Alzheimer’s disease(AD)is the most prevalent neurodegenerative disorder worldwide,causing dementia and affecting millions of individuals.One prominent characteristic in the brains of AD patients is glucose hypometabo...Alzheimer’s disease(AD)is the most prevalent neurodegenerative disorder worldwide,causing dementia and affecting millions of individuals.One prominent characteristic in the brains of AD patients is glucose hypometabolism.In the context of galactose metabolism,intracellular glucose levels are heightened.Galactose mutarotase(GALM)plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion ofβ-D-galactose intoα-D-galactose(α-D-G).The latter is then converted into glucose-6-phosphate,improving glucose metabolism levels.However,the involvement of GALM in AD progression is still unclear.In the present study,we found that the expression of GALM was significantly increased in AD patients and model mice.Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein(APP)and APP-cleaving enzymes including a disintegrin and metalloprotease 10(ADAM10),β-site APP-cleaving enzyme 1(BACE1),and presenilin-1(PS1).Interestingly,genetic overexpression of GALM reduced APP and Aβdeposition by increasing the maturation of ADAM10,although it did not alter the expression of BACE1 and PS1.Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation(LTP)and spatial learning and memory in AD model mice.Importantly,directα-D-G(20 mg/kg,i.p.)also inhibited Aβdeposition by increasing the maturation of ADAM10,thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice.Taken together,our results indicate that GALM shifts APP processing towardsα-cleavage,preventing Aβgeneration by increasing the level of mature ADAM10.These findings indicate that GALM may be a potential therapeutic target for AD,andα-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.展开更多
锂电池健康状态(state of health,SoH)不仅直接影响荷电状态的准确估计,还关系到电池整个生命周期的安全运行,其精确估计是锂电池应用领域的核心问题。针对基于数据驱动的SoH估计方法存在泛化能力弱、估计精度低的不足,提出一种基于充...锂电池健康状态(state of health,SoH)不仅直接影响荷电状态的准确估计,还关系到电池整个生命周期的安全运行,其精确估计是锂电池应用领域的核心问题。针对基于数据驱动的SoH估计方法存在泛化能力弱、估计精度低的不足,提出一种基于充电曲线和改进反向传播(back propagation,BP)神经网络的锂电池SoH估计方法。首先,基于恒流充电曲线,设计等充电压差时间间隔(time interval for equal charging voltage difference,TI-ECVD)作为健康特征,以模拟随机恒流充电片段,简化SoH估计模型的输入参数。其次,结合BP网络结构简单的特点,在BP网络基础上加入遗传算法(genetic algorithm,GA)并引入莱文伯格-马夸特(levenberg-marquardt,LM)算法,提出GA-LM-BP网络结构,GA算法用以降低BP网络陷入局部最优解的概率,LM算法则用于提高BP网络的收敛速度。最后,基于自主实验平台测试数据搭建SoH估计模型,通过与同类型估计方法的对比分析,表明了所提估计方法在估计精度与运行速度方面的优势。展开更多
基金supported by grants from the National Natural Science Foundation of China(32371030,82371194,and 82071395)the Natural Science Foundation of Chongqing(CSTB2022NSCQ-LZX0010 and CSTB2024NSCQ-MSX0269)the CQMU Program for Youth Innovation in Future Medicine(W0044).
文摘Alzheimer’s disease(AD)is the most prevalent neurodegenerative disorder worldwide,causing dementia and affecting millions of individuals.One prominent characteristic in the brains of AD patients is glucose hypometabolism.In the context of galactose metabolism,intracellular glucose levels are heightened.Galactose mutarotase(GALM)plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion ofβ-D-galactose intoα-D-galactose(α-D-G).The latter is then converted into glucose-6-phosphate,improving glucose metabolism levels.However,the involvement of GALM in AD progression is still unclear.In the present study,we found that the expression of GALM was significantly increased in AD patients and model mice.Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein(APP)and APP-cleaving enzymes including a disintegrin and metalloprotease 10(ADAM10),β-site APP-cleaving enzyme 1(BACE1),and presenilin-1(PS1).Interestingly,genetic overexpression of GALM reduced APP and Aβdeposition by increasing the maturation of ADAM10,although it did not alter the expression of BACE1 and PS1.Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation(LTP)and spatial learning and memory in AD model mice.Importantly,directα-D-G(20 mg/kg,i.p.)also inhibited Aβdeposition by increasing the maturation of ADAM10,thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice.Taken together,our results indicate that GALM shifts APP processing towardsα-cleavage,preventing Aβgeneration by increasing the level of mature ADAM10.These findings indicate that GALM may be a potential therapeutic target for AD,andα-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
文摘锂电池健康状态(state of health,SoH)不仅直接影响荷电状态的准确估计,还关系到电池整个生命周期的安全运行,其精确估计是锂电池应用领域的核心问题。针对基于数据驱动的SoH估计方法存在泛化能力弱、估计精度低的不足,提出一种基于充电曲线和改进反向传播(back propagation,BP)神经网络的锂电池SoH估计方法。首先,基于恒流充电曲线,设计等充电压差时间间隔(time interval for equal charging voltage difference,TI-ECVD)作为健康特征,以模拟随机恒流充电片段,简化SoH估计模型的输入参数。其次,结合BP网络结构简单的特点,在BP网络基础上加入遗传算法(genetic algorithm,GA)并引入莱文伯格-马夸特(levenberg-marquardt,LM)算法,提出GA-LM-BP网络结构,GA算法用以降低BP网络陷入局部最优解的概率,LM算法则用于提高BP网络的收敛速度。最后,基于自主实验平台测试数据搭建SoH估计模型,通过与同类型估计方法的对比分析,表明了所提估计方法在估计精度与运行速度方面的优势。
