Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice

In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

Attitudes Toward People Who Stutter in the Chinese Context: An Exploratory Study on the Impact of Knowledge Sources

The public’s attitudes can affect the experience of stuttering of people who stutter.This study investigated the attitudes held by the public about people who stutter in China.A web-based written survey with closed and open-ended questions was implemented to develop a rich understanding.One hundred and two respondents in 26 provinces and 3 municipalities provided comments on people who stutter in their life aspects such as personality,speech,social life,work,life participation,education,dating and marriage,capability,and communication skills.The predominantly negative attitudes towards the overall domains were identified.Attitudes to people who stutter varied according to the different sources of knowledge.Familiarity with people who stutter might reduce stereotypes.However,knowledge from the media might aggravate stereotypes.Implications and future research orientation were also discussed.

Strengthening Active Aging through Older People’s Association and Economic Activity of the Older People in Nepal

Aging is a natural lifelong process ending in death. Many older people are living in poverty. Older people are generally considered dependent on others as they grow older. The purpose of this article is to explore the entrepreneurship activities of Nepalese older adults. Data for this study were collected from the project Help Age International (HAI) implemented in Nepal. Qualitative data observations and interviews were used to collect data. The findings of this study show the formation of the Older People’s Association (OPA) has supported many older people to participate outside the home in various social activities. Moreover, regular deposits through OPAs offer little help. OPAs support older people in their need of financial support to implement minor entrepreneurship. Older people who received support were pleased and were actively involved in their activities and also regularly deposited money in them. Subsequently, older people’s participation in social activities has increased and also helped to lower elderly abuse, loneliness, and depression. Local governments should promote such activities which will help with healthy aging.

Design of a Landscape Device for Children from the Perspective of Embodied Cognition in the New Era

In recent years,embodied cognition has ushered in a new research upsurge in the academic field,and has become a hot topic in the field of cognitive psychology.In this paper,from the perspective of embodied cognition,the interaction ways of a landscape device for children were discussed to achieve a more real and harmonious interaction between children and scenes.The research data of embodied cognition used by children was analyzed,and the drawbacks and breakthrough points of current landscape devices for children were discussed.The core characteristics of children’s growth period were extracted to establish children’s interaction model and summarize the interactive design methods of landscape devices for children.Embodied cognition has become the most intuitive way for children to know and understand the environment,and plays a pivotal role in children’s growth.Based on embodied cognition principle and interactive behavior mode,the interactive design of a landscape device for children was studied,and three interactive design modes,including simple and convenient interaction mode,multi-sensory interaction mode and game natural interaction mode were summarized.On the basis of this research,relevant design practice and research were carried out to bring a new vision to the design of children’s landscape.

A Study of the People’s Nature in Woodcuts During the Anti-Japanese War in Shanxi

The anti-Japanese woodcuts focus on the red revolutionary culture and describe the connotation of the Anti-Japanese War era,which is self-evident in the commemorative value of China’s revolutionary struggle history.For example,in Shanxi,China,woodcut art activities and social practice promotion activities organized around the theme of the Anti-Japanese War are also everywhere,which all show the people’s nature of the Chinese people during the revolutionary struggle from the two aspects of the red culture of the Anti-Japanese War and traditional art and culture,and its humanistic connotation is quite profound.In this paper,we first introduce the historical origin of woodcut during the Anti-Japanese War,and then show the people’s value connotation of woodcut art activities in Shanxi.This paper mainly discusses the image narration,language and picture narration and construction significance of woodcuts in Shanxi’s War of Resistance,fully reveals the narrative nature of image media,strives to arouse people’s recognition of this period of Shanxi’s War of Resistance culture and history,and reflects the realistic value and significance of Shanxi’s War of Resistance Woodcuts art activities.

Research on Children’s Game Activity Design Strategies Based on Embodied Cognition Theory

Edutainment,in the kindergarten education stage,emphasizes the game as the basic activity and combines the content of education with the form of the game,thus it also forms the educational method of gamification teaching.Through investigation and analysis,it is found that the current kindergarten game activity design has the problem of improper combination of educational content and game form.The current kindergarten game activity design has problems such as stereotypes,children’s lack of active learning opportunities in activities,teachers’insufficient theoretical understanding,inappropriate teacher guidance methods,and so on.Embodied cognition theory attaches importance to the important role of the body in the development of cognition,provides new guidance for classroom teaching,and opens up a new path for classroom teaching reform.Based on the perspective of embodied cognition theory,the concept of body and mind integration should be adhered to in kindergarten teaching with games as the basic activity,experiential teaching situation should be created,children’s subjective experience should be respected,and games and interactions should be designed to promote children’s physical and mental participation,thus laying a foundation for the realization of children’s individual freedom,autonomy,and all-round development.Therefore,this paper aims at the existing problems in the current kindergarten gamification teaching and discusses the design strategy of children’s game activities based on embodied cognition theory.

Historical review and reflections on the participation of acupuncture and moxibustion in the treatment of epidemics in the People’s Republic of China (from 1950 until now)

Since the establishment of the People’s Republic of China, both the Communist Party and the government have placed great emphasis on the advancement of traditional Chinese medicine. Acupuncture and moxibustion have been actively involved in combating major epidemics such as malaria, schistosomiasis, and COVID-19. This article conducts a historical review of these three significant cases to elucidate how the acupuncture community has effectively utilized its unique advantages and characteristics through theoretical discussions, clinical practices, experimental research, as well as receiving administrative leadership and political support from the Communist Party of China and government. We provide an objective evaluation of their effectiveness while summarizing historical experiences to serve as a reference for future utilization of acupuncture and moxibustion therapy in epidemic relief efforts. Additionally, propose four suggestions: strengthening Party leadership and enhancing political support;timely summarization of experiences to establish programs and systems;deepening scientific research by integrating experimental findings with clinical practice;focusing on public awareness campaigns and education to solidify grassroots foundations.

Measuring the Cognitive Impact of Laughter on Elderly People with Mild Cognitive Impairment in Japan

Objective: To evaluate the effect of laughter on cognition in elderly with mild cognitive impairment (MCI) through an appropriately designed intervention. Methods: The intervention involved watching a Japanese comedy routine (Manzai) for approximately twenty minutes, once a week for ten weeks. Participants were asked to paint, as a simple exercise, in addition to watching the show. Twenty-seven patients with MCI from the convalescent ward of a general hospital in the Kansai region of Japan. We measured cognition by evaluating five cognitive function domains before (baseline) and after the intervention. We used the Wilcoxon signed rank test, a distribution-free method, to compare baseline and post-intervention data. Ethical Consideration: Participants were given a document explaining the study. Only those who officially agreed to participate were enrolled. Results: Mean age of patients was 85.0 ± 2.8 years;average education was 8.6 ± 2.8 years. Three cognitive function domains had significantly different average scores after the intervention: 1) Exercise: 44.4 ± 8.9 points at baseline, 36.3 ± 10.2 post-intervention (p = 0.014);2) Word memory: 40.6 ± 7.2 at baseline, 43.1 ± 8.8 post-intervention (p = 0.002);and 3) Animal name recollection: 35.3 ± 8.4 at baseline, 38.1 ± 9.0 post-intervention (p = 0.003). Discussion: The intervention led to significantly higher cognitive scores in exercise, word memory, and animal name recollection domains, suggesting that interventions focused on laughter and simple exercise may improve cognition in elderly patients with MCI.

Improving wellbeing of community-dwelling people with mild cognitive impairment: the SENIOR (SystEm of Nudge theory based ICT applications for OldeR citizens) project

Population aging with longer life expectancy represents one of the most relevant challenges of the next future,also because of a significant proportion of older adult people may present with dementia.Motivating senior citizens with mild cognitive impairment to maintain their independence and functional abilities,improve health status and quality of life as well as social interactions,constitutes the main target of preventive medicine.According to a nudge theoretical approach,the SENIOR(SystEm of Nudge theory based ICT applications for OldeR citizens)project–developed thanks to the collaboration among Catholic University of the Sacred Heart,Bicocca University and IRCCS Auxiologico Institute in Milan(Italy)–has been designed to adopt an advanced information and communication technology coaching system able to collect and integrate physiological,psychological and behavioral data,with the final aim of interacting with community-dwelling elderly people suffering from mild cognitive impairment and of providing them personalized feedback on lifestyle management.The SENIOR project proposes to use a smart-watch app for alerting family doctors,sharing information with family members in specific cases and monitoring patients at higher risk in hospital Units,in order to ameliorate health of senior citizens with mild cognitive impairment.

The Effect of Brain Gym on Global Cognitive Function of Institutionalized Older People

Cognitive function of older adults is influenced by several factors such as age,sex,education,and physical activity so that it can impact the decrease in progressive cognitive function.It is necessary to implement cognitive training in old people’s care to prevent or delay the onset of age-related cognitive decline.Brain gym is a series of simple motion exercises and is an alternative therapy that stimulates the brain.This study aims to evaluate the effect of brain gym as a cognitive training intervention on global cognitive functioning of institutionalized older population.The study is a non-randomized quasi-experimental one using pre-and post-test control group design.The participants of the study were 65 years old or older who had been part of gerontological centers from a local community.They were divided into two groups:control and intervention,each one with 15 people.Mini-Mental State Examination was applied to the sample before and after the cognitive training.The brain gym training consists of bi-weekly group meeting for 12 weeks,lasting 50 min each.The treated group had a significantly better global cognitive function.Recalling(memory),orientation and language skills were the domains with the most significant changes(p<0.05).On the other hand,no significant changes were found in the participants of control groups during post test.Our results suggest that cognitive training based in brain gym improves global cognitive function of institutionalized older people lease type your abstract here.Abstract of a research paper is typically 200 to 400 words in length,and 150 to 300 words for a review paper.Abstract shall be running continuously(not structured)and shall not include reference citations.Abbreviations that appear only once in the abstract should be defined in full.If abbreviations appear more than once,the full definitions should be provided first before they can be used elsewhere.

A cognitive function predicted method by Useful Field of View tests among elder people in Beijing

Objective:To analyze the visual functions of the elder people in China by Useful Field of View (UFOV) to verify performances in Chinese elders.Methods:A total of 90 participants aged 60 years or above were recruited from residents in the Jiade Senior Apartment and the Fuchengmen Public Health Community in Beijing.Participants completed three tests,Mini Mental State Examination (NMSE),Digit Span test and UFOV.We also tested the digit span and UFOV the following year.Results:The correlation between age and MMSE score was significant (r =-0.422,P <.001).Digit Span scores showed significant negative relationships for all three subtests (P <.01) between ages.The scores of UFOV test 1 showed a non-significant correlation with age,r =0.147,P >.1,while UFOV test 2 and UFOV test 3 showed significant positive relationships with ages,(both P <.01).Thirty-nine participants (out of 90) finished the digit span and UFOV the following year.Only UFOV test 3 has a significant differential performance between two years (t =-2.95,P <.01).We found UFOV tests showed the visual response capacity and had a strong correlation with ages (statistically significant).Conclusion:UFOV could be an effective way to evaluate cognitive ability in Chinese elderly people and the selective-attention test of UFOV may be a more sensitive measurement.

People’s Daily对我国应对新冠疫情的报道研究

本文用定量与定性相结合的研究方法构建了《人民日报》英文版People’s Daily对我国应对新冠肺炎疫情报道的语料库,从新闻文本、话语实践、社会实践三个维度对其进行批评性话语分析,发现其中或明或暗的意识形态、不甚清晰的权力结构以及政治控制等话语特征,并在此基础上得出相关结论,提出相关建议。

STAT3 ameliorates truncated tau-induced cognitive deficits

Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.

A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

Distinguishing normal brain aging from the development of Alzheimer＇s disease：inflammation,insulin signaling and cognition

As populations age, prevalence of Alzheimer＇s disease（AD） is rising. Over 100 years of research has provided valuable insights into the pathophysiology of the disease, for which age is the principal risk factor. However, in recent years, a multitude of clinical trial failures has led to pharmaceutical corporations becoming more and more unwilling to support drug development in AD. It is possible that dependence on the amyloid cascade hypothesis as a guide for preclinical research and drug discovery is part of the problem. Accumulating evidence suggests that amyloid plaques and tau tangles are evident in non-demented individuals and that reducing or clearing these lesions does not always result in clinical improvement. Normal aging is associated with pathologies and cognitive decline that are similar to those observed in AD, making differentiation of AD-related cognitive decline and neuropathology challenging. In this mini-review, we discuss the difficulties with discerning normal, age-related cognitive decline with that related to AD. We also discuss some neuropathological features of AD and aging, including amyloid and tau pathology, synapse loss, inflammation and insulin signaling in the brain, with a view to highlighting cognitive or neuropathological markers that distinguish AD from normal aging. It is hoped that this review will help to bolster future preclinical research and support the development of clinical tools and therapeutics for AD.

Simulation of people's evacuation in tunnel fire

The simulation model Tunev（tunnel evacuation） was developed for people＇s evacuation in tunnel fire. It contains simple database of the people＇s behavioral reaction and structure characteristic parameters of tunnel fireproofing. The model can be used to calculate the total evacuation time in various scenes when fire occurs in the different locations of the tunnel. Combined with fire simulation soft ware CFD- POENICS3.5, Tunev model can be used to calculate the fire danger coming time; by comparing with these two kinds of time, it can be used to assess the safety of the evacuation, and the evacuation process also have a dynamic demo. The simulation results show that the Tunev model can be used to predict the reliability of safe evacuation for people in tunnel fire and provide references for people＇s safe escape scheme. Some relevant concepts of the model were described and an evacuation simulation of a typical tunnel case, i.e. Xuefeng Mountain Tunnel was performed by using this model. And the model＇s validation and actual aoolication were also described.

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.

SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aβ generation

SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study,the role of SIL1 in APP processing was explored both in vitro and in vivo.In the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695.In the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates.Western blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant parameters.Results indicated that SIL1 expression decreased in APP23/PS45 mice.Overexpression of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in vitro.Conversely,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 cells.Furthermore,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice.Importantly,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice.These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.

Rotating magnetic field inhibits Aβ protein aggregation and alleviates cognitive impairment in Alzheimer’s disease mice

Amyloid beta(Aβ)monomers aggregate to form fibrils and amyloid plaques,which are critical mechanisms in the pathogenesis of Alzheimer’s disease(AD).Given the important role of Aβ1-42 aggregation in plaque formation,leading to brain lesions and cognitive impairment,numerous studies have aimed to reduce Aβaggregation and slow AD progression.The diphenylalanine(FF)sequence is critical for amyloid aggregation,and magnetic fields can affect peptide alignment due to the diamagnetic anisotropy of aromatic rings.In this study,we examined the effects of a moderate-intensity rotating magnetic field(RMF)on Aβaggregation and AD pathogenesis.Results indicated that the RMF directly inhibited Aβamyloid fibril formation and reduced Aβ-induced cytotoxicity in neural cells in vitro.Using the AD mouse model APP/PS1,RMF restored motor abilities to healthy control levels and significantly alleviated cognitive impairments,including exploration and spatial and non-spatial memory abilities.Tissue examinations demonstrated that RMF reduced amyloid plaque accumulation,attenuated microglial activation,and reduced oxidative stress in the APP/PS1 mouse brain.These findings suggest that RMF holds considerable potential as a non-invasive,high-penetration physical approach for AD treatment.