Global look-up table strategy proposed recently has been proven to be an efficient method to accelerate the interpolation, which is the most time-consuming part in the iterative sub-pixel digital image correlation （...Global look-up table strategy proposed recently has been proven to be an efficient method to accelerate the interpolation, which is the most time-consuming part in the iterative sub-pixel digital image correlation （DIC） algorithms. In this paper, a global look-up table strategy with cubic B-spline interpolation is developed for the DIC method based on the inverse compositional Gauss-Newton （IC-GN） algorithm. The performance of this strategy, including accuracy, precision, and computation efficiency, is evaluated through a theoretical and experimental study, using the one with widely employed bicubic interpolation as a benchmark. The global look-up table strategy with cubic B-spline interpolation improves significantly the accuracy of the IC-GN algorithm-based DIC method compared with the one using the bicubic interpolation, at a trivial price of computation efficiency.展开更多
The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a global pandemic of novel coronavirus disease(COVID-19).The neutralizing monoclonal antibodies(mAbs)targeting the receptor-binding domain(RBD)...The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a global pandemic of novel coronavirus disease(COVID-19).The neutralizing monoclonal antibodies(mAbs)targeting the receptor-binding domain(RBD)of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19.However,SARS-CoV-2 variants of concern(VOCs)profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use.Herein,we demonstrated mAb 35B5 efficiently neutralizes both wild-type(WT)SARS-CoV-2 and VOCs.展开更多
Chemical modifications of proteins induced by ambient ozone(O_(3))and nitrogen oxides(NOx)are of public health concerns due to their potential to trigger respiratory diseases.The laboratory and environmental exposure ...Chemical modifications of proteins induced by ambient ozone(O_(3))and nitrogen oxides(NOx)are of public health concerns due to their potential to trigger respiratory diseases.The laboratory and environmental exposure systems have been widely used to investigate their relevant mechanism in the atmosphere.Using bovine serum albumin(BSA)as a model protein,we evaluated the two systems and aimed to reduce the uncertainties of both the reactants and products in the corresponding kinetic study.In the laboratory simulation system,the generated gaseous pollutants showed negligible losses.Ten layers of BSA were coated on the flow tube with protein extraction recovery of 87.4%.For environmental exposure experiment,quartz fiber filter was selected as the upper filter with low gaseous O_(3)(8.0%)and NO_(2)(1.7%)losses,and cellulose acetate filter was appropriate for the lower filter with protein extraction efficiency of 95.2%.The protein degradation process was observed without the exposure to atmospheric oxidants and contributed to the loss of protein monomer mass fractions,while environmental factors(e.g.,molecular oxygen and ultraviolet)may cause greater protein monomer losses.Based on the evaluation,the study exemplarily applied the two systems to protein modification and both showed that O_(3) promotes the protein oligomerization and nitration,while increased temperature can accelerate the oligomerization and increased relative humidity can inhibit the nitration in the environmental exposure samples.The developed laboratory and environmental systems are suitable for studying protein modifications formed under different atmospheric conditions.A combination of the two will further reveal the actual mechanism of protein modifications.展开更多
According to the World Health Organization(WHO)newly updated situation report on March 18th,2020,the coronavirus disease 2019(COVID-19)pandemic has confirmed 191,127 cases and claimed 7807 deaths worldwide.1 The etiol...According to the World Health Organization(WHO)newly updated situation report on March 18th,2020,the coronavirus disease 2019(COVID-19)pandemic has confirmed 191,127 cases and claimed 7807 deaths worldwide.1 The etiological agent of COVID-19 has been identified as a novel coronavirus,the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),belonging to Sarbecovirus subgenus(genus Betacoronavirus,family Coronaviridae)and showing 79.6 and 96.2%sequence identity in nucleotide to SARS-CoV and a bat coronavirus(BatCoV RaTG13),respectively.2–4 Like SARS-CoV infection,a substantial fraction of COVID-19 patients exhibits severe respiratory symptoms and has to be hospitalized in intensive care unit.5–8 Although the mortality rate of COVID-19 is significantly lower than that of SARS-CoV infection,SARS-CoV-2 shows much higher human-to-human transmission rate,rapidly leading to a global pandemic declared by WHO on March 11th,2020.展开更多
COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection.It is currently unknown as to the correlation between the magnitude of neutralizing antibody(NAb)responses and the disease severity in...COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection.It is currently unknown as to the correlation between the magnitude of neutralizing antibody(NAb)responses and the disease severity in COVID-19 patients.In a cohort of 59 recovered patients with disease severity including severe,moderate,mild,and asymptomatic,we observed the positive correlation between serum neutralizing capacity and disease severity,in particular,the highest NAb capacity in sera from the patients with severe disease,while a lack of ability of asymptomatic patients to mount competent NAbs.Furthermore,the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-tomoderate symptoms.These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity,highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.展开更多
Epigenetic modifications to histones dictate the differentiation of naïve CD4^(+) T cells into different subsets of effector T helper(TH)cells.The histone methyltransferase enhancer of zeste homolog 2(EZH2)has be...Epigenetic modifications to histones dictate the differentiation of naïve CD4^(+) T cells into different subsets of effector T helper(TH)cells.The histone methyltransferase enhancer of zeste homolog 2(EZH2)has been implicated in the mechanism regulating the differentiation of TH1,TH2 and regulatory T(Treg)cells.However,whether and how EZH2 regulates follicular helper T(TFH)cell differentiation remain unknown.Using a mouse model of acute lymphocytic choriomeningitis virus(LCMV)infection,we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific TFH cells compared to those in TH1 cells.Ablation of EZH2 in LCMV-specific CD4^(+) T cells leads to a selective impairment of early TFH cell fate commitment,but not late TFH differentiation or memory TFH maintenance.Mechanistically,EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for TFH fate commitment,particularly B cell lymphoma 6(Bcl6),and thus directs TFH cell commitment.Therefore,we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early TFH differentiation during acute viral infection.展开更多
The adaptive immunity that protects patients from coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is not well characterized.In particular,the asymptomatic patie...The adaptive immunity that protects patients from coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is not well characterized.In particular,the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses,but the underlying mechanisms remain unknown;meanwhile,the protective immunity that guide the recovery of these asymptomatic patients is elusive.Here,we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 64 patients with other disease severity(mild,n=10,moderate,n=32,severe,n=12)and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center(GC)B cell responses that result in robust and prolonged humoral immunity,assessed by GC response indicators including follicular helper T(TFH)cell and memory B cell responses as well as serum CXCL13 levels.Alternatively,these patients mounted potent virus-specific TH1 and CD8+T cell responses.In sharp contrast,patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses;however,the virus-specific TH1 and CD8+T cells were minimally induced in these patients.These results,therefore,uncovered the protective immunity in asymptomatic patients and also revealed the strikingly dichotomous and incomplete humoral and cellular immune responses in COVID-19 patients with different disease severity,providing important insights into rational design of effective COVID-19 vaccines.展开更多
基金financially supported by the National Natural Science Foundation of China(11202081,11272124,and 11472109)the State Key Lab of Subtropical Building Science,South China University of Technology(2014ZC17)
文摘Global look-up table strategy proposed recently has been proven to be an efficient method to accelerate the interpolation, which is the most time-consuming part in the iterative sub-pixel digital image correlation （DIC） algorithms. In this paper, a global look-up table strategy with cubic B-spline interpolation is developed for the DIC method based on the inverse compositional Gauss-Newton （IC-GN） algorithm. The performance of this strategy, including accuracy, precision, and computation efficiency, is evaluated through a theoretical and experimental study, using the one with widely employed bicubic interpolation as a benchmark. The global look-up table strategy with cubic B-spline interpolation improves significantly the accuracy of the IC-GN algorithm-based DIC method compared with the one using the bicubic interpolation, at a trivial price of computation efficiency.
基金We thank Guangdong Center for Human Pathogen Culture Collection(GDPCC)for providing SARS-CoV-2 isolates.We thank Dr.Junyu Xiao(Peking University)for providing the plasmids encoding the ectodomains of the SARS-CoV-2 S-2P and S-6P mutants.This work was supported by grants from the National Natural Science Fund for Distinguished Young Scholars(No.31825011 to L.Y.)the National Science and Technology Major Project(No.2017ZX10202102-006-002 to L.Y.)+2 种基金Guangdong Innovative and Entrepreneurial Research Team Program(2016ZT06S638 to K.D.)High-level Biosafety Laboratory Construction and Operation Program of the Science and Technology Projects of Guangdong Province of China to K.D.,the National Natural Science Fund(81925024 to Y.Z.)the National Key Research and Development Program of China(2017YFA0503900 to Y.Z.),and the Fundamental Research Funds for the Central Universities to Y.Z.
文摘The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a global pandemic of novel coronavirus disease(COVID-19).The neutralizing monoclonal antibodies(mAbs)targeting the receptor-binding domain(RBD)of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19.However,SARS-CoV-2 variants of concern(VOCs)profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use.Herein,we demonstrated mAb 35B5 efficiently neutralizes both wild-type(WT)SARS-CoV-2 and VOCs.
基金supported by the National Natural Science Foundation of China(Nos.41975156,41675119)。
文摘Chemical modifications of proteins induced by ambient ozone(O_(3))and nitrogen oxides(NOx)are of public health concerns due to their potential to trigger respiratory diseases.The laboratory and environmental exposure systems have been widely used to investigate their relevant mechanism in the atmosphere.Using bovine serum albumin(BSA)as a model protein,we evaluated the two systems and aimed to reduce the uncertainties of both the reactants and products in the corresponding kinetic study.In the laboratory simulation system,the generated gaseous pollutants showed negligible losses.Ten layers of BSA were coated on the flow tube with protein extraction recovery of 87.4%.For environmental exposure experiment,quartz fiber filter was selected as the upper filter with low gaseous O_(3)(8.0%)and NO_(2)(1.7%)losses,and cellulose acetate filter was appropriate for the lower filter with protein extraction efficiency of 95.2%.The protein degradation process was observed without the exposure to atmospheric oxidants and contributed to the loss of protein monomer mass fractions,while environmental factors(e.g.,molecular oxygen and ultraviolet)may cause greater protein monomer losses.Based on the evaluation,the study exemplarily applied the two systems to protein modification and both showed that O_(3) promotes the protein oligomerization and nitration,while increased temperature can accelerate the oligomerization and increased relative humidity can inhibit the nitration in the environmental exposure samples.The developed laboratory and environmental systems are suitable for studying protein modifications formed under different atmospheric conditions.A combination of the two will further reveal the actual mechanism of protein modifications.
基金supported by grants from the National Natural Science Fund for Distinguished Young Scholars(No.31825011 to L.Y.)the Chongqing Special Research Project for Novel Coronavirus Pneumonia Prevention and Control(No.cstc2020jscx-2 to L.Y.,No.cstc2020jscx-fyzx0074 to Y.C.,cstc2020jscx-fyzx0135 to Y.C.).
文摘According to the World Health Organization(WHO)newly updated situation report on March 18th,2020,the coronavirus disease 2019(COVID-19)pandemic has confirmed 191,127 cases and claimed 7807 deaths worldwide.1 The etiological agent of COVID-19 has been identified as a novel coronavirus,the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),belonging to Sarbecovirus subgenus(genus Betacoronavirus,family Coronaviridae)and showing 79.6 and 96.2%sequence identity in nucleotide to SARS-CoV and a bat coronavirus(BatCoV RaTG13),respectively.2–4 Like SARS-CoV infection,a substantial fraction of COVID-19 patients exhibits severe respiratory symptoms and has to be hospitalized in intensive care unit.5–8 Although the mortality rate of COVID-19 is significantly lower than that of SARS-CoV infection,SARS-CoV-2 shows much higher human-to-human transmission rate,rapidly leading to a global pandemic declared by WHO on March 11th,2020.
基金supported by grants from the National Science and Technology Major Project(No.2017ZX10202102-006-002 to L.Y.)the National Natural Science Fund for Distinguished Young Scholars(No.31825011 to L.Y.)the National Science and Technology Major Project(2016ZX09J16105-001-002 to L.Y.).
文摘COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection.It is currently unknown as to the correlation between the magnitude of neutralizing antibody(NAb)responses and the disease severity in COVID-19 patients.In a cohort of 59 recovered patients with disease severity including severe,moderate,mild,and asymptomatic,we observed the positive correlation between serum neutralizing capacity and disease severity,in particular,the highest NAb capacity in sera from the patients with severe disease,while a lack of ability of asymptomatic patients to mount competent NAbs.Furthermore,the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-tomoderate symptoms.These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity,highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.
基金This study was supported by grants from the National Key Research Development Plan(No.2016YFA0502202 to L.Y.)the Open Research Fund of State Key Laboratory of Veterinary Biotechnology(No.SKLVBF2018XX to L.Ye)+3 种基金the National Natural Science Foundation of China(No.31825011 to L.Y.No.31800742 to Q.T.No.31700774 to L.Xu and No.31470870 to X.Z.)Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust(to J.H.).
文摘Epigenetic modifications to histones dictate the differentiation of naïve CD4^(+) T cells into different subsets of effector T helper(TH)cells.The histone methyltransferase enhancer of zeste homolog 2(EZH2)has been implicated in the mechanism regulating the differentiation of TH1,TH2 and regulatory T(Treg)cells.However,whether and how EZH2 regulates follicular helper T(TFH)cell differentiation remain unknown.Using a mouse model of acute lymphocytic choriomeningitis virus(LCMV)infection,we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific TFH cells compared to those in TH1 cells.Ablation of EZH2 in LCMV-specific CD4^(+) T cells leads to a selective impairment of early TFH cell fate commitment,but not late TFH differentiation or memory TFH maintenance.Mechanistically,EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for TFH fate commitment,particularly B cell lymphoma 6(Bcl6),and thus directs TFH cell commitment.Therefore,we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early TFH differentiation during acute viral infection.
基金This work was supported by grants from the National Science and Technology Major Project(No.2017ZX10202102-006-002 to L.Y.)National Key Research Development Plan(No.2016YFA0502202 to L.Ye)+1 种基金the National Natural Science Fund for Distinguished Young Scholars(No.31825011 to L.Y.)the Chongqing Special Research Project for Novel Coronavirus Pneumonia Prevention and Control(No.cstc2020jscx-2 to L.Y.,No.cstc2020jscx-fyzx0074 to Y.C.,ocstc2020jscx-fyzx0135 to Y.C.).
文摘The adaptive immunity that protects patients from coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is not well characterized.In particular,the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses,but the underlying mechanisms remain unknown;meanwhile,the protective immunity that guide the recovery of these asymptomatic patients is elusive.Here,we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 64 patients with other disease severity(mild,n=10,moderate,n=32,severe,n=12)and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center(GC)B cell responses that result in robust and prolonged humoral immunity,assessed by GC response indicators including follicular helper T(TFH)cell and memory B cell responses as well as serum CXCL13 levels.Alternatively,these patients mounted potent virus-specific TH1 and CD8+T cell responses.In sharp contrast,patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses;however,the virus-specific TH1 and CD8+T cells were minimally induced in these patients.These results,therefore,uncovered the protective immunity in asymptomatic patients and also revealed the strikingly dichotomous and incomplete humoral and cellular immune responses in COVID-19 patients with different disease severity,providing important insights into rational design of effective COVID-19 vaccines.
