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
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
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
Sandwich structures are widely favored for their lightweight,high strength and superior impact mitigation capabilities in blast mitigation and transportation safety applications.Their application in large-scale,high-e...Sandwich structures are widely favored for their lightweight,high strength and superior impact mitigation capabilities in blast mitigation and transportation safety applications.Their application in large-scale,high-energy rockfall protection remains limited due to their relatively low volumetric energy absorption efficiency and the complex fabrication processes of key energy-absorbing components.To address these limitations,this study proposes a novel sandwich structure incorporating mild steel tubes as core energy absorbers to efficiently mitigate highenergy rockfall impacts.A finite element model was developed in LS-DYNA to systematically investigate the deformation and energy absorption behaviors.Comprehensive parametric analyses were conducted to quantify the effects of key design variables,including tube wall thickness,tube spacing(number of tubes),and infill materials.The results demonstrate that increasing tube wall thickness significantly enhances ultimate energy absorption,with 12-mm-thick tubes absorbing 2.2 times more energy than 6-mm-thick tubes.Lateral constraints induced by adjacent tubes improve specific energy absorption per unit displacement by approximately 30%-45%.Furthermore,incorporating infill materials considerably enhances energy absorption,with aluminum foam infills achieving an 81%increase compared to empty tubes.Nevertheless,higher energy absorption capacity typically leads to greater peak impact forces,increasing the number of tubes offers a better balance between energy absorption and impact force,optimizing the structural performance.These findings provide valuable theoretical insights and practical guidelines for designing sandwich structures in civil and infrastructure engineering applications for effective rockfall protection.展开更多
The carbonylation of amines offers a promising route for synthesizing N-substituted carbamates with high atom economy.However,conventional catalysts exhibit limited catalytic efficiency,and the underlying proton trans...The carbonylation of amines offers a promising route for synthesizing N-substituted carbamates with high atom economy.However,conventional catalysts exhibit limited catalytic efficiency,and the underlying proton transfer mechanism remains elusive.Herein,we reported a metal-free,room-temperature strategy utilizing 1,5,7-triazabicyclo[4.4.0]dec-5-ene(TBD)as a dual hydrogen bond catalyst to synergistically activate propylamine(PA)and dimethyl carbonate(DMC).This green catalytic system achieves a 10-fold acceleration in reaction rate compared to other hydrogen bonding catalysts under mild conditions.This is enabled by dual hydrogen bonding of TBD with PA and DMC,which facilitates rapid proton transfer and stabilizes tetrahedral intermediates.Theoretical calculations confirm that the dual hydrogen bond system significantly lowers activation energy compared to single hydrogen bond analogs.Furthermore,it was revealed that the hydrogen bonding network within the product is the primary factor responsible for the sluggish reaction rate.This study demonstrates the effectiveness of a dual hydrogen bond system in accelerating the carbonylation of amines and provides a green route to access carbamates.展开更多
The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests suc...The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests such as the Mini-Mental State Examination and the Montreal Cognitive Assessment,exhibit inherent limitations with respect to accessibility,administration burden,and sensitivity to subtle cognitive decline,particularly among diverse populations.This commentary critically examines a recent study that champions a novel approach:The integration of gait and handwriting kinematic parameters analyzed via machine learning for MCI screening.The present study positions itself within the broader landscape of MCI detection,with a view to comparing its advantages against established neuropsychological batteries,advanced neuroimaging(e.g.,positron emission tomography,magnetic resonance imaging),and emerging fluid biomarkers(e.g.,cerebrospinal fluid,blood-based assays).While the study demonstrates promising accuracy(74.44%area under the curve 0.74 with gait and graphic handwriting)and addresses key unmet needs in accessibility and objectivity,we highlight its cross-sectional nature,limited sample diversity,and lack of dual-task assessment as areas for future refinement.This commentary posits that kinematic biomarkers offer a distinctive,scalable,and ecologically valid approach to widespread MCI screening,thereby complementing existing methods by providing real-world functional insights.Future research should prioritize longitudinal validation,expansion to diverse cohorts,integration with multimodal data including dual-tasking,and the development of highly portable,artificial intelligence-driven solutions to achieve the democratization of early MCI detection and enable timely interventions.展开更多
BACKGROUND The therapeutic role of neurodynamic mobilization in improving lower limb function in patients with mild post-traumatic knee osteoarthritis remains poorly understood.AIM To further elucidate the role of neu...BACKGROUND The therapeutic role of neurodynamic mobilization in improving lower limb function in patients with mild post-traumatic knee osteoarthritis remains poorly understood.AIM To further elucidate the role of neurodynamic mobilization in facilitating knee joint functional recovery.METHODS Thirty-two patients with post-traumatic knee osteoarthritis treated at Chonghua Hospital of Traditional Chinese Medicine(Guilin)from March 2024 to August 2025 were randomly assigned to a control group(n=16)or an intervention group(n=16).Both groups received eight weeks of conventional treatment;and the intervention group additionally underwent neurodynamic mobilization.Outcomes including pain assessed by the visual analogue scale,active range of motion,Lysholm score,stork stand test,single hop test,and Y-balance test were assessed before and after the intervention.RESULTS There were no significant differences between the two groups in baseline characteristics,including gender,age,body mass index,or surgical side(P>0.05).Two-way repeated-measures analysis of variance demonstrated significant time×group interaction effects for the visual analogue scale score(F=13.364,P<0.05),Lysholm knee score(F=20.385,P<0.05),stork stand test(F=103.756,P<0.05),and Y-balance test score(F=8.089,P<0.05).CONCLUSION Neurodynamic mobilization effectively reduces pain,improves knee function,and enhances lower limb balance in patients with mild post-traumatic knee osteoarthritis.展开更多
Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic ...Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.展开更多
Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increa...Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increased interleukin-33(IL-33)levels in the peripheral blood of patients with rmTBI,suggesting IL-33 may participate in regulating the pathological development of rmTBI.The study aims to elucidate the impact and mechanism of IL-33 in the progression of neuropathology following rmTBI,and to explore its potential as a therapeutic target to improve the neurological outcome.Methods:The study employed an rmTBI mouse model using the wild-type(WT)and IL-33 knockout mice.Cognitive function was assessed via the Y-maze and Barnes tests.The main cell type expressing IL-33 and its receptor,suppression of tumorigenicity 2(ST2),was then investigated in the mouse brain through immunofluorescence colocalization.As the primary neural cell responsible for ST2 expression,microglia were studied in vitro using the BV2 cell line.The effects of lipid droplets(LDs)accumulation and amyloid-beta(Aβ)phagocytosis were measured to elucidate the impact of IL-33 on BV2 cells'phagocytosis.Additionally,HT22 neuronal apoptosis was assessed by flow cytometry.Finally,the cognitive effects of intranasal administration of IL-33 were evaluated in mice.Results:IL-33 KO mice exhibited pronounced cognitive impairment after rmTBI.In the mouse brain,astrocytes were identified as the primary source of IL-33 secretion,while microglia predominantly expressed ST2.Transcriptome sequencing revealed that IL-33 significantly influenced phagocytosis function.IL-33 mitigated LDs accumulation in BV2 cells and enhanced Aβphagocytosis in vitro.In addition,the culture medium of BV2 cells with activated IL-33/ST2 signaling reduced HT22 neuronal apoptosis and axonal damage.Furthermore,intranasal administration of IL-33 was observed to be effective in alleviating neurodegeneration and cognitive outcome of rmTBI mice.Conclusions:Dysfunction of the IL-33/ST2 axis following rmTBI leads to cognitive dysfunction via impairing microglial phagocytosis capacity and promoting neuronal damage.IL-33 would be a promising therapeutic target for alleviating neurodegeneration following rmTBI.展开更多
Alzheimer’s disease-associated transcriptomic landscapes have been defined in brain tissue.However,changes in blood RNA and their clinical relevance remain poorly understood.In this study,we developed an RNA profile ...Alzheimer’s disease-associated transcriptomic landscapes have been defined in brain tissue.However,changes in blood RNA and their clinical relevance remain poorly understood.In this study,we developed an RNA profile based on 1468 blood samples from both human and mouse studies,which include bulk RNA sequencing(RNA-seq),microRNA-seq,and single-cell RNA-seq data.We developed a comprehensive analysis pipeline that conducted over 11 million comparisons and correlations to identify more than 20,000 blood features.With these findings,we established a blood RNA database related to Alzheimer’s disease,RNAs in Blood of AD(RBAD,http://www.bioinform.cn/RBAD/).Using RBAD,we initially validated well-established Alzheimer’s disease-related pathways,including olfactory transduction.We then observed a decrease in both the proportion and functionality of erythroid cells,likely attributed to their elevated CD45 levels and interactions with GZMK^(+)CD8^(+)T cells.Furthermore,we identified 449 blood RNAs linked to patients’overall survival,along with two mRNAs(H4C3 and CTU1)associated with cognitive decline.In summary,RBAD is the first web-based analysis platform dedicated to investigating blood RNA changes in Alzheimer’s disease,and provides valuable insights into potential peripheral biomarkers and pathogenic mechanisms related to Alzheimer’s disease.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
氨气(NH_(3))作为一种兼具储能的无碳燃料,在能源领域具有极大的应用前景。然而,NH_(3)的燃烧特性与常规碳氢燃料有着明显差异。该文通过数值模拟方法,研究了CH_(4)/NH_(3)的混合燃料低氧稀释(moderate or intense low-oxygen dilution,...氨气(NH_(3))作为一种兼具储能的无碳燃料,在能源领域具有极大的应用前景。然而,NH_(3)的燃烧特性与常规碳氢燃料有着明显差异。该文通过数值模拟方法,研究了CH_(4)/NH_(3)的混合燃料低氧稀释(moderate or intense low-oxygen dilution,MILD)燃烧特性。结果表明,在甲烷MILD燃烧中添加NH_(3)使出口NO排放亟剧增加。过量空气系数大于1时,减小过量空气系数使NO和CO的排放降低。NH_(3)中的N元素转化成NO的转化率随燃料中NH_(3)的增加和过量空气系数的降低而减小。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
中强度低氧稀释(Moderate or Intense Low-oxygen Dilution,MILD)燃烧是一种新型低氧稀释燃烧技术,能够同时实现低NO_(x)和碳烟排放。基于化学动力学分析软件CHEMKIN-PRO中的对冲火焰模型,通过数值模拟研究了丙烷MILD燃烧方式下碳烟的...中强度低氧稀释(Moderate or Intense Low-oxygen Dilution,MILD)燃烧是一种新型低氧稀释燃烧技术,能够同时实现低NO_(x)和碳烟排放。基于化学动力学分析软件CHEMKIN-PRO中的对冲火焰模型,通过数值模拟研究了丙烷MILD燃烧方式下碳烟的生成路径及其与常规燃烧之间的差异,并深入探讨了拉伸率(50~80 s^(-1))和CO_(2)稀释(体积分数0~60%)对丙烷MILD方式下碳烟生成路径的影响。结果表明:MILD燃烧方式下碳烟生成的主要路径是2C_(3)H_(3)→A1、A1^(−)+H(+M)⇌A1(+M)、A1^(−)+CH_(4)⇌A1+CH_(3)、A1^(−)+C_(2)H_(4)⇌A1+C_(2)H_(3)、C_(6)H_(5)CH_(3)+H=A1+CH_(3)和C_(4)H_(5)^(-2)+C_(2)H_(2)=A1+H;与常规燃烧相比,MILD燃烧方式下2C_(3)H_(3)→A1和A1^(−)+H(+M)⇌A1(+M)反应速率降低,减少了A1生成进而抑制了碳烟成核,最终导致碳烟表面质量生长速率降低78.6%,最终碳烟峰值体积分数降低了83.7%;相比之下,MILD燃烧方式下2C_(3)H_(3)→A1路径对碳烟生成的贡献率降低了7.7%,而C_(6)H_(5)CH_(3)+H=A1+CH_(3)和C_(4)H_(5)^(-2)+C_(2)H_(2)=A1+H路径的贡献率重要性明显上升,分别提升5.36%和7.59%;此外,MILD燃烧方式下碳烟峰值体积分数随拉伸率的变化呈非线性特征,碳烟峰值体积分数随拉伸率的增加呈现先升高后降低的趋势,其机理源于成核速率的非单调变化与表面生长速率的持续上升之间的竞争效应。CO_(2)的物理和化学效应随着稀释比例的上升呈增加趋势,在稀释范围为0~40%时,CO_(2)的物理效应对碳烟峰值影响不大,CO_(2)通过CO+OH⇌CO_(2)+H反应促进H消耗从而削弱PAH生长所需的HACA机制,导致A1和A4物质的量分数显著降低,在CO_(2)稀释比例为60%时碳烟峰值体积分数进一步降低至6.4×10^(−9),从而进一步减少MILD燃烧方式下碳烟的生成。展开更多
Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal t...Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal therapy hydrogel with a pulsed drug delivery mechanism.The system is predicated on a hydrogel matrix that is thermally responsive,characteristic of bone defect sites,facilitating controlled and site-specific drug release.The cornerstone of this system is the incorporation of mild photothermal nanoparticles,which are activated within the temperature range of 40–43°C,thereby enhancing the precision and efficacy of drug delivery.Our findings demonstrate that the photothermal response significantly augments the localized delivery of therapeutic agents,mitigating systemic side effects and bolstering efficacy at the defect site.The synchronized pulsed release,cooperated with mild photothermal therapy,effectively addresses infection control,and promotes bone regeneration.This approach signifies a considerable advancement in the management of infectious bone defects,offering an effective and patient-centric alternative to traditional methods.Our research endeavors to extend its applicability to a wider spectrum of tissue regeneration scenarios,underscoring its transformative potential in the realm of regenerative medicine.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.
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supported by the National Key R&D Program of China(Grant No.2019YFC1509703)the Tianjin Science and Technology Program Project(Grant No.23YFYSHZ00130)。
文摘Sandwich structures are widely favored for their lightweight,high strength and superior impact mitigation capabilities in blast mitigation and transportation safety applications.Their application in large-scale,high-energy rockfall protection remains limited due to their relatively low volumetric energy absorption efficiency and the complex fabrication processes of key energy-absorbing components.To address these limitations,this study proposes a novel sandwich structure incorporating mild steel tubes as core energy absorbers to efficiently mitigate highenergy rockfall impacts.A finite element model was developed in LS-DYNA to systematically investigate the deformation and energy absorption behaviors.Comprehensive parametric analyses were conducted to quantify the effects of key design variables,including tube wall thickness,tube spacing(number of tubes),and infill materials.The results demonstrate that increasing tube wall thickness significantly enhances ultimate energy absorption,with 12-mm-thick tubes absorbing 2.2 times more energy than 6-mm-thick tubes.Lateral constraints induced by adjacent tubes improve specific energy absorption per unit displacement by approximately 30%-45%.Furthermore,incorporating infill materials considerably enhances energy absorption,with aluminum foam infills achieving an 81%increase compared to empty tubes.Nevertheless,higher energy absorption capacity typically leads to greater peak impact forces,increasing the number of tubes offers a better balance between energy absorption and impact force,optimizing the structural performance.These findings provide valuable theoretical insights and practical guidelines for designing sandwich structures in civil and infrastructure engineering applications for effective rockfall protection.
基金financially supported by the National Key R&D Program of China(2023YFC3905400)the Clean Combustion and Low-carbon Utilization of Coal,Strategic Priority Research Program of the Chinese Academy of Sciences,Grant No.XDA 29000000.
文摘The carbonylation of amines offers a promising route for synthesizing N-substituted carbamates with high atom economy.However,conventional catalysts exhibit limited catalytic efficiency,and the underlying proton transfer mechanism remains elusive.Herein,we reported a metal-free,room-temperature strategy utilizing 1,5,7-triazabicyclo[4.4.0]dec-5-ene(TBD)as a dual hydrogen bond catalyst to synergistically activate propylamine(PA)and dimethyl carbonate(DMC).This green catalytic system achieves a 10-fold acceleration in reaction rate compared to other hydrogen bonding catalysts under mild conditions.This is enabled by dual hydrogen bonding of TBD with PA and DMC,which facilitates rapid proton transfer and stabilizes tetrahedral intermediates.Theoretical calculations confirm that the dual hydrogen bond system significantly lowers activation energy compared to single hydrogen bond analogs.Furthermore,it was revealed that the hydrogen bonding network within the product is the primary factor responsible for the sluggish reaction rate.This study demonstrates the effectiveness of a dual hydrogen bond system in accelerating the carbonylation of amines and provides a green route to access carbamates.
文摘The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests such as the Mini-Mental State Examination and the Montreal Cognitive Assessment,exhibit inherent limitations with respect to accessibility,administration burden,and sensitivity to subtle cognitive decline,particularly among diverse populations.This commentary critically examines a recent study that champions a novel approach:The integration of gait and handwriting kinematic parameters analyzed via machine learning for MCI screening.The present study positions itself within the broader landscape of MCI detection,with a view to comparing its advantages against established neuropsychological batteries,advanced neuroimaging(e.g.,positron emission tomography,magnetic resonance imaging),and emerging fluid biomarkers(e.g.,cerebrospinal fluid,blood-based assays).While the study demonstrates promising accuracy(74.44%area under the curve 0.74 with gait and graphic handwriting)and addresses key unmet needs in accessibility and objectivity,we highlight its cross-sectional nature,limited sample diversity,and lack of dual-task assessment as areas for future refinement.This commentary posits that kinematic biomarkers offer a distinctive,scalable,and ecologically valid approach to widespread MCI screening,thereby complementing existing methods by providing real-world functional insights.Future research should prioritize longitudinal validation,expansion to diverse cohorts,integration with multimodal data including dual-tasking,and the development of highly portable,artificial intelligence-driven solutions to achieve the democratization of early MCI detection and enable timely interventions.
基金Supported by the Central Guided Local Science and Technology Development Fund Project for Science and Technology Innovation Base Construction,No.Guike ZY24212046National Natural Science Foundation of China,No.U22A2092+3 种基金Guangxi Education Science“the 14th Five-Year Plan”2024 Special Project“Research on Steam Education Practice in Rehabilitation Engineering”,No.2024ZJY304the Research Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi,No.2025KY2255the Innovation Project of GUET Graduate Education,No.2025YCXB010Natural Science Research Project of Guilin Life and Health Career Technical College,No.2025GKKY04.
文摘BACKGROUND The therapeutic role of neurodynamic mobilization in improving lower limb function in patients with mild post-traumatic knee osteoarthritis remains poorly understood.AIM To further elucidate the role of neurodynamic mobilization in facilitating knee joint functional recovery.METHODS Thirty-two patients with post-traumatic knee osteoarthritis treated at Chonghua Hospital of Traditional Chinese Medicine(Guilin)from March 2024 to August 2025 were randomly assigned to a control group(n=16)or an intervention group(n=16).Both groups received eight weeks of conventional treatment;and the intervention group additionally underwent neurodynamic mobilization.Outcomes including pain assessed by the visual analogue scale,active range of motion,Lysholm score,stork stand test,single hop test,and Y-balance test were assessed before and after the intervention.RESULTS There were no significant differences between the two groups in baseline characteristics,including gender,age,body mass index,or surgical side(P>0.05).Two-way repeated-measures analysis of variance demonstrated significant time×group interaction effects for the visual analogue scale score(F=13.364,P<0.05),Lysholm knee score(F=20.385,P<0.05),stork stand test(F=103.756,P<0.05),and Y-balance test score(F=8.089,P<0.05).CONCLUSION Neurodynamic mobilization effectively reduces pain,improves knee function,and enhances lower limb balance in patients with mild post-traumatic knee osteoarthritis.
文摘Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.
基金supported by the National Natural Science Foundation of China(82271401,82071394)the Tianjin Health Research Project(TJWJ2024RC002)。
文摘Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increased interleukin-33(IL-33)levels in the peripheral blood of patients with rmTBI,suggesting IL-33 may participate in regulating the pathological development of rmTBI.The study aims to elucidate the impact and mechanism of IL-33 in the progression of neuropathology following rmTBI,and to explore its potential as a therapeutic target to improve the neurological outcome.Methods:The study employed an rmTBI mouse model using the wild-type(WT)and IL-33 knockout mice.Cognitive function was assessed via the Y-maze and Barnes tests.The main cell type expressing IL-33 and its receptor,suppression of tumorigenicity 2(ST2),was then investigated in the mouse brain through immunofluorescence colocalization.As the primary neural cell responsible for ST2 expression,microglia were studied in vitro using the BV2 cell line.The effects of lipid droplets(LDs)accumulation and amyloid-beta(Aβ)phagocytosis were measured to elucidate the impact of IL-33 on BV2 cells'phagocytosis.Additionally,HT22 neuronal apoptosis was assessed by flow cytometry.Finally,the cognitive effects of intranasal administration of IL-33 were evaluated in mice.Results:IL-33 KO mice exhibited pronounced cognitive impairment after rmTBI.In the mouse brain,astrocytes were identified as the primary source of IL-33 secretion,while microglia predominantly expressed ST2.Transcriptome sequencing revealed that IL-33 significantly influenced phagocytosis function.IL-33 mitigated LDs accumulation in BV2 cells and enhanced Aβphagocytosis in vitro.In addition,the culture medium of BV2 cells with activated IL-33/ST2 signaling reduced HT22 neuronal apoptosis and axonal damage.Furthermore,intranasal administration of IL-33 was observed to be effective in alleviating neurodegeneration and cognitive outcome of rmTBI mice.Conclusions:Dysfunction of the IL-33/ST2 axis following rmTBI leads to cognitive dysfunction via impairing microglial phagocytosis capacity and promoting neuronal damage.IL-33 would be a promising therapeutic target for alleviating neurodegeneration following rmTBI.
基金supported by Research and Innovation Foundation of Wuhan Asia General Hospital,No.2022KYCX1-B10(to FH)the Natural ScienceFoundation of Hubei Province,No.2023AFB550(to FH)+2 种基金the National Natural Science Foundation of China,Nos.32400554(to FH),82371444(to YZ)theGuiding Project of the Scientific Research Program of the Department of Education of Hubei Province,No.B2021016(to FH)the Natural Science Foundationof Hubei Province,No.2024AFB853(to QW).
文摘Alzheimer’s disease-associated transcriptomic landscapes have been defined in brain tissue.However,changes in blood RNA and their clinical relevance remain poorly understood.In this study,we developed an RNA profile based on 1468 blood samples from both human and mouse studies,which include bulk RNA sequencing(RNA-seq),microRNA-seq,and single-cell RNA-seq data.We developed a comprehensive analysis pipeline that conducted over 11 million comparisons and correlations to identify more than 20,000 blood features.With these findings,we established a blood RNA database related to Alzheimer’s disease,RNAs in Blood of AD(RBAD,http://www.bioinform.cn/RBAD/).Using RBAD,we initially validated well-established Alzheimer’s disease-related pathways,including olfactory transduction.We then observed a decrease in both the proportion and functionality of erythroid cells,likely attributed to their elevated CD45 levels and interactions with GZMK^(+)CD8^(+)T cells.Furthermore,we identified 449 blood RNAs linked to patients’overall survival,along with two mRNAs(H4C3 and CTU1)associated with cognitive decline.In summary,RBAD is the first web-based analysis platform dedicated to investigating blood RNA changes in Alzheimer’s disease,and provides valuable insights into potential peripheral biomarkers and pathogenic mechanisms related to Alzheimer’s disease.
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.
文摘氨气(NH_(3))作为一种兼具储能的无碳燃料,在能源领域具有极大的应用前景。然而,NH_(3)的燃烧特性与常规碳氢燃料有着明显差异。该文通过数值模拟方法,研究了CH_(4)/NH_(3)的混合燃料低氧稀释(moderate or intense low-oxygen dilution,MILD)燃烧特性。结果表明,在甲烷MILD燃烧中添加NH_(3)使出口NO排放亟剧增加。过量空气系数大于1时,减小过量空气系数使NO和CO的排放降低。NH_(3)中的N元素转化成NO的转化率随燃料中NH_(3)的增加和过量空气系数的降低而减小。
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(32171354,82222015,82171001)The National Key Research and Development Program of China2023YFC2413600Research Funding from West China School/Hospital of Stomatology,Sichuan University(No.RCDWIS2023-1).
文摘Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal therapy hydrogel with a pulsed drug delivery mechanism.The system is predicated on a hydrogel matrix that is thermally responsive,characteristic of bone defect sites,facilitating controlled and site-specific drug release.The cornerstone of this system is the incorporation of mild photothermal nanoparticles,which are activated within the temperature range of 40–43°C,thereby enhancing the precision and efficacy of drug delivery.Our findings demonstrate that the photothermal response significantly augments the localized delivery of therapeutic agents,mitigating systemic side effects and bolstering efficacy at the defect site.The synchronized pulsed release,cooperated with mild photothermal therapy,effectively addresses infection control,and promotes bone regeneration.This approach signifies a considerable advancement in the management of infectious bone defects,offering an effective and patient-centric alternative to traditional methods.Our research endeavors to extend its applicability to a wider spectrum of tissue regeneration scenarios,underscoring its transformative potential in the realm of regenerative medicine.
