Repressing iron overload ameliorates central poststroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke

Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic area.However,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea r.Here,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus neurons.Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central pain.However,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain symptoms.Moreover,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain rats.These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.

Brain-derived neurotrophic factor prevents beta-amyloid-induced apoptosis of pheochromocytoma cells by regulating Bax/Bcl-2 expression

Brain-derived neurotrophic factor was utilized in the present study to treat cell injury models induced by aggregated β-amyloid(25-35).Methylthiazolyldiphenyl-tetrazolium bromide assay and western blot analysis showed that brain-derived neurotrophic factor provided neuroprotection against cellular apoptosis by suppressing the decline in β-amyloid(25-35)-induced cell activity and the increasing ratio of Bax/Bcl-2.After treating pheochromocytoma cells with tyrosine kinase receptor B receptor inhibitor K252a,brain-derived neurotrophic factor reverses the above-mentioned changes.The experimental findings suggested that brain-derived neurotrophic factor prevented β-amyloid peptide-induced cellular apoptosis by modulating Bax/Bcl-2 expression,and this effect was associated with binding to the specific tyrosine kinase receptor B receptor.

S14G-humanin restored cellular homeostasis disturbed by amyloid-beta protein

Humanin is a potential therapeutic agent for Alzheimer's disease,and its derivative,S14G-humanin,is 1 000-fold stronger in its neuroprotective effect against Alzheimer's disease-relevant insults.Although effective,the detailed molecular mechanism through which S14G-humanin exerts its effects remains unclear.Data from this study showed that fibrillar amyloid-beta 40 disturbed cellular homeostasis through the cell membrane,increasing intracellular calcium,generating reactive oxygen species,and decreasing the mitochondrial membrane potential.S14G-humanin restored these responses.The results suggested that S14G-humanin blocked the effects of amyloid-beta 40 on the neuronal cell membrane,and restored the disturbed cellular homeostasis,thereby exerting a neuroprotective effect on hippocampal neurons.

Brain-derived neurotrophic factor protects PC12 cells from beta-amyloid-induced neurotoxicity through the tropomyosin-related kinase B receptor pathway

The present study utilized beta amyloid (Aβ)-induced cell apoptosis in PC12 cells as a cell model of Alzheimer's disease to investigate the interaction between brain-derived neurotrophic factor (BDNF) and the tropomyosin-related kinase B receptor. Results showed that Aβ(25-35) can reduce survival of PC12 cells and increase cleaved caspase-3 expression in PC12 cells. However, BDNF inhibited Aβ(25-35)-induced cytotoxicity and cleaved casapase-3 expression. Interestingly, pretreatment with the tropomyosin-related kinase receptor inhibitor K252a for 20 minutes prior to BDNF blocked the neuroprotective effect of BDNF on PC12 cells.

Charge trapping memory device based on the Ga2O3 films as trapping and blocking layer

We present a new charge trapping memory(CTM) device with the Au/Ga2O3/SiO2/Si structure, which is fabricated by using the magnetron sputtering, high-temperature annealing, and vacuum evaporation techniques. Transmission electron microscopy diagrams show that the thickness of the SiO2 tunneling layer can be controlled by the annealing temperature.When the devices are annealed at 760℃, the measured C-V hysteresis curves exhibit a maximum 6 V memory window under a ±13 V sweeping voltage. In addition, a slight degradation of the device voltage and capacitance indicates the robust retention properties of flat-band voltage and high/low state capacitance. These distinctive advantages are attributed to oxygen vacancies and inter-diffusion layers, which play a critical role in the charge trapping process.

MULTI-PARAMETER TIKHONOV REGULARIZATION FOR LINEAR ILL-POSED OPERATOR EQUATIONS

我们考虑解决线性提出病的操作员方程。基于多尺度的分解解决方案空格，我们为解决方程建议多参数规则化。我们为多参数规则化答案建立弱、强壮的集中定理。基于特徵函数分解，特别地，我们为与最佳的错误界限给一个规则化答案的多参数开发后验选择策略。多参数的几种实际选择被建议。我们也介绍数字实验示威外面在单个参数规则化上的经产妇米规则化的性能。

A DISCRETIZING LEVENBERG-MARQUARDT SCHEME FOR SOLVING NONLIEAR ILL-POSED INTEGRAL EQUATIONS

To reduce the computational cost,we propose a regularizing modified LevenbergMarquardt scheme via multiscale Galerkin method for solving nonlinear ill-posed problems.Convergence results for the regularizing modified Levenberg-Marquardt scheme for the solution of nonlinear ill-posed problems have been proved.Based on these results,we propose a modified heuristic parameter choice rule to terminate the regularizing modified Levenberg-Marquardt scheme.By imposing certain conditions on the noise,we derive optimal convergence rates on the approximate solution under special source conditions.Numerical results are presented to illustrate the performance of the regularizing modified Levenberg-Marquardt scheme under the modified heuristic parameter choice.