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.

Therapeutic potential of Carum carvi in depression,memory loss,and hippocampal sclerosis reversal in temporal lobe epilepsy

Background:Epilepsy is a disease characterized by unprovoked seizures,and it affects around 70 million people worldwide.Standard treatment is ineffective in one third of all epilepsy patients.Temporal Lobe Epilepsy with Hippocampal Sclerosis(TLE-HS)is the most drug-resistant form of epilepsy,and it also impacts physical,mental,and psychological well-being of patients.Carum carvi extract has demonstrated anti-convulsant,anti-depressant,and anxiolytic properties.This study was designed to investigate if Carum carvi extract can alleviate depression and memory loss symptoms in a TLE-HS animal model.Methods:Male Sprague Dawley rats were used to create a model of TLE-HS and Carum carvi extract treatment,along with appropriate controls,was used to test the efficacy of this herbal extract in reducing the symptoms of depression and memory loss.Results:Forced swim test showed that Carum carvi extract treated TLE-HS rats resulted in significant improvement of the symptoms of depression.However,novel object recognition test showed that memory improvement did not occur.Conclusion:Depression significantly impacts the quality of life in TLE-HS patients,and this study has shown that Carum carvi extract should be explored further as an adjuvant treatment for TLE-HS patients to improve their quality of life.

Evaluation of the long-term memory for thermosensation regulated by neuronal calcium sensor-1 in Caenorhabditis elegans

Objective To evaluate whether the thermotaxis tracking model is suitable for assessing long-term memory （LTM） in the nematode Caenorhabditis elegans. Methods Animals were trained at 20℃ overnight in presence of food. The percentage of animals performing isothermal tracking （IT） behavior was measured at different time intervals after the training. Results The percentage of animals performing IT behavior, the numbers of body bends inside and outside the training temperature, and the expression patterns of AFD and AIY neurons were similar to those in control animals at 36 and 48 h after training; whereas when extending to 60, 72, and 84 h, locomotory behavior defects were observed in the assayed animals, suggesting that this thermal tracking model is feasible for analyzing LTM at 36 and 48 h after training. Moreover, the percent-age of animals performing IT behavior was reduced at 18, 36, and 48 h after training in neuronal calcium sensor-1 gene （nsc-1） mutant animals compared with that in wild-type N2 animals. In addition, exposure to plumbum （Pb） significantly repressed the LTM at 18, 36, and 48 h after training in both wild-type N2 and ncs-1 mutant animals. Conclusion The thermotaxis tracking model is suitable for evaluating the LTM regulated by NCS-1, and can be employed for elucidating regulatory functions of specific genes or effects of stimuli on memory in C. elegans.

The Screening of Genes Sensitive to Long-Term, Low-Level Microwave Exposure and Bioinformatic Analysis of Potential Correlations to Learning and Memory

Objective To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction. Methods Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR. Results The gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memory. Conclusion Long-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases.

A new isolation device using shape memory alloy and its application for long-span structures

The key points to consider in determining the effectiveness of using structural isolation with shape memory alloys （SMA） are the constitutive model, the SMA isolation device and the analysis method. In this paper, a simplified constitutive model based on the classic theory of plasticity is proposed to simulate the behavior of the superelasticity of the SMA, in which the martensite volume fraction is considered as one of the state variables. Comparisons between simulation results and experimental results are made and indicate that the proposed constitutive model yields stress-strain curves that are in good agreement with the experimental ones. Thus, the proposed model can correctly simulate the yield mechanism and energy dissipation capacity of the SMA. Next, in order to make full use of the superelasticity of SMA, a new SMA isolator composed of pre-tensioned SMA bars is presented. Then, a finite element analytical model is established to simulate the behavior of the SMA isolator according to its configuration and simplified constitutive model. Finally, a simplified design method for long-span structures installed with SMA isolators is proposed, which is further used to investigate the isolation effects of a space grid structure. Results show that the SMA isolator can reduce the seismic responses of the structure effectively, which indicates the effectiveness of the proposed SMA isolation method.

Ro 20-1724 Ameliorates Learning Deficit and Long-Term Memory Impairment Secondary to Repeated Ketamine Anesthesia in Young Rats

To investigate effects and possible mechanism of Ro 20-1724, a PDE4 inhibitor, on long-time learning and memory ability following repeated ketamine exposure in immature rats. Methods: Sixty 21-day-old SD rats were randomly divided into five groups (n = 12): C: Normal control group, S: Saline control group, K: Ketamine, K + Ro:?Ketamine + Ro 20-1724, K + E: Ketamine + ethanol vehicle. Ro 20-1724 (0.5 mg·kg-1) or its vehicle (ethanol) was administered intraperitoneally 30 minutes after ketamine anesthesia (70 mg·kg-1), daily for seven days. Nine weeks after birth, the Morris water maze was used to test the ability of learning and spatial localization memory on the rats. Following behavioral testing, animals’ hippocampi were removed for Western blot and electron microscopic examination. Results: In the Morris water maze test, compared with controls, the escape latency in groups exposed to ketamine or ketamine plus the ethanol vehicle were significantly prolonged (P P < 0.05), and the expression of p-CREB in the hippocampus was also decreased (P 0.05), while there was no significant difference between control groups and animals treated with Ro 20-1724 following ketamine exposure (P > 0.05). Electron microscopy demonstrated degenerative changes in hippocampal neurons of animals repetitively exposed to 70 mg·kg-1 Ketamine, which was ameliorated by Ro 20-1724 (0.5 mg·kg-1). Conclusion: The PDE-4 inhibitor Ro 20-1724 (0.5 mg·kg-1<span

Understanding long-term memory in global mean temperature:An attribution study based on model simulations

Long-term memory(LTM)in the climate system has been well recognized and applied in different research fields,but the origins of this property are still not clear.In this work,the authors contribute to this issue by studying model simulations under different scenarios.The global mean temperatures from pre-industrial control runs(pi Control),historical(all forcings)simulations,natural forcing only simulations(Historical Nat),greenhouse gas forcing only simulations(Historical GHG),etc.,are analyzed using the detrended fluctuation analysis.The authors find that the LTM already exists in the pi Control simulations,indicating the important roles of internal natural variability in producing the LTM.By comparing the results among different scenarios,the LTM from the piControl runs is further found to be strengthened by adding natural forcings such as the volcanic forcing and the solar forcing.Accordingly,the observed LTM in the climate system is suggested to be mainly controlled by both the‘internal’natural variability and the‘external’natural forcings.The anthropogenic forcings,however,may weaken the LTM.In the projections from RCP2.6 to RCP8.5,a weakening trend of the LTM strength is found.In view of the close relations between the climate memory and the climate predictability,a reduced predictability may be expected in a warming climate.

Long-term spatial memory and morphological changes in hippocampus of Wistar rats exposed to smoke from Carica papaya leaves

Objective:To investigate the effects of smoking of dried leaves of Carica papaya(pawpaw)based on ethnopharmacological information which indicated that smoking of papaya leaves could influence motor performance and learning.Methods:Twenty-four rats were used for the study,and were grouped into four groups.Groups 1served as the control(not exposed to papaya leaves smoke),while Groups 2,3 and 4 were exposed to smoke from 6.25 g,12.50 g and 18.75 g of dry pawpaw leaves respectively in a smoking chamber twice daily for 21 d with each exposure lasting for 3 min.Lastly,hippocampus was harvested in each group for histological study.Result:The results showed that there were significant(P<0.05)increases in mean of recall latencies of long-term spatial memory in the animal administered the high dose while the other groups had significantly(P<0.05)lower frequencies.Histological investigation showed signs of mild neural degeneration in high dose group and hypochromic appcarance of the Nissl substance in all treated groups.Conclusions:In conclusion,the findings from this study has demonstrated that smoking of papaya leaves has the ability to maintain an intact long-term spatial memory at all doses but retrieving such memory is faster with the low and medium dosages.

Estimation of unloading relaxation depth of Baihetan Arch Dam foundation using long-short term memory network

The unloading relaxation caused by excavation for construction of high arch dams is an important factor influencing the foundation’s integrity and strength.To evaluate the degree of unloading relaxation,the long-short term memory(LSTM)network was used to estimate the depth of unloading relaxation zones on the left bank foundation of the Baihetan Arch Dam.Principal component analysis indicates that rock charac-teristics,the structural plane,the protection layer,lithology,and time are the main factors.The LSTM network results demonstrate the unloading relaxation characteristics of the left bank,and the relationships with the factors were also analyzed.The structural plane has the most significant influence on the distribution of unloading relaxation zones.Compared with massive basalt,the columnar jointed basalt experiences a more significant unloading relaxation phenomenon with a clear time effect,with the average unloading relaxation period being 50 d.The protection layer can effectively reduce the unloading relaxation depth by approximately 20%.

Correlating learning and memory improvements to long-term potentiation in patients with brain injury

BACKGROUND： Brain injury patients often exhibit learning and memory functional deficits. Long-term potentiation （LTP） is a representative index for studying learning and memory cellular models; the LTP index correlates to neural plasticity. OBJECTIVE： This study was designed to investigate correlations of learning and memory functions to LTP in brain injury patients, and to summarize the research advancements in mechanisms underlying brain functional improvements after rehabilitation intervention. RETRIEVAL STRATEGY： Using the terms ＂brain injuries, rehabilitation, learning and memory, long-term potentiation＂, manuscripts that were published from 2000-2007 were retrieved from the PubMed database. At the same time, manuscripts published from 2000-2007 were also retrieved from the Database of Chinese Scientific and Technical Periodicals with the same terms in the Chinese language. A total of 64 manuscripts were obtained and primarily screened. Inclusion criteria： studies on learning and memory, as well as LTP in brain injury patients, and studies focused on the effects of rehabilitation intervention on the two indices; studies that were recently published or in high-impact journals. Exclusion criteria： repetitive studies. LITERATURE EVALUATION： The included manuscripts primarily focused on correlations between learning and memory and LTP, the effects of brain injury on learning and memory, as well as LTP, and the effects of rehabilitation intervention on learning and memory after brain injury. The included 39 manuscripts were clinical, basic experimental, or review studies. DATA SYNTHESIS： Learning and memory closely correlates to LTP. The neurobiological basis of learning and memory is central nervous system plasticity, which involves neural networks, neural circuits, and synaptic connections, in particular, synaptic plasticity. LTP is considered to be an ideal model for studying synaptic plasticity, and it is also a classic model for studying neural plasticity of learning and memory. Brain injury patients clinically present with various manifestations, such as paralysis and sensory disability, which closely correlate to injured regions. In addition, learning and memory abilities decrease in brain injury patients and LTP decreases following brain injury. Brain tissue injury will lead to brain functional deficits. Hippocampal LTP is very sensitive. Difficulties in LTP induction are apparent even prior to morphological changes in brain tissue. There are no specific treatments for learning and memory functional deficits following brain injury. At present, behavioral and compensative therapies are the typical forms of rehabilitation. These results indicate that rehabilitation promotes learning and memory functional recovery in brain injury patients by speeding up LTP formation in the hippocampal CA3 region. CONCLUSION： Rehabilitation intervention increases LTP formation in the hippocampal CA3 region and recovers learning and memory functions in brain injury patients.

Microstructure and diffraction pattern changes resulted from long-term aging of martensite CuZnAlMnNi shape memory alloy

Microstructures of a CuZnAlMnNi shape memory alloy in the as-quenched andlong-term aged conditions were investigated by transmission electron microscopy. Aged for one yearin martensite phase, an equilibrium α-phase with fcc structure was observed in the M18R martensitematrix, accompanied by the appearance of a novel diffraction pattern. By analysis, it was suggestedthat the novel pattern results from the α-phase and the martensite matrix remaining in seven fineplates which produce intense secondary diffraction effect when the diffraction beams enter from onephase into another.

Long-Term Electrophysiological and Behavioral Analysis on the Improvement of Visual Working Memory Load, Training Gains, and Transfer Benefits

Recent evidence demonstrates that with training, one can enhance visual working memory (VWM) capacity and attention over time in the near transfer tasks. Not only do these studies reveal the characteristics of VWM load and the influences of training, they may also provide insights into developing effective rehabilitation for patients with VWM deficiencies. However, few studies have investigated VWM over extended periods of time and evaluated transfer benefits on non-trained tasks. Here, we combined behavioral and electroencephalographical approaches to investigate VWM load, training gains, and transfer benefits. Our results reveal that VWM capacity is directly correlated to the difference of event-related potential waveforms. In particular, the “magic number 4” can be observed through the contralateral delay amplitude and the average capacity is 3.25-item over 15 participants. Furthermore, our findings indicate that VWM capacity can be improved through training;and after training exercises, participants from the training group are able to dramatically improve their performance. Likewise, the training effects on non-trained tasks can also be observed at the 12th week after training. Therefore, we conclude that participants can benefit from training gains, and augmented VWM capacity sustained over long periods of time on specific variety of tasks.

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.

Analyses of fear memory in Arc/Arg3.1-deficient mice: intact short-term memory and impaired long-term and remote memory

Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) was originally identified in patients with seizures. It is densely distributed in the hip-pocampus and amygdala in particular. Because the expression of Arc/Arg3.1 is regulated by nerve in-puts, it is thought to be an immediate early gene. As shown both in vitro and in vivo, Arc/Arg3.1 is in-volved in synaptic consolidation and regulates some forms of learning and memory in rats and mice [1,2]. Furthermore, a recent study suggests that Arc/Arg3.1 may play a significant role in signal transmission via AMPA-type glutamate receptors [3-5]. Therefore, we conducted a detailed analysis of fear memory in Arc/Arg3.1-deficient mice. As previously reported, the knockout animals exhib-ited impaired fear memory in both contextual and cued test situations. Although Arc/Arg3.1-deficient mice showed almost the same performance as wild-type littermates 4 hr after a conditioning trial, their performance was impaired in the retention test after 24 hr or longer, either with or without reconsolidation. Immunohistochemical analyses showed an abnormal density of GluR1 in the hip-pocampus of Arc/Arg3.1-deficient mice;however, an application of AMPA potentiator did not improve memory performance in the mutant mice. Memory impairment in Arc/Arg3.1-deficient mice is so ro-bust that the mice provide a useful tool for devel-oping treatments for memory impairment.

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.

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.

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.