The aldo-keto reductase 1B(AKR1B)subfamily was initially known for its association with the pathogenesis of secondary diabetic complications such as retinopathy,neuropathy,nephropathy,and cataracts.Unfortunately,over ...The aldo-keto reductase 1B(AKR1B)subfamily was initially known for its association with the pathogenesis of secondary diabetic complications such as retinopathy,neuropathy,nephropathy,and cataracts.Unfortunately,over the past few decades,all drug development efforts targeting this family have failed for one reason or another.Recently,a growing body of evidence showing the deep involvement of AKR1B in metabolic reprogramming and production of signaling metabolites has led to a re-evaluation of their role in the pathogenesis of several immunometabolism-related diseases,such as gastrointestinal diseases,psoriasis,congenital disorders of glycosylation,carcinogenesis,even progression,and acquired chemoresistance.Therefore,in this review,we will summarize the current knowledge of AKR1B,highlighting their potential function in regulating immune cell function and then inflammatory complications.We will also explore how discovering this new insight into this old enzyme is essential for envisioning potential therapeutic strategies to prevent or treat inflammatory diseases.展开更多
Experimental and theoretical studies have reported that the precise firing of neurons is crucial for sensory representation.Autapse serves as a special synapse connecting neuron and itself,which has also been found to...Experimental and theoretical studies have reported that the precise firing of neurons is crucial for sensory representation.Autapse serves as a special synapse connecting neuron and itself,which has also been found to improve the accuracy of neuronal response.In current work,the effect of autaptic delay signal on the spike-timing precision is investigated on a single autaptic Hodgkin–Huxley neuron in the present of noise.The simulation results show that both excitatory and inhibitory autaptic signals can effectively adjust the precise spike time of neurons with noise by choosing the appropriate coupling strength g and time delay of autaptic signalτ.The g–τparameter space is divided into two regions:one is the region where the spike-timing precision is effectively regulated;the other is the region where the neuronal firing is almost not regulated.For the excitatory and inhibitory autapse,the range of parameters causing the accuracy of neuronal firing is different.Moreover,it is also found that the mechanisms of the spike-timing precision regulation are different for the two kinds of autaptic signals.展开更多
基金supported by grants from the National Key Research and Development Program of China(2022YFC2303504)the National Natural Science Foundation of China(92157106,32270917,82003361)+2 种基金the Shanghai Municipal Sci-ence and Technology Major Project(2019SHZDZX02)the Shanghai Committee of Science and Technology,China(22ZR1469900)supported by Youth Innovation Promo-tion Association of CAS,China(YIPA2023291).
文摘The aldo-keto reductase 1B(AKR1B)subfamily was initially known for its association with the pathogenesis of secondary diabetic complications such as retinopathy,neuropathy,nephropathy,and cataracts.Unfortunately,over the past few decades,all drug development efforts targeting this family have failed for one reason or another.Recently,a growing body of evidence showing the deep involvement of AKR1B in metabolic reprogramming and production of signaling metabolites has led to a re-evaluation of their role in the pathogenesis of several immunometabolism-related diseases,such as gastrointestinal diseases,psoriasis,congenital disorders of glycosylation,carcinogenesis,even progression,and acquired chemoresistance.Therefore,in this review,we will summarize the current knowledge of AKR1B,highlighting their potential function in regulating immune cell function and then inflammatory complications.We will also explore how discovering this new insight into this old enzyme is essential for envisioning potential therapeutic strategies to prevent or treat inflammatory diseases.
基金the Fundamental Research Funds for the Central Universities,China(Grant No.GK201903020)the National Natural Science Foundation of China(Grant No.12005006)Scientific research project of Education Department of Gansu Province,China(Grant No.2016A-049).
文摘Experimental and theoretical studies have reported that the precise firing of neurons is crucial for sensory representation.Autapse serves as a special synapse connecting neuron and itself,which has also been found to improve the accuracy of neuronal response.In current work,the effect of autaptic delay signal on the spike-timing precision is investigated on a single autaptic Hodgkin–Huxley neuron in the present of noise.The simulation results show that both excitatory and inhibitory autaptic signals can effectively adjust the precise spike time of neurons with noise by choosing the appropriate coupling strength g and time delay of autaptic signalτ.The g–τparameter space is divided into two regions:one is the region where the spike-timing precision is effectively regulated;the other is the region where the neuronal firing is almost not regulated.For the excitatory and inhibitory autapse,the range of parameters causing the accuracy of neuronal firing is different.Moreover,it is also found that the mechanisms of the spike-timing precision regulation are different for the two kinds of autaptic signals.