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.

EXACT CONTROLLABILITY AND CONTINUOUS DEPENDENCE OF FRACTIONAL NEUTRAL INTEGRO-DIFFERENTIAL EQUATIONS WITH STATE-DEPENDENT DELAY

In the present paper,with the help of the resolvent operator and some analytic methods,the exact controllability and continuous dependence are investigated for a fractional neutral integro-differential equations with state-dependent delay.As an application,we also give one example to demonstrate our results.

Attitude controller for reentry vehicles using state-dependent Riccati equation method

To get better tracking performance of attitude command over the reentry phase of vehicles, the use of state-dependent Riccati equation (SDRE) method for attitude controller design of reentry vehicles was investigated. Guidance commands are generated based on optimal guidance law. SDRE control method employs factorization of the nonlinear dynamics into a state vector and state dependent matrix valued function. State-dependent coefficients are derived based on reentry motion equations in pitch and yaw channels. Unlike constant weighting matrix Q, elements of Q are set as the functions of state error so as to get satisfactory feedback and eliminate state error rapidly, then formulation of SDRE is realized. Riccati equation is solved real-timely with Schur algorithm. State feedback control law u(x) is derived with linear quadratic regulator (LQR) method. Simulation results show that SDRE controller steadily tracks attitude command, and impact point error of reentry vehicle is acceptable. Compared with PID controller, tracking performance of attitude command using SDRE controller is better with smaller control surface deflection. The attitude tracking error with SDRE controller is within 5°, and the control deflection is within 30°.

A numerical study of comparison of two one-state-variable,rate-and state-dependent friction evolution laws

The two one-state-variable, rate- and state-dependent friction laws, i.e., the slip and slowness laws, are com- pared on the basis of dynamical behavior of a one-degree-of-freedom spring-slider model through numerical simulations. Results show that two （normalized） model parameters, i.e., A （the normalized characteristic slip distance） and β-α （the difference in two normalized parameters of friction laws）, control the solutions. From given values of △, β, and α, for the slowness laws, the solution exists and the unique non-zero fixed point is stable when △〉（β-α）, yet not when △ 〈（β-α）. For the slip law, the solution exists for large ranges of model parameters and the number and stability of the non-zero fixed points change from one case to another. Results suggest that the slip law is more appropriate for controlling earthquake dynamics than the slowness law.

Solution of the HJI equations for nonlinear H_∞ control design by state-dependent Riccati equations approach

The relationship between the technique by state- dependent Riccati equations （SDRE） and Hamilton-Jacobi-lsaacs （HJI） equations for nonlinear H∞ control design is investigated. By establishing the Lyapunov matrix equations for partial derivates of the solution of the SDREs and introducing symmetry measure for some related matrices, a method is proposed for examining whether the SDRE method admits a global optimal control equiva- lent to that solved by the HJI equation method. Two examples with simulation are given to illustrate the method is effective.

Discontinuous event-trigger scheme for global stabilization of state-dependent switching neural networks with communication delay

This paper is concerned with the global stabilization of state-dependent switching neural networks(SDSNNs)viadiscontinuous event-triggered control with network-induced communication delay.Aiming at decreasing triggering times,a discontinuous event-trigger scheme is utilized to determine whether the sampling information is required to be sent outor not.Meanwhile,under the effect of communication delay,the trigger condition and SDSNNs are transformed into twotractable models by designing a fictitious delay function.Then,using the Lyapunov–Krasovskii stability theory,someinequality estimation techniques,and extended reciprocally convex combination method,two sufficient criteria are established for ensuring the global stabilization of the resulting closed-loop SDSNNs,respectively.A unified framework isderived that has the ability to handle the simultaneous existence of the communication delay,the properties of discontinuousevent-trigger scheme,as well as feedback controller design.Additionally,the developed results demonstrate a quantitativerelationship among the event trigger parameter,communication delay,and triggering times.Finally,two numerical examples are presented to illustrate the usefulness of the developed stabilization scheme.

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.

Suggested New Terms for Describing Chiral States and the State-Dependent Behavior of Chiral Systems

Deficiencies in the terminology used to describe chiral systems exist for behaviors under various processes and thus a more general, robust terminology is considered. For example, the descriptions for characterizing melting point, solubility, and recrystallization behaviors were adopted well before it was realized that perturbation of the enantiomeric com-position (ec) due to self-disproportionation could be effected by processes other than recrystallization such as sublimation, chromatography over achiral substrates, and even distillation. Thus, an endeavor has been made to address the question of universally describing behaviors under processes that effect, or are dependent on, the ec. The main terms that have been defined with respect to behavior are homomate (analogous to a conglomerate), heteromate, bimate (analogous to a racemic compound), and unimate (analogous to a solid solution) and they apply to melting point, solubility, recrystallization, sublimation, distillation, and chromatographic processes. Additionally, suggestions for improving the terminology for describing the states of chiral systems are also considered and the defined terms are: holemate (hol, ec = 100%), scalemate (scl, 50% ec eqm, ec = 50%).

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.

EXISTENCE,UNIQUENESS AND APPROXIMATION OF THE SOLUTION OF AN ODE WITH (INFINITELY MANY) STATE-DEPENDENT IMPULSES VIA FIXED MESH GALERKIN FORMULATION

A fixed mesh variational formulation is used to establish existence and uniqueness of the solution of ordinary differential equations with (in finitely many) state-dependent in pulses on the right-hand side. This approach gives a natural numerical scheme to approximate the solution.The convergence of the approximation is proved and its asymptatic order obtained.

The Effect of State-Dependent Control for an SIRS Epidemic Model with Varying Total Population

Based on the mechanism of prevention and control of infectious disease, we propose, in this paper, an SIRS epidemic model with varying total population size and state-dependent control, where the fraction of susceptible individuals in population is as the detection threshold value. By the Poincaré map, theory of differential inequalities and differential equation geometry, the existence and orbital stability of the disease-free periodic solution are discussed. Theoretical results show that by state-dependent pulse vaccination we can make the proportion of infected individuals tend to zero, and control the transmission of disease in population.

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.

Finite-Time H∞ Control of Switched Nonlinear Systems under State-Dependent Switching

This paper investigates the finite-time H∞ control problem of switched nonlinear systems via state-dependent switching and state feedback control. Unlike the existing approach based on time-dependent switching strategy, in which the switching instants must be given in advance, the state-dependent switching strategy is used to design switching signals. Based on multiple Lyapunov-like functions method, several criteria for switched nonlinear systems to be finite-time H∞ control are derived. Finally, a numerical example with simulation results is provided to show the validity of the conclusions.

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.

Long-Time Behavior of Solution for Autonomous Suspension Bridge Equations with State-Dependent Delay

This work is devoted to the following suspension bridge with state-dependent delay: . The main goal of this paper is to investigate the long-time behavior of the system. Under suitable hypothesis, the quasi-stability estimates of the system are established, based on which the existence of global attractor with finite fractal dimension is obtained. Furthermore, the existence of exponential attractor is proved.

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.