Alzheimer ’s disease(AD) is a leading cause of dementia in the elderly.Mitogen-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in AD.However,the molecular mechanisms underlying the effects ...Alzheimer ’s disease(AD) is a leading cause of dementia in the elderly.Mitogen-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in AD.However,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied.MicroRNAs(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA translation.Here,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model cells.We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation.More importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.展开更多
Strength theory is the basic theory for calculating and designing the strength of engineering materials in civil,hydraulic,mechanical,aerospace,military,and other engineering disciplines.Therefore,the comprehensive st...Strength theory is the basic theory for calculating and designing the strength of engineering materials in civil,hydraulic,mechanical,aerospace,military,and other engineering disciplines.Therefore,the comprehensive study of the generalized nonlinear strength theory(GNST)of geomaterials has significance for the construction of engineering rock strength.This paper reviews the GNST of geomaterials to demonstrate the research status of nonlinear strength characteristics of geomaterials under complex stress paths.First,it systematically summarizes the research progress of GNST(classical and empirical criteria).Then,the latest research the authors conducted over the past five years on the GNST is introduced,and a generalized three-dimensional(3D)nonlinear Hoek‒Brown(HB)criterion(NGHB criterion)is proposed for practical applications.This criterion can be degenerated into the existing three modified HB criteria and has a better prediction performance.The strength prediction errors for six rocks and two in-situ rock masses are 2.0724%-3.5091%and 1.0144%-3.2321%,respectively.Finally,the development and outlook of the GNST are expounded,and a new topic about the building strength index of rock mass and determining the strength of in-situ engineering rock mass is proposed.The summarization of the GNST provides theoretical traceability and optimization for constructing in-situ engineering rock mass strength.展开更多
Neuromorphic computing,inspired by the human brain,uses memristor devices for complex tasks.Recent studies show that self-organizing random nanowires can implement neuromorphic information processing,enabling data ana...Neuromorphic computing,inspired by the human brain,uses memristor devices for complex tasks.Recent studies show that self-organizing random nanowires can implement neuromorphic information processing,enabling data analysis.This paper presents a model based on these nanowire networks,with an improved conductance variation profile.We suggest using these networks for temporal information processing via a reservoir computing scheme and propose an efficient data encoding method using voltage pulses.The nanowire network layer generates dynamic behaviors for pulse voltages,allowing time series prediction analysis.Our experiment uses a double stochastic nanowire network architecture for processing multiple input signals,outperforming traditional reservoir computing in terms of fewer nodes,enriched dynamics and improved prediction accuracy.Experimental results confirm the high accuracy of this architecture on multiple real-time series datasets,making neuromorphic nanowire networks promising for physical implementation of reservoir computing.展开更多
In the realm of acoustic signal detection,the identification of weak signals,particularly in the presence of negative signal-to-noise ratios,poses a significant challenge.This challenge is further heightened when sign...In the realm of acoustic signal detection,the identification of weak signals,particularly in the presence of negative signal-to-noise ratios,poses a significant challenge.This challenge is further heightened when signals are acquired through fiber-optic hydrophones,as these signals often lack physical significance and resist clear systematic modeling.Conventional processing methods,e.g.,low-pass filter(LPF),require a thorough understanding of the effective signal bandwidth for noise reduction,and may introduce undesirable time lags.This paper introduces an innovative feedback control method with dual Kalman filters for the demodulation of phase signals with noises in fiber-optic hydrophones.A mathematical model of the closed-loop system is established to guide the design of the feedback control,aiming to achieve a balance with the input phase signal.The dual Kalman filters are instrumental in mitigating the effects of signal noise,observation noise,and control execution noise,thereby enabling precise estimation for the input phase signals.The effectiveness of this feedback control method is demonstrated through examples,showcasing the restoration of low-noise signals,negative signal-to-noise ratio signals,and multi-frequency signals.This research contributes to the technical advancement of high-performance devices,including fiber-optic hydrophones and phase-locked amplifiers.展开更多
基金supported by grants from the National Natural Science Foundation of China (32371030, 82371194, 82071395 and 82001158)the Natural Science Foundation of Chongqing(CSTB2022NSCQ-LZX0010 and cstc2021ycjh-bgzxm0186, China)+1 种基金the Scientific and Technological Innovation Project for the Construction of Chengdu-Chongqing Economic Circle (KJCX ZD2020021, China)CQMU Program for Youth Innovation in Future Medicine (W0044, China)
文摘Alzheimer ’s disease(AD) is a leading cause of dementia in the elderly.Mitogen-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in AD.However,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied.MicroRNAs(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA translation.Here,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model cells.We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation.More importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.
基金This research was financially supported by the National Natural Science Foundation of China(Nos.51934003,52334004)Yunnan Innovation Team(No.202105AE 160023)+2 种基金Major Science and Technology Special Project of Yunnan Province,China(No.202102AF080001)Yunnan Major Scientific and Technological Projects,China(No.202202AG050014)Key Laboratory of Geohazard Forecast and Geoecological Restoration in Plateau Mountainous Area,MNR,and Yunnan Key Laboratory of Geohazard Forecast and Geoecological Restoration in Plateau Mountainous Area.
文摘Strength theory is the basic theory for calculating and designing the strength of engineering materials in civil,hydraulic,mechanical,aerospace,military,and other engineering disciplines.Therefore,the comprehensive study of the generalized nonlinear strength theory(GNST)of geomaterials has significance for the construction of engineering rock strength.This paper reviews the GNST of geomaterials to demonstrate the research status of nonlinear strength characteristics of geomaterials under complex stress paths.First,it systematically summarizes the research progress of GNST(classical and empirical criteria).Then,the latest research the authors conducted over the past five years on the GNST is introduced,and a generalized three-dimensional(3D)nonlinear Hoek‒Brown(HB)criterion(NGHB criterion)is proposed for practical applications.This criterion can be degenerated into the existing three modified HB criteria and has a better prediction performance.The strength prediction errors for six rocks and two in-situ rock masses are 2.0724%-3.5091%and 1.0144%-3.2321%,respectively.Finally,the development and outlook of the GNST are expounded,and a new topic about the building strength index of rock mass and determining the strength of in-situ engineering rock mass is proposed.The summarization of the GNST provides theoretical traceability and optimization for constructing in-situ engineering rock mass strength.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. U20A20227,62076208, and 62076207)Chongqing Talent Plan “Contract System” Project (Grant No. CQYC20210302257)+3 种基金National Key Laboratory of Smart Vehicle Safety Technology Open Fund Project (Grant No. IVSTSKL-202309)the Chongqing Technology Innovation and Application Development Special Major Project (Grant No. CSTB2023TIAD-STX0020)College of Artificial Intelligence, Southwest UniversityState Key Laboratory of Intelligent Vehicle Safety Technology
文摘Neuromorphic computing,inspired by the human brain,uses memristor devices for complex tasks.Recent studies show that self-organizing random nanowires can implement neuromorphic information processing,enabling data analysis.This paper presents a model based on these nanowire networks,with an improved conductance variation profile.We suggest using these networks for temporal information processing via a reservoir computing scheme and propose an efficient data encoding method using voltage pulses.The nanowire network layer generates dynamic behaviors for pulse voltages,allowing time series prediction analysis.Our experiment uses a double stochastic nanowire network architecture for processing multiple input signals,outperforming traditional reservoir computing in terms of fewer nodes,enriched dynamics and improved prediction accuracy.Experimental results confirm the high accuracy of this architecture on multiple real-time series datasets,making neuromorphic nanowire networks promising for physical implementation of reservoir computing.
基金Project supported by the National Key Research and Development Program of China(No.2022YFB3203600)the National Natural Science Foundation of China(Nos.12172323,12132013+1 种基金12332003)the Zhejiang Provincial Natural Science Foundation of China(No.LZ22A020003)。
文摘In the realm of acoustic signal detection,the identification of weak signals,particularly in the presence of negative signal-to-noise ratios,poses a significant challenge.This challenge is further heightened when signals are acquired through fiber-optic hydrophones,as these signals often lack physical significance and resist clear systematic modeling.Conventional processing methods,e.g.,low-pass filter(LPF),require a thorough understanding of the effective signal bandwidth for noise reduction,and may introduce undesirable time lags.This paper introduces an innovative feedback control method with dual Kalman filters for the demodulation of phase signals with noises in fiber-optic hydrophones.A mathematical model of the closed-loop system is established to guide the design of the feedback control,aiming to achieve a balance with the input phase signal.The dual Kalman filters are instrumental in mitigating the effects of signal noise,observation noise,and control execution noise,thereby enabling precise estimation for the input phase signals.The effectiveness of this feedback control method is demonstrated through examples,showcasing the restoration of low-noise signals,negative signal-to-noise ratio signals,and multi-frequency signals.This research contributes to the technical advancement of high-performance devices,including fiber-optic hydrophones and phase-locked amplifiers.
