Fixed-time synchronization(FTS)of delayed memristor-based neural networks(MNNs)with discontinuous activations is studied in this paper.Both continuous and discontinuous activations are considered forMNNs.And the mixed...Fixed-time synchronization(FTS)of delayed memristor-based neural networks(MNNs)with discontinuous activations is studied in this paper.Both continuous and discontinuous activations are considered forMNNs.And the mixed delays which are closer to reality are taken into the system.Besides,two kinds of control schemes are proposed,including feedback and adaptive control strategies.Based on some lemmas,mathematical inequalities and the designed controllers,a few synchronization criteria are acquired.Moreover,the upper bound of settling time(ST)which is independent of the initial values is given.Finally,the feasibility of our theory is attested by simulation examples.展开更多
Arsenic in drinking water is a worldwide health problem that is associated with cardiovascular disease, but the cause is currently unknown. In order to examine whether arsenic affects vasomotor tone in blood vessels, ...Arsenic in drinking water is a worldwide health problem that is associated with cardiovascular disease, but the cause is currently unknown. In order to examine whether arsenic affects vasomotor tone in blood vessels, we investigated the effect of arsenic on agonist-induced vasorelaxation and vasoconstriction using the isolated rat aortic rings in in vitro organ bath system. Treatment with inorganic arsenite (AsⅢ) inhibited acetylcholine-induced relaxation of aortic rings by inhibiting production of nitric oxide in endothelium.展开更多
BACKGROUND:Point-of-care ultrasound(POCUS)has become increasingly integrated into the practice of emergency medicine.A common application is the extended focused assessment with sonography in trauma(eFAST)exam.The Ame...BACKGROUND:Point-of-care ultrasound(POCUS)has become increasingly integrated into the practice of emergency medicine.A common application is the extended focused assessment with sonography in trauma(eFAST)exam.The American College of Emergency Physicians has guidelines regarding the scope of ultrasound in the emergency department and the appropriate documentation.The objective of this study was to conduct a review of performed,documented and billed eFAST ultrasounds on trauma activation patients.METHODS:This was a retrospective review of all trauma activation patients during a 10-month period at an academic level-one trauma center.A list comparing all trauma activations was crossreferenced with a list of all billed eFAST scans.Medical records were reviewed to determine whether an eFAST was indicated,performed,and appropriately documented.RESULTS:We found that 1,507 of 1,597 trauma patients had indications for eFAST,but 396(27%)of these patients did not have a billed eFAST.Of these 396 patients,87(22%)had documentation in the provider note that an eFAST was performed but there was no separate procedure note.The remaining 309(78%)did not have any documentation of the eFAST in the patient’s chart although an eFAST was recorded and reviewed during ultrasound quality assurance.CONCLUSION:A significant proportion of trauma patients had eFAST exams performed but were not documented or billed.Lack of documentation was multifactorial.Emergency ultrasound programs require appropriate reimbursement to support training,credentialing,equipment,quality assurance,and device maintenance.Our study demonstrates a significant absence of adequate documentation leading to potential revenue loss for an emergency ultrasound program.展开更多
Durian rind wastes are an important raw material for activated carbon production due to their renewable sources and low-cost materials.The efficiency of increasing surface area and the quantity of oxygen groups on the...Durian rind wastes are an important raw material for activated carbon production due to their renewable sources and low-cost materials.The efficiency of increasing surface area and the quantity of oxygen groups on the surface of activated carbon were studied for the preparation of activated carbon.The preparation of activated carbon has been studied with the different methods as follows:activation by acid,activation by base,hydrothermal and activation by acid,and hydrothermal and activation by base.The results showed that hydrothermal and activation by acid had high iodine number which was chosen to determine the optimum condition for activated carbon preparation.The optimum condition for preparation of durian rind activated carbon was studied by Box-Behnken design.Solid/water ratio,solid/acid ratio and temperature were chosen as the important parameters for achieving the optimum reaction condition.The reaction products were analyzed by iodine number.Based on the results,the optimum condition for preparation of durian rind activated carbon was predicted using RSM.The maximum iodine number of 626.47 mg/g was expected at the optimum condition:solid/water ratio(1:175,g/mL),solid/acid ratio(1:23,g/mL)and temperature(500℃).The preparation of durian rind activated carbon at the optimal condition was carried;the percentages of iodine number achieved(666.73±6 mg/g)were close to the maximum predicted value(666.73 mg/g),thus verifying the model.At the optimum condition,the functional group on surface of durian rind activated carbon was characterized by FT-IR.The result showed that the oxygen content on surface was increased in the form of carbonyl and sulfonyl group.展开更多
The fixed-time synchronization and preassigned-time synchronization are investigated for a class of quaternion-valued neural networks with time-varying delays and discontinuous activation functions. Unlike previous ef...The fixed-time synchronization and preassigned-time synchronization are investigated for a class of quaternion-valued neural networks with time-varying delays and discontinuous activation functions. Unlike previous efforts that employed separation analysis and the real-valued control design, based on the quaternion-valued signum function and several related properties, a direct analytical method is proposed here and the quaternion-valued controllers are designed in order to discuss the fixed-time synchronization for the relevant quaternion-valued neural networks. In addition, the preassigned-time synchronization is investigated based on a quaternion-valued control design, where the synchronization time is preassigned and the control gains are finite. Compared with existing results, the direct method without separation developed in this article is beneficial in terms of simplifying theoretical analysis, and the proposed quaternion-valued control schemes are simpler and more effective than the traditional design, which adds four real-valued controllers. Finally, two numerical examples are given in order to support the theoretical results.展开更多
Preparation of Zr2Al3C4-Al2O3 in situ composites was investigated by self-propagating high-temperature synthesis(SHS)involving both aluminothermic reduction of ZrO2 and chemical activation of PTFE(Teflon).The starting...Preparation of Zr2Al3C4-Al2O3 in situ composites was investigated by self-propagating high-temperature synthesis(SHS)involving both aluminothermic reduction of ZrO2 and chemical activation of PTFE(Teflon).The starting materials included ZrO2,Al,carbon black and PTFE.In addition to the conventional SHS method,the experiments were conducted by a chemical-oven SHS(COSHS)route to thermally assist the synthesis reaction.The threshold amount of 2%(mass fraction)PTFE was required to induce self-sustaining combustion.When the conventional SHS scheme was utilized,due to low combustion temperatures between 1152 and 1272°C and insufficient reaction time,the dominant carbide forming in the composite was ZrC instead of Zr2Al3C4.On the other hand,the COSHS technique increased the combustion temperature of the reactant compact to about 1576°C,lengthened the high-temperature duration for the reaction,and prevented Al vapor from escaping away.As a consequence,Zr2Al3C4-Al2O3 composites with a small amount of Zr3Al3C5 were obtained.The microstructure of the COSHS-derived product showed that plate-like Zr2Al3C4 grains were about 2μm in thickness and 10-30μm in length,and most of them were closely stacked into a laminated configuration.展开更多
As a vital energy resource and raw material for many industrial products,syngas(CO and H_(2))is of great significance.Dry reforming of methane(DRM)is an important approach to producing syngas(with a hydrogen-to-carbon...As a vital energy resource and raw material for many industrial products,syngas(CO and H_(2))is of great significance.Dry reforming of methane(DRM)is an important approach to producing syngas(with a hydrogen-to-carbon-monoxide ratio of 1:1 in principle)from methane and carbon dioxide,with a lower operational cost as compared to other reforming techniques.However,many pure metallic catalysts used in DRM face deactivation issues due to coke formation or sintering of the metal particles.A systematic search for highly efficient metallic catalysts,which reduce the reaction barriers for the rate-determining steps and resist carbon deposition,is urgently needed.Nickel is a typical low-cost transition metal for activating the C–H bond in methane.In this work,we applied a two-step workflow to search for nickel-based bimetallic catalysts with doping metals M(M-Ni)by combining density functional theory(DFT)calculations and machine learning(ML).We focus on the two critical steps in DRM—CH_(4) and CO_(2) direct activations.We used DFT and slab models for the Ni(111)facet to explore the relevant reaction pathways and constructed a data set containing structural and energetic information for representative M-Ni systems.We used this dataset to train ML models with chemical-knowledge-based features and predicted CH_(4) and CO_(2) dissociation energies and barriers,which revealed the composition–activity relationships of the bimetallic catalysts.We also used these models to rank the predicted catalytic performance of candidate systems to demonstrate the applicability of ML for catalyst screening.We emphasized that ML ranking models would be more valuable than regression models in high-throughput screenings.Finally,we used our trained model to screen 12 unexplored M-Ni systems and showed that the DFT-computed energies and barriers are very close to the ML-predicted values for top candidates,validating the robustness of the trained model.展开更多
Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
To elucidate the effect of calcite-regulated activated carbon(AC)structure on low-temperature denitrification performance of SCR catalysts,this work prepared a series of Mn-Ce/De-AC-xCaCO_(3)(x is the calcite content ...To elucidate the effect of calcite-regulated activated carbon(AC)structure on low-temperature denitrification performance of SCR catalysts,this work prepared a series of Mn-Ce/De-AC-xCaCO_(3)(x is the calcite content in coal)catalysts were prepared by the incipient wetness impregnation method,followed by acid washing to remove calcium-containing minerals.Comprehensive characterization and low-temperature denitrification tests revealed that calcite-induced structural modulation of coal-derived AC significantly enhances catalytic activity.Specifically,NO conversion increased from 88.3%of Mn-Ce/De-AC to 91.7%of Mn-Ce/De-AC-1CaCO_(3)(210℃).The improved SCR denitrification activity results from the enhancement of physicochemical properties including higher Mn^(4+)content and Ce^(4+)/Ce^(3+)ratio,an abundance of chemisorbed oxygen and acidic sites,which could strengthen the SCR reaction pathways(richer NH_(3)activated species and bidentate nitrate active species).Therefore,NO removal is enhanced.展开更多
BACKGROUND:Hemiplegia,a prevalent stroke-related condition,is often studied for motor dysfunction;however,spasticity remains under-researched.Abnormal muscle tone significantly hinders hemiplegic patients’walking rec...BACKGROUND:Hemiplegia,a prevalent stroke-related condition,is often studied for motor dysfunction;however,spasticity remains under-researched.Abnormal muscle tone significantly hinders hemiplegic patients’walking recovery.OBJECTIVE:To determine whether early suspension-protected training with a personal assistant machine for stroke patients enhances walking ability and prevents muscle spasms.METHODS:Thirty-two early-stage stroke patients from Shenzhen University General Hospital and the China Rehabilitation Research Center were randomly assigned to the experimental group(n=16)and the control group(n=16).Both groups underwent 4 weeks of gait training under the suspension protection system for 30 minutes daily,5 days a week.The experimental group used the personal assistant machine during training.Three-dimensional gait analysis(using the Cortex motion capture system),Brunnstrom staging,Fugl-Meyer Assessment for lower limb motor function,Fugl-Meyer balance function,and the modified Ashworth Scale were evaluated within 1 week before the intervention and after 4 weeks of intervention.RESULTS AND CONCLUSION:After the 4-week intervention,all outcome measures showed significant changes in each group.The experimental group had a small but significant increase in the modified Ashworth Scale score(P<0.05,d=|0.15|),while the control group had a large significant increase(P<0.05,d=|1.48|).The experimental group demonstrated greater improvements in walking speed(16.5 to 38.44 cm/s,P<0.05,d=|4.01|),step frequency(46.44 to 64.94 steps/min,P<0.05,d=|2.32|),stride length(15.50 to 29.81 cm,P<0.05,d=|3.44|),and peak hip and knee flexion(d=|1.82|to|2.17|).After treatment,the experimental group showed significantly greater improvements than the control group in walking speed(38.44 vs.26.63 cm/s,P<0.05,d=|2.75|),stride length,peak hip and knee flexion(d=|1.31|to|1.45|),step frequency(64.94 vs.59.38 steps/min,P<0.05,d=|0.85|),and a reduced support phase(bilateral:24.31%vs.28.38%,P<0.05,d=|0.88|;non-paretic:66.19%vs.70.13%,P<0.05,d=|0.94|).For early hemiplegia,personal assistant machine-assisted gait training under the suspension protection system helps establish a correct gait pattern,prevents muscle spasms,and improves motor function.展开更多
Passiflora incarnata L.,commonly known as passionflower,is traditionally cultivated as an ornamental plant but has demonstrated diverse therapeutic potential.Its pharmacological effects are attributed to bioactive com...Passiflora incarnata L.,commonly known as passionflower,is traditionally cultivated as an ornamental plant but has demonstrated diverse therapeutic potential.Its pharmacological effects are attributed to bioactive compounds such as flavonoids and alkaloids,which influence multiple biological pathways.This review aims to summarise and critically analyse recent findings on the pharmacological properties of Passiflora incarnata L.,focusing on its neuropsychiatric,antioxidant,antimicrobial,and anticancer activities.A targeted literature search was conducted in PubMed,Scopus,Web of Science,and Google Scholar for peer-reviewed publications between 2000 to 2025.Relevant articles were screened,and a more appropriate article related to the objective of the review was selected.Some classical papers are also cited as per the requirement of the topic.Passiflora incarnata L.showed multifunctional medicinal properties with various applications in neuropsychiatry,oxidative stress management,antimicrobial agent,and as an anticancer agent.The U.S.Food and Drug Administration categorizes passionflower extracts as“generally recognized as safe”.However,most evidence remains preclinical,with methodological variation limiting generalisation.Standardised formulation,robust clinical trials,and in-depth in vivo studies are essential to establish its therapeutic relevance and safety in modern medicine.展开更多
BACKGROUND Postoperative delirium(POD)is a common and serious complication in surgical patients,particularly older adults.Alterations in cholinergic function have been implicated in its pathophysiology.AIM To evaluate...BACKGROUND Postoperative delirium(POD)is a common and serious complication in surgical patients,particularly older adults.Alterations in cholinergic function have been implicated in its pathophysiology.AIM To evaluate the association between preoperative serum cholinesterase(ChE)activity—specifically butyrylcholinesterase(BuChE)and acetylcholinesterase(AChE)—and the risk of POD in adult surgical patients in a meta-analysis.METHODS A systematic search was conducted in PubMed,EMBASE,and Web of Science up to March 28,2025 for studies reporting preoperative serum BuChE or AChE activity in relation to subsequent POD incidence.Standardized mean differences(SMDs)and odds ratios(ORs)with 95%confidence intervals(CIs)were pooled using random-effects models.Subgroup and sensitivity analyses were performed based on follow-up duration and analytic models.RESULTS Thirteen studies(n=2730 patients)were included.Patients who developed POD had significantly lower preoperative BuChE activity than those who did not(SMD=-0.28;95%CI:-0.39 to-0.16;I²=18%).Higher BuChE activity was associated with a reduced risk of POD(OR per 100 unit increment=0.97;95%CI:0.95-0.99;I2=0%).In contrast,pooled AChE activity did not differ significantly between POD and non-POD groups(SMD=-0.25;95%CI:-0.53 to 0.03;P=0.08;I2=80%),and the ORs per 1 unit increment in AChE activity were not statistically significant(OR=0.98;95%CI:0.95-1.01).CONCLUSION Lower preoperative serum BuChE activity is associated with an increased risk of POD in adults undergoing surgery.BuChE activity may serve as a potential preoperative biomarker for POD risk stratification.展开更多
BACKGROUND Major depressive disorder(MDD)and obesity(OB)are bidirectionally comorbid conditions with common neurobiological underpinnings.However,the neurocognitive mechanisms of their comorbidity remain poorly unders...BACKGROUND Major depressive disorder(MDD)and obesity(OB)are bidirectionally comorbid conditions with common neurobiological underpinnings.However,the neurocognitive mechanisms of their comorbidity remain poorly understood.AIM To examine regional abnormalities in spontaneous brain activity among patients with MDD-OB comorbidity.METHODS This study adopted a regional homogeneity(ReHo)analysis of resting-state functional magnetic resonance imaging.The study included 149 hospital patients divided into four groups:Patients experiencing their first episode of drug-naive MDD with OB,patients with MDD without OB,and age-and sex-matched healthy individuals with and without OB.Whole-brain ReHo analysis was conducted using SPM12 software and RESTplus toolkits,with group comparisons via ANOVA and post-hoc tests.Correlations between ReHo values and behavioral measures were examined.RESULTS ANOVA revealed significant whole-brain ReHo differences among the four groups in four key regions:The left middle temporal gyrus(MTG.L),right cuneus,left precuneus,and left thalamus.Post-hoc analyses confirmed pairwise differences between all groups across these regions(P<0.05).OB was associated with ReHo alterations in the MTG.L,right cuneus,and left thalamus,whereas abnormalities in the precuneus suggested synergistic pathological mechanisms between MDD and OB.Statistically significant correlations were found between the drive and fun-seeking dimensions of the behavioral activation system,as well as behavioral inhibition and the corresponding ReHo values.CONCLUSION Our findings provide novel evidence for the neuroadaptive mechanisms underlying the MDD-OB comorbidity.Further validation could lead to personalized interventions targeting MTG.L hyperactivity and targeting healthy food cues.展开更多
AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analy...AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.展开更多
Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process...Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.展开更多
Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and...Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources,adding a substantial burden to the healthcare system and patients'families.In this context,chondroitinase ABC,a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals,has emerged as a promising therapeutic agent.It works by degrading chondroitin sulfate proteoglycans,cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides.Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains.Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting,enhancing the plasticity of perineuronal nets,inhibiting neuronal apoptosis,and modulating immune responses in various animal models.In this review,we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury.We also highlight research advancements in spinal cord injury treatment strategies,with a focus on chondroitinase ABC,and illustrate how improvements in chondroitinase ABC stability,enzymatic activity,and delivery methods have enhanced injured spinal cord repair.Furthermore,we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy.This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC-based spinal cord injury therapies,with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.展开更多
Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More r...Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More recently,advances in the development of Lecanemab,an anti-amyloid-βmonoclonal antibody,have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer’s disease in the Phase Ⅲ clinical trial(Clarity Alzheimer’s disease).Despite these promising results,side effects such as amyloid-related imaging abnormalities(ARIA)may limit its usage.ARIA can manifest as ARIA-E(cerebral edema or effusions)and ARIA-H(microhemorrhages or superficial siderosis)and is thought to be caused by increased vascular permeability due to inflammatory responses,leading to leakages of blood products and protein-rich fluid into brain parenchyma.Endothelial dysfunction is an early pathological feature of Alzheimer’s disease,and the blood-brain barrier becomes increasingly leaky as the disease progresses.In addition,APOE4,the strongest genetic risk factor for Alzheimer’s disease,is associated with higher vascular amyloid burden,increased ARIA incidence,and accelerated blood-brain barrier disruptions.These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer’s disease.Here,we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer’s disease progression.展开更多
Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et a...Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et al.,2022).This molecular event is believed to lead to activation of stress pathways ultimately resulting in cellular dysfunction(Eldeeb et al.,2022).Accordingly,many lines of research investigations focused on dampening the formation of protein aggregates or augmenting the clearance of protein aggregates as a potential therapeutic strategy to counteract the progression of neurodegenerative diseases,albeit with little success(Costa-Mattioli and Walter,2020).Cell stress cues such as the accumulation of protein aggregates lead to the activation of stress response pathways that aid cells in responding to the damage.Despite the notion that the transient activation of these pathways helps cells cope with stressors,persistent activation can induce unwanted apoptosis of cells and reduce overall tissue strength as well as lead to an accumulation of aggregation-prone proteins(Hetz and Papa,2018).Mutations in proteins involved in stress signaling termination can cause conditions like ataxia and early-onset dementia(Conroy et al.,2014).Therefore,it is crucial for stress response signaling to be turned off once conditions have improved.Nevertheless,the mechanisms by which cells silence these signals are still elusive.展开更多
BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to...BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to activate CD.Additionally,n-3 PUFAs are metabolized by the same enzyme as n-6 PUFAs and known to inhibit the arachidonic acid cascade.Our previous study noted that the presence of erythrocyte membrane fatty acids is a characteristic finding in Japanese CD patients.It was thus speculated that FADS2 gene polymorphisms,which induce PUFA metabolizing enzymes,are involved in the pathogenesis of CD,though no such relationship was found.AIM To investigate the relationship of FADS2 polymorphisms with serum and erythrocyte membrane fatty acid composition ratios,and disease activity.METHODS Using previously reported findings regarding FADS2 genetic polymorphisms,the records of 52 CD patients undergoing treatment at Jikei University Kashiwa Hospital were analyzed.Mutations noted were divided into three groups;wild-type(GG),heterozygous mutants(GA),and homozygous(AA),with the activities of delta-6 and delta-5 desaturases compared using redefined d6d index(rd.d6di)and d5d index(d5di).Additionally,comparisons of serum and erythrocyte membranes for fatty acid composition,and also gene polymorphisms and CD activity index(CDAI)were performed.RESULTS The presence of the rs174538 mutation in FADS2 resulted in reduction of only rd.d6di in the erythrocyte membrane(P<0.01).In contrast,that mutation was found to be associated with d5di induced by FADS1 in serum(P=0.019)as well as the erythrocyte membrane(P<0.0001),and also with reduction in the fatty acid composition of arachidonic acid in both serum(P<0.0001)and the erythrocyte membrane(P<0.01).Regarding disease activity,a positive correlation of CDAI score with rd.d6di in both serum(P<0.05)and the erythrocyte membrane(P<0.05)was found only in the rs174538 wild-type group.In contrast,there was no correction between CDAI and d5di in either serum or erythrocyte membrane samples.CONCLUSION The rs174538 mutation alters the fatty acid profile through strong linkage to the FADS1 gene.In wild-type individuals,rd.d6di was positively correlated with CDAI,suggesting predictive utility of disease severity.展开更多
Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory v...Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.展开更多
基金supported by National Natural Science Foundation of China under(Grant Nos.62173175,12026235,12026234,61903170,11805091,61877033,61833005)by 111 Project under Grant B17040+2 种基金by the Natural Science Foundation of Shandong Province under Grant Nos.ZR2019BF045,ZR2019MF021,ZR2019QF004by the Project of Shandong Province Higher Educational Science and Technology Program No.J18KA354by the Key Research and Development Project of Shandong Province of China,No.2019GGX101003.
文摘Fixed-time synchronization(FTS)of delayed memristor-based neural networks(MNNs)with discontinuous activations is studied in this paper.Both continuous and discontinuous activations are considered forMNNs.And the mixed delays which are closer to reality are taken into the system.Besides,two kinds of control schemes are proposed,including feedback and adaptive control strategies.Based on some lemmas,mathematical inequalities and the designed controllers,a few synchronization criteria are acquired.Moreover,the upper bound of settling time(ST)which is independent of the initial values is given.Finally,the feasibility of our theory is attested by simulation examples.
文摘Arsenic in drinking water is a worldwide health problem that is associated with cardiovascular disease, but the cause is currently unknown. In order to examine whether arsenic affects vasomotor tone in blood vessels, we investigated the effect of arsenic on agonist-induced vasorelaxation and vasoconstriction using the isolated rat aortic rings in in vitro organ bath system. Treatment with inorganic arsenite (AsⅢ) inhibited acetylcholine-induced relaxation of aortic rings by inhibiting production of nitric oxide in endothelium.
文摘BACKGROUND:Point-of-care ultrasound(POCUS)has become increasingly integrated into the practice of emergency medicine.A common application is the extended focused assessment with sonography in trauma(eFAST)exam.The American College of Emergency Physicians has guidelines regarding the scope of ultrasound in the emergency department and the appropriate documentation.The objective of this study was to conduct a review of performed,documented and billed eFAST ultrasounds on trauma activation patients.METHODS:This was a retrospective review of all trauma activation patients during a 10-month period at an academic level-one trauma center.A list comparing all trauma activations was crossreferenced with a list of all billed eFAST scans.Medical records were reviewed to determine whether an eFAST was indicated,performed,and appropriately documented.RESULTS:We found that 1,507 of 1,597 trauma patients had indications for eFAST,but 396(27%)of these patients did not have a billed eFAST.Of these 396 patients,87(22%)had documentation in the provider note that an eFAST was performed but there was no separate procedure note.The remaining 309(78%)did not have any documentation of the eFAST in the patient’s chart although an eFAST was recorded and reviewed during ultrasound quality assurance.CONCLUSION:A significant proportion of trauma patients had eFAST exams performed but were not documented or billed.Lack of documentation was multifactorial.Emergency ultrasound programs require appropriate reimbursement to support training,credentialing,equipment,quality assurance,and device maintenance.Our study demonstrates a significant absence of adequate documentation leading to potential revenue loss for an emergency ultrasound program.
基金The authors gratefully acknowledgement funding of this research(KREF116101)King Mongkut’s Institute of Technology Ladkrabang Research Fund,Thailand.
文摘Durian rind wastes are an important raw material for activated carbon production due to their renewable sources and low-cost materials.The efficiency of increasing surface area and the quantity of oxygen groups on the surface of activated carbon were studied for the preparation of activated carbon.The preparation of activated carbon has been studied with the different methods as follows:activation by acid,activation by base,hydrothermal and activation by acid,and hydrothermal and activation by base.The results showed that hydrothermal and activation by acid had high iodine number which was chosen to determine the optimum condition for activated carbon preparation.The optimum condition for preparation of durian rind activated carbon was studied by Box-Behnken design.Solid/water ratio,solid/acid ratio and temperature were chosen as the important parameters for achieving the optimum reaction condition.The reaction products were analyzed by iodine number.Based on the results,the optimum condition for preparation of durian rind activated carbon was predicted using RSM.The maximum iodine number of 626.47 mg/g was expected at the optimum condition:solid/water ratio(1:175,g/mL),solid/acid ratio(1:23,g/mL)and temperature(500℃).The preparation of durian rind activated carbon at the optimal condition was carried;the percentages of iodine number achieved(666.73±6 mg/g)were close to the maximum predicted value(666.73 mg/g),thus verifying the model.At the optimum condition,the functional group on surface of durian rind activated carbon was characterized by FT-IR.The result showed that the oxygen content on surface was increased in the form of carbonyl and sulfonyl group.
基金supported by the National Natural Science Foundation of China (61963033, 61866036, 62163035)the Key Project of Natural Science Foundation of Xinjiang (2021D01D10)+1 种基金the Xinjiang Key Laboratory of Applied Mathematics (XJDX1401)the Special Project for Local Science and Technology Development Guided by the Central Government (ZYYD2022A05)。
文摘The fixed-time synchronization and preassigned-time synchronization are investigated for a class of quaternion-valued neural networks with time-varying delays and discontinuous activation functions. Unlike previous efforts that employed separation analysis and the real-valued control design, based on the quaternion-valued signum function and several related properties, a direct analytical method is proposed here and the quaternion-valued controllers are designed in order to discuss the fixed-time synchronization for the relevant quaternion-valued neural networks. In addition, the preassigned-time synchronization is investigated based on a quaternion-valued control design, where the synchronization time is preassigned and the control gains are finite. Compared with existing results, the direct method without separation developed in this article is beneficial in terms of simplifying theoretical analysis, and the proposed quaternion-valued control schemes are simpler and more effective than the traditional design, which adds four real-valued controllers. Finally, two numerical examples are given in order to support the theoretical results.
基金sponsored by the Ministry of Science and Technology of Taiwan,China,under the grant of MOST 105-2221-E-035-039-MY2
文摘Preparation of Zr2Al3C4-Al2O3 in situ composites was investigated by self-propagating high-temperature synthesis(SHS)involving both aluminothermic reduction of ZrO2 and chemical activation of PTFE(Teflon).The starting materials included ZrO2,Al,carbon black and PTFE.In addition to the conventional SHS method,the experiments were conducted by a chemical-oven SHS(COSHS)route to thermally assist the synthesis reaction.The threshold amount of 2%(mass fraction)PTFE was required to induce self-sustaining combustion.When the conventional SHS scheme was utilized,due to low combustion temperatures between 1152 and 1272°C and insufficient reaction time,the dominant carbide forming in the composite was ZrC instead of Zr2Al3C4.On the other hand,the COSHS technique increased the combustion temperature of the reactant compact to about 1576°C,lengthened the high-temperature duration for the reaction,and prevented Al vapor from escaping away.As a consequence,Zr2Al3C4-Al2O3 composites with a small amount of Zr3Al3C5 were obtained.The microstructure of the COSHS-derived product showed that plate-like Zr2Al3C4 grains were about 2μm in thickness and 10-30μm in length,and most of them were closely stacked into a laminated configuration.
基金support provided by the American Chemical Society Petroleum Research Fund(PRF No.65744-DNI6).
文摘As a vital energy resource and raw material for many industrial products,syngas(CO and H_(2))is of great significance.Dry reforming of methane(DRM)is an important approach to producing syngas(with a hydrogen-to-carbon-monoxide ratio of 1:1 in principle)from methane and carbon dioxide,with a lower operational cost as compared to other reforming techniques.However,many pure metallic catalysts used in DRM face deactivation issues due to coke formation or sintering of the metal particles.A systematic search for highly efficient metallic catalysts,which reduce the reaction barriers for the rate-determining steps and resist carbon deposition,is urgently needed.Nickel is a typical low-cost transition metal for activating the C–H bond in methane.In this work,we applied a two-step workflow to search for nickel-based bimetallic catalysts with doping metals M(M-Ni)by combining density functional theory(DFT)calculations and machine learning(ML).We focus on the two critical steps in DRM—CH_(4) and CO_(2) direct activations.We used DFT and slab models for the Ni(111)facet to explore the relevant reaction pathways and constructed a data set containing structural and energetic information for representative M-Ni systems.We used this dataset to train ML models with chemical-knowledge-based features and predicted CH_(4) and CO_(2) dissociation energies and barriers,which revealed the composition–activity relationships of the bimetallic catalysts.We also used these models to rank the predicted catalytic performance of candidate systems to demonstrate the applicability of ML for catalyst screening.We emphasized that ML ranking models would be more valuable than regression models in high-throughput screenings.Finally,we used our trained model to screen 12 unexplored M-Ni systems and showed that the DFT-computed energies and barriers are very close to the ML-predicted values for top candidates,validating the robustness of the trained model.
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
基金Supported by the Science and Technology Cooperation and Exchange special project of Cooperation of Shanxi Province(202404041101014)the Fundamental Research Program of Shanxi Province(202403021212333)+3 种基金the Joint Funds of the National Natural Science Foundation of China(U24A20555)the Lvliang Key R&D of University-Local Cooperation(2023XDHZ10)the Initiation Fund for Doctoral Research of Taiyuan University of Science and Technology(20242026)the Outstanding Doctor Funding Award of Shanxi Province(20242080).
文摘To elucidate the effect of calcite-regulated activated carbon(AC)structure on low-temperature denitrification performance of SCR catalysts,this work prepared a series of Mn-Ce/De-AC-xCaCO_(3)(x is the calcite content in coal)catalysts were prepared by the incipient wetness impregnation method,followed by acid washing to remove calcium-containing minerals.Comprehensive characterization and low-temperature denitrification tests revealed that calcite-induced structural modulation of coal-derived AC significantly enhances catalytic activity.Specifically,NO conversion increased from 88.3%of Mn-Ce/De-AC to 91.7%of Mn-Ce/De-AC-1CaCO_(3)(210℃).The improved SCR denitrification activity results from the enhancement of physicochemical properties including higher Mn^(4+)content and Ce^(4+)/Ce^(3+)ratio,an abundance of chemisorbed oxygen and acidic sites,which could strengthen the SCR reaction pathways(richer NH_(3)activated species and bidentate nitrate active species).Therefore,NO removal is enhanced.
文摘BACKGROUND:Hemiplegia,a prevalent stroke-related condition,is often studied for motor dysfunction;however,spasticity remains under-researched.Abnormal muscle tone significantly hinders hemiplegic patients’walking recovery.OBJECTIVE:To determine whether early suspension-protected training with a personal assistant machine for stroke patients enhances walking ability and prevents muscle spasms.METHODS:Thirty-two early-stage stroke patients from Shenzhen University General Hospital and the China Rehabilitation Research Center were randomly assigned to the experimental group(n=16)and the control group(n=16).Both groups underwent 4 weeks of gait training under the suspension protection system for 30 minutes daily,5 days a week.The experimental group used the personal assistant machine during training.Three-dimensional gait analysis(using the Cortex motion capture system),Brunnstrom staging,Fugl-Meyer Assessment for lower limb motor function,Fugl-Meyer balance function,and the modified Ashworth Scale were evaluated within 1 week before the intervention and after 4 weeks of intervention.RESULTS AND CONCLUSION:After the 4-week intervention,all outcome measures showed significant changes in each group.The experimental group had a small but significant increase in the modified Ashworth Scale score(P<0.05,d=|0.15|),while the control group had a large significant increase(P<0.05,d=|1.48|).The experimental group demonstrated greater improvements in walking speed(16.5 to 38.44 cm/s,P<0.05,d=|4.01|),step frequency(46.44 to 64.94 steps/min,P<0.05,d=|2.32|),stride length(15.50 to 29.81 cm,P<0.05,d=|3.44|),and peak hip and knee flexion(d=|1.82|to|2.17|).After treatment,the experimental group showed significantly greater improvements than the control group in walking speed(38.44 vs.26.63 cm/s,P<0.05,d=|2.75|),stride length,peak hip and knee flexion(d=|1.31|to|1.45|),step frequency(64.94 vs.59.38 steps/min,P<0.05,d=|0.85|),and a reduced support phase(bilateral:24.31%vs.28.38%,P<0.05,d=|0.88|;non-paretic:66.19%vs.70.13%,P<0.05,d=|0.94|).For early hemiplegia,personal assistant machine-assisted gait training under the suspension protection system helps establish a correct gait pattern,prevents muscle spasms,and improves motor function.
文摘Passiflora incarnata L.,commonly known as passionflower,is traditionally cultivated as an ornamental plant but has demonstrated diverse therapeutic potential.Its pharmacological effects are attributed to bioactive compounds such as flavonoids and alkaloids,which influence multiple biological pathways.This review aims to summarise and critically analyse recent findings on the pharmacological properties of Passiflora incarnata L.,focusing on its neuropsychiatric,antioxidant,antimicrobial,and anticancer activities.A targeted literature search was conducted in PubMed,Scopus,Web of Science,and Google Scholar for peer-reviewed publications between 2000 to 2025.Relevant articles were screened,and a more appropriate article related to the objective of the review was selected.Some classical papers are also cited as per the requirement of the topic.Passiflora incarnata L.showed multifunctional medicinal properties with various applications in neuropsychiatry,oxidative stress management,antimicrobial agent,and as an anticancer agent.The U.S.Food and Drug Administration categorizes passionflower extracts as“generally recognized as safe”.However,most evidence remains preclinical,with methodological variation limiting generalisation.Standardised formulation,robust clinical trials,and in-depth in vivo studies are essential to establish its therapeutic relevance and safety in modern medicine.
文摘BACKGROUND Postoperative delirium(POD)is a common and serious complication in surgical patients,particularly older adults.Alterations in cholinergic function have been implicated in its pathophysiology.AIM To evaluate the association between preoperative serum cholinesterase(ChE)activity—specifically butyrylcholinesterase(BuChE)and acetylcholinesterase(AChE)—and the risk of POD in adult surgical patients in a meta-analysis.METHODS A systematic search was conducted in PubMed,EMBASE,and Web of Science up to March 28,2025 for studies reporting preoperative serum BuChE or AChE activity in relation to subsequent POD incidence.Standardized mean differences(SMDs)and odds ratios(ORs)with 95%confidence intervals(CIs)were pooled using random-effects models.Subgroup and sensitivity analyses were performed based on follow-up duration and analytic models.RESULTS Thirteen studies(n=2730 patients)were included.Patients who developed POD had significantly lower preoperative BuChE activity than those who did not(SMD=-0.28;95%CI:-0.39 to-0.16;I²=18%).Higher BuChE activity was associated with a reduced risk of POD(OR per 100 unit increment=0.97;95%CI:0.95-0.99;I2=0%).In contrast,pooled AChE activity did not differ significantly between POD and non-POD groups(SMD=-0.25;95%CI:-0.53 to 0.03;P=0.08;I2=80%),and the ORs per 1 unit increment in AChE activity were not statistically significant(OR=0.98;95%CI:0.95-1.01).CONCLUSION Lower preoperative serum BuChE activity is associated with an increased risk of POD in adults undergoing surgery.BuChE activity may serve as a potential preoperative biomarker for POD risk stratification.
基金Supported by Provincial Key Research Project of Henan Province,No.232102310081.
文摘BACKGROUND Major depressive disorder(MDD)and obesity(OB)are bidirectionally comorbid conditions with common neurobiological underpinnings.However,the neurocognitive mechanisms of their comorbidity remain poorly understood.AIM To examine regional abnormalities in spontaneous brain activity among patients with MDD-OB comorbidity.METHODS This study adopted a regional homogeneity(ReHo)analysis of resting-state functional magnetic resonance imaging.The study included 149 hospital patients divided into four groups:Patients experiencing their first episode of drug-naive MDD with OB,patients with MDD without OB,and age-and sex-matched healthy individuals with and without OB.Whole-brain ReHo analysis was conducted using SPM12 software and RESTplus toolkits,with group comparisons via ANOVA and post-hoc tests.Correlations between ReHo values and behavioral measures were examined.RESULTS ANOVA revealed significant whole-brain ReHo differences among the four groups in four key regions:The left middle temporal gyrus(MTG.L),right cuneus,left precuneus,and left thalamus.Post-hoc analyses confirmed pairwise differences between all groups across these regions(P<0.05).OB was associated with ReHo alterations in the MTG.L,right cuneus,and left thalamus,whereas abnormalities in the precuneus suggested synergistic pathological mechanisms between MDD and OB.Statistically significant correlations were found between the drive and fun-seeking dimensions of the behavioral activation system,as well as behavioral inhibition and the corresponding ReHo values.CONCLUSION Our findings provide novel evidence for the neuroadaptive mechanisms underlying the MDD-OB comorbidity.Further validation could lead to personalized interventions targeting MTG.L hyperactivity and targeting healthy food cues.
基金Supported by the Central High Level Hospital Clinical Research Funding(No.BJ-2024-089).
文摘AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.
基金supported by the National Natural Science Foundation of China,Nos.82171344(to ZY),82471313(to CKT)the Guangdong Basic and Applied Basic Research Foundation,China,Nos.2023B1515120035,2024A1515012035(to CKT)The Science and Technology Projects in Guangzhou Nos.2025A03J4169(to ZY)。
文摘Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.
基金supported by the National Natural Science Foundation of China,No.82002645China Postdoctoral Science Foundation,No.2022M722321Jiangsu Funding Program for Excellent Postdoctoral Talent,No.2022ZB552(all to YH)。
文摘Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources,adding a substantial burden to the healthcare system and patients'families.In this context,chondroitinase ABC,a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals,has emerged as a promising therapeutic agent.It works by degrading chondroitin sulfate proteoglycans,cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides.Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains.Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting,enhancing the plasticity of perineuronal nets,inhibiting neuronal apoptosis,and modulating immune responses in various animal models.In this review,we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury.We also highlight research advancements in spinal cord injury treatment strategies,with a focus on chondroitinase ABC,and illustrate how improvements in chondroitinase ABC stability,enzymatic activity,and delivery methods have enhanced injured spinal cord repair.Furthermore,we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy.This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC-based spinal cord injury therapies,with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.
基金supported by the National Natural Science Foundation of China,Nos.82404892(to QY),82061160374(to ZZ)the Science and Technology Development Fund,Macao Special Administrative Region,China,Nos.0023/2020/AFJ,0035/2020/AGJ+2 种基金the University of Macao Research Grant,Nos.MYRG2022-00248-ICMS,MYRG-CRG2022-00010-ICMS(to MPMH)the Natural Science Foundation of Guangdong Province,No.2024A1515012818(to ZZ)the Fundamental Research Funds for the Central Universities,No.21623114(to ZZ).
文摘Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More recently,advances in the development of Lecanemab,an anti-amyloid-βmonoclonal antibody,have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer’s disease in the Phase Ⅲ clinical trial(Clarity Alzheimer’s disease).Despite these promising results,side effects such as amyloid-related imaging abnormalities(ARIA)may limit its usage.ARIA can manifest as ARIA-E(cerebral edema or effusions)and ARIA-H(microhemorrhages or superficial siderosis)and is thought to be caused by increased vascular permeability due to inflammatory responses,leading to leakages of blood products and protein-rich fluid into brain parenchyma.Endothelial dysfunction is an early pathological feature of Alzheimer’s disease,and the blood-brain barrier becomes increasingly leaky as the disease progresses.In addition,APOE4,the strongest genetic risk factor for Alzheimer’s disease,is associated with higher vascular amyloid burden,increased ARIA incidence,and accelerated blood-brain barrier disruptions.These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer’s disease.Here,we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer’s disease progression.
文摘Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et al.,2022).This molecular event is believed to lead to activation of stress pathways ultimately resulting in cellular dysfunction(Eldeeb et al.,2022).Accordingly,many lines of research investigations focused on dampening the formation of protein aggregates or augmenting the clearance of protein aggregates as a potential therapeutic strategy to counteract the progression of neurodegenerative diseases,albeit with little success(Costa-Mattioli and Walter,2020).Cell stress cues such as the accumulation of protein aggregates lead to the activation of stress response pathways that aid cells in responding to the damage.Despite the notion that the transient activation of these pathways helps cells cope with stressors,persistent activation can induce unwanted apoptosis of cells and reduce overall tissue strength as well as lead to an accumulation of aggregation-prone proteins(Hetz and Papa,2018).Mutations in proteins involved in stress signaling termination can cause conditions like ataxia and early-onset dementia(Conroy et al.,2014).Therefore,it is crucial for stress response signaling to be turned off once conditions have improved.Nevertheless,the mechanisms by which cells silence these signals are still elusive.
文摘BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to activate CD.Additionally,n-3 PUFAs are metabolized by the same enzyme as n-6 PUFAs and known to inhibit the arachidonic acid cascade.Our previous study noted that the presence of erythrocyte membrane fatty acids is a characteristic finding in Japanese CD patients.It was thus speculated that FADS2 gene polymorphisms,which induce PUFA metabolizing enzymes,are involved in the pathogenesis of CD,though no such relationship was found.AIM To investigate the relationship of FADS2 polymorphisms with serum and erythrocyte membrane fatty acid composition ratios,and disease activity.METHODS Using previously reported findings regarding FADS2 genetic polymorphisms,the records of 52 CD patients undergoing treatment at Jikei University Kashiwa Hospital were analyzed.Mutations noted were divided into three groups;wild-type(GG),heterozygous mutants(GA),and homozygous(AA),with the activities of delta-6 and delta-5 desaturases compared using redefined d6d index(rd.d6di)and d5d index(d5di).Additionally,comparisons of serum and erythrocyte membranes for fatty acid composition,and also gene polymorphisms and CD activity index(CDAI)were performed.RESULTS The presence of the rs174538 mutation in FADS2 resulted in reduction of only rd.d6di in the erythrocyte membrane(P<0.01).In contrast,that mutation was found to be associated with d5di induced by FADS1 in serum(P=0.019)as well as the erythrocyte membrane(P<0.0001),and also with reduction in the fatty acid composition of arachidonic acid in both serum(P<0.0001)and the erythrocyte membrane(P<0.01).Regarding disease activity,a positive correlation of CDAI score with rd.d6di in both serum(P<0.05)and the erythrocyte membrane(P<0.05)was found only in the rs174538 wild-type group.In contrast,there was no correction between CDAI and d5di in either serum or erythrocyte membrane samples.CONCLUSION The rs174538 mutation alters the fatty acid profile through strong linkage to the FADS1 gene.In wild-type individuals,rd.d6di was positively correlated with CDAI,suggesting predictive utility of disease severity.
文摘Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.
