,and radiological characteristics,as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen,China.All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS).The most common laboratory abnormalities were hypoalbuminemia,lymphopenia,decreased percentage of lymphocytes (LYM) and neutrophils (NEU),elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH),and decreased CD8 count.The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity.ALB,LYM,LYM (%),LDH,NEU (%),and CRP were highly correlated to the acute lung injury.Age,viral load,lung injury score,and blood biochemistry indexes,albumin (ALB),CRP,LDH,LYM (%),LYM,and NEU (%),may be predictors of disease severity.Moreover,the Angiotensin Ⅱlevel in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury.Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.展开更多
Objective: Liver cancer is one of the most common cancers and major cause of cancer deaths in China,which accounts for over 50% of new cases and deaths worldwide.The systematic liver cancer statistics including of pro...Objective: Liver cancer is one of the most common cancers and major cause of cancer deaths in China,which accounts for over 50% of new cases and deaths worldwide.The systematic liver cancer statistics including of projection through 2030 could provide valuable information for prevention and control strategies in China,and experience for other countries.Methods: The burden of liver cancer in China in 2014 was estimated using 339 cancer registries’ data selected from Chinese National Cancer Center(NCC).Incident cases of 22 cancer registries were applied for temporal trends from 2000 to 2014.The burden of liver cancer through 2030 was projected using age-period-cohort model.Results: About 364,800 new cases of liver cancer(268,900 males and 95,900 females) occurred in China,and about 318,800 liver cancer deaths(233,500 males and 85,300 females) in 2014.Western regions of China had the highest incidence and mortality rates.Incidence and mortality rates decreased by about 2.3% and 2.6% per year during the period of 2000-2014,respectively,and would decrease by more than 44% between 2014 and 2030 in China.The young generation,particularly for those aged under 40 years,showed a faster down trend.Conclusions: Based on the analysis,incidence and mortality rates of liver cancer are expected to decrease through 2030,but the burden of liver cancer is still serious in China,especially in rural and western areas.Most cases of liver cancer in China can be prevented through vaccination and more prevention efforts should be focused on high risk groups.展开更多
An acute respiratory disease,caused by a novel coronavirus(SARS-CoV-2,previously known as 2019-nCoV),the coronavirus disease 2019(COVID-19)has spread throughout China and received worldwide attention.On 30 January 202...An acute respiratory disease,caused by a novel coronavirus(SARS-CoV-2,previously known as 2019-nCoV),the coronavirus disease 2019(COVID-19)has spread throughout China and received worldwide attention.On 30 January 2020,World Health Organization(WHO)officially declared the COVID-19 epidemic as a public health emergency of international concern.The emergence of SARS-CoV-2,since the severe acute respiratory syndrome coronavirus(SARSCoV)in 2002 and Middle East respiratory syndrome coronavirus(MERS-CoV)in 2012,marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century.As of 1 March 2020,a total of 87,137 confirmed cases globally,79,968 confirmed in China and 7169 outside of China,with 2977 deaths(3.4%)had been reported by WHO.Meanwhile,several independent research groups have identified that SARS-CoV-2 belongs toβ-coronavirus,with highly identical genome to bat coronavirus,pointing to bat as the natural host.The novel coronavirus uses the same receptor,angiotensin-converting enzyme 2(ACE2)as that for SARS-CoV,and mainly spreads through the respiratory tract.Importantly,increasingly evidence showed sustained human-tohuman transmission,along with many exported cases across the globe.The clinical symptoms of COVID-19 patients include fever,cough,fatigue and a small population of patients appeared gastrointestinal infection symptoms.The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes,which may be associated with acute respiratory distress syndrome(ARDS)and cytokine storm.Currently,there are few specific antiviral strategies,but several potent candidates of antivirals and repurposed drugs are under urgent investigation.In this review,we summarized the latest research progress of the epidemiology,pathogenesis,and clinical characteristics of COVID-19,and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.展开更多
Abiotic stresses and soil nutrient limitations are major environmental conditions that reduce plant growth,productivity and quality.Plants have evolved mechanisms to perceive these environmental challenges,transmit th...Abiotic stresses and soil nutrient limitations are major environmental conditions that reduce plant growth,productivity and quality.Plants have evolved mechanisms to perceive these environmental challenges,transmit the stress signals within cells as well as between cells and tissues,and make appropriate adjustments in their growth and development in order to survive and reproduce.In recent years,significant progress has been made on many fronts of the stress signaling research,particularly in understanding the downstream signaling events that culminate at the activation of stress-and nutrient limitation-responsive genes,cellular ion homeostasis,and growth adjustment.However,the revelation of the early events of stress signaling,particularly the identification of primary stress sensors,still lags behind.In this review,we summarize recent work on the genetic and molecular mechanisms of plant abiotic stress and nutrient limitation sensing and signaling and discuss new directions for future studies.展开更多
AIM:To investigate the diagnostic accuracy of acoustic radiation force impulse (ARFI) imaging as a noninvasive method for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients.METHODS:We performed a p...AIM:To investigate the diagnostic accuracy of acoustic radiation force impulse (ARFI) imaging as a noninvasive method for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients.METHODS:We performed a prospective blind com-parison of ARFI elastography,APRI index and FibroMax in a consecutive series of patients who underwent liver biopsy for CHC in University Hospital Bucharest. His-topathological staging of liver fibrosis according to the METAVIR scoring system served as the reference. A to-tal of 74 patients underwent ARFI elastography,APRI index,FibroMax and successful liver biopsy. RESULTS:The noninvasive tests had a good correlation with the liver biopsy results. The most powerful test in predicting fibrosis was ARFI elastography. The diagnostic accuracy of ARFI elastography,expressedas area under receiver operating characteristic curve (AUROC) had a validity of 90.2% (95% CI AUROC = 0.831-0.972,P < 0.001) for the diagnosis of significant f ibrosis (F ≥ 2). ARFI sonoelastography predicted even better F3 or F4 fibrosis (AUROC = 0.993,95% CI = 0.979-1).CONCLUSION:ARFI elastography had very good accuracy for the assessment of liver fibrosis and was superior to other noninvasive methods (APRI Index,FibroMax) for staging liver fibrosis.展开更多
AIM:To evaluate the covalently closed circle DNA (cccDNA) level of hepatitis B virus (HBV) in patients' liver and sera. METHODS:HBV DNA was isolated from patients' liver biopsies and sera.A sensitive real-time...AIM:To evaluate the covalently closed circle DNA (cccDNA) level of hepatitis B virus (HBV) in patients' liver and sera. METHODS:HBV DNA was isolated from patients' liver biopsies and sera.A sensitive real-time PCR method,which is capable of differentiation of HBV viral genomic DNA and cccDNA,was used to quantify the total HBV cccDNA.The total HBV viral DNA was quantitated by real-time PCR using a HBV diagnostic kit (PG Biotech,LTD,Shenzhen,China) described previously. RESULTS:For the first time,we measured the level of HBV DNA and cccDNA isolated from ten HBV patients' liver biopsies and sera.In the liver biopsies,cccDNA was detected from all the biopsy samples.The copy number of cccDNA ranged from from 0.03 to 173.1 per cell,the copy number of total HBV DNA ranged from 0.08 to 3 717 per cell.The ratio of total HBV DNA to cccDNA ranged from 1 to 3 406.In the sera, cccDNA was only detected from six samples whereas HBV viral DNA was detected from all ten samples.The ratio of cccDNA to total HBV DNA ranged from 0 to 1.77%.To further investigate the reason why cccDNA could only be detected in some patients' sera,we performed longitudinal studies.The cccDNA was detected from the patients' sera with HBV reactivation but not from the patients' sera without HBV reactivation.The level of cccDNA in the sera was correlated with ALT and viral load in the HBV reactivation patients. CONCLUSION:HBV cccDNA is actively transcribed and replicated in some patients' hepatoo/tes,which is reflected by a high ratio of HBV total DNA vs cccDNA.Detection of cccDNA in the liver biopsy will provide an end-point for the anti-HBV therapy.The occurrence of cccDNA in the sera is an early signal of liver damage,which may be another important clinical parameter.展开更多
Seed plants have evolved to maintain the dormancy of freshly matured seeds until the appropriate time for germination. Seed dormancy and germination are distinct physiological processes, and the transition from dorman...Seed plants have evolved to maintain the dormancy of freshly matured seeds until the appropriate time for germination. Seed dormancy and germination are distinct physiological processes, and the transition from dormancy to germination is not only a critical developmental step in the life cycle of plants but is also impor- tant for agricultural production. These processes are precisely regulated by diverse endogenous hormones and environmental cues. Although ABA （abscisic acid） and GAs （gibberellins） are known to be the primary phytohormones that antagonistically regulate seed dormancy, recent findings demonstrate that another phytohormone, auxin, is also critical for inducing and maintaining seed dormancy, and therefore might act as a key protector of seed dormancy. In this review, we summarize our current understanding of the sophisticated molecular networks involving the critical roles of phytohormones in regulating seed dormancy and germination, in which AP2-domain-containing transcription factors play key roles. We also discuss the interactions （crosstalk） of diverse hormonal signals in seed dormancy and germination, focusing on the ABA/GA balance that constitutes the central node.展开更多
Abscisic acid(ABA)is an important phytohormone regulating plant growth,development,and stress responses.It has an essential role in multiple physiological processes of plants,such as stomatal closure,cuticular wax acc...Abscisic acid(ABA)is an important phytohormone regulating plant growth,development,and stress responses.It has an essential role in multiple physiological processes of plants,such as stomatal closure,cuticular wax accumulation,leaf senescence,bud dormancy,seed germination,osmotic regulation,and growth inhibition among many others.Abscisic acid controls downstream responses to abiotic and biotic environmental changes through both transcriptional and posttranscriptional mechanisms.During the past 20 years,ABA biosynthesis and many of its signaling pathways have been well characterized.Here we review the dynamics of ABA metabolic pools and signaling that affects many of its physiological functions.展开更多
The WRKY gene family is among the largest families of transcription factors （TFs） in higher plants. By regulating the plant hormone signal transduction pathway, these TFs play critical roles in some plant processes ...The WRKY gene family is among the largest families of transcription factors （TFs） in higher plants. By regulating the plant hormone signal transduction pathway, these TFs play critical roles in some plant processes in response to biotic and abiotic stress, Various bodies of research have demonstrated the important biological functions of WRKY TFs in plant response to different kinds of biotic and abiotic stresses and working mecha- nisms. However, very li2ttle summarization has been done to review their research progress. Not iust important TFs function in plant response to biotic and abiotic stresses, WRKY also participates in carbohydrate synthesis, senes- cence, development, and secondary metabolites synthesis. WRKY proteins can bind to W-box （TGACC （A/T）） in the promoter of its target genes and activate or repress the expression of downstream genes to regulate their stress response. Moreover, WRKY proteins can interact with other TFs to regulate plant defensive responses. In the present review, we focus on the structural characteristics of WRKY TFs and the research progress on their functions in plant responses to a variety of stresses.展开更多
The most striking morphological feature of eukaryotic cells is the presence of various membrane-enclosed compartments. These compartments, including organelles and transient transport intermediates, are not static. Ra...The most striking morphological feature of eukaryotic cells is the presence of various membrane-enclosed compartments. These compartments, including organelles and transient transport intermediates, are not static. Rather, dynamic exchange of proteins and membrane is needed to maintain cellular homeostasis. One of the most dramatic examples of membrane mobilization is seen during the process ofmacroautophagy. Macroautophagy is the primary cellular pathway for degradation of long-lived proteins and organelles. In response to environmental cues, such as starvation or other types of stress, the cell produces a unique membrane structure, the phagophore. The phagophore sequesters cytoplasm as it forms a double-membrane cytosolic vesicle, an autophagosome. Upon completion, the autophagosome fuses with a lysosome or a vacuole in yeast, which delivers hydrolases that break down the inner autophagosome membrane along with its cargo, and the resulting macromolecules are released back into the cytosol for reuse. Autophagy is therefore a recycling process, allowing cells to survive periods of nutrient limitation; however, it has a wider physiological role, participating in development and aging, and also in protection against pathogen invasion, cancer and certain neurodegenerative diseases. In many cases, the role ofautophagy is identified through studies of an autophagy-related protein, Atg6/Beclin 1. This protein is part of a lipid kinase complex, and recent studies suggest that it plays a central role in coordinating the cytoprotective function ofautophagy and in opposing the cellular death process of apoptosis. Here, we summarize our current knowledge ofAtg6/Beclin 1 in different model organisms and its unique function in the cell.展开更多
Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs,and to maintain redox homeostasis.One nutrient transporter frequently overexpressed in human cancers i...Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs,and to maintain redox homeostasis.One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT).SLC7A11 promotes cystine uptake and glutathione biosynthesis,resulting in protection from oxidative stress and ferroptotic cell death.Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells.This review discusses the roles of SLC7A11 in regulating the anti-oxidant response and nutrient dependency of cancer cells,explores our current understanding of SLC7A11 regulation in cancer metabolism,and highlights key open questions for future studies in this emerging research area.A deeper understanding of SLC7A11 in cancer metabolism may identify new therapeutic opportunities to target this important amino acid transporter for cancer treatment.展开更多
The importance of cancer stem cells （CSCs） in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression,...The importance of cancer stem cells （CSCs） in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression, particularly with respect to metastasis, has not been well-defined. Cancer metastasis requires the seeding and successful colonization of specialized CSCs at distant organs. The biology of normal stem cells and CSCs share remarkable similarities and may have important implications when applied to the study of cancer metastasis. Furthermore, overlapping sets of molecules and pathways have recently been identified to regulate both stem cell migration and cancer metastasis. These molecules constitute a complex network of cellular interactions that facilitate both the initiation of the pre-metastasis niche by the primary tumor and the formation of a nurturing organ microenvironment for migrating CSCs. In this review, we surveyed the recent advances in this dynamic field and propose a unified model of cancer progression in which CSCs assume a central role in both tumorigenesis and metastasis. Better understanding of CSCs as a fundamental component of the metastatic cascade will lead to novel therapeutic strategies against metastatic cancer.展开更多
The cell-biological program termed the epithelial-to-mesenchymal transition （EMT） plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circui...The cell-biological program termed the epithelial-to-mesenchymal transition （EMT） plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenehymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.展开更多
CRISPR/Cas9 （clustered regularly interspaced short palindromic repeats/CRISPR-associated Cas9） has been widely used in genome editing in a variety of organisms, including rice （Cong et al., 2013; Feng et al., 2013）.
基金This work was supported in part by grants from the National Science and Technology Major Projects for“Major New Drugs Innovation and Development”(directed by Dr.Song Li)(2018ZX09711003)of Chinathe National Key R&D Program(2018YFC0310600)of China+1 种基金the National Natural Science Foundation of China(31771412)Special Fund for strategic bio-resources from Chinese Academy of Sciences(ZSYS-014).
文摘Dear Editor,The occurrence of concentrated pneumonia cases in Wuhan city,Hubei province of China was first reported on December 30,2019 by the Wuhan Municipal Health Commission(WHO,2020).The pneumonia cases were found to be linked to a large seafood and animal market in Wuhan,and measures for sanitation and disinfection were taken swiftly by the local government agency.The Centers for Disease Control and Prevention(CDC)and Chinese health authorities later determined and announced that a novel coronavirus(CoV),denoted as 2019-nCoV,had caused the pneumonia outbreak in Wuhan city(CDC,2020).Scientists from multiple groups had obtained the virus samples from hospitalized patients(Normile,2020).The isolated viruses were morphologically identical when observed under electron microscopy.
文摘CRISPR/Cas9 genome targeting systems have been applied to a variety of species. However, most CRISPR/Cas9 systems reported for plants can only modify one or a few target sites. Here, we report a robust CRISPR/Cas9 vector system, utilizing a plant codon optimized Cas9 gene, for convenient and high- efficiency multiplex genome editing in monocot and dicot plants. We designed PCR-based procedures to rapidly generate multiple sgRNA expression cassettes, which can be assembled into the binary CRISPR/ Cas9 vectors in one round of cloning by Golden Gate ligation or Gibson Assembly. With this system, we edi- ted 46 target sites in rice with an average 85.4% rate of mutation, mostly in biallelic and homozygous status. We reasoned that about 16% of the homozygous mutations in rice were generated through the non-homol- ogous end-joining mechanism followed by homologous recombination-based repair. We also obtained uni- form biallelic, heterozygous, homozygous, and chimeric mutations in Arabidopsis T1 plants. The targeted mutations in both rice and Arabidopsis were heritable. We provide examples of loss-of-function gene mu- tations in To rice and T1Arabidopsis plants by simultaneous targeting of multiple （up to eight） members of a gene family, multiple genes in a biosynthetic pathway, or multiple sites in a single gene. This system has provided a versatile toolbox for studying functions of multiple genes and gene families in plants for basic research and genetic improvement.
基金supported by the National Natural Science Foundation of China(Project Nos.U1802231&31701978)the Second Tibetan Plateau Scientific Expedition and Research(STEP)Program(Grant No.2019QZKK0503)+2 种基金The Biodiversity Survey and Assessment Project of the Ministry of Ecology and Environment,China(2019HJ2096001006)LWZ and ZLY thanks to the financial supports by Youth Innovation Promotion Association CAS(No.2017240)the Yunling scholars funds of Yunnan Provincial Government,respectively.
文摘The huge land areas in China provide highly diverse habitats for macrofungi.Of these macrofungi,many are directly related to people’s daily life and have been utilized by ancient Chinese for at least 6800 years.In this study,we evaluate the current known resource diversity of Chinese macrofungi.A total of 1662 taxa are summarized,and all species names and their authorities have been checked and corrected according to authentic mycological databases.Among the 1662 taxa,1020,692,and 480 are considered to be edible,medicinal and poisonous mushrooms,respectively.A few of edible macrofungi in China are commonly used for commercial production.All known medicinal functions are labeled for medicinal species.The most common medicinal functions possessed by Chinese macrofungi are antitumor or anticancer,followed by antioxidant and antimicrobial.A total of 277 Chinese macrofungi are edible simultaneously with certain medicinal functions and without known toxicity.These species could be treated as“Gold Mushrooms”.Contrarily,193 edible and/or medicinal species are also recognized as poisonous mushrooms.To avoid poisoning caused by these species,ingestion either in a proper way or in small amounts is important.However,the mycotoxins metabolized by these poisonous species could be a huge wealth of natural products yet to be explored.How to utilize these Chinese macrofungal resources is a critical to benefit humans worldwide.
基金This work was supported by the National Science and Technology Major Project(2017ZX10103011 and 2017ZX10204401)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2017-I2M-1-009)+1 种基金Shenzhen Science and Technology Research and Development Project(JCYJ20180504165549581 and JCYJ20170413141236903)China Postdoctoral Science Foundation(2019T120147).
文摘The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,and radiological characteristics,as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen,China.All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS).The most common laboratory abnormalities were hypoalbuminemia,lymphopenia,decreased percentage of lymphocytes (LYM) and neutrophils (NEU),elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH),and decreased CD8 count.The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity.ALB,LYM,LYM (%),LDH,NEU (%),and CRP were highly correlated to the acute lung injury.Age,viral load,lung injury score,and blood biochemistry indexes,albumin (ALB),CRP,LDH,LYM (%),LYM,and NEU (%),may be predictors of disease severity.Moreover,the Angiotensin Ⅱlevel in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury.Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.
基金supported by National Natural Science Foundation of China(No.81602931)Ministry of Science and Technology(No.2014FY121100)State Key Projects Specialized on Infectious Diseases(No.2012ZX10002008)
文摘Objective: Liver cancer is one of the most common cancers and major cause of cancer deaths in China,which accounts for over 50% of new cases and deaths worldwide.The systematic liver cancer statistics including of projection through 2030 could provide valuable information for prevention and control strategies in China,and experience for other countries.Methods: The burden of liver cancer in China in 2014 was estimated using 339 cancer registries’ data selected from Chinese National Cancer Center(NCC).Incident cases of 22 cancer registries were applied for temporal trends from 2000 to 2014.The burden of liver cancer through 2030 was projected using age-period-cohort model.Results: About 364,800 new cases of liver cancer(268,900 males and 95,900 females) occurred in China,and about 318,800 liver cancer deaths(233,500 males and 85,300 females) in 2014.Western regions of China had the highest incidence and mortality rates.Incidence and mortality rates decreased by about 2.3% and 2.6% per year during the period of 2000-2014,respectively,and would decrease by more than 44% between 2014 and 2030 in China.The young generation,particularly for those aged under 40 years,showed a faster down trend.Conclusions: Based on the analysis,incidence and mortality rates of liver cancer are expected to decrease through 2030,but the burden of liver cancer is still serious in China,especially in rural and western areas.Most cases of liver cancer in China can be prevented through vaccination and more prevention efforts should be focused on high risk groups.
基金by the National Natural Science Foundation of China(81870019)Guangdong Provincial Natural Science Foundation(2018A030313554)+2 种基金National Key R&D Program of China(2018YFC0910601)the National Medical Research Council,Singapore(NMRC/CIRG/1458/2016)a recipient of fellowship support from European Allergy and Clinical Immunology(EAACI)Research Fellowship 2019。
文摘An acute respiratory disease,caused by a novel coronavirus(SARS-CoV-2,previously known as 2019-nCoV),the coronavirus disease 2019(COVID-19)has spread throughout China and received worldwide attention.On 30 January 2020,World Health Organization(WHO)officially declared the COVID-19 epidemic as a public health emergency of international concern.The emergence of SARS-CoV-2,since the severe acute respiratory syndrome coronavirus(SARSCoV)in 2002 and Middle East respiratory syndrome coronavirus(MERS-CoV)in 2012,marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century.As of 1 March 2020,a total of 87,137 confirmed cases globally,79,968 confirmed in China and 7169 outside of China,with 2977 deaths(3.4%)had been reported by WHO.Meanwhile,several independent research groups have identified that SARS-CoV-2 belongs toβ-coronavirus,with highly identical genome to bat coronavirus,pointing to bat as the natural host.The novel coronavirus uses the same receptor,angiotensin-converting enzyme 2(ACE2)as that for SARS-CoV,and mainly spreads through the respiratory tract.Importantly,increasingly evidence showed sustained human-tohuman transmission,along with many exported cases across the globe.The clinical symptoms of COVID-19 patients include fever,cough,fatigue and a small population of patients appeared gastrointestinal infection symptoms.The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes,which may be associated with acute respiratory distress syndrome(ARDS)and cytokine storm.Currently,there are few specific antiviral strategies,but several potent candidates of antivirals and repurposed drugs are under urgent investigation.In this review,we summarized the latest research progress of the epidemiology,pathogenesis,and clinical characteristics of COVID-19,and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.
文摘Abiotic stresses and soil nutrient limitations are major environmental conditions that reduce plant growth,productivity and quality.Plants have evolved mechanisms to perceive these environmental challenges,transmit the stress signals within cells as well as between cells and tissues,and make appropriate adjustments in their growth and development in order to survive and reproduce.In recent years,significant progress has been made on many fronts of the stress signaling research,particularly in understanding the downstream signaling events that culminate at the activation of stress-and nutrient limitation-responsive genes,cellular ion homeostasis,and growth adjustment.However,the revelation of the early events of stress signaling,particularly the identification of primary stress sensors,still lags behind.In this review,we summarize recent work on the genetic and molecular mechanisms of plant abiotic stress and nutrient limitation sensing and signaling and discuss new directions for future studies.
基金Supported by Grant 41066/2007, financed by the Ministry of Education and Research
文摘AIM:To investigate the diagnostic accuracy of acoustic radiation force impulse (ARFI) imaging as a noninvasive method for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients.METHODS:We performed a prospective blind com-parison of ARFI elastography,APRI index and FibroMax in a consecutive series of patients who underwent liver biopsy for CHC in University Hospital Bucharest. His-topathological staging of liver fibrosis according to the METAVIR scoring system served as the reference. A to-tal of 74 patients underwent ARFI elastography,APRI index,FibroMax and successful liver biopsy. RESULTS:The noninvasive tests had a good correlation with the liver biopsy results. The most powerful test in predicting fibrosis was ARFI elastography. The diagnostic accuracy of ARFI elastography,expressedas area under receiver operating characteristic curve (AUROC) had a validity of 90.2% (95% CI AUROC = 0.831-0.972,P < 0.001) for the diagnosis of significant f ibrosis (F ≥ 2). ARFI sonoelastography predicted even better F3 or F4 fibrosis (AUROC = 0.993,95% CI = 0.979-1).CONCLUSION:ARFI elastography had very good accuracy for the assessment of liver fibrosis and was superior to other noninvasive methods (APRI Index,FibroMax) for staging liver fibrosis.
基金SuppoSed by CRCG grant from the University of Hong KongCERG grant from University Grant Council of Hong Kong Research Fund from Science and Technology Commission of Shanghai,China
文摘AIM:To evaluate the covalently closed circle DNA (cccDNA) level of hepatitis B virus (HBV) in patients' liver and sera. METHODS:HBV DNA was isolated from patients' liver biopsies and sera.A sensitive real-time PCR method,which is capable of differentiation of HBV viral genomic DNA and cccDNA,was used to quantify the total HBV cccDNA.The total HBV viral DNA was quantitated by real-time PCR using a HBV diagnostic kit (PG Biotech,LTD,Shenzhen,China) described previously. RESULTS:For the first time,we measured the level of HBV DNA and cccDNA isolated from ten HBV patients' liver biopsies and sera.In the liver biopsies,cccDNA was detected from all the biopsy samples.The copy number of cccDNA ranged from from 0.03 to 173.1 per cell,the copy number of total HBV DNA ranged from 0.08 to 3 717 per cell.The ratio of total HBV DNA to cccDNA ranged from 1 to 3 406.In the sera, cccDNA was only detected from six samples whereas HBV viral DNA was detected from all ten samples.The ratio of cccDNA to total HBV DNA ranged from 0 to 1.77%.To further investigate the reason why cccDNA could only be detected in some patients' sera,we performed longitudinal studies.The cccDNA was detected from the patients' sera with HBV reactivation but not from the patients' sera without HBV reactivation.The level of cccDNA in the sera was correlated with ALT and viral load in the HBV reactivation patients. CONCLUSION:HBV cccDNA is actively transcribed and replicated in some patients' hepatoo/tes,which is reflected by a high ratio of HBV total DNA vs cccDNA.Detection of cccDNA in the liver biopsy will provide an end-point for the anti-HBV therapy.The occurrence of cccDNA in the sera is an early signal of liver damage,which may be another important clinical parameter.
文摘Seed plants have evolved to maintain the dormancy of freshly matured seeds until the appropriate time for germination. Seed dormancy and germination are distinct physiological processes, and the transition from dormancy to germination is not only a critical developmental step in the life cycle of plants but is also impor- tant for agricultural production. These processes are precisely regulated by diverse endogenous hormones and environmental cues. Although ABA （abscisic acid） and GAs （gibberellins） are known to be the primary phytohormones that antagonistically regulate seed dormancy, recent findings demonstrate that another phytohormone, auxin, is also critical for inducing and maintaining seed dormancy, and therefore might act as a key protector of seed dormancy. In this review, we summarize our current understanding of the sophisticated molecular networks involving the critical roles of phytohormones in regulating seed dormancy and germination, in which AP2-domain-containing transcription factors play key roles. We also discuss the interactions （crosstalk） of diverse hormonal signals in seed dormancy and germination, focusing on the ABA/GA balance that constitutes the central node.
基金supported by the Shanghai Center for Plant Stress Biology from the Chinese Academy of Sciences, the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB27040107)the National Natural Science Foundation of China (31970293)the Shanghai Pujiang Program (18PJ1410900)
文摘Abscisic acid(ABA)is an important phytohormone regulating plant growth,development,and stress responses.It has an essential role in multiple physiological processes of plants,such as stomatal closure,cuticular wax accumulation,leaf senescence,bud dormancy,seed germination,osmotic regulation,and growth inhibition among many others.Abscisic acid controls downstream responses to abiotic and biotic environmental changes through both transcriptional and posttranscriptional mechanisms.During the past 20 years,ABA biosynthesis and many of its signaling pathways have been well characterized.Here we review the dynamics of ABA metabolic pools and signaling that affects many of its physiological functions.
基金supported by the Natural Science Foundation of China(No.31301790)Guangdong Natural Science Foundation (S2013040016220)+1 种基金China Postdoctoral Science Foundation (2013M530375,2014T70827)Shenzhen Vegetable Molecular Biotechnological Engineering Lab Scheme (Development and Reform Commission of Shenzhen Municipal Government)
文摘The WRKY gene family is among the largest families of transcription factors （TFs） in higher plants. By regulating the plant hormone signal transduction pathway, these TFs play critical roles in some plant processes in response to biotic and abiotic stress, Various bodies of research have demonstrated the important biological functions of WRKY TFs in plant response to different kinds of biotic and abiotic stresses and working mecha- nisms. However, very li2ttle summarization has been done to review their research progress. Not iust important TFs function in plant response to biotic and abiotic stresses, WRKY also participates in carbohydrate synthesis, senes- cence, development, and secondary metabolites synthesis. WRKY proteins can bind to W-box （TGACC （A/T）） in the promoter of its target genes and activate or repress the expression of downstream genes to regulate their stress response. Moreover, WRKY proteins can interact with other TFs to regulate plant defensive responses. In the present review, we focus on the structural characteristics of WRKY TFs and the research progress on their functions in plant responses to a variety of stresses.
文摘The most striking morphological feature of eukaryotic cells is the presence of various membrane-enclosed compartments. These compartments, including organelles and transient transport intermediates, are not static. Rather, dynamic exchange of proteins and membrane is needed to maintain cellular homeostasis. One of the most dramatic examples of membrane mobilization is seen during the process ofmacroautophagy. Macroautophagy is the primary cellular pathway for degradation of long-lived proteins and organelles. In response to environmental cues, such as starvation or other types of stress, the cell produces a unique membrane structure, the phagophore. The phagophore sequesters cytoplasm as it forms a double-membrane cytosolic vesicle, an autophagosome. Upon completion, the autophagosome fuses with a lysosome or a vacuole in yeast, which delivers hydrolases that break down the inner autophagosome membrane along with its cargo, and the resulting macromolecules are released back into the cytosol for reuse. Autophagy is therefore a recycling process, allowing cells to survive periods of nutrient limitation; however, it has a wider physiological role, participating in development and aging, and also in protection against pathogen invasion, cancer and certain neurodegenerative diseases. In many cases, the role ofautophagy is identified through studies of an autophagy-related protein, Atg6/Beclin 1. This protein is part of a lipid kinase complex, and recent studies suggest that it plays a central role in coordinating the cytoprotective function ofautophagy and in opposing the cellular death process of apoptosis. Here, we summarize our current knowledge ofAtg6/Beclin 1 in different model organisms and its unique function in the cell.
基金supported by the Andrew Sabin Family Fellow Award and Institutional Research Grant from the University of Texas MD Anderson Cancer Center,Grants from National Institutes of Health(CA181196 and CA190370)Anna Fuller Fund,and Ellison Medical Foundation(AG-NS-0973-13).
文摘Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs,and to maintain redox homeostasis.One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT).SLC7A11 promotes cystine uptake and glutathione biosynthesis,resulting in protection from oxidative stress and ferroptotic cell death.Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells.This review discusses the roles of SLC7A11 in regulating the anti-oxidant response and nutrient dependency of cancer cells,explores our current understanding of SLC7A11 regulation in cancer metabolism,and highlights key open questions for future studies in this emerging research area.A deeper understanding of SLC7A11 in cancer metabolism may identify new therapeutic opportunities to target this important amino acid transporter for cancer treatment.
文摘The importance of cancer stem cells （CSCs） in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression, particularly with respect to metastasis, has not been well-defined. Cancer metastasis requires the seeding and successful colonization of specialized CSCs at distant organs. The biology of normal stem cells and CSCs share remarkable similarities and may have important implications when applied to the study of cancer metastasis. Furthermore, overlapping sets of molecules and pathways have recently been identified to regulate both stem cell migration and cancer metastasis. These molecules constitute a complex network of cellular interactions that facilitate both the initiation of the pre-metastasis niche by the primary tumor and the formation of a nurturing organ microenvironment for migrating CSCs. In this review, we surveyed the recent advances in this dynamic field and propose a unified model of cancer progression in which CSCs assume a central role in both tumorigenesis and metastasis. Better understanding of CSCs as a fundamental component of the metastatic cascade will lead to novel therapeutic strategies against metastatic cancer.
文摘The cell-biological program termed the epithelial-to-mesenchymal transition （EMT） plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenehymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.
文摘CRISPR/Cas9 （clustered regularly interspaced short palindromic repeats/CRISPR-associated Cas9） has been widely used in genome editing in a variety of organisms, including rice （Cong et al., 2013; Feng et al., 2013）.
