A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellul...A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellular receptor as for SARS-CoV and the N-terminus of the S proteins only share 64%amino acid identity,suggesting there are fundamental differences between these two groups of coronaviruses.To gain insight into the basis of this difference,we established a recombinant adenovirus system expressing the S protein from SL-CoV(rAd-Rp3-S)to investigate its immune characterization.Our results showed that immunized mice generated strong humoral immune responses against the SL-CoV S protein.Moreover,a strong cellular immune response demonstrated by elevated IFN-γand IL-6 levels was also observed in these mice.However,the induced antibody from these mice had weaker cross-reaction with the SARS-CoV S protein,and did not neutralize HIV pseudotyped with SARS-CoV S protein.These results demonstrated that the immunogenicity of the SL-CoV S protein is distinct from that of SARS-CoV,which may cause the immunological differences between human SARS-CoV and bat SL-CoV.Furthermore,the recombinant virus could serve as a potential vaccine candidate against bat SL-CoV infection.展开更多
Bat SARS-Iike coronavirus (SL-CoV) has a genome organization almost identical to that of SARS-CoV, but the N-terminus of the Spike (S) proteins, which interacts with host receptor and is a major target of neutrali...Bat SARS-Iike coronavirus (SL-CoV) has a genome organization almost identical to that of SARS-CoV, but the N-terminus of the Spike (S) proteins, which interacts with host receptor and is a major target of neutralizing antibodies against CoVs, of the two viruses has only 63-64% sequence identity. Although there have been reports studying the overall immunogenicity of SsL, knowledge on the precise location of immunodominant determinants for SSL is still lacking. In this study, using a series of truncated expressed SsL fragments and SsL specific mouse sera, we identified two immunogenic determinants for SSL. Importantly, one of the two regions seems to be located in a region not shared by known immunogenic determinants of the SSARS. This finding will be of potential use in future monitoring of SL-CoV infection in bats and spillover animals and in development of more effective vaccine to cover broad protection against this new group of coronaviruses.展开更多
Objective To study whether free triiodothyronine (FT3) within normal range has effects on the presence and severity of coronary ar- tery disease (CAD) in different gender and age groups. Methods A total of 4206 eu...Objective To study whether free triiodothyronine (FT3) within normal range has effects on the presence and severity of coronary ar- tery disease (CAD) in different gender and age groups. Methods A total of 4206 euthyroid patients were consecutively enrolled and di- vided into CAD group (n = 3306) and non-CAD group (n = 900). All patients underwent coronary angiography (CAG). Gensini score (GS) was used to determine the severity of coronary artery stenosis. Severe CAD was defined as GS 〉 32 and mild CAD was defined as GS 〈 32. Logistic regression analysis and linear regression analysis were conducted to determine the association of FT3 with CAD in patients with different gender and ages. Results Concentration of FT3 was lower in patients with CAD than that in angiography-normal control group (P 〈 0.05). In addition, concentration of FT3 was lower in severe CAD than that in mild CAD. After adjusting for traditional cardiovascular risk factors and potential confounders, FT3 was negatively correlated with the presence of CAD, but not in the old patients (〉 65 years old). Mul- tivariable linear regression analysis showed that FT3 was negatively associated with GS in male and young patients with stable CAD, but not in the old patients. Conclusions Low FT3 within normal range was negatively associated with the presence and severity of CAD in young patients, but not in the old ones. Further studies are needed to confirm our findings.展开更多
Severe Acute Respiratory Syndrome (SARS) is a deadly infectious disease caused by SARS Coronavirus (SARS-CoV). Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvan...Severe Acute Respiratory Syndrome (SARS) is a deadly infectious disease caused by SARS Coronavirus (SARS-CoV). Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvants, especially with more efficient and economical needle-free vaccination are alw needed more urgently in a pandemic. The development of a safe and effective mucosal adjuvant and vaccine ays for prevention of emergent infectious diseases such as SARS will be an important advancement. PIKA, a stabilized derivative of Poly (I:C), was previously reported to be safe and potent as adjuvant in mouse models. In the present study, we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly (I:C) derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus. Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites, co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity. When intranasal immunization was used, PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response. Overall, PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.展开更多
Plant carbon sequestration is an effective way to abate the global warming. However, the field-scale carbon exchange on a peach orchard remains unclear. Here, using an eddy covariance technique, the net ecosystem carb...Plant carbon sequestration is an effective way to abate the global warming. However, the field-scale carbon exchange on a peach orchard remains unclear. Here, using an eddy covariance technique, the net ecosystem carbon dioxide exchange and energy balance were analyzed on a coarse-sand-field, no-tillage, 12-year-old-peach orchard. The results showed that during full flowering, the ability to sequestrate carbon was significant, it reached on the peak of-0.33 mg (CO2) m^-2 s^-1. During rapid growth, the Bowen ratio was under 0.3 and daily net carbon sequestration reached on the peak of-25.1 g (CO2) m^-2 d^-1. During the leaf fall stage, there is a great deal of CO2 emissions, the peak value of carbon sequestration reached +0.60 mg (CO2) m^-2 s^-1. During monitoring period, the daily average of net carbon sequestration and Bowen ratio was 1.22 ± 1.56 and -2.90 ± 6.63 g (CO2) m^-2 d^-1, respectively. The net carbon sequestration could reach -1,052 g (CO2) m^-2 in a year. These results reveal that there is high carbon sequestration on a coarse-sand-field, no-tillage peach orchard.展开更多
In 2012,a novel coronavirus,initially named as human coronavirus EMC(HCoV-EMC) but recently renamed as Middle East respiratory syndrome human coronavirus(MERS-CoV),was identified in patients who suffered severe acute ...In 2012,a novel coronavirus,initially named as human coronavirus EMC(HCoV-EMC) but recently renamed as Middle East respiratory syndrome human coronavirus(MERS-CoV),was identified in patients who suffered severe acute respiratory infection and subsequent renal failure that resulted in death.Ongoing epidemiological investigations together with retrospective studies have found 61 laboratory-confirmed cases of infection with this novel coronavirus,including 34 deaths to date.This novel coronavirus is culturable and two complete genome sequences are now available.Furthermore,molecular detection and indirect immunofluorescence assay have been developed.The present paper summarises the limited recent advances of this novel human coronavirus,including its discovery,genomic characterisation and detection.展开更多
Objective:The gene for mast cell chymase (CMA1) is an ideal candidate for investigating the genetic predisposition to coronary heart disease (CHD),as activated mast cells have been found to be present in a greater pro...Objective:The gene for mast cell chymase (CMA1) is an ideal candidate for investigating the genetic predisposition to coronary heart disease (CHD),as activated mast cells have been found to be present in a greater proportion in the shoulder region of atheroma than in normal coronary intimae.Previous studies have indicated that CMA1 promoter polymorphism rs1800875 may be involved in regulating immunoglobulin E (IgE) levels in patients with eczema,and it is associated with the progression of immunoglobulin A nephropathy.Methods:The association between single nucleotide polymorphism (SNP) rs1800875,serum chymase,and serum IgE levels was examined in 175 CHD subjects and 95 non-CHD subjects.Results:Statistical analysis indicated no significant difference in allele frequency between CHD and non-CHD.However,a significant association was found between CMA1 genotypes and total IgE levels in CHD subjects.Meanwhile,crossover analysis revealed that,in GG homozygotes,CHD risk was nearly six times higher in those with IgE (U/ml) level <2.58 (natural logarithm conversion),while no association was found with chymase level.Conclusions:Polymorphism rs1800875 of CMA1 may be associated with serum IgE level in CHD subjects,but not with chymase level in both groups.In GG homozygotes,high IgE level is a protective factor against coronary disease.展开更多
Huntington's disease (HD) is caused by abnormal CAG repeat expansion in the 5'-end of the Huntingtin (HTT) gene. In addition to the canonical C-terminal full-length huntingtin (htt) nuclear export signal, a cy...Huntington's disease (HD) is caused by abnormal CAG repeat expansion in the 5'-end of the Huntingtin (HTT) gene. In addition to the canonical C-terminal full-length huntingtin (htt) nuclear export signal, a cytoplasmic localization-related domain (CLRD) in the N-terminus of htt has recently been reported. Here, we analyzed this domain by introducing deletion and substitution mutations in a truncated N-terminal htt protein and subsequently monitored htt expression, aggregation and subcellular localization by immunocytochemistry and Western blot analysis. We demonstrated that Htt1-17 was the essential sequence for htt cytoplasmic localization. We also found that the subcellular distribution of htt was altered when Htt1_17 was mutated to contain amino acids of different charges, suggesting a structural requirement of Htt1-17 for the cytoplasmic localization of htt. Deletion of the first three amino acids did not affect its association with mitochondria. We observed that defective cytoplasmic localization resulted in a reduction of total htt aggregates and increased nuclear aggregates, indicating that the subcellular distribution of the protein might influence the aggregation process. These studies provide new insight into the molecular mechanism of htt aggregation in HD.展开更多
基金supported by the State Key Program for Basic Research Grant(2005CB523004)from the Chinese Ministry of Science and Technologythe Knowledge Innovation Program Key Project administered by the Chinese Academy of Sciences(KSCX1-YW-R-07)
文摘A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellular receptor as for SARS-CoV and the N-terminus of the S proteins only share 64%amino acid identity,suggesting there are fundamental differences between these two groups of coronaviruses.To gain insight into the basis of this difference,we established a recombinant adenovirus system expressing the S protein from SL-CoV(rAd-Rp3-S)to investigate its immune characterization.Our results showed that immunized mice generated strong humoral immune responses against the SL-CoV S protein.Moreover,a strong cellular immune response demonstrated by elevated IFN-γand IL-6 levels was also observed in these mice.However,the induced antibody from these mice had weaker cross-reaction with the SARS-CoV S protein,and did not neutralize HIV pseudotyped with SARS-CoV S protein.These results demonstrated that the immunogenicity of the SL-CoV S protein is distinct from that of SARS-CoV,which may cause the immunological differences between human SARS-CoV and bat SL-CoV.Furthermore,the recombinant virus could serve as a potential vaccine candidate against bat SL-CoV infection.
基金funded by the State Key Program for Basic Research Grant (2010CB530100,2011CB504700)special project for infectious diseases(2009ZX10004-109) from the Chinese Ministry of Science and Technology
文摘Bat SARS-Iike coronavirus (SL-CoV) has a genome organization almost identical to that of SARS-CoV, but the N-terminus of the Spike (S) proteins, which interacts with host receptor and is a major target of neutralizing antibodies against CoVs, of the two viruses has only 63-64% sequence identity. Although there have been reports studying the overall immunogenicity of SsL, knowledge on the precise location of immunodominant determinants for SSL is still lacking. In this study, using a series of truncated expressed SsL fragments and SsL specific mouse sera, we identified two immunogenic determinants for SSL. Importantly, one of the two regions seems to be located in a region not shared by known immunogenic determinants of the SSARS. This finding will be of potential use in future monitoring of SL-CoV infection in bats and spillover animals and in development of more effective vaccine to cover broad protection against this new group of coronaviruses.
文摘Objective To study whether free triiodothyronine (FT3) within normal range has effects on the presence and severity of coronary ar- tery disease (CAD) in different gender and age groups. Methods A total of 4206 euthyroid patients were consecutively enrolled and di- vided into CAD group (n = 3306) and non-CAD group (n = 900). All patients underwent coronary angiography (CAG). Gensini score (GS) was used to determine the severity of coronary artery stenosis. Severe CAD was defined as GS 〉 32 and mild CAD was defined as GS 〈 32. Logistic regression analysis and linear regression analysis were conducted to determine the association of FT3 with CAD in patients with different gender and ages. Results Concentration of FT3 was lower in patients with CAD than that in angiography-normal control group (P 〈 0.05). In addition, concentration of FT3 was lower in severe CAD than that in mild CAD. After adjusting for traditional cardiovascular risk factors and potential confounders, FT3 was negatively correlated with the presence of CAD, but not in the old patients (〉 65 years old). Mul- tivariable linear regression analysis showed that FT3 was negatively associated with GS in male and young patients with stable CAD, but not in the old patients. Conclusions Low FT3 within normal range was negatively associated with the presence and severity of CAD in young patients, but not in the old ones. Further studies are needed to confirm our findings.
基金supported by the National Natural Science Foundation of China (30670097)National Basic Research Program of China (973 Program) (2005CB522903)+1 种基金National Key R&D Program (2007BAI28B04)National S&T Major Project on Major Infectious Diseases (2008ZX10001-010)from the Ministry of Science and Technology of the People’s Republic of China
文摘Severe Acute Respiratory Syndrome (SARS) is a deadly infectious disease caused by SARS Coronavirus (SARS-CoV). Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvants, especially with more efficient and economical needle-free vaccination are alw needed more urgently in a pandemic. The development of a safe and effective mucosal adjuvant and vaccine ays for prevention of emergent infectious diseases such as SARS will be an important advancement. PIKA, a stabilized derivative of Poly (I:C), was previously reported to be safe and potent as adjuvant in mouse models. In the present study, we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly (I:C) derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus. Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites, co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity. When intranasal immunization was used, PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response. Overall, PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.
基金This work was supported by National Key Technology Supported Program of China (Project 2008BAD95B07, 2011BAD32B03), the China National Natural Science Foundation (Project 31040006).
文摘Plant carbon sequestration is an effective way to abate the global warming. However, the field-scale carbon exchange on a peach orchard remains unclear. Here, using an eddy covariance technique, the net ecosystem carbon dioxide exchange and energy balance were analyzed on a coarse-sand-field, no-tillage, 12-year-old-peach orchard. The results showed that during full flowering, the ability to sequestrate carbon was significant, it reached on the peak of-0.33 mg (CO2) m^-2 s^-1. During rapid growth, the Bowen ratio was under 0.3 and daily net carbon sequestration reached on the peak of-25.1 g (CO2) m^-2 d^-1. During the leaf fall stage, there is a great deal of CO2 emissions, the peak value of carbon sequestration reached +0.60 mg (CO2) m^-2 s^-1. During monitoring period, the daily average of net carbon sequestration and Bowen ratio was 1.22 ± 1.56 and -2.90 ± 6.63 g (CO2) m^-2 d^-1, respectively. The net carbon sequestration could reach -1,052 g (CO2) m^-2 in a year. These results reveal that there is high carbon sequestration on a coarse-sand-field, no-tillage peach orchard.
基金supported by grants from the National Basic Research Program of China (2011CB504704)the State Megaproject for Infectious Disease Research of China (2011ZX10004-001)
文摘In 2012,a novel coronavirus,initially named as human coronavirus EMC(HCoV-EMC) but recently renamed as Middle East respiratory syndrome human coronavirus(MERS-CoV),was identified in patients who suffered severe acute respiratory infection and subsequent renal failure that resulted in death.Ongoing epidemiological investigations together with retrospective studies have found 61 laboratory-confirmed cases of infection with this novel coronavirus,including 34 deaths to date.This novel coronavirus is culturable and two complete genome sequences are now available.Furthermore,molecular detection and indirect immunofluorescence assay have been developed.The present paper summarises the limited recent advances of this novel human coronavirus,including its discovery,genomic characterisation and detection.
基金Project supported by the National Natural Science Foundation of China (No. 30670867) to Mei-xiang XIANGthe Major Program of Science and Technology Department of Zhejiang Province,China(No. 2007C13058) to Mei-xiang XIANG
文摘Objective:The gene for mast cell chymase (CMA1) is an ideal candidate for investigating the genetic predisposition to coronary heart disease (CHD),as activated mast cells have been found to be present in a greater proportion in the shoulder region of atheroma than in normal coronary intimae.Previous studies have indicated that CMA1 promoter polymorphism rs1800875 may be involved in regulating immunoglobulin E (IgE) levels in patients with eczema,and it is associated with the progression of immunoglobulin A nephropathy.Methods:The association between single nucleotide polymorphism (SNP) rs1800875,serum chymase,and serum IgE levels was examined in 175 CHD subjects and 95 non-CHD subjects.Results:Statistical analysis indicated no significant difference in allele frequency between CHD and non-CHD.However,a significant association was found between CMA1 genotypes and total IgE levels in CHD subjects.Meanwhile,crossover analysis revealed that,in GG homozygotes,CHD risk was nearly six times higher in those with IgE (U/ml) level <2.58 (natural logarithm conversion),while no association was found with chymase level.Conclusions:Polymorphism rs1800875 of CMA1 may be associated with serum IgE level in CHD subjects,but not with chymase level in both groups.In GG homozygotes,high IgE level is a protective factor against coronary disease.
基金supported by the National Natural Science Foundation of China(Grant Nos.30770761 and 30971000)
文摘Huntington's disease (HD) is caused by abnormal CAG repeat expansion in the 5'-end of the Huntingtin (HTT) gene. In addition to the canonical C-terminal full-length huntingtin (htt) nuclear export signal, a cytoplasmic localization-related domain (CLRD) in the N-terminus of htt has recently been reported. Here, we analyzed this domain by introducing deletion and substitution mutations in a truncated N-terminal htt protein and subsequently monitored htt expression, aggregation and subcellular localization by immunocytochemistry and Western blot analysis. We demonstrated that Htt1-17 was the essential sequence for htt cytoplasmic localization. We also found that the subcellular distribution of htt was altered when Htt1_17 was mutated to contain amino acids of different charges, suggesting a structural requirement of Htt1-17 for the cytoplasmic localization of htt. Deletion of the first three amino acids did not affect its association with mitochondria. We observed that defective cytoplasmic localization resulted in a reduction of total htt aggregates and increased nuclear aggregates, indicating that the subcellular distribution of the protein might influence the aggregation process. These studies provide new insight into the molecular mechanism of htt aggregation in HD.