CsABF3-activated CsSUT1 pathway is implicated in pre-harvest water deficit inducing sucrose accumulation in citrus fruit

Pre-harvest water deficit(PHWD)plays an important role in sugar accumulation of citrus fruit.However,the mechanism is not known well.Here,it was confirmed that PHWD promoted sucrose accumulation of citrus fruit,but had limited effect on fructose,glucose and total acid.A sucrose transporter,Cs SUT1,which localizes to the plasma membrane,was demonstrated to function in sucrose transport induced by PHWD.Compared to wild-type,Cs SUT1 overexpression in citrus calli stimulated sucrose,fructose and glucose accumulation,while its silencing in juice sacs reduced sucrose accumulation.Increased sugar accumulation in transgenic lines enhanced plant drought tolerance,and resulted in decreased electrolyte leakage,malondialdehyde and hydrogen peroxide contents,as well as increased superoxide dismutase activity and proline contents.An abscisic acid(ABA)-responsive transcription factor,Cs ABF3,was found with a same expression pattern with Cs SUT1 under PHWD.Yeast one-hybrid,electrophoretic mobility shift assay and dual-luciferase assays all revealed that Cs ABF3 directly bound with the Cs SUT1 promoter by ABA responsive elements.When Cs ABF3 was overexpressed in citrus calli,the sucrose,fructose and glucose concentration increased correspondingly.Further,transgenic studies demonstrated that Cs ABF3 could affect sucrose accumulation by regulating Cs SUT1.Overall,this study revealed a regulation of Cs ABF3 promoting Cs SUT1 expression and sucrose accumulation in response to PHWD.Our results provide a detail insight into the quality formation of citrus fruit.

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.

Neurological Insights into Attentional Deficits in High Trait Anxiety: a Commentary on Hu et al.’s Paper in Cerebral Cortex (2023)

In a recent publication,Hu et al.(2023)have reported that individuals with high trait anxiety exhibit attentional deficits characterized by reduced inhibition of distractors and delayed attentional selection of targets,indicating impaired top-down attentional control.This commentary underscores their significant contributions to the cognitive theory of anxiety.Based on their findings,we propose a novel training approach called attentional inhibition training(AIT),aimed at improving top-down attentional control to alleviate symptoms of anxiety.Furthermore,we explore the potential application of non-invasive transcranial magnetic stimulation(TMS)for rapidly enhancing attentional control function.

Main focus of parents of children with attention deficit hyperactivity disorder and the effectiveness of early clinical screening

BACKGROUND Attention deficit hyperactivity disorder(ADHD)is a common mental and behavioral disorder among children.AIM To explore the focus of attention deficit hyperactivity disorder parents and the effectiveness of early clinical screening METHODS This study found that the main directions of parents seeking medical help were short attention time for children under 7 years old(16.6%)and poor academic performance for children over 7 years old(12.1%).We employed a two-stage experiment to diagnose ADHD.Among the 5683 children evaluated from 2018 to 2021,360 met the DSM-5 criteria.Those diagnosed with ADHD underwent assessments for letter,number,and figure attention.Following the exclusion of ADHD-H diagnoses,the detection rate rose to 96.0%,with 310 out of 323 cases identified.RESULTS This study yielded insights into the primary concerns of parents regarding their children's symptoms and validated the efficacy of a straightforward diagnostic test,offering valuable guidance for directing ADHD treatment,facilitating early detection,and enabling timely intervention.Our research delved into the predominant worries of parents across various age groups.Furthermore,we showcased the precision of the simple exclusion experiment in discerning between ADHD-I and ADHD-C in children.CONCLUSION Our study will help diagnose and guide future treatment directions for ADHD.

Exploring the impact of high density planting system and deficit irrigation in cotton(Gossypium hirsutum L.):a comprehensive review

Lessons learned from past experiences push for an alternate way of crop production.In India,adopting high density planting system(HDPS)to boost cotton yield is becoming a growing trend.HDPS has recently been considered a replacement for the current Indian production system.It is also suitable for mechanical harvesting,which reducing labour costs,increasing input use efficiency,timely harvesting timely,maintaining cotton quality,and offering the potential to increase productivity and profitability.This technology has become widespread in globally cotton growing regions.Water management is critical for the success of high density cotton planting.Due to the problem of freshwater availability,more crops should be produced per drop of water.In the high-density planting system,optimum water application is essential to control excessive vegetative growth and improve the translocation of photoassimilates to reproductive organs.Deficit irrigation is a tool to save water without compromising yield.At the same time,it consumes less water than the normal evapotranspiration of crops.This review comprehensively documents the importance of growing cotton under a high-density planting system with deficit irrigation.Based on the current research and combined with cotton production reality,this review discusses the application and future development of deficit irrigation,which may provide theoretical guidance for the sustainable advancement of cotton planting systems.

Unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy

Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.

MicroRNAs as potential biomarkers for diagnosis of attention deficit hyperactivity disorder

Inappropriate levels of hyperactivity,impulsivity,and inattention characterize attention deficit hyperactivity disorder,a common childhood-onset neuropsychiatric disorder.The cognitive function and learning ability of children with attention deficit hyperactivity disorder are affected,and these symptoms may persist to adulthood if they are not treated.The diagnosis of attention deficit hyperactivity disorder is only based on symptoms and objective tests for attention deficit hyperactivity disorder are missing.Treatments for attention deficit hyperactivity disorder in children include medications,behavior therapy,counseling,and education services which can relieve many of the symptoms of attention deficit hyperactivity disorder but cannot cure it.There is a need for a molecular biomarker to distinguish attention deficit hyperactivity disorder from healthy subjects and other neurological conditions,which would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of attention deficit hyperactivity disorder.The recent studies reviewed had performed microRNA profiling in whole blood,white blood cells,blood plasma,and blood serum of children with attention deficit hyperactivity disorder.A large number of microRNAs were dysregulated when compared to healthy controls and with some overlap between individual studies.From the studies that had included a validation set of patients and controls,potential candidate biomarkers for attention deficit hyperactivity disorder in children could be miR-140-3p,let-7g-5p,-30e-5p,-223-3p,-142-5p,-486-5p,-151a-3p,-151a-5p,and-126-5p in total white blood cells,and miR-4516,-6090,-4763-3p,-4281,-4466,-101-3p,-130a-3p,-138-5p,-195-5p,and-106b-5p in blood serum.Further studies are warranted with children and adults with attention deficit hyperactivity disorder,and consideration should be given to utilizing rat models of attention deficit hyperactivity disorder.Animal studies could be used to confirm microRNA findings in human patients and to test the effects of targeting specific microRNAs on disease progression and behavior.

Nutritional epigenetics education improves diet and attitude of parents of children with autism or attention deficit/hyperactivity disorder

BACKGROUND Unhealthy maternal diet leads to heavy metal exposures from the consumption of ultra-processed foods that may impact gene behavior across generations,creating conditions for the neurodevelopmental disorders known as autism and attention deficit/hyperactivity disorder(ADHD).Children with these disorders have difficulty metabolizing and excreting heavy metals from their bloodstream,and the severity of their symptoms correlates with the heavy metal levels measured in their blood.Psychiatrists may play a key role in helping parents reduce their ultra-processed food and dietary heavy metal intake by providing access to effective nutritional epigenetics education.AIM To test the efficacy of nutritional epigenetics instruction in reducing parental ultra-processed food intake.METHODS The study utilized a semi-randomized test and control group pretest-posttest pilot study design with participants recruited from parents having a learning-disabled child with autism or ADHD.Twenty-two parents who met the inclusion criteria were randomly selected to serve in the test(n=11)or control(n=11)group.The test group participated in the six-week online nutritional epigenetics tutorial,while the control group did not.The efficacy of the nutritional epigenetics instruction was determined by measuring changes in parent diet and attitude using data derived from an online diet survey administered to the participants during the pre and post intervention periods.Diet intake scores were derived for both ultra-processed and whole/organic foods.Paired sample t-tests were conducted to determine any differences in mean diet scores within each group.RESULTS There was a significant difference in the diet scores of the test group between the pre-and post-intervention periods.The parents in the test group significantly reduced their intake of ultra-processed foods with a preintervention diet score of 70(mean=5.385,SD=2.534)and a post-intervention diet score of 113(mean=8.692,SD=1.750)and the paired t-test analysis showing a significance of P<0.001.The test group also significantly increased their consumption of whole and/or organic foods with a pre-intervention diet score of 100(mean=5.882,SD=2.472)and post-intervention diet score of 121(mean=7.118,SD=2.390)and the paired t-test analysis showing a significance of P<0.05.CONCLUSION Here we show nutritional epigenetics education can be used to reduce ultra-processed food intake and improve attitude among parents having learning-disabled children with autism or ADHD.

Association of premature birth and maternal education level on attention deficit hyperactivity disorder in children:A meta-analysis

BACKGROUND Attention deficit hyperactivity disorder(ADHD)is a prevalent neurodevelopmental disorder in childhood.There is growing evidence that both preterm birth and maternal education levels substantially affect the likelihood of ADHD in children.However,there are limited systematic reviews and meta-analyses examining these associations.AIM To systematically review and conduct a meta-analysis on the association of preterm birth and maternal education level on the risk of ADHD in children.METHODS We conducted a comprehensive literature search across MEDLINE(PubMed),Web of Science,Embase,and the Cochrane Library,including studies published up to June 17,2024.Data synthesis was performed using random-effect models,and the quality of studies was assessed using the Newcastle-Ottawa Scale.RESULTS This study included twelve studies,which revealed a significant association between premature delivery and an increased risk of ADHD in children[odds ratio(OR)=2.76,95%confidence interval(CI):2.52-3.04,P<0.001,I^(2)=1.9%).Conversely,higher maternal education levels were significantly associated with a reduced risk of ADHD in children(OR=0.59,95%CI:0.48-0.73,P<0.001,I^(2)=47.1%).Subgroup analysis further indicated that maternal education levels significantly influenced ADHD risk,particularly in studies conducted in China(OR=0.59,95%CI:0.46-0.75,P<0.001,I^(2)=81.2%),while no significant association was observed in studies from other regions(OR=1.25,95%CI:0.66-2.40,P=0.495,I^(2)=92.3%).The sensitivity analysis confirmed the robustness of our findings,showing no significant publication bias.CONCLUSION This study found that preterm birth significantly increases the risk of ADHD in children,while a higher maternal education level serves as a protective factor against ADHD.To reduce the incidence of ADHD in children,public health policies should focus on early intervention for preterm infants and improving maternal education levels.

Spatial Heterogeneity of Embedded Water Consumption from the Perspective of Virtual Water Surplus and Deficit in the Yellow River Basin,China

Virtual water trade(VWT)provides a new perspective for alleviating water crisis and has thus attracted widespread attention.However,the heterogeneity of virtual water trade inside and outside the river basin and its influencing factors remains further study.In this study,for better investigating the pattern and heterogeneity of virtual water trade inside and outside provincial regions along the Yellow River Basin in 2015 using the input-output model(MRIO),we proposed two new concepts,i.e.,virtual water surplus and virtual water deficit,and then used the Logarithmic Mean Divisia Index(LMDI)model to identify the inherent mechanism of the imbalance of virtual water trade between provincial regions along the Yellow River Basin and the other four regions in China.The results show that:1)in provincial regions along the Yellow River Basin,the less developed the economy was,the larger the contribution of the agricultural sector in virtual water trade,while the smaller the contribution of the industrial sector.2)Due to the large output of agricultural products,the upstream and midstream provincial regions of the Yellow River Basin had a virtual water surplus,with a net outflow of virtual water of 2.7×10^(8) m^(3) and 0.9×10^(8) m^(3),respectively.3)provincial regions along the Yellow River Basin were in a virtual water deficit with the rest of China,and the decisive factor was the active degree of trade with the outside.This study would be beneficial to illuminate the trade-related water use issues in provincial regions along the Yellow River Basin,which has farreaching practical signific-ance for alleviating water scarcity.

Clipping Effect on Growth and Plant Water Use Response to Diurnal Variation of Vapor Pressure Deficit in Cenchrus biflorus Roxb

Cenchrus biflorus called Karangiya in the Hausa language is an annual pastoral grass which is a valuable herbaceous fodder in dry land region in the context of climate change. However, little is known about the plant water use under the effects of cut in West Africa Sahel like Niger where the plant is a multipurpose grass species. Therefore, this study investigated the impact of grazing (simulated by shoot cuts) on biomass production. Cenchrus biflorus Roxb was grown on field plots and in pots and subjected to shoot cuts at different levels (3 cm and 5 cm from soil surface). The effect of shoot cuts on drought tolerance was evaluated by assessing the response of transpiration to the diurnal variation of vapor pressure deficit (VPD). Results showed that the biomass production varied in response to shoot cuts depending on the culture system, and the level or frequency of cuts. The mean biomass production increased significantly especially in field plots for 5 cm cuts compared to those at 3 cm and the control treatment. In addition, transpiration was highly increased in response to the VPD increase. Shoot cuts significantly reduced transpiration, whatever the level, largely because they reduced leaf surface. We concluded that moderate grazing (cuts to 5cm) can improve biomass production and allow better adaptation to water deficit as they significantly reduced water loss through transpiration. The study recommends the cropping of the Cenchrus biflorus as climate solution as it performs better under water deficit for improving grazing resilience in Niger.

Influence of vapor pressure deficit on vegetation growth in China

Vapor pressure deficit(VPD)plays a crucial role in determining plant physiological functions and exerts a substantial influence on vegetation,second only to carbon dioxide(CO_(2)).As a robust indicator of atmospheric water demand,VPD has implications for global water resources,and its significance extends to the structure and functioning of ecosystems.However,the influence of VPD on vegetation growth under climate change remains unclear in China.This study employed empirical equations to estimate the VPD in China from 2000 to 2020 based on meteorological reanalysis data of the Climatic Research Unit(CRU)Time-Series version 4.06(TS4.06)and European Centre for Medium-Range Weather Forecasts(ECMWF)Reanalysis 5(ERA-5).Vegetation growth status was characterized using three vegetation indices,namely gross primary productivity(GPP),leaf area index(LAI),and near-infrared reflectance of vegetation(NIRv).The spatiotemporal dynamics of VPD and vegetation indices were analyzed using the Theil-Sen median trend analysis and Mann-Kendall test.Furthermore,the influence of VPD on vegetation growth and its relative contribution were assessed using a multiple linear regression model.The results indicated an overall negative correlation between VPD and vegetation indices.Three VPD intervals for the correlations between VPD and vegetation indices were identified:a significant positive correlation at VPD below 4.820 hPa,a significant negative correlation at VPD within 4.820–9.000 hPa,and a notable weakening of negative correlation at VPD above 9.000 hPa.VPD exhibited a pronounced negative impact on vegetation growth,surpassing those of temperature,precipitation,and solar radiation in absolute magnitude.CO_(2) contributed most positively to vegetation growth,with VPD offsetting approximately 30.00%of the positive effect of CO_(2).As the rise of VPD decelerated,its relative contribution to vegetation growth diminished.Additionally,the intensification of spatial variations in temperature and precipitation accentuated the spatial heterogeneity in the impact of VPD on vegetation growth in China.This research provides a theoretical foundation for addressing climate change in China,especially regarding the challenges posed by increasing VPD.

Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

Impact of applying the theory of human becoming and self-care deficit theory of nursing on insomnia in after stroke urinary incontinence patients

Objective:To determine the impact of applying the theory of human becoming and self-care deficit theory of nursing in overcoming insomnia in patients of urinary incontinence(UI)after stroke.Insomnia is a sleep disorder experienced by UI patients after stroke which can exacerbate problems related to brain damage and can complicate the recovery process.Methods:This study was a quasi-experimental conducted in 4 hospitals.Fifty-six patients were selected by convenience sampling and divided into 2 groups(the intervention and control group).Participants in the intervention group received“applying the theory of Human becoming and self-care deficit theory of nursing,”starting when the patient is about to go home from the hospital and continuing at the house.Measurement of insomnia is done using the Pittsburgh Sleep Quality Index(PSQI).Results:The mean insomnia scores of participants from both groups increased in the first and third measurements.The second and third insomnia measurements found a significant difference(P<0.001).This intervention decreased the average score of insomnia by 4.11 times in the second measurement and 5.82 times in the third measurement.The most important item that decreased in the third measurement of insomnia was sleep efficiency.Conclusions:Applying the theory of human becoming and self-care deficit theory of nursing in this study significantly decreased the insomnia score of post-stroke UI patients.It can be used as a guide for nurses,patients,and families in managing insomnia.In addition,the application of nursing theory in nursing practice can systematize nursing care plans and organize the knowledge of professionals into a conceptual framework,as well as provide effective guidance for nurses on what to do.

Early Intervention Facilitates Neuropsychological Development in Children with Autism and Attention Deficit Hyperactivity Disorder

Objective:This study aims to investigate the impact of early intervention on neuropsychological development in children with autism and attention deficit hyperactivity disorder(ADHD),providing effective intervention strategies for clinical practice.Methods:A total of 130 children with autism and ADHD who visited the hospital between June 2023 and June 2024 were selected as study subjects and randomly divided into an intervention group and a control group,with 65 children in each group.The intervention group received a one-year early comprehensive intervention,including behavioral therapy,cognitive training,and family guidance,while the control group only received routine medical care.The neuropsychological development assessment scale was used to evaluate both groups before and after the intervention to compare changes in their neuropsychological development levels.Results:Children in the intervention group showed significant improvements in cognitive function,social skills,language ability,and attention concentration,with an average improvement score of 23.5 points.Children in the control group did not show significant improvements in these areas,with an average improvement score of only 5.8 points.The difference between the two groups was statistically significant(P<0.05).Conclusion:Early comprehensive intervention has a significant promoting effect on the neuropsychological development of children with autism and ADHD.Targeted behavioral therapy,cognitive training,and family guidance can effectively enhance children’s cognitive,social,language,and attention abilities,laying a solid foundation for their future overall development.Therefore,it is recommended to actively promote and apply early intervention strategies in clinical practice.

Positive Effect of Transcranial Direct Current Stimulation on Visual Verbal Working Memory in Patients with Attention-Deficit/Hyperactivity Disorder

Background: Working memory is an executive function that plays an important role in many aspects of daily life, and its impairment in patients with attention-deficit/hyperactivity disorder (ADHD) affects quality of life. The dorsolateral prefrontal cortex (DLPFC) has been a good target site for transcranial direct current stimulation (tDCS) due to its intense involvement in working memory. In our 2018 study, tDCS improved visual-verbal working memory in healthy subjects. Objective: This study examines the effects of tDCS on ADHD patients, particularly on verbal working memory. Methods: We conducted an experiment involving verbal working memory of two modalities, visual and auditory, and a sustained attention task that could affect working memory in 9 ADHD patients. Active or sham tDCS was applied to the left DLPFC in a single-blind crossover design. Results: tDCS significantly improved the accuracy of visual-verbal working memory. In contrast, tDCS did not affect auditory-verbal working memory and sustained attention. Conclusion: tDCS to the left DLPFC improved visual-verbal working memory in ADHD patients, with important implications for potential ADHD treatments.

Study on the Soil Moisture Stress Level in Regulated Deficit Irrigation Experiment

On the basis of discussing the influencing mode of plant moisture stress on plant physiological process and the division of soil moisture availability range, the water suction values partitioning soil moisture were put forward, and then the corresponding water moistures under water stress were obtained by conversing together with characteristic curve of water moisture.

身体还是认知努力的损害?抑郁症努力奖赏动机评估及计算模型应用

动机损害是抑郁症的常见特征,患者常表现出异常的奖励评估或体验等行为。理解抑郁症患者努力奖赏动机活动中不愿意付出努力的类型——是不愿意付出身体努力还是不愿意付出认知努力,对帮助患者恢复社会功能活动具有重要作用。然而,当前缺少研究探讨努力类型(身体或认知努力)对研究认识的影响,同时,计算模型方法具有能够精细评估动机相关变量的优势,这一方法在该领域中并未得到普及应用。通过实验方法区分评估抑郁症患者“认知努力”和“身体努力”这两种不同的努力决策,并结合计算模型的数据分析方式,从努力奖赏动机这一角度探索抑郁症动机损害行为,对揭示这一损害潜在的认知神经基础具有促进作用。

Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This review presents a brief background of the development of novel concepts and their clinical potentials.The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal function.An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic site.This Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity.Furthermore,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways.Based on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis.The N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity.Ischemic stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time courses.It is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia.This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.

补气活血合剂干预脑缺血再灌注模型大鼠相关因子及自噬蛋白的表达

背景:补气活血合剂治疗气虚痰瘀型缺血性脑卒中有显著的临床疗效,然而其具体起效机制尚不明确。目的:观察补气活血合剂对脑缺血再灌注模型大鼠血管内皮细胞生长因子、碱性成纤维细胞生长因子、脑源性神经营养因子及自噬蛋白Beclin1、p62表达的影响。方法:取40只雄性SD大鼠,采用随机数字表法分为假手术组、模型组、补气活血合剂组与自噬抑制剂组,每组10只。模型组、补气活血合剂组与自噬抑制剂组建立大脑缺血再灌注损伤模型,补气活血合剂组大鼠再灌注2 h后灌胃给予补气活血合剂(6.49 g/kg,每天分3次给药),自噬抑制剂组大鼠再灌注2 h后灌胃给予补气活血合剂(6.49 g/kg,每天分3次给药)+腹腔注射自噬抑制剂3-甲基腺嘌呤(灌胃前2 h注射,灌胃第1-3天注射),假手术组、模型组灌胃给予等量生理盐水,连续灌胃给药7 d。末次给药24 h后,进行大鼠神经功能、脑梗死体积、脑组织形态及大脑缺血皮质区血管内皮细胞生长因子、碱性成纤维细胞生长因子、脑源性神经营养因子及自噬蛋白Beclin1、p62表达检测。结果与结论:①Zea-Longa评分结果显示,造模后大鼠神经功能受到严重损伤,补气活血合剂组大鼠神经功能损伤轻于模型组、自噬抑制剂组(P<0.05);②TTC染色结果显示,模型组、补气活血合剂组与自噬抑制剂组大鼠均可见大脑梗死灶,补气活血合剂组大鼠脑梗死体积低于模型组、自噬抑制剂组(P<0.05);③缺血侧脑组织苏木精-伊红染色结果显示,模型组神经细胞间有较大的空隙且排列不整齐,神经细胞出现胞质凝集、核固缩现象;补气活血合剂组和自噬抑制剂组神经细胞间隙减小且排列较规律,存在部分细胞出现胞质凝集、核固缩表现;④免疫组化染色结果显示,血管内皮生长因子多表达在神经元细胞、神经胶质细胞及毛细血管内皮;碱性成纤维细胞生长因子和脑源性神经营养因子多表达在神经元细胞、神经胶质细胞,4组间血管内皮细胞生长因子、碱性成纤维细胞生长因子、脑源性神经营养因子表达比较差异无显著性意义(P>0.05);⑤Western blot检测结果显示,与假手术组相比,模型组Beclin1蛋白表达降低(P<0.05),p62蛋白表达升高(P<0.05);与模型组相比,补气活血合剂组Beclin1蛋白表达升高(P<0.05),p62蛋白表达降低(P<0.05);与补气活血合剂组相比,自噬抑制剂Beclin1蛋白表达降低(P<0.05),p62蛋白表达升高(P<0.05);⑥结果表明,补气活血合剂可通过促进自噬来减轻大鼠脑缺血再灌注损伤。