With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic...With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.展开更多
As mining activities expand deeper,deep high-temperature formations seriously threaten the future safe exploitation,while deep geothermal energy has great potential for development.Combining the formation cooling and ...As mining activities expand deeper,deep high-temperature formations seriously threaten the future safe exploitation,while deep geothermal energy has great potential for development.Combining the formation cooling and geothermal mining in mines to establish a thermos-hydraulic coupling numerical model for fractured formation.The study investigates the formation heat transfer behaviour,heat recovery performance and thermal economic benefits influenced during the life cycle.The results show that the accumulation of cold energy during the cold storage phase induces a decline in formation temperature.The heat recovery phase is determined by the extent of the initial cold domain,which contracts inward from the edge and decelerates the heat recovery rate gradually.With groundwater velocity increases,the thermal regulation efficiency gradually increases,the production temperature decreases,while the effective radius and thermal power increase first and then decrease.The injected volume and temperature significantly affect,with higher injection temperatures slowing thermal recovery,and the thermal regulation efficiency is more sensitive to changes in formation permeability and thermal conductivity.The heat extraction performance is positively correlated with all factors.The levelized cost of electricity is estimated at 0.1203$/(kW·h)during the cold storage.During the heat recovery,annual profit is primarily driven by cooling benefits.展开更多
Cytotoxic T lymphocytes （CTLs） and natural killer （NK） cells contribute to the body＇s immune defenses. Current chimeric antigen receptor （CAR）-modified T cell immunotherapy shows strong promise for treating var...Cytotoxic T lymphocytes （CTLs） and natural killer （NK） cells contribute to the body＇s immune defenses. Current chimeric antigen receptor （CAR）-modified T cell immunotherapy shows strong promise for treating var- ious cancers and infectious diseases. Although CAR- modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use. To alleviate these disadvantages of CAR-modified T cell immunotherapy, additional cyto- toxic cell-mediated immunotherapies are urgently nee- ded. The unique biology of NK cells allows them to serve as a safe, effective, alternative immunotherapeutic strategy to CAR-modified T cells in the clinic. While the fundamental mechanisms underlying the cytotoxicity and side effects of CAR-modified T and NK cell immunotherapies remain poorly understood, the for- mation of the immunological synapse （IS） between CAR- modified T or NK cells and their susceptible target cells is known to be essential. The role of the IS in CAR T and NK cell immunotherapies will allow scientists to harness the power of CAR-modified T and NK cells to treat can- cer and infectious diseases. In this review, we highlight the potential applications of CAR-modified NK cells to treat cancer and human immunodeficiency virus （HIV）, and discuss the challenges and possible future directions of CAR-modified NK cell immunotherapy, as well as the importance of understanding the molecular mechanisms of CAR-modified T cell- or NK cell-medi- ated cytotoxicity and side effects, with a focus on the CAR-modified NK cell IS.展开更多
Alzheimer's disease(AD)is a neurodegenerative disease characterized by progressive cognitive decline,accompanied by amyloid-β(Aβ)overload and hyperphosphorylated tau accumulation in the brain.Synaptic dysfunctio...Alzheimer's disease(AD)is a neurodegenerative disease characterized by progressive cognitive decline,accompanied by amyloid-β(Aβ)overload and hyperphosphorylated tau accumulation in the brain.Synaptic dysfunction,an important pathological hallmark in AD;is recognized as the main cause of the cognitive impairments.Accumulating evidence suggests that synaptic dysfunction could be an early pathological event in AD.Pathological tau,which is detached from axonal microtubules and mislocalized into pre-and postsynaptic neuronal compartments,is suggested to induce synaptic dysfunction in several ways,including reducing mobility and release of presynaptic vesicles,decreasing glutamatergic receptors,impairing the maturation of dendritic spines at postsynaptic terminals,disrupting mitochondrial transport and function in synapses,and promoting the phagocytosis of synapses by microglia.Here,we review the current understanding of how pathological tau mediates synaptic dysfunction and contributes to cognitive decline in AD.We propose that elucidating the mechanism by which pathological tau impairs synaptic function is essential for exploring novel therapeutic strategies for AD.展开更多
This study reports the growth of aligned monolayer molybdenum disulfide(MoS2)ribbons on a sapphire substrate via NaOH-assisted chemical vapor deposition.The length of MoS2 ribbon is up to 400μm.The MoS2 ribbon has ex...This study reports the growth of aligned monolayer molybdenum disulfide(MoS2)ribbons on a sapphire substrate via NaOH-assisted chemical vapor deposition.The length of MoS2 ribbon is up to 400μm.The MoS2 ribbon has excellent single crystal properties,a carrier mobility of^150 cm^2V^-1s^-1,and a optical response of 103 mA W^-1 at a wavelength of 550 nm.The growth model of MoS2 ribbons was given.NaOH reacts with MoO3 to form sodium molybdate droplets,which increase the fluidity of the molybdenum source on the substrate,realizing the vapor-liquid-solid growth of MoS2 on sapphire.The monolayer MoS2 ribbons have two kinds of arrangements on the sapphire substrate,one is the oriented growth affected by the interlayer van der Waals force and the lattice,and the other is the aligned growth constrained by the sapphire step.Our results promote the basic research and device applications of MoS2,and introduce a new way of synthesizing other one dimensional(1D)and 2D nanostructures.展开更多
Efficient large-scale nondestructive quality assessment of graphene on Pt is essential to the in-depth growth research and practical applications of graphene.Here,we present a very simple method for directly observing...Efficient large-scale nondestructive quality assessment of graphene on Pt is essential to the in-depth growth research and practical applications of graphene.Here,we present a very simple method for directly observing the domains and defects in graphene on Pt using an ordinary optical microscope.This was achieved by modifying graphene on Pt using methylene blue(MB).Because the chemical activities of graphene and Pt surface differ significantly,the adsorption and reaction of MB on graphene and platinum surface differ.We can determine the distribution of graphene crystal domains and defects by comparing the colors in the optical images.In addition,this characterization method causes no obvious damage to the Pt substrate and graphene.Moreover,it does not affect the recycling of the substrate or the subsequent characterization or application of graphene.Our study provides a nondestructive method for measuring the quality of graphene on Pt on a large scale,as well as a reference for the characterization and doping of other two-dimensional materials.展开更多
Blueberry extract contains diversiform monomers of anthocyanins, whose antioxidant activity determines the functionality of anthocyanidins and the efficacy of extraction technology. The evaluation of the antioxidant a...Blueberry extract contains diversiform monomers of anthocyanins, whose antioxidant activity determines the functionality of anthocyanidins and the efficacy of extraction technology. The evaluation of the antioxidant activity of anthocyanidins of blueberry ethanol extracts (BEE) was investigated by considering the monomers' identification and thermal degradation in microwave-assisted extraction (MAE). Thirteen monomers of anthocyanins were identified from the extracts of blueberry under MAE, where the highest content was for cyanidin glycosides, and the lowest content was for the malvidin glycosides. The onset temperatures of degradation for anthocyanidins monomers in BEE were 41.07°C-48.50°C, and the glycoside contents of delphinidin, cyanidin, petunidin, peonidin, peonidin, and malvidin, in turn, decreased obviously. The degradation of anthocyanidins with extraction temperature improved, other than weakened, its antioxidant activities in BEE under MAE. The research results may provide valuable guidance for the antioxidant application of extracts from blueberries.展开更多
基金supported by the National Key R&D Program of China,No.2019YFE0121200(to LQZ)the National Natural Science Foundation of China,Nos.82325017(to LQZ),82030032(to LQZ),82261138555(to DL)+2 种基金the Natural Science Foundation of Hubei Province,No.2022CFA004(to LQZ)the Natural Science Foundation of Jiangxi Province,No.20224BAB206040(to XZ)Research Project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province,No.RZYB202201(to XZ).
文摘With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.
基金financial support from the National Natural Science Foundation of China(Nos.52434006,52374151,and 51927808)。
文摘As mining activities expand deeper,deep high-temperature formations seriously threaten the future safe exploitation,while deep geothermal energy has great potential for development.Combining the formation cooling and geothermal mining in mines to establish a thermos-hydraulic coupling numerical model for fractured formation.The study investigates the formation heat transfer behaviour,heat recovery performance and thermal economic benefits influenced during the life cycle.The results show that the accumulation of cold energy during the cold storage phase induces a decline in formation temperature.The heat recovery phase is determined by the extent of the initial cold domain,which contracts inward from the edge and decelerates the heat recovery rate gradually.With groundwater velocity increases,the thermal regulation efficiency gradually increases,the production temperature decreases,while the effective radius and thermal power increase first and then decrease.The injected volume and temperature significantly affect,with higher injection temperatures slowing thermal recovery,and the thermal regulation efficiency is more sensitive to changes in formation permeability and thermal conductivity.The heat extraction performance is positively correlated with all factors.The levelized cost of electricity is estimated at 0.1203$/(kW·h)during the cold storage.During the heat recovery,annual profit is primarily driven by cooling benefits.
文摘Cytotoxic T lymphocytes （CTLs） and natural killer （NK） cells contribute to the body＇s immune defenses. Current chimeric antigen receptor （CAR）-modified T cell immunotherapy shows strong promise for treating var- ious cancers and infectious diseases. Although CAR- modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use. To alleviate these disadvantages of CAR-modified T cell immunotherapy, additional cyto- toxic cell-mediated immunotherapies are urgently nee- ded. The unique biology of NK cells allows them to serve as a safe, effective, alternative immunotherapeutic strategy to CAR-modified T cells in the clinic. While the fundamental mechanisms underlying the cytotoxicity and side effects of CAR-modified T and NK cell immunotherapies remain poorly understood, the for- mation of the immunological synapse （IS） between CAR- modified T or NK cells and their susceptible target cells is known to be essential. The role of the IS in CAR T and NK cell immunotherapies will allow scientists to harness the power of CAR-modified T and NK cells to treat can- cer and infectious diseases. In this review, we highlight the potential applications of CAR-modified NK cells to treat cancer and human immunodeficiency virus （HIV）, and discuss the challenges and possible future directions of CAR-modified NK cell immunotherapy, as well as the importance of understanding the molecular mechanisms of CAR-modified T cell- or NK cell-medi- ated cytotoxicity and side effects, with a focus on the CAR-modified NK cell IS.
基金supported partially by the National Natural Science Foundation of China(82030032,32070960,81871108 to DL,81760221 and 81960221 to XPY,and 81660209 to ZYC)the National Science&Technology Fundamental Resource Investigation Program of China(2018FY100903 to XPY)Science and Technology Project Founded by the Education Department of Jiangxi Province(GJJ201834 to MXW).
文摘Alzheimer's disease(AD)is a neurodegenerative disease characterized by progressive cognitive decline,accompanied by amyloid-β(Aβ)overload and hyperphosphorylated tau accumulation in the brain.Synaptic dysfunction,an important pathological hallmark in AD;is recognized as the main cause of the cognitive impairments.Accumulating evidence suggests that synaptic dysfunction could be an early pathological event in AD.Pathological tau,which is detached from axonal microtubules and mislocalized into pre-and postsynaptic neuronal compartments,is suggested to induce synaptic dysfunction in several ways,including reducing mobility and release of presynaptic vesicles,decreasing glutamatergic receptors,impairing the maturation of dendritic spines at postsynaptic terminals,disrupting mitochondrial transport and function in synapses,and promoting the phagocytosis of synapses by microglia.Here,we review the current understanding of how pathological tau mediates synaptic dysfunction and contributes to cognitive decline in AD.We propose that elucidating the mechanism by which pathological tau impairs synaptic function is essential for exploring novel therapeutic strategies for AD.
基金This work was financially supported by the Science and Technology Commission of Shanghai Municipality(18511110700).
文摘This study reports the growth of aligned monolayer molybdenum disulfide(MoS2)ribbons on a sapphire substrate via NaOH-assisted chemical vapor deposition.The length of MoS2 ribbon is up to 400μm.The MoS2 ribbon has excellent single crystal properties,a carrier mobility of^150 cm^2V^-1s^-1,and a optical response of 103 mA W^-1 at a wavelength of 550 nm.The growth model of MoS2 ribbons was given.NaOH reacts with MoO3 to form sodium molybdate droplets,which increase the fluidity of the molybdenum source on the substrate,realizing the vapor-liquid-solid growth of MoS2 on sapphire.The monolayer MoS2 ribbons have two kinds of arrangements on the sapphire substrate,one is the oriented growth affected by the interlayer van der Waals force and the lattice,and the other is the aligned growth constrained by the sapphire step.Our results promote the basic research and device applications of MoS2,and introduce a new way of synthesizing other one dimensional(1D)and 2D nanostructures.
基金financially supported by the National Defense Technology Innovation Special Zone Project, the National Natural Science Foundation of China (51402342)the Science and Technology Commission of Shanghai Municipality (20501130200)。
文摘Efficient large-scale nondestructive quality assessment of graphene on Pt is essential to the in-depth growth research and practical applications of graphene.Here,we present a very simple method for directly observing the domains and defects in graphene on Pt using an ordinary optical microscope.This was achieved by modifying graphene on Pt using methylene blue(MB).Because the chemical activities of graphene and Pt surface differ significantly,the adsorption and reaction of MB on graphene and platinum surface differ.We can determine the distribution of graphene crystal domains and defects by comparing the colors in the optical images.In addition,this characterization method causes no obvious damage to the Pt substrate and graphene.Moreover,it does not affect the recycling of the substrate or the subsequent characterization or application of graphene.Our study provides a nondestructive method for measuring the quality of graphene on Pt on a large scale,as well as a reference for the characterization and doping of other two-dimensional materials.
基金The authors acknowledge that this work was financially supported by the National Natural Science Foundation of China(Grant No.3207235231571848).
文摘Blueberry extract contains diversiform monomers of anthocyanins, whose antioxidant activity determines the functionality of anthocyanidins and the efficacy of extraction technology. The evaluation of the antioxidant activity of anthocyanidins of blueberry ethanol extracts (BEE) was investigated by considering the monomers' identification and thermal degradation in microwave-assisted extraction (MAE). Thirteen monomers of anthocyanins were identified from the extracts of blueberry under MAE, where the highest content was for cyanidin glycosides, and the lowest content was for the malvidin glycosides. The onset temperatures of degradation for anthocyanidins monomers in BEE were 41.07°C-48.50°C, and the glycoside contents of delphinidin, cyanidin, petunidin, peonidin, peonidin, and malvidin, in turn, decreased obviously. The degradation of anthocyanidins with extraction temperature improved, other than weakened, its antioxidant activities in BEE under MAE. The research results may provide valuable guidance for the antioxidant application of extracts from blueberries.
