OBJECTIVEα-Dstroglycan(α-DG)is a predominant component in the dystrophin-glycoprotein complex(DGC)and a recently char⁃acterized receptor for several extracellular matrix components with high affinity.Recent research...OBJECTIVEα-Dstroglycan(α-DG)is a predominant component in the dystrophin-glycoprotein complex(DGC)and a recently char⁃acterized receptor for several extracellular matrix components with high affinity.Recent research⁃es have reported that hypoglycosylation ofα-DG is associated with the pathophysiology of diseas⁃es,especially muscular dystrophy,but little is known about major depressive disorder(MDD).Like-acetylglucosaminyl transferase(Large)is a key enzyme for glycosylation ofα-DG,which mainly modifies two points in the middle domain ofα-DG:Thr-317 and Thr-319.Glycosylatedα-DG(GLY-α-DG)can bind with high affinity to extracellular matrix(ECM)molecules that con⁃tain laminin globular(LG)domains,including per⁃lecan,agrin and neurexin.Agrin is mainly derived from neurons rather than glial cells.In cultured hippocampal neurons,it was found that agrin could regulate the homeostatic plasticity of inhibi⁃tory neurons by acting on GLY-α-DG.Mdx mice are transgenetic models for the investigation of Duchenne muscular dystrophy.Many studies have shown that the expression of GLY-α-DG in the peripheral and brain tissues of Mdx mice is significantly down-regulated.Mdx mice show cognitive impairment and high levels of anxiety.In this study,we employed chronic social defeat stress(CSDS)to establish an animal model of depression and detected the expression of GLY-α-DG among the brain areas associated with the pathophysiology of depression.METHODS So⁃cial interaction test(SIT)and sucrose preference test(SPT)were used to evaluate depressive-like behavior.Open field(OF)and elevated plus maze(EPM)test were used to determine the anxiety-like behavior of Mdx mice.Novelty-sup⁃pressed feeding test(NSFT)forced swim test(FST)and tail suspension test(TST)were used to detect the depressive-like behavior of Mdx mice.Novel object recognition test(NOR)was applied to evaluate the cognition of Mdx mice.Subthreshold social defeat stress was used to explore the susceptibility to stress in Mdx mice.Stereotactic infusion of agrin into the ventral hippocampus(vHip),FST and TST were used to investigate the antidepressant effects of agrin.Adeno-associated virus(AAV)-mediated overex⁃pression techniques,behavior tests and whole-cell path-clamp technique were conducted to determine the impact of Large overexpression on CSDS susceptible mice.RESULTS The expres⁃sion ofα-DG and GLY-α-DG were significantly decreased in the vHip of CSDS susceptible mice.Mdx mice showed decreased expression of GLY-α-DG and increased anxiety-like behav⁃iors.Mdx mice displayed some depressive-like behaviors,and the susceptibility to stress was significantly increased.Downregulation of the expressionα-DG in the vHip by lentivirus increased the susceptibility to stress.Administra⁃tion of agrin to CSDS susceptible mice exerted antidepressant effects,and this effect could par⁃tially sustain for a week.The expression of Large was decreased in vHip.Overexpression of Large through AAV-Large reversed the depressive-like behaviors and restored the decreased frequency and amplitude of mIPSC.CONCLUSION GLY-α-DG and its glycosylase are significantly decreased in CSDS susceptible mice.Adminis⁃tration of agrin and overexpression of Large displays antidepressant effect,which may be related to its promotion of inhibitory synaptic transmission.展开更多
In this paper, we consider the Timoshenko system as an initial-boundary value problem in a one-dimensional bounded domain. And then we establish the global existence and asymptotic behavior of solution by using the se...In this paper, we consider the Timoshenko system as an initial-boundary value problem in a one-dimensional bounded domain. And then we establish the global existence and asymptotic behavior of solution by using the semigroup method and multiplicative techniques, then further prove the existence of a uniform attractor by using the method of uniform contractive function. The main advantage of this method is that we need only to verify compactness condition with the same type of energy estimate as that for establishing absorbing sets.展开更多
A new type of semi-rigid thin-walled steel-concrete composite beam-to-column joint has been proposed in this paper.Five semi-rigid composite beam-to-column joint specimens subjected to hogging moments under monotonic ...A new type of semi-rigid thin-walled steel-concrete composite beam-to-column joint has been proposed in this paper.Five semi-rigid composite beam-to-column joint specimens subjected to hogging moments under monotonic loading were tested to study the static behavior of this new type of joint.The main variable parameters for the five joint specimens were the longitudinal reinforcement ratio and the joint type.The experimental results designated that the magnitude of extension of the longitudinal reinforcement is the most important factor that influenced the moment-rotation characteristic of the new type of joint.The concrete slabs could resist 3.8%-19.1% of the total shear load applied to the cross-sections near the beam-to-column connection.The edge stiffened elements,such as the flange of the lipped I-section thin-walled steel beam,were capable of having considerable inelastic deformation capacity although they had comparatively large width-to-thickness ratios.The shear failure of the concrete cantilever edge strip must be taken into account in practical design because it has significant influence on the anchorage of the longitudinal reinforcement in the new type of external joints.展开更多
The pedestrian movement is more complex than vehicular flow for the reason that people are more flexible and intelligent than car. Without the limit of 搇anes?pedestrian movement is loose and free. Furthermore, they a...The pedestrian movement is more complex than vehicular flow for the reason that people are more flexible and intelligent than car. Without the limit of 搇anes?pedestrian movement is loose and free. Furthermore, they are easily affected by other walkers as well as the environ-ment around. In this paper some special technique is intro-duced considering human behavior to make the rules more reasonable. By simulating the two-dimension pedestrian movement, the phase transition phenomena of pedestrian movement, including the up walkers moving from the bottom to the upper boundary and the right walkers moving from the left to the right boundary, are presented. Studying on the effect of the system size on the critical density shows that the critical density is independent of the system size in the scope studied in this paper.展开更多
目的:从“肿瘤异质化”角度出发,通过多种基因编码蛋白(Bcl-2／Bax,Cath-D和VEGF)在肠型胃癌和弥漫型胃癌中的表达,探讨二型胃癌不同生物学特性的分子学基础．方法:采用免疫组化SP法检测Bcl-2／Bax, cathepsin-D(Cath-D)和VEGF在胃癌及...目的:从“肿瘤异质化”角度出发,通过多种基因编码蛋白(Bcl-2／Bax,Cath-D和VEGF)在肠型胃癌和弥漫型胃癌中的表达,探讨二型胃癌不同生物学特性的分子学基础．方法:采用免疫组化SP法检测Bcl-2／Bax, cathepsin-D(Cath-D)和VEGF在胃癌及正常胃组织的表达．结果:Bcl-2／Bax,Cath-D和VEGF阳性表达率在胃癌组织中与癌旁正常胃黏膜组织中比较 (分别为44．59％ vs 27.30％;58．11％ vs 71．62％; 77．00％vs 21．60％;71．62％vs 14．86％)均有显著性差异(P<0．05),弥漫型胃癌中Bcl-2和 Cath-D阳性细胞指数明显高于肠型胃癌(分别为29．14±24．70 vs 19．80±27．37和52．59± 33．76 vs 29．21±39．67),而Bax阳性细胞指数 (分别为32．56±35．55 vs 47．74±27．43)明显低于肠型胃癌,差异均有显著性(P<0．05),VEGF 阳性细胞表达指数在不同胃癌浸润深度组间比较(早期胃癌7．13±15．81 vs 肌层浸润62．77 ±44．37 vs 浆膜浸润40．82±42．70)及有无淋巴结转移组间比较(42．05±42．61 vs 34．15± 42．52)有显著性差异(P<0．05)．结论:Bcl-2／Bax,Cath-D和VEGF分别参与了胃癌的发生,浸润进展和转移．二型胃癌在组织学发生相同的基础上由于在胃癌演进过程中有不同附加基因参与(Bcl-2／Bax和Cath-D), 使弥漫型胃癌获得了与肠型胃癌有所不同的亚克隆过程,因而表现为生物学特性的异质化．展开更多
文摘OBJECTIVEα-Dstroglycan(α-DG)is a predominant component in the dystrophin-glycoprotein complex(DGC)and a recently char⁃acterized receptor for several extracellular matrix components with high affinity.Recent research⁃es have reported that hypoglycosylation ofα-DG is associated with the pathophysiology of diseas⁃es,especially muscular dystrophy,but little is known about major depressive disorder(MDD).Like-acetylglucosaminyl transferase(Large)is a key enzyme for glycosylation ofα-DG,which mainly modifies two points in the middle domain ofα-DG:Thr-317 and Thr-319.Glycosylatedα-DG(GLY-α-DG)can bind with high affinity to extracellular matrix(ECM)molecules that con⁃tain laminin globular(LG)domains,including per⁃lecan,agrin and neurexin.Agrin is mainly derived from neurons rather than glial cells.In cultured hippocampal neurons,it was found that agrin could regulate the homeostatic plasticity of inhibi⁃tory neurons by acting on GLY-α-DG.Mdx mice are transgenetic models for the investigation of Duchenne muscular dystrophy.Many studies have shown that the expression of GLY-α-DG in the peripheral and brain tissues of Mdx mice is significantly down-regulated.Mdx mice show cognitive impairment and high levels of anxiety.In this study,we employed chronic social defeat stress(CSDS)to establish an animal model of depression and detected the expression of GLY-α-DG among the brain areas associated with the pathophysiology of depression.METHODS So⁃cial interaction test(SIT)and sucrose preference test(SPT)were used to evaluate depressive-like behavior.Open field(OF)and elevated plus maze(EPM)test were used to determine the anxiety-like behavior of Mdx mice.Novelty-sup⁃pressed feeding test(NSFT)forced swim test(FST)and tail suspension test(TST)were used to detect the depressive-like behavior of Mdx mice.Novel object recognition test(NOR)was applied to evaluate the cognition of Mdx mice.Subthreshold social defeat stress was used to explore the susceptibility to stress in Mdx mice.Stereotactic infusion of agrin into the ventral hippocampus(vHip),FST and TST were used to investigate the antidepressant effects of agrin.Adeno-associated virus(AAV)-mediated overex⁃pression techniques,behavior tests and whole-cell path-clamp technique were conducted to determine the impact of Large overexpression on CSDS susceptible mice.RESULTS The expres⁃sion ofα-DG and GLY-α-DG were significantly decreased in the vHip of CSDS susceptible mice.Mdx mice showed decreased expression of GLY-α-DG and increased anxiety-like behav⁃iors.Mdx mice displayed some depressive-like behaviors,and the susceptibility to stress was significantly increased.Downregulation of the expressionα-DG in the vHip by lentivirus increased the susceptibility to stress.Administra⁃tion of agrin to CSDS susceptible mice exerted antidepressant effects,and this effect could par⁃tially sustain for a week.The expression of Large was decreased in vHip.Overexpression of Large through AAV-Large reversed the depressive-like behaviors and restored the decreased frequency and amplitude of mIPSC.CONCLUSION GLY-α-DG and its glycosylase are significantly decreased in CSDS susceptible mice.Adminis⁃tration of agrin and overexpression of Large displays antidepressant effect,which may be related to its promotion of inhibitory synaptic transmission.
基金Supported by the National Natural Science Foundation of China（l1671075）
文摘In this paper, we consider the Timoshenko system as an initial-boundary value problem in a one-dimensional bounded domain. And then we establish the global existence and asymptotic behavior of solution by using the semigroup method and multiplicative techniques, then further prove the existence of a uniform attractor by using the method of uniform contractive function. The main advantage of this method is that we need only to verify compactness condition with the same type of energy estimate as that for establishing absorbing sets.
基金Sponsored by the National Natural Science Foundation of China (Grant No.50478027)
文摘A new type of semi-rigid thin-walled steel-concrete composite beam-to-column joint has been proposed in this paper.Five semi-rigid composite beam-to-column joint specimens subjected to hogging moments under monotonic loading were tested to study the static behavior of this new type of joint.The main variable parameters for the five joint specimens were the longitudinal reinforcement ratio and the joint type.The experimental results designated that the magnitude of extension of the longitudinal reinforcement is the most important factor that influenced the moment-rotation characteristic of the new type of joint.The concrete slabs could resist 3.8%-19.1% of the total shear load applied to the cross-sections near the beam-to-column connection.The edge stiffened elements,such as the flange of the lipped I-section thin-walled steel beam,were capable of having considerable inelastic deformation capacity although they had comparatively large width-to-thickness ratios.The shear failure of the concrete cantilever edge strip must be taken into account in practical design because it has significant influence on the anchorage of the longitudinal reinforcement in the new type of external joints.
基金supported by the National Natural Science Foundation of China(Grant Nos.50276058 and 50006012)the Chinese National Key Basic Research Science Foundation Project(Grant No.2001CB409603)
文摘The pedestrian movement is more complex than vehicular flow for the reason that people are more flexible and intelligent than car. Without the limit of 搇anes?pedestrian movement is loose and free. Furthermore, they are easily affected by other walkers as well as the environ-ment around. In this paper some special technique is intro-duced considering human behavior to make the rules more reasonable. By simulating the two-dimension pedestrian movement, the phase transition phenomena of pedestrian movement, including the up walkers moving from the bottom to the upper boundary and the right walkers moving from the left to the right boundary, are presented. Studying on the effect of the system size on the critical density shows that the critical density is independent of the system size in the scope studied in this paper.
文摘目的:从“肿瘤异质化”角度出发,通过多种基因编码蛋白(Bcl-2／Bax,Cath-D和VEGF)在肠型胃癌和弥漫型胃癌中的表达,探讨二型胃癌不同生物学特性的分子学基础．方法:采用免疫组化SP法检测Bcl-2／Bax, cathepsin-D(Cath-D)和VEGF在胃癌及正常胃组织的表达．结果:Bcl-2／Bax,Cath-D和VEGF阳性表达率在胃癌组织中与癌旁正常胃黏膜组织中比较 (分别为44．59％ vs 27.30％;58．11％ vs 71．62％; 77．00％vs 21．60％;71．62％vs 14．86％)均有显著性差异(P<0．05),弥漫型胃癌中Bcl-2和 Cath-D阳性细胞指数明显高于肠型胃癌(分别为29．14±24．70 vs 19．80±27．37和52．59± 33．76 vs 29．21±39．67),而Bax阳性细胞指数 (分别为32．56±35．55 vs 47．74±27．43)明显低于肠型胃癌,差异均有显著性(P<0．05),VEGF 阳性细胞表达指数在不同胃癌浸润深度组间比较(早期胃癌7．13±15．81 vs 肌层浸润62．77 ±44．37 vs 浆膜浸润40．82±42．70)及有无淋巴结转移组间比较(42．05±42．61 vs 34．15± 42．52)有显著性差异(P<0．05)．结论:Bcl-2／Bax,Cath-D和VEGF分别参与了胃癌的发生,浸润进展和转移．二型胃癌在组织学发生相同的基础上由于在胃癌演进过程中有不同附加基因参与(Bcl-2／Bax和Cath-D), 使弥漫型胃癌获得了与肠型胃癌有所不同的亚克隆过程,因而表现为生物学特性的异质化．
