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
OBJECTIVE: To investigate the effects of combined acupuncture and eugenol on learning-memory ability and the antioxidation system of the hippocampus in Alzheimer disease (AD) rats. METHODS: Sixty Sprague Dawley rats, ...OBJECTIVE: To investigate the effects of combined acupuncture and eugenol on learning-memory ability and the antioxidation system of the hippocampus in Alzheimer disease (AD) rats. METHODS: Sixty Sprague Dawley rats, weighing (300±10) g, were randomly divided with 10 rats per group into a normal control group, AD model group, AD with cut olfactory nerve group, Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group. The AD model was established by injection of amyloid β1-40 (Aβ 1-40). Morris maze tests were conducted for evaluating the learning-memory ability. Content of malo- ndialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus were detected. RESULTS: The average escape latency and the mean swimming distance in the normal control group, the Xiu three-needle group, the eugenol group, and the combined acupuncture and euge-nol group were significantly shorter than those in the AD model group (all P<0.01). The combined acupuncture and eugenol group had shorter escape latency and mean swimming distance than those in the Xiu three-needle group and the eugenol group. There were no significant differences between the Xiu three-needle group and the eugenol group and between the AD group and the AD with cut olfactory nerve group (P>0.05). Compared with the normal control group, the MDA content in the hippocampus significantly increased (P<0.05) and GSH-Px and SOD activities significantly decreased in the AD model group (P<0.01). Compared with the AD model group, significantly decreased (P< 0.01) and SOD and GSH-Px activities significantly increased in the Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group (P<0.05). Compared with the Xiu three-needle group and eugenol group, the MDA content significantly decreased (P<0.05) and SOD and GSH-Px activities increased (P<0.05) in the combined acupuncture and eugenol group. There were no significant differences among the three indices between the Xiu three-needle group and the eugenol group and between the AD model group and the AD with cut olfactory nerve group (P>0.05). CONCLUSION: Both Xiu three-needle and eugenol can increase learning-memory ability, decrease MDA content, and increase SOD and GSH-Px activities in the hippocampus in AD rats. The combination of acupuncture with eugenol has stronger effects, and the effects depend on the olfactory pathway.展开更多
Objective:To observe the effect of scalp acupoint cluster needling on learning and memory ability and inflammatory mediators in CA1 area of hippocampus in rats with Alzheimer's disease(AD).Methods:A total of 40 SP...Objective:To observe the effect of scalp acupoint cluster needling on learning and memory ability and inflammatory mediators in CA1 area of hippocampus in rats with Alzheimer's disease(AD).Methods:A total of 40 SPF Wistar rats were randomly divided into blank group,sham operation group,model group and scalp acupoint cluster needling group,with 10 rats in each group.The AD model was duplicated by injecting Abeta 1-42 solution into bilateral hippocampus in model group and scalp acupoint cluster needling group.The sham operation group was injected with the same amount of sterile hydrogen peroxide,while the blank group was not treated.The scalp acupoint cluster needling group was given acupuncture intervention from 2 d after model establishment.The blank group,sham operation group and model group were only bundled and fixed in the dorsal position once a day for 14 consecutive days.After treatment,the learning and memory ability of AD rats was tested by Morris water maze test,the contents and activities of Ach,ChAT and AcE in hippocampal CA1 area were detected by ELISA,and the expressions of IL-6,IL-10 protein and mRNA in hippocampal CA1 area were detected by immunohistochemistry and RT-PCR,respectively.Results:Ach content,ChAT activity,IL-10 protein and mRNA expression in hippocampus were significantly lower than those in blank group,while AchE activity and IL-6 protein and mRNA expression were significantly higher than those in blank group.Compared with the model group,scalp acupoint cluster needling could significantly reduce the escape latency time,increase the number of crossing platforms and effective residence time,increase the content of Ach,the activity of ChAT,the expression of IL-10 protein and mRNA in hippocampus,and decrease the activity of AchE and the expression of IL-6 protein and mRNA.Conclusion:Controlling the expression of inflammatory factors and promoting the content of Ach in hippocampal CA1 region of AD rats can improve the learning and memory ability of AD rats.展开更多
In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error cou...In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error counts,indicating a learning and memory disorder.After treatment with 30,60,90,120,or 200 mg/kg lithium chloride,the learning and memory abilities of the Fmr1 KO mice were significantly ameliorated,in particular,the 200 mg/kg lithium chloride treatment had the most significant effect.Western blot analysis showed that lithium chloride significantly enhanced the expression of phosphorylated glycogen synthase kinase 3 beta,an inactive form of glycogen synthase kinase 3 beta,in the cerebral cortex and hippocampus of the Fmr1 KO mice.These results indicated that lithium chloride improved learning and memory in the Fmr1 KO mice,possibly by inhibiting glycogen synthase kinase 3 beta activity.展开更多
Transthyretin (TTR), a carrier protein present in the liver and choroid plexus of the brain, has been shown to be responsible for binding thyroid hormone thyroxin (T4) and retinol in plasma and cerebrospinal fluid (CS...Transthyretin (TTR), a carrier protein present in the liver and choroid plexus of the brain, has been shown to be responsible for binding thyroid hormone thyroxin (T4) and retinol in plasma and cerebrospinal fluid (CSF). TTR aids in sequestering of beta-amyloid peptides Aβ deposition, and protects the brain from trauma, ischemic stroke and Alzheimer disease (AD). Accordingly, hippocampal gene expression of TTR plays a significant role in learning and memory as well as in simulation of spatial memory tasks. TTR via interacting with transcription factor CREB regulates this process and decreased expression leads to memory deficits. By different signaling pathways, like MAPK, AKT, and ERK via Src, TTR provides tropical support through megalin receptor by promoting neurite outgrowth and protecting the neurons from traumatic brain injury. TTR is also responsible for the transient rise in intracellular Ca2+ via NMDA receptor, playing a dominant role under excitotoxic conditions. In this review, we tried to shed light on how TTR is involved in maintaining normal cognitive processes, its role in learning and memory, under memory deficit conditions;by which mechanisms it promotes neurite outgrowth;and how it protects the brain from Alzheimer disease (AD).展开更多
A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presente...A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presented to highlight the role of emotional factors in causing the disease. The question of whether Alzheimer’s disease is an adaptability disorder is raised, given the patient blocked out her memory of her childhood experience. The importance of “happiness” as a treatment goal raises issues of advocacy and Guardianship as well as capacity, which is addressed by actual case reference and court action in defence of the patient’s rights to have their wishes respected and observed. Functional mental capacity assessment, using the Functional Mental State Measure (FMSM) gives a greater indication of neuronal reserve than standard cognitive testing, as it helps to unravel the dilemma associated with pure cognitive assessment in Alzheimer’s Disease as well as vascular dementia patients and patients who, despite retained and intact functional capacity and ability to express their wishes, i.e. “best interest”, are “wrongly” placed under Guardianship. Maladaptive responses, to control the change in external environment that are sensed or perceived, and which lead to disorder or to susceptibility to disease, exemplify a General Systems Theory approach, in which appropriate and adequate responses to environmental change, in behavioural terms, by a person, whether independently, or as the recipient or giver, or both, leads to functional interaction and happiness.展开更多
An inverse vulcanized polymer,SZIM combining Zn2+-imidazole coordination bonds and polysulfide bonds was synthesized and incorporated into bio-based Eucommia ulmoides gum (EUG) to generate EUG-SZIM-xs.The residual cry...An inverse vulcanized polymer,SZIM combining Zn2+-imidazole coordination bonds and polysulfide bonds was synthesized and incorporated into bio-based Eucommia ulmoides gum (EUG) to generate EUG-SZIM-xs.The residual crystallinity of the EUG matrix synergistically interacted with the dual cross-linking networks to establish reversible deformation domains,providing EUG-SZIM-xs with quick shape memory capability at moderate temperatures.The damping properties were also investigated,and EUG-SZIM-xs displayed high tanδ values (>0.3) when the SZIM dosage was higher than 5.5 phr,which showed a positive correlation with SZIM concentration.Such good damping performance endowed the EUG-SZIM-xs with broadband low-frequency sound absorption.In addition,the dual cross-linking networks endowed the materials with reprocessability under different catalytic systems,and the 1,8-diazobicyclic[5.4.0]undeca-7-ene (DBU)-catalyzed samples exhibited better mechanical properties than EUG-SZIM-xs.展开更多
Objective To determine the impact of passive smoking and the protective effect of antioxidants such as vitamin E and quercetin on learning and memory ability of mouse offsprings. Methods A passive smoking model of pre...Objective To determine the impact of passive smoking and the protective effect of antioxidants such as vitamin E and quercetin on learning and memory ability of mouse offsprings. Methods A passive smoking model of pregnant mice was established. Learning and memory ability was evaluated by the water maze test and long term potentiation （LTP）. Nitric oxide （NO）, content, nitric oxide synthase （NOS）, acetylcholinesteras （Ache） activity in brain, vitamin E concentration, and reactive oxygen species （ROS） in serum were determined. The latency period （the time during which the mice swim from the starting position to the ending position） and errors （the number of mice entering the blind end） in control and antioxidant intervention groups were compared with those in the smoke exposure group after 6 days. Results The latency period as well as errors in the air, control diet, tobacco smoke （TS）, and vitamin E diet groups were decreased significantly as compared with the TS and control diet groups （P〈O.05）. LTP was restrained in the TS and control diet groups. LTP in all the antioxidant diet groups was significantly increased compared with the TS and control diet groups. In addition, NOS and acetylcholinesteras （Ache） activitiy was significantly higher in the TS and control diet groups than in the air and control diet group. NO content was not significantly different among the different groups, and significantly lower in the TS and vitamin E diet groups than in the TS group, control diet group, quercetin diet group, and mixture diet group （P〈0.05）. Vitamin E concentration and ROS activity in serum were correlated with the outcome of water maze and LTP. Conclusion Passive smoking reduces LTP formation by disturbing the hippocampus function of mice, by decreasing NOS （especially vitamin E） partially improve the learning and memory smoke during pregnancy. and Ache activity and increasing NO content. Antioxidants ability of offsprings whose mothers are exposed to tobacco展开更多
Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However,...Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However, the mechanisms that mediate its effects remain unclear. In this study, the expression of N-methyI-D-aspartate receptor 1 mRNA, the content of nitric oxide, and the concentration of calcium in neurons was determined with in situ hybridization, spectrophotometry and flow cytometry, respectively. In addition, the expressions of N-methyI-D-aspartate receptor 1, nerve growth factor protein, and glial cell line-derived neurotrophic factor protein were detected with immunohistochemistry. We found that KSZZP could significantly decrease the expression of N-methyI-D-aspartate receptor 1 mRNA and protein, the content of nitric oxide, and the concentration of calcium in neurons. KSZZP also increased the expression of nerve growth factor and glial cell line-derived neurotrophic factor protein in the hippocampus CA1 region and in the cerebral cortex. Morris water maze and passive avoidance tests verified that KSZZP ameliorated the cognitive impairments of vascular dementia rats. Moreover, the KSZZP-induced improvements in the cognitive functions of vascular dementia rats were correlated with both inhibition of N-methyl-D-aspartate-induced excitable neurotoxicity and elevation of neurotrophic factor expression.展开更多
We studied on the effect of Curcuma longa extract on spatial learning-related memory ability of old rats in eight-arm radial maze task. Rats were randomly divided into two groups: one group was orally administered 100...We studied on the effect of Curcuma longa extract on spatial learning-related memory ability of old rats in eight-arm radial maze task. Rats were randomly divided into two groups: one group was orally administered 100 mg/KgBW/day C. longa extract (CLE) dissolved in deionized water and the other group was administered the vehicle alone for 10 weeks. The rats were tested with the partially baited eight-arm radial maze to evaluate two types of spatial memory-related learning ability displayed by reference memory errors (RMEs) and working memory errors (WMEs). Chronic administration of CLE significantly decreased the number of RMEs and WMEs, concurrently with the decreases in the cortico-hippocampal levels of lipid peroxides (LPO) and tumor necrosis factor alpha (TNF-α). In a parallel set of experiments, CLE-pretreated rats of the same age group were subjected to hypoxia-reperfusion injury by carotid artery occlusion to induce oxidative stress in the brains in order to examine whether such an in vivo hypoxia-induced oxidative stress could be ameliorated by the extract. Again, the levels of LPO were significantly decreased in the cortico-hippocampal tissues of the CLE-fed hypoxic rats. The histology of the brains also revealed that the CLE-pretreated rats had retained improved cellular integrity. Finally, our results provide the evidence that oral administration of C. longa extract increases the defense against oxidative stress and proinflammatory TNF-α, concurrently with the improvement of memory-related brain cognitive ability of the aged rats.展开更多
This study investigates the application of Learnable Memory Vision Transformers(LMViT)for detecting metal surface flaws,comparing their performance with traditional CNNs,specifically ResNet18 and ResNet50,as well as o...This study investigates the application of Learnable Memory Vision Transformers(LMViT)for detecting metal surface flaws,comparing their performance with traditional CNNs,specifically ResNet18 and ResNet50,as well as other transformer-based models including Token to Token ViT,ViT withoutmemory,and Parallel ViT.Leveraging awidely-used steel surface defect dataset,the research applies data augmentation and t-distributed stochastic neighbor embedding(t-SNE)to enhance feature extraction and understanding.These techniques mitigated overfitting,stabilized training,and improved generalization capabilities.The LMViT model achieved a test accuracy of 97.22%,significantly outperforming ResNet18(88.89%)and ResNet50(88.90%),aswell as the Token to TokenViT(88.46%),ViT without memory(87.18),and Parallel ViT(91.03%).Furthermore,LMViT exhibited superior training and validation performance,attaining a validation accuracy of 98.2%compared to 91.0%for ResNet 18,96.0%for ResNet50,and 89.12%,87.51%,and 91.21%for Token to Token ViT,ViT without memory,and Parallel ViT,respectively.The findings highlight the LMViT’s ability to capture long-range dependencies in images,an areawhere CNNs struggle due to their reliance on local receptive fields and hierarchical feature extraction.The additional transformer-based models also demonstrate improved performance in capturing complex features over CNNs,with LMViT excelling particularly at detecting subtle and complex defects,which is critical for maintaining product quality and operational efficiency in industrial applications.For instance,the LMViT model successfully identified fine scratches and minor surface irregularities that CNNs often misclassify.This study not only demonstrates LMViT’s potential for real-world defect detection but also underscores the promise of other transformer-based architectures like Token to Token ViT,ViT without memory,and Parallel ViT in industrial scenarios where complex spatial relationships are key.Future research may focus on enhancing LMViT’s computational efficiency for deployment in real-time quality control systems.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
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 rehabilitatio...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.展开更多
Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, bu...Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.展开更多
Heat sinks were invented to absorb heat from an electronic circuit conduct, and then to dissipate or radiate this heat to the surrounding supposedly, ventilated space, at a rate equal to or faster than that of its bui...Heat sinks were invented to absorb heat from an electronic circuit conduct, and then to dissipate or radiate this heat to the surrounding supposedly, ventilated space, at a rate equal to or faster than that of its buildup. Ventilation was not initially recognized as an essential factor to thermal dispersion. However, as electronic circuit-boards continued to heat up, circuit failure became a problem, forcing the inclusion of miniaturized high speed fans. Later, heat sinks with fins and quiet fans were incorporated in most manufactured circuits. Now heat sinks come in the form of a fan with fans made to function as fins to disperse heat. Heat sinks absorb and radiate excess heat from circuit-boards in order to prolong the circuit’s life span. The higher the thermal conductivity of the material used the more efficient and effective the heat sink is. This paper is an attempt to theoretically design a heat sink with a temperature gradient lower than that of the circuit board’s excess heat.展开更多
The study aims to determine the validity and reliability of the Wechsler Preschool and Primary Scale of Intelligence–Third Edition(WPPSI-III)scores in a sample of kindergarten and lower primary pupils from Khartoum S...The study aims to determine the validity and reliability of the Wechsler Preschool and Primary Scale of Intelligence–Third Edition(WPPSI-III)scores in a sample of kindergarten and lower primary pupils from Khartoum State,Sudan.It also aims to examine whether test’s factor structure in this sample replicated that of the original WPPSI-III.The study sample consisted of 384 kindergarten and primary school children in Khartoum State(females=50%mean age=4.14,SD=1.37),selected using stratified random sampling across its seven localities:Khartoum,Jebel Awliya,Khartoum Bahri,East Nile,Omdurman,Ombada,Karari.For concurrent validation,the children additionally completed the Goodenough Draw-a-Man Test,and the Colored Progressive Matrices.WPPSI-III scores demonstrated high internal consistency across the subtest items.Confirmatory factor analysis indicators for total,verbal,and performance intelligence were all excellent.The scale also showed weak to strong score stability ranging from 0.25(weak)to 0.88(strong)based on the Spearman-Brown equation,0.25 to 0.75 based on the Guttman split-half method.The Cronbach’s alpha coefficient scores ranged from 0.54 to 0.93.The WPPSI-III and Goodenough Draw-a-Man Test scores concurrent validity scores were poor(0.05)to modest(0.31),and while those with the Colored Progressive Matrices test were poor(r=0.04–0.18).Thesefindings provide evidence to suggest that the WPPSI-III is appropriate for research use with kindergarten and lower primary school students in Khartoum State,Sudan.展开更多
A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presente...A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presented to highlight the role of emotional factors in causing the disease. The question of whether Alzheimer’s disease is an adaptability disorder is raised, given the patient blocked out her memory of her childhood experience. The importance of “happiness” as a treatment goal raises issues of advocacy and Guardianship as well as capacity, which is addressed by actual case reference and court action in defence of the patient’s rights to have their wishes respected and observed. Functional mental capacity assessment, using the Functional Mental State Measure (FMSM) gives a greater indication of neuronal reserve than standard cognitive testing, as it helps to unravel the dilemma associated with pure cognitive assessment in Alzheimer’s Disease as well as vascular dementia patients and patients who, despite retained and intact functional capacity and ability to express their wishes, i.e. “best interest”, are “wrongly” placed under Guardianship. A General Systems approach, which recognises functional interaction as optimal and withdrawal or inadequate and/or inappropriate response as not, provides further understanding of the relationship between emotional factors, memory and neurodegenerative (Alzheimer’s) disease.展开更多
Background:Mitochondrial dysfunction plays a critical role in the pathogenesis of Alzheimer’s disease(AD).Resveratrol is a promising compound for the treatment of various neurodegenerative diseases,including AD.Aims:...Background:Mitochondrial dysfunction plays a critical role in the pathogenesis of Alzheimer’s disease(AD).Resveratrol is a promising compound for the treatment of various neurodegenerative diseases,including AD.Aims:To investigate mitochondrial damage and the effects of resveratrol on inflammation,cognitive function,and mitochondrial quality control in APP/PS1 mice.Methods:Comparative analysis of mitochondrial DNA(mtDNA)damage was conducted between 10-month-old APP/PS1 mice and age-matched C57BL/6 mice.Assessments included measurement of amyloid-βlevels,inflammatory markers,swimming distance in the Morris water maze,and gut microbiome composition.Resveratrol’s effects on cytokine expression,mtDNA levels in plasma,and activation of Nuclear factor erythroid 2-related factor 2/Antioxidant response element(Nrf2/ARE)and phosphoinositide 3-kinase/protein kinase B(also known as Akt)/mechanistic target of rapamycin complex 1(PI3K/Akt/mTORC1)signaling pathways were also evaluated.Results:APP/PS1 mice exhibited significantly increased mtDNA damage in the prefrontal cortex,midbrain,and cerebellum,alongside higher amyloid-βlevels and inflammatory markers.Resveratrol treatment led to reduced expression of pro-inflammatory cytokines,a decrease in Proteobacteria levels,and lower cell-free mtDNA in plasma.Partial improvement in long-term spatial memory was observed in APP/PS1 mice following resveratrol treatment,likely due to its anti-inflammatory properties.Activation of the Nrf2/ARE signaling pathway and markers of PI3K/Akt/mTORC1 axis activation were noted,with the latter regulating long-term potentiation.Conclusion:Resveratrol demonstrates potential in mitigating inflammation and improving mitochondrial quality control in APP/PS1 mice,but it does not reduce amyloid-βlevels,highlighting the complexity of AD pathology and the need for further research.展开更多
There are presently no in-depth published neuropsychological studies of West Nile Virus (WNV) encephalitis patients that have been well-correlated with high resolution structural MRI. In this study a middleaged male w...There are presently no in-depth published neuropsychological studies of West Nile Virus (WNV) encephalitis patients that have been well-correlated with high resolution structural MRI. In this study a middleaged male who developed West Nile Virus encephalitis five years previously was examined three times over a two year period. We examined him with the Wechsler Adult Intelligence Scales—Fourth Edition and the Wechsler Memory Scale—Fourth Edition (WAIS-IV/WMS-IV) and Advanced Clinical Solutions battery supplemented by tests of attention, executive, motor and sensory functions. Neuroradiological imaging revealed hypodensities within the left hippocampus in the axial and coronal planes with T2-FLAIR MRI. The man was previously high functioning and although he had prior history of well-controlled epilepsy it seems unlikely that the epilepsy could fully account for the neuropathological changes. The patient had previously completed a demanding six year double science degree program before he became ill with WNV and he had been a successful manager and director of a research company. Delayed auditory memory scores were at least two standard deviation units below age expected levels and semantic fluency and Booklet Category Tests of executive function were also in the impaired range. Moreover the illness onset profile of muscle weakness, extreme fatigue, memory complaints as well as inability to carry out research projects involving planning on the job were highly consistent with WNV encephalitis. If the memory and executive function deficits had been premorbid manifestations of epilepsy it is unlikely he would have attained the levels he did educationally and occupationally. This left hippocampal lesion is characteristic of other encephalitic viral infections such as herpes simplex virus. To our knowledge this is the first lateralized WNV encephalitis medial temporal lobe patient in the published literature.展开更多
Fluoroalkyl end-capped vinyltrimethoxysilane oligomer [RF-(CH2CHSi(OMe)3)n-RF;RF = CF(CF3)OCF7, n = 2, 3;RF-(VM)n-RF] was applied to the preparation of fluoroalkyl end-capped vinyltrimethoxysilane oligomer/α-, β-, ...Fluoroalkyl end-capped vinyltrimethoxysilane oligomer [RF-(CH2CHSi(OMe)3)n-RF;RF = CF(CF3)OCF7, n = 2, 3;RF-(VM)n-RF] was applied to the preparation of fluoroalkyl end-capped vinyltrimethoxysilane oligomer/α-, β-, γ-cyclodextrin polymers (α-, β-, γ-CDPs) composites [RF-(VM-SiO2)n-RF/α-, β-, γ-CDPs] by the sol-gel reaction of the corresponding oligomer in the presence of the α-, β-, γ-CDPs under alkaline conditions. The RF-(VM-SiO2)n-RF/α-, β-, γ-CDPs composites thus obtained were found to give a good dispersibility toward the traditional organic media except for water, and were applied to the surface modification of glass to provide a sueperoleophilic/superhydrophobic characteristic on the modified surface, although the corresponding RF-(VM-SiO2)n-RF nanocomposites can give a usual oleophobic/superhydrophobic property on the surface. These composites powders were also found to be applicable to the packing material for the column chromatography to separate the mixture of oil/water and the water in oil (W/O) emulsions. More interestingly, these composite powders were found to have a higher adsorption ability toward not only low-molecular weight aromatic compounds such as bisphenol A and bisphenol AF but also volatile organic compounds, compared to that of the pristine α-, β-, γ-CDPs.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Supported by a Grant from the National Natural Sciences Foundation of China(No.30973792)
文摘OBJECTIVE: To investigate the effects of combined acupuncture and eugenol on learning-memory ability and the antioxidation system of the hippocampus in Alzheimer disease (AD) rats. METHODS: Sixty Sprague Dawley rats, weighing (300±10) g, were randomly divided with 10 rats per group into a normal control group, AD model group, AD with cut olfactory nerve group, Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group. The AD model was established by injection of amyloid β1-40 (Aβ 1-40). Morris maze tests were conducted for evaluating the learning-memory ability. Content of malo- ndialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus were detected. RESULTS: The average escape latency and the mean swimming distance in the normal control group, the Xiu three-needle group, the eugenol group, and the combined acupuncture and euge-nol group were significantly shorter than those in the AD model group (all P<0.01). The combined acupuncture and eugenol group had shorter escape latency and mean swimming distance than those in the Xiu three-needle group and the eugenol group. There were no significant differences between the Xiu three-needle group and the eugenol group and between the AD group and the AD with cut olfactory nerve group (P>0.05). Compared with the normal control group, the MDA content in the hippocampus significantly increased (P<0.05) and GSH-Px and SOD activities significantly decreased in the AD model group (P<0.01). Compared with the AD model group, significantly decreased (P< 0.01) and SOD and GSH-Px activities significantly increased in the Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group (P<0.05). Compared with the Xiu three-needle group and eugenol group, the MDA content significantly decreased (P<0.05) and SOD and GSH-Px activities increased (P<0.05) in the combined acupuncture and eugenol group. There were no significant differences among the three indices between the Xiu three-needle group and the eugenol group and between the AD model group and the AD with cut olfactory nerve group (P>0.05). CONCLUSION: Both Xiu three-needle and eugenol can increase learning-memory ability, decrease MDA content, and increase SOD and GSH-Px activities in the hippocampus in AD rats. The combination of acupuncture with eugenol has stronger effects, and the effects depend on the olfactory pathway.
基金Scientific Research Project of Heilongjiang Health and Family Planning Commission(2018231).
文摘Objective:To observe the effect of scalp acupoint cluster needling on learning and memory ability and inflammatory mediators in CA1 area of hippocampus in rats with Alzheimer's disease(AD).Methods:A total of 40 SPF Wistar rats were randomly divided into blank group,sham operation group,model group and scalp acupoint cluster needling group,with 10 rats in each group.The AD model was duplicated by injecting Abeta 1-42 solution into bilateral hippocampus in model group and scalp acupoint cluster needling group.The sham operation group was injected with the same amount of sterile hydrogen peroxide,while the blank group was not treated.The scalp acupoint cluster needling group was given acupuncture intervention from 2 d after model establishment.The blank group,sham operation group and model group were only bundled and fixed in the dorsal position once a day for 14 consecutive days.After treatment,the learning and memory ability of AD rats was tested by Morris water maze test,the contents and activities of Ach,ChAT and AcE in hippocampal CA1 area were detected by ELISA,and the expressions of IL-6,IL-10 protein and mRNA in hippocampal CA1 area were detected by immunohistochemistry and RT-PCR,respectively.Results:Ach content,ChAT activity,IL-10 protein and mRNA expression in hippocampus were significantly lower than those in blank group,while AchE activity and IL-6 protein and mRNA expression were significantly higher than those in blank group.Compared with the model group,scalp acupoint cluster needling could significantly reduce the escape latency time,increase the number of crossing platforms and effective residence time,increase the content of Ach,the activity of ChAT,the expression of IL-10 protein and mRNA in hippocampus,and decrease the activity of AchE and the expression of IL-6 protein and mRNA.Conclusion:Controlling the expression of inflammatory factors and promoting the content of Ach in hippocampal CA1 region of AD rats can improve the learning and memory ability of AD rats.
基金the National Natural Science Foundation of China,No.30870876the Natural Science Foundation of Guangdong Province,No.815101700100005+2 种基金the Science and Technology Program of Guangdong Province,No.2005B60302004,2008B030301371,2009B030801368the Traditional Chinese Medicineand Combination of Traditional Chinese and Western Medicine Program of Guangzhou,No.2008A52the Medical and Health Scientific Research Program of Guangzhou,No.2009-YB-167
文摘In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error counts,indicating a learning and memory disorder.After treatment with 30,60,90,120,or 200 mg/kg lithium chloride,the learning and memory abilities of the Fmr1 KO mice were significantly ameliorated,in particular,the 200 mg/kg lithium chloride treatment had the most significant effect.Western blot analysis showed that lithium chloride significantly enhanced the expression of phosphorylated glycogen synthase kinase 3 beta,an inactive form of glycogen synthase kinase 3 beta,in the cerebral cortex and hippocampus of the Fmr1 KO mice.These results indicated that lithium chloride improved learning and memory in the Fmr1 KO mice,possibly by inhibiting glycogen synthase kinase 3 beta activity.
文摘Transthyretin (TTR), a carrier protein present in the liver and choroid plexus of the brain, has been shown to be responsible for binding thyroid hormone thyroxin (T4) and retinol in plasma and cerebrospinal fluid (CSF). TTR aids in sequestering of beta-amyloid peptides Aβ deposition, and protects the brain from trauma, ischemic stroke and Alzheimer disease (AD). Accordingly, hippocampal gene expression of TTR plays a significant role in learning and memory as well as in simulation of spatial memory tasks. TTR via interacting with transcription factor CREB regulates this process and decreased expression leads to memory deficits. By different signaling pathways, like MAPK, AKT, and ERK via Src, TTR provides tropical support through megalin receptor by promoting neurite outgrowth and protecting the neurons from traumatic brain injury. TTR is also responsible for the transient rise in intracellular Ca2+ via NMDA receptor, playing a dominant role under excitotoxic conditions. In this review, we tried to shed light on how TTR is involved in maintaining normal cognitive processes, its role in learning and memory, under memory deficit conditions;by which mechanisms it promotes neurite outgrowth;and how it protects the brain from Alzheimer disease (AD).
文摘A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presented to highlight the role of emotional factors in causing the disease. The question of whether Alzheimer’s disease is an adaptability disorder is raised, given the patient blocked out her memory of her childhood experience. The importance of “happiness” as a treatment goal raises issues of advocacy and Guardianship as well as capacity, which is addressed by actual case reference and court action in defence of the patient’s rights to have their wishes respected and observed. Functional mental capacity assessment, using the Functional Mental State Measure (FMSM) gives a greater indication of neuronal reserve than standard cognitive testing, as it helps to unravel the dilemma associated with pure cognitive assessment in Alzheimer’s Disease as well as vascular dementia patients and patients who, despite retained and intact functional capacity and ability to express their wishes, i.e. “best interest”, are “wrongly” placed under Guardianship. Maladaptive responses, to control the change in external environment that are sensed or perceived, and which lead to disorder or to susceptibility to disease, exemplify a General Systems Theory approach, in which appropriate and adequate responses to environmental change, in behavioural terms, by a person, whether independently, or as the recipient or giver, or both, leads to functional interaction and happiness.
基金supported by the Natural Science Foundation of Hunan Province(No.2024JJ7392)the National Natural Science Foundation of China(No.52463002)+1 种基金Educational Commission of Hunan Province(No.22A0383)Special Funds for Construction of Innovative Provinces in Hunan Province(No.2020SK2028).
文摘An inverse vulcanized polymer,SZIM combining Zn2+-imidazole coordination bonds and polysulfide bonds was synthesized and incorporated into bio-based Eucommia ulmoides gum (EUG) to generate EUG-SZIM-xs.The residual crystallinity of the EUG matrix synergistically interacted with the dual cross-linking networks to establish reversible deformation domains,providing EUG-SZIM-xs with quick shape memory capability at moderate temperatures.The damping properties were also investigated,and EUG-SZIM-xs displayed high tanδ values (>0.3) when the SZIM dosage was higher than 5.5 phr,which showed a positive correlation with SZIM concentration.Such good damping performance endowed the EUG-SZIM-xs with broadband low-frequency sound absorption.In addition,the dual cross-linking networks endowed the materials with reprocessability under different catalytic systems,and the 1,8-diazobicyclic[5.4.0]undeca-7-ene (DBU)-catalyzed samples exhibited better mechanical properties than EUG-SZIM-xs.
文摘Objective To determine the impact of passive smoking and the protective effect of antioxidants such as vitamin E and quercetin on learning and memory ability of mouse offsprings. Methods A passive smoking model of pregnant mice was established. Learning and memory ability was evaluated by the water maze test and long term potentiation （LTP）. Nitric oxide （NO）, content, nitric oxide synthase （NOS）, acetylcholinesteras （Ache） activity in brain, vitamin E concentration, and reactive oxygen species （ROS） in serum were determined. The latency period （the time during which the mice swim from the starting position to the ending position） and errors （the number of mice entering the blind end） in control and antioxidant intervention groups were compared with those in the smoke exposure group after 6 days. Results The latency period as well as errors in the air, control diet, tobacco smoke （TS）, and vitamin E diet groups were decreased significantly as compared with the TS and control diet groups （P〈O.05）. LTP was restrained in the TS and control diet groups. LTP in all the antioxidant diet groups was significantly increased compared with the TS and control diet groups. In addition, NOS and acetylcholinesteras （Ache） activitiy was significantly higher in the TS and control diet groups than in the air and control diet group. NO content was not significantly different among the different groups, and significantly lower in the TS and vitamin E diet groups than in the TS group, control diet group, quercetin diet group, and mixture diet group （P〈0.05）. Vitamin E concentration and ROS activity in serum were correlated with the outcome of water maze and LTP. Conclusion Passive smoking reduces LTP formation by disturbing the hippocampus function of mice, by decreasing NOS （especially vitamin E） partially improve the learning and memory smoke during pregnancy. and Ache activity and increasing NO content. Antioxidants ability of offsprings whose mothers are exposed to tobacco
基金the National Basic Research Program of China(973Program),No.2007CB512601Science and Technology Development Plan of TCM in Shandong Province,No.2009-006Science and Technology Plan in Colleges and Universities of Shandong Province,No.J11LF60,J11LF08
文摘Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However, the mechanisms that mediate its effects remain unclear. In this study, the expression of N-methyI-D-aspartate receptor 1 mRNA, the content of nitric oxide, and the concentration of calcium in neurons was determined with in situ hybridization, spectrophotometry and flow cytometry, respectively. In addition, the expressions of N-methyI-D-aspartate receptor 1, nerve growth factor protein, and glial cell line-derived neurotrophic factor protein were detected with immunohistochemistry. We found that KSZZP could significantly decrease the expression of N-methyI-D-aspartate receptor 1 mRNA and protein, the content of nitric oxide, and the concentration of calcium in neurons. KSZZP also increased the expression of nerve growth factor and glial cell line-derived neurotrophic factor protein in the hippocampus CA1 region and in the cerebral cortex. Morris water maze and passive avoidance tests verified that KSZZP ameliorated the cognitive impairments of vascular dementia rats. Moreover, the KSZZP-induced improvements in the cognitive functions of vascular dementia rats were correlated with both inhibition of N-methyl-D-aspartate-induced excitable neurotoxicity and elevation of neurotrophic factor expression.
文摘We studied on the effect of Curcuma longa extract on spatial learning-related memory ability of old rats in eight-arm radial maze task. Rats were randomly divided into two groups: one group was orally administered 100 mg/KgBW/day C. longa extract (CLE) dissolved in deionized water and the other group was administered the vehicle alone for 10 weeks. The rats were tested with the partially baited eight-arm radial maze to evaluate two types of spatial memory-related learning ability displayed by reference memory errors (RMEs) and working memory errors (WMEs). Chronic administration of CLE significantly decreased the number of RMEs and WMEs, concurrently with the decreases in the cortico-hippocampal levels of lipid peroxides (LPO) and tumor necrosis factor alpha (TNF-α). In a parallel set of experiments, CLE-pretreated rats of the same age group were subjected to hypoxia-reperfusion injury by carotid artery occlusion to induce oxidative stress in the brains in order to examine whether such an in vivo hypoxia-induced oxidative stress could be ameliorated by the extract. Again, the levels of LPO were significantly decreased in the cortico-hippocampal tissues of the CLE-fed hypoxic rats. The histology of the brains also revealed that the CLE-pretreated rats had retained improved cellular integrity. Finally, our results provide the evidence that oral administration of C. longa extract increases the defense against oxidative stress and proinflammatory TNF-α, concurrently with the improvement of memory-related brain cognitive ability of the aged rats.
基金funded by Woosong University Academic Research 2024.
文摘This study investigates the application of Learnable Memory Vision Transformers(LMViT)for detecting metal surface flaws,comparing their performance with traditional CNNs,specifically ResNet18 and ResNet50,as well as other transformer-based models including Token to Token ViT,ViT withoutmemory,and Parallel ViT.Leveraging awidely-used steel surface defect dataset,the research applies data augmentation and t-distributed stochastic neighbor embedding(t-SNE)to enhance feature extraction and understanding.These techniques mitigated overfitting,stabilized training,and improved generalization capabilities.The LMViT model achieved a test accuracy of 97.22%,significantly outperforming ResNet18(88.89%)and ResNet50(88.90%),aswell as the Token to TokenViT(88.46%),ViT without memory(87.18),and Parallel ViT(91.03%).Furthermore,LMViT exhibited superior training and validation performance,attaining a validation accuracy of 98.2%compared to 91.0%for ResNet 18,96.0%for ResNet50,and 89.12%,87.51%,and 91.21%for Token to Token ViT,ViT without memory,and Parallel ViT,respectively.The findings highlight the LMViT’s ability to capture long-range dependencies in images,an areawhere CNNs struggle due to their reliance on local receptive fields and hierarchical feature extraction.The additional transformer-based models also demonstrate improved performance in capturing complex features over CNNs,with LMViT excelling particularly at detecting subtle and complex defects,which is critical for maintaining product quality and operational efficiency in industrial applications.For instance,the LMViT model successfully identified fine scratches and minor surface irregularities that CNNs often misclassify.This study not only demonstrates LMViT’s potential for real-world defect detection but also underscores the promise of other transformer-based architectures like Token to Token ViT,ViT without memory,and Parallel ViT in industrial scenarios where complex spatial relationships are key.Future research may focus on enhancing LMViT’s computational efficiency for deployment in real-time quality control systems.
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.
基金supported by STI2030-Major Projects,No.2022ZD0207600(to LZ)the National Natural Science Foundation of China,Nos.32070955(to LZ),U22A20301(to KFS)+3 种基金the Natural Science Foundation of Guangdong Province,No.2021A1515012197(to HO)Guangzhou Core Medical Disciplines Project,No.2021-2023(to HO)Key Research and Development Plan of Ningxia Hui Automomous Region,No.2022BEG01004(to KFS)Science and Technology Program of Guangzhou,China,No.202007030012(to KFS and LZ)。
文摘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.
基金supported by the National Natural Science Foundation of China,No.81171191(to LYZ)the Shenzhen Special Fund Project on Strategic Emerging Industry Development of China,No.JCYJ20160422170522075(to LYZ)the Shenzhen Healthcare Research Project of China,No.201601015(to LYZ)
文摘Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.
文摘Heat sinks were invented to absorb heat from an electronic circuit conduct, and then to dissipate or radiate this heat to the surrounding supposedly, ventilated space, at a rate equal to or faster than that of its buildup. Ventilation was not initially recognized as an essential factor to thermal dispersion. However, as electronic circuit-boards continued to heat up, circuit failure became a problem, forcing the inclusion of miniaturized high speed fans. Later, heat sinks with fins and quiet fans were incorporated in most manufactured circuits. Now heat sinks come in the form of a fan with fans made to function as fins to disperse heat. Heat sinks absorb and radiate excess heat from circuit-boards in order to prolong the circuit’s life span. The higher the thermal conductivity of the material used the more efficient and effective the heat sink is. This paper is an attempt to theoretically design a heat sink with a temperature gradient lower than that of the circuit board’s excess heat.
基金The authors extend their appreciation to the Ongoing Research Funding Program,number(ORF2025R705),King Saud University,Riyadh,Saudi Arabia,for funding this work.
文摘The study aims to determine the validity and reliability of the Wechsler Preschool and Primary Scale of Intelligence–Third Edition(WPPSI-III)scores in a sample of kindergarten and lower primary pupils from Khartoum State,Sudan.It also aims to examine whether test’s factor structure in this sample replicated that of the original WPPSI-III.The study sample consisted of 384 kindergarten and primary school children in Khartoum State(females=50%mean age=4.14,SD=1.37),selected using stratified random sampling across its seven localities:Khartoum,Jebel Awliya,Khartoum Bahri,East Nile,Omdurman,Ombada,Karari.For concurrent validation,the children additionally completed the Goodenough Draw-a-Man Test,and the Colored Progressive Matrices.WPPSI-III scores demonstrated high internal consistency across the subtest items.Confirmatory factor analysis indicators for total,verbal,and performance intelligence were all excellent.The scale also showed weak to strong score stability ranging from 0.25(weak)to 0.88(strong)based on the Spearman-Brown equation,0.25 to 0.75 based on the Guttman split-half method.The Cronbach’s alpha coefficient scores ranged from 0.54 to 0.93.The WPPSI-III and Goodenough Draw-a-Man Test scores concurrent validity scores were poor(0.05)to modest(0.31),and while those with the Colored Progressive Matrices test were poor(r=0.04–0.18).Thesefindings provide evidence to suggest that the WPPSI-III is appropriate for research use with kindergarten and lower primary school students in Khartoum State,Sudan.
文摘A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presented to highlight the role of emotional factors in causing the disease. The question of whether Alzheimer’s disease is an adaptability disorder is raised, given the patient blocked out her memory of her childhood experience. The importance of “happiness” as a treatment goal raises issues of advocacy and Guardianship as well as capacity, which is addressed by actual case reference and court action in defence of the patient’s rights to have their wishes respected and observed. Functional mental capacity assessment, using the Functional Mental State Measure (FMSM) gives a greater indication of neuronal reserve than standard cognitive testing, as it helps to unravel the dilemma associated with pure cognitive assessment in Alzheimer’s Disease as well as vascular dementia patients and patients who, despite retained and intact functional capacity and ability to express their wishes, i.e. “best interest”, are “wrongly” placed under Guardianship. A General Systems approach, which recognises functional interaction as optimal and withdrawal or inadequate and/or inappropriate response as not, provides further understanding of the relationship between emotional factors, memory and neurodegenerative (Alzheimer’s) disease.
基金supported by the Russian science foundation(grant#22-74-00115 to A.P.G.).
文摘Background:Mitochondrial dysfunction plays a critical role in the pathogenesis of Alzheimer’s disease(AD).Resveratrol is a promising compound for the treatment of various neurodegenerative diseases,including AD.Aims:To investigate mitochondrial damage and the effects of resveratrol on inflammation,cognitive function,and mitochondrial quality control in APP/PS1 mice.Methods:Comparative analysis of mitochondrial DNA(mtDNA)damage was conducted between 10-month-old APP/PS1 mice and age-matched C57BL/6 mice.Assessments included measurement of amyloid-βlevels,inflammatory markers,swimming distance in the Morris water maze,and gut microbiome composition.Resveratrol’s effects on cytokine expression,mtDNA levels in plasma,and activation of Nuclear factor erythroid 2-related factor 2/Antioxidant response element(Nrf2/ARE)and phosphoinositide 3-kinase/protein kinase B(also known as Akt)/mechanistic target of rapamycin complex 1(PI3K/Akt/mTORC1)signaling pathways were also evaluated.Results:APP/PS1 mice exhibited significantly increased mtDNA damage in the prefrontal cortex,midbrain,and cerebellum,alongside higher amyloid-βlevels and inflammatory markers.Resveratrol treatment led to reduced expression of pro-inflammatory cytokines,a decrease in Proteobacteria levels,and lower cell-free mtDNA in plasma.Partial improvement in long-term spatial memory was observed in APP/PS1 mice following resveratrol treatment,likely due to its anti-inflammatory properties.Activation of the Nrf2/ARE signaling pathway and markers of PI3K/Akt/mTORC1 axis activation were noted,with the latter regulating long-term potentiation.Conclusion:Resveratrol demonstrates potential in mitigating inflammation and improving mitochondrial quality control in APP/PS1 mice,but it does not reduce amyloid-βlevels,highlighting the complexity of AD pathology and the need for further research.
文摘There are presently no in-depth published neuropsychological studies of West Nile Virus (WNV) encephalitis patients that have been well-correlated with high resolution structural MRI. In this study a middleaged male who developed West Nile Virus encephalitis five years previously was examined three times over a two year period. We examined him with the Wechsler Adult Intelligence Scales—Fourth Edition and the Wechsler Memory Scale—Fourth Edition (WAIS-IV/WMS-IV) and Advanced Clinical Solutions battery supplemented by tests of attention, executive, motor and sensory functions. Neuroradiological imaging revealed hypodensities within the left hippocampus in the axial and coronal planes with T2-FLAIR MRI. The man was previously high functioning and although he had prior history of well-controlled epilepsy it seems unlikely that the epilepsy could fully account for the neuropathological changes. The patient had previously completed a demanding six year double science degree program before he became ill with WNV and he had been a successful manager and director of a research company. Delayed auditory memory scores were at least two standard deviation units below age expected levels and semantic fluency and Booklet Category Tests of executive function were also in the impaired range. Moreover the illness onset profile of muscle weakness, extreme fatigue, memory complaints as well as inability to carry out research projects involving planning on the job were highly consistent with WNV encephalitis. If the memory and executive function deficits had been premorbid manifestations of epilepsy it is unlikely he would have attained the levels he did educationally and occupationally. This left hippocampal lesion is characteristic of other encephalitic viral infections such as herpes simplex virus. To our knowledge this is the first lateralized WNV encephalitis medial temporal lobe patient in the published literature.
文摘Fluoroalkyl end-capped vinyltrimethoxysilane oligomer [RF-(CH2CHSi(OMe)3)n-RF;RF = CF(CF3)OCF7, n = 2, 3;RF-(VM)n-RF] was applied to the preparation of fluoroalkyl end-capped vinyltrimethoxysilane oligomer/α-, β-, γ-cyclodextrin polymers (α-, β-, γ-CDPs) composites [RF-(VM-SiO2)n-RF/α-, β-, γ-CDPs] by the sol-gel reaction of the corresponding oligomer in the presence of the α-, β-, γ-CDPs under alkaline conditions. The RF-(VM-SiO2)n-RF/α-, β-, γ-CDPs composites thus obtained were found to give a good dispersibility toward the traditional organic media except for water, and were applied to the surface modification of glass to provide a sueperoleophilic/superhydrophobic characteristic on the modified surface, although the corresponding RF-(VM-SiO2)n-RF nanocomposites can give a usual oleophobic/superhydrophobic property on the surface. These composites powders were also found to be applicable to the packing material for the column chromatography to separate the mixture of oil/water and the water in oil (W/O) emulsions. More interestingly, these composite powders were found to have a higher adsorption ability toward not only low-molecular weight aromatic compounds such as bisphenol A and bisphenol AF but also volatile organic compounds, compared to that of the pristine α-, β-, γ-CDPs.
