The rate performance and cycle stability of graphitized needle coke(GNC)as anode are still limited by the sluggish kinetics and volume expansion during the Li ions intercalation and de-intercalation process.Especially...The rate performance and cycle stability of graphitized needle coke(GNC)as anode are still limited by the sluggish kinetics and volume expansion during the Li ions intercalation and de-intercalation process.Especially,the output of energy density for lithium ion batteries(LIBs)is directly affected by the delithiation capacity below 0.5 V.Here,the mildly expanded graphitized needle coke(MEGNC)with the enlarged interlayer spacing from 0.346 to 0.352 nm is obtained by the two-step mild oxidation intercalation modification.The voltage plateau of MEGNC anode below 0.5 V is obviously broadened as compared to the initial GNC anode,contributing to the enhancement of Li storage below the low voltage plateau.Moreover,the coin full cell and pouch full cell configured with MEGNC anode exhibit much enhanced Li storage ability,energy density and better cycling stability than those full cells configured with GNC and commercial graphite anodes,demonstrating the practical application value of MEGNC.The superior anode behaviors of MEGNC including the increased effective capacity at low voltage and superior cyclic stability are mainly benefited from the enlarged interlayer spacing,which not only accelerates the Li ions diffusion rate,but also effectively alleviates the volume expansion and fragmentation during the Li ions intercalation process.In addition,the above result is further confirmed by the density functional theory simulation.This work provides an effective modification strategy for the NC-based graphite to enhance the delithiation capacity at a low voltage plateau,dedicated to improving the energy density and durability of LIBs.展开更多
In this study,a series of Co_3O_4/ mildly oxidized graphite oxide(mGO) nanocatalysts(Co_3O_4/ mGO-l,Co_3O_4/ mGO-2 and Co_3O_4/mGO-3) were synthesized through solvothermal method and used as a mediator for the heterog...In this study,a series of Co_3O_4/ mildly oxidized graphite oxide(mGO) nanocatalysts(Co_3O_4/ mGO-l,Co_3O_4/ mGO-2 and Co_3O_4/mGO-3) were synthesized through solvothermal method and used as a mediator for the heterogeneous peroxymonosulfate(PMS)activation.The performance of CO_3O_4 / mGO/PMS system was investigated using acid orange 7(AO7).Results showed that Co_3O_4/mGO-3 had the best degradation efficiency of AO7 and the removal rate was above 90%in about 6 min.The phenomenon indicated the catalytic activity of Co_3O_4/mGO composites was related to the oxidation degree of graphite oxide(GO).In addition,experiments showed the content of Co_3O_4 had an effect on the catalytic activity.The composites were characterized with X-ray powder diffraction(XRD),FTIR,Raman,X-ray photoelectron spectroscopy(XPS) and transmission electron microscopy(TEM).According to the charactrization and synergistic catalytic mechanism,the generation of Co—OH complexes found to be the initial step to activate PMS in the heterogeneous system of Co_3O_4/mGO hybrid.展开更多
In this paper, the characteristics of different forms of mild slope equations for non-linear wave are analyzed, and new non-linear theoretic models for wave propagation are presented, with non-linear terms added to th...In this paper, the characteristics of different forms of mild slope equations for non-linear wave are analyzed, and new non-linear theoretic models for wave propagation are presented, with non-linear terms added to the mild slope equations for non-stationary linear waves and dissipative effects considered. Numerical simulation models are developed of non-linear wave propagation for waters of mildly varying topography with complicated boundary, and the effects are studied of different non-linear corrections on calculation results of extended mild slope equations. Systematical numerical simulation tests show that the present models can effectively reflect non-linear effects.展开更多
Objective:To observe the clinical efficacy of dapagliflozin in the treatment of type 2 diabetes mellitus(T2DM)complicated with heart failure with mildly reduced ejection fraction(HFmrEF,40%≤LVEF<50%).Methods:A tot...Objective:To observe the clinical efficacy of dapagliflozin in the treatment of type 2 diabetes mellitus(T2DM)complicated with heart failure with mildly reduced ejection fraction(HFmrEF,40%≤LVEF<50%).Methods:A total of 84 patients with T2DM complicated with HFmrEF hospitalized in our hospital from October 2019 to October 2021 were selected,and random number table method was used to divide into the control group and the study group each 42 cases.Both groups used basal hypoglycemic and standardized anti-heart failure therapy,and the study group was treated with dapagliflozin simultaneously.Nine months later,the following indexes were compared between the two groups before and after treatment:the cardiac function indicators:N-terminal pro brain natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF);exercise endurance:6-minute walk distance(6MWD),NYHA cardiac function class,the score of the Minnesota living with heart failure questionnaire(MLHFQ)and the incidence of major adverse cardiovascular events(MACE).Results:Nine months later,the two groups showed decreased NT-proBNP level,increased LVEF,prolonged 6MWD,improved NYHA cardiac function grade,decreased MLHFQ score,and statistically significant differences within both groups compared with before treatment(P<0.05),after treatment significant differences were displayed between the two groups(P<0.05).Less patients had MACE events and adverse drug reactions in the study group compared with the control group.Conclusion:Dapagliflozin in the treatment of T2DM patients with HFmrEF can improve cardiac function indicators,improve exercise endurance,improve NYHA cardiac function class,improve patient's quality of life,and reduce the incidence of MACE events,with no obvious side effects.展开更多
Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment ...Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment methods.Hibernation has the characteristics of low temperature,low metabolism,and hibernation rhythm,as well as protective effects on the nervous,cardiovascular,and motor systems.Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body’s metabolism,lowering the body’s core temperature,and allowing the body to enter a state similar to hibernation.This review introduces artificial hibernation technology,including mild hypothermia treatment technology,central nervous system regulation technology,and artificial hibernation-inducer technology.Upon summarizing the relevant research on artificial hibernation technology in acute brain injury,the research results show that artificial hibernation technology has neuroprotective,anti-inflammatory,and oxidative stress-resistance effects,indicating that it has therapeutic significance in acute brain injury.Furthermore,artificial hibernation technology can alleviate the damage of ischemic stroke,traumatic brain injury,cerebral hemorrhage,cerebral infarction,and other diseases,providing new strategies for treating acute brain injury.However,artificial hibernation technology is currently in its infancy and has some complications,such as electrolyte imbalance and coagulation disorders,which limit its use.Further research is needed for its clinical application.展开更多
Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP...Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP is determined by the presence of pancreatic complications and end-organ damage.While moderate/severe pancreatitis can be associated with significant morbidity and mortality,the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%.Despite favorable outcomes,the majority of mild AP patients are admitted,contributing to healthcare cost and burden.In this Editorial we review the performance of an emergency department(ED)pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations,resource utilization,and costs after several years of implementation of the pathway.We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital,and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway.We conclude that by implementing innovative clinical pathways which are established and reproducible,selected AP patients can be safely discharged from the ED,reducing hospitalizations and healthcare costs,without compromising clinical outcomes.We also identify a subset of patients most likely to succeed in this pathway.展开更多
The metallurgical quality control of magnesium(Mg)and Mg alloys in melting process is required to ensure a satisfied mechanical and corrosion performance,while the typical used steel crucible introduces impurities and...The metallurgical quality control of magnesium(Mg)and Mg alloys in melting process is required to ensure a satisfied mechanical and corrosion performance,while the typical used steel crucible introduces impurities and interfacial interaction during melting process.Therefore,a systematic study about impurities diffusion and interfacial interaction between molten Mg and steel is necessary.In the present study,the interfacial reaction between molten AZ91D Mg alloy and mild steel during melting process was investigated with the melting temperatures of 700℃,750℃ and 800℃.The results show that Al(Fe,Mn)intermetallic layer is the intermetallic primarily formed at the interfaces of AZ91D melt and mild steel.Meanwhile,Al_(8)(Mn,Fe)5is indexed between Al(Fe,Mn)and AZ91D.AlFe_(3)C appears between the mild steel and Al(Fe,Mn)at 700℃ and 750℃,but absent at 800℃ due to the increased solubility of carbon in Mg matrix.It is found that the growth of the intermetallic layer is controlled by diffusion mechanism,and Al and Mn are the dominant diffusing species in the whole interfacial reaction process.By measuring the thickness of different layers,the growth constant was calculated.It increases from 1.89(±0.03)×10^(-12)m^(2)·s^(-1)at 700℃ to 3.05(±0.05)×10^(-12)m^(2)·s^(-1)at 750℃,and 5.18(±0.05)×10^(-12)m^(2)·s^(-1)at 800℃.Meanwhile,the content of Fe is linearly increased in AZ91D with the increase of holding time at 700℃ and 750℃,while it shows a significantly increment after holding for 8 h at 800℃,indicating holding temperature is more crucial to determine the Fe content of AZ91D than holding time.展开更多
Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely u...Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury.These findings highlight the importance of integrating structural and functional connectivity in unde rstanding the occurrence and evolution of mild traumatic brain injury.Additionally,exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.展开更多
Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice ...Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.展开更多
Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.Howev...Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.However,additional research is needed to dissect the mechanisms of its anti-depressive effects.Methods:For this study,Sprague-Dawley(SD)rats were randomized into the control,model,quercetin,or fluoxetine group.The latter three groups were exposed to chronic unpredictable mild stress(CUMS)for 42 d.The first two groups received saline solution daily via oral gavage.Meanwhile,the quercetin group was orally administered a quercetin suspension(52.08 mg/kg)every day,while the fluoxetine group was orally administered a fluoxetine solution(2.08 mg/kg).Here,fluoxetine served as the positive control drug to compare the therapeutic effects of quercetin.The experimental period was 6 weeks.Depressive behaviors in rats were assessed through various physiological and behavioral measures.Additionally,pathological changes in hippocampal tissues were examined using Nissl staining.Serum cytokines were detected using an enzymelinked immunosorbent assay(ELISA),and immunohistochemistry was employed to quantify the levels and integral optical density(IOD)values of ionized calcium binding adaptor molecule-1(Iba-1)expression in the brain.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to evaluate the mRNA levels of inflammatory indicators as well as toll-like receptor 4(TLR4),and nuclear factor-κappa B P65(NF-κB P65)in hippocampus.Western blot(WB)technique was employed to observe the protein levels of TLR4,NF-κB P65,and phospho-NF-κB P65(p-NF-κB P65).Results:After 42 d of exposure to CUMS,rats exhibited a slow increase in body weight,a reduction in food intake,an abnormal preference for sugar water,and aberrant open-field behaviors.Pathological analysis revealed the disintegration,rupture,interruption,and disorganization of hippocampal neuronal cells after CUMS exposure,along with a decrease in Nissl bodies in the CA1 region.This was accompanied by the elevated expression of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in the serum and the upregulation of IL-1β,IL-6,and TNF-αmRNA expression in the hippocampus.Increases in Iba-1-positive cells and the IOD values of Iba-1 were detected in hippocampal microglia.Furthermore,TLR4 and NF-κB P65 mRNA and protein levels were upregulated in hippocampal tissues.Quercetin,an antidepressant,could alleviate depression-like symptoms in rats and downregulate inflammatory factors associated with the TLR4/NF-κB signaling pathway in hippocampal microglia,and its therapeutic effect was comparable to fluoxetine.Conclusion:In rat models of CUMS,quercetin may act as an antidepressant by inhibiting inflammation in hippocampal microglia via TLR4/NF-κB signaling pathway.These results offer experimental and theoretical support for applying quercetin in the clinical management of depression.展开更多
We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repet...We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.展开更多
Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) a...Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.展开更多
[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362...[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection.展开更多
Functional connectivity networks (FCNs) are important in the diagnosis of neurological diseases and the understanding of brain tissue patterns. Recently, many methods, such as Pearson’s correlation (PC), Sparse repre...Functional connectivity networks (FCNs) are important in the diagnosis of neurological diseases and the understanding of brain tissue patterns. Recently, many methods, such as Pearson’s correlation (PC), Sparse representation (SR), and Sparse low-rank representation have been proposed to estimate FCNs. Despite their popularity, they only capture the low-order connections of the brain regions, failing to encode more complex relationships (i.e. , high-order relationships). Although researchers have proposed high-order methods, like PC + PC and SR + SR, aiming to build FCNs that can reflect more real state of the brain. However, such methods only consider the relationships between brain regions during the FCN construction process, neglecting the potential shared topological structure information between FCNs of different subjects. In addition, the low-order relationships are always neglected during the construction of high-order FCNs. To address these issues, in this paper we proposed a novel method, namely Ho-FCN<sub>Tops</sub>, towards estimating high-order FCNs based on brain topological structure. Specifically, inspired by the Group-constrained sparse representation (GSR), we first introduced a prior assumption that all subjects share the same topological structure in the construction of the low-order FCNs. Subsequently, we employed the Correlation-reserved embedding (COPE) to eliminate noise and redundancy from the low-order FCNs. Meanwhile, we retained the original low-order relationships during the embedding process to obtain new node representations. Finally, we utilized the SR method on the obtained new node representations to construct the Ho-FCN<sub>Tops</sub> required for disease identification. To validate the effectiveness of the proposed method, experiments were conducted on 137 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to identify Mild Cognitive Impairment (MCI) patients from the normal controls. The experimental results demonstrate superior performance compared to baseline methods.展开更多
Background:Tau vaccination and administration of anti-tau antibodies can prevent pathology and cognitive impairment in transgenic mouse models of tauopathy,suggesting that therapies which increase anti-tau antibodies ...Background:Tau vaccination and administration of anti-tau antibodies can prevent pathology and cognitive impairment in transgenic mouse models of tauopathy,suggesting that therapies which increase anti-tau antibodies might slow the development and/or progression of Alzheimer’s disease(AD).The extent to which individuals with no cognitive impairment(NCI)possess serum anti-tau antibodies,and whether their concentrations of these antibodies differ from anti-tau antibody levels in persons with mild cognitive impairment(MCI)or AD,are unclear.Previous studies measuring these antibodies did not account for antibody polyvalent binding,which can be extensive,nor that antibody binding to phosphorylated tau peptides could be due to binding to non-phosphorylated epitopes on those peptides.Methods:An ELISA controlling for these factors was used to measure the specific binding of serum IgG and IgM to phosphorylated(“pTau;”phosphorylated at Serine-199 and Serine-202)and non-phosphorylated(“non-pTau”)tau 196-207 in subjects with NCI,MCI,or AD(n=10/group).Between-group differences in these antibody levels were evaluated for statistical significance,and correlations were examined in pooled data from all subjects between these antibody levels and subject age,global cognitive functioning,and NFT counts.Results:Specific IgG binding to pTau and non-pTau was detected in all subjects except for one NCI control.Specific IgM binding was detected to pTau in all subjects except for two AD patients,and to non-pTau in all subjects.Mean pTau IgG was increased in MCI subjects by 53% and 70% vs.AD and NCI subjects respectively(both p<0.05),while no significant differences were found between groups for non-pTau IgG(p=0.052),pTau IgM,or non-pTau IgM.Non-pTau IgG was negatively associated with global cognition(Spearman rho=−0.50).Conclusions:Specific binding of serum IgG and IgM to phosphorylated and non-phosphorylated tau may be present in older persons regardless of their cognitive status.Serum IgG to phosphorylated tau may be increased in individuals with MCI,but this unexpected finding requires confirmation.The approach used in this study to measure specific serum antibodies to phosphorylated tau should be useful for measuring antibodies to other post-translationally-modified proteins that are of relevance to neurodegenerative disorders.展开更多
为了探究液体燃料的中低氧稀释(moderate and intense low-oxygen dilution,MILD)燃烧的特性,采用数值模拟方法,分析了MILD燃烧过程中空气与燃料的入口条件对燃烧室烟气回流比、流场结构和污染物排放量的影响规律.研究结果表明:MILD燃...为了探究液体燃料的中低氧稀释(moderate and intense low-oxygen dilution,MILD)燃烧的特性,采用数值模拟方法,分析了MILD燃烧过程中空气与燃料的入口条件对燃烧室烟气回流比、流场结构和污染物排放量的影响规律.研究结果表明:MILD燃烧室内流场结构对燃料与空气的混合起到决定作用;随着当量比的增加,燃烧室温度逐渐升高,CO的排放量逐渐增大,NO_(x)排放量也随之增大,当量比为0.9时,NO_(x)排放量达到峰值;随着空气入口速度的增加,燃烧室中心面温度分布均匀,没有明显的局部高温峰值点,NO_(x)排放量逐渐减小,CO排放量呈先减小、后增大的趋势,空气入口速度为110 m/s时的CO排放量最小;随着燃料入口速度的增大,燃烧室内峰值温度逐渐升高,NO_(x)排放量逐渐增加,CO排放量呈先减小、后增大的趋势.展开更多
The spleen is critical for immunity.It is the largest immune organ and immune center in the peripheral system.While the relationship between behavior and immunity has been demonstrated in physiology and diseases,the r...The spleen is critical for immunity.It is the largest immune organ and immune center in the peripheral system.While the relationship between behavior and immunity has been demonstrated in physiology and diseases,the role of the spleen in behavior is not clear.To investigate the effects of the spleen on behaviors,we performed a refined splenectomy procedure on C57BL/6J mice and performed an open field test,circadian rhythm test,elevated plus maze,sucrose preference test,and Barnes maze test.Splenectomy did not induce changes in general locomotion,circadian rhythms,learning and memory,or depression/anxiety-related behaviors.To further investigate the effects of spleen on stress susceptibility,we established mouse models of depression through chronic unpredictable mild stress.The behavioral performances of mice subjected to splenectomy showed no differences from control animals.These findings suggest that splenectomy does not cause changes in baseline behavioral performance in mice.展开更多
基金supported by the National Natural Science Foundation of China(21776309,22122807 and 21706283)。
文摘The rate performance and cycle stability of graphitized needle coke(GNC)as anode are still limited by the sluggish kinetics and volume expansion during the Li ions intercalation and de-intercalation process.Especially,the output of energy density for lithium ion batteries(LIBs)is directly affected by the delithiation capacity below 0.5 V.Here,the mildly expanded graphitized needle coke(MEGNC)with the enlarged interlayer spacing from 0.346 to 0.352 nm is obtained by the two-step mild oxidation intercalation modification.The voltage plateau of MEGNC anode below 0.5 V is obviously broadened as compared to the initial GNC anode,contributing to the enhancement of Li storage below the low voltage plateau.Moreover,the coin full cell and pouch full cell configured with MEGNC anode exhibit much enhanced Li storage ability,energy density and better cycling stability than those full cells configured with GNC and commercial graphite anodes,demonstrating the practical application value of MEGNC.The superior anode behaviors of MEGNC including the increased effective capacity at low voltage and superior cyclic stability are mainly benefited from the enlarged interlayer spacing,which not only accelerates the Li ions diffusion rate,but also effectively alleviates the volume expansion and fragmentation during the Li ions intercalation process.In addition,the above result is further confirmed by the density functional theory simulation.This work provides an effective modification strategy for the NC-based graphite to enhance the delithiation capacity at a low voltage plateau,dedicated to improving the energy density and durability of LIBs.
基金Innovation Program of Shanghai Municipal Education Commission,China(No.12ZZ069)Research Fund for the Doctoral Program of Higher Education,China(No.20130075110006)
文摘In this study,a series of Co_3O_4/ mildly oxidized graphite oxide(mGO) nanocatalysts(Co_3O_4/ mGO-l,Co_3O_4/ mGO-2 and Co_3O_4/mGO-3) were synthesized through solvothermal method and used as a mediator for the heterogeneous peroxymonosulfate(PMS)activation.The performance of CO_3O_4 / mGO/PMS system was investigated using acid orange 7(AO7).Results showed that Co_3O_4/mGO-3 had the best degradation efficiency of AO7 and the removal rate was above 90%in about 6 min.The phenomenon indicated the catalytic activity of Co_3O_4/mGO composites was related to the oxidation degree of graphite oxide(GO).In addition,experiments showed the content of Co_3O_4 had an effect on the catalytic activity.The composites were characterized with X-ray powder diffraction(XRD),FTIR,Raman,X-ray photoelectron spectroscopy(XPS) and transmission electron microscopy(TEM).According to the charactrization and synergistic catalytic mechanism,the generation of Co—OH complexes found to be the initial step to activate PMS in the heterogeneous system of Co_3O_4/mGO hybrid.
文摘In this paper, the characteristics of different forms of mild slope equations for non-linear wave are analyzed, and new non-linear theoretic models for wave propagation are presented, with non-linear terms added to the mild slope equations for non-stationary linear waves and dissipative effects considered. Numerical simulation models are developed of non-linear wave propagation for waters of mildly varying topography with complicated boundary, and the effects are studied of different non-linear corrections on calculation results of extended mild slope equations. Systematical numerical simulation tests show that the present models can effectively reflect non-linear effects.
基金Suqian Science and Technology Plan Project(No.Z2019178)。
文摘Objective:To observe the clinical efficacy of dapagliflozin in the treatment of type 2 diabetes mellitus(T2DM)complicated with heart failure with mildly reduced ejection fraction(HFmrEF,40%≤LVEF<50%).Methods:A total of 84 patients with T2DM complicated with HFmrEF hospitalized in our hospital from October 2019 to October 2021 were selected,and random number table method was used to divide into the control group and the study group each 42 cases.Both groups used basal hypoglycemic and standardized anti-heart failure therapy,and the study group was treated with dapagliflozin simultaneously.Nine months later,the following indexes were compared between the two groups before and after treatment:the cardiac function indicators:N-terminal pro brain natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF);exercise endurance:6-minute walk distance(6MWD),NYHA cardiac function class,the score of the Minnesota living with heart failure questionnaire(MLHFQ)and the incidence of major adverse cardiovascular events(MACE).Results:Nine months later,the two groups showed decreased NT-proBNP level,increased LVEF,prolonged 6MWD,improved NYHA cardiac function grade,decreased MLHFQ score,and statistically significant differences within both groups compared with before treatment(P<0.05),after treatment significant differences were displayed between the two groups(P<0.05).Less patients had MACE events and adverse drug reactions in the study group compared with the control group.Conclusion:Dapagliflozin in the treatment of T2DM patients with HFmrEF can improve cardiac function indicators,improve exercise endurance,improve NYHA cardiac function class,improve patient's quality of life,and reduce the incidence of MACE events,with no obvious side effects.
基金supported by the National Defense Science and Technology Outstanding Youth Science Fund Project,No.2021-JCJQ-ZQ-035National Defense Innovation Special Zone Project,No.21-163-12-ZT-006-002-13Key Program of the National Natural Science Foundation of China,No.11932013(all to XuC).
文摘Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment methods.Hibernation has the characteristics of low temperature,low metabolism,and hibernation rhythm,as well as protective effects on the nervous,cardiovascular,and motor systems.Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body’s metabolism,lowering the body’s core temperature,and allowing the body to enter a state similar to hibernation.This review introduces artificial hibernation technology,including mild hypothermia treatment technology,central nervous system regulation technology,and artificial hibernation-inducer technology.Upon summarizing the relevant research on artificial hibernation technology in acute brain injury,the research results show that artificial hibernation technology has neuroprotective,anti-inflammatory,and oxidative stress-resistance effects,indicating that it has therapeutic significance in acute brain injury.Furthermore,artificial hibernation technology can alleviate the damage of ischemic stroke,traumatic brain injury,cerebral hemorrhage,cerebral infarction,and other diseases,providing new strategies for treating acute brain injury.However,artificial hibernation technology is currently in its infancy and has some complications,such as electrolyte imbalance and coagulation disorders,which limit its use.Further research is needed for its clinical application.
文摘Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP is determined by the presence of pancreatic complications and end-organ damage.While moderate/severe pancreatitis can be associated with significant morbidity and mortality,the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%.Despite favorable outcomes,the majority of mild AP patients are admitted,contributing to healthcare cost and burden.In this Editorial we review the performance of an emergency department(ED)pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations,resource utilization,and costs after several years of implementation of the pathway.We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital,and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway.We conclude that by implementing innovative clinical pathways which are established and reproducible,selected AP patients can be safely discharged from the ED,reducing hospitalizations and healthcare costs,without compromising clinical outcomes.We also identify a subset of patients most likely to succeed in this pathway.
基金supported by the Natural Science Foundation of Chongqing,China(Grant Nos.cstc2020jcyj-msxm X0544,CSTB2022NSCQ-MSX0352,CSTB2022NSCQ-MSX0891,cstc2020jcyj-msxm X0184)Scientific and Technological Research Program of Chongqing Municipal Education Commission(Grant No.KJQN202001416)National Natural Science Foundation of China(Grant Nos.11847077,52001028)。
文摘The metallurgical quality control of magnesium(Mg)and Mg alloys in melting process is required to ensure a satisfied mechanical and corrosion performance,while the typical used steel crucible introduces impurities and interfacial interaction during melting process.Therefore,a systematic study about impurities diffusion and interfacial interaction between molten Mg and steel is necessary.In the present study,the interfacial reaction between molten AZ91D Mg alloy and mild steel during melting process was investigated with the melting temperatures of 700℃,750℃ and 800℃.The results show that Al(Fe,Mn)intermetallic layer is the intermetallic primarily formed at the interfaces of AZ91D melt and mild steel.Meanwhile,Al_(8)(Mn,Fe)5is indexed between Al(Fe,Mn)and AZ91D.AlFe_(3)C appears between the mild steel and Al(Fe,Mn)at 700℃ and 750℃,but absent at 800℃ due to the increased solubility of carbon in Mg matrix.It is found that the growth of the intermetallic layer is controlled by diffusion mechanism,and Al and Mn are the dominant diffusing species in the whole interfacial reaction process.By measuring the thickness of different layers,the growth constant was calculated.It increases from 1.89(±0.03)×10^(-12)m^(2)·s^(-1)at 700℃ to 3.05(±0.05)×10^(-12)m^(2)·s^(-1)at 750℃,and 5.18(±0.05)×10^(-12)m^(2)·s^(-1)at 800℃.Meanwhile,the content of Fe is linearly increased in AZ91D with the increase of holding time at 700℃ and 750℃,while it shows a significantly increment after holding for 8 h at 800℃,indicating holding temperature is more crucial to determine the Fe content of AZ91D than holding time.
基金supported by the National Natural Science Foundation of China,Nos.81671671(to JL),61971451(to JL),U22A2034(to XK),62177047(to XK)the National Defense Science and Technology Collaborative Innovation Major Project of Central South University,No.2021gfcx05(to JL)+6 种基金Clinical Research Cen terfor Medical Imaging of Hunan Province,No.2020SK4001(to JL)Key Emergency Project of Pneumonia Epidemic of Novel Coronavirus Infection of Hu nan Province,No.2020SK3006(to JL)Innovative Special Construction Foundation of Hunan Province,No.2019SK2131(to JL)the Science and Technology lnnovation Program of Hunan Province,Nos.2021RC4016(to JL),2021SK53503(to ML)Scientific Research Program of Hunan Commission of Health,No.202209044797(to JL)Central South University Research Program of Advanced Interdisciplinary Studies,No.2023Q YJC020(to XK)the Natural Science Foundation of Hunan Province,No.2022JJ30814(to ML)。
文摘Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury.These findings highlight the importance of integrating structural and functional connectivity in unde rstanding the occurrence and evolution of mild traumatic brain injury.Additionally,exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.
基金supported financially by the National Natural Science Foundation of China,No.82071272(to YZ).
文摘Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.
基金supported by the National Natural Science Foundation of China(Nos.81673881 and 81202644)Hebei Province Natural Science Foundation Traditional Chinese Medicine Joint Fund Cultivation Project(No.H2022423375)Graduate Innovation Project of Hebei University of Chinese Medicine in 2023(No.XCXZZBS2023003).
文摘Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.However,additional research is needed to dissect the mechanisms of its anti-depressive effects.Methods:For this study,Sprague-Dawley(SD)rats were randomized into the control,model,quercetin,or fluoxetine group.The latter three groups were exposed to chronic unpredictable mild stress(CUMS)for 42 d.The first two groups received saline solution daily via oral gavage.Meanwhile,the quercetin group was orally administered a quercetin suspension(52.08 mg/kg)every day,while the fluoxetine group was orally administered a fluoxetine solution(2.08 mg/kg).Here,fluoxetine served as the positive control drug to compare the therapeutic effects of quercetin.The experimental period was 6 weeks.Depressive behaviors in rats were assessed through various physiological and behavioral measures.Additionally,pathological changes in hippocampal tissues were examined using Nissl staining.Serum cytokines were detected using an enzymelinked immunosorbent assay(ELISA),and immunohistochemistry was employed to quantify the levels and integral optical density(IOD)values of ionized calcium binding adaptor molecule-1(Iba-1)expression in the brain.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to evaluate the mRNA levels of inflammatory indicators as well as toll-like receptor 4(TLR4),and nuclear factor-κappa B P65(NF-κB P65)in hippocampus.Western blot(WB)technique was employed to observe the protein levels of TLR4,NF-κB P65,and phospho-NF-κB P65(p-NF-κB P65).Results:After 42 d of exposure to CUMS,rats exhibited a slow increase in body weight,a reduction in food intake,an abnormal preference for sugar water,and aberrant open-field behaviors.Pathological analysis revealed the disintegration,rupture,interruption,and disorganization of hippocampal neuronal cells after CUMS exposure,along with a decrease in Nissl bodies in the CA1 region.This was accompanied by the elevated expression of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in the serum and the upregulation of IL-1β,IL-6,and TNF-αmRNA expression in the hippocampus.Increases in Iba-1-positive cells and the IOD values of Iba-1 were detected in hippocampal microglia.Furthermore,TLR4 and NF-κB P65 mRNA and protein levels were upregulated in hippocampal tissues.Quercetin,an antidepressant,could alleviate depression-like symptoms in rats and downregulate inflammatory factors associated with the TLR4/NF-κB signaling pathway in hippocampal microglia,and its therapeutic effect was comparable to fluoxetine.Conclusion:In rat models of CUMS,quercetin may act as an antidepressant by inhibiting inflammation in hippocampal microglia via TLR4/NF-κB signaling pathway.These results offer experimental and theoretical support for applying quercetin in the clinical management of depression.
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBSS00047(to PL)the National Natural Science Foundation of China,Nos.82072166(to PL),82071394(to XG)+4 种基金Science and Technology Planning Project of Tianjin,No.20YFZCSY00030(to PL)Science and Technology Project of Tianjin Municipal Health Commission,No.TJWJ2021QN005(to XG)Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-006ATianjin Municipal Education Commission Scientific Research Program Project,No.2020KJ164(to JZ)China Postdoctoral Science Foundation,No.2022M712392(to ZY).
文摘We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.
文摘Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.
基金Supported by the Science and Medicine Joint Fund Project of Natural Science Foundation of Hunan Province(2022JJ80001).
文摘[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection.
文摘Functional connectivity networks (FCNs) are important in the diagnosis of neurological diseases and the understanding of brain tissue patterns. Recently, many methods, such as Pearson’s correlation (PC), Sparse representation (SR), and Sparse low-rank representation have been proposed to estimate FCNs. Despite their popularity, they only capture the low-order connections of the brain regions, failing to encode more complex relationships (i.e. , high-order relationships). Although researchers have proposed high-order methods, like PC + PC and SR + SR, aiming to build FCNs that can reflect more real state of the brain. However, such methods only consider the relationships between brain regions during the FCN construction process, neglecting the potential shared topological structure information between FCNs of different subjects. In addition, the low-order relationships are always neglected during the construction of high-order FCNs. To address these issues, in this paper we proposed a novel method, namely Ho-FCN<sub>Tops</sub>, towards estimating high-order FCNs based on brain topological structure. Specifically, inspired by the Group-constrained sparse representation (GSR), we first introduced a prior assumption that all subjects share the same topological structure in the construction of the low-order FCNs. Subsequently, we employed the Correlation-reserved embedding (COPE) to eliminate noise and redundancy from the low-order FCNs. Meanwhile, we retained the original low-order relationships during the embedding process to obtain new node representations. Finally, we utilized the SR method on the obtained new node representations to construct the Ho-FCN<sub>Tops</sub> required for disease identification. To validate the effectiveness of the proposed method, experiments were conducted on 137 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to identify Mild Cognitive Impairment (MCI) patients from the normal controls. The experimental results demonstrate superior performance compared to baseline methods.
基金This study was supported by a donation from the Erb family to the Beaumont Foundation,and by NIH grants R01AG17917,P30AG10161,and R01AG15819 to Dr.Bennett.
文摘Background:Tau vaccination and administration of anti-tau antibodies can prevent pathology and cognitive impairment in transgenic mouse models of tauopathy,suggesting that therapies which increase anti-tau antibodies might slow the development and/or progression of Alzheimer’s disease(AD).The extent to which individuals with no cognitive impairment(NCI)possess serum anti-tau antibodies,and whether their concentrations of these antibodies differ from anti-tau antibody levels in persons with mild cognitive impairment(MCI)or AD,are unclear.Previous studies measuring these antibodies did not account for antibody polyvalent binding,which can be extensive,nor that antibody binding to phosphorylated tau peptides could be due to binding to non-phosphorylated epitopes on those peptides.Methods:An ELISA controlling for these factors was used to measure the specific binding of serum IgG and IgM to phosphorylated(“pTau;”phosphorylated at Serine-199 and Serine-202)and non-phosphorylated(“non-pTau”)tau 196-207 in subjects with NCI,MCI,or AD(n=10/group).Between-group differences in these antibody levels were evaluated for statistical significance,and correlations were examined in pooled data from all subjects between these antibody levels and subject age,global cognitive functioning,and NFT counts.Results:Specific IgG binding to pTau and non-pTau was detected in all subjects except for one NCI control.Specific IgM binding was detected to pTau in all subjects except for two AD patients,and to non-pTau in all subjects.Mean pTau IgG was increased in MCI subjects by 53% and 70% vs.AD and NCI subjects respectively(both p<0.05),while no significant differences were found between groups for non-pTau IgG(p=0.052),pTau IgM,or non-pTau IgM.Non-pTau IgG was negatively associated with global cognition(Spearman rho=−0.50).Conclusions:Specific binding of serum IgG and IgM to phosphorylated and non-phosphorylated tau may be present in older persons regardless of their cognitive status.Serum IgG to phosphorylated tau may be increased in individuals with MCI,but this unexpected finding requires confirmation.The approach used in this study to measure specific serum antibodies to phosphorylated tau should be useful for measuring antibodies to other post-translationally-modified proteins that are of relevance to neurodegenerative disorders.
基金supported by the National Natural Science Foundation of China,Nos.81772438,81974357the Guangzhou Municipal Science and Technology Program,No.202206010197(all to YL)。
文摘The spleen is critical for immunity.It is the largest immune organ and immune center in the peripheral system.While the relationship between behavior and immunity has been demonstrated in physiology and diseases,the role of the spleen in behavior is not clear.To investigate the effects of the spleen on behaviors,we performed a refined splenectomy procedure on C57BL/6J mice and performed an open field test,circadian rhythm test,elevated plus maze,sucrose preference test,and Barnes maze test.Splenectomy did not induce changes in general locomotion,circadian rhythms,learning and memory,or depression/anxiety-related behaviors.To further investigate the effects of spleen on stress susceptibility,we established mouse models of depression through chronic unpredictable mild stress.The behavioral performances of mice subjected to splenectomy showed no differences from control animals.These findings suggest that splenectomy does not cause changes in baseline behavioral performance in mice.
