Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type ...Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.展开更多
典型海洋摇摆对压水堆堆芯的热工水力特性有显著影响,从而导致一回路腐蚀产物的沉积生长规律发生变化。本文基于数据交换方法,通过多尺度耦合建立反应堆一回路系统模型,将摇摆条件下的冷却剂流动数学模型和腐蚀产物沉积生长模型加入模拟...典型海洋摇摆对压水堆堆芯的热工水力特性有显著影响,从而导致一回路腐蚀产物的沉积生长规律发生变化。本文基于数据交换方法,通过多尺度耦合建立反应堆一回路系统模型,将摇摆条件下的冷却剂流动数学模型和腐蚀产物沉积生长模型加入模拟中,对摇摆条件下3×3棒束上腐蚀产物的生长过程进行了研究。结果表明,摇摆会导致冷却剂流速和棒外壁温发生周期性变化,流量脉动和温度波动会加剧摇摆切线方向上的剥蚀作用,削弱沉积过程。在轴向高度较低的通道截面上,靠近外围绝热壁面的棒表面上生长的多孔介质沉积层(Chalk River Unidentified Deposit,CRUD)最厚;在轴向高度较高的通道截面上,所有位置的棒上的CRUD分布规律趋于一致,并且在燃料棒周向的分布体现在极坐标系中呈现出趋近于椭圆形的规律。展开更多
Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder.The subtle and insidious onset of its pathogenesis makes early detection of a formidable challenge in both contemporary neuroscience and clin...Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder.The subtle and insidious onset of its pathogenesis makes early detection of a formidable challenge in both contemporary neuroscience and clinical practice.In this study,we introduce an advanced diagnostic methodology rooted in theMed-3D transfermodel and enhanced with an attention mechanism.We aim to improve the precision of AD diagnosis and facilitate its early identification.Initially,we employ a spatial normalization technique to address challenges like clarity degradation and unsaturation,which are commonly observed in imaging datasets.Subsequently,an attention mechanism is incorporated to selectively focus on the salient features within the imaging data.Building upon this foundation,we present the novelMed-3D transfermodel,designed to further elucidate and amplify the intricate features associated withADpathogenesis.Our proposedmodel has demonstrated promising results,achieving a classification accuracy of 92%.To emphasize the robustness and practicality of our approach,we introduce an adaptive‘hot-updating’auxiliary diagnostic system.This system not only enables continuous model training and optimization but also provides a dynamic platform to meet the real-time diagnostic and therapeutic demands of AD.展开更多
Over-production of nitric oxide is pathogenic for neuronal apoptosis around the ischemic area fol- lowing ischemic brain injury. In this study, an apoptotic model in rat hippocampal neurons was es- tablished by 0.5 mm...Over-production of nitric oxide is pathogenic for neuronal apoptosis around the ischemic area fol- lowing ischemic brain injury. In this study, an apoptotic model in rat hippocampal neurons was es- tablished by 0.5 mmol/L 3-morpholinosyndnomine （SIN-l）, a nitric oxide donor. The models were then cultured with 0.1 mmol/L of 4,4＇-diisothiocyanostilbene-2,2＇-disulfonic acid （DIDS; the chloride channel blocker）for 18 hours. Neuronal survival was detected using the 3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, and apoptosis was assayed by Hoechst 33342-labeled neuronal DNA fluorescence staining. Western blot analysis and immunochemilumi- nescence staining were applied to determine the changes of activated caspase-3 and CIC-3 channel proteins. Real-time PCR was used to detect the mRNA expression of CIC-3. The results showed that SIN-1 reduced the neuronal survival rate, induced neuronal apoptosis, and promoted CIC-3 chloride channel protein and mRNA expression in the apoptotic neurons. DIDS reversed the effect of SIN-I. Our findings indicate that the increased activities of the CIC-3 chloride channel may be involved in hippocampal neuronal apoptosis induced by nitric oxide.展开更多
Currently, numerical simulations of seismic channel waves for the advance detection of geological structures in coal mine roadways focus mainly on modeling two- dimensional wave fields and therefore cannot accurately ...Currently, numerical simulations of seismic channel waves for the advance detection of geological structures in coal mine roadways focus mainly on modeling two- dimensional wave fields and therefore cannot accurately simulate three-dimensional （3-D） full-wave fields or seismic records in a full-space observation system. In this study, we use the first-order velocity-stress staggered-grid finite difference algorithm to simulate 3-D full-wave fields with P-wave sources in front of coal mine roadways. We determine the three components of velocity Vx, Vy, and Vz for the same node in 3-D staggered-grid finite difference models by calculating the average value of Vy, and Vz of the nodes around the same node. We ascertain the wave patterns and their propagation characteristics in both symmetrical and asymmetric coal mine roadway models. Our simulation results indicate that the Rayleigh channel wave is stronger than the Love channel wave in front of the roadway face. The reflected Rayleigh waves from the roadway face are concentrated in the coal seam, release less energy to the roof and floor, and propagate for a longer distance. There are surface waves and refraction head waves around the roadway. In the seismic records, the Rayleigh wave energy is stronger than that of the Love channel wave along coal walls of the roadway, and the interference of the head waves and surface waves with the Rayleigh channel wave is weaker than with the Love channel wave. It is thus difficult to identify the Love channel wave in the seismic records. Increasing the depth of the receivers in the coal walls can effectively weaken the interference of surface waves with the Rayleigh channel wave, but cannot weaken the interference of surface waves with the Love channel wave. Our research results also suggest that the Love channel wave, which is often used to detect geological structures in coal mine stopes, is not suitable for detecting geological structures in front of coal mine roadways. Instead, the Rayleigh channel wave can be used for the advance detection of geological structures in coal mine roadways.展开更多
Previous studies have demonstrated that increased chloride channel activity plays a role in nitric oxide-induced neuronal apoptosis in the rat hippocampus. The present study investigated the effects of the broad-spect...Previous studies have demonstrated that increased chloride channel activity plays a role in nitric oxide-induced neuronal apoptosis in the rat hippocampus. The present study investigated the effects of the broad-spectrum calcium channel blocker CdCI2 on survival rate, percentage of apoptosis, and morphological changes in hippocampal neurons cultured in vitro, as well as the effects of calcium channels on neuronal apoptosis. The chloride channel blockers 4-acetamido-4＇-isothiocyanatostilbene-2, 2＇-disulfonic acid （SITS） or 4, 4＇-diisethiocyanostilbene-2, 2＇-disulfonic acid （DIDS） increased the survival rate of 3-morpholinosydnonimine （SIN-1）-treated neurons and suppressed SIN-l-induced neuronal apoptosis. The calcium channel blocker CdCI2 did not increase the survival rate of neurons and did not affect SIN-l-induced apoptosis or SITS- or DIDS-suppressed neuronal apoptosis. Results demonstrated that calcium channels did not significantly affect neuronal apoptosis.展开更多
In this paper, we study the low-complexity channel reconstruction methods for downlink precoding in massive multiple-Input multiple-Output(MIMO) systems. When the user is allocated less streams than the number of its ...In this paper, we study the low-complexity channel reconstruction methods for downlink precoding in massive multiple-Input multiple-Output(MIMO) systems. When the user is allocated less streams than the number of its antennas, the base station(BS) or user usually utilizes the singular value decomposition(SVD) to get the effective channels, whose dimension is equal to the number of streams. This process is called channel reconstruction and done in BS for time division duplex(TDD) mode. However, with the increasing of antennas in BS, the computation burden of SVD is getting incredible. Here, we propose a series of novel low-complexity channel reconstruction methods for downlink precoding in 3D spatial channel model. We consider different correlations between elevation and azimuth antennas, and divide the large dimensional matrix SVD into two kinds of small-size matrix SVD. The simulation results show that the proposed methods only produce less than 10% float computation than the traditional SVD zero-forcing(SVD-ZF) precoding method, while keeping nearly the same performance of 1Gbps.展开更多
Although previous studies have shown the neuroprotective effects of the adenosine triphosphate （ATP）-sensitive potassium （KATP） channel opener against ischemic neuronal damage, little is known about the mechanisms...Although previous studies have shown the neuroprotective effects of the adenosine triphosphate （ATP）-sensitive potassium （KATP） channel opener against ischemic neuronal damage, little is known about the mechanisms involved. Phosphatidylinositol-3 kinase （PI3K）/v-akt murine thy-moma viral oncogene homolog （Akt） and Bcl-2 are thought to be important factors that mediate neuroprotection. The present study investigated the effects of KATP openers on hypoxia-induced PC12 cell apoptosis, as well as mRNA and protein expression of Akt and Bcl-2. Results demon-strated that pretreatment of PC12 cells with pinacidil, a KATP opener, resulted in decreased PC12 cell apoptosis following hypoxia, as detected by Annexin-V fluorescein isothiocyanate/ propidium iodide double staining flow cytometry. In addition, mRNA and protein expression of phosphorylated Akt （p-Akt） and Bcl-2 increased, as detected by immunofluorescence, Western blot analysis, and reverse-transcription polymerase chain reaction. The protective effect of this preconditioning was attenuated by glipizide, a selective KATP blocker. These results demonstrate for the first time that the protective mechanisms of KATP openers on PC12 cell apoptosis following hypoxia could result from activation of the PI3K/Akt signaling pathway, which further activates expression of the downstream Bcl-2 gene.展开更多
Objective: To examine the effects of Tribulus terrestris L.(T. terrestris) extract on the modulation of calcium channels to evaluate its use in topical agents for treatment of atopic dermatitis.Methods: The 70% methan...Objective: To examine the effects of Tribulus terrestris L.(T. terrestris) extract on the modulation of calcium channels to evaluate its use in topical agents for treatment of atopic dermatitis.Methods: The 70% methanol extract of T. terrestris was prepared. Human HEK293 T cells with over-expressed calcium release-activated calcium channel protein 1(Orai1),transient receptor potential vanilloid 1, or transient receptor potential vanilloid 3(TRPV3)were treated with T. terrestris extract. Modulation of ion channels was measured using a conventional whole-cell patch-clamp technique.Results: T. terrestris extract(100 mg/m L) significantly inhibited Orai1 activity in Orai1-stromal interaction molecule 1 co-overexpressed HEK293 T cells. In addition, T. terrestris extract significantly increased the TRPV3 activity compared with 2-Aminoethyl diphenylborinate(100 mmol/L), which induces the full activation of TRPV3.Conclusions: Our results suggest that T. terrestris extract may have a therapeutic potential for recovery of abnormal skin barrier pathologies in atopic dermatitis through modulating the activities of calcium ion channels, Orai1 and TRPV3. This is the first study to report the modulatory effect of a medicinal plant on the function of ion channels in skin barrier.展开更多
基金supported by the Natural Science Foundation of Anhui Province of China,No.2208085Y32Scientific Research Plan Project of Anhui Province of China,No.2022AH020076the Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province,No.CXPJJH12000005-07-115(all to CT).
文摘Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.
文摘典型海洋摇摆对压水堆堆芯的热工水力特性有显著影响,从而导致一回路腐蚀产物的沉积生长规律发生变化。本文基于数据交换方法,通过多尺度耦合建立反应堆一回路系统模型,将摇摆条件下的冷却剂流动数学模型和腐蚀产物沉积生长模型加入模拟中,对摇摆条件下3×3棒束上腐蚀产物的生长过程进行了研究。结果表明,摇摆会导致冷却剂流速和棒外壁温发生周期性变化,流量脉动和温度波动会加剧摇摆切线方向上的剥蚀作用,削弱沉积过程。在轴向高度较低的通道截面上,靠近外围绝热壁面的棒表面上生长的多孔介质沉积层(Chalk River Unidentified Deposit,CRUD)最厚;在轴向高度较高的通道截面上,所有位置的棒上的CRUD分布规律趋于一致,并且在燃料棒周向的分布体现在极坐标系中呈现出趋近于椭圆形的规律。
基金funded by the National Natural Science Foundation of China(No.62076044)Scientific Research Foundation of Chongqing University of Technology(No.2020ZDZ015).
文摘Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder.The subtle and insidious onset of its pathogenesis makes early detection of a formidable challenge in both contemporary neuroscience and clinical practice.In this study,we introduce an advanced diagnostic methodology rooted in theMed-3D transfermodel and enhanced with an attention mechanism.We aim to improve the precision of AD diagnosis and facilitate its early identification.Initially,we employ a spatial normalization technique to address challenges like clarity degradation and unsaturation,which are commonly observed in imaging datasets.Subsequently,an attention mechanism is incorporated to selectively focus on the salient features within the imaging data.Building upon this foundation,we present the novelMed-3D transfermodel,designed to further elucidate and amplify the intricate features associated withADpathogenesis.Our proposedmodel has demonstrated promising results,achieving a classification accuracy of 92%.To emphasize the robustness and practicality of our approach,we introduce an adaptive‘hot-updating’auxiliary diagnostic system.This system not only enables continuous model training and optimization but also provides a dynamic platform to meet the real-time diagnostic and therapeutic demands of AD.
基金supported by the National Natural Science Foundation of China,No.81160157a grant from Guizhou Science and Technology Department in China,No.SY20093075Technological Talents Funds of Guizhou Province in China,No.201209
文摘Over-production of nitric oxide is pathogenic for neuronal apoptosis around the ischemic area fol- lowing ischemic brain injury. In this study, an apoptotic model in rat hippocampal neurons was es- tablished by 0.5 mmol/L 3-morpholinosyndnomine （SIN-l）, a nitric oxide donor. The models were then cultured with 0.1 mmol/L of 4,4＇-diisothiocyanostilbene-2,2＇-disulfonic acid （DIDS; the chloride channel blocker）for 18 hours. Neuronal survival was detected using the 3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, and apoptosis was assayed by Hoechst 33342-labeled neuronal DNA fluorescence staining. Western blot analysis and immunochemilumi- nescence staining were applied to determine the changes of activated caspase-3 and CIC-3 channel proteins. Real-time PCR was used to detect the mRNA expression of CIC-3. The results showed that SIN-1 reduced the neuronal survival rate, induced neuronal apoptosis, and promoted CIC-3 chloride channel protein and mRNA expression in the apoptotic neurons. DIDS reversed the effect of SIN-I. Our findings indicate that the increased activities of the CIC-3 chloride channel may be involved in hippocampal neuronal apoptosis induced by nitric oxide.
基金supported by National Natural Science Foundation of China(Nos.41204077,41372290,41572244,51034003,51174210,and 51304126)natural science foundation of Shandong Province(Nos.ZR2011EEZ002 and ZR2013EEQ019)State Key Research Development Program of China(No.2016YFC0600708-3)
文摘Currently, numerical simulations of seismic channel waves for the advance detection of geological structures in coal mine roadways focus mainly on modeling two- dimensional wave fields and therefore cannot accurately simulate three-dimensional （3-D） full-wave fields or seismic records in a full-space observation system. In this study, we use the first-order velocity-stress staggered-grid finite difference algorithm to simulate 3-D full-wave fields with P-wave sources in front of coal mine roadways. We determine the three components of velocity Vx, Vy, and Vz for the same node in 3-D staggered-grid finite difference models by calculating the average value of Vy, and Vz of the nodes around the same node. We ascertain the wave patterns and their propagation characteristics in both symmetrical and asymmetric coal mine roadway models. Our simulation results indicate that the Rayleigh channel wave is stronger than the Love channel wave in front of the roadway face. The reflected Rayleigh waves from the roadway face are concentrated in the coal seam, release less energy to the roof and floor, and propagate for a longer distance. There are surface waves and refraction head waves around the roadway. In the seismic records, the Rayleigh wave energy is stronger than that of the Love channel wave along coal walls of the roadway, and the interference of the head waves and surface waves with the Rayleigh channel wave is weaker than with the Love channel wave. It is thus difficult to identify the Love channel wave in the seismic records. Increasing the depth of the receivers in the coal walls can effectively weaken the interference of surface waves with the Rayleigh channel wave, but cannot weaken the interference of surface waves with the Love channel wave. Our research results also suggest that the Love channel wave, which is often used to detect geological structures in coal mine stopes, is not suitable for detecting geological structures in front of coal mine roadways. Instead, the Rayleigh channel wave can be used for the advance detection of geological structures in coal mine roadways.
基金Supported by the Science and Technology Department of Guizhou Province, No. C20072127, SY20093075the Science and Technology Department of Zhuhai City, No. PC20081010
文摘Previous studies have demonstrated that increased chloride channel activity plays a role in nitric oxide-induced neuronal apoptosis in the rat hippocampus. The present study investigated the effects of the broad-spectrum calcium channel blocker CdCI2 on survival rate, percentage of apoptosis, and morphological changes in hippocampal neurons cultured in vitro, as well as the effects of calcium channels on neuronal apoptosis. The chloride channel blockers 4-acetamido-4＇-isothiocyanatostilbene-2, 2＇-disulfonic acid （SITS） or 4, 4＇-diisethiocyanostilbene-2, 2＇-disulfonic acid （DIDS） increased the survival rate of 3-morpholinosydnonimine （SIN-1）-treated neurons and suppressed SIN-l-induced neuronal apoptosis. The calcium channel blocker CdCI2 did not increase the survival rate of neurons and did not affect SIN-l-induced apoptosis or SITS- or DIDS-suppressed neuronal apoptosis. Results demonstrated that calcium channels did not significantly affect neuronal apoptosis.
基金supported by the National High Technology Research and Development Program of China(863 Program)(Grant No.2014AA01A705)National Science and Technology Major Project of China(Grant No.2015ZX03001034)
文摘In this paper, we study the low-complexity channel reconstruction methods for downlink precoding in massive multiple-Input multiple-Output(MIMO) systems. When the user is allocated less streams than the number of its antennas, the base station(BS) or user usually utilizes the singular value decomposition(SVD) to get the effective channels, whose dimension is equal to the number of streams. This process is called channel reconstruction and done in BS for time division duplex(TDD) mode. However, with the increasing of antennas in BS, the computation burden of SVD is getting incredible. Here, we propose a series of novel low-complexity channel reconstruction methods for downlink precoding in 3D spatial channel model. We consider different correlations between elevation and azimuth antennas, and divide the large dimensional matrix SVD into two kinds of small-size matrix SVD. The simulation results show that the proposed methods only produce less than 10% float computation than the traditional SVD zero-forcing(SVD-ZF) precoding method, while keeping nearly the same performance of 1Gbps.
基金the Natural Science Foundation of Liaoning Province,No.20052097,2008225010
文摘Although previous studies have shown the neuroprotective effects of the adenosine triphosphate （ATP）-sensitive potassium （KATP） channel opener against ischemic neuronal damage, little is known about the mechanisms involved. Phosphatidylinositol-3 kinase （PI3K）/v-akt murine thy-moma viral oncogene homolog （Akt） and Bcl-2 are thought to be important factors that mediate neuroprotection. The present study investigated the effects of KATP openers on hypoxia-induced PC12 cell apoptosis, as well as mRNA and protein expression of Akt and Bcl-2. Results demon-strated that pretreatment of PC12 cells with pinacidil, a KATP opener, resulted in decreased PC12 cell apoptosis following hypoxia, as detected by Annexin-V fluorescein isothiocyanate/ propidium iodide double staining flow cytometry. In addition, mRNA and protein expression of phosphorylated Akt （p-Akt） and Bcl-2 increased, as detected by immunofluorescence, Western blot analysis, and reverse-transcription polymerase chain reaction. The protective effect of this preconditioning was attenuated by glipizide, a selective KATP blocker. These results demonstrate for the first time that the protective mechanisms of KATP openers on PC12 cell apoptosis following hypoxia could result from activation of the PI3K/Akt signaling pathway, which further activates expression of the downstream Bcl-2 gene.
基金Supported by the Convergence of Conventional Medicine and Traditional Koran Medicine R&D Program funded by the Ministry of Health&Welfare through the Korean Health Industry Development Institute(Grant No.HI15C0256)
文摘Objective: To examine the effects of Tribulus terrestris L.(T. terrestris) extract on the modulation of calcium channels to evaluate its use in topical agents for treatment of atopic dermatitis.Methods: The 70% methanol extract of T. terrestris was prepared. Human HEK293 T cells with over-expressed calcium release-activated calcium channel protein 1(Orai1),transient receptor potential vanilloid 1, or transient receptor potential vanilloid 3(TRPV3)were treated with T. terrestris extract. Modulation of ion channels was measured using a conventional whole-cell patch-clamp technique.Results: T. terrestris extract(100 mg/m L) significantly inhibited Orai1 activity in Orai1-stromal interaction molecule 1 co-overexpressed HEK293 T cells. In addition, T. terrestris extract significantly increased the TRPV3 activity compared with 2-Aminoethyl diphenylborinate(100 mmol/L), which induces the full activation of TRPV3.Conclusions: Our results suggest that T. terrestris extract may have a therapeutic potential for recovery of abnormal skin barrier pathologies in atopic dermatitis through modulating the activities of calcium ion channels, Orai1 and TRPV3. This is the first study to report the modulatory effect of a medicinal plant on the function of ion channels in skin barrier.
