In this study,we investigated worldvolume fermions on the flavor brane in the D0-D4/D8 model,which is holographically equivalent to four-dimensional quantum chromodynamics with instantons or equivalently with a theta ...In this study,we investigated worldvolume fermions on the flavor brane in the D0-D4/D8 model,which is holographically equivalent to four-dimensional quantum chromodynamics with instantons or equivalently with a theta angle.The action involving the worldvolume fermions was obtained by the T-duality rules in string theory,and we accordingly derived their effective five-dimensional and canonical four-dimensional forms by using the systematic dimensional reduction and decomposition of the spinor.Subsequently,we used the AdS/CFT dictionary to evaluate the two-point correlation function as the spectral function for the worldvolume fermions and interpreted the fermions as baryons by analyzing their quantum number with the baryon vertex in holography.In this sense,the interacted action involving the worldvolume fermions and gauge field on the flavor brane was finally derived in holography,which describes the various interactions of mesons and baryons with instantons in the large-N limit.Therefore,this study provides a holographic picture to describe baryons and their interactions based on string theory,particularly in the presence of instantons or a theta angle.展开更多
In order to rapidly respond to the complex and mutational market, a new facility layout plan based on cellular manufacturing is proposed, which gives consideration to high efficiency and flexibility. The plan designs ...In order to rapidly respond to the complex and mutational market, a new facility layout plan based on cellular manufacturing is proposed, which gives consideration to high efficiency and flexibility. The plan designs two phases of integrated cell layout, i.e., cell construction and cell system layout, on the condition of adding/removing machines. First, in view of the costs of logics and machine-relocation, the cell construction based on the alternative processing routes and intra-cell layout are integrated as a whole, which achieves cell formation, process planning and the intra-cell layout in a single step. Secondly, an approach of a continuous optimized multi-line layout for solving the cell system layout problem is proposed, which eliminates the coupling relationship from the machine-relocation and realizes an integrated design of the two phases of the cell layout. An application based on real factory data is optimally solved by the Matlab 7.0 software to validate and verify the models.展开更多
Neuroinflammation is a crucial factor in the progression of various diseases,ranging from immune-related conditions such as sepsis to neurodegenerative disorders such as Alzheimer’s disease(AD)(Ravichandran and Henek...Neuroinflammation is a crucial factor in the progression of various diseases,ranging from immune-related conditions such as sepsis to neurodegenerative disorders such as Alzheimer’s disease(AD)(Ravichandran and Heneka,2024).This perspective article,which draws on insights from diverse fields including neuroscience,immunology,and pathology,p rovides a critical analysis of ongoing research efforts in inflammasome biology,with specific emphasis on Nod-like receptor(NLR)and pyrin domain-containing protein 3(NLRP3).展开更多
Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzhe...Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).展开更多
Alzheimer’s disease(AD)remains an incurable neurodegenerative disorder with devastating societal and personal impacts.Despite decades of intensive research,therapeutic efforts targeting the clinical stages of AD have...Alzheimer’s disease(AD)remains an incurable neurodegenerative disorder with devastating societal and personal impacts.Despite decades of intensive research,therapeutic efforts targeting the clinical stages of AD have largely failed to halt or reverse disease progression.This has prompted a critical shift in focus toward the earlier,preclinical stages of AD,where interventions may hold greater promise for altering the disease trajectory.展开更多
[Objectives]To investigate the ameliorative effects of Huanglian Jiedu Decoction(HLJDD)on cognitive function impairment in an Alzheimer s disease(AD)mouse model induced by Porphyromonas gingivalis infection.[Methods]T...[Objectives]To investigate the ameliorative effects of Huanglian Jiedu Decoction(HLJDD)on cognitive function impairment in an Alzheimer s disease(AD)mouse model induced by Porphyromonas gingivalis infection.[Methods]Thirty-six male C57BL/6 mice were randomly assigned to six groups:control group,model group,low-dose HLJDD group,medium-dose HLJDD group,high-dose HLJDD group,and positive drug group(treated with moxifloxacin).With the exception of the control group,all groups underwent an 8-week P.gingivalis chronic infection model induced via oral administration.Subsequently,each treatment group received corresponding doses of HLJDD(2.5,5,and 10 mg/g)or moxifloxacin for 8 weeks intervention.The novel object recognition test was employed to evaluate the non-spatial memory abilities of mice,and the novel object exploration preference index was calculated to assess cognitive function.[Results]Compared to the control group,the novel object exploration preference index of mice in the model group was significantly reduced(P<0.01),indicating that P.gingivalis infection effectively induced cognitive impairment.Relative to the model group,mice treated with medium and high doses of HLJDD exhibited a significant,dose-dependent increase in the novel object exploration preference index,whereas the low-dose group showed no significant improvement.Additionally,the positive drug moxifloxacin demonstrated a significant neuroprotective effect on cognition.[Conclusions]HLJDD effectively improves cognitive function impairment in AD model mice induced by P.gingivalis infection,offering novel experimental evidence supporting the heat-clearing and detoxification approach as well as the therapeutic potential of traditional Chinese medicine(TCM)compounds in the intervention of AD.展开更多
Alzheimer’s disease(AD)is the most common form of dementia characterized pathologically by the deposition of amyloid plaques and hyperphosphorylated tau containing neurofibrillary tangles.The disease presents clinica...Alzheimer’s disease(AD)is the most common form of dementia characterized pathologically by the deposition of amyloid plaques and hyperphosphorylated tau containing neurofibrillary tangles.The disease presents clinically with progressive memory loss and disruption of cognitive function.Currently,there is no cure for AD;recent advances in the therapeutics aimed at clearing the amyloid protein from the brain have led to potential disease stabilization,however,this does not prevent eventual disease progression(Cummings et al.,2024).展开更多
Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellul...Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellular tau neurofibrillary tangles,leading to synaptic dysfunction,neuronal loss,and cognitive decline.These pathological changes can begin decades before clinical symptoms emerge,highlighting the critical need for early,accessible,and accurate diagnostic tools.展开更多
Alzheimer’s disease(AD)is the most common form of dementia.In addition to the lack of effective treatments,there are limitations in diagnostic capabilities.The complexity of AD itself,together with a variety of other...Alzheimer’s disease(AD)is the most common form of dementia.In addition to the lack of effective treatments,there are limitations in diagnostic capabilities.The complexity of AD itself,together with a variety of other diseases often observed in a patient’s history in addition to their AD diagnosis,make deciphering the molecular mechanisms that underlie AD,even more important.Large datasets of single-cell RNA sequencing,single-nucleus RNA-sequencing(snRNA-seq),and spatial transcriptomics(ST)have become essential in guiding and supporting new investigations into the cellular and regional susceptibility of AD.However,with unique technology,software,and larger databases emerging;a lack of integration of these data can contribute to ineffective use of valuable knowledge.Importantly,there was no specialized database that concentrates on ST in AD that offers comprehensive differential analyses under various conditions,such as sex-specific,region-specific,and comparisons between AD and control groups until the new Single-cell and Spatial RNA-seq databasE for Alzheimer’s Disease(ssREAD)database(Wang et al.,2024)was introduced to meet the scientific community’s growing demand for comprehensive,integrated,and accessible data analysis.展开更多
Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyl...Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.展开更多
Tel Ad办公空间坐落于以色列卡法萨巴一栋翻新建筑内。因自然采光条件有限,设计团队引入中央人工照明中庭,重塑空间流线,并通过材料运用,明确空间界定与功能分区。该中庭既是空间锚点,亦是氛围焦点。鉴于建筑进深较大,难以持续获取自然...Tel Ad办公空间坐落于以色列卡法萨巴一栋翻新建筑内。因自然采光条件有限,设计团队引入中央人工照明中庭,重塑空间流线,并通过材料运用,明确空间界定与功能分区。该中庭既是空间锚点,亦是氛围焦点。鉴于建筑进深较大,难以持续获取自然光线,中庭采用全光谱农业照明系统,以确保绿植全年茂盛生长。同时,空间流线也经重新设计,形成环绕绿色核心的环形路径,既确保了与绿植的持续视觉联系,又使各工作区域间的流线直观且流畅。除满足空间功能需求外,中庭在提升员工福祉与工作效率方面亦扮演关键角色:研究显示,相较于传统无窗办公环境,接触绿植及动态照明等自然元素,可有效降低压力、增强专注力并缓解视疲劳。室内统一采用水磨石地面、不锈钢装饰及天然木饰面,实现了整体空间的连贯性。展开更多
N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory lo...N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.12005033)the Fundamental Research Funds for the Central Universities(Grant No.3132024192)。
文摘In this study,we investigated worldvolume fermions on the flavor brane in the D0-D4/D8 model,which is holographically equivalent to four-dimensional quantum chromodynamics with instantons or equivalently with a theta angle.The action involving the worldvolume fermions was obtained by the T-duality rules in string theory,and we accordingly derived their effective five-dimensional and canonical four-dimensional forms by using the systematic dimensional reduction and decomposition of the spinor.Subsequently,we used the AdS/CFT dictionary to evaluate the two-point correlation function as the spectral function for the worldvolume fermions and interpreted the fermions as baryons by analyzing their quantum number with the baryon vertex in holography.In this sense,the interacted action involving the worldvolume fermions and gauge field on the flavor brane was finally derived in holography,which describes the various interactions of mesons and baryons with instantons in the large-N limit.Therefore,this study provides a holographic picture to describe baryons and their interactions based on string theory,particularly in the presence of instantons or a theta angle.
文摘In order to rapidly respond to the complex and mutational market, a new facility layout plan based on cellular manufacturing is proposed, which gives consideration to high efficiency and flexibility. The plan designs two phases of integrated cell layout, i.e., cell construction and cell system layout, on the condition of adding/removing machines. First, in view of the costs of logics and machine-relocation, the cell construction based on the alternative processing routes and intra-cell layout are integrated as a whole, which achieves cell formation, process planning and the intra-cell layout in a single step. Secondly, an approach of a continuous optimized multi-line layout for solving the cell system layout problem is proposed, which eliminates the coupling relationship from the machine-relocation and realizes an integrated design of the two phases of the cell layout. An application based on real factory data is optimally solved by the Matlab 7.0 software to validate and verify the models.
基金supported by Texas Alzheimer’s Research and Care Consortium-TARCC 2022-26,The National Football League Players Association-NFLPA,NIH/NIA Grant 1R01 AG072491 to TB and FDP.
文摘Neuroinflammation is a crucial factor in the progression of various diseases,ranging from immune-related conditions such as sepsis to neurodegenerative disorders such as Alzheimer’s disease(AD)(Ravichandran and Heneka,2024).This perspective article,which draws on insights from diverse fields including neuroscience,immunology,and pathology,p rovides a critical analysis of ongoing research efforts in inflammasome biology,with specific emphasis on Nod-like receptor(NLR)and pyrin domain-containing protein 3(NLRP3).
基金supported by National Institute on Aging(NIH-NIA)R01AG054459(to ALL).
文摘Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).
基金supported by the Canadian Institutes of Health Research Project grant(PJT-169197)to QY.BFH was supported by a CGS-M fellowship from the Canadian Institutes of Health Research.
文摘Alzheimer’s disease(AD)remains an incurable neurodegenerative disorder with devastating societal and personal impacts.Despite decades of intensive research,therapeutic efforts targeting the clinical stages of AD have largely failed to halt or reverse disease progression.This has prompted a critical shift in focus toward the earlier,preclinical stages of AD,where interventions may hold greater promise for altering the disease trajectory.
基金Supported by National Natural Science Foundation of China(82160832)Natural Science Foundation of Guangxi Zhuang Autonomous Region(2017GXNS-FAA198255)+2 种基金Open Project of Guangxi Key Laboratory of Brain and Cognitive Neuroscience(GKLBCN-202206-02)Guangxi Undergraduate Innovation and Entrepreneurship Training Program(202410601029,S202410601113)The 4th Thousand Young and Middle-Aged Backbone Teachers Cultivation Program of Guangxi Higher Education Institutions.
文摘[Objectives]To investigate the ameliorative effects of Huanglian Jiedu Decoction(HLJDD)on cognitive function impairment in an Alzheimer s disease(AD)mouse model induced by Porphyromonas gingivalis infection.[Methods]Thirty-six male C57BL/6 mice were randomly assigned to six groups:control group,model group,low-dose HLJDD group,medium-dose HLJDD group,high-dose HLJDD group,and positive drug group(treated with moxifloxacin).With the exception of the control group,all groups underwent an 8-week P.gingivalis chronic infection model induced via oral administration.Subsequently,each treatment group received corresponding doses of HLJDD(2.5,5,and 10 mg/g)or moxifloxacin for 8 weeks intervention.The novel object recognition test was employed to evaluate the non-spatial memory abilities of mice,and the novel object exploration preference index was calculated to assess cognitive function.[Results]Compared to the control group,the novel object exploration preference index of mice in the model group was significantly reduced(P<0.01),indicating that P.gingivalis infection effectively induced cognitive impairment.Relative to the model group,mice treated with medium and high doses of HLJDD exhibited a significant,dose-dependent increase in the novel object exploration preference index,whereas the low-dose group showed no significant improvement.Additionally,the positive drug moxifloxacin demonstrated a significant neuroprotective effect on cognition.[Conclusions]HLJDD effectively improves cognitive function impairment in AD model mice induced by P.gingivalis infection,offering novel experimental evidence supporting the heat-clearing and detoxification approach as well as the therapeutic potential of traditional Chinese medicine(TCM)compounds in the intervention of AD.
基金funded by Wellcome 4ward North(Ref:216340/Z/19/Z)ARUK Yorkshire Network Centre Small Grant Scheme,ARUK Preparatory Clinical Fellowship scheme(Ref:ARUK-PCRF2016A-1)+3 种基金Academy of Medical Sciences Starter Grants for Clinical Lecturers Scheme(Ref:SGL028\1097),Parkinson’s UK(Ref:F1301)Michael J Fox Foundation(Ref:005021),Australian Research Council(CE200100012)European Union Seventh Framework Programme(Ref:FP7/2007-2013)under grant agreement no.601055the NIHR Sheffield Biomedical Research Centre award(NIHR 203321)(to SMB).
文摘Alzheimer’s disease(AD)is the most common form of dementia characterized pathologically by the deposition of amyloid plaques and hyperphosphorylated tau containing neurofibrillary tangles.The disease presents clinically with progressive memory loss and disruption of cognitive function.Currently,there is no cure for AD;recent advances in the therapeutics aimed at clearing the amyloid protein from the brain have led to potential disease stabilization,however,this does not prevent eventual disease progression(Cummings et al.,2024).
文摘Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellular tau neurofibrillary tangles,leading to synaptic dysfunction,neuronal loss,and cognitive decline.These pathological changes can begin decades before clinical symptoms emerge,highlighting the critical need for early,accessible,and accurate diagnostic tools.
文摘Alzheimer’s disease(AD)is the most common form of dementia.In addition to the lack of effective treatments,there are limitations in diagnostic capabilities.The complexity of AD itself,together with a variety of other diseases often observed in a patient’s history in addition to their AD diagnosis,make deciphering the molecular mechanisms that underlie AD,even more important.Large datasets of single-cell RNA sequencing,single-nucleus RNA-sequencing(snRNA-seq),and spatial transcriptomics(ST)have become essential in guiding and supporting new investigations into the cellular and regional susceptibility of AD.However,with unique technology,software,and larger databases emerging;a lack of integration of these data can contribute to ineffective use of valuable knowledge.Importantly,there was no specialized database that concentrates on ST in AD that offers comprehensive differential analyses under various conditions,such as sex-specific,region-specific,and comparisons between AD and control groups until the new Single-cell and Spatial RNA-seq databasE for Alzheimer’s Disease(ssREAD)database(Wang et al.,2024)was introduced to meet the scientific community’s growing demand for comprehensive,integrated,and accessible data analysis.
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN).
文摘Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.
基金supported by the National Institute on Aging(Nos.AG000723 and AG000578)(to VAB)the Fondation Sante(No.19656),Greece 2.0+1 种基金the National Recovery and Resilience Plan’s flagship program TAEDR-0535850the European Research Council(No.101077374-Synapto Mitophagy)(to KP)。
文摘N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.
