AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in vario...AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.展开更多
目的研究孕妇血清叶酸(FA)、单核细胞趋化蛋白-1(MCP-1)和孕酮诱导的阻断因子(PIBF)水平与早期妊娠胚胎停止发育的相关性。方法选取2021年12月~2023年12月荆州市第二人民医院收治的早期妊娠胚胎停止发育孕妇98例为胎停组,另选同期进行...目的研究孕妇血清叶酸(FA)、单核细胞趋化蛋白-1(MCP-1)和孕酮诱导的阻断因子(PIBF)水平与早期妊娠胚胎停止发育的相关性。方法选取2021年12月~2023年12月荆州市第二人民医院收治的早期妊娠胚胎停止发育孕妇98例为胎停组,另选同期进行孕检的正常早期妊娠孕妇50例为对照组,收集一般临床资料,酶联免疫吸附试验(ELISA)检测血清FA,MCP-1和PIBF水平。多因素Logistic回归分析早期妊娠胚胎停止发育的影响因素;绘制受试者工作特征(ROC)曲线分析血清FA,MCP-1和PIBF对早期妊娠胚胎停止发育的预测价值;Pearson法分析血清FA,MCP-1,PIBF与孕酮(PROG)、雌二醇(E2)以及β-人绒毛膜促性腺激素(β-HCG)的相关性。结果与对照组相比,胎停组的血清FA(9.51±1.21nmol/L vs 11.32±1.56nmol/L),PIBF(295.46±30.22 ng/ml vs 342.14±36.97ng/ml)水平降低,血清MCP-1(1.02±0.15 mg/ml vs 0.82±0.11 mg/ml)水平升高,差异具有统计学意义(t=7.785,8.347,8.229,均P<0.001)。两组孕妇的胎停史(75.64%vs 25.36%),PROG(13.32±1.81 ng/ml vs 23.65±2.74 ng/ml),E2(221.34±25.69 pmol/L vs 298.65±31.64 pmol/L)以及β-HCG(5323.62±536.85 U/L vs 8562.31±924.55 U/L)水平比较,差异具有统计学意义(t/χ^(2)=6.548~27.428,均P<0.05)。孕妇胎停史、MCP-1水平升高为影响早期妊娠胎停的危险因素(Waldχ^(2)=4.239,4.613,均P<0.05),β-HCG,FA以及PIBF水平升高为影响早期妊娠胎停的保护因素(Waldχ^(2)=4.476,4.423,5.974,均P<0.05);FA,MCP-1,PIBF以及联合预测早期妊娠胚胎停止发育的AUC分别为0.811,0.805,0.816和0.908,联合预测显著优于FA,MCP-1,PIBF单独预测(Z=2.749,2.381,1.993,均P<0.05)。FA,PIBF与PROG,E2,β-HCG呈正相关(r=0.433~0.512,均P<0.05),MCP-1与PROG,E2,β-HCG呈负相关(r=-0.432,-0.487,-0.458,均P<0.05)。结论早期妊娠胚胎停止发育孕妇血清FA,PIBF水平降低,MCP-1水平升高,三者均为影响孕妇胚胎停止发育的影响因素,对早期妊娠胚胎停止发育具有一定辅助预测价值。展开更多
Dear Editor,This letter presents a novel latent factorization model for high dimensional and incomplete (HDI) tensor, namely the neural Tucker factorization (Neu Tuc F), which is a generic neural network-based latent-...Dear Editor,This letter presents a novel latent factorization model for high dimensional and incomplete (HDI) tensor, namely the neural Tucker factorization (Neu Tuc F), which is a generic neural network-based latent-factorization-of-tensors model under the Tucker decomposition framework.展开更多
Substantial effects of photochemical reaction losses of volatile organic compounds(VOCs)on factor profiles can be investigated by comparing the differences between daytime and nighttime dispersion-normalized VOC data ...Substantial effects of photochemical reaction losses of volatile organic compounds(VOCs)on factor profiles can be investigated by comparing the differences between daytime and nighttime dispersion-normalized VOC data resolved profiles.Hourly speciated VOC data measured in Shijiazhuang,China from May to September 2021 were used to conduct study.The mean VOC concentration in the daytime and at nighttime were 32.8 and 36.0 ppbv,respectively.Alkanes and aromatics concentrations in the daytime(12.9 and 3.08 ppbv)were lower than nighttime(15.5 and 3.63 ppbv),whereas that of alkenes showed the opposite tendency.The concentration differences between daytime and nighttime for alkynes and halogenated hydrocarbonswere uniformly small.The reactivities of the dominant species in factor profiles for gasoline emissions,natural gas and diesel vehicles,and liquefied petroleum gas were relatively low and their profiles were less affected by photochemical losses.Photochemical losses produced a substantial impact on the profiles of solvent use,petrochemical industry emissions,combustion sources,and biogenic emissions where the dominant species in these factor profiles had high reactivities.Although the profile of biogenic emissions was substantially affected by photochemical loss of isoprene,the low emissions at nighttime also had an important impact on its profile.Chemical losses of highly active VOC species substantially reduced their concentrations in apportioned factor profiles.This study results were consistent with the analytical results obtained through initial concentration estimation,suggesting that the initial concentration estimation could be the most effective currently availablemethod for the source analyses of active VOCs although with uncertainty.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81870921(to YW),81974179(to ZZ),82271320(to ZZ),82071284(to YT)National Key R&D Program of China,No.2022YFA1603600(to ZZ),2019YFA0112000(to YT)+1 种基金Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY).
文摘AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.
文摘目的研究孕妇血清叶酸(FA)、单核细胞趋化蛋白-1(MCP-1)和孕酮诱导的阻断因子(PIBF)水平与早期妊娠胚胎停止发育的相关性。方法选取2021年12月~2023年12月荆州市第二人民医院收治的早期妊娠胚胎停止发育孕妇98例为胎停组,另选同期进行孕检的正常早期妊娠孕妇50例为对照组,收集一般临床资料,酶联免疫吸附试验(ELISA)检测血清FA,MCP-1和PIBF水平。多因素Logistic回归分析早期妊娠胚胎停止发育的影响因素;绘制受试者工作特征(ROC)曲线分析血清FA,MCP-1和PIBF对早期妊娠胚胎停止发育的预测价值;Pearson法分析血清FA,MCP-1,PIBF与孕酮(PROG)、雌二醇(E2)以及β-人绒毛膜促性腺激素(β-HCG)的相关性。结果与对照组相比,胎停组的血清FA(9.51±1.21nmol/L vs 11.32±1.56nmol/L),PIBF(295.46±30.22 ng/ml vs 342.14±36.97ng/ml)水平降低,血清MCP-1(1.02±0.15 mg/ml vs 0.82±0.11 mg/ml)水平升高,差异具有统计学意义(t=7.785,8.347,8.229,均P<0.001)。两组孕妇的胎停史(75.64%vs 25.36%),PROG(13.32±1.81 ng/ml vs 23.65±2.74 ng/ml),E2(221.34±25.69 pmol/L vs 298.65±31.64 pmol/L)以及β-HCG(5323.62±536.85 U/L vs 8562.31±924.55 U/L)水平比较,差异具有统计学意义(t/χ^(2)=6.548~27.428,均P<0.05)。孕妇胎停史、MCP-1水平升高为影响早期妊娠胎停的危险因素(Waldχ^(2)=4.239,4.613,均P<0.05),β-HCG,FA以及PIBF水平升高为影响早期妊娠胎停的保护因素(Waldχ^(2)=4.476,4.423,5.974,均P<0.05);FA,MCP-1,PIBF以及联合预测早期妊娠胚胎停止发育的AUC分别为0.811,0.805,0.816和0.908,联合预测显著优于FA,MCP-1,PIBF单独预测(Z=2.749,2.381,1.993,均P<0.05)。FA,PIBF与PROG,E2,β-HCG呈正相关(r=0.433~0.512,均P<0.05),MCP-1与PROG,E2,β-HCG呈负相关(r=-0.432,-0.487,-0.458,均P<0.05)。结论早期妊娠胚胎停止发育孕妇血清FA,PIBF水平降低,MCP-1水平升高,三者均为影响孕妇胚胎停止发育的影响因素,对早期妊娠胚胎停止发育具有一定辅助预测价值。
基金supported by the National Natural Science Foundation of China(62272078)Chongqing Natural Science Foundation(CSTB2023NSCQ-LZX0069)the Science and Technology Research Program of Chongqing Municipal Education Commission(KJQN202300210)
文摘Dear Editor,This letter presents a novel latent factorization model for high dimensional and incomplete (HDI) tensor, namely the neural Tucker factorization (Neu Tuc F), which is a generic neural network-based latent-factorization-of-tensors model under the Tucker decomposition framework.
基金supported by the National Key R&D Program of China(No.2023YFC3705801)the National Natural Science Foundation of China(No.42177085).
文摘Substantial effects of photochemical reaction losses of volatile organic compounds(VOCs)on factor profiles can be investigated by comparing the differences between daytime and nighttime dispersion-normalized VOC data resolved profiles.Hourly speciated VOC data measured in Shijiazhuang,China from May to September 2021 were used to conduct study.The mean VOC concentration in the daytime and at nighttime were 32.8 and 36.0 ppbv,respectively.Alkanes and aromatics concentrations in the daytime(12.9 and 3.08 ppbv)were lower than nighttime(15.5 and 3.63 ppbv),whereas that of alkenes showed the opposite tendency.The concentration differences between daytime and nighttime for alkynes and halogenated hydrocarbonswere uniformly small.The reactivities of the dominant species in factor profiles for gasoline emissions,natural gas and diesel vehicles,and liquefied petroleum gas were relatively low and their profiles were less affected by photochemical losses.Photochemical losses produced a substantial impact on the profiles of solvent use,petrochemical industry emissions,combustion sources,and biogenic emissions where the dominant species in these factor profiles had high reactivities.Although the profile of biogenic emissions was substantially affected by photochemical loss of isoprene,the low emissions at nighttime also had an important impact on its profile.Chemical losses of highly active VOC species substantially reduced their concentrations in apportioned factor profiles.This study results were consistent with the analytical results obtained through initial concentration estimation,suggesting that the initial concentration estimation could be the most effective currently availablemethod for the source analyses of active VOCs although with uncertainty.
