Cyclic adenosine monophosphate(cA MP) and/or cyclic guanosine monophosphate(cG MP)have been suggested to play specific roles in processes of memory. These cyclic nucleotides are hydrolyzed by specific enzymes,ie phosp...Cyclic adenosine monophosphate(cA MP) and/or cyclic guanosine monophosphate(cG MP)have been suggested to play specific roles in processes of memory. These cyclic nucleotides are hydrolyzed by specific enzymes,ie phosphodiesterases(PDEs). Thus,selective PDE inhibitors preventing the breakdown of cAMP and/or cGMP could improve memory. Studies with different timing of treatment with specific PDE inhibitors indicated that distinct underlying signaling pathways for early and late consolidation processes exist corresponding to specific time-windows for memory consolidation into longterm memory. There is evidence that the underlying mechanisms of PDE inhibition on the observed behavioral effects are independent of possible cerebrovascular effects. Most likely the underlying mechanisms are a cGMP/PKG pathway for early consolidation processes and a cAMP/PKA pathway for late consolidation processes. In addition,the early-phase cG MP/PKG signaling actually requires late-phase cAMP/PKA-signaling in long-term memory formation. Recently,the effects of specific PDE inhibitors are explored on other cognitive domains including acquisition processes/short-term memory and information processing. It will be shown that elevation of central cG MP levels or cA MP levels after treatment with a specific PDE inhibitor both improve acquisition processes/short-term memory. In vitro studying the effects of PDE inhibitors on long-term potentiation,the physiological substrate of memory,supportthe in vivo data and further show that AMPA receptor trafficking very likely mediates the memory enhancing effects. In a translational approach we initially also investigated the effects of cG MP elevation via PDE5 inhibition with vardenafil or sildenafil on cognition in humans. However,in contrast to studies with rodents and monkeys,PDE5 inhibition had no effect in humans on cognition including memory processes. It is clear that the transition of a drug from preclinical to clinical creates translational hurdles. Nevertheless,based on the expression patterns of its isoforms in the brain,PDE4,which is cAMP specific,appears more interesting for CNS targeting than PDE5. Indeed we found that a low dose of the PDE inhibitor roflumilast clearly improved cognition in humans. Interestingly,this pro-cognitive effect was not associated with emetic side effects(nausea,vomiting),which are commonly associated with PDE4 inhibition. Based on our data we suggest that the future for disease-specific PDE4 enzyme inhibition lies in the development of PDE4 isoform-specific inhibitors without emetic effects. Within the context as described above,the latest results of specific PDE inhibitors on cognitive processes will be presented and its implications will be discussed for finding and testing new cognition enhancers.展开更多
The process of human natural scene categorization consists of two correlated stages: visual perception and visual cognition of natural scenes.Inspired by this fact,we propose a biologically plausible approach for natu...The process of human natural scene categorization consists of two correlated stages: visual perception and visual cognition of natural scenes.Inspired by this fact,we propose a biologically plausible approach for natural scene image classification.This approach consists of one visual perception model and two visual cognition models.The visual perception model,composed of two steps,is used to extract discriminative features from natural scene images.In the first step,we mimic the oriented and bandpass properties of human primary visual cortex by a special complex wavelets transform,which can decompose a natural scene image into a series of 2D spatial structure signals.In the second step,a hybrid statistical feature extraction method is used to generate gist features from those 2D spatial structure signals.Then we design a cognitive feedback model to realize adaptive optimization for the visual perception model.At last,we build a multiple semantics based cognition model to imitate human cognitive mode in rapid natural scene categorization.Experiments on natural scene datasets show that the proposed method achieves high efficiency and accuracy for natural scene classification.展开更多
To address the problem of the weak anti-noise and macro-trend extraction abilities of the current methods for identifying radar antenna scan type,a recognition method for radar antenna scan types based on limited pene...To address the problem of the weak anti-noise and macro-trend extraction abilities of the current methods for identifying radar antenna scan type,a recognition method for radar antenna scan types based on limited penetrable visibility graph(LPVG)is proposed.Firstly,seven types of radar antenna scans are analyzed,which include the circular scan,sector scan,helical scan,raster scan,conical scan,electromechanical hybrid scan and two-dimensional electronic scan.Then,the time series of the pulse amplitude in the radar reconnaissance receiver is converted into an LPVG network,and the feature parameters are extracted.Finally,the recognition result is obtained by using a support vector machine(SVM)classifier.The experimental results show that the recognition accuracy and noise resistance of this new method are improved,where the average recognition accuracy for radar antenna type is at least 90%when the signalto-noise ratio(SNR)is 5 dB and above.展开更多
OBJECTIVE Phosphodiesterase 4(PDE4),specific for cyclicAMP(cAMP)-hydrolyzing,has four isoforms(PDE4A-D) with at least 25 splice variants. PDE4 inhibitors produce definite antidepressant-like and cognitive-enhancing ef...OBJECTIVE Phosphodiesterase 4(PDE4),specific for cyclicAMP(cAMP)-hydrolyzing,has four isoforms(PDE4A-D) with at least 25 splice variants. PDE4 inhibitors produce definite antidepressant-like and cognitive-enhancing effects. However,none of PDE4 inhibitors has yet been approved for clinical utility so far due to the concomitant side effects. The present research is to explore the splice variants of PDE4 D responsible for antidepressant-like and cognitive-enhancing effects of PDE4 inhibitors but not side effects. METHODS Long-form PDE4 Ds were silenced by the bilateral microinfusion of lentiviral vector containing mi RNAs(4Dmi R) into the prefrontal cortex(PFC),PDE4D4 or D5 was overexpressed by the bilateral microinfusion of lentiviral vector containing full c DNA into hippocampus. Antidepressant-like behaviors were measured by tail-suspension test(TST),forced swimming test(FST)and chronic unpredictable stress model. Cognitive behaviors were measured by the novel object recognition test(NOR) and Morris water maze test(MWM) in both normal mice and the mice with chronic unpredictable stress-induced memory deficits. The emetic potential was evaluated by the assessment of the anaesthetic reversal effect,a surrogate of the emesis test in non-vomiting species. The expressions of PDE4 isoforms/splice variants and cAMP level were examined by Western-blot and ELISA analysis. The dendritic complexity and spine density were assessed by Golgi staining. RESULTS(1)High and specific expression of EGFP(green,indicator of 4Dmi R expression) in PFC was observed under fluorescence microscopy.(2) 4Dmi R significantly down-regulated PDE4D4/5 splice variants,but not PDE4 A,PDE4 B or PDE4D1/2/3.(3) 4Dmi R treatments significantly increased cAMP signaling and dendritic complexity in PFC.(4) Rolipram and/or 4Dmi R treatments significantly decreased immobility in TST and FST.(5) Rolipram and/or 4Dmi R treatments reversed the depressive-like behaviors in chronically stressed mice,including the reduced sucrose preference,prolonged latency to novelty-suppressed feeding and increased immobility in FST.(6) Rolipram and/or 4Dmi R treatments significantly increased the recognition index in NOR task and both the entries and durations in MWM task.(7) Rolipram and/or 4Dmi R treatments reversed the memory deficits in chronically stressed mice,including the reduced the recognition index in NOR task and the decreased durations in MWM task.(8) Rolipram and/or 4DmiR treatments reversed the decreased cA MP signaling,dendritic complexity and spine density.(9) Rolipram or plus 4Dmi R treatment significantly decreased the duration of anaesthesia in the alpha2 adrenergic receptor-mediated anesthesia,but not 4Dmi R treatment alone.(10)Hippocampal overexpression of PDE4D5,but not PDE4D4,produced depressive-like and cognitive defect behaviors,which were reversed by rolipram.The measurements including cAMP signaling,dendritic complexity and in vivo hippocampal LTP,showed the same changes. CONCLUSION Long-form PDE4 Ds,especially the PDE4D5,are the major isoforms responsible for antidepressant-like and cognitive-enhancing effects with little side effects. The critical roles of long-form PDE4 Ds are mediated by their regulation of cAMP signaling pathway and neuroplasticity.展开更多
Cognitive bias,stemming from electronic measurement error and variability in human perception,exists in cognitive electronic warfare and affects the outcomes of conflicts.In this paper,the dynamic game approach is emp...Cognitive bias,stemming from electronic measurement error and variability in human perception,exists in cognitive electronic warfare and affects the outcomes of conflicts.In this paper,the dynamic game approach is employed to develop a model for cognitive bias induced by incomplete information and measurement errors in cognitive radar countermeasures.The payoffs for both parties are calculated using the radar's anti-jamming strategy matrix A and the jammer's jamming strategy matrix B.With perfect Bayesian equilibrium,a dynamic radar countermeasure model is established,and the impact of cognitive bias is analyzed.Drawing inspiration from the cognitive bias analysis method used in stock market trading,a cognitive bias model for cognitive radar countermeasures is introduced,and its correctness is mathematically proved.A gaming scenario involving the AN/SPY-1 radar and a smart jammer is set up to analyze the influence of cognitive bias on game outcomes.Simulation results validate the effectiveness of the proposed method.展开更多
Alzheimer's disease(AD)is a prevalent neurodegenerative disease characterized by cognitive decline in the early stage.Mild cognitive impairment(MCI)is considered as an intermediate stage between normal aging and A...Alzheimer's disease(AD)is a prevalent neurodegenerative disease characterized by cognitive decline in the early stage.Mild cognitive impairment(MCI)is considered as an intermediate stage between normal aging and AD.In recent years,studies related to resting-state functional MRI(rs-fMRI)indicated that the occurrence and development process of MCI and AD might be closely linked to spontaneous brain activity and alterations in functional connectivity among brain regions,and rs-fMRI could provide important reference for specific diagnosis and early treatment of MCI and AD.The research progresses of rs-fMRI for MCI and AD were reviewed in this article.展开更多
The construction of shiology system is the premise for comprehensively solving the issues of human shiance.The core of the construction of the shiology system is to reveal the inclusion and juxtaposition of relationsh...The construction of shiology system is the premise for comprehensively solving the issues of human shiance.The core of the construction of the shiology system is to reveal the inclusion and juxtaposition of relationships within shiance based on a comprehensive understanding of human shiance issues.The shiology system discussed in this paper is a four-level discipline system with the basic structure of shiology triangle composed of eaters'demands,food acquisition and shiance order,and it is currently in the form of"1-3-13-36".From a longitudinal point of view,53 inclusion relationships are established among disciplines at all levels.Horizontally,53 juxtapositions are established between disciplines at the same level.The shiology system is bounded by human shiance issues,not involving non-shiance issues areas.Human cognition of shiance and shiance issues must go through three historical stages as fragmented cognition,block-based cognition and holistic cognition.The construction of the shiology system marks that humans have entered the stage of"holistic cognition"of shiance.As the Chinese proverb goes,"food is the paramount necessity of the people".Shiology system interprets its connotation and extension.To solve shiance issues holistically,it need to ensure food security,enable people to eat healthy,and foster an enduring and stable society.And shiology system is a global public product which comprehensively solves shiance issues.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
Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflamm...Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment.Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγantagonist GW9662 to confirm the involvement of this pathway in MaR1’s effects.Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P<0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P<0.05).No significant difference in efficacy was observed between the 2 doses(all P>0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1’s protective effects.Real-time RTPCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P<0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P>0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P<0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P<0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P<0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P<0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγcompared to the MaR1-LD group(all P<0.05).Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.展开更多
In a recent publication,Hu et al.(2023)have reported that individuals with high trait anxiety exhibit attentional deficits characterized by reduced inhibition of distractors and delayed attentional selection of target...In a recent publication,Hu et al.(2023)have reported that individuals with high trait anxiety exhibit attentional deficits characterized by reduced inhibition of distractors and delayed attentional selection of targets,indicating impaired top-down attentional control.This commentary underscores their significant contributions to the cognitive theory of anxiety.Based on their findings,we propose a novel training approach called attentional inhibition training(AIT),aimed at improving top-down attentional control to alleviate symptoms of anxiety.Furthermore,we explore the potential application of non-invasive transcranial magnetic stimulation(TMS)for rapidly enhancing attentional control function.展开更多
Objective Chronic stress can induce cognitive dysfunction,but the underlying mechanisms remain unknown.Studies have confirmed that the high mobility group box 1/Toll-like receptor 4(HMGB1/TLR4)pathway is closely assoc...Objective Chronic stress can induce cognitive dysfunction,but the underlying mechanisms remain unknown.Studies have confirmed that the high mobility group box 1/Toll-like receptor 4(HMGB1/TLR4)pathway is closely associated with cognitive impairment.Therefore,this research aimed to explore whether the HMGB1/TLR4 pathway involves in chronic stress-induced cognitive dysfunction.Methods The chronic unpredictable mild stress(CUMS)mouse model was established by randomly giving different types of stress every day for four consecutive weeks.Cognitive function was detected by novel object recognition test,Y-maze test,and Morris water maze test.The protein expressions of HMGB1,TLR4,B-cell lymphoma 2(BCL2),and BCL2 associated X(BAX)were determined by Western blot.The damage of neurons in the hippocampal CA1 region was observed by hematoxylin-eosin(HE)staining.Results The protein expressions of HMGB1 and TLR4 were significantly increased in the hippocampus of chronic stress mice.Furthermore,inhibition of the HMGB1/TLR4 pathway induced by ethyl pyruvate(EP,a specific inhibitor of HMGB1)and TAK242(a selective inhibitor of TLR4)treatment attenuated cognitive impairment in chronic stress mice,according to the novel object recognition test,Y-maze test,and Morris water maze test.In addition,administration of EP and TAK242 also mitigated the increase of apoptosis in the hippocampus of chronic stress mice.Conclusion These results indicate that the hippocampal HMGB1/TLR4 pathway contributes to chronic stress-induced apoptosis and cognitive dysfunction.展开更多
In the research on the smart community pension service,it is found that the problems encountered in the promotion of the smart pension can not be solved in the short term because of the lack of information and the acc...In the research on the smart community pension service,it is found that the problems encountered in the promotion of the smart pension can not be solved in the short term because of the lack of information and the acceptance of the intelligent products by the elderly. This paper puts forward the research ideas based on the cognitive characteristics and demand prediction of the specific population. Focusing on the research on the pension needs of people born in the 1960 s or 1970 s,it provides support for the solution of smart pension services in the peak period of aging population in the future.展开更多
An approach for modeling a human cognitive framework in time-stressed decision making is presented. The recognitive and metacognitive processes that represent the cognitive framework are modeled by the colored Petri n...An approach for modeling a human cognitive framework in time-stressed decision making is presented. The recognitive and metacognitive processes that represent the cognitive framework are modeled by the colored Petri nets （CPNs）. A structural and behavioral analysis method is adopted to obtain the static and dynamic property used to verify the CPNs model of the cognitive framework. Finally, an example from the command and control radar recognition system is used to evaluate the feasibility and availability of the CPNs model adopted in practical systems.展开更多
According to schema theory resulting from the psycholinguistic model of reading,comprehending a text is an interactive process between the reader background knowledge and the text. This article first views the psychol...According to schema theory resulting from the psycholinguistic model of reading,comprehending a text is an interactive process between the reader background knowledge and the text. This article first views the psycholinguistic model of reading and research in learning strategies, then discusses the application of socioaffective,cognitive, metacognitive learning strategies in Chinese EFL learners’ reading comprehension.展开更多
Cyclic-nucleotide phosphodiesterase 1(PDE1) is a unique enzyme family hydrolyzing both cyclic guanosine monophosphate(cGMP) and cyclic adenosine monophosphate(cAMP) intra-cellular signaling molecules. A unique aspect ...Cyclic-nucleotide phosphodiesterase 1(PDE1) is a unique enzyme family hydrolyzing both cyclic guanosine monophosphate(cGMP) and cyclic adenosine monophosphate(cAMP) intra-cellular signaling molecules. A unique aspect of this enzyme family is its activation by calcium-calmodulin upon excitation of excitatory cells such as neurons and cardiomyocytes. In chronic degenerative diseases such as Parkinson disease,Alzheimer disease and heart failure,over-stimulation and chronic excessive levels of intra-cellular calcium leads to cell death. Targeting the PDE1 enzyme family with enzyme inhibitors is a novel approach to develop therapeutic agents for degenerative disorders. ITI-214 is a potent,and selective PDE1 inhibitor that has been tested in four human clinical trials. It is safe and well tolerated even at high dose levels that lead to high plasma and cerebral spinal fluid levels. In animal models,ITI-214 has cognitive enhancing properties as demonstrated in the rat novel object recognition model. Using a unilateral 6-hydroxy-dopamine lesion mouse model,the cylinder test readout of front paw use indicated that ITI-214 displays L-DOPA sparing effects ITI-214 reverses catalepsy induced by the potent dopamine D2 receptor antagonist haloperidol,indicating potential applications in Parkinson disease and as an adjunctive treatment in schizophrenia. Aspects of the Intra-Cellular Therapies PDE1 inhibitor program wil be outlined and the potential application to multiple therapeutic areas wil be discussed.展开更多
Alzheimer disease(AD)is the leading cause of dementia that affects millions of elderly people worldwide.The currently available therapies have limited efficacy.Liuwei Dihuang formula(LW),a classical traditional Chines...Alzheimer disease(AD)is the leading cause of dementia that affects millions of elderly people worldwide.The currently available therapies have limited efficacy.Liuwei Dihuang formula(LW),a classical traditional Chinese medicine(TCM)prescription,has long been used to treat various diseases,including dementia.A great number of pharmacological studies have showed that LW and its active fractions had beneficial effects on AD associated cognitive impairments.Our recent study found that LW,especially its oligosaccharide fraction CA-30,could improve the gastrointestinal microbiota dysbiosis in senescence-accelerated mouse prone 8(SAMP8),an AD mouse model.Here,we sought to determine the effects of CA-30 on the composition and function of the intestinal microbiome in SAMP8 mice.Administration with CA-30 decreased the degree of senescence,increased the nest building and locomotor activity,ameliorated the impairments in object recognition,spatial learningand memory behavour,and decreased the active avoidance response in SAMP8 mice.Meanwhile,CA-30 improvedthe cytokine and hormone secretion and lymphocyte subset dysregulation in SAMP8 mice.Moreover,we found that CA-30 altered the abundance of 4 genera and 10 newborn genera.Advantageous changes in carbohydrate-active enzymes of SAMP8 mice following CA-30 treatment,especially GH85,were also noted.We further found that 7 genera were significantly correlated with the NIM network and cognitive performance.CA-30 influenced the relative abundance of these intestinal microbiomes in SAMP8 mice and restored them to SAMR1 mouse levels.CA-30 ameliorated the intestinal microbiome,rebalanced the NIM network,improved the AD-like cognitive impairments in SAMP8,and might thus be a potential therapeutic agent for AD.展开更多
文摘Cyclic adenosine monophosphate(cA MP) and/or cyclic guanosine monophosphate(cG MP)have been suggested to play specific roles in processes of memory. These cyclic nucleotides are hydrolyzed by specific enzymes,ie phosphodiesterases(PDEs). Thus,selective PDE inhibitors preventing the breakdown of cAMP and/or cGMP could improve memory. Studies with different timing of treatment with specific PDE inhibitors indicated that distinct underlying signaling pathways for early and late consolidation processes exist corresponding to specific time-windows for memory consolidation into longterm memory. There is evidence that the underlying mechanisms of PDE inhibition on the observed behavioral effects are independent of possible cerebrovascular effects. Most likely the underlying mechanisms are a cGMP/PKG pathway for early consolidation processes and a cAMP/PKA pathway for late consolidation processes. In addition,the early-phase cG MP/PKG signaling actually requires late-phase cAMP/PKA-signaling in long-term memory formation. Recently,the effects of specific PDE inhibitors are explored on other cognitive domains including acquisition processes/short-term memory and information processing. It will be shown that elevation of central cG MP levels or cA MP levels after treatment with a specific PDE inhibitor both improve acquisition processes/short-term memory. In vitro studying the effects of PDE inhibitors on long-term potentiation,the physiological substrate of memory,supportthe in vivo data and further show that AMPA receptor trafficking very likely mediates the memory enhancing effects. In a translational approach we initially also investigated the effects of cG MP elevation via PDE5 inhibition with vardenafil or sildenafil on cognition in humans. However,in contrast to studies with rodents and monkeys,PDE5 inhibition had no effect in humans on cognition including memory processes. It is clear that the transition of a drug from preclinical to clinical creates translational hurdles. Nevertheless,based on the expression patterns of its isoforms in the brain,PDE4,which is cAMP specific,appears more interesting for CNS targeting than PDE5. Indeed we found that a low dose of the PDE inhibitor roflumilast clearly improved cognition in humans. Interestingly,this pro-cognitive effect was not associated with emetic side effects(nausea,vomiting),which are commonly associated with PDE4 inhibition. Based on our data we suggest that the future for disease-specific PDE4 enzyme inhibition lies in the development of PDE4 isoform-specific inhibitors without emetic effects. Within the context as described above,the latest results of specific PDE inhibitors on cognitive processes will be presented and its implications will be discussed for finding and testing new cognition enhancers.
文摘The process of human natural scene categorization consists of two correlated stages: visual perception and visual cognition of natural scenes.Inspired by this fact,we propose a biologically plausible approach for natural scene image classification.This approach consists of one visual perception model and two visual cognition models.The visual perception model,composed of two steps,is used to extract discriminative features from natural scene images.In the first step,we mimic the oriented and bandpass properties of human primary visual cortex by a special complex wavelets transform,which can decompose a natural scene image into a series of 2D spatial structure signals.In the second step,a hybrid statistical feature extraction method is used to generate gist features from those 2D spatial structure signals.Then we design a cognitive feedback model to realize adaptive optimization for the visual perception model.At last,we build a multiple semantics based cognition model to imitate human cognitive mode in rapid natural scene categorization.Experiments on natural scene datasets show that the proposed method achieves high efficiency and accuracy for natural scene classification.
基金supported by the National Natural Science Foundation of China(1127105011371183+2 种基金61403036)the Science and Technology Development Foundation of CAEP(2013A04030202013B0403068)
基金supported by the China Postdoctoral Science Foundation(2015M572694,2016T90979).
文摘To address the problem of the weak anti-noise and macro-trend extraction abilities of the current methods for identifying radar antenna scan type,a recognition method for radar antenna scan types based on limited penetrable visibility graph(LPVG)is proposed.Firstly,seven types of radar antenna scans are analyzed,which include the circular scan,sector scan,helical scan,raster scan,conical scan,electromechanical hybrid scan and two-dimensional electronic scan.Then,the time series of the pulse amplitude in the radar reconnaissance receiver is converted into an LPVG network,and the feature parameters are extracted.Finally,the recognition result is obtained by using a support vector machine(SVM)classifier.The experimental results show that the recognition accuracy and noise resistance of this new method are improved,where the average recognition accuracy for radar antenna type is at least 90%when the signalto-noise ratio(SNR)is 5 dB and above.
文摘OBJECTIVE Phosphodiesterase 4(PDE4),specific for cyclicAMP(cAMP)-hydrolyzing,has four isoforms(PDE4A-D) with at least 25 splice variants. PDE4 inhibitors produce definite antidepressant-like and cognitive-enhancing effects. However,none of PDE4 inhibitors has yet been approved for clinical utility so far due to the concomitant side effects. The present research is to explore the splice variants of PDE4 D responsible for antidepressant-like and cognitive-enhancing effects of PDE4 inhibitors but not side effects. METHODS Long-form PDE4 Ds were silenced by the bilateral microinfusion of lentiviral vector containing mi RNAs(4Dmi R) into the prefrontal cortex(PFC),PDE4D4 or D5 was overexpressed by the bilateral microinfusion of lentiviral vector containing full c DNA into hippocampus. Antidepressant-like behaviors were measured by tail-suspension test(TST),forced swimming test(FST)and chronic unpredictable stress model. Cognitive behaviors were measured by the novel object recognition test(NOR) and Morris water maze test(MWM) in both normal mice and the mice with chronic unpredictable stress-induced memory deficits. The emetic potential was evaluated by the assessment of the anaesthetic reversal effect,a surrogate of the emesis test in non-vomiting species. The expressions of PDE4 isoforms/splice variants and cAMP level were examined by Western-blot and ELISA analysis. The dendritic complexity and spine density were assessed by Golgi staining. RESULTS(1)High and specific expression of EGFP(green,indicator of 4Dmi R expression) in PFC was observed under fluorescence microscopy.(2) 4Dmi R significantly down-regulated PDE4D4/5 splice variants,but not PDE4 A,PDE4 B or PDE4D1/2/3.(3) 4Dmi R treatments significantly increased cAMP signaling and dendritic complexity in PFC.(4) Rolipram and/or 4Dmi R treatments significantly decreased immobility in TST and FST.(5) Rolipram and/or 4Dmi R treatments reversed the depressive-like behaviors in chronically stressed mice,including the reduced sucrose preference,prolonged latency to novelty-suppressed feeding and increased immobility in FST.(6) Rolipram and/or 4Dmi R treatments significantly increased the recognition index in NOR task and both the entries and durations in MWM task.(7) Rolipram and/or 4Dmi R treatments reversed the memory deficits in chronically stressed mice,including the reduced the recognition index in NOR task and the decreased durations in MWM task.(8) Rolipram and/or 4DmiR treatments reversed the decreased cA MP signaling,dendritic complexity and spine density.(9) Rolipram or plus 4Dmi R treatment significantly decreased the duration of anaesthesia in the alpha2 adrenergic receptor-mediated anesthesia,but not 4Dmi R treatment alone.(10)Hippocampal overexpression of PDE4D5,but not PDE4D4,produced depressive-like and cognitive defect behaviors,which were reversed by rolipram.The measurements including cAMP signaling,dendritic complexity and in vivo hippocampal LTP,showed the same changes. CONCLUSION Long-form PDE4 Ds,especially the PDE4D5,are the major isoforms responsible for antidepressant-like and cognitive-enhancing effects with little side effects. The critical roles of long-form PDE4 Ds are mediated by their regulation of cAMP signaling pathway and neuroplasticity.
文摘Cognitive bias,stemming from electronic measurement error and variability in human perception,exists in cognitive electronic warfare and affects the outcomes of conflicts.In this paper,the dynamic game approach is employed to develop a model for cognitive bias induced by incomplete information and measurement errors in cognitive radar countermeasures.The payoffs for both parties are calculated using the radar's anti-jamming strategy matrix A and the jammer's jamming strategy matrix B.With perfect Bayesian equilibrium,a dynamic radar countermeasure model is established,and the impact of cognitive bias is analyzed.Drawing inspiration from the cognitive bias analysis method used in stock market trading,a cognitive bias model for cognitive radar countermeasures is introduced,and its correctness is mathematically proved.A gaming scenario involving the AN/SPY-1 radar and a smart jammer is set up to analyze the influence of cognitive bias on game outcomes.Simulation results validate the effectiveness of the proposed method.
文摘Alzheimer's disease(AD)is a prevalent neurodegenerative disease characterized by cognitive decline in the early stage.Mild cognitive impairment(MCI)is considered as an intermediate stage between normal aging and AD.In recent years,studies related to resting-state functional MRI(rs-fMRI)indicated that the occurrence and development process of MCI and AD might be closely linked to spontaneous brain activity and alterations in functional connectivity among brain regions,and rs-fMRI could provide important reference for specific diagnosis and early treatment of MCI and AD.The research progresses of rs-fMRI for MCI and AD were reviewed in this article.
文摘The construction of shiology system is the premise for comprehensively solving the issues of human shiance.The core of the construction of the shiology system is to reveal the inclusion and juxtaposition of relationships within shiance based on a comprehensive understanding of human shiance issues.The shiology system discussed in this paper is a four-level discipline system with the basic structure of shiology triangle composed of eaters'demands,food acquisition and shiance order,and it is currently in the form of"1-3-13-36".From a longitudinal point of view,53 inclusion relationships are established among disciplines at all levels.Horizontally,53 juxtapositions are established between disciplines at the same level.The shiology system is bounded by human shiance issues,not involving non-shiance issues areas.Human cognition of shiance and shiance issues must go through three historical stages as fragmented cognition,block-based cognition and holistic cognition.The construction of the shiology system marks that humans have entered the stage of"holistic cognition"of shiance.As the Chinese proverb goes,"food is the paramount necessity of the people".Shiology system interprets its connotation and extension.To solve shiance issues holistically,it need to ensure food security,enable people to eat healthy,and foster an enduring and stable society.And shiology system is a global public product which comprehensively solves shiance issues.
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supported by the National Natural Science Foundation (81601728,31500726)the Natural Science Foundation of Hunan Province (2021JJ41002),China。
文摘Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment.Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγantagonist GW9662 to confirm the involvement of this pathway in MaR1’s effects.Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P<0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P<0.05).No significant difference in efficacy was observed between the 2 doses(all P>0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1’s protective effects.Real-time RTPCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P<0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P>0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P<0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P<0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P<0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P<0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγcompared to the MaR1-LD group(all P<0.05).Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.
文摘In a recent publication,Hu et al.(2023)have reported that individuals with high trait anxiety exhibit attentional deficits characterized by reduced inhibition of distractors and delayed attentional selection of targets,indicating impaired top-down attentional control.This commentary underscores their significant contributions to the cognitive theory of anxiety.Based on their findings,we propose a novel training approach called attentional inhibition training(AIT),aimed at improving top-down attentional control to alleviate symptoms of anxiety.Furthermore,we explore the potential application of non-invasive transcranial magnetic stimulation(TMS)for rapidly enhancing attentional control function.
文摘Objective Chronic stress can induce cognitive dysfunction,but the underlying mechanisms remain unknown.Studies have confirmed that the high mobility group box 1/Toll-like receptor 4(HMGB1/TLR4)pathway is closely associated with cognitive impairment.Therefore,this research aimed to explore whether the HMGB1/TLR4 pathway involves in chronic stress-induced cognitive dysfunction.Methods The chronic unpredictable mild stress(CUMS)mouse model was established by randomly giving different types of stress every day for four consecutive weeks.Cognitive function was detected by novel object recognition test,Y-maze test,and Morris water maze test.The protein expressions of HMGB1,TLR4,B-cell lymphoma 2(BCL2),and BCL2 associated X(BAX)were determined by Western blot.The damage of neurons in the hippocampal CA1 region was observed by hematoxylin-eosin(HE)staining.Results The protein expressions of HMGB1 and TLR4 were significantly increased in the hippocampus of chronic stress mice.Furthermore,inhibition of the HMGB1/TLR4 pathway induced by ethyl pyruvate(EP,a specific inhibitor of HMGB1)and TAK242(a selective inhibitor of TLR4)treatment attenuated cognitive impairment in chronic stress mice,according to the novel object recognition test,Y-maze test,and Morris water maze test.In addition,administration of EP and TAK242 also mitigated the increase of apoptosis in the hippocampus of chronic stress mice.Conclusion These results indicate that the hippocampal HMGB1/TLR4 pathway contributes to chronic stress-induced apoptosis and cognitive dysfunction.
基金This paper is the research result of the social science planning project of Chongqing(subject number:2018QNYS70)and the educational planning project of Chongqing(subject number:2017-GX-273).
文摘In the research on the smart community pension service,it is found that the problems encountered in the promotion of the smart pension can not be solved in the short term because of the lack of information and the acceptance of the intelligent products by the elderly. This paper puts forward the research ideas based on the cognitive characteristics and demand prediction of the specific population. Focusing on the research on the pension needs of people born in the 1960 s or 1970 s,it provides support for the solution of smart pension services in the peak period of aging population in the future.
基金supported by the National Natural Science Foundation of China(60874068).
文摘An approach for modeling a human cognitive framework in time-stressed decision making is presented. The recognitive and metacognitive processes that represent the cognitive framework are modeled by the colored Petri nets （CPNs）. A structural and behavioral analysis method is adopted to obtain the static and dynamic property used to verify the CPNs model of the cognitive framework. Finally, an example from the command and control radar recognition system is used to evaluate the feasibility and availability of the CPNs model adopted in practical systems.
文摘According to schema theory resulting from the psycholinguistic model of reading,comprehending a text is an interactive process between the reader background knowledge and the text. This article first views the psycholinguistic model of reading and research in learning strategies, then discusses the application of socioaffective,cognitive, metacognitive learning strategies in Chinese EFL learners’ reading comprehension.
文摘Cyclic-nucleotide phosphodiesterase 1(PDE1) is a unique enzyme family hydrolyzing both cyclic guanosine monophosphate(cGMP) and cyclic adenosine monophosphate(cAMP) intra-cellular signaling molecules. A unique aspect of this enzyme family is its activation by calcium-calmodulin upon excitation of excitatory cells such as neurons and cardiomyocytes. In chronic degenerative diseases such as Parkinson disease,Alzheimer disease and heart failure,over-stimulation and chronic excessive levels of intra-cellular calcium leads to cell death. Targeting the PDE1 enzyme family with enzyme inhibitors is a novel approach to develop therapeutic agents for degenerative disorders. ITI-214 is a potent,and selective PDE1 inhibitor that has been tested in four human clinical trials. It is safe and well tolerated even at high dose levels that lead to high plasma and cerebral spinal fluid levels. In animal models,ITI-214 has cognitive enhancing properties as demonstrated in the rat novel object recognition model. Using a unilateral 6-hydroxy-dopamine lesion mouse model,the cylinder test readout of front paw use indicated that ITI-214 displays L-DOPA sparing effects ITI-214 reverses catalepsy induced by the potent dopamine D2 receptor antagonist haloperidol,indicating potential applications in Parkinson disease and as an adjunctive treatment in schizophrenia. Aspects of the Intra-Cellular Therapies PDE1 inhibitor program wil be outlined and the potential application to multiple therapeutic areas wil be discussed.
文摘Alzheimer disease(AD)is the leading cause of dementia that affects millions of elderly people worldwide.The currently available therapies have limited efficacy.Liuwei Dihuang formula(LW),a classical traditional Chinese medicine(TCM)prescription,has long been used to treat various diseases,including dementia.A great number of pharmacological studies have showed that LW and its active fractions had beneficial effects on AD associated cognitive impairments.Our recent study found that LW,especially its oligosaccharide fraction CA-30,could improve the gastrointestinal microbiota dysbiosis in senescence-accelerated mouse prone 8(SAMP8),an AD mouse model.Here,we sought to determine the effects of CA-30 on the composition and function of the intestinal microbiome in SAMP8 mice.Administration with CA-30 decreased the degree of senescence,increased the nest building and locomotor activity,ameliorated the impairments in object recognition,spatial learningand memory behavour,and decreased the active avoidance response in SAMP8 mice.Meanwhile,CA-30 improvedthe cytokine and hormone secretion and lymphocyte subset dysregulation in SAMP8 mice.Moreover,we found that CA-30 altered the abundance of 4 genera and 10 newborn genera.Advantageous changes in carbohydrate-active enzymes of SAMP8 mice following CA-30 treatment,especially GH85,were also noted.We further found that 7 genera were significantly correlated with the NIM network and cognitive performance.CA-30 influenced the relative abundance of these intestinal microbiomes in SAMP8 mice and restored them to SAMR1 mouse levels.CA-30 ameliorated the intestinal microbiome,rebalanced the NIM network,improved the AD-like cognitive impairments in SAMP8,and might thus be a potential therapeutic agent for AD.
