在要求高速数据生成和采集的市场中,性能的好坏是关键环节。目前业内在获取实时数据时,从高速的数模转换器(DAC)/模数转换器(ADC)、模拟前端(AFE)都需要用FPGA或ASIC芯片做个桥,LVDS串行高速转换信号总线连接到DSP处理器上。为了让模数...在要求高速数据生成和采集的市场中,性能的好坏是关键环节。目前业内在获取实时数据时,从高速的数模转换器(DAC)/模数转换器(ADC)、模拟前端(AFE)都需要用FPGA或ASIC芯片做个桥,LVDS串行高速转换信号总线连接到DSP处理器上。为了让模数转换器、数模转换器以及模拟前端实现更简易的直接连接,德州仪器(TI)日前宣布推出基于Key Stone TM的高集成度66AK2L06片上系统(So C)解决方案,把原来的FPGA芯片所做的桥整合到DSP里。展开更多
Using chemoproteomic techniques,we first identified EIF2AK2,eEF1A1,PRDX3 and VPS4B as direct targets of berberine(BBR)for its synergistically anti-inflammatory effects.Of them,BBR has the strongest affinity with EIF2A...Using chemoproteomic techniques,we first identified EIF2AK2,eEF1A1,PRDX3 and VPS4B as direct targets of berberine(BBR)for its synergistically anti-inflammatory effects.Of them,BBR has the strongest affinity with EIF2AK2 via two ionic bonds,and regulates several key inflammatory pathways through EIF2AK2,indicating the dominant role of EIF2AK2.Also,BBR could subtly inhibit the dimerization of EIF2AK2,rather than its enzyme activity,to selectively modulate its downstream pathways including JNK,NF-κB,AKT and NLRP3,with an advantage of good safety profile.In EIF2AK2 gene knockdown mice,the inhibitory IL-1β,IL-6,IL-18 and TNF-a secretion of BBR was obviously attenuated,confirming an EIF2AK2-dependent anti-inflammatory efficacy.The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target,and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammationrelated disorders.展开更多
Aim Idiopathic pulmonary arterial hypertension(IPAH) and pulmonary veno-occlusive disease (PVOD) are undistinguished on clinical practice. We proposed that gene test might be a promising and feasible method in the fut...Aim Idiopathic pulmonary arterial hypertension(IPAH) and pulmonary veno-occlusive disease (PVOD) are undistinguished on clinical practice. We proposed that gene test might be a promising and feasible method in the future.Methods A 20-year-old woman was diagnosed as IPAH in 2013while a diagnosis of PVOD was also suspected. The genomic DNA was extracted from peripheral blood and gene panel testing was performed.展开更多
Objective Obesity is becoming a worldwide health problem. The genome wide association （GWA） study particularly for body mass index （BMI） has not been successfully conducted in the Chinese. In order to identify nov...Objective Obesity is becoming a worldwide health problem. The genome wide association （GWA） study particularly for body mass index （BMI） has not been successfully conducted in the Chinese. In order to identify novel genes for BMI variation in the Chinese, an initial GWA study and a follow up replication study were performed. Methods Affymetrix 500K SNPs were genotyped for initial GWA of 597 Northern Chinese. After quality control, 281 533 SNPs were included in the association analysis. Three SNPs were genotyped in a Southern Chinese replication sample containing 2 955 Chinese Han subjects. Association analyses were performed by Plink software. Results Eight SNPs were significantly associated with BMI variation after false discovery rate （FDR） correction （P=5.45×10-7-7.26×106, FDR q=0.033-0.048）. Two adjacent SNPs （rs4432245 ＆ rs711906） in the eukaryotic translation initiation factor 2 alpha kinase 4 （EIF2AK4） gene were significantly associated with BMI （P=6.38×10-6＆ 4.39×106, FDR q=0.048）. In the follow-up replication study, we confirmed the associations between BMI and rs4432245, rs711906 in the EIF2AKE gene （P=0.03 ＆ 0.01, respectively）. Conclusion Our study suggests novel mechanisms for BMI, where EIF2AK4 has exerted a profound effect on the synthesis and storage of triglycerides and may impact on overall energy homeostasis associated with obesity. The minor allele frequencies for the two SNPs in the EIF2AK4 gene have marked ethnic differences between Caucasians and the Chinese. The association of the EIF2AK4 gene with BMI is suggested to be ＇ethnic specific＇ in the Chinese.展开更多
We have studied the expression of a subset of genes encoding important tumor growth related factors in U87 glioma cells with IRE1 (inositol requiring enzyme-1) knockdown as well as their hypoxic regulation. It was sho...We have studied the expression of a subset of genes encoding important tumor growth related factors in U87 glioma cells with IRE1 (inositol requiring enzyme-1) knockdown as well as their hypoxic regulation. It was shown that the expression levels of activating transcription factor 6 (ATF6), clusterin (CLU), adhesion G protein-coupled receptor E5 (ADGRE5), transglutaminase?2, C polypeptide (TGM2), leukemia inhibitory factor (LIF), phosphoserine aminotransferase 1 (PSAT1), glyoxalase I (GLO1) and tetraspanin 13 (TSPAN13) are significantly down-regulated in glioma cells with the knockdown of IRE1 signaling enzyme. It was also shown that in glioma cells subjected to hypoxia, the expression levels of PSAT1, TSPAN13, EIF2AK3, and TGM2 genes were up-regulated, whereas the expression of ATF6 gene was down-regulated. At the same time, the expression levels of LIF, CLU, and ADGRE5 genes did not change in response to hypoxic treatment.?Furthermore, inhibition of IRE1, a key effector of an unfolded protein response pathway, modified the effect of hypoxia on the expression of most studied genes. Present study demonstrates that IRE1 knockdown down-regulated the expression of most studied genes and modified their hypoxic regulation and that these changes possibly contributed to the suppression of glioma growth in cells without IRE1 signaling enzyme function.展开更多
Polycomb group(Pc G)proteins are crucial chromatin regulators during development.H2 AK119 ub1(H2 Aub)and H3 K27 me3 are catalyzed by Polycomb-repressive complex 1 and 2(PRC1/2)respectively,and they largely overlap in ...Polycomb group(Pc G)proteins are crucial chromatin regulators during development.H2 AK119 ub1(H2 Aub)and H3 K27 me3 are catalyzed by Polycomb-repressive complex 1 and 2(PRC1/2)respectively,and they largely overlap in the genome due to mutual recruitment of the two complexes.However,it is unclear whether PRC1/H2 Aub and PRC2/H3 K27 me3 can also function independently.By developing an ultra-sensitive carrier-DNA-assisted chromatin immunoprecipitation sequencing method termed CATCH-Seq,we generated allelic H2 Aub profiles in mouse gametes and early embryos.Our results revealed an unexpected genomewide decoupling of H2 Aub and H3 K27 me3 in mouse preimplantation embryos,where H2 Aub but not H3 K27 me3 was enriched at Pc G targets while only H3 K27 me3 was deposited in the broad distal domains associated with DNA methylation-independent non-canonical imprinting.These observations suggest that H2 Aub represses future bivalent genes during early embryogenesis without H3 K27 me3,but it is not required for the maintenance of non-canonical imprinting,which is mediated by maternal H3 K27 me3.Thus,our study reveals the distinct depositions and independent functions of H2 Aub and H3 K27 me3 during early mammalian development.展开更多
Epigenetic regulation has been attracting increasing attention due to its role in cell differentiation and behaviors.However,the epigenetic mechanisms that regulate human dendritic cell(DC)differentiation and developm...Epigenetic regulation has been attracting increasing attention due to its role in cell differentiation and behaviors.However,the epigenetic mechanisms that regulate human dendritic cell(DC)differentiation and development remain poorly understood.Our previous studies show that extracellular heat shock protein 70-like protein(HSP70L1)is a potent adjuvant of Th1 responses via stimulating DCs when released from cells;however,the role of intracellular HSP70L1 in DC differentiation and maturation remains unknown.Herein,we demonstrate that intracellular HSP70L1 inhibits human DC maturation by suppressing MHC and costimulatory molecule expression,in contrast to the adjuvant activity of extracellular HSP70L1.The stability of intracellular HSP70L1 is dependent on DNAJC2,a known epigenetic regulator.Mechanistically,intracellular HSP70L1 inhibits the recruitment of Ash1l to and maintains the repressive H3K27me3 and H2AK119Ub1 modifications on the promoter regions of costimulatory,MHC and STAT3 genes.Thus,intracellular HSP70L1 is an inhibitor of human DC maturation.Our results provide new insights into the epigenetic regulation of cell development by intracellular HSP70L1.展开更多
文摘在要求高速数据生成和采集的市场中,性能的好坏是关键环节。目前业内在获取实时数据时,从高速的数模转换器(DAC)/模数转换器(ADC)、模拟前端(AFE)都需要用FPGA或ASIC芯片做个桥,LVDS串行高速转换信号总线连接到DSP处理器上。为了让模数转换器、数模转换器以及模拟前端实现更简易的直接连接,德州仪器(TI)日前宣布推出基于Key Stone TM的高集成度66AK2L06片上系统(So C)解决方案,把原来的FPGA芯片所做的桥整合到DSP里。
基金the CAMS initiative for innovative medicine(2022-I2M-2-002,China)National Natural Science Foundation of China(32141003)。
文摘Using chemoproteomic techniques,we first identified EIF2AK2,eEF1A1,PRDX3 and VPS4B as direct targets of berberine(BBR)for its synergistically anti-inflammatory effects.Of them,BBR has the strongest affinity with EIF2AK2 via two ionic bonds,and regulates several key inflammatory pathways through EIF2AK2,indicating the dominant role of EIF2AK2.Also,BBR could subtly inhibit the dimerization of EIF2AK2,rather than its enzyme activity,to selectively modulate its downstream pathways including JNK,NF-κB,AKT and NLRP3,with an advantage of good safety profile.In EIF2AK2 gene knockdown mice,the inhibitory IL-1β,IL-6,IL-18 and TNF-a secretion of BBR was obviously attenuated,confirming an EIF2AK2-dependent anti-inflammatory efficacy.The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target,and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammationrelated disorders.
文摘Aim Idiopathic pulmonary arterial hypertension(IPAH) and pulmonary veno-occlusive disease (PVOD) are undistinguished on clinical practice. We proposed that gene test might be a promising and feasible method in the future.Methods A 20-year-old woman was diagnosed as IPAH in 2013while a diagnosis of PVOD was also suspected. The genomic DNA was extracted from peripheral blood and gene panel testing was performed.
基金supported by grants from Natural Science Foundation of China(30600364,30470534,30771222,30731160618,30230210,and 81101655)the grant from the China Postdoctoral Science Foundation(2011M501282)
文摘Objective Obesity is becoming a worldwide health problem. The genome wide association （GWA） study particularly for body mass index （BMI） has not been successfully conducted in the Chinese. In order to identify novel genes for BMI variation in the Chinese, an initial GWA study and a follow up replication study were performed. Methods Affymetrix 500K SNPs were genotyped for initial GWA of 597 Northern Chinese. After quality control, 281 533 SNPs were included in the association analysis. Three SNPs were genotyped in a Southern Chinese replication sample containing 2 955 Chinese Han subjects. Association analyses were performed by Plink software. Results Eight SNPs were significantly associated with BMI variation after false discovery rate （FDR） correction （P=5.45×10-7-7.26×106, FDR q=0.033-0.048）. Two adjacent SNPs （rs4432245 ＆ rs711906） in the eukaryotic translation initiation factor 2 alpha kinase 4 （EIF2AK4） gene were significantly associated with BMI （P=6.38×10-6＆ 4.39×106, FDR q=0.048）. In the follow-up replication study, we confirmed the associations between BMI and rs4432245, rs711906 in the EIF2AKE gene （P=0.03 ＆ 0.01, respectively）. Conclusion Our study suggests novel mechanisms for BMI, where EIF2AK4 has exerted a profound effect on the synthesis and storage of triglycerides and may impact on overall energy homeostasis associated with obesity. The minor allele frequencies for the two SNPs in the EIF2AK4 gene have marked ethnic differences between Caucasians and the Chinese. The association of the EIF2AK4 gene with BMI is suggested to be ＇ethnic specific＇ in the Chinese.
文摘We have studied the expression of a subset of genes encoding important tumor growth related factors in U87 glioma cells with IRE1 (inositol requiring enzyme-1) knockdown as well as their hypoxic regulation. It was shown that the expression levels of activating transcription factor 6 (ATF6), clusterin (CLU), adhesion G protein-coupled receptor E5 (ADGRE5), transglutaminase?2, C polypeptide (TGM2), leukemia inhibitory factor (LIF), phosphoserine aminotransferase 1 (PSAT1), glyoxalase I (GLO1) and tetraspanin 13 (TSPAN13) are significantly down-regulated in glioma cells with the knockdown of IRE1 signaling enzyme. It was also shown that in glioma cells subjected to hypoxia, the expression levels of PSAT1, TSPAN13, EIF2AK3, and TGM2 genes were up-regulated, whereas the expression of ATF6 gene was down-regulated. At the same time, the expression levels of LIF, CLU, and ADGRE5 genes did not change in response to hypoxic treatment.?Furthermore, inhibition of IRE1, a key effector of an unfolded protein response pathway, modified the effect of hypoxia on the expression of most studied genes. Present study demonstrates that IRE1 knockdown down-regulated the expression of most studied genes and modified their hypoxic regulation and that these changes possibly contributed to the suppression of glioma growth in cells without IRE1 signaling enzyme function.
基金supported by the National Natural Science Foundation of China(32022023 and 31871478)the National Key Research and Development Programs of China(2017YFC1001500)Zhejiang Provincial Natural Science Foundation of China(LR18C060001)。
文摘Polycomb group(Pc G)proteins are crucial chromatin regulators during development.H2 AK119 ub1(H2 Aub)and H3 K27 me3 are catalyzed by Polycomb-repressive complex 1 and 2(PRC1/2)respectively,and they largely overlap in the genome due to mutual recruitment of the two complexes.However,it is unclear whether PRC1/H2 Aub and PRC2/H3 K27 me3 can also function independently.By developing an ultra-sensitive carrier-DNA-assisted chromatin immunoprecipitation sequencing method termed CATCH-Seq,we generated allelic H2 Aub profiles in mouse gametes and early embryos.Our results revealed an unexpected genomewide decoupling of H2 Aub and H3 K27 me3 in mouse preimplantation embryos,where H2 Aub but not H3 K27 me3 was enriched at Pc G targets while only H3 K27 me3 was deposited in the broad distal domains associated with DNA methylation-independent non-canonical imprinting.These observations suggest that H2 Aub represses future bivalent genes during early embryogenesis without H3 K27 me3,but it is not required for the maintenance of non-canonical imprinting,which is mediated by maternal H3 K27 me3.Thus,our study reveals the distinct depositions and independent functions of H2 Aub and H3 K27 me3 during early mammalian development.
基金We thank Yanfeng Li for the technical assistance.This work was supported by grants from the National Key R&D Program of China(2018YFA0507401)the National Natural Science Foundation of China(31670875 and 31470858).
文摘Epigenetic regulation has been attracting increasing attention due to its role in cell differentiation and behaviors.However,the epigenetic mechanisms that regulate human dendritic cell(DC)differentiation and development remain poorly understood.Our previous studies show that extracellular heat shock protein 70-like protein(HSP70L1)is a potent adjuvant of Th1 responses via stimulating DCs when released from cells;however,the role of intracellular HSP70L1 in DC differentiation and maturation remains unknown.Herein,we demonstrate that intracellular HSP70L1 inhibits human DC maturation by suppressing MHC and costimulatory molecule expression,in contrast to the adjuvant activity of extracellular HSP70L1.The stability of intracellular HSP70L1 is dependent on DNAJC2,a known epigenetic regulator.Mechanistically,intracellular HSP70L1 inhibits the recruitment of Ash1l to and maintains the repressive H3K27me3 and H2AK119Ub1 modifications on the promoter regions of costimulatory,MHC and STAT3 genes.Thus,intracellular HSP70L1 is an inhibitor of human DC maturation.Our results provide new insights into the epigenetic regulation of cell development by intracellular HSP70L1.
