Niemann-Pick disease type C（NPC） is a fatal, neurovisceral lipid storage disease, neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons, progressive neuronal loss, neurofibrillary ...Niemann-Pick disease type C（NPC） is a fatal, neurovisceral lipid storage disease, neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons, progressive neuronal loss, neurofibrillary tangles（NFTs） formation, and axonal spheroids（AS）. Cytoskeletal pathology including accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological hallmark of the mouse model of NPC（npc mice）. With a goal of elucidating the mechanisms underlying the lesion formation, we investigated the temporal and spatial characteristics of cytoskeletal lesions and the roles of cdc2, cdk4, and cdk5 in lesion formation in young npc mice. Cytoskeletal lesions were detectable in npc mice at three weeks of age. Importantly, concomitant activation of cdc2/cyclin B1 kinase and accumulation of a subsequently generated cohort of phospho-epitopes were detected. The activation of cdk4/cyclin D1 and cdk5/p25 kinases was observed during the fourth week of life in npc mice, and this activation contributed to the lesion formation. We concluded that the progression of cytoskeletal pathology in npc mice older than four weeks is accelerated by the cumulative effect of cdc2, cdk4, and cdk5 activation. Furthermore, cdc2/cyclin B1 may act as a key initial player one week earlier. Targeting cell cycle activation may be beneficial to slow down the NPC pathogenesis.展开更多
In order to investigate the neuroprotective effects of cyclin-dependent kinase-5 （cdk-5） inhibition in mice with Niemarm-Pick disease type C （NPC） （npc^-/-）, recombinant adeno-associated virus （rAAV） carrying ...In order to investigate the neuroprotective effects of cyclin-dependent kinase-5 （cdk-5） inhibition in mice with Niemarm-Pick disease type C （NPC） （npc^-/-）, recombinant adeno-associated virus （rAAV） carrying the small interfering RNA （siRNA） specific for cdk-5 gene was injected into 3-day-old npc^-/- mice intracerebroventricularly. The rAAV-GFP-injected age-matched npc^-/- mice and non-surgery age-matched npc^-/- mice were employed as controls （n=6-10/group）. From the 4th to 8th week after the treatment, mice were weighed, and evaluated for limb motor activity by using the coat hanger test once a week. Eight-week-old npc^-/- mice were sacrificed by decapitation, and brains were quickly dissected and halved sagittally. Immunohistochemistry, Western blotting, and HE staining were used to evaluate the neuropathology in npc^-/- mice. The results showed that rAAV-cdk-5-siRNA-GFP significantly reduced the number of axonal spheroids, delayed the death of Purkinje neurons, ameliorated motor defects in npc^-/- mice, and significantly attenuated the hyperphosphorylation oftau proteins. These data suggested that inhibition of cdk-5 activity has neuroprotective effect on neurons in NPC mice.展开更多
Bovine parainfluenza virus type 3（BPIV3） is considered as one of the most important respiratory tract pathogens of both young and adult cattle, and widespread among cattle in the world. BPIV3 was first reported in C...Bovine parainfluenza virus type 3（BPIV3） is considered as one of the most important respiratory tract pathogens of both young and adult cattle, and widespread among cattle in the world. BPIV3 was first reported in China in 2008 and four strains of BPIV3 were isolated from Shandong Province, known as genotype C（BPIV3c）. Pathogen investigations had shown that BPIV3 c infection was very common among cattle in China. To date, BPIV3 can be classified into genotypes A, B and C based on genetic and phylogenetic analysis. Serological survey also demonstrates that BPIV3 infection is widespread in China, however, there is still no available vaccine for BPIV3 prevention in China nowadays. In the present study, the BPIV3 c strain SD0835 was continuously passaged on Madin-Darby bovine kidney（MDBK） cells for hundreds of times, and the pathogenicity of passage 209 was reduced in guinea pigs. The passage 209 of BPIV3 c strain SD0835 was used as a live vaccine candidate to immunize the guinea pigs. The vaccination results revealed that two vaccinations could induce excellent serum neutralizing antibody responses as well as proliferation of T lymphocytes. The vaccinated guinea pigs were well protected against challenge with a low passage of BPIV3 c strain SD0835. Additionally, the percentages of CD4~＋ and CD8~＋ T cell subsets of animals in vaccinated group increased after immunization; T cell subsets on day 2 after challenge in both groups decreased, and the decline of CD4~＋ and CD8~＋ T cell subsets levels of four guinea pigs in vaccinated group was relatively moderate, comparing with that of the control group. These data support further testing of the attenuated virus as an effective candidate vaccine.展开更多
采用自制的SnXX无铅钎料代替生产中常用的SnBi钎料,并分别采用超声波辅助钎焊技术和常规钎焊技术实现USB3.1 Type C中的铜导线和铜端子的可靠焊接互连,以阐明新型超声辅助钎焊技术在数据线连接领域内的优越性。焊后PIN位焊点锡点饱满,PI...采用自制的SnXX无铅钎料代替生产中常用的SnBi钎料,并分别采用超声波辅助钎焊技术和常规钎焊技术实现USB3.1 Type C中的铜导线和铜端子的可靠焊接互连,以阐明新型超声辅助钎焊技术在数据线连接领域内的优越性。焊后PIN位焊点锡点饱满,PIN位的前端未见未融的锡膏,焊杯界面无过多的锡珠。焊点横截面宏观形貌呈圆滑过渡,界面结合良好并形成Cu_6Sn_5化合物,无宏观缺陷,良品率较高。展开更多
AIM:To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma(HCC).METHODS:We studied 232 patients,who underwent liver biopsy for type C c...AIM:To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma(HCC).METHODS:We studied 232 patients,who underwent liver biopsy for type C chronic liver disease between 1992 and 2009,with sustained virological response(SVR)after interferon therapy.The patients were divided into two groups according to the F stage 0+1+2 group(n = 182)and F3+4 group(n = 50).We prospectively observed and compared the incidence of HCC of the patients with SVR in the F0+1+2 and F3+4 groups.Then,the background factors and liver histopathological findings,including the degree of fibrosis,F stage,inflammation,necrosis,bile duct obstruction,fat deposition,and degree of irregular regeneration(IR)of hepatocytes,were correlated with the risk of developing HCC.RESULTS:HCC developed in three of 182(1.6%)patients in the F0+1+2 group,and four of 50(8.0%)in the F3+4 group.The cumulative incidence of HCC in the former group was found to be significantly lower than in the F3+4 group(log rank test P = 0.0224).The presence of atypical hepatocytes among IR of hepatocytes in the F3+4 group resulted in a higher cumulative incidence of HCC,and was significantly correlated with risk of HCC development(RR = 20.748,95%CI:1.335-322.5,P = 0.0303).CONCLUSION:Atypical hepatocytes among the histopathological findings of type C liver disease may be an important risk factor for HCC development along with progression of liver fibrosis.展开更多
为了便于实际项目需要,设计了一种采用对绞线结构且带有E-Marker芯片的全功能USB Type-C高速电缆。采用polar SI 9000仿真软件对整条Type C线缆链路按产品实际制程的要求进行阻抗模拟仿真,得出Type C整条链路阻抗的曲线。实验结果表明, ...为了便于实际项目需要,设计了一种采用对绞线结构且带有E-Marker芯片的全功能USB Type-C高速电缆。采用polar SI 9000仿真软件对整条Type C线缆链路按产品实际制程的要求进行阻抗模拟仿真,得出Type C整条链路阻抗的曲线。实验结果表明, Type C整条链路阻抗一致性越好,其IMR、IRL性能就越好。采用一种新的线夹工艺,解决在Type C接头外模尺寸不变的情况下Type C Gen2 SI性能及可制造的问题。实验证明,通过这种新的线夹工艺,不但可以解决困扰Type C SI性能的串扰难点,还可以解决可制造问题。目前,采用该设计方案的Type C线缆已拿到USB协会的1M Type C Gen 2证书。展开更多
Catalytic activities for direct NO decomposition were investigated over C-type cubic Y2O3–Tb4O7–ZrO2 prepared by a coprecipitation method. The NO decomposition activity was enhanced by partial substitution of the yt...Catalytic activities for direct NO decomposition were investigated over C-type cubic Y2O3–Tb4O7–ZrO2 prepared by a coprecipitation method. The NO decomposition activity was enhanced by partial substitution of the yttrium sites with terbium in a (Y0.97Zr0.03)2O3.03 catalyst, which shows high NO decomposition activity. Among the catalysts synthesized in this study, the (Y0.67Tb0.30Zr0.03)2O3.33 catalyst exhibited the highest NO decomposition activity;NO conversion to N2 was as high as 67% at 900℃ in the absence of O2 (NO/He atmosphere), and a relatively high conversion ratio was observed even in the presence of O2 or CO2, compared with those obtained over conventional direct NO decomposition catalysts. These results indicate that the C-type cubic Y2O3–Tb4O7–ZrO2 catalyst is a new potential candidate for direct NO decomposition.展开更多
基金supported by the National Natural Science Foundation of China(No.81271406)
文摘Niemann-Pick disease type C（NPC） is a fatal, neurovisceral lipid storage disease, neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons, progressive neuronal loss, neurofibrillary tangles（NFTs） formation, and axonal spheroids（AS）. Cytoskeletal pathology including accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological hallmark of the mouse model of NPC（npc mice）. With a goal of elucidating the mechanisms underlying the lesion formation, we investigated the temporal and spatial characteristics of cytoskeletal lesions and the roles of cdc2, cdk4, and cdk5 in lesion formation in young npc mice. Cytoskeletal lesions were detectable in npc mice at three weeks of age. Importantly, concomitant activation of cdc2/cyclin B1 kinase and accumulation of a subsequently generated cohort of phospho-epitopes were detected. The activation of cdk4/cyclin D1 and cdk5/p25 kinases was observed during the fourth week of life in npc mice, and this activation contributed to the lesion formation. We concluded that the progression of cytoskeletal pathology in npc mice older than four weeks is accelerated by the cumulative effect of cdc2, cdk4, and cdk5 activation. Furthermore, cdc2/cyclin B1 may act as a key initial player one week earlier. Targeting cell cycle activation may be beneficial to slow down the NPC pathogenesis.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30400141, 30670737)
文摘In order to investigate the neuroprotective effects of cyclin-dependent kinase-5 （cdk-5） inhibition in mice with Niemarm-Pick disease type C （NPC） （npc^-/-）, recombinant adeno-associated virus （rAAV） carrying the small interfering RNA （siRNA） specific for cdk-5 gene was injected into 3-day-old npc^-/- mice intracerebroventricularly. The rAAV-GFP-injected age-matched npc^-/- mice and non-surgery age-matched npc^-/- mice were employed as controls （n=6-10/group）. From the 4th to 8th week after the treatment, mice were weighed, and evaluated for limb motor activity by using the coat hanger test once a week. Eight-week-old npc^-/- mice were sacrificed by decapitation, and brains were quickly dissected and halved sagittally. Immunohistochemistry, Western blotting, and HE staining were used to evaluate the neuropathology in npc^-/- mice. The results showed that rAAV-cdk-5-siRNA-GFP significantly reduced the number of axonal spheroids, delayed the death of Purkinje neurons, ameliorated motor defects in npc^-/- mice, and significantly attenuated the hyperphosphorylation oftau proteins. These data suggested that inhibition of cdk-5 activity has neuroprotective effect on neurons in NPC mice.
基金funded by a grant from the National Natural Science Foundation of China(31372452)a fund for Science and Technology Plan from Harbin Science and Technology Bureau,Heilongjiang Province,China(2012AA6BN020)a grant from the National Key Technologies R&D Program of China during the 12th Five-Year Plan period(2012BAD12B03-3)
文摘Bovine parainfluenza virus type 3（BPIV3） is considered as one of the most important respiratory tract pathogens of both young and adult cattle, and widespread among cattle in the world. BPIV3 was first reported in China in 2008 and four strains of BPIV3 were isolated from Shandong Province, known as genotype C（BPIV3c）. Pathogen investigations had shown that BPIV3 c infection was very common among cattle in China. To date, BPIV3 can be classified into genotypes A, B and C based on genetic and phylogenetic analysis. Serological survey also demonstrates that BPIV3 infection is widespread in China, however, there is still no available vaccine for BPIV3 prevention in China nowadays. In the present study, the BPIV3 c strain SD0835 was continuously passaged on Madin-Darby bovine kidney（MDBK） cells for hundreds of times, and the pathogenicity of passage 209 was reduced in guinea pigs. The passage 209 of BPIV3 c strain SD0835 was used as a live vaccine candidate to immunize the guinea pigs. The vaccination results revealed that two vaccinations could induce excellent serum neutralizing antibody responses as well as proliferation of T lymphocytes. The vaccinated guinea pigs were well protected against challenge with a low passage of BPIV3 c strain SD0835. Additionally, the percentages of CD4~＋ and CD8~＋ T cell subsets of animals in vaccinated group increased after immunization; T cell subsets on day 2 after challenge in both groups decreased, and the decline of CD4~＋ and CD8~＋ T cell subsets levels of four guinea pigs in vaccinated group was relatively moderate, comparing with that of the control group. These data support further testing of the attenuated virus as an effective candidate vaccine.
文摘采用自制的SnXX无铅钎料代替生产中常用的SnBi钎料,并分别采用超声波辅助钎焊技术和常规钎焊技术实现USB3.1 Type C中的铜导线和铜端子的可靠焊接互连,以阐明新型超声辅助钎焊技术在数据线连接领域内的优越性。焊后PIN位焊点锡点饱满,PIN位的前端未见未融的锡膏,焊杯界面无过多的锡珠。焊点横截面宏观形貌呈圆滑过渡,界面结合良好并形成Cu_6Sn_5化合物,无宏观缺陷,良品率较高。
文摘AIM:To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma(HCC).METHODS:We studied 232 patients,who underwent liver biopsy for type C chronic liver disease between 1992 and 2009,with sustained virological response(SVR)after interferon therapy.The patients were divided into two groups according to the F stage 0+1+2 group(n = 182)and F3+4 group(n = 50).We prospectively observed and compared the incidence of HCC of the patients with SVR in the F0+1+2 and F3+4 groups.Then,the background factors and liver histopathological findings,including the degree of fibrosis,F stage,inflammation,necrosis,bile duct obstruction,fat deposition,and degree of irregular regeneration(IR)of hepatocytes,were correlated with the risk of developing HCC.RESULTS:HCC developed in three of 182(1.6%)patients in the F0+1+2 group,and four of 50(8.0%)in the F3+4 group.The cumulative incidence of HCC in the former group was found to be significantly lower than in the F3+4 group(log rank test P = 0.0224).The presence of atypical hepatocytes among IR of hepatocytes in the F3+4 group resulted in a higher cumulative incidence of HCC,and was significantly correlated with risk of HCC development(RR = 20.748,95%CI:1.335-322.5,P = 0.0303).CONCLUSION:Atypical hepatocytes among the histopathological findings of type C liver disease may be an important risk factor for HCC development along with progression of liver fibrosis.
文摘为了便于实际项目需要,设计了一种采用对绞线结构且带有E-Marker芯片的全功能USB Type-C高速电缆。采用polar SI 9000仿真软件对整条Type C线缆链路按产品实际制程的要求进行阻抗模拟仿真,得出Type C整条链路阻抗的曲线。实验结果表明, Type C整条链路阻抗一致性越好,其IMR、IRL性能就越好。采用一种新的线夹工艺,解决在Type C接头外模尺寸不变的情况下Type C Gen2 SI性能及可制造的问题。实验证明,通过这种新的线夹工艺,不但可以解决困扰Type C SI性能的串扰难点,还可以解决可制造问题。目前,采用该设计方案的Type C线缆已拿到USB协会的1M Type C Gen 2证书。
文摘Catalytic activities for direct NO decomposition were investigated over C-type cubic Y2O3–Tb4O7–ZrO2 prepared by a coprecipitation method. The NO decomposition activity was enhanced by partial substitution of the yttrium sites with terbium in a (Y0.97Zr0.03)2O3.03 catalyst, which shows high NO decomposition activity. Among the catalysts synthesized in this study, the (Y0.67Tb0.30Zr0.03)2O3.33 catalyst exhibited the highest NO decomposition activity;NO conversion to N2 was as high as 67% at 900℃ in the absence of O2 (NO/He atmosphere), and a relatively high conversion ratio was observed even in the presence of O2 or CO2, compared with those obtained over conventional direct NO decomposition catalysts. These results indicate that the C-type cubic Y2O3–Tb4O7–ZrO2 catalyst is a new potential candidate for direct NO decomposition.
