The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.

Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.

Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

A Novel Long-Time Coherent Integration Method for Moving Target Detection

Long-time coherent integration(LTCI)can remarkably improve the detection ability of radar for moving target.To increase the processing efficiency,this paper proposes a novel LTCI method based on segment time reversing transform(STRT)and chirp z-transform(CZT).In this method,STRT operation is first presented to estimate the Doppler ambiguity factor,and keystone transform(KT)is used to correct the whole range migration(RM).Then,CZT and non-uniform fast Fourier transform(NUFFT)are used to estimate the parameters as well as correct the second and third order Doppler frequency migration(DFM).Compared with the existing methods,the proposed method can achieve RM correction and DFM correction without repetitive operation.The effectiveness of the proposed method is validated by both simulated and real data.

LONG-TIME CONVERGENCE OF GENERALIZED DIFFERENCE METHOD FOR NAVIER-STOKES EQUATIONS

In this paper, we first provide a generalized difference method for the 2-dimensional Navier-Stokes equations by combing the ideas of staggered scheme m and generalized upwind scheme in space, and by backward Euler time-stepping. Then we apply the abstract framework of to prove its long-time convergence. Finally, a numerical example for solving driven cavity flows is given.

Long-time limit behavior of the solution to an atom's master equation

We study the long-time limit behavior of the solution to an atom＇s master equation. For the first time we derive that the probability of the atom being in the α-th （α = j ＋ 1 -jz, j is the angular momentum quantum number, jz is the z-component of angular momentum） state is {（1 - K/G）/[1 - （K/G）2j＋1]}（K/G）^α-1 as t → ＋∞, which coincides with the fact that when K/G 〉 1, the larger the a is, the larger the probability of the atom being in the α-th state （the lower excited state） is. We also consider the case for some possible generaizations of the atomic master equation.

Machine learning-assisted efficient design of Cu-based shape memory alloy with specific phase transition temperature

The martensitic transformation temperature is the basis for the application of shape memory alloys(SMAs),and the ability to quickly and accurately predict the transformation temperature of SMAs has very important practical significance.In this work,machine learning(ML)methods were utilized to accelerate the search for shape memory alloys with targeted properties(phase transition temperature).A group of component data was selected to design shape memory alloys using reverse design method from numerous unexplored data.Component modeling and feature modeling were used to predict the phase transition temperature of the shape memory alloys.The experimental results of the shape memory alloys were obtained to verify the effectiveness of the support vector regression(SVR)model.The results show that the machine learning model can obtain target materials more efficiently and pertinently,and realize the accurate and rapid design of shape memory alloys with specific target phase transition temperature.On this basis,the relationship between phase transition temperature and material descriptors is analyzed,and it is proved that the key factors affecting the phase transition temperature of shape memory alloys are based on the strength of the bond energy between atoms.This work provides new ideas for the controllable design and performance optimization of Cu-based shape memory alloys.

Long-time evolution of charged grains in plasma under harmonic external force and after being withdrawn

Evolution of the charged grains in a two-dimensional dusty plasma under a spatially harmonic external force,in particular,their long-time behaviors after the force has been withdrawn,is studied by using molecular dynamics simulation.Under an external force and a grain–grain interaction force,initially homogeneously distributed grains can reach a quasistationary state in the form of a disk crystal.After the external force is withdrawn,the disk moves initially with its size and shape nearly unchanged until it rapidly stops moving,and eventually the disk grain rotates like a vortex.The time needed to reach the final state increases with the strength of the initial external force increasing.

LONG-TIME BEHAVIOR OF TRANSIENT SOLUTIONS FOR CELLULAR NEURAL NETWORK SYSTEMS

By establishing concept an transient solutions of general nonlinear systems converging to its equilibrium set, long-time behavior of solutions for cellular neural network systems is studied. A stability condition in generalized sense is obtained. This result reported has an important guide to concrete neural network designs.

Fabrication and integration of photonic devices for phase-change memory and neuromorphic computing

In the past decade,there has been tremendous progress in integrating chalcogenide phase-change materials(PCMs)on the silicon photonic platform for non-volatile memory to neuromorphic in-memory computing applications.In particular,these non von Neumann computational elements and systems benefit from mass manufacturing of silicon photonic integrated circuits(PICs)on 8-inch wafers using a 130 nm complementary metal-oxide semiconductor line.Chip manufacturing based on deep-ultraviolet lithography and electron-beam lithography enables rapid prototyping of PICs,which can be integrated with high-quality PCMs based on the wafer-scale sputtering technique as a back-end-of-line process.In this article,we present an overview of recent advances in waveguide integrated PCM memory cells,functional devices,and neuromorphic systems,with an emphasis on fabrication and integration processes to attain state-of-the-art device performance.After a short overview of PCM based photonic devices,we discuss the materials properties of the functional layer as well as the progress on the light guiding layer,namely,the silicon and germanium waveguide platforms.Next,we discuss the cleanroom fabrication flow of waveguide devices integrated with thin films and nanowires,silicon waveguides and plasmonic microheaters for the electrothermal switching of PCMs and mixed-mode operation.Finally,the fabrication of photonic and photonic–electronic neuromorphic computing systems is reviewed.These systems consist of arrays of PCM memory elements for associative learning,matrix-vector multiplication,and pattern recognition.With large-scale integration,the neuromorphic photonic computing paradigm holds the promise to outperform digital electronic accelerators by taking the advantages of ultra-high bandwidth,high speed,and energy-efficient operation in running machine learning algorithms.

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

Radar fast long-time coherent integration via TR-SKT and robust sparse FRFT

Long-time coherent integration(LTCI)is an effective way for radar maneuvering target detection,but it faces the problem of a large number of search parameters and large amount of calculation.Realizing the simultaneous compensation of the range and Doppler migrations in complex clutter back-ground,and at the same time improving the calculation efficiency has become an urgent problem to be solved.The sparse transformation theory is introduced to LTCI in this paper,and a non-parametric searching sparse LTCI(SLTCI)based maneuvering target detection method is proposed.This method performs time reversal(TR)and second-order Keystone transform(SKT)in the range frequency&slow-time data to complete high-order range walk compensation,and achieves the coherent integra-tion of maneuvering target across range and Doppler units via the robust sparse fractional Fourier transform(RSFRFT).It can compensate for the nonlinear range migration caused by high-order motion.S-band and X-band radar data measured in sea clutter background are used to verify the detection performance of the proposed method,which can achieve better detection performance of maneuvering targets with less computational burden compared with several popular integration methods.

Long-Time Relaxation and Residual Conductivity in GaP Irradiated by High-Energy Electrons

This paper presents the results of a study of long-time relaxation (LR) and residual conductivity in n-type gallium phosphide (GaP) crystals irradiated by 50 MeV electrons. A manifold increase in photosensitivity and quenching of residual conductivity was found as a result of irradiation. It is shown that LR in GaP is due to disordered regions (generated by electron irradiation) which have conductivity close to self one. The Fermi level in the disordered regions is determined by which is located deep in the forbidden band (Ее - 1.0 eV). LR effect is mainly explained by a spatial separation of electrons and holes, recombination of which is prevented by potential barriers. The observed increase in conductivity is associated with the increase in the concentration of minority carriers as well as with increase of the Hall mobility at the sample illumination.

Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

Between the City and Images:An Analysis of Mainstream Media’s Paths of Constructing the Cultural Memory of a City:Taking Chengdu Radio and Television’s“Hi Chengdu”as an Example

Mainstream media play a crucial role in constructing the cultural memory of a city.This study used 319 short videos released by“Hi Chengdu,”a new media product of Chengdu Radio and Television,as samples.Based on the grounded theory,a research framework encompassing“content,technology,and discourse”was established to explore the paths through which mainstream media construct the cultural memory.Regarding content,this paper emphasized temporal and spatial contexts and urban spaces,delving deep into the themes of the cultural memory and vehicles for it.In terms of technology,this paper discussed the practice of leveraging audio/visual-mode discourse to stitch together the impressions of a city and evoke emotional resonance to create a“flow”of memory.As for discourse,this paper looked at the performance of a communication ritual to frame concepts and shape urban identity.It is essential to break free from conventional thinking and leverage local culture as the primary driving force to further boost a city’s productivity,in order to excel in cultural communication.

The Effect of the Menstrual Cycle on Cognitive Performance: Spatial Reasoning, Visual & Numerical Memory

The menstrual cycle has been a topic of interest in relation to behavior and cognition for many years, with historical beliefs associating it with cognitive impairment. However, recent research has challenged these beliefs and suggested potential positive effects of the menstrual cycle on cognitive performance. Despite these emerging findings, there is still a lack of consensus regarding the impact of the menstrual cycle on cognition, particularly in domains such as spatial reasoning, visual memory, and numerical memory. Hence, this study aimed to explore the relationship between the menstrual cycle and cognitive performance in these specific domains. Previous studies have reported mixed findings, with some suggesting no significant association and others indicating potential differences across the menstrual cycle. To contribute to this body of knowledge, we explored the research question of whether the menstrual cycles have a significant effect on cognition, particularly in the domains of spatial reasoning, visual and numerical memory in a regionally diverse sample of menstruating females. A total of 30 menstruating females from mixed geographical backgrounds participated in the study, and a repeated measures design was used to assess their cognitive performance in two phases of the menstrual cycle: follicular and luteal. The results of the study revealed that while spatial reasoning was not significantly related to the menstrual cycle (p = 0.256), both visual and numerical memory had significant positive associations (p < 0.001) with the luteal phase. However, since the effect sizes were very small, the importance of this relationship might be commonly overestimated. Future studies could thus entail designs with larger sample sizes, including neuro-biological measures of menstrual stages, and consequently inform competent interventions and support systems.

The Impact of Opioid Drugs on Memory and Other Cognitive Functions: A Review

Background and Purpose: Opioids, used for centuries to alleviate pain, have become a double-edged sword. While effective, they come with a host of adverse effects, including memory and cognition impairment. This review delves into the impact of opioid drugs on cognitive functions, explores underlying mechanisms, and investigates their prevalence in both medical care and illicit drug use. The ultimate goal is to find ways to mitigate their potential harm and address the ongoing opioid crisis. Methods: We sourced data from PubMed and Google Scholar, employing search combinations like “opioids,” “memory,” “cognition,” “amnesia,” “cognitive function,” “executive function,” and “inhibition.” Our focus was on English-language articles spanning from the inception of these databases up to the present. Results: The literature consistently reveals that opioid use, particularly at high doses, adversely affects memory and other cognitive functions. Longer deliberation times, impaired decision-making, impulsivity, and behavioral disorders are common consequences. Chronic high-dose opioid use is associated with conditions such as amnesiac syndrome (OAS), post-operative cognitive dysfunction (POCD), neonatal abstinence syndrome (NAS), depression, anxiety, sedation, and addiction. Alarming trends show increased opioid use over recent decades, amplifying the risk of these outcomes. Conclusion: Opioids cast a shadow over memory and cognitive function. These effects range from amnesiac effects, lessened cognitive function, depression, and more. Contributing factors include over-prescription, misuse, misinformation, and prohibition policies. Focusing on correct informational campaigns, removing punitive policies, and focusing on harm reduction strategies have been shown to lessen the abuse and use of opioids and thus helping to mitigate the adverse effects of these drugs. Further research into the impacts of opioids on cognitive abilities is also needed as they are well demonstrated in the literature, but the mechanism is not often completely understood.

Enhanced Memory-Safe Linux Security Modules (eLSMs) for Improving Security of Docker Containers for Data Centers

The adoption of Docker containers has revolutionized software deployment by providing a lightweight and efficient way to isolate applications in data centers. However, securing these containers, especially when handling sensitive data, poses significant challenges. Traditional Linux Security Modules (LSMs) such as SELinux and AppArmor have limitations in providing fine-grained access control to files within containers. This paper presents a novel approach using eBPF (extended Berkeley Packet Filter) to implement a LSM that focuses on file-oriented access control within Docker containers. The module allows the specification of policies that determine which programs can access sensitive files, providing enhanced security without relying solely on the host operating system’s major LSM.

Design and implementation of dual-mode configurable memory architecture for CNN accelerator

With the rapid development of deep learning algorithms,the computational complexity and functional diversity are increasing rapidly.However,the gap between high computational density and insufficient memory bandwidth under the traditional von Neumann architecture is getting worse.Analyzing the algorithmic characteristics of convolutional neural network(CNN),it is found that the access characteristics of convolution(CONV)and fully connected(FC)operations are very different.Based on this feature,a dual-mode reronfigurable distributed memory architecture for CNN accelerator is designed.It can be configured in Bank mode or first input first output(FIFO)mode to accommodate the access needs of different operations.At the same time,a programmable memory control unit is designed,which can effectively control the dual-mode configurable distributed memory architecture by using customized special accessing instructions and reduce the data accessing delay.The proposed architecture is verified and tested by parallel implementation of some CNN algorithms.The experimental results show that the peak bandwidth can reach 13.44 GB·s^(-1)at an operating frequency of 120 MHz.This work can achieve 1.40,1.12,2.80 and 4.70 times the peak bandwidth compared with the existing work.