Background Pork quality can directly affect customer purchase tendency and meat quality traits have become valu-able in modern pork production.However,genetic improvement has been slow due to high phenotyping costs.In...Background Pork quality can directly affect customer purchase tendency and meat quality traits have become valu-able in modern pork production.However,genetic improvement has been slow due to high phenotyping costs.In this study,whole genome sequence(WGS)data was used to evaluate the prediction accuracy of genomic best linear unbiased prediction(GBLUP)for meat quality in large-scale crossbred commercial pigs.Results We produced WGS data(18,695,907 SNPs and 2,106,902 INDELs exceed quality control)from 1,469 sequenced Duroc×(Landrace×Yorkshire)pigs and developed a reference panel for meat quality including meat color score,marbling score,L*(lightness),a*(redness),and b*(yellowness)of genomic prediction.The prediction accuracy was defined as the Pearson correlation coefficient between adjusted phenotypes and genomic estimated breeding values in the validation population.Using different marker density panels derived from WGS data,accuracy differed substantially among meat quality traits,varied from 0.08 to 0.47.Results showed that MultiBLUP outperform GBLUP and yielded accuracy increases ranging from 17.39%to 75%.We optimized the marker density and found medium-and high-density marker panels are beneficial for the estimation of heritability for meat quality.Moreover,we conducted genotype imputation from 50K chip to WGS level in the same population and found average concord-ance rate to exceed 95%and r^(2)=0.81.Conclusions Overall,estimation of heritability for meat quality traits can benefit from the use of WGS data.This study showed the superiority of using WGS data to genetically improve pork quality in genomic prediction.展开更多
Air nanobubbles(A-NBs)were used to inhibit the brass corrosion in circulating cooling water for the first time in the study.The results of mass loss method and electrochemical method showed that A-NBs had the obvious ...Air nanobubbles(A-NBs)were used to inhibit the brass corrosion in circulating cooling water for the first time in the study.The results of mass loss method and electrochemical method showed that A-NBs had the obvious corrosion inhibition effect.The inhibition rate reached 52%at 35℃.The impedance and surface characterization results of corrosion samples indicated that the corrosion inhibition mechanisms of A-NBs mainly included adsorption of corrosion ions,promoting the formation of the passivation film on metal surface and the formation of the bubble layer and scale film on metal surface.A-NBs are potential excellent corrosion inhibitors.展开更多
In this study,we investigated on the application of planar lightwave circuit(PLC)technology in energy-saving control of tunnel lighting.The application status of PLC in the field of energy saving followed by the neces...In this study,we investigated on the application of planar lightwave circuit(PLC)technology in energy-saving control of tunnel lighting.The application status of PLC in the field of energy saving followed by the necessity of energy saving in tunnel lighting was analyzed.Finally,the application of PLC in tunnel lighting energy-saving control around the three dimensions of system overall architecture design,control scheme,and program control process was investigated.The results showed that the system meets the requirements of control effect,robustness,and visual effect after trial operation,and is suitable for practical applications.展开更多
Objective: The purpose of this study was to explore the optimal cutoffs of the three parameters of Ki67 during NAC for predicting patient prognosis and investigate whether the optimal cutoffs of the Ki67 values were a...Objective: The purpose of this study was to explore the optimal cutoffs of the three parameters of Ki67 during NAC for predicting patient prognosis and investigate whether the optimal cutoffs of the Ki67 values were associated with relapse-free survival(RFS) or breast cancer-specific survival(BCSS).Methods: A total of 92 patients with locally advanced breast cancer(LABC), who had residual disease after NAC were retrospectively investigated.The optimal cutoff values of the Ki67 parameters were assessed by the online algorithm Cutoff Finder.Kaplan-Meier analysis, the log-rank test and Cox regression analysis were carried out to analyze survival.Results: The optimal cutoff values for the postsurgical Ki67 level and the decrease in the Ki67 level during NAC were defined as 25% and 12.5%, respectively.According to the univariate survival analysis, a higher Ki67 level in residual disease was associated with poor RFS(P = 0.004) and BCSS(P = 0.014).In addition, a Ki67 expression decrease > 12.5% during NAC was related to favorable RFS(P = 0.007), but was not related to BCSS(P = 0.452).Cox regression analysis showed that the Ki67 expression decrease(> 12.5% vs.≤ 12.5%) and histological grade(grade 3 vs.grade 1-2) were the independent factors associated with RFS(P =0.020 and P = 0.023, respectively), with HR values of 0.353(95% CI: 0.147-0.850) and 3.422(95% CI: 1.188-9.858), respectively.Conclusions: The Ki67 decrease was one of the independent factors associated with RFS in LABC patients with residual disease after receiving NAC.展开更多
There are more than eight different design standards in use for the existing railway bridges in China, which have different applicabilities for bridges built in different periods. In this paper, the design load standa...There are more than eight different design standards in use for the existing railway bridges in China, which have different applicabilities for bridges built in different periods. In this paper, the design load standards in different periods are introduced and compared; The working status of the railway is investigated. According to the developing trend of separating passenger and freight transports, by comparing the computed results of the bridge effect and the fatigue cumulative damage, the applicabilities of bearing capacity and fatigue are analyzed for existing bridges. The results indicate that the bearing capacities of 99% existing bridges are suitable for the demand of 26.5 t （axle-weight） freight trains. However, for culverts, bridges with spans less than 20 m, longitudinal and transverse beams of through bridges, suspenders of truss bridges and other locally-stressed members should be evaluated and reinforced due to the increasing axle-weight.展开更多
This study was designed to verify the stem cell properties of sheep amniotic epithelial cells and their capacity for neural differentiation. Immunofluorescence microscopy and reverse transcription-PCR revealed that th...This study was designed to verify the stem cell properties of sheep amniotic epithelial cells and their capacity for neural differentiation. Immunofluorescence microscopy and reverse transcription-PCR revealed that the sheep amniotic epithelial cells were positive for the embryonic stem cell marker proteins SSEA-1, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81, and the totipotency-associated genes Oct-4, Sox-2 and Rex-1, but negative for Nanog. Amniotic epithelial cells expressed β-Ⅲ-tubulin, glial fibrillary acidic protein, nestin and microtubule-associated protein-2 at 28 days after induction with serum-free neurobasal-A medium containing B-27. Thus, sheep amniotic epithelial cells could differentiate into neurons expressing β-Ⅲ-tubulin and microtubule-associated protein-2, and glial-like cells expressing glial fibrillary acidic protein, under specific conditions.展开更多
Bone morphogenetic protein-7 is widely accepted as an inducer for bone marrow stem cells differentiating into osteoblasts and chondrocytes. Whether bone marrow stromal cells differentiate into neuron-like cells remain...Bone morphogenetic protein-7 is widely accepted as an inducer for bone marrow stem cells differentiating into osteoblasts and chondrocytes. Whether bone marrow stromal cells differentiate into neuron-like cells remains unclear. The current study examined the presence of positive cells for intermediate filament protein and microtubule associated protein-2 in the cytoplasm of bone marrow stromal cells induced by bone morphogenetic protein-7 under an inverted microscope, while no expression of glial fibrillary acidic protein was found. Reverse transcription PCR electrophoresis also revealed a positive target band for intermediate filament protein and microtubule-associated protein 2 mRNA. These results confirmed that bone morphogenetic protein-7 induces rat bone marrow stromal cells differentiating into neuron-like cells.展开更多
The spatial and temporal evolution of real contact area of contact interface with loads is a challenge.It is generally believed that there is a positive linear correlation between real contact area and normal load.How...The spatial and temporal evolution of real contact area of contact interface with loads is a challenge.It is generally believed that there is a positive linear correlation between real contact area and normal load.However,with the development of measuring instruments and methods,some scholars have found that the growth rate of real contact area will slow down with the increase of normal load under certain conditions,such as large-scale interface contact with small roughness surface,which is called the nonlinear phenomenon of real contact area.At present,there is no unified conclusion on the explanation of this phenomenon.We set up an experimental apparatus based on the total reflection principle to verify this phenomenon and analyze its mechanism.An image processing method is proposed,which can be used to quantitative analysis micro contact behaviors on macro contact phenomenon.The weighted superposition method is used to identify micro contact spots,to calculate the real contact area,and the color superimposed image is used to identify micro contact behaviors.Based on this method,the spatiotemporal evolution mechanism of real contact area nonlinear phenomena is quantitatively analyzed.Furthermore,the influence of nonlinear phenomenon of real contact area on the whole loading and unloading process is analyzed experimentally.It is found that the effects of fluid between contact interface,normal load amplitude and initial contact state on contact behavior cannot be ignored in large-scale interface contact with small roughness surface.展开更多
Objective Insulin has been reported to influence cholesterol removal from different cells,but the Results have been controversial.Based on our previous study,which we found that insulin promote cholesterol efflux from...Objective Insulin has been reported to influence cholesterol removal from different cells,but the Results have been controversial.Based on our previous study,which we found that insulin promote cholesterol efflux from HepG2 cells and can reverse the decreased cholesterol efflux to HDL though PI3K-Akt pathway,we further investigate the effects of insulin on damaged cholesterol efflux by MCP-1 in this report.展开更多
Objective Evidence is lacking for the exercise characteristics in increasing HDL-C level regardless of endurance exercise elevating HDL-Clevel. The aim of this study is to clarify the effect and characteristics of exe...Objective Evidence is lacking for the exercise characteristics in increasing HDL-C level regardless of endurance exercise elevating HDL-Clevel. The aim of this study is to clarify the effect and characteristics of exercise in increasing HDL-C in randomized control trials (RCTs).展开更多
Railway steel bridge belongs to large-scale weld structures suffered with cyclic dynamic stress generated by the train. In recent years, the section of bridge member becomes bigger, plate becomes thicker, connection f...Railway steel bridge belongs to large-scale weld structures suffered with cyclic dynamic stress generated by the train. In recent years, the section of bridge member becomes bigger, plate becomes thicker, connection form becomes more complicated and steel bridge is applied to wider districts even in the lower temperature environment. Thus, fatigue and fracture problems become more serious. On the basis of CTOD （crack tip open displacement） test data of 372 specimens tested in different temperatures, this paper discusses research work about fracture proof design that involves how to determine the criterion of CVN （Charpy V-notch） impact toughness by establishing the relationship between CTOD and CVN, how to prevent from brittle fracture by stress control in railway steel bridge design based on COD （crack open displacement） design curve through the test data and how to do the fatigue design for railway steel bridge at -50 ℃ of design temperature in an easy way. The method of fatigue design at -50 ℃ environment has been used for railway steel bridge structure of Qinghai-Tibet Railway in China.展开更多
With the coordinated development of today's social economy with science and technology,various advanced technologies are being used in highway engineering,especially the distributed intelligent power supply techno...With the coordinated development of today's social economy with science and technology,various advanced technologies are being used in highway engineering,especially the distributed intelligent power supply technology in expressway tunnels,which has a very significant advantage.In order to realize the effective application of this technology and promote the power supply effect in expressway tunnel,this study analyzes the advantages of this technology and its application in expressway tunnel,hoping to provide scientific reference for the application of distributed intelligent power supply technology and the engineering development of expressway tunnels.展开更多
At present,the number of road engineering projects is increasing,and the corresponding street lighting work is receiving much more attention.In order to improve the lighting,operation,convenience,and energy-saving eff...At present,the number of road engineering projects is increasing,and the corresponding street lighting work is receiving much more attention.In order to improve the lighting,operation,convenience,and energy-saving effect of urban streets,the concept of“smart lighting”needs to be implemented.This includes the planning of an urban street lighting design scheme and the use of appropriate software as well as components to realize significant optimization of the lighting work in urban streets.Therefore,this paper discusses the application measures of smart lighting in urban street lighting to provide reference.展开更多
Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone mar...Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone marrow(BM)cells,putative autoantigens,and oligoclonal expansion of CD8+T cells.1 For SAA patients,the definitive therapies are immunosuppressive therapy(IST)or hematopoietic stem transplantation(HSCT).展开更多
Enterovirus D68(EV-D68)can cause respiratory diseases and acute flaccid paralysis,posing a great threat to public health.Interferons are cytokines secreted by host cells that have broad-spectrum antiviral effects,indu...Enterovirus D68(EV-D68)can cause respiratory diseases and acute flaccid paralysis,posing a great threat to public health.Interferons are cytokines secreted by host cells that have broad-spectrum antiviral effects,inducing the expression of hundreds of interferon-stimulated genes(ISGs).EV-D68 activates ISG expression early in infection,but at a later stage,the virus suppresses ISG expression,a strategy evolved by EV-D68 to antagonize interferons.Here,we explore a host protein,suppressor of cytokine signaling 3(SOCS3),is upregulated during EV-D68 infection and antagonizes the antiviral effects of type I interferon.We subsequently demonstrate that the structural protein of EV-D68 upregulated the expression of RFX7,a transcriptional regulator of SOCS3,leading to the upregulation of SOCS3 expression.Further exploration revealed that SOCS3 plays its role by inhibiting the phosphorylation of signal transducer and activator of transcription 3(STAT3).The expression of SOCS3 inhibited the expression of ISG,thereby inhibiting the antiviral effect of type I interferon and promoting EV-D68 transcription,protein production,and viral titer.Notably,a truncated SOCS3,generated by deleting the kinase inhibitory region(KIR)domain,failed to promote replication and translation of EV-D68.Based on the above studies,we designed a short peptide named SOCS3 inhibitor,which can specifically bind and inhibit the KIR structural domain of SOCS3,significantly reducing the RNA and protein levels of EV-D68.In summary,our results demonstrated a novel mechanism by which EV-D68 inhibits ISG transcription and antagonizes the antiviral responses of host type I interferon.展开更多
基金supported by a Technical Innovation of Crossbred in Swine and Breed High Fertility Lines Project(2022B0202090002)a Local Innovative and Research Teams Project of Guangdong Province(2019BT02N630)+1 种基金a Natural Science Foundation of Guangdong Province project(2018B030313011)Innovative Teams of Modern Agriculture and Industry Technology System of Guangdong Province(2022KJ26).
文摘Background Pork quality can directly affect customer purchase tendency and meat quality traits have become valu-able in modern pork production.However,genetic improvement has been slow due to high phenotyping costs.In this study,whole genome sequence(WGS)data was used to evaluate the prediction accuracy of genomic best linear unbiased prediction(GBLUP)for meat quality in large-scale crossbred commercial pigs.Results We produced WGS data(18,695,907 SNPs and 2,106,902 INDELs exceed quality control)from 1,469 sequenced Duroc×(Landrace×Yorkshire)pigs and developed a reference panel for meat quality including meat color score,marbling score,L*(lightness),a*(redness),and b*(yellowness)of genomic prediction.The prediction accuracy was defined as the Pearson correlation coefficient between adjusted phenotypes and genomic estimated breeding values in the validation population.Using different marker density panels derived from WGS data,accuracy differed substantially among meat quality traits,varied from 0.08 to 0.47.Results showed that MultiBLUP outperform GBLUP and yielded accuracy increases ranging from 17.39%to 75%.We optimized the marker density and found medium-and high-density marker panels are beneficial for the estimation of heritability for meat quality.Moreover,we conducted genotype imputation from 50K chip to WGS level in the same population and found average concord-ance rate to exceed 95%and r^(2)=0.81.Conclusions Overall,estimation of heritability for meat quality traits can benefit from the use of WGS data.This study showed the superiority of using WGS data to genetically improve pork quality in genomic prediction.
基金supported by National Natural Science Foundation of China(52170074).
文摘Air nanobubbles(A-NBs)were used to inhibit the brass corrosion in circulating cooling water for the first time in the study.The results of mass loss method and electrochemical method showed that A-NBs had the obvious corrosion inhibition effect.The inhibition rate reached 52%at 35℃.The impedance and surface characterization results of corrosion samples indicated that the corrosion inhibition mechanisms of A-NBs mainly included adsorption of corrosion ions,promoting the formation of the passivation film on metal surface and the formation of the bubble layer and scale film on metal surface.A-NBs are potential excellent corrosion inhibitors.
文摘In this study,we investigated on the application of planar lightwave circuit(PLC)technology in energy-saving control of tunnel lighting.The application status of PLC in the field of energy saving followed by the necessity of energy saving in tunnel lighting was analyzed.Finally,the application of PLC in tunnel lighting energy-saving control around the three dimensions of system overall architecture design,control scheme,and program control process was investigated.The results showed that the system meets the requirements of control effect,robustness,and visual effect after trial operation,and is suitable for practical applications.
基金supported by grants from the Department of Education of Guangdong Province (Grant No.2016KQNCX051)Key International Collaborative Project of National Natural Science Fund Committee (Grant No.81320108015)+1 种基金National Natural Science Foundation of China (Grant No.31271068)Natural Science Foundation of Guangdong Province (Grant No.2015A030313429)
文摘Objective: The purpose of this study was to explore the optimal cutoffs of the three parameters of Ki67 during NAC for predicting patient prognosis and investigate whether the optimal cutoffs of the Ki67 values were associated with relapse-free survival(RFS) or breast cancer-specific survival(BCSS).Methods: A total of 92 patients with locally advanced breast cancer(LABC), who had residual disease after NAC were retrospectively investigated.The optimal cutoff values of the Ki67 parameters were assessed by the online algorithm Cutoff Finder.Kaplan-Meier analysis, the log-rank test and Cox regression analysis were carried out to analyze survival.Results: The optimal cutoff values for the postsurgical Ki67 level and the decrease in the Ki67 level during NAC were defined as 25% and 12.5%, respectively.According to the univariate survival analysis, a higher Ki67 level in residual disease was associated with poor RFS(P = 0.004) and BCSS(P = 0.014).In addition, a Ki67 expression decrease > 12.5% during NAC was related to favorable RFS(P = 0.007), but was not related to BCSS(P = 0.452).Cox regression analysis showed that the Ki67 expression decrease(> 12.5% vs.≤ 12.5%) and histological grade(grade 3 vs.grade 1-2) were the independent factors associated with RFS(P =0.020 and P = 0.023, respectively), with HR values of 0.353(95% CI: 0.147-0.850) and 3.422(95% CI: 1.188-9.858), respectively.Conclusions: The Ki67 decrease was one of the independent factors associated with RFS in LABC patients with residual disease after receiving NAC.
文摘There are more than eight different design standards in use for the existing railway bridges in China, which have different applicabilities for bridges built in different periods. In this paper, the design load standards in different periods are introduced and compared; The working status of the railway is investigated. According to the developing trend of separating passenger and freight transports, by comparing the computed results of the bridge effect and the fatigue cumulative damage, the applicabilities of bearing capacity and fatigue are analyzed for existing bridges. The results indicate that the bearing capacities of 99% existing bridges are suitable for the demand of 26.5 t （axle-weight） freight trains. However, for culverts, bridges with spans less than 20 m, longitudinal and transverse beams of through bridges, suspenders of truss bridges and other locally-stressed members should be evaluated and reinforced due to the increasing axle-weight.
基金funded by the National High-Tech Research and Development Program of China(863Program),No.2008AA101005
文摘This study was designed to verify the stem cell properties of sheep amniotic epithelial cells and their capacity for neural differentiation. Immunofluorescence microscopy and reverse transcription-PCR revealed that the sheep amniotic epithelial cells were positive for the embryonic stem cell marker proteins SSEA-1, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81, and the totipotency-associated genes Oct-4, Sox-2 and Rex-1, but negative for Nanog. Amniotic epithelial cells expressed β-Ⅲ-tubulin, glial fibrillary acidic protein, nestin and microtubule-associated protein-2 at 28 days after induction with serum-free neurobasal-A medium containing B-27. Thus, sheep amniotic epithelial cells could differentiate into neurons expressing β-Ⅲ-tubulin and microtubule-associated protein-2, and glial-like cells expressing glial fibrillary acidic protein, under specific conditions.
基金Science and Technology Research and Development Program of Shihezi University, No. ZRKX2009YB23
文摘Bone morphogenetic protein-7 is widely accepted as an inducer for bone marrow stem cells differentiating into osteoblasts and chondrocytes. Whether bone marrow stromal cells differentiate into neuron-like cells remains unclear. The current study examined the presence of positive cells for intermediate filament protein and microtubule associated protein-2 in the cytoplasm of bone marrow stromal cells induced by bone morphogenetic protein-7 under an inverted microscope, while no expression of glial fibrillary acidic protein was found. Reverse transcription PCR electrophoresis also revealed a positive target band for intermediate filament protein and microtubule-associated protein 2 mRNA. These results confirmed that bone morphogenetic protein-7 induces rat bone marrow stromal cells differentiating into neuron-like cells.
基金the National Natural Science Foundation of China(Grant No.11872033)the Beijing Natural Science Foundation,China(Grant No.3172017).
文摘The spatial and temporal evolution of real contact area of contact interface with loads is a challenge.It is generally believed that there is a positive linear correlation between real contact area and normal load.However,with the development of measuring instruments and methods,some scholars have found that the growth rate of real contact area will slow down with the increase of normal load under certain conditions,such as large-scale interface contact with small roughness surface,which is called the nonlinear phenomenon of real contact area.At present,there is no unified conclusion on the explanation of this phenomenon.We set up an experimental apparatus based on the total reflection principle to verify this phenomenon and analyze its mechanism.An image processing method is proposed,which can be used to quantitative analysis micro contact behaviors on macro contact phenomenon.The weighted superposition method is used to identify micro contact spots,to calculate the real contact area,and the color superimposed image is used to identify micro contact behaviors.Based on this method,the spatiotemporal evolution mechanism of real contact area nonlinear phenomena is quantitatively analyzed.Furthermore,the influence of nonlinear phenomenon of real contact area on the whole loading and unloading process is analyzed experimentally.It is found that the effects of fluid between contact interface,normal load amplitude and initial contact state on contact behavior cannot be ignored in large-scale interface contact with small roughness surface.
文摘Objective Insulin has been reported to influence cholesterol removal from different cells,but the Results have been controversial.Based on our previous study,which we found that insulin promote cholesterol efflux from HepG2 cells and can reverse the decreased cholesterol efflux to HDL though PI3K-Akt pathway,we further investigate the effects of insulin on damaged cholesterol efflux by MCP-1 in this report.
文摘Objective Evidence is lacking for the exercise characteristics in increasing HDL-C level regardless of endurance exercise elevating HDL-Clevel. The aim of this study is to clarify the effect and characteristics of exercise in increasing HDL-C in randomized control trials (RCTs).
文摘Railway steel bridge belongs to large-scale weld structures suffered with cyclic dynamic stress generated by the train. In recent years, the section of bridge member becomes bigger, plate becomes thicker, connection form becomes more complicated and steel bridge is applied to wider districts even in the lower temperature environment. Thus, fatigue and fracture problems become more serious. On the basis of CTOD （crack tip open displacement） test data of 372 specimens tested in different temperatures, this paper discusses research work about fracture proof design that involves how to determine the criterion of CVN （Charpy V-notch） impact toughness by establishing the relationship between CTOD and CVN, how to prevent from brittle fracture by stress control in railway steel bridge design based on COD （crack open displacement） design curve through the test data and how to do the fatigue design for railway steel bridge at -50 ℃ of design temperature in an easy way. The method of fatigue design at -50 ℃ environment has been used for railway steel bridge structure of Qinghai-Tibet Railway in China.
文摘With the coordinated development of today's social economy with science and technology,various advanced technologies are being used in highway engineering,especially the distributed intelligent power supply technology in expressway tunnels,which has a very significant advantage.In order to realize the effective application of this technology and promote the power supply effect in expressway tunnel,this study analyzes the advantages of this technology and its application in expressway tunnel,hoping to provide scientific reference for the application of distributed intelligent power supply technology and the engineering development of expressway tunnels.
文摘At present,the number of road engineering projects is increasing,and the corresponding street lighting work is receiving much more attention.In order to improve the lighting,operation,convenience,and energy-saving effect of urban streets,the concept of“smart lighting”needs to be implemented.This includes the planning of an urban street lighting design scheme and the use of appropriate software as well as components to realize significant optimization of the lighting work in urban streets.Therefore,this paper discusses the application measures of smart lighting in urban street lighting to provide reference.
基金supported by grants from the Innovative Clinical Technique of Guangzhou,China(No.2019GX04 and 2023C-GX01 to YPZ and SQW,respectively)2019 Annual Research Project of The China Marrow Donor Program(No.CMDP201902 to SQW)+1 种基金Guangzhou Municipal Science and Technology project(China)(No.202002030035 to SQW)the Natural Science Foundation of Guangdong Province,China(No.2018A0303130179 to MZ).
文摘Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone marrow(BM)cells,putative autoantigens,and oligoclonal expansion of CD8+T cells.1 For SAA patients,the definitive therapies are immunosuppressive therapy(IST)or hematopoietic stem transplantation(HSCT).
基金This work was supported by the National Natural Science Foundation of China(32170144).
文摘Enterovirus D68(EV-D68)can cause respiratory diseases and acute flaccid paralysis,posing a great threat to public health.Interferons are cytokines secreted by host cells that have broad-spectrum antiviral effects,inducing the expression of hundreds of interferon-stimulated genes(ISGs).EV-D68 activates ISG expression early in infection,but at a later stage,the virus suppresses ISG expression,a strategy evolved by EV-D68 to antagonize interferons.Here,we explore a host protein,suppressor of cytokine signaling 3(SOCS3),is upregulated during EV-D68 infection and antagonizes the antiviral effects of type I interferon.We subsequently demonstrate that the structural protein of EV-D68 upregulated the expression of RFX7,a transcriptional regulator of SOCS3,leading to the upregulation of SOCS3 expression.Further exploration revealed that SOCS3 plays its role by inhibiting the phosphorylation of signal transducer and activator of transcription 3(STAT3).The expression of SOCS3 inhibited the expression of ISG,thereby inhibiting the antiviral effect of type I interferon and promoting EV-D68 transcription,protein production,and viral titer.Notably,a truncated SOCS3,generated by deleting the kinase inhibitory region(KIR)domain,failed to promote replication and translation of EV-D68.Based on the above studies,we designed a short peptide named SOCS3 inhibitor,which can specifically bind and inhibit the KIR structural domain of SOCS3,significantly reducing the RNA and protein levels of EV-D68.In summary,our results demonstrated a novel mechanism by which EV-D68 inhibits ISG transcription and antagonizes the antiviral responses of host type I interferon.
