For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language defi...For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language deficits.The exact cause of Alzheimer's disease is still under debate,making it challenging to establish an effective therapy or early diagnosis.It is widely accepted that the accumulation of amyloid-beta peptide in the brain parenchyma leads to synaptic dysfunction,a critical step in Alzheimer's disease development.The traditional amyloid cascade model is initiated by accumulating extracellular amyloid-beta in brain areas essential for memory and language.However,while it is possible to reduce the presence of amyloid-beta plaques in the brain with newer immunotherapies,cognitive symptoms do not necessarily improve.Interestingly,recent studies support the notion that early alterations in subcortical brain regions also contribute to brain damage and precognitive decline in Alzheimer's disease.A body of recent evidence suggests that early Alzheimer's disease is associated with alterations(e.g.,motivation,anxiety,and motor impairment)in subcortical areas,such as the striatum and amygdala,in both human and animal models.Also,recent data indicate that intracellular amyloid-beta appears early in subcortical regions such as the nucleus accumbens,locus coeruleus,and raphe nucleus,even without extracellular amyloid plaques.The reported effects are mainly excitatory,increasing glutamatergic transmission and neuronal excitability.In agreement,data in Alzheimer's disease patients and animal models show an increase in neuronal synchronization that leads to electroencephalogram disturbances and epilepsy.The data indicate that early subcortical brain dysfunctions might be associated with non-cognitive symptoms such as anxiety,irritability,and motivation deficits,which precede memory loss and language alterations.Overall,the evidence reviewed suggests that subcortical brain regions could explain early dysfunctions and perhaps be targets for therapies to slow disease progression.Future research should focus on these non-traditional brain regions to reveal early pathological alterations and underlying mechanisms to advance our understanding of Alzheimer's disease beyond the traditionally studied hippocampal and cortical circuits.展开更多
Acalypha gaumeri(Euphorbiaceae)is the only endemic species of the genus in the Yucatan Peninsula.It is dioecious and has antifungal properties against various phytopathogens.In the present study,molecular identificati...Acalypha gaumeri(Euphorbiaceae)is the only endemic species of the genus in the Yucatan Peninsula.It is dioecious and has antifungal properties against various phytopathogens.In the present study,molecular identification of A.gaumeri was performed using the rbcL region,confirming its belonging to the Acalypha genus.Its genetic diversity was evaluated using 10 SPAR markers(ISSR and DAMD)from 60 individuals collected from female and male plants of the Kiuic,Tinum and Yaxcaba ex-situ populations.The results showed a high level of genetic polymorphism(PIC=0.980)and significant differences among the populations.Ethanol and aqueous extracts from leaves,stems,and roots of both genders and three populations were evaluated against three phytopathogenic fungi.Only the ethanol extracts of the roots showed inhibitory antifungal activity,whereas Kiuic and Tinum,both male and female individuals,showed inhibitory effects at 1000μg/mL against the three pathogens.The ethanol extract of the female flowering plant of Kiuic showed activity at minimum inhibitory concentrations of 250μg/mL against Alternaria chrysanthemi CICY004 and 500μg/mL against Colletotrichum gloeosporioides CICY002 and Penicillium oxalicum ITC25.Chromatographic profile of the ethanol extracts confirmed the presence of alkaloidal components in the ex-situ cultivated plants,which were analyzed by HPLC.The results revealed that the peaks at T_(R) of 7.60,7.88,and 8.49 min were the most abundant components(9.95%-21.93%),with differences between female and male plants of the three populations.This research confirms that A.gaumeri cultivated and genetically characterized is a potential raw material to develop an eco-friendly product for the control of fungal diseases in crops.展开更多
Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined ex...Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.展开更多
Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortal...Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortality.Mitochondrial dysfunction,a major hallmark of aging,plays a central role in the loss of muscle mass and strength observed in frailty and sarcopenia.With age,mitochondrial quality control processes,including biogenesis,mitophagy,and dynamics,become dysregulated,impairing energy metabolism and muscle homeostasis.Mitochondrial dysfunction correlates with clinical biomarkers of sarcopenia and frailty,such as the decrease in walking speed and muscle strength,making it a therapeutic target for mitohormesis-based strategies aimed at preserving functional capacity.Mitohormetic agents induce reversible mitochondrial stress,triggering adaptive responses that enhance function.Among these interventions,physical exercise,particularly endurance and resistance training(RT),has been reported to be among the most effective,as it may modulate mitochondrial biogenesis,dynamics,and mitophagy through increases in proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)and mitochondrial transcription factor A(TFAM)expression,mitochondrial deoxyribonucleic acid(mtDNA)copy number,and mitochondrial content.Chronic RT can also elevate fusion and fission markers,potentially as a compensatory mechanism to mitigate mitochondrial damage.Apart from exercise,mitohormetic compounds such as harmol and piceid are emerging as promising supplements in the aging field.By modulating mitochondrial bioenergetics and dynamics,they may complement lifestyle-based interventions to improve mitochondrial fitness and extend health span.展开更多
Background:Low relative sit-to-stand(STS)power has emerged as a critical predictor of adverse health outcomes,such as frailty and disability,in older adults.However,its impact on falls,fractures,hospitalizations,and a...Background:Low relative sit-to-stand(STS)power has emerged as a critical predictor of adverse health outcomes,such as frailty and disability,in older adults.However,its impact on falls,fractures,hospitalizations,and all-cause mortality remains unclear.Therefore,this longitudinal study aimed to investigate the potential associations between low relative STS power and these adverse health outcomes in older adults.Methods:A total of 1876 older adults(aged≥65 years,56.4%women)were included from the Toledo Study for Healthy Aging.Relative STS power was assessed using the 30-s STS test and the Alcazar equation.Participants were categorized as having low relative STS power based on previously established cut-off points(2.53 W/kg for men and 2.01 W/kg for women).Falls and fractures(hip and all-type)within the previous year were recorded.Hospitalizations and all-cause mortality were obtained during a follow-up of 6.8±3.1 years(mean±SD;median=7.8 years;interquartile range:3.9-10.1 years)and 9.7±3.5 years(median=10.9 years;interquartile range:8.2-12.5 years),respectively.Generalized linear mixed models,binary logistic regression,and proportional hazards regression adjusted for age,educational level,and comorbidities were used.Results:In men,low relative STS power was significantly associated with an increased likelihood of history of falls(odds ratio(OR)=1.73,95%confidence interval(95%CI):1.08-2.75,p=0.022)and all-type fractures(OR=1.86,95%CI:1.21-2.84,p=0.004)in the previous year.In women,low relative STS power was associated with a higher probability of hip fractures within the previous year(OR=3.25,95%CI:1.07-9.86,p=0.038).Low relative STS power predicted hospitalizations in women(hazard ratio(HR)=1.29,95%CI:1.06-1.58,p=0.012)and longer hospital stays in both men(p=0.020)and women(p=0.033).Low relative STS power significantly increased all-cause mortality in both men(HR=1.57,95%CI:1.26-1.97,p<0.001)and women(HR=2.04,95%CI:1.51-2.74,p<0.001).Conclusion:Low relative STS power was associated with history of hip fractures in women,whereas in men it was associated with history of falls and all-type fractures.Low relative STS power predicted hospitalizations in women but not in men.In both men and women,low relative STS power was associated with longer hospital stays and increased risk of all-cause mortality.展开更多
This review provides a comprehensive overview of recent advancements in aluminum-based conductor alloys engineered to achieve superior mechanical strength and thermal stability without sacrificing electrical conductiv...This review provides a comprehensive overview of recent advancements in aluminum-based conductor alloys engineered to achieve superior mechanical strength and thermal stability without sacrificing electrical conductivity.Particular emphasis is placed on the role of microalloying elements—particularly Sc and Zr-in promoting the formation of coherent nanoscale precipitates such as Al_(3)Zr,Al_(3)Sc,and core-shell Al_(3)(Sc,Zr)with metastable L1_(2)crystal structures.These precipitates contribute significantly to high-temperature performance by enabling precipitation strengthening and stabilizing grain boundaries.The review also explores the emerging role of other rare earth elements(REEs),such as erbium(Er),in accelerating precipitation kinetics and improving thermal stability by retarding coarsening.Additionally,recent advancements in thermomechanical processing strategies are examined,with a focus on scalable approaches to optimize the strength-conductivity balance.These approaches involve multi-step heat treatments and carefully controlled manufacturing sequences,particularly the combination of cold drawing and aging treatment to promote uniform and effective precipitation.This review offers valuable insights to guide the development of cost-effective,high-strength,heat-resistant aluminum alloys beyond conductor applications,particularly those strengthened through microalloying with Sc and Zr.展开更多
Earthquakes are highly destructive spatio-temporal phenomena whose analysis is essential for disaster preparedness and risk mitigation.Modern seismological research produces vast volumes of heterogeneous data from sei...Earthquakes are highly destructive spatio-temporal phenomena whose analysis is essential for disaster preparedness and risk mitigation.Modern seismological research produces vast volumes of heterogeneous data from seismic networks,satellite observations,and geospatial repositories,creating the need for scalable infrastructures capable of integrating and analyzing such data to support intelligent decision-making.Data warehousing technologies provide a robust foundation for this purpose;however,existing earthquake-oriented data warehouses remain limited,often relying on simplified schemas,domain-specific analytics,or cataloguing efforts.This paper presents the design and implementation of a spatio-temporal data warehouse for seismic activity.The framework integrates spatial and temporal dimensions in a unified schema and introduces a novel array-based approach for managing many-to-many relationships between facts and dimensions without intermediate bridge tables.A comparative evaluation against a conventional bridge-table schema demonstrates that the array-based design improves fact-centric query performance,while the bridge-table schema remains advantageous for dimension-centric queries.To reconcile these trade-offs,a hybrid schema is proposed that retains both representations,ensuring balanced efficiency across heterogeneous workloads.The proposed framework demonstrates how spatio-temporal data warehousing can address schema complexity,improve query performance,and support multidimensional visualization.In doing so,it provides a foundation for integrating seismic analysis into broader big data-driven intelligent decision systems for disaster resilience,risk mitigation,and emergency management.展开更多
Purpose:The purpose of this study was to examine the associations between adherence to the 24-Hour Movement Guidelines and all-cause and cause-specific mortality in a large Spanish prospective cohort.Methods:We analyz...Purpose:The purpose of this study was to examine the associations between adherence to the 24-Hour Movement Guidelines and all-cause and cause-specific mortality in a large Spanish prospective cohort.Methods:We analyzed data from 14,288 participants of the Seguimiento Universidad de Navarra(SUN)Project,followed for a mean of 12.8 years(mean baseline age=38.3 years;60.1%women).Data were collected at baseline and through biennial follow-up questionnaires(up to 10 waves,depending on year of entry).The participants self-reported 24-h movement behaviors at baseline and were categorized based on the number of guidelines met(0-3).Behaviors were assessed at baseline only;changes in adherence during follow-up were not accounted for.Cox proportional hazards models were used to estimate hazard ratios(HRs)for all-cause and cause-specific mortality,adjusting for sociodemographic,lifestyle,and clinical covariates.Results:Meeting a greater number of 24-Hour Movement Guidelines at baseline was associated with a progressively lower risk of all-cause mortality.Compared with those meeting none,the multivariable-adjusted HRs were 0.52(95%confidence interval(95%CI):0.33-0.82)for meeting 1 guideline,0.47(95%CI:0.30-0.73)for meeting 2 guidelines,and 0.44(95%CI:0.28-0.71)for meeting all 3 guidelines.Only adherence to the physical activity guidelines was independently associated with a significantly lower mortality risk(HR=0.70;95%CI:0.55-0.89).A reduced risk was also observed for cancer and other-cause mortality among those meeting 2 or more guidelines.Conclusion:Adherence to the 24-Hour Movement Guidelines at baseline,particularly physical activity,was associated with a lower risk of mortality.Promoting an integrated approach to movement behaviors may be an effective strategy for improving population health and longevity.展开更多
Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanoca...Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites,enabling efficient and targeted cancer treatment.In this study,hyaluronic acid(HA)-modified copper-N,N-dimethyl-Nphenylsulfonylbisamine(DMSA)-assembled nanoparticles(Cu-DMSA-HA NPs)are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry.Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells,which enhances nanoparticle uptake.Once internalized,intracellular glutathione is depleted by the NPs,followed by a Fenton-like reaction that sustains ROS production.Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication,prevents cell cycle progression,downregulates glutathione peroxidase 4 expression,induces ferroptosis,and ultimately suppresses NSCLC progression.Overall,the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity,highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.展开更多
BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We ...BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We aim to study its utility by conducting a meta-analysis of this specific population.AIM To determine whether elevated NLR is associated with all-cause mortality(ACM)and cardiovascular mortality(CVM)in patients undergoing chronic HD.METHODS A comprehensive search from PubMed,Google Scholar,and Scopus identified studies showing the association between NLR and mortality outcomes in patients with chronic HD.Random-effects models with 95%CIs were employed to pool adjusted hazard ratios(aHRs),odds ratios(ORs),and I²statistics for evaluating the heterogeneity of findings.Leave-one-out sensitivity and meta-regression analyses assessed changes in overall effects and identified confounders,respectively.The Joanna Briggs Institute(JBI)tool was used to assess the quality of studies.RESULTS 19 studies comprising 9047 patients with a mean age of 59.5±5.86 years and a mean follow-up duration of 46.7 months were included in our study.Our meta-analysis revealed a significant association between NLR>2.5 and increased risks of ACM(aHR:1.25,95%CI:1.14-1.37,P<0.0001)and CVM(aHR:1.24,95%CI:1.02-1.49,P=0.03).Studies reporting outcomes in OR reported similar findings for ACM(OR:4.59,95%CI:1.74-12.11,P=0.002)and CVM(OR:1.11,95%CI:1.01-1.23,P=0.03).Sensitivity analysis revealed no variations.Meta-regression revealed increasing male proportion is positively associated with ACM.Pooled area under the curve(AUC)was 0.71(95%CI:0.63-0.80,P<0.0001).The JBI tool revealed high-quality studies.CONCLUSION This meta-analysis suggests that elevated NLR may serve as a useful prognostic marker for ACM and CVM in patients on chronic HD and can be useful in planning for the prevention of mortality-related strategies.展开更多
Myocardial ischemia(MI)is a pathophysiological condition in which the myocardium is unable to maintain normal cardiac function due to insufficient coronary artery blood and oxygen supply,as well as abnormal myocardial...Myocardial ischemia(MI)is a pathophysiological condition in which the myocardium is unable to maintain normal cardiac function due to insufficient coronary artery blood and oxygen supply,as well as abnormal myocardial energy metabolism[1].Ginsenoside Rbi(Rbi),one of the most abundant natural ingredients in ginseng and Panax notoginseng,has been proven to protect the heart from MI/reperfusion injury(RI)[2].展开更多
Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regula...Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.展开更多
The malicious dissemination of hate speech via compromised accounts,automated bot networks and malware-driven social media campaigns has become a growing cybersecurity concern.Automatically detecting such content in S...The malicious dissemination of hate speech via compromised accounts,automated bot networks and malware-driven social media campaigns has become a growing cybersecurity concern.Automatically detecting such content in Spanish is challenging due to linguistic complexity and the scarcity of annotated resources.In this paper,we compare two predominant AI-based approaches for the forensic detection of malicious hate speech:(1)finetuning encoder-only models that have been trained in Spanish and(2)In-Context Learning techniques(Zero-and Few-Shot Learning)with large-scale language models.Our approach goes beyond binary classification,proposing a comprehensive,multidimensional evaluation that labels each text by:(1)type of speech,(2)recipient,(3)level of intensity(ordinal)and(4)targeted group(multi-label).Performance is evaluated using an annotated Spanish corpus,standard metrics such as precision,recall and F1-score and stability-oriented metrics to evaluate the stability of the transition from zero-shot to few-shot prompting(Zero-to-Few Shot Retention and Zero-to-Few Shot Gain)are applied.The results indicate that fine-tuned encoder-only models(notably MarIA and BETO variants)consistently deliver the strongest and most reliable performance:in our experiments their macro F1-scores lie roughly in the range of approximately 46%–66%depending on the task.Zero-shot approaches are much less stable and typically yield substantially lower performance(observed F1-scores range approximately 0%–39%),often producing invalid outputs in practice.Few-shot prompting(e.g.,Qwen 38B,Mistral 7B)generally improves stability and recall relative to pure zero-shot,bringing F1-scores into a moderate range of approximately 20%–51%but still falling short of fully fine-tuned models.These findings highlight the importance of supervised adaptation and discuss the potential of both paradigms as components in AI-powered cybersecurity and malware forensics systems designed to identify and mitigate coordinated online hate campaigns.展开更多
Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating ga...Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.展开更多
Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A ...Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.展开更多
To ensure the efficient use of resources,particularly in water-scarce arid and semi-arid regions where abiotic stress threatens food security,assessing soil and climate suitability for specific crops is crucial.Simult...To ensure the efficient use of resources,particularly in water-scarce arid and semi-arid regions where abiotic stress threatens food security,assessing soil and climate suitability for specific crops is crucial.Simultaneously,food production must align with sustainable development goals by minimizing negative environmental impacts.Therefore,establishing agro-climatic suitability using a spatiotemporal approach is essential.This involves three key steps:first,determining the climatically appropriate months based on the species’requirements(temporal suitability),and second,establishing the soil suitability of specific plots(spatial suitability).Following this,quantifying crop evapotranspiration allows for optimized water use.This study used climatic and soil variables from diverse data sources to characterize the study area.Subsequently,suitability classes for Portulaca oleracea were determined based on existing literature.Our analysis concerning temporal suitability revealed that June and July are the optimal months for sowing this species in all of the municipalities.Spatially,approximately 30%of the agricultural land use of the study area exhibits a highly suitable class in most municipalities.Both dimensions,the temporal and the spatially,were validated through Chi square(χ^(2))Goodness-of-Fit test and theχ^(2)test of independence,respectively.Consequently,for a one-month production cycle during periods of high suitability,estimated evapotranspiration values are between 210 and 245 mm.In brief,the study area demonstrates favorable agro-climatic conditions for P.oleracea cultivation in specific months of the year according to parameters used,with potential in a large proportion of agricultural land and achievable water requirements.展开更多
Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues.Classically,cartilage and bone formation have been considered independent processes at cellular level...Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues.Classically,cartilage and bone formation have been considered independent processes at cellular level.However,the recently described multiple cell differentiation dynamics suggest that some bone cells are indeed the progeny of cartilage cells,or chondrocyte-derived osteoblasts.We hypothesized that the cartilage-to-bone phenotype transition is triggered by specific molecular events.First,the process was assessed in mouse bone tissue,and then,it was mimicked using in vivo cell implantation and in vitro serial differentiation protocols.Data indicates that cartilage cells transition to bone cell phenotype during postnatal physiological bone formation.This process can be reproduced using cartilage precursor cells coupled to specific implantation procedures or differentiation protocols.Gene expression profiling reveals that NOTCH,BMP and MAPK signaling pathways are relevant at the phenotype-switch,while the transcription factors Mesp1,Alx1,Grhl3 and Hmx3 are the feasible driver genes for chondrocyte-derived osteoblasts formation.Altogether,this report shows that endochondral ossification can be modeled using primary cell cultures and data indicate that this process is regulated by specific molecular events,previously described at skeleton morphogenesis during embryo development,and from now on also linkable to postnatal bone development and regeneration processes.展开更多
In this paper,we study the asymptotic behavior of the micropolar fluid flow through a thin domain,assuming zero Dirichlet boundary condition on the top boundary,which is rapidly oscillating,and non-standard boundary c...In this paper,we study the asymptotic behavior of the micropolar fluid flow through a thin domain,assuming zero Dirichlet boundary condition on the top boundary,which is rapidly oscillating,and non-standard boundary conditions on the flat bottom.Assuming“Reynolds roughness regime”,in which the thickness of the domain is very small compared to the wavelength of the roughness(i.e.a very slight roughness),we rigorously derive a generalized Reynolds equation for pressure,clearly showing the roughness-induced effects.Moreover,we give expressions for the average velocity and microrotation.展开更多
The informal term‘dahongjun’or‘big red mushroom’is a group of red-coloured russulas widely collected and consumed in southern China,originally mistakenly recognized as the European Russula vinosa.Russula griseocar...The informal term‘dahongjun’or‘big red mushroom’is a group of red-coloured russulas widely collected and consumed in southern China,originally mistakenly recognized as the European Russula vinosa.Russula griseocarnosa was described from China in 2009,and since then,it has become the only available scientific name for‘dahongjun’.Nevertheless,several lineages exist within this complex,and whether these lineages represent real species is still an open question.Sampling in major producing areas of‘dahongjun’and phylogenetic species recognition using multi-locus data were conducted.Besides R.griseocarnosa nine additional species were identified under the commercial name‘dahongjun’,including R.dhakuriana,R.quercina,R.purpureozonata,R.yanheensis and a new species sister to R.griseocarnosa here described as R.occulta.The others were undescribed species close to R.laricina,R.lepida,and R.purpureozonata respectively.Six evolutionary lineages within R.griseocarnosa were defined by genealogical concordance phylogenetic species recognition based on five-locus DNA data.Conflicts among different genealogies suggested that R.griseocarnosa is best considered as a single phylogenetic species,comprising several infraspecific taxa.Lower coverage whole genome sequencing of R.griseocarnosa holotype discovered that its three individuals belong to three different clades.Lectotypification was made using one of the three individuals.A new variety R.griseocarnosa var.ailaoshanensis is described to name one of the terminal clades that is mainly distributed in Ailao Mountains.This variety differs morphologically from the type variety in its nearly white context,bigger spores and more inflated hyphae in the pileipellis.The morphological and molecular data provided in this study are helpful to identify wild edible mushrooms of Russula subgen.Russula.展开更多
The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well define...The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well defined.We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6,24,and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy.To understand the changes that these oligodendrocytes undergo during regeneration,we used Sox2 immunohistochemistry,a stem cell marker involved in oligodendrocyte differentiation.We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation.Before optic nerve crush,sox10:tagRFP oligodendrocytes are located in the retina,in the optic nerve head,and through all the entire optic nerve.Sox2-positive cells are present in the peripheral germinal zone,the mature retina,and the optic nerve.After optic nerve crush,sox10:tagRFP cells disappeared from the optic nerve crush zone,suggesting that they died,although they were not TUNEL positive.Concomitantly,the number of Sox2-positive cells increased around the crushed area,the optic nerve head,and the retina.Then,between 24 hours post-lesion and 14 days post-lesion,double sox10:tagRFP/Sox2-positive cells were detected in the retina,optic nerve head,and whole optic nerve,together with a proliferation response at 72 hours post-lesion.Our results confirm that a degenerating process may occur prior to regeneration.First,sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them,change their“myelinating oligodendrocyte”morphology to a“nonmyelinating oligodendrocyte”morphology,and die.Then,residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination.As new axons arise from the surviving retinal ganglion cells,new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide,nourish and myelinate them.Thus,oligodendrocytes play an active role in zebrafish axon regeneration and remyelination.展开更多
文摘For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language deficits.The exact cause of Alzheimer's disease is still under debate,making it challenging to establish an effective therapy or early diagnosis.It is widely accepted that the accumulation of amyloid-beta peptide in the brain parenchyma leads to synaptic dysfunction,a critical step in Alzheimer's disease development.The traditional amyloid cascade model is initiated by accumulating extracellular amyloid-beta in brain areas essential for memory and language.However,while it is possible to reduce the presence of amyloid-beta plaques in the brain with newer immunotherapies,cognitive symptoms do not necessarily improve.Interestingly,recent studies support the notion that early alterations in subcortical brain regions also contribute to brain damage and precognitive decline in Alzheimer's disease.A body of recent evidence suggests that early Alzheimer's disease is associated with alterations(e.g.,motivation,anxiety,and motor impairment)in subcortical areas,such as the striatum and amygdala,in both human and animal models.Also,recent data indicate that intracellular amyloid-beta appears early in subcortical regions such as the nucleus accumbens,locus coeruleus,and raphe nucleus,even without extracellular amyloid plaques.The reported effects are mainly excitatory,increasing glutamatergic transmission and neuronal excitability.In agreement,data in Alzheimer's disease patients and animal models show an increase in neuronal synchronization that leads to electroencephalogram disturbances and epilepsy.The data indicate that early subcortical brain dysfunctions might be associated with non-cognitive symptoms such as anxiety,irritability,and motivation deficits,which precede memory loss and language alterations.Overall,the evidence reviewed suggests that subcortical brain regions could explain early dysfunctions and perhaps be targets for therapies to slow disease progression.Future research should focus on these non-traditional brain regions to reveal early pathological alterations and underlying mechanisms to advance our understanding of Alzheimer's disease beyond the traditionally studied hippocampal and cortical circuits.
基金supported by the SECIHTI project PDCPN-2015-266,México.
文摘Acalypha gaumeri(Euphorbiaceae)is the only endemic species of the genus in the Yucatan Peninsula.It is dioecious and has antifungal properties against various phytopathogens.In the present study,molecular identification of A.gaumeri was performed using the rbcL region,confirming its belonging to the Acalypha genus.Its genetic diversity was evaluated using 10 SPAR markers(ISSR and DAMD)from 60 individuals collected from female and male plants of the Kiuic,Tinum and Yaxcaba ex-situ populations.The results showed a high level of genetic polymorphism(PIC=0.980)and significant differences among the populations.Ethanol and aqueous extracts from leaves,stems,and roots of both genders and three populations were evaluated against three phytopathogenic fungi.Only the ethanol extracts of the roots showed inhibitory antifungal activity,whereas Kiuic and Tinum,both male and female individuals,showed inhibitory effects at 1000μg/mL against the three pathogens.The ethanol extract of the female flowering plant of Kiuic showed activity at minimum inhibitory concentrations of 250μg/mL against Alternaria chrysanthemi CICY004 and 500μg/mL against Colletotrichum gloeosporioides CICY002 and Penicillium oxalicum ITC25.Chromatographic profile of the ethanol extracts confirmed the presence of alkaloidal components in the ex-situ cultivated plants,which were analyzed by HPLC.The results revealed that the peaks at T_(R) of 7.60,7.88,and 8.49 min were the most abundant components(9.95%-21.93%),with differences between female and male plants of the three populations.This research confirms that A.gaumeri cultivated and genetically characterized is a potential raw material to develop an eco-friendly product for the control of fungal diseases in crops.
基金supported by the National Natural Science Foundation of China,No.81472235(to HF)the Shanghai Jiao Tong University Medical and Engineering Project,Nos.YG2021QN53(to HF),YG2017MS71(to HF)+1 种基金the International Cooperation Project of the National Natural Science Foundation of China,No.82020108017(to DC)the Innovation Group Project of the National Natural Science Foundation of China,No.81921002(to DC).
文摘Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.
基金Instituto de Salud CarlosⅢCB16/10/00435(CIBERFES)(PID2022-142470OB-I00)from the Spanish Ministry of Innovation and Science+3 种基金PROMETEO(CIPROM/2022/56)de"Consellería de Educación,Universidades,y Empleo de la Generalitat Valenciana"EU Funded H2020-DIABFRAIL-LATAM(Ref:825546)Red EXERNET-RED DE EJERCICIO FISICO Y SALUD(RED2022-134800-T)Agencia Estatal de Investigacion(Ministerio de Ciencias e Innovación)funded by Generalitat Valenciana and co-financed with FEDER funds(OP FEDER of Comunitat Valenciana 2014–2020).A.G-G(FPU22/02539)and S.S-R(PREP2022-000563)received a predoctoral grant financed by the Spanish Ministry of Universities.
文摘Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortality.Mitochondrial dysfunction,a major hallmark of aging,plays a central role in the loss of muscle mass and strength observed in frailty and sarcopenia.With age,mitochondrial quality control processes,including biogenesis,mitophagy,and dynamics,become dysregulated,impairing energy metabolism and muscle homeostasis.Mitochondrial dysfunction correlates with clinical biomarkers of sarcopenia and frailty,such as the decrease in walking speed and muscle strength,making it a therapeutic target for mitohormesis-based strategies aimed at preserving functional capacity.Mitohormetic agents induce reversible mitochondrial stress,triggering adaptive responses that enhance function.Among these interventions,physical exercise,particularly endurance and resistance training(RT),has been reported to be among the most effective,as it may modulate mitochondrial biogenesis,dynamics,and mitophagy through increases in proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)and mitochondrial transcription factor A(TFAM)expression,mitochondrial deoxyribonucleic acid(mtDNA)copy number,and mitochondrial content.Chronic RT can also elevate fusion and fission markers,potentially as a compensatory mechanism to mitigate mitochondrial damage.Apart from exercise,mitohormetic compounds such as harmol and piceid are emerging as promising supplements in the aging field.By modulating mitochondrial bioenergetics and dynamics,they may complement lifestyle-based interventions to improve mitochondrial fitness and extend health span.
基金supported by Centro de Investigaci on Biom edica en Red Fragilidad y Envejecimiento Saludable(CIBERFES)(Grant Nos.CB16/10/00477,CB16/10/00456,and CB16/10/00464)Plan Propio de Investigaci on of the University of Castilla-La Mancha,and Fondo Europeo de Desarrollo Regional(FEDER)funds from the European Union(Grant No.2022-GRIN-34296)+3 种基金further funded by grants from the Instituto de Salud Carlos III(Grant Nos.PI031558,PI07/90637,PI07/90306,RD 06/0013,and PI18/00972)the Government of Castilla-La Mancha(Grant Nos.03031 and SBPLY/19/180501/000312)Red EXERNETRED DE EJERCICIO FISICO Y SALUD:RED2022-134800T from the Spanish Ministry of Innovation and Sciencesupported by a research grant from the University of Castilla-La Mancha(Programa Investigo,Grant No.2024INVGO-12359)。
文摘Background:Low relative sit-to-stand(STS)power has emerged as a critical predictor of adverse health outcomes,such as frailty and disability,in older adults.However,its impact on falls,fractures,hospitalizations,and all-cause mortality remains unclear.Therefore,this longitudinal study aimed to investigate the potential associations between low relative STS power and these adverse health outcomes in older adults.Methods:A total of 1876 older adults(aged≥65 years,56.4%women)were included from the Toledo Study for Healthy Aging.Relative STS power was assessed using the 30-s STS test and the Alcazar equation.Participants were categorized as having low relative STS power based on previously established cut-off points(2.53 W/kg for men and 2.01 W/kg for women).Falls and fractures(hip and all-type)within the previous year were recorded.Hospitalizations and all-cause mortality were obtained during a follow-up of 6.8±3.1 years(mean±SD;median=7.8 years;interquartile range:3.9-10.1 years)and 9.7±3.5 years(median=10.9 years;interquartile range:8.2-12.5 years),respectively.Generalized linear mixed models,binary logistic regression,and proportional hazards regression adjusted for age,educational level,and comorbidities were used.Results:In men,low relative STS power was significantly associated with an increased likelihood of history of falls(odds ratio(OR)=1.73,95%confidence interval(95%CI):1.08-2.75,p=0.022)and all-type fractures(OR=1.86,95%CI:1.21-2.84,p=0.004)in the previous year.In women,low relative STS power was associated with a higher probability of hip fractures within the previous year(OR=3.25,95%CI:1.07-9.86,p=0.038).Low relative STS power predicted hospitalizations in women(hazard ratio(HR)=1.29,95%CI:1.06-1.58,p=0.012)and longer hospital stays in both men(p=0.020)and women(p=0.033).Low relative STS power significantly increased all-cause mortality in both men(HR=1.57,95%CI:1.26-1.97,p<0.001)and women(HR=2.04,95%CI:1.51-2.74,p<0.001).Conclusion:Low relative STS power was associated with history of hip fractures in women,whereas in men it was associated with history of falls and all-type fractures.Low relative STS power predicted hospitalizations in women but not in men.In both men and women,low relative STS power was associated with longer hospital stays and increased risk of all-cause mortality.
文摘This review provides a comprehensive overview of recent advancements in aluminum-based conductor alloys engineered to achieve superior mechanical strength and thermal stability without sacrificing electrical conductivity.Particular emphasis is placed on the role of microalloying elements—particularly Sc and Zr-in promoting the formation of coherent nanoscale precipitates such as Al_(3)Zr,Al_(3)Sc,and core-shell Al_(3)(Sc,Zr)with metastable L1_(2)crystal structures.These precipitates contribute significantly to high-temperature performance by enabling precipitation strengthening and stabilizing grain boundaries.The review also explores the emerging role of other rare earth elements(REEs),such as erbium(Er),in accelerating precipitation kinetics and improving thermal stability by retarding coarsening.Additionally,recent advancements in thermomechanical processing strategies are examined,with a focus on scalable approaches to optimize the strength-conductivity balance.These approaches involve multi-step heat treatments and carefully controlled manufacturing sequences,particularly the combination of cold drawing and aging treatment to promote uniform and effective precipitation.This review offers valuable insights to guide the development of cost-effective,high-strength,heat-resistant aluminum alloys beyond conductor applications,particularly those strengthened through microalloying with Sc and Zr.
文摘Earthquakes are highly destructive spatio-temporal phenomena whose analysis is essential for disaster preparedness and risk mitigation.Modern seismological research produces vast volumes of heterogeneous data from seismic networks,satellite observations,and geospatial repositories,creating the need for scalable infrastructures capable of integrating and analyzing such data to support intelligent decision-making.Data warehousing technologies provide a robust foundation for this purpose;however,existing earthquake-oriented data warehouses remain limited,often relying on simplified schemas,domain-specific analytics,or cataloguing efforts.This paper presents the design and implementation of a spatio-temporal data warehouse for seismic activity.The framework integrates spatial and temporal dimensions in a unified schema and introduces a novel array-based approach for managing many-to-many relationships between facts and dimensions without intermediate bridge tables.A comparative evaluation against a conventional bridge-table schema demonstrates that the array-based design improves fact-centric query performance,while the bridge-table schema remains advantageous for dimension-centric queries.To reconcile these trade-offs,a hybrid schema is proposed that retains both representations,ensuring balanced efficiency across heterogeneous workloads.The proposed framework demonstrates how spatio-temporal data warehousing can address schema complexity,improve query performance,and support multidimensional visualization.In doing so,it provides a foundation for integrating seismic analysis into broader big data-driven intelligent decision systems for disaster resilience,risk mitigation,and emergency management.
文摘Purpose:The purpose of this study was to examine the associations between adherence to the 24-Hour Movement Guidelines and all-cause and cause-specific mortality in a large Spanish prospective cohort.Methods:We analyzed data from 14,288 participants of the Seguimiento Universidad de Navarra(SUN)Project,followed for a mean of 12.8 years(mean baseline age=38.3 years;60.1%women).Data were collected at baseline and through biennial follow-up questionnaires(up to 10 waves,depending on year of entry).The participants self-reported 24-h movement behaviors at baseline and were categorized based on the number of guidelines met(0-3).Behaviors were assessed at baseline only;changes in adherence during follow-up were not accounted for.Cox proportional hazards models were used to estimate hazard ratios(HRs)for all-cause and cause-specific mortality,adjusting for sociodemographic,lifestyle,and clinical covariates.Results:Meeting a greater number of 24-Hour Movement Guidelines at baseline was associated with a progressively lower risk of all-cause mortality.Compared with those meeting none,the multivariable-adjusted HRs were 0.52(95%confidence interval(95%CI):0.33-0.82)for meeting 1 guideline,0.47(95%CI:0.30-0.73)for meeting 2 guidelines,and 0.44(95%CI:0.28-0.71)for meeting all 3 guidelines.Only adherence to the physical activity guidelines was independently associated with a significantly lower mortality risk(HR=0.70;95%CI:0.55-0.89).A reduced risk was also observed for cancer and other-cause mortality among those meeting 2 or more guidelines.Conclusion:Adherence to the 24-Hour Movement Guidelines at baseline,particularly physical activity,was associated with a lower risk of mortality.Promoting an integrated approach to movement behaviors may be an effective strategy for improving population health and longevity.
基金supported by National Natural Science Foundation of China (82272943)Shanghai Municipal Science and Technology Commission (21Y11913400)+1 种基金Fundamental Research Funds for the Central UniversitiesNational Key Research and Development Program of China (2022YFC2407405)
文摘Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites,enabling efficient and targeted cancer treatment.In this study,hyaluronic acid(HA)-modified copper-N,N-dimethyl-Nphenylsulfonylbisamine(DMSA)-assembled nanoparticles(Cu-DMSA-HA NPs)are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry.Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells,which enhances nanoparticle uptake.Once internalized,intracellular glutathione is depleted by the NPs,followed by a Fenton-like reaction that sustains ROS production.Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication,prevents cell cycle progression,downregulates glutathione peroxidase 4 expression,induces ferroptosis,and ultimately suppresses NSCLC progression.Overall,the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity,highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.
文摘BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We aim to study its utility by conducting a meta-analysis of this specific population.AIM To determine whether elevated NLR is associated with all-cause mortality(ACM)and cardiovascular mortality(CVM)in patients undergoing chronic HD.METHODS A comprehensive search from PubMed,Google Scholar,and Scopus identified studies showing the association between NLR and mortality outcomes in patients with chronic HD.Random-effects models with 95%CIs were employed to pool adjusted hazard ratios(aHRs),odds ratios(ORs),and I²statistics for evaluating the heterogeneity of findings.Leave-one-out sensitivity and meta-regression analyses assessed changes in overall effects and identified confounders,respectively.The Joanna Briggs Institute(JBI)tool was used to assess the quality of studies.RESULTS 19 studies comprising 9047 patients with a mean age of 59.5±5.86 years and a mean follow-up duration of 46.7 months were included in our study.Our meta-analysis revealed a significant association between NLR>2.5 and increased risks of ACM(aHR:1.25,95%CI:1.14-1.37,P<0.0001)and CVM(aHR:1.24,95%CI:1.02-1.49,P=0.03).Studies reporting outcomes in OR reported similar findings for ACM(OR:4.59,95%CI:1.74-12.11,P=0.002)and CVM(OR:1.11,95%CI:1.01-1.23,P=0.03).Sensitivity analysis revealed no variations.Meta-regression revealed increasing male proportion is positively associated with ACM.Pooled area under the curve(AUC)was 0.71(95%CI:0.63-0.80,P<0.0001).The JBI tool revealed high-quality studies.CONCLUSION This meta-analysis suggests that elevated NLR may serve as a useful prognostic marker for ACM and CVM in patients on chronic HD and can be useful in planning for the prevention of mortality-related strategies.
文摘Myocardial ischemia(MI)is a pathophysiological condition in which the myocardium is unable to maintain normal cardiac function due to insufficient coronary artery blood and oxygen supply,as well as abnormal myocardial energy metabolism[1].Ginsenoside Rbi(Rbi),one of the most abundant natural ingredients in ginseng and Panax notoginseng,has been proven to protect the heart from MI/reperfusion injury(RI)[2].
基金supported by Shenzhen Science and Technology Program, No. JCYJ20230807110259002 (to JL)The Seventh Affiliated Hospital of Sun Yat-sen University, No. ZSQYRSFPD0050 (to JL)The Postdoctoral Fellowship Program of CPSF, No. GZC20242074 (to KT)
文摘Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.
基金the research project LaTe4PoliticES(PID2022-138099OB-I00)funded by MCIN/AEI/10.13039/501100011033 and the European Fund for Regional Development(ERDF)-a way to make Europe.Tomás Bernal-Beltrán is supported by University of Murcia through the predoctoral programme.
文摘The malicious dissemination of hate speech via compromised accounts,automated bot networks and malware-driven social media campaigns has become a growing cybersecurity concern.Automatically detecting such content in Spanish is challenging due to linguistic complexity and the scarcity of annotated resources.In this paper,we compare two predominant AI-based approaches for the forensic detection of malicious hate speech:(1)finetuning encoder-only models that have been trained in Spanish and(2)In-Context Learning techniques(Zero-and Few-Shot Learning)with large-scale language models.Our approach goes beyond binary classification,proposing a comprehensive,multidimensional evaluation that labels each text by:(1)type of speech,(2)recipient,(3)level of intensity(ordinal)and(4)targeted group(multi-label).Performance is evaluated using an annotated Spanish corpus,standard metrics such as precision,recall and F1-score and stability-oriented metrics to evaluate the stability of the transition from zero-shot to few-shot prompting(Zero-to-Few Shot Retention and Zero-to-Few Shot Gain)are applied.The results indicate that fine-tuned encoder-only models(notably MarIA and BETO variants)consistently deliver the strongest and most reliable performance:in our experiments their macro F1-scores lie roughly in the range of approximately 46%–66%depending on the task.Zero-shot approaches are much less stable and typically yield substantially lower performance(observed F1-scores range approximately 0%–39%),often producing invalid outputs in practice.Few-shot prompting(e.g.,Qwen 38B,Mistral 7B)generally improves stability and recall relative to pure zero-shot,bringing F1-scores into a moderate range of approximately 20%–51%but still falling short of fully fine-tuned models.These findings highlight the importance of supervised adaptation and discuss the potential of both paradigms as components in AI-powered cybersecurity and malware forensics systems designed to identify and mitigate coordinated online hate campaigns.
文摘Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.
基金supported by ANID FONDECYT No.1221178Centro Ciencia&Vida,FB210008,Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia de ANID to CTR.
文摘Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.
文摘To ensure the efficient use of resources,particularly in water-scarce arid and semi-arid regions where abiotic stress threatens food security,assessing soil and climate suitability for specific crops is crucial.Simultaneously,food production must align with sustainable development goals by minimizing negative environmental impacts.Therefore,establishing agro-climatic suitability using a spatiotemporal approach is essential.This involves three key steps:first,determining the climatically appropriate months based on the species’requirements(temporal suitability),and second,establishing the soil suitability of specific plots(spatial suitability).Following this,quantifying crop evapotranspiration allows for optimized water use.This study used climatic and soil variables from diverse data sources to characterize the study area.Subsequently,suitability classes for Portulaca oleracea were determined based on existing literature.Our analysis concerning temporal suitability revealed that June and July are the optimal months for sowing this species in all of the municipalities.Spatially,approximately 30%of the agricultural land use of the study area exhibits a highly suitable class in most municipalities.Both dimensions,the temporal and the spatially,were validated through Chi square(χ^(2))Goodness-of-Fit test and theχ^(2)test of independence,respectively.Consequently,for a one-month production cycle during periods of high suitability,estimated evapotranspiration values are between 210 and 245 mm.In brief,the study area demonstrates favorable agro-climatic conditions for P.oleracea cultivation in specific months of the year according to parameters used,with potential in a large proportion of agricultural land and achievable water requirements.
基金funded by Grants PID2021-127191OB-I00,RTI2018-101708-A-I00,PRE2018-084542 and PRE2022-102680 funded by MCIN/AEI/10.13039/501100011033 and by“ERDF A way of making Europe”Grant RYC2018-025502-I is funded by MCIN/AEI/10.13039/501100011033 and by“ESF Investing in your future”+1 种基金Grant MDM-20170720 Maria de Maeztu Units of Excellence Program funded by the Spanish State Research Agencysupported by Instituto de Salud CarlosⅢ,Infrastructure of Precision Medicine associated with Science and Technology(IMPaCT)of the Strategic Action in Health(iDATA-MP)。
文摘Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues.Classically,cartilage and bone formation have been considered independent processes at cellular level.However,the recently described multiple cell differentiation dynamics suggest that some bone cells are indeed the progeny of cartilage cells,or chondrocyte-derived osteoblasts.We hypothesized that the cartilage-to-bone phenotype transition is triggered by specific molecular events.First,the process was assessed in mouse bone tissue,and then,it was mimicked using in vivo cell implantation and in vitro serial differentiation protocols.Data indicates that cartilage cells transition to bone cell phenotype during postnatal physiological bone formation.This process can be reproduced using cartilage precursor cells coupled to specific implantation procedures or differentiation protocols.Gene expression profiling reveals that NOTCH,BMP and MAPK signaling pathways are relevant at the phenotype-switch,while the transcription factors Mesp1,Alx1,Grhl3 and Hmx3 are the feasible driver genes for chondrocyte-derived osteoblasts formation.Altogether,this report shows that endochondral ossification can be modeled using primary cell cultures and data indicate that this process is regulated by specific molecular events,previously described at skeleton morphogenesis during embryo development,and from now on also linkable to postnatal bone development and regeneration processes.
文摘In this paper,we study the asymptotic behavior of the micropolar fluid flow through a thin domain,assuming zero Dirichlet boundary condition on the top boundary,which is rapidly oscillating,and non-standard boundary conditions on the flat bottom.Assuming“Reynolds roughness regime”,in which the thickness of the domain is very small compared to the wavelength of the roughness(i.e.a very slight roughness),we rigorously derive a generalized Reynolds equation for pressure,clearly showing the roughness-induced effects.Moreover,we give expressions for the average velocity and microrotation.
基金supported by the National Natural Science Foundation of China(32170022)the 2023 Biodiversity Monitoring-special Investigation of Wild Fungi Issued by Chuxiong Management Bureau of Yunnan Ailao Mountains National Nature Reserve,the Biodiversity Survey and Assessment Project(2019HJ2096001006)the“Investigation of Macrofungi of Maguan County”Issued by Ministry of Ecology and Environment of the People’s Republic of China.
文摘The informal term‘dahongjun’or‘big red mushroom’is a group of red-coloured russulas widely collected and consumed in southern China,originally mistakenly recognized as the European Russula vinosa.Russula griseocarnosa was described from China in 2009,and since then,it has become the only available scientific name for‘dahongjun’.Nevertheless,several lineages exist within this complex,and whether these lineages represent real species is still an open question.Sampling in major producing areas of‘dahongjun’and phylogenetic species recognition using multi-locus data were conducted.Besides R.griseocarnosa nine additional species were identified under the commercial name‘dahongjun’,including R.dhakuriana,R.quercina,R.purpureozonata,R.yanheensis and a new species sister to R.griseocarnosa here described as R.occulta.The others were undescribed species close to R.laricina,R.lepida,and R.purpureozonata respectively.Six evolutionary lineages within R.griseocarnosa were defined by genealogical concordance phylogenetic species recognition based on five-locus DNA data.Conflicts among different genealogies suggested that R.griseocarnosa is best considered as a single phylogenetic species,comprising several infraspecific taxa.Lower coverage whole genome sequencing of R.griseocarnosa holotype discovered that its three individuals belong to three different clades.Lectotypification was made using one of the three individuals.A new variety R.griseocarnosa var.ailaoshanensis is described to name one of the terminal clades that is mainly distributed in Ailao Mountains.This variety differs morphologically from the type variety in its nearly white context,bigger spores and more inflated hyphae in the pileipellis.The morphological and molecular data provided in this study are helpful to identify wild edible mushrooms of Russula subgen.Russula.
基金supported by the Lanzadera TCUE and C2 program(Universidad de Salamanca)(to ASL)the Spanish National Research Council(CSIC)funded by the Junta de Castilla y León and co-financed by the European Regional Development Fund(ERDF“Europe drives our growth”):Internationalization Project“CL-EI-2021-08-IBFG Unit of Excellence”,Grant(PID2022-138478OA-100)funded by MICIU/AEI/10.13039/501100011033 and,by FEDER,UE(to MGM)+3 种基金Junta de Castilla y León(SA225P23)Gerencia Regional de Salud(2701/A1/2023)(to AV)the Plan Especial Grado Medicina(USAL)(to CPM)a Ramón y Cajal researcher:Grant RYC2021-033684-I funded by MICIU/AEI/10.13039/501100011033 and,by European Union NextGenerationEU/PRTR.
文摘The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well defined.We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6,24,and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy.To understand the changes that these oligodendrocytes undergo during regeneration,we used Sox2 immunohistochemistry,a stem cell marker involved in oligodendrocyte differentiation.We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation.Before optic nerve crush,sox10:tagRFP oligodendrocytes are located in the retina,in the optic nerve head,and through all the entire optic nerve.Sox2-positive cells are present in the peripheral germinal zone,the mature retina,and the optic nerve.After optic nerve crush,sox10:tagRFP cells disappeared from the optic nerve crush zone,suggesting that they died,although they were not TUNEL positive.Concomitantly,the number of Sox2-positive cells increased around the crushed area,the optic nerve head,and the retina.Then,between 24 hours post-lesion and 14 days post-lesion,double sox10:tagRFP/Sox2-positive cells were detected in the retina,optic nerve head,and whole optic nerve,together with a proliferation response at 72 hours post-lesion.Our results confirm that a degenerating process may occur prior to regeneration.First,sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them,change their“myelinating oligodendrocyte”morphology to a“nonmyelinating oligodendrocyte”morphology,and die.Then,residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination.As new axons arise from the surviving retinal ganglion cells,new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide,nourish and myelinate them.Thus,oligodendrocytes play an active role in zebrafish axon regeneration and remyelination.
