Based on the general equilibrium theory of microeconomics,this study first analyzed the causes of sharp fluctuations in live pig prices,and then explored the financial capabilities of enterprises during the sharp fluc...Based on the general equilibrium theory of microeconomics,this study first analyzed the causes of sharp fluctuations in live pig prices,and then explored the financial capabilities of enterprises during the sharp fluctuations of live pig prices by using the financial data of 4 typical top listed enterprises from 2018 to 2021.By comparing the changes in the capabilities of enterprises,the impact of price on the financial capability of enterprises and differences were identified.The research results showed that the price of live pigs played a decisive role in enterprise profits,and there were huge differences in the fluctuation period.In the sharp increase period of price,price temptation is easy to cause enterprises to over-invest,resulting in excessive growth of enterprise assets,and increasing the business risk of enterprises.Based on the above conclusions,some policy suggestions were put forward to promote the stable development of industry from the three levels of enterprises,industries and government departments.展开更多
To fight against invasion by pathogens,plants have evolved an elaborate innate immune system,of which the nucleotide-binding domain leucine-rich repeat-containing receptor(NLR)acts as the sensor and immune executor.Po...To fight against invasion by pathogens,plants have evolved an elaborate innate immune system,of which the nucleotide-binding domain leucine-rich repeat-containing receptor(NLR)acts as the sensor and immune executor.Potyviruses,comprising one of the largest genera of plant viruses,cause severe crop yield losses worldwide.Inherited crop resistance to potyviruses can be used in breeding and plant transgenesis to control disease development.This review summarizes achievements in mapping and cloning NLR genes conferring dominant resistance against potyvirus in the families Fabaceae,Solanaceae,Brassicaceae,and Cucurbitaceae.It compares mechanisms of potyviral protein recognition and downstream signaling employed by NLRs and discusses strategies for exploiting NLRs to better control diseases caused by potyviruses.展开更多
Alternative splicing is a tightly regulated process that contributes to cancer development.CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers.However,wheth...Alternative splicing is a tightly regulated process that contributes to cancer development.CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers.However,whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear.In this study,we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies.The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner.Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies,including 3 reported and 8 unreported,and also implicated that the overexpressed isoforms differed in various cancer types.Furthermore,anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples,and even had different impacts on the expression of CRNDE isoforms.Finally,experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types.Collectively,our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms,and may provide promising targets for cancer diagnosis and therapy.展开更多
Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important ...Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important role in the replacement therapy of severe valvular heart disease,while their durability is limited by degeneration due to calcification,thrombus,endothelialization difficulty and prosthetic valve endocarditis.Herein,we develop a novel BHV,namely,TPly-BP,based on natural tannic acid and polylysine to improve the durability of Glut crosslinked bovine pericardium(Glut-BP).Impressively,tannic acid and polylysine could form nanoaggregates via multiple hydrogen bonds and covalent bonds,and the introduction of nanoaggregates not only improved the mechanical properties and collagen stability but also endowed TPIy-BP with good biocompatibility and hemocompatibility.Compared to Glut-BP,TPIy-BP showed significantly reduced cytotoxicity,improved endothelial cell adhesion,a low hemolysis ratio and obviously reduced platelet adhesion.Importantly,TPly-BP exhibited great antibacterial and in vivo anti-calcification ability,which was expected to improve the in vivo durability of BHVs.These results suggested that TPly-BP would be a potential candidate for BHV.展开更多
Since the discovery of leptin as an adipokine in 1994, much progress has been made in the research about leptin. Circulating leptin binds to leptin receptor, activates STAT3-dependent and STAT3-independent signaling p...Since the discovery of leptin as an adipokine in 1994, much progress has been made in the research about leptin. Circulating leptin binds to leptin receptor, activates STAT3-dependent and STAT3-independent signaling pathways, and plays an effective role in energy home- ostasis, neuroendocrine function and metabolism mainly through acting on the central nervous system, especially the hypothalamus. Leptin resistance is considered as a key risk factor for obesity. Various mechanisms have been formu- lated in order to explain leptin resistance, including impairment in leptin transport, attenuation in leptin sig- naling, ER stress, inflammation and deficiency in autop- hagy. Here, we review our current knowledge about leptin action, leptin signaling and leptin resistance, hoping to provide new ideas for the battle against obesity.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can lead to respiratory illness and multi-organ failure in critically ill patients.Although the virus-induced lung damage and inflammatory cytokine ...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can lead to respiratory illness and multi-organ failure in critically ill patients.Although the virus-induced lung damage and inflammatory cytokine storm are believed to be directly associated with coronavirus disease 2019(COVID-19)clinical manifestations,the underlying mechanisms of virus-triggered inflammatory responses are currently unknown.Here we report that SARS-CoV-2 infection activates caspase-8 to trigger cell apoptosis and inflammatory cytokine processing in the lung epithelial cells.The processed inflammatory cytokines are released through the virus-induced necroptosis pathway.Virus-induced apoptosis,necroptosis,and inflammation activation were also observed in the lung sections of SARS-CoV-2-infected HFH4-hACE2 transgenic mouse model,a valid model for studying SARS-CoV-2 pathogenesis.Furthermore,analysis of the postmortem lung sections of fatal COVID-19 patients revealed not only apoptosis and necroptosis but also massive inflammatory cell infiltration,necrotic cell debris,and pulmonary interstitial fibrosis,typical of immune pathogenesis in the lung.The SARS-CoV-2 infection triggered a dual mode of cell death pathways and caspase-8-dependent inflammatory responses may lead to the lung damage in the COVID-19 patients.These discoveries might assist the development of therapeutic strategies to treat COVID-19.展开更多
Dear Editor,Rift Valley fever(RVF)is an anthropozoonosis caused by Rift Valley fever virus(RVFV).RVFV belongs to the Phlebovirus genus in the family Bunyaviridae,which is circulating among ruminants.Human infection wi...Dear Editor,Rift Valley fever(RVF)is an anthropozoonosis caused by Rift Valley fever virus(RVFV).RVFV belongs to the Phlebovirus genus in the family Bunyaviridae,which is circulating among ruminants.Human infection with RVFV is generally asymptomatic,however,minority of patients develop severe RVF diseases like encephalitis展开更多
Changes in the abundance and activity of long non-coding RNAs(lncRNAs)have an important impact on the development of cancer.The nuclear paraspeckle assembly transcript 1(NEAT1)has been reported to be overexpressed in ...Changes in the abundance and activity of long non-coding RNAs(lncRNAs)have an important impact on the development of cancer.The nuclear paraspeckle assembly transcript 1(NEAT1)has been reported to be overexpressed in many types of cancer since its discovery.However,inconsistencies exist as NEAT1 can also function as a tumor suppressor in certain types of cancer,such as acute promyelocytic leukemia.Here we systematically describe our current understanding of NEAT1 in tumor initiation and progression.First,we analyzed the expression patterns of NEAT1 in various normal tissues and malignant cancers using data from public data portals,the Genotype-Tissue Expression Project(GTEx)and the Cancer Genome Atlas(TCGA),together with recent progress in the study of NEAT1 in various types of cancer.Second,we discussed the functions and mechanisms of NEAT1 in modulating tumor activity.Then,the upstream transcription factors and downstream microRNA targets of NEAT1 in the transcription cascade of cancers were also summarized.These data highlight the emerging role of NEAT1 in tumorigenesis,and present promising targetable pathways and clinical opportunities for tumor prevention and classifications.展开更多
Antibody-dependent cellular cytotoxicity(ADCC)responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment.Whether severe acute respiratory syndrome coronavirus 2(SAR...Antibody-dependent cellular cytotoxicity(ADCC)responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment.Whether severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)triggered ADCC responses contributes to COVID-19 disease development is currently not well understood.To understand the potential correlation between ADCC responses and COVID-19 disease development,we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post disease.ADCC was elicited by 10 days post-infection,peaked by 11-20 days,and remained detectable until 400 days post-infection.In general,patients with severe disease had higher ADCC activities.Notably,patients who had severe disease and recovered had higher ADCC activities than patients who had severe disease and deceased.Importantly,ADCC activities were mediated by a diversity of epitopes in SARS-COV-2-infected mice and induced to comparable levels against SARS-CoV-2 variants of concern(VOCs)(B.1.1.7,B.1.351,and P.1)as that against the D614G mutant in human patients and vaccinated mice.Our study indicates anti-SARS-CoV-2 ADCC as a major trait of COVID-19 patients with various conditions,which can be applied to estimate the extra-neutralization level against COVID-19,especially lethal COVID-19.展开更多
Over 40% of the coronavirus disease 2019(COVID-19)COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the immune responses of these asymptomatic individ...Over 40% of the coronavirus disease 2019(COVID-19)COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic.Here,we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020.Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy.The incidence rate of asymptomatic infection is〜2.92/100,000.These individuals had low viral copy numbers(peaked at 315 copies/mL)and short-lived antibody responses with the estimated diminish time of 69 days.The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days.These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection,which has recently been reported in recovered COVID-19 patients.This casts doubt on the efficacy of forming"herd-immunity"through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.展开更多
The transfer of mitochondrial DNA to the nuclear genome gives rise to the nuclear DNA sequences of mitochon-drial origin(NUMTs),considered as a driving force in genome evolution.In this study,NUMTs in 23 bat genomes w...The transfer of mitochondrial DNA to the nuclear genome gives rise to the nuclear DNA sequences of mitochon-drial origin(NUMTs),considered as a driving force in genome evolution.In this study,NUMTs in 23 bat genomes were investigated and compared systematically.The results showed that NUMTs existed in 22 genomes except for Noctilio leporinus,suggesting that mitochondrial fragment insertion in the nuclear genome was a common event in bat genomes.However,remarkable variations in NUMTs number,cumulative length,and proportion in the nu-clear genome were discovered across bat species.Further orthologous NUMT loci analysis of the Phyllostomidae family indicated that the NUMTs insertion events in bat genomes were homoplasy-free.The NUMTs were mainly inserted into the intergenic regions,particularly,co-localized with repetitive sequences(especially transposable el-ements).However,several NUMTs were inserted into genes,some of which were in the exon region of functional genes.One NUMT in the genome of Pteropus alecto surprisingly matched with cDNA of ATP8B3 that provided evidence of NUMTs with coding function.Phylogenic analysis on NUMTs originating from COXI and COXII loci highlighted 2 clusters of Yinpterochiroptera and Yangochiroptera for Chiroptera.Seven NUMTs from Rhinolophus ferrumequinum were amplified,and the sequencing results confirmed the reliability of the NUMT analysis.One of them was polymorphic for the presence or absence of the NUMT insertion,and each genotype of NUMT loci showed a distinct regional distribution pattern.The information obtained in this study provides novel insights into the NUMT organization and features in bat genomes and establishes a basis for further studying of the evolution of bat species.展开更多
Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important ...Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important role in the replacement therapy of severe valvular heart disease,while their durability is limited by degeneration due to calcification,thrombus,endothelialization difficulty and prosthetic valve endocarditis.Herein,we develop a novel BHV,namely,TPly-BP,based on natural tannic acid and polylysine to improve the durability of Glut crosslinked bovine pericardium(Glut-BP).Impressively,tannic acid and polylysine could form nanoaggregates via multiple hydrogen bonds and covalent bonds,and the introduction of nanoaggregates not only improved the mechanical properties and collagen stability but also endowed TPly-BP with good biocompatibility and hemocompatibility.Compared to Glut-BP,TPly-BP showed significantly reduced cytotoxicity,improved endothelial cell adhesion,a low hemolysis ratio and obviously reduced platelet adhesion.Importantly,TPly-BP exhibited great antibacterial and in vivo anti-calcification ability,which was expected to improve the in vivo durability of BHVs.These results suggested that TPly-BP would be a potential candidate for BHV.展开更多
文摘Based on the general equilibrium theory of microeconomics,this study first analyzed the causes of sharp fluctuations in live pig prices,and then explored the financial capabilities of enterprises during the sharp fluctuations of live pig prices by using the financial data of 4 typical top listed enterprises from 2018 to 2021.By comparing the changes in the capabilities of enterprises,the impact of price on the financial capability of enterprises and differences were identified.The research results showed that the price of live pigs played a decisive role in enterprise profits,and there were huge differences in the fluctuation period.In the sharp increase period of price,price temptation is easy to cause enterprises to over-invest,resulting in excessive growth of enterprise assets,and increasing the business risk of enterprises.Based on the above conclusions,some policy suggestions were put forward to promote the stable development of industry from the three levels of enterprises,industries and government departments.
基金supported by the National Natural Science Foundation of China(31770164)Jiangsu Province’s Innovation Program(JSSCTD202142).
文摘To fight against invasion by pathogens,plants have evolved an elaborate innate immune system,of which the nucleotide-binding domain leucine-rich repeat-containing receptor(NLR)acts as the sensor and immune executor.Potyviruses,comprising one of the largest genera of plant viruses,cause severe crop yield losses worldwide.Inherited crop resistance to potyviruses can be used in breeding and plant transgenesis to control disease development.This review summarizes achievements in mapping and cloning NLR genes conferring dominant resistance against potyvirus in the families Fabaceae,Solanaceae,Brassicaceae,and Cucurbitaceae.It compares mechanisms of potyviral protein recognition and downstream signaling employed by NLRs and discusses strategies for exploiting NLRs to better control diseases caused by potyviruses.
基金National Natural Science Foundation of China (Nos.81530003,81300403,81770153 and 91440114)The National Key Research and Development Program (No.2016YFC0902800)+1 种基金Shanghai Leading Talent Projects (No.2015008)the Academic Leader Program of Shanghai Science and Technology Committee (No.2015137).
文摘Alternative splicing is a tightly regulated process that contributes to cancer development.CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers.However,whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear.In this study,we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies.The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner.Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies,including 3 reported and 8 unreported,and also implicated that the overexpressed isoforms differed in various cancer types.Furthermore,anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples,and even had different impacts on the expression of CRNDE isoforms.Finally,experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types.Collectively,our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms,and may provide promising targets for cancer diagnosis and therapy.
基金supported by the National Natural Science Foundation of China(81970325 and 82170375)Key Research and Development Support Project of Science&Technology Department of Chengdu(2021-YF08-00121-GX)+3 种基金Post-Doctor Research Project,West China Hospital,Sichuan University(Grant No.20HXBH164 and 20HXBH105)Chinese Medical Association Cardiovascular Branch(CSC)Clinical Research Special Fund Project(CSCF2020B04)West China Hospital"1.3.5"Discipline of Excellence Project-"Percutaneous transcatheter aortic valve implantation""Mechanisms of aortic stenosis and the clinical applications"(ZYGD20002).
文摘Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important role in the replacement therapy of severe valvular heart disease,while their durability is limited by degeneration due to calcification,thrombus,endothelialization difficulty and prosthetic valve endocarditis.Herein,we develop a novel BHV,namely,TPly-BP,based on natural tannic acid and polylysine to improve the durability of Glut crosslinked bovine pericardium(Glut-BP).Impressively,tannic acid and polylysine could form nanoaggregates via multiple hydrogen bonds and covalent bonds,and the introduction of nanoaggregates not only improved the mechanical properties and collagen stability but also endowed TPIy-BP with good biocompatibility and hemocompatibility.Compared to Glut-BP,TPIy-BP showed significantly reduced cytotoxicity,improved endothelial cell adhesion,a low hemolysis ratio and obviously reduced platelet adhesion.Importantly,TPly-BP exhibited great antibacterial and in vivo anti-calcification ability,which was expected to improve the in vivo durability of BHVs.These results suggested that TPly-BP would be a potential candidate for BHV.
基金Acknowledgments This work was supported by the National Basic Research Program of China (2013CB530601, 2011CB910201), the National Natural Science Foundation of China (31571401, 81270954, 31030048, 81390350), the Shanghai Rising Star Program (13QH1400800). The Department of Biochemistry and Molecular Biology at Fudan University Shanghai Medical College is supported by the Shanghai Leading Academic Discipline Projects B 110 and by "985" Project 985III-YFX0302.
文摘Since the discovery of leptin as an adipokine in 1994, much progress has been made in the research about leptin. Circulating leptin binds to leptin receptor, activates STAT3-dependent and STAT3-independent signaling pathways, and plays an effective role in energy home- ostasis, neuroendocrine function and metabolism mainly through acting on the central nervous system, especially the hypothalamus. Leptin resistance is considered as a key risk factor for obesity. Various mechanisms have been formu- lated in order to explain leptin resistance, including impairment in leptin transport, attenuation in leptin sig- naling, ER stress, inflammation and deficiency in autop- hagy. Here, we review our current knowledge about leptin action, leptin signaling and leptin resistance, hoping to provide new ideas for the battle against obesity.
基金supported by the National Science and Technology Major Project(number 2018ZX10101004001005)the National Key R&D Program of China(2018YFA0507201)+4 种基金the National Natural Science Foundation of China(numbers 31770188 and 31900144)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010204)the Hundred Talents Program of Chinese Academy of Sciences(to K.P.)the Special major program of Wuhan Institute of Virology(number WIV-135-TP1),the State Key Laboratory of Virology open projects(number 2017IOV003)the Advanced Customer Cultivation Project of Wuhan National Biosafety Laboratory Chinese Academy of Sciences(number 2018ACCPMS01).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can lead to respiratory illness and multi-organ failure in critically ill patients.Although the virus-induced lung damage and inflammatory cytokine storm are believed to be directly associated with coronavirus disease 2019(COVID-19)clinical manifestations,the underlying mechanisms of virus-triggered inflammatory responses are currently unknown.Here we report that SARS-CoV-2 infection activates caspase-8 to trigger cell apoptosis and inflammatory cytokine processing in the lung epithelial cells.The processed inflammatory cytokines are released through the virus-induced necroptosis pathway.Virus-induced apoptosis,necroptosis,and inflammation activation were also observed in the lung sections of SARS-CoV-2-infected HFH4-hACE2 transgenic mouse model,a valid model for studying SARS-CoV-2 pathogenesis.Furthermore,analysis of the postmortem lung sections of fatal COVID-19 patients revealed not only apoptosis and necroptosis but also massive inflammatory cell infiltration,necrotic cell debris,and pulmonary interstitial fibrosis,typical of immune pathogenesis in the lung.The SARS-CoV-2 infection triggered a dual mode of cell death pathways and caspase-8-dependent inflammatory responses may lead to the lung damage in the COVID-19 patients.These discoveries might assist the development of therapeutic strategies to treat COVID-19.
基金funded by the Science andTechnology Planning Project of Guangdong province(Grant No.2015A020213007)the Science and Technology Planning Project of General Administration of Quality Supervision,Inspection and Quarantine of China(Grant No.2015IK066)
文摘Dear Editor,Rift Valley fever(RVF)is an anthropozoonosis caused by Rift Valley fever virus(RVFV).RVFV belongs to the Phlebovirus genus in the family Bunyaviridae,which is circulating among ruminants.Human infection with RVFV is generally asymptomatic,however,minority of patients develop severe RVF diseases like encephalitis
基金This work was supported in part by National Natural Science Foundation Grants of China(81530003)China Postdoctoral Science Foundation(2017M611580).
文摘Changes in the abundance and activity of long non-coding RNAs(lncRNAs)have an important impact on the development of cancer.The nuclear paraspeckle assembly transcript 1(NEAT1)has been reported to be overexpressed in many types of cancer since its discovery.However,inconsistencies exist as NEAT1 can also function as a tumor suppressor in certain types of cancer,such as acute promyelocytic leukemia.Here we systematically describe our current understanding of NEAT1 in tumor initiation and progression.First,we analyzed the expression patterns of NEAT1 in various normal tissues and malignant cancers using data from public data portals,the Genotype-Tissue Expression Project(GTEx)and the Cancer Genome Atlas(TCGA),together with recent progress in the study of NEAT1 in various types of cancer.Second,we discussed the functions and mechanisms of NEAT1 in modulating tumor activity.Then,the upstream transcription factors and downstream microRNA targets of NEAT1 in the transcription cascade of cancers were also summarized.These data highlight the emerging role of NEAT1 in tumorigenesis,and present promising targetable pathways and clinical opportunities for tumor prevention and classifications.
基金supported by grants from the National Science Fund for Distinguished Young Scholars(No.81825019)National Natural Science Foundation of China(No.82073621)the China Mega-Project on Infectious Disease Prevention(Nos.2018ZX10713002,2018ZX10101003).
文摘Antibody-dependent cellular cytotoxicity(ADCC)responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment.Whether severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)triggered ADCC responses contributes to COVID-19 disease development is currently not well understood.To understand the potential correlation between ADCC responses and COVID-19 disease development,we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post disease.ADCC was elicited by 10 days post-infection,peaked by 11-20 days,and remained detectable until 400 days post-infection.In general,patients with severe disease had higher ADCC activities.Notably,patients who had severe disease and recovered had higher ADCC activities than patients who had severe disease and deceased.Importantly,ADCC activities were mediated by a diversity of epitopes in SARS-COV-2-infected mice and induced to comparable levels against SARS-CoV-2 variants of concern(VOCs)(B.1.1.7,B.1.351,and P.1)as that against the D614G mutant in human patients and vaccinated mice.Our study indicates anti-SARS-CoV-2 ADCC as a major trait of COVID-19 patients with various conditions,which can be applied to estimate the extra-neutralization level against COVID-19,especially lethal COVID-19.
基金supported by the National Science and Technology Major Project(No.2018ZX10101004001005)the National Key R&D Program of China(2018YFA0507201)+3 种基金the National Natural Science Foundation of China(No.31770188,32070179 and 31900144)Fundamental Research Funds for Central Public Welfare Scientific Research Institutes sponsored by National Institute of Metrology,P.R.China(grant no.31-ZYZJ2001 and grant no.AKYYJ2009)the Advanced Customer Cultivation Project of Wuhan National Biosafety Laboratory Chinese Academy of Sciences(No.2018ACCP-MS01)the Key Technology Development Program of Shenzhen(grant no.JSGG20200225153042494).
文摘Over 40% of the coronavirus disease 2019(COVID-19)COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic.Here,we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020.Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy.The incidence rate of asymptomatic infection is〜2.92/100,000.These individuals had low viral copy numbers(peaked at 315 copies/mL)and short-lived antibody responses with the estimated diminish time of 69 days.The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days.These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection,which has recently been reported in recovered COVID-19 patients.This casts doubt on the efficacy of forming"herd-immunity"through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.
基金supported by the National Natural Science Foundation of China(NSFC,No.U1704102 and No.31172056).
文摘The transfer of mitochondrial DNA to the nuclear genome gives rise to the nuclear DNA sequences of mitochon-drial origin(NUMTs),considered as a driving force in genome evolution.In this study,NUMTs in 23 bat genomes were investigated and compared systematically.The results showed that NUMTs existed in 22 genomes except for Noctilio leporinus,suggesting that mitochondrial fragment insertion in the nuclear genome was a common event in bat genomes.However,remarkable variations in NUMTs number,cumulative length,and proportion in the nu-clear genome were discovered across bat species.Further orthologous NUMT loci analysis of the Phyllostomidae family indicated that the NUMTs insertion events in bat genomes were homoplasy-free.The NUMTs were mainly inserted into the intergenic regions,particularly,co-localized with repetitive sequences(especially transposable el-ements).However,several NUMTs were inserted into genes,some of which were in the exon region of functional genes.One NUMT in the genome of Pteropus alecto surprisingly matched with cDNA of ATP8B3 that provided evidence of NUMTs with coding function.Phylogenic analysis on NUMTs originating from COXI and COXII loci highlighted 2 clusters of Yinpterochiroptera and Yangochiroptera for Chiroptera.Seven NUMTs from Rhinolophus ferrumequinum were amplified,and the sequencing results confirmed the reliability of the NUMT analysis.One of them was polymorphic for the presence or absence of the NUMT insertion,and each genotype of NUMT loci showed a distinct regional distribution pattern.The information obtained in this study provides novel insights into the NUMT organization and features in bat genomes and establishes a basis for further studying of the evolution of bat species.
基金the National Natural Science Foundation of China(81970325 and 82170375)Key Research and Develop-ment Support Project of Science&Technology Department of Chengdu(2021-YF08-00121-GX)+2 种基金Post-Doctor Research Project,West China Hospital,Sichuan University(Grant No.20HXBH164 and 20HXBH105)Chinese Medical Association Cardiovascular Branch(CSC)Clinical Research Special Fund Project(CSCF2020B04)West China Hospital“1·3·5”Discipline of Excellence Project-“Percutaneous transcatheter aortic valve implantation”and“Mechanisms of aortic stenosis and the clinical applications”(ZYGD20002).
文摘Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important role in the replacement therapy of severe valvular heart disease,while their durability is limited by degeneration due to calcification,thrombus,endothelialization difficulty and prosthetic valve endocarditis.Herein,we develop a novel BHV,namely,TPly-BP,based on natural tannic acid and polylysine to improve the durability of Glut crosslinked bovine pericardium(Glut-BP).Impressively,tannic acid and polylysine could form nanoaggregates via multiple hydrogen bonds and covalent bonds,and the introduction of nanoaggregates not only improved the mechanical properties and collagen stability but also endowed TPly-BP with good biocompatibility and hemocompatibility.Compared to Glut-BP,TPly-BP showed significantly reduced cytotoxicity,improved endothelial cell adhesion,a low hemolysis ratio and obviously reduced platelet adhesion.Importantly,TPly-BP exhibited great antibacterial and in vivo anti-calcification ability,which was expected to improve the in vivo durability of BHVs.These results suggested that TPly-BP would be a potential candidate for BHV.