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...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.展开更多
Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this co...Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative diseases.This review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative stress.The role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's disease.However,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific functions.Further studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological target.This will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.展开更多
Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its appl...Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.展开更多
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 prac...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.展开更多
Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s dis...Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.展开更多
随着国民生活水平的提高,越来越多的人投身于股票市场.为了科学有效地量化选股,通过将量化投资、深度学习及文本分析进行有机结合,来建立量化选股模型.首先,通过文本分析筛选出基本面利好的股票;然后,通过长短期记忆(long-short term me...随着国民生活水平的提高,越来越多的人投身于股票市场.为了科学有效地量化选股,通过将量化投资、深度学习及文本分析进行有机结合,来建立量化选股模型.首先,通过文本分析筛选出基本面利好的股票;然后,通过长短期记忆(long-short term memory,LSTM)选出预测准确度良好的股票;最后,预测所选出的股票在未来几天的股价趋势.在实证分析方面,通过本模型对部分股票进行运算,选取预测效果较好的股票:赢合科技.展开更多
In recent years,there has been considerable exploration into methods aimed at enhancing the regenerative capacity of transplanted and/or tissue-resident cells.Biomaterials,in particular,have garnered significant inter...In recent years,there has been considerable exploration into methods aimed at enhancing the regenerative capacity of transplanted and/or tissue-resident cells.Biomaterials,in particular,have garnered significant interest for their potential to serve as natural scaffolds for cells.In this editorial,we provide commentary on the study by Wang et al,in a recently published issue of World J Stem Cells,which investigates the use of a decellularized xenogeneic extracellular matrix(ECM)derived from antler stem cells for repairing osteochondral defects in rat knee joints.Our focus lies specifically on the crucial role of biological scaffolds as a strategy for augmenting stem cell potential and regenerative capabilities,thanks to the establishment of a favorable microenvironment(niche).Stem cell differen-tiation heavily depends on exposure to intrinsic properties of the ECM,including its chemical and protein composition,as well as the mechanical forces it can generate.Collectively,these physicochemical cues contribute to a bio-instructive signaling environment that offers tissue-specific guidance for achieving effective repair and regeneration.The interest in mechanobiology,often conceptualized as a form of“structural memory”,is steadily gaining more validation and momen-tum,especially in light of findings such as these.展开更多
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 ...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.展开更多
Spark,a distributed computing platform,has rapidly developed in the field of big data.Its in-memory computing feature reduces disk read overhead and shortens data processing time,making it have broad application prosp...Spark,a distributed computing platform,has rapidly developed in the field of big data.Its in-memory computing feature reduces disk read overhead and shortens data processing time,making it have broad application prospects in large-scale computing applications such as machine learning and image processing.However,the performance of the Spark platform still needs to be improved.When a large number of tasks are processed simultaneously,Spark’s cache replacementmechanismcannot identify high-value data partitions,resulting inmemory resources not being fully utilized and affecting the performance of the Spark platform.To address the problem that Spark’s default cache replacement algorithm cannot accurately evaluate high-value data partitions,firstly the weight influence factors of data partitions are modeled and evaluated.Then,based on this weighted model,a cache replacement algorithm based on dynamic weighted data value is proposed,which takes into account hit rate and data difference.Better integration and usage strategies are implemented based on LRU(LeastRecentlyUsed).Theweight update algorithm updates the weight value when the data partition information changes,accurately measuring the importance of the partition in the current job;the cache removal algorithm clears partitions without useful values in the cache to releasememory resources;the weight replacement algorithm combines partition weights and partition information to replace RDD partitions when memory remaining space is insufficient.Finally,by setting up a Spark cluster environment,the algorithm proposed in this paper is experimentally verified.Experiments have shown that this algorithmcan effectively improve cache hit rate,enhance the performance of the platform,and reduce job execution time by 7.61%compared to existing improved algorithms.展开更多
With the rapid development of machine learning,the demand for high-efficient computing becomes more and more urgent.To break the bottleneck of the traditional Von Neumann architecture,computing-in-memory(CIM)has attra...With the rapid development of machine learning,the demand for high-efficient computing becomes more and more urgent.To break the bottleneck of the traditional Von Neumann architecture,computing-in-memory(CIM)has attracted increasing attention in recent years.In this work,to provide a feasible CIM solution for the large-scale neural networks(NN)requiring continuous weight updating in online training,a flash-based computing-in-memory with high endurance(10^(9) cycles)and ultrafast programming speed is investigated.On the one hand,the proposed programming scheme of channel hot electron injection(CHEI)and hot hole injection(HHI)demonstrate high linearity,symmetric potentiation,and a depression process,which help to improve the training speed and accuracy.On the other hand,the low-damage programming scheme and memory window(MW)optimizations can suppress cell degradation effectively with improved computing accuracy.Even after 109 cycles,the leakage current(I_(off))of cells remains sub-10pA,ensuring the large-scale computing ability of memory.Further characterizations are done on read disturb to demonstrate its robust reliabilities.By processing CIFAR-10 tasks,it is evident that~90%accuracy can be achieved after 109 cycles in both ResNet50 and VGG16 NN.Our results suggest that flash-based CIM has great potential to overcome the limitations of traditional Von Neumann architectures and enable high-performance NN online training,which pave the way for further development of artificial intelligence(AI)accelerators.展开更多
The clathrate hydrate memory effect is a fascinating phenomenon with potential applications in carbon capture,utilization and storage(CCUS),gas separation,and gas storage as it can accelerate the secondary formation o...The clathrate hydrate memory effect is a fascinating phenomenon with potential applications in carbon capture,utilization and storage(CCUS),gas separation,and gas storage as it can accelerate the secondary formation of clathrate hydrate.However,the underlying mechanism of this effect remains unclear.To gain a better understanding of the mechanism,we conducted molecular dynamic simulations to simulate the initial formation and reformation processes of methane hydrate.In this work,we showed the evolution process of hydrate residual structures into hydrate cages.The simulation results indicate that the residual structures are closely related to the existence of hydrate memory effect,and the higher the contribution of hydrate dissociated water to the hydrate nucleation process,the faster the hydrate nucleation.After hydrate dissociation,the locally ordered structures still exist after hydrate dissociation and can promote the formation of cluster structures,thus accelerating hydrate nucleation.Additionally,the nucleation process of hydrate and the formation process of clusters are inseparable.The size of clusters composed of cup-cage structures is critical for hydrate nucleation.The residence time at high temperature after hydrate decomposition will affect the strength of the hydrate memory effect.Our simulation results provide microscopic insights into the occurrence of the hydrate memory effect and shed light on the hydrate reformation process at the molecular scale.展开更多
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.I...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.展开更多
Today’s explosion of data urgently requires memory technologies capable of storing large volumes of data in shorter time frames,a feat unattain-able with Flash or DRAM.Intel Optane,commonly referred to as three-dimen...Today’s explosion of data urgently requires memory technologies capable of storing large volumes of data in shorter time frames,a feat unattain-able with Flash or DRAM.Intel Optane,commonly referred to as three-dimensional phase change memory,stands out as one of the most promising candidates.The Optane with cross-point architecture is constructed through layering a storage element and a selector known as the ovonic threshold switch(OTS).The OTS device,which employs chalcogenide film,has thereby gathered increased attention in recent years.In this paper,we begin by providing a brief introduction to the discovery process of the OTS phenomenon.Subsequently,we summarize the key elec-trical parameters of OTS devices and delve into recent explorations of OTS materials,which are categorized as Se-based,Te-based,and S-based material systems.Furthermore,we discuss various models for the OTS switching mechanism,including field-induced nucleation model,as well as several carrier injection models.Additionally,we review the progress and innovations in OTS mechanism research.Finally,we highlight the successful application of OTS devices in three-dimensional high-density memory and offer insights into their promising performance and extensive prospects in emerging applications,such as self-selecting memory and neuromorphic computing.展开更多
Skyrmions, with their vortex-like structures and inherent topological protection, play a pivotal role in developing innovative low-power memory and logic devices. The efficient generation and control of skyrmions in g...Skyrmions, with their vortex-like structures and inherent topological protection, play a pivotal role in developing innovative low-power memory and logic devices. The efficient generation and control of skyrmions in geometrically confined systems are crucial for the development of skyrmion-based spintronic devices. In this study, we focus on investigating the non-reciprocal transport behavior of skyrmions and their interactions with boundaries of various shapes. The shape of the notch structure in the nanotrack significantly affects the dynamic behavior of magnetic skyrmions. Through micromagnetic simulation, the non-reciprocal transport properties of skyrmions in nanowires with different notch structures are investigated in this work.展开更多
Reducing the process variation is a significant concern for resistive random access memory(RRAM).Due to its ultrahigh integration density,RRAM arrays are prone to lithographic variation during the lithography process,...Reducing the process variation is a significant concern for resistive random access memory(RRAM).Due to its ultrahigh integration density,RRAM arrays are prone to lithographic variation during the lithography process,introducing electrical variation among different RRAM devices.In this work,an optical physical verification methodology for the RRAM array is developed,and the effects of different layout parameters on important electrical characteristics are systematically investigated.The results indicate that the RRAM devices can be categorized into three clusters according to their locations and lithography environments.The read resistance is more sensitive to the locations in the array(~30%)than SET/RESET voltage(<10%).The increase in the RRAM device length and the application of the optical proximity correction technique can help to reduce the variation to less than 10%,whereas it reduces RRAM read resistance by 4×,resulting in a higher power and area consumption.As such,we provide design guidelines to minimize the electrical variation of RRAM arrays due to the lithography process.展开更多
Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inh...Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.展开更多
A notable portion of cachelines in real-world workloads exhibits inner non-uniform access behaviors.However,modern cache management rarely considers this fine-grained feature,which impacts the effective cache capacity...A notable portion of cachelines in real-world workloads exhibits inner non-uniform access behaviors.However,modern cache management rarely considers this fine-grained feature,which impacts the effective cache capacity of contemporary high-performance spacecraft processors.To harness these non-uniform access behaviors,an efficient cache replacement framework featuring an auxiliary cache specifically designed to retain evicted hot data was proposed.This framework reconstructs the cache replacement policy,facilitating data migration between the main cache and the auxiliary cache.Unlike traditional cacheline-granularity policies,the approach excels at identifying and evicting infrequently used data,thereby optimizing cache utilization.The evaluation shows impressive performance improvement,especially on workloads with irregular access patterns.Benefiting from fine granularity,the proposal achieves superior storage efficiency compared with commonly used cache management schemes,providing a potential optimization opportunity for modern resource-constrained processors,such as spacecraft processors.Furthermore,the framework complements existing modern cache replacement policies and can be seamlessly integrated with minimal modifications,enhancing their overall efficacy.展开更多
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 a...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.展开更多
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042 (both to XC)the Pearl River S&T Nova Program of Guangzhou,No.201806010025 (to XC)+3 种基金the Specialty Program of Guangdong Province Hospital of Chinese Medicine of China,No.YN2018ZD07 (to XC)the Natural Science Foundatior of Guangdong Province of China,No.2023A1515012174 (to JL)the Science and Technology Program of Guangzhou of China,No.20210201 0268 (to XC),20210201 0339 (to JS)Guangdong Provincial Key Laboratory of Research on Emergency in TCM,Nos.2018-75,2019-140 (to JS)
文摘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.
基金funded by FEDER/Ministerio de CienciaInnovacion y Universidades Agencia Estatal de Investigacion(MCIN/AEI 10.13039/501100011033)Grant(SAF2017-87595-R and PID2020-119729G8-100)(to EP)"Amigos de Ia Universidad de Navarra"and the Spanish Ministry of Universities for a fellowship(FPU)to NSS。
文摘Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative diseases.This review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative stress.The role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's disease.However,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific functions.Further studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological target.This will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.
基金supported by STI2030-Major Projects,No.2022ZD0207600 (to LZ)the National Natural Science Foundation of China,Nos.821 71446 (to JY),U22A20301 (to KFS),32070955 (to LZ)+1 种基金Guangdong Basic and Applied Basic Research Foundation,No.202381515040015 (to LZ)Science and Technology Program of Guangzhou of China,No.202007030012 (to KFS and LZ)
文摘Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.
基金financially supported by the National Natural Science Foundation of China(No.51974028)。
文摘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.
基金supported in parts by the National Natural Science Foundation of China,Nos.82101501(to QF),and 82201589(to XH)。
文摘Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.
文摘随着国民生活水平的提高,越来越多的人投身于股票市场.为了科学有效地量化选股,通过将量化投资、深度学习及文本分析进行有机结合,来建立量化选股模型.首先,通过文本分析筛选出基本面利好的股票;然后,通过长短期记忆(long-short term memory,LSTM)选出预测准确度良好的股票;最后,预测所选出的股票在未来几天的股价趋势.在实证分析方面,通过本模型对部分股票进行运算,选取预测效果较好的股票:赢合科技.
文摘In recent years,there has been considerable exploration into methods aimed at enhancing the regenerative capacity of transplanted and/or tissue-resident cells.Biomaterials,in particular,have garnered significant interest for their potential to serve as natural scaffolds for cells.In this editorial,we provide commentary on the study by Wang et al,in a recently published issue of World J Stem Cells,which investigates the use of a decellularized xenogeneic extracellular matrix(ECM)derived from antler stem cells for repairing osteochondral defects in rat knee joints.Our focus lies specifically on the crucial role of biological scaffolds as a strategy for augmenting stem cell potential and regenerative capabilities,thanks to the establishment of a favorable microenvironment(niche).Stem cell differen-tiation heavily depends on exposure to intrinsic properties of the ECM,including its chemical and protein composition,as well as the mechanical forces it can generate.Collectively,these physicochemical cues contribute to a bio-instructive signaling environment that offers tissue-specific guidance for achieving effective repair and regeneration.The interest in mechanobiology,often conceptualized as a form of“structural memory”,is steadily gaining more validation and momen-tum,especially in light of findings such as these.
基金supported by grants from the Ministerio de Economia y Competitividad(BFU2013-43458-R)Junta de Andalucia(P12-CTS-1694 and Proyexcel-00422)to ZUK。
文摘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.
基金the National Natural Science Foundation of China(61872284)Key Research and Development Program of Shaanxi(2023-YBGY-203,2023-YBGY-021)+3 种基金Industrialization Project of Shaanxi ProvincialDepartment of Education(21JC017)“Thirteenth Five-Year”National Key R&D Program Project(Project Number:2019YFD1100901)Natural Science Foundation of Shannxi Province,China(2021JLM-16,2023-JC-YB-825)Key R&D Plan of Xianyang City(L2023-ZDYF-QYCX-021)。
文摘Spark,a distributed computing platform,has rapidly developed in the field of big data.Its in-memory computing feature reduces disk read overhead and shortens data processing time,making it have broad application prospects in large-scale computing applications such as machine learning and image processing.However,the performance of the Spark platform still needs to be improved.When a large number of tasks are processed simultaneously,Spark’s cache replacementmechanismcannot identify high-value data partitions,resulting inmemory resources not being fully utilized and affecting the performance of the Spark platform.To address the problem that Spark’s default cache replacement algorithm cannot accurately evaluate high-value data partitions,firstly the weight influence factors of data partitions are modeled and evaluated.Then,based on this weighted model,a cache replacement algorithm based on dynamic weighted data value is proposed,which takes into account hit rate and data difference.Better integration and usage strategies are implemented based on LRU(LeastRecentlyUsed).Theweight update algorithm updates the weight value when the data partition information changes,accurately measuring the importance of the partition in the current job;the cache removal algorithm clears partitions without useful values in the cache to releasememory resources;the weight replacement algorithm combines partition weights and partition information to replace RDD partitions when memory remaining space is insufficient.Finally,by setting up a Spark cluster environment,the algorithm proposed in this paper is experimentally verified.Experiments have shown that this algorithmcan effectively improve cache hit rate,enhance the performance of the platform,and reduce job execution time by 7.61%compared to existing improved algorithms.
基金This work was supported by the National Natural Science Foundation of China(Nos.62034006,92264201,and 91964105)the Natural Science Foundation of Shandong Province(Nos.ZR2020JQ28 and ZR2020KF016)the Program of Qilu Young Scholars of Shandong University.
文摘With the rapid development of machine learning,the demand for high-efficient computing becomes more and more urgent.To break the bottleneck of the traditional Von Neumann architecture,computing-in-memory(CIM)has attracted increasing attention in recent years.In this work,to provide a feasible CIM solution for the large-scale neural networks(NN)requiring continuous weight updating in online training,a flash-based computing-in-memory with high endurance(10^(9) cycles)and ultrafast programming speed is investigated.On the one hand,the proposed programming scheme of channel hot electron injection(CHEI)and hot hole injection(HHI)demonstrate high linearity,symmetric potentiation,and a depression process,which help to improve the training speed and accuracy.On the other hand,the low-damage programming scheme and memory window(MW)optimizations can suppress cell degradation effectively with improved computing accuracy.Even after 109 cycles,the leakage current(I_(off))of cells remains sub-10pA,ensuring the large-scale computing ability of memory.Further characterizations are done on read disturb to demonstrate its robust reliabilities.By processing CIFAR-10 tasks,it is evident that~90%accuracy can be achieved after 109 cycles in both ResNet50 and VGG16 NN.Our results suggest that flash-based CIM has great potential to overcome the limitations of traditional Von Neumann architectures and enable high-performance NN online training,which pave the way for further development of artificial intelligence(AI)accelerators.
基金Financial support from the National Natural Science Foundation of China(22208329,22178378,22127812,21908116 and U19B2005)Jiangxi Provincial Natural Science Foundation of China(20232BAB213044)。
文摘The clathrate hydrate memory effect is a fascinating phenomenon with potential applications in carbon capture,utilization and storage(CCUS),gas separation,and gas storage as it can accelerate the secondary formation of clathrate hydrate.However,the underlying mechanism of this effect remains unclear.To gain a better understanding of the mechanism,we conducted molecular dynamic simulations to simulate the initial formation and reformation processes of methane hydrate.In this work,we showed the evolution process of hydrate residual structures into hydrate cages.The simulation results indicate that the residual structures are closely related to the existence of hydrate memory effect,and the higher the contribution of hydrate dissociated water to the hydrate nucleation process,the faster the hydrate nucleation.After hydrate dissociation,the locally ordered structures still exist after hydrate dissociation and can promote the formation of cluster structures,thus accelerating hydrate nucleation.Additionally,the nucleation process of hydrate and the formation process of clusters are inseparable.The size of clusters composed of cup-cage structures is critical for hydrate nucleation.The residence time at high temperature after hydrate decomposition will affect the strength of the hydrate memory effect.Our simulation results provide microscopic insights into the occurrence of the hydrate memory effect and shed light on the hydrate reformation process at the molecular scale.
基金the support of the National Natural Science Foundation of China(Grant No.62204201)。
文摘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.
基金M.Zhu acknowledges support by the National Outstanding Youth Program(62322411)the Hundred Talents Program(Chinese Academy of Sciences)+1 种基金the Shanghai Rising-Star Program(21QA1410800)The financial support was provided by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB44010200).
文摘Today’s explosion of data urgently requires memory technologies capable of storing large volumes of data in shorter time frames,a feat unattain-able with Flash or DRAM.Intel Optane,commonly referred to as three-dimensional phase change memory,stands out as one of the most promising candidates.The Optane with cross-point architecture is constructed through layering a storage element and a selector known as the ovonic threshold switch(OTS).The OTS device,which employs chalcogenide film,has thereby gathered increased attention in recent years.In this paper,we begin by providing a brief introduction to the discovery process of the OTS phenomenon.Subsequently,we summarize the key elec-trical parameters of OTS devices and delve into recent explorations of OTS materials,which are categorized as Se-based,Te-based,and S-based material systems.Furthermore,we discuss various models for the OTS switching mechanism,including field-induced nucleation model,as well as several carrier injection models.Additionally,we review the progress and innovations in OTS mechanism research.Finally,we highlight the successful application of OTS devices in three-dimensional high-density memory and offer insights into their promising performance and extensive prospects in emerging applications,such as self-selecting memory and neuromorphic computing.
基金Project supported by the Key-Area Research and Development Program of Guangdong Province,China(Grant No.2021B0101300003)the Guangdong Basic and Applied Basic Research Foundation,China(Grant Nos.2022A1515110863 and 2023A1515010837)+5 种基金the National Key Research and Development Program of China(Grant No.2016YFA0300803)the National Natural Science Foundation of China(Grant Nos.12304136,61427812,11774160,12241403,51771127,52171188,and 52111530143)the Natural Science Foundation of Jiangsu Province,China(Grant Nos.BK20192006 and BK20200307)the Fundamental Research Funds for the Central Universities,China(Grant No.021014380113)International Exchanges 2020 Cost Share(NSFC),China(Grant No.IECNSFC201296)the Project for Maiden Voyage of Guangzhou Basic and Applied Basic Research Scheme,China(Grant No.2024A04J4186)。
文摘Skyrmions, with their vortex-like structures and inherent topological protection, play a pivotal role in developing innovative low-power memory and logic devices. The efficient generation and control of skyrmions in geometrically confined systems are crucial for the development of skyrmion-based spintronic devices. In this study, we focus on investigating the non-reciprocal transport behavior of skyrmions and their interactions with boundaries of various shapes. The shape of the notch structure in the nanotrack significantly affects the dynamic behavior of magnetic skyrmions. Through micromagnetic simulation, the non-reciprocal transport properties of skyrmions in nanowires with different notch structures are investigated in this work.
基金supported in part by the Open Fund of State Key Laboratory of Integrated Chips and Systems,Fudan Universityin part by the National Science Foundation of China under Grant No.62304133 and No.62350610271.
文摘Reducing the process variation is a significant concern for resistive random access memory(RRAM).Due to its ultrahigh integration density,RRAM arrays are prone to lithographic variation during the lithography process,introducing electrical variation among different RRAM devices.In this work,an optical physical verification methodology for the RRAM array is developed,and the effects of different layout parameters on important electrical characteristics are systematically investigated.The results indicate that the RRAM devices can be categorized into three clusters according to their locations and lithography environments.The read resistance is more sensitive to the locations in the array(~30%)than SET/RESET voltage(<10%).The increase in the RRAM device length and the application of the optical proximity correction technique can help to reduce the variation to less than 10%,whereas it reduces RRAM read resistance by 4×,resulting in a higher power and area consumption.As such,we provide design guidelines to minimize the electrical variation of RRAM arrays due to the lithography process.
文摘Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.
文摘A notable portion of cachelines in real-world workloads exhibits inner non-uniform access behaviors.However,modern cache management rarely considers this fine-grained feature,which impacts the effective cache capacity of contemporary high-performance spacecraft processors.To harness these non-uniform access behaviors,an efficient cache replacement framework featuring an auxiliary cache specifically designed to retain evicted hot data was proposed.This framework reconstructs the cache replacement policy,facilitating data migration between the main cache and the auxiliary cache.Unlike traditional cacheline-granularity policies,the approach excels at identifying and evicting infrequently used data,thereby optimizing cache utilization.The evaluation shows impressive performance improvement,especially on workloads with irregular access patterns.Benefiting from fine granularity,the proposal achieves superior storage efficiency compared with commonly used cache management schemes,providing a potential optimization opportunity for modern resource-constrained processors,such as spacecraft processors.Furthermore,the framework complements existing modern cache replacement policies and can be seamlessly integrated with minimal modifications,enhancing their overall efficacy.
基金supported by the Natural Science Foundation of Heilongjiang Province of China,Outstanding Youth Foundation,No.YQ2022H003 (to DW)。
文摘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.