This paper proposes a relay selection scheme based on geometric optimum principle to maximize the cognitive link' s connectivity with limited interference to primary user in cooperative cognitive systems. A dual-hop ...This paper proposes a relay selection scheme based on geometric optimum principle to maximize the cognitive link' s connectivity with limited interference to primary user in cooperative cognitive systems. A dual-hop cognitive relay system is considered, in which the channel impulse response follows independent non-identical distribution (i. n. d. ) each hop, such as Rician, Rayleigh and Nakagami-m distribution. Then, closed-form expressions in terms of outage probability and average bit error rate (ABER) are obtained using amplify-and-forward (AF) relaying protocol over such mixed fading channels. Furthermore, the best range of the relay is derived. Extensive simulation re- suits are conducted to verify the theoretical analysis, which is useful to the network optimal design.展开更多
The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNA...The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.展开更多
The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent bu...The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.展开更多
Background:There is mounting evidence that regular physical activity is an important prerequisite for healthy cognitive aging.Consequently,the finding that almost one-third of the adult population does not reach the r...Background:There is mounting evidence that regular physical activity is an important prerequisite for healthy cognitive aging.Consequently,the finding that almost one-third of the adult population does not reach the recommended level of regular physical activity calls for further public health actions.In this context,digital and home-based physical training interventions might be a promising alternative to center-based intervention programs.Thus,this systematic review aimed to summarize the current state of the literature on the effects of digital and home-based physical training interventions on adult cognitive performance.Methods:In this pre-registered systematic review(PROSPERO;ID:CRD42022320031),5 electronic databases(PubMed,Web of Science,Psyclnfo,SPORTDiscus,and Cochrane Library)were searched by 2 independent researchers(FH and PT)to identify eligible studies investigating the effects of digital and home-based physical training interventions on cognitive performance in adults.The systematic literature search yielded 8258 records(extra17 records from other sources),of which 27 controlled trials were considered relevant.Two reviewers(FH and PT)independently extracted data and assessed the risk of bias using a modified version of the Tool for the assEssment of Study qualiTy and reporting in EXercise(TESTEX scale).Results:Of the 27 reviewed studies,15 reported positive effects on cognitive and motor-cognitive outcomes(i.e.,performance improvements in measures of executive functions,working memory,and choice stepping reaction test),and a considerable heterogeneity concerning study-related,population-related,and intervention-related characteristics was noticed.A more detailed analysis suggests that,in particular,interventions using online classes and technology-based exercise devices(i.e.,step-based exergames)can improve cognitive performance in healthy older adults.Approximately one-half of the reviewed studies were rated as having a high risk of bias with respect to completion adherence(≤85%)and monitoring of the level of regular physical activity in the control group.Conclusion:The current state of evidence concerning the effectiveness of digital and home-based physical training interventions is mixed overall,though there is limited evidence that specific types of digital and home-based physical training interventions(e.g.,online classes and step-based exergames)can be an effective strategy for improving cognitive performance in older adults.However,due to the limited number of available studies,future high-quality studies are needed to buttress this assumption empirically and to allow for more solid and nuanced conclusions.展开更多
In this paper,we propose the Two-way Deep Reinforcement Learning(DRL)-Based resource allocation algorithm,which solves the problem of resource allocation in the cognitive downlink network based on the underlay mode.Se...In this paper,we propose the Two-way Deep Reinforcement Learning(DRL)-Based resource allocation algorithm,which solves the problem of resource allocation in the cognitive downlink network based on the underlay mode.Secondary users(SUs)in the cognitive network are multiplexed by a new Power Domain Sparse Code Multiple Access(PD-SCMA)scheme,and the physical resources of the cognitive base station are virtualized into two types of slices:enhanced mobile broadband(eMBB)slice and ultrareliable low latency communication(URLLC)slice.We design the Double Deep Q Network(DDQN)network output the optimal codebook assignment scheme and simultaneously use the Deep Deterministic Policy Gradient(DDPG)network output the optimal power allocation scheme.The objective is to jointly optimize the spectral efficiency of the system and the Quality of Service(QoS)of SUs.Simulation results show that the proposed algorithm outperforms the CNDDQN algorithm and modified JEERA algorithm in terms of spectral efficiency and QoS satisfaction.Additionally,compared with the Power Domain Non-orthogonal Multiple Access(PD-NOMA)slices and the Sparse Code Multiple Access(SCMA)slices,the PD-SCMA slices can dramatically enhance spectral efficiency and increase the number of accessible users.展开更多
Introduction: Prostate cancer (PCa) is the third most prevalent cancer among Malaysian males, often diagnosed at advanced stages, leading to suboptimal outcomes. While transrectal ultrasound-guided systematic biopsy (...Introduction: Prostate cancer (PCa) is the third most prevalent cancer among Malaysian males, often diagnosed at advanced stages, leading to suboptimal outcomes. While transrectal ultrasound-guided systematic biopsy (TRUS-SB) is the primary diagnostic method, prebiopsy multiparametric magnetic resonance imaging (mpMRI) is gaining popularity in identifying suspicious lesions. This study addresses the lack of comprehensive investigations into the efficacy of cognitive registration TRUS targeted biopsy (COG-TB) compared to conventional TRUS-SB, considering the resource limitations of the Malaysian healthcare system. Materials and Methods: A retrospective cohort study was conducted in two Malaysian healthcare facilities. 116 adult patients with a prostate-specific antigen (PSA) level of more than 4 ng/mL who underwent both COG-TB and TRUS-SB between October 2020 and March 2022 were included. Primary outcomes were cancer detection rate and histopathological outcomes, including Gleason score. Results: COG-TB showed a higher overall cancer detection rate (50%) compared to TRUS-SB (44%). Clinically significant cancer detection rates were similar between COG-TB and TRUS-SB (37.1%). Further analysis revealed that both COG-TB and TRUS-SB detected clinically significant cancer in 30.2% of patients, did not detect it in 56.0%, and had conflicting findings in 16 patients (p Conclusion: COG-TB and TRUS-SB have comparable detection rates for clinically significant prostate cancer, with COG-TB showing a higher tendency to detect insignificant prostate cancer. Further studies comparing these methods are warranted.展开更多
Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s dis...Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.展开更多
Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,sub...Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).展开更多
Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension a...Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.展开更多
Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its appl...Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.展开更多
To solve the problem of the low interference success rate of air defense missile radio fuzes due to the unified interference form of the traditional fuze interference system,an interference decision method based Q-lea...To solve the problem of the low interference success rate of air defense missile radio fuzes due to the unified interference form of the traditional fuze interference system,an interference decision method based Q-learning algorithm is proposed.First,dividing the distance between the missile and the target into multiple states to increase the quantity of state spaces.Second,a multidimensional motion space is utilized,and the search range of which changes with the distance of the projectile,to select parameters and minimize the amount of ineffective interference parameters.The interference effect is determined by detecting whether the fuze signal disappears.Finally,a weighted reward function is used to determine the reward value based on the range state,output power,and parameter quantity information of the interference form.The effectiveness of the proposed method in selecting the range of motion space parameters and designing the discrimination degree of the reward function has been verified through offline experiments involving full-range missile rendezvous.The optimal interference form for each distance state has been obtained.Compared with the single-interference decision method,the proposed decision method can effectively improve the success rate of interference.展开更多
BACKGROUND The aging of the population has become increasingly obvious in recent years,and the incidence of cerebral infarction has shown an increasing trend annually,with high death and disability rates.AIM To analyz...BACKGROUND The aging of the population has become increasingly obvious in recent years,and the incidence of cerebral infarction has shown an increasing trend annually,with high death and disability rates.AIM To analyze the effects of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction.METHODS Between January 2020 and December 2023,we treated 98 cases of elderly acute insula,patients with cerebral infarction in the cerebral infarction acute phase(3-4 weeks)and for the course of 6 months in Montreal Cognitive Assessment Scale(MoCA)for screening of cognition.Notably,58 and 40 patients were placed in the cognitive impairment group and without-cognitive impairment group,respec-tively.In patients with cerebral infarction,magnetic resonance imaging was used to screen and clearly analyze the MoCA scores of two groups of patients with different infarctions,the relationship between the parts of the infarction volume,and analysis of acute insula cognitive disorder in elderly patients with cerebral RESULTS The number of patients with cognitive impairment in the basal ganglia and thalamus was significantly higher than that without cognitive impairment(P<0.05).The total infarct volume in the cognitive impairment group was higher than that in the non-cognitive impairment group,and the difference was statistically significant(P<0.05).The infarct volumes at different sites in the cognitive impairment group was higher than in the non-cognitive impairment group(P<0.05).In the cognitive impairment group,the infarct volumes in the basal ganglia,thalamus,and mixed lesions were negatively correlated with the total MoCA score,with correlation coefficients of-0.67,-0.73,and-0.77,respectively.CONCLUSION In elderly patients with acute insular infarction,infarction in the basal ganglia,thalamus,and mixed lesions were more likely to lead to cognitive dysfunction than in other areas,and patients with large infarct volumes were more likely to develop cognitive dysfunction.The infarct volume in the basal ganglia,thalamus,and mixed lesions was significantly negatively correlated with the MoCA score.展开更多
BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To i...BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.展开更多
The optimization of cognitive radio(CR)system using an enhanced firefly algorithm(EFA)is presented in this work.The Firefly algorithm(FA)is a nature-inspired algorithm based on the unique light-flashing behavior of fi...The optimization of cognitive radio(CR)system using an enhanced firefly algorithm(EFA)is presented in this work.The Firefly algorithm(FA)is a nature-inspired algorithm based on the unique light-flashing behavior of fireflies.It has already proved its competence in various optimization prob-lems,but it suffers from slow convergence issues.To improve the convergence performance of FA,a new variant named EFA is proposed.The effectiveness of EFA as a good optimizer is demonstrated by optimizing benchmark functions,and simulation results show its superior performance compared to biogeography-based optimization(BBO),bat algorithm,artificial bee colony,and FA.As an application of this algorithm to real-world problems,EFA is also applied to optimize the CR system.CR is a revolutionary technique that uses a dynamic spectrum allocation strategy to solve the spectrum scarcity problem.However,it requires optimization to meet specific performance objectives.The results obtained by EFA in CR system optimization are compared with results in the literature of BBO,simulated annealing,and genetic algorithm.Statistical results further prove that the proposed algorithm is highly efficient and provides superior results.展开更多
Intelligent reflecting surface(IRS)has been widely regarded as a promising technology for configuring wireless propagation environments.In this paper,we utilize IRS to assist transmission of a secondary user(SU)in a c...Intelligent reflecting surface(IRS)has been widely regarded as a promising technology for configuring wireless propagation environments.In this paper,we utilize IRS to assist transmission of a secondary user(SU)in a cognitive radio-inspired rate-splitting multiple access(CR-RSMA)system in which a primary user's(PU's)quality of service(QoS)requirements must be guaranteed.Without introducing intolerable interference to deteriorate the PU's outage performance,the SU conducts rate-splitting to transmit its signal to the base-station through the direct link and IRS reflecting channels.For the IRS-assisted CR-RSMA(IRS-CR-RSMA)scheme,we derive the optimal transmit power allocation,target rate allocation,and successive interference cancellation decoding order to enhance the outage performance of the SU.The closed-form expression for the SU's outage probability achieved by the IRS-CR-RSMA scheme is derived.Various simulation results are presented to clarify the enhanced outage performance achieved by the proposed IRS-CR-RSMA scheme over the CR-RSMA scheme.展开更多
There are abundant research results related to cognitive radio systems (CR systems), but using queueing models to portray CR systems is a new research trend. In this paper, a single-server retrial cognitive radio syst...There are abundant research results related to cognitive radio systems (CR systems), but using queueing models to portray CR systems is a new research trend. In this paper, a single-server retrial cognitive radio system with a linear retrial rate has been considered. The system has two types of users: primary users and secondary users. Secondary users have no effect on primary users because primary users have preemptive precedence. As a result, our purpose is to examine some performance indicators such as the expected queue length for primary users, the probability of the system being idle or occupied by a secondary user, and the probability of the system being busy. This paper begins by deriving the expressions for the generating functions based on the balance equations, so that we can calculate our goal conveniently.展开更多
Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function....Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.展开更多
Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that c...Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.展开更多
Background:One of the pathological hallmarks distinguishing Alzheimer’s disease from other dementias is the accumulation of amyloid beta(Aβ).Higher physical activity is associated with decreased dementia risk,and on...Background:One of the pathological hallmarks distinguishing Alzheimer’s disease from other dementias is the accumulation of amyloid beta(Aβ).Higher physical activity is associated with decreased dementia risk,and one potential path could be through Aβlevels modulation.We aimed to explore the relationship between physical activity and Aβin middle-aged and older adults.Methods:A systematic search of PubMed,Web of Science,PsycINFO,Cochrane Central Register of Controlled Trials,and SPORTDiscus was performed from inception to April 28,2022.Studies were eligible if they included physical activity and Aβdata in adults aged 45 years or older.Multi-level metaanalyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβlevels.Results:In total,37 articles were included(8 randomized controlled trials,3 non-randomized controlled trials,4 prospective longitudinal studies,and 22 cross-sectional studies).The overall effect size of physical activity interventions on changes in blood Aβwas medium(pooled standardized mean difference=-0.69,95%confidence interval(95%CI):-1.41 to 0.03;I^(2)=74.6%).However,these results were not statistically significant,and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid(CSF)and brain Aβ.Data from observational studies were examined based on measurements of Aβin the brain using positron emission tomography scans,CSF,and blood.Higher physical activity was positively associated with Aβonly in the CSF(Estimate r=0.12;95%CI:0.05-0.18;I^(2)=38.00%).Conclusion:Physical activity might moderately reduce blood Aβin middle-aged and older adults.However,results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies.In observational studies,higher levels of physical activity were positively associated with Aβonly in CSF.Therefore,further research is needed to understand the modulating role of physical activity in the brain,CSF,and blood Aβ,as well as its implication for cognitive health.展开更多
In this work,we investigate the covert communication in cognitive radio(CR)networks with the existence of multiple cognitive jammers(CJs).Specifically,the secondary transmitter(ST)helps the primary transmitter(PT)to r...In this work,we investigate the covert communication in cognitive radio(CR)networks with the existence of multiple cognitive jammers(CJs).Specifically,the secondary transmitter(ST)helps the primary transmitter(PT)to relay information to primary receiver(PR),as a reward,the ST can use PT's spectrum to transmit private information against the eavesdropper(Eve)under the help of one selected cognitive jammer(CJ).Meanwhile,we propose three jammer-selection schemes,namely,link-oriented jammer selection(LJS),min-max jammer selection(MMJS)and random jammer selection(RJS).For each scheme,we analyze the average covert throughput(ACT)and covert outage probability(COP).Our simulation results show that CJ is helpful to ST's covert communication,the expected minimum detection error probability and ACT can be significantly improved with the increase of false alarm of CJ.Moreover,the LJS scheme achieves best performance in ACT and COP,followed by RJS scheme,and MMJS scheme shows the worst performance.展开更多
基金Supported by the National Natural Science Foundation of China(No.61271184)New Century Excellent Talents in University(NCET-110594)Fundamental Research Funds for the Central Universities(No.2013RC1001)
文摘This paper proposes a relay selection scheme based on geometric optimum principle to maximize the cognitive link' s connectivity with limited interference to primary user in cooperative cognitive systems. A dual-hop cognitive relay system is considered, in which the channel impulse response follows independent non-identical distribution (i. n. d. ) each hop, such as Rician, Rayleigh and Nakagami-m distribution. Then, closed-form expressions in terms of outage probability and average bit error rate (ABER) are obtained using amplify-and-forward (AF) relaying protocol over such mixed fading channels. Furthermore, the best range of the relay is derived. Extensive simulation re- suits are conducted to verify the theoretical analysis, which is useful to the network optimal design.
基金funded by Notingham University and the Neuroscience Support Group Charity,UK(to HMK)supported by a CONACYT PhD scholarshipMD?was supported by the Postdoctoral Research Fellowship Program of TUBITAK。
文摘The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.
基金supported by the National Natural Science Foundation of China,No.82071419Key Research and Development Program of Guangzhou,No.202206010086+1 种基金High-level Hospital Construction Project,No.DFJH201907Supporting Research Funds for Outstanding Young Medical Talents in Guangdong Province,No.KJ012019442(all to YZ)。
文摘The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.
文摘Background:There is mounting evidence that regular physical activity is an important prerequisite for healthy cognitive aging.Consequently,the finding that almost one-third of the adult population does not reach the recommended level of regular physical activity calls for further public health actions.In this context,digital and home-based physical training interventions might be a promising alternative to center-based intervention programs.Thus,this systematic review aimed to summarize the current state of the literature on the effects of digital and home-based physical training interventions on adult cognitive performance.Methods:In this pre-registered systematic review(PROSPERO;ID:CRD42022320031),5 electronic databases(PubMed,Web of Science,Psyclnfo,SPORTDiscus,and Cochrane Library)were searched by 2 independent researchers(FH and PT)to identify eligible studies investigating the effects of digital and home-based physical training interventions on cognitive performance in adults.The systematic literature search yielded 8258 records(extra17 records from other sources),of which 27 controlled trials were considered relevant.Two reviewers(FH and PT)independently extracted data and assessed the risk of bias using a modified version of the Tool for the assEssment of Study qualiTy and reporting in EXercise(TESTEX scale).Results:Of the 27 reviewed studies,15 reported positive effects on cognitive and motor-cognitive outcomes(i.e.,performance improvements in measures of executive functions,working memory,and choice stepping reaction test),and a considerable heterogeneity concerning study-related,population-related,and intervention-related characteristics was noticed.A more detailed analysis suggests that,in particular,interventions using online classes and technology-based exercise devices(i.e.,step-based exergames)can improve cognitive performance in healthy older adults.Approximately one-half of the reviewed studies were rated as having a high risk of bias with respect to completion adherence(≤85%)and monitoring of the level of regular physical activity in the control group.Conclusion:The current state of evidence concerning the effectiveness of digital and home-based physical training interventions is mixed overall,though there is limited evidence that specific types of digital and home-based physical training interventions(e.g.,online classes and step-based exergames)can be an effective strategy for improving cognitive performance in older adults.However,due to the limited number of available studies,future high-quality studies are needed to buttress this assumption empirically and to allow for more solid and nuanced conclusions.
基金supported by the National Natural Science Foundation of China(Grant No.61971057).
文摘In this paper,we propose the Two-way Deep Reinforcement Learning(DRL)-Based resource allocation algorithm,which solves the problem of resource allocation in the cognitive downlink network based on the underlay mode.Secondary users(SUs)in the cognitive network are multiplexed by a new Power Domain Sparse Code Multiple Access(PD-SCMA)scheme,and the physical resources of the cognitive base station are virtualized into two types of slices:enhanced mobile broadband(eMBB)slice and ultrareliable low latency communication(URLLC)slice.We design the Double Deep Q Network(DDQN)network output the optimal codebook assignment scheme and simultaneously use the Deep Deterministic Policy Gradient(DDPG)network output the optimal power allocation scheme.The objective is to jointly optimize the spectral efficiency of the system and the Quality of Service(QoS)of SUs.Simulation results show that the proposed algorithm outperforms the CNDDQN algorithm and modified JEERA algorithm in terms of spectral efficiency and QoS satisfaction.Additionally,compared with the Power Domain Non-orthogonal Multiple Access(PD-NOMA)slices and the Sparse Code Multiple Access(SCMA)slices,the PD-SCMA slices can dramatically enhance spectral efficiency and increase the number of accessible users.
文摘Introduction: Prostate cancer (PCa) is the third most prevalent cancer among Malaysian males, often diagnosed at advanced stages, leading to suboptimal outcomes. While transrectal ultrasound-guided systematic biopsy (TRUS-SB) is the primary diagnostic method, prebiopsy multiparametric magnetic resonance imaging (mpMRI) is gaining popularity in identifying suspicious lesions. This study addresses the lack of comprehensive investigations into the efficacy of cognitive registration TRUS targeted biopsy (COG-TB) compared to conventional TRUS-SB, considering the resource limitations of the Malaysian healthcare system. Materials and Methods: A retrospective cohort study was conducted in two Malaysian healthcare facilities. 116 adult patients with a prostate-specific antigen (PSA) level of more than 4 ng/mL who underwent both COG-TB and TRUS-SB between October 2020 and March 2022 were included. Primary outcomes were cancer detection rate and histopathological outcomes, including Gleason score. Results: COG-TB showed a higher overall cancer detection rate (50%) compared to TRUS-SB (44%). Clinically significant cancer detection rates were similar between COG-TB and TRUS-SB (37.1%). Further analysis revealed that both COG-TB and TRUS-SB detected clinically significant cancer in 30.2% of patients, did not detect it in 56.0%, and had conflicting findings in 16 patients (p Conclusion: COG-TB and TRUS-SB have comparable detection rates for clinically significant prostate cancer, with COG-TB showing a higher tendency to detect insignificant prostate cancer. Further studies comparing these methods are warranted.
基金supported in parts by the National Natural Science Foundation of China,Nos.82101501(to QF),and 82201589(to XH)。
文摘Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.
基金supported by the National Natural Science Foundation of China,Nos.82271222(to ZL),81971012(to ZL),82071189(to XG),and 82201335(to YL)Key Clinical Projects of Peking University Third Hospital,No.BYSYZD2019027(to ZL)。
文摘Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).
基金supported by the National Natural Science Foundation of China,Nos.82274611 (to LZ),82104419 (to DM)Capital Science and Technology Leading Talent Training Project,No.Z1 91100006119017 (to LZ)+3 种基金Beijing Hospitals Authority Ascent Plan,No.DFL20190803 (to LZ)Cultivation Fund of Hospital Management Center in Beijing,No.PZ2022006 (to DM)R&D Program of Beijing Municipal Education Commission,No.KM202210025017 (to DM)Beijing Gold-Bridge Project,No.ZZ20145 (to DM)。
文摘Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.
基金supported by STI2030-Major Projects,No.2022ZD0207600 (to LZ)the National Natural Science Foundation of China,Nos.821 71446 (to JY),U22A20301 (to KFS),32070955 (to LZ)+1 种基金Guangdong Basic and Applied Basic Research Foundation,No.202381515040015 (to LZ)Science and Technology Program of Guangzhou of China,No.202007030012 (to KFS and LZ)
文摘Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.
基金National Natural Science Foundation of China(61973037)National 173 Program Project(2019-JCJQ-ZD-324).
文摘To solve the problem of the low interference success rate of air defense missile radio fuzes due to the unified interference form of the traditional fuze interference system,an interference decision method based Q-learning algorithm is proposed.First,dividing the distance between the missile and the target into multiple states to increase the quantity of state spaces.Second,a multidimensional motion space is utilized,and the search range of which changes with the distance of the projectile,to select parameters and minimize the amount of ineffective interference parameters.The interference effect is determined by detecting whether the fuze signal disappears.Finally,a weighted reward function is used to determine the reward value based on the range state,output power,and parameter quantity information of the interference form.The effectiveness of the proposed method in selecting the range of motion space parameters and designing the discrimination degree of the reward function has been verified through offline experiments involving full-range missile rendezvous.The optimal interference form for each distance state has been obtained.Compared with the single-interference decision method,the proposed decision method can effectively improve the success rate of interference.
基金Zhangjiakou City Science and Technology Bureau Municipal Science and Technology Plan Project,No.2121136D.
文摘BACKGROUND The aging of the population has become increasingly obvious in recent years,and the incidence of cerebral infarction has shown an increasing trend annually,with high death and disability rates.AIM To analyze the effects of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction.METHODS Between January 2020 and December 2023,we treated 98 cases of elderly acute insula,patients with cerebral infarction in the cerebral infarction acute phase(3-4 weeks)and for the course of 6 months in Montreal Cognitive Assessment Scale(MoCA)for screening of cognition.Notably,58 and 40 patients were placed in the cognitive impairment group and without-cognitive impairment group,respec-tively.In patients with cerebral infarction,magnetic resonance imaging was used to screen and clearly analyze the MoCA scores of two groups of patients with different infarctions,the relationship between the parts of the infarction volume,and analysis of acute insula cognitive disorder in elderly patients with cerebral RESULTS The number of patients with cognitive impairment in the basal ganglia and thalamus was significantly higher than that without cognitive impairment(P<0.05).The total infarct volume in the cognitive impairment group was higher than that in the non-cognitive impairment group,and the difference was statistically significant(P<0.05).The infarct volumes at different sites in the cognitive impairment group was higher than in the non-cognitive impairment group(P<0.05).In the cognitive impairment group,the infarct volumes in the basal ganglia,thalamus,and mixed lesions were negatively correlated with the total MoCA score,with correlation coefficients of-0.67,-0.73,and-0.77,respectively.CONCLUSION In elderly patients with acute insular infarction,infarction in the basal ganglia,thalamus,and mixed lesions were more likely to lead to cognitive dysfunction than in other areas,and patients with large infarct volumes were more likely to develop cognitive dysfunction.The infarct volume in the basal ganglia,thalamus,and mixed lesions was significantly negatively correlated with the MoCA score.
文摘BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.
基金funded by King Saud University,Riyadh,Saudi Arabia.Researchers Supporting Proiect Number(RSP2023R167)King Saud University,Riyadh,Saudi Arabia.
文摘The optimization of cognitive radio(CR)system using an enhanced firefly algorithm(EFA)is presented in this work.The Firefly algorithm(FA)is a nature-inspired algorithm based on the unique light-flashing behavior of fireflies.It has already proved its competence in various optimization prob-lems,but it suffers from slow convergence issues.To improve the convergence performance of FA,a new variant named EFA is proposed.The effectiveness of EFA as a good optimizer is demonstrated by optimizing benchmark functions,and simulation results show its superior performance compared to biogeography-based optimization(BBO),bat algorithm,artificial bee colony,and FA.As an application of this algorithm to real-world problems,EFA is also applied to optimize the CR system.CR is a revolutionary technique that uses a dynamic spectrum allocation strategy to solve the spectrum scarcity problem.However,it requires optimization to meet specific performance objectives.The results obtained by EFA in CR system optimization are compared with results in the literature of BBO,simulated annealing,and genetic algorithm.Statistical results further prove that the proposed algorithm is highly efficient and provides superior results.
基金supported in part by National Natural Science Foundation of China under Grant 62071202in part by Shandong Provincial Natural Science Foundation under Grants ZR2020MF009,ZR2020MF075in part by Shandong Key Laboratory of Intelligent Buildings Technology undert Grant SDIBT202004.
文摘Intelligent reflecting surface(IRS)has been widely regarded as a promising technology for configuring wireless propagation environments.In this paper,we utilize IRS to assist transmission of a secondary user(SU)in a cognitive radio-inspired rate-splitting multiple access(CR-RSMA)system in which a primary user's(PU's)quality of service(QoS)requirements must be guaranteed.Without introducing intolerable interference to deteriorate the PU's outage performance,the SU conducts rate-splitting to transmit its signal to the base-station through the direct link and IRS reflecting channels.For the IRS-assisted CR-RSMA(IRS-CR-RSMA)scheme,we derive the optimal transmit power allocation,target rate allocation,and successive interference cancellation decoding order to enhance the outage performance of the SU.The closed-form expression for the SU's outage probability achieved by the IRS-CR-RSMA scheme is derived.Various simulation results are presented to clarify the enhanced outage performance achieved by the proposed IRS-CR-RSMA scheme over the CR-RSMA scheme.
文摘There are abundant research results related to cognitive radio systems (CR systems), but using queueing models to portray CR systems is a new research trend. In this paper, a single-server retrial cognitive radio system with a linear retrial rate has been considered. The system has two types of users: primary users and secondary users. Secondary users have no effect on primary users because primary users have preemptive precedence. As a result, our purpose is to examine some performance indicators such as the expected queue length for primary users, the probability of the system being idle or occupied by a secondary user, and the probability of the system being busy. This paper begins by deriving the expressions for the generating functions based on the balance equations, so that we can calculate our goal conveniently.
基金supported by grant PID2021-125875OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by"ERDF A way of making Europe"(to RL)supported by a grant from Junta de Comunidades de Castilla-La Mancha (SBPLY/21/180501/000064)+3 种基金Universidad de Castilla-La Mancha (2023-GRIN-34187)(to RL).Grant PID201 9-104921RB-I00/MCI/AEI/10.13039/501100011033 (to AGO)the Foundation for Applied Medical Research,the University of Navarra (Pamplona,Spain)for financial supporthe Asociación de Amigos of the University of Navarra for the grant (to SB)Margarita Salas fellowship from Ministerio de Universidades and Universidad de Castilla-La Mancha (to AMB)
文摘Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.
基金supported by MH101874 (to CFZ)MH122379 (to CFZ)the Taylor Family Institute for Innovative Psychiatric Research and the Bantly Foundation (to CFZ)。
文摘Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.
基金funded by the Ramón Areces Foundation.IEC is supported by the Spanish Ministry of Science and Innovation(RYC2019-027287-I)the Spanish Ministry of Economy and Competitiveness(RTI2018-095284-J-100)+1 种基金supported by a grant from ANID/BECAS Chile(Grant No.72180543)through a Margarita Salas grant from the Spanish Ministry Universities。
文摘Background:One of the pathological hallmarks distinguishing Alzheimer’s disease from other dementias is the accumulation of amyloid beta(Aβ).Higher physical activity is associated with decreased dementia risk,and one potential path could be through Aβlevels modulation.We aimed to explore the relationship between physical activity and Aβin middle-aged and older adults.Methods:A systematic search of PubMed,Web of Science,PsycINFO,Cochrane Central Register of Controlled Trials,and SPORTDiscus was performed from inception to April 28,2022.Studies were eligible if they included physical activity and Aβdata in adults aged 45 years or older.Multi-level metaanalyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβlevels.Results:In total,37 articles were included(8 randomized controlled trials,3 non-randomized controlled trials,4 prospective longitudinal studies,and 22 cross-sectional studies).The overall effect size of physical activity interventions on changes in blood Aβwas medium(pooled standardized mean difference=-0.69,95%confidence interval(95%CI):-1.41 to 0.03;I^(2)=74.6%).However,these results were not statistically significant,and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid(CSF)and brain Aβ.Data from observational studies were examined based on measurements of Aβin the brain using positron emission tomography scans,CSF,and blood.Higher physical activity was positively associated with Aβonly in the CSF(Estimate r=0.12;95%CI:0.05-0.18;I^(2)=38.00%).Conclusion:Physical activity might moderately reduce blood Aβin middle-aged and older adults.However,results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies.In observational studies,higher levels of physical activity were positively associated with Aβonly in CSF.Therefore,further research is needed to understand the modulating role of physical activity in the brain,CSF,and blood Aβ,as well as its implication for cognitive health.
基金supported in part by the National Natural Science Foundation of China(No.61941105,No.61901327 and No.62101450)in part by the National Natural Science Foundation for Distinguished Young Scholar(No.61825104)+1 种基金in part by the Fundamental Research Funds for the Central Universities(JB210109)in part by the Foundation of State Key Laboratory of Integrated Services Networks of Xidian University(ISN22-03)。
文摘In this work,we investigate the covert communication in cognitive radio(CR)networks with the existence of multiple cognitive jammers(CJs).Specifically,the secondary transmitter(ST)helps the primary transmitter(PT)to relay information to primary receiver(PR),as a reward,the ST can use PT's spectrum to transmit private information against the eavesdropper(Eve)under the help of one selected cognitive jammer(CJ).Meanwhile,we propose three jammer-selection schemes,namely,link-oriented jammer selection(LJS),min-max jammer selection(MMJS)and random jammer selection(RJS).For each scheme,we analyze the average covert throughput(ACT)and covert outage probability(COP).Our simulation results show that CJ is helpful to ST's covert communication,the expected minimum detection error probability and ACT can be significantly improved with the increase of false alarm of CJ.Moreover,the LJS scheme achieves best performance in ACT and COP,followed by RJS scheme,and MMJS scheme shows the worst performance.