Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol chan...Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol changes that occur in the brain during Alzheimer’s disease remains unclear.In this study,we compared brain tissues extracted from 32-week-old male wild-type mice and 5×FAD transgenic Alzheimer’s disease model mice,which carry mutations in the amyloid precursor protein(APP)and presenilin 1(PS1)genes.Using untargeted lipidomics and sterolomics techniques,we investigated the metabolic profiles of lipids,with a focus on sterols specifically,in three brain regions:cerebellum,hippocampus,and olfactory bulb.Our results revealed significant alterations in various lipids,particularly in the hippocampus and olfactory bulb,suggesting changes in energy levels in these regions.Further pathway analysis indicated notable disruptions in key metabolic processes,particularly those related to fatty acids and cell membrane components.Additionally,we observed decreased expression of 15 genes involved in lipid and sterol regulation.Collectively,these findings provide new insights into how imbalances in lipid and sterol metabolism may contribute to the progression of Alzheimer’s disease,highlighting potential metabolic pathways involved in the development of this debilitating disease.展开更多
Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders...Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.展开更多
Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patien...Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patients,caregivers,and healthcare workers.Alzheimer’s disease(AD)and Parkinson’s disease represent the two most common neurodegenerative disorders in the population,affecting over 65 million people,worldwide.展开更多
Background:Healthy non-pharmacological lifestyle factors,such as regular physical exercise and dietary supplementation,have been shown to significantly improve cognitive outcomes over time compared to a more sedentary...Background:Healthy non-pharmacological lifestyle factors,such as regular physical exercise and dietary supplementation,have been shown to significantly improve cognitive outcomes over time compared to a more sedentary lifestyle and poor diet.Furthermore,exercise may serve as a potential protective factor in attenuating the effects associated with cognitive decline that are characteristic of neurodegenerative disorders,such as Alzheimer's disease(AD).Evidence indicates that certain dietary interventions can also attenuate the effects of neurodegeneration and positively impact longevity.Supplementation with polyphenols such as ellagic acid(EA),which is abundant in pomegranate juice,may help provide neuroprotective and longevity benefits.Methods:This study examined the potential protective potential of EA and exercise and provides insight into the combined use of a polyphenol-rich diet and exercise to enhance behavioral outcomes and lifespan in a transgenic Drosophila melanogaster(fruit fly)model of AD with the Aβ_(42) gene.Results:Fruit flies subjected to a 120-minute exercise regimen performed better on a climbing assay than flies that did not exercise.Conversely,flies that exercised for 30 min passed marginally more trials on a learning and memory assay using an aversive stimulus than flies that did not exercise,whereas both groups performed better than flies subjected to the more intense exercise condition.Conclusion:These results suggest a hormetic effect of exercise regarding memory performance.Finally,flies fed a low dose of dietary EA(0.24 mg/mL)lived significantly longer than flies fed the control diet or higher concentrations of EA,again suggesting a hormetic effect of EA on longevity.展开更多
Background:Alzheimer's disease(AD)represents the most prevalent neurodegenerative disorder,with mitochondrial dysfunction being observed in both AD patients and mouse models.Nonetheless,further investigation is re...Background:Alzheimer's disease(AD)represents the most prevalent neurodegenerative disorder,with mitochondrial dysfunction being observed in both AD patients and mouse models.Nonetheless,further investigation is required to elucidate the pathogenic genes associated with AD and to develop early diagnostic methodologies centered on mitochondrial function.Methods:In this study,the dataset GSE132903 was retrieved from the GEO database,encompassing both non-demented(ND)control and AD samples.Through the combination of differential expression gene analysis,weighted gene co-expression network analysis,and intersection with mitochondrial database gene sets,four hub genes associated with AD were identified.These four hub genes were subsequently validated in APP/PS1 and 5xFAD mouse models using molecular biology techniques.Results:The hub genes identified through bioinformatics analysis include SYNJ2BP,VDAC1,NUBPL,and COX19.Within the GSE132903 dataset,the expression levels of SYNJ2BP,NUBPL,and COX19 were significantly elevated in the AD group compared to the non-demented(ND)group,whereas VDAC1 expression was reduced in the AD group relative to the ND group.Furthermore,in the hippocampus of APP/PS1 and 5xFAD mouse models,the expression patterns of SYNJ2BP and NUBPL were consistent with the bioinformatics analysis results.Conclusion:Hub genes identified here through bioinformatics and molecular biology may help early diagnosis of AD patients and may also help build new AD models to explore its pathogenesis.展开更多
The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
Tomato is a major economic crop worldwide,and diseases on tomato leaves can significantly reduce both yield and quality.Traditional manual inspection is inefficient and highly subjective,making it difficult to meet th...Tomato is a major economic crop worldwide,and diseases on tomato leaves can significantly reduce both yield and quality.Traditional manual inspection is inefficient and highly subjective,making it difficult to meet the requirements of early disease identification in complex natural environments.To address this issue,this study proposes an improved YOLO11-based model,YOLO-SPDNet(Scale Sequence Fusion,Position-Channel Attention,and Dual Enhancement Network).The model integrates the SEAM(Self-Ensembling Attention Mechanism)semantic enhancement module,the MLCA(Mixed Local Channel Attention)lightweight attention mechanism,and the SPA(Scale-Position-Detail Awareness)module composed of SSFF(Scale Sequence Feature Fusion),TFE(Triple Feature Encoding),and CPAM(Channel and Position Attention Mechanism).These enhancements strengthen fine-grained lesion detection while maintaining model lightweightness.Experimental results show that YOLO-SPDNet achieves an accuracy of 91.8%,a recall of 86.5%,and an mAP@0.5 of 90.6%on the test set,with a computational complexity of 12.5 GFLOPs.Furthermore,the model reaches a real-time inference speed of 987 FPS,making it suitable for deployment on mobile agricultural terminals and online monitoring systems.Comparative analysis and ablation studies further validate the reliability and practical applicability of the proposed model in complex natural scenes.展开更多
BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models ...BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.展开更多
Objective:To explore the application effect of combined exercise intervention based on the hospital-community-family model on intrinsic capacity in elderly patients with diabetes mellitus complicated by chronic kidney...Objective:To explore the application effect of combined exercise intervention based on the hospital-community-family model on intrinsic capacity in elderly patients with diabetes mellitus complicated by chronic kidney disease.Methods:Using convenience sampling,100 elderly patients with diabetes mellitus complicated by chronic kidney disease who received treatment in the endocrinology department of a tertiary A-level hospital from May 2024 to May 2025 were selected as the study subjects.They were randomly divided into an experimental group(50 cases)and a control group(50 cases)using a random number table method.The control group received routine health education and telephone follow-up,while the experimental group,in addition to the control group’s interventions,underwent combined exercise intervention based on the hospital-community-family model.Remote medical guidance was utilized to monitor and study the application effect of exercise intervention on intrinsic capacity in elderly patients with diabetes mellitus complicated by chronic kidney disease.Fasting blood glucose,2-hour postprandial blood glucose,glomerular filtration rate,6-minute walk distance,and scores in five dimensions of intrinsic capacity(exercise,cognition,psychology,vitality,and sensation)were measured before the intervention,at 4 weeks of intervention,and at 12 weeks of intervention for both groups.Results:Before the exercise intervention,there were no statistically significant differences(p>0.05)between the two groups in terms of fasting blood glucose,2-hour postprandial blood glucose,glomerular filtration rate,6-minute walk distance,and scores across five dimensions of intrinsic capacity:mobility,cognition,psychology,vitality,and sensation.After 12 weeks of intervention,the experimental group demonstrated significantly higher scores than the control group in glomerular filtration rate,6-minute walk distance,and the dimensions of mobility,cognition,and vitality within intrinsic capacity,with all differences being statistically significant(p<0.05).Conversely,the experimental group showed significantly lower scores than the control group in fasting blood glucose,2-hour postprandial blood glucose,and the psychological dimension of intrinsic capacity,with these differences also being statistically significant(p<0.05).Conclusion:Continuous nursing care utilizing telemedicine based on a hospital-community-family model combined with exercise intervention can effectively enhance exercise tolerance and intrinsic capacity in elderly patients with diabetes mellitus complicated by chronic kidney disease,thereby improving their quality of life.The effectiveness of the intervention is positively correlated with the duration of the intervention.展开更多
Background: Social determinants of health (SDOH) significantly influence diseases with environmental components, like vector-borne parasitic diseases. This study aims to examine how these factors influence vector-born...Background: Social determinants of health (SDOH) significantly influence diseases with environmental components, like vector-borne parasitic diseases. This study aims to examine how these factors influence vector-borne parasitic diseases (VBPDs) transmission in Chad and provide recommendations for policy improvements. Methods: The study adopts the WHO Conceptual Framework of SDOH to compare two regions in Southern Chad: Kouh-Est, which has an ongoing vector control program, and Grand-Sido, which lacks such a program. The study includes both nomadic and sedentary populations to provide a comprehensive understanding of the SDOH influencing VBPDs. Households were randomly selected. Data on sociodemographic characteristics, literacy, knowledge of VBPDs and protective measures, and access to education and health facilities were collected. Results: A total of 202 households from 17 villages, including 820 participants, were surveyed. Agriculture, livestock, and fishing were the main occupations, involving 84.1% of participants. Literacy was low, with 36.7% non-educated, 47.7% completing primary school, 14.5% secondary school, and only 0.3% reaching tertiary education. Most villages lacked schools beyond the primary level, and nomadic populations were significantly less educated than sedentary ones (p Conclusion: Educational deficiencies, lack of protective measures against vectors, inadequate healthcare resources, and lifestyle conditions aggravated by poor road infrastructure, limited transportation, and economic constraints contribute to worsened VBPDs outcomes in these rural populations. Addressing these systemic issues in the surveyed communities is essential for improving health equity and VBPDs outcomes in these regions specifically and in similar populations settings more broadly.展开更多
This paper proposes a vector-borne plant disease model with discontinuous treatment strategies. Constructing Lyapunov function and applying non-smooth theory to analyze discontinuous differential equations, the basic ...This paper proposes a vector-borne plant disease model with discontinuous treatment strategies. Constructing Lyapunov function and applying non-smooth theory to analyze discontinuous differential equations, the basic reproductive number R0 is proved, which determines whether the plant disease will be extinct or not. If R0 R0 > 1 , there exists a unique endemic equilibrium which is globally stable. The numerical simulations are provided to verify our theoretical results, which indicate that after infective individuals reach some level, strengthening treatment measures is proved to be beneficial in controlling disease transmission.展开更多
Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequence...Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequences to livestock sector. Animal and human movements have a fundamental impact on RVF transmission. In recent years, there has been a growing interest in the use of mathematics and agent based models to represent and analyze the dynamic of RFV transmission. However, no previous study has taken into consideration animal herds’ mobility and precipitation factors to understand the disease spread. This limitation underlines the necessity to use computational model approach based on multi-agent system in the study of vector-borne diseases transmission and diffusion. In this paper, a multi-agent system combining conceptual model expressiveness is used to study animal herds’ mobility and the precipitation parameter impact on the Rift Valley Fever outbreak in Ferlo Barkedji in Northern Senegal. Simulation scenarios with various parameters, including rain quality, hosts, vectors, camp dispersal around ponds, etc., are unrolled. The different results we have obtained show that the evolution of the number of infected hosts and infected vectors depend on the degree of animal herds’ mobility and on precipitations. Our model provides a framework that permits predicting the spread of the disease associated with the mobility of animal herds.展开更多
Rice is one of the most important staple crops globally.Rice plant diseases can severely reduce crop yields and,in extreme cases,lead to total production loss.Early diagnosis enables timely intervention,mitigates dise...Rice is one of the most important staple crops globally.Rice plant diseases can severely reduce crop yields and,in extreme cases,lead to total production loss.Early diagnosis enables timely intervention,mitigates disease severity,supports effective treatment strategies,and reduces reliance on excessive pesticide use.Traditional machine learning approaches have been applied for automated rice disease diagnosis;however,these methods depend heavily on manual image preprocessing and handcrafted feature extraction,which are labor-intensive and time-consuming and often require domain expertise.Recently,end-to-end deep learning(DL) models have been introduced for this task,but they often lack robustness and generalizability across diverse datasets.To address these limitations,we propose a novel end-toend training framework for convolutional neural network(CNN) and attention-based model ensembles(E2ETCA).This framework integrates features from two state-of-the-art(SOTA) CNN models,Inception V3 and DenseNet-201,and an attention-based vision transformer(ViT) model.The fused features are passed through an additional fully connected layer with softmax activation for final classification.The entire process is trained end-to-end,enhancing its suitability for realworld deployment.Furthermore,we extract and analyze the learned features using a support vector machine(SVM),a traditional machine learning classifier,to provide comparative insights.We evaluate the proposed E2ETCA framework on three publicly available datasets,the Mendeley Rice Leaf Disease Image Samples dataset,the Kaggle Rice Diseases Image dataset,the Bangladesh Rice Research Institute dataset,and a combined version of all three.Using standard evaluation metrics(accuracy,precision,recall,and F1-score),our framework demonstrates superior performance compared to existing SOTA methods in rice disease diagnosis,with potential applicability to other agricultural disease detection tasks.展开更多
Cynomolgus macaques,a species of Old World primate native to southeastern and eastern Asia and the island of Mauritius,are one of the most important nonhuman primate models for infectious disease.Although the closely ...Cynomolgus macaques,a species of Old World primate native to southeastern and eastern Asia and the island of Mauritius,are one of the most important nonhuman primate models for infectious disease.Although the closely related rhesus macaque is classified into subspecies based on geographic origin,no such subdivision exists for cynomolgus macaques,and they continue to be used interchangeably in infectious disease research,reducing the comparability of data produced from these studies.Research into the population genetics of cynomolgus macaques has found significant differences between macaques native to different areas,including their genetic diversity,with macaques from insular populations such as Mauritius and the Philippines exhibiting highly restricted heterozygosity compared to mainland populations native to Indonesia or Cambodia.In the context of infectious disease studies,research into pathogens,including Ebola virus,Crimean-Congo hemorrhagic fever virus,and Mycobacterium tuberculosis have found differences in study outcomes,survival times,and immune cell responses between different populations of macaques.This review provides an overview of the differences between cynomolgus macaque populations in the context of genetic diversity,and in response to infection,and highlights the need for clear reporting of geographic origin of primates used in research.This will improve data comparison between studies and help to further refine this important animal model.展开更多
Alterations in RNA methylation may affect the initiation and development of Alzheimer’s disease.However,the exact nature of the relationship between RNA methylation and Alzheimer’s disease remains unclear.In this st...Alterations in RNA methylation may affect the initiation and development of Alzheimer’s disease.However,the exact nature of the relationship between RNA methylation and Alzheimer’s disease remains unclear.In this study,RNA methylation levels were analyzed by bulk transcriptomic and single-cell RNA sequencing.The expression levels of RNA methylation regulators were confirmed using molecular biology techniques.Co-expression network analysis was used to identify relevant long non-coding RNAs.Molecular subtypes related to RNA methylation were classified,and variations in clinical characteristics,biological behavior,and immune signatures between subtypes were assessed.Machine learning approaches were applied to identify methylation-associated long non-coding RNAs,which were used to construct a risk model and nomogram for Alzheimer’s disease.Potential therapeutic agents for different risk groups were predicted,and in vitro experiments were conducted to identify key RNA methylation events.Single-cell analysis demonstrated enhanced RNA methylation in patients with Alzheimer’s disease,particularly within T cells,B cells,and NK cells.Quantitative reverse transcription-polymerase chain reaction and western blot confirmed alterations in RNA methylation regulators in neurons treated with amyloid-βoligomers in vitro.This evidence supported the classification of patients with Alzheimer’s disease into heterogeneous subtypes.Specifically,subtype 1 was identified as the immune-active subtype,while subtype 2 was characterized by a metabolic phenotype.Machine learning algorithms identified five significant methylation-associated long non-coding RNAs-LINC01007,MAP4K3-DT,MIR302CHG,VAC14-AS1,and TGFB2-OT1-that accurately predict clinical outcomes for patients with Alzheimer’s disease.These patients were classified into low-and high-risk categories;the latter group displayed higher immune infiltration,upregulated immune regulatory gene expression,and elevated immune scores and responded better to treatment with arachidonic-trifluoroethane.These findings suggest that dysregulated RNA methylation alters the immune microenvironment in Alzheimer’s disease and is closely associated with its progression.This phenomenon provides novel insights into potential therapeutic strategies for Alzheimer’s disease that target RNA methylation.展开更多
Oxidative stress has long been implicated as a driving force in neurodegenerative disease,with studies of human brain tissue and animal models revealing its important role.Parkinson’s disease(PD),in particular,highli...Oxidative stress has long been implicated as a driving force in neurodegenerative disease,with studies of human brain tissue and animal models revealing its important role.Parkinson’s disease(PD),in particular,highlights the selective vulnerability of neurons to the insults of reactive oxygen species.The motor symptoms of PD are caused by degeneration of dopamine neurons in the substantia nigra.These neurons experience increased oxidative stress due in part to highly active mitochondria that support their high bioenergetic demand and the generation of reactive oxygen species by dopamine metabolism(Watanabe et al.,2024).展开更多
BACKGROUND Solid fuel use for cooking and heating is a major environmental risk factor,yet its association with new-onset heart disease(HD)remains unclear.The aim of this study was to investigate the relationship betw...BACKGROUND Solid fuel use for cooking and heating is a major environmental risk factor,yet its association with new-onset heart disease(HD)remains unclear.The aim of this study was to investigate the relationship between solid fuel exposure and new-onset HD in a large cohort.METHODS Multivariable logistic regression models assessed associations between cooking/heating fuel types(coal,crop residue/wood,liquefied petroleum gas,natural gas,and others)and new-onset HD.Subgroup analyses explored effect modification by age,sex,education,smoking,alcohol use,and region.RESULTS A prospective cohort study included 5915 participants,with 781 participants(13.2%)developing new-onset HD.Coal use for cooking showed an initial association with new-onset HD risk(OR=1.41,95%CI:1.06–1.86,P=0.02),which attenuated after full adjustment(OR=1.28,95%CI:0.96–1.72,P=0.10).Coal use for heating demonstrated robust associations across all models(OR=1.86,95%CI:1.42–2.43,P<0.001).Crop residue/wood burning for heating was also significant(Model 2:OR=1.40,95%CI:1.06–1.86,P=0.02).Subgroup analyses revealed stronger associations among females,non-smokers,non-drinkers,and less-educated participants.Geographic stratification showed significant associations in southern but not northern regions.CONCLUSIONS Solid fuel use,particularly coal for heating,is associated with increased new-onset HD risk.Reducing solid fuel exposure is crucial for HD prevention in low-resource settings.展开更多
Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrog...Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.展开更多
Alzheimer s disease is a neurodegenerative disorder that leads to progressive memory loss,cognitive decline,and behavioral changes.Des pite ongoing research,its exa ct causes and effective treatments remain elusive.Tr...Alzheimer s disease is a neurodegenerative disorder that leads to progressive memory loss,cognitive decline,and behavioral changes.Des pite ongoing research,its exa ct causes and effective treatments remain elusive.Traditional approaches have focused on symptom management,but breakthroughs in bioinformatics and high-thro ughput drug screening are offering new pathways to potential therapies.This review highlights our recent effo rts to identify novel drug candidates for Alzheimer's disease by leve raging computational methods and la rge-scale biological datasets.Our work introduces two key innovations in Alzheimer's disease research:addressing sex-specific diffe rences and leve raging drug repurposing for accelerated treatment discove ry.By combining sex-stratified preclinical data with machine learning and in vivo validation,we improve translational relevance and support precision medicine.Using the TgF344-AD rat model,which mimics human Alzheimer's disease spatial memory deficits and pathology,we explored the efficacy of various US Food and Drug Administrationapproved and investigational drugs.These included ibudilast,timapiprant,RG2833,diazoxide/dibenzoylmethane(combined),and BT-11,which targeted key Alzheimer's disease-related molecular pathways such as amyloid-beta plaques,Ta u tangles,and neuroinflammation.These drugs,at various stages of development,offer hope for not only managing symptoms but also addressing the underlying mechanisms of Alzheimer's disease.This review underscores the need for a multifaceted approach to Alzheimer's disease treatment,combining symptom relief with disease modification.展开更多
AIM:To assess the possibility of using different large language models(LLMs)in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surfa...AIM:To assess the possibility of using different large language models(LLMs)in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surface diseases:ChatGPT-4,ChatGPT-3.5,Claude 2,PaLM2,and SenseNova.METHODS:A group of experienced ophthalmology professors were asked to develop a 100-question singlechoice question on ocular surface diseases designed to assess the performance of LLMs and human participants in answering ophthalmology specialty exam questions.The exam includes questions on the following topics:keratitis disease(20 questions),keratoconus,keratomalaciac,corneal dystrophy,corneal degeneration,erosive corneal ulcers,and corneal lesions associated with systemic diseases(20 questions),conjunctivitis disease(20 questions),trachoma,pterygoid and conjunctival tumor diseases(20 questions),and dry eye disease(20 questions).Then the total score of each LLMs and compared their mean score,mean correlation,variance,and confidence were calculated.RESULTS:GPT-4 exhibited the highest performance in terms of LLMs.Comparing the average scores of the LLMs group with the four human groups,chief physician,attending physician,regular trainee,and graduate student,it was found that except for ChatGPT-4,the total score of the rest of the LLMs is lower than that of the graduate student group,which had the lowest score in the human group.Both ChatGPT-4 and PaLM2 were more likely to give exact and correct answers,giving very little chance of an incorrect answer.ChatGPT-4 showed higher credibility when answering questions,with a success rate of 59%,but gave the wrong answer to the question 28% of the time.CONCLUSION:GPT-4 model exhibits excellent performance in both answer relevance and confidence.PaLM2 shows a positive correlation(up to 0.8)in terms of answer accuracy during the exam.In terms of answer confidence,PaLM2 is second only to GPT4 and surpasses Claude 2,SenseNova,and GPT-3.5.Despite the fact that ocular surface disease is a highly specialized discipline,GPT-4 still exhibits superior performance,suggesting that its potential and ability to be applied in this field is enormous,perhaps with the potential to be a valuable resource for medical students and clinicians in the future.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82200784,32271311Qizhen Foundation,No.226‐2023‐00008(all to LH).
文摘Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol changes that occur in the brain during Alzheimer’s disease remains unclear.In this study,we compared brain tissues extracted from 32-week-old male wild-type mice and 5×FAD transgenic Alzheimer’s disease model mice,which carry mutations in the amyloid precursor protein(APP)and presenilin 1(PS1)genes.Using untargeted lipidomics and sterolomics techniques,we investigated the metabolic profiles of lipids,with a focus on sterols specifically,in three brain regions:cerebellum,hippocampus,and olfactory bulb.Our results revealed significant alterations in various lipids,particularly in the hippocampus and olfactory bulb,suggesting changes in energy levels in these regions.Further pathway analysis indicated notable disruptions in key metabolic processes,particularly those related to fatty acids and cell membrane components.Additionally,we observed decreased expression of 15 genes involved in lipid and sterol regulation.Collectively,these findings provide new insights into how imbalances in lipid and sterol metabolism may contribute to the progression of Alzheimer’s disease,highlighting potential metabolic pathways involved in the development of this debilitating disease.
基金supported by the NIA/NIH(1K01AG060040).Studies performed by JN were funded by the NICHD/NIH(5R00HD096117)Microscopy Core Facility supported,in part,with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.
文摘Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.
基金supported by the Canadian Institutes of Health Research(DFD-181599)the National Institutes of Health(T32AG058527)to RJB and R0190106435 to VM.
文摘Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patients,caregivers,and healthcare workers.Alzheimer’s disease(AD)and Parkinson’s disease represent the two most common neurodegenerative disorders in the population,affecting over 65 million people,worldwide.
基金supported by the Hartman Behavioral Neuroscience Laboratory.
文摘Background:Healthy non-pharmacological lifestyle factors,such as regular physical exercise and dietary supplementation,have been shown to significantly improve cognitive outcomes over time compared to a more sedentary lifestyle and poor diet.Furthermore,exercise may serve as a potential protective factor in attenuating the effects associated with cognitive decline that are characteristic of neurodegenerative disorders,such as Alzheimer's disease(AD).Evidence indicates that certain dietary interventions can also attenuate the effects of neurodegeneration and positively impact longevity.Supplementation with polyphenols such as ellagic acid(EA),which is abundant in pomegranate juice,may help provide neuroprotective and longevity benefits.Methods:This study examined the potential protective potential of EA and exercise and provides insight into the combined use of a polyphenol-rich diet and exercise to enhance behavioral outcomes and lifespan in a transgenic Drosophila melanogaster(fruit fly)model of AD with the Aβ_(42) gene.Results:Fruit flies subjected to a 120-minute exercise regimen performed better on a climbing assay than flies that did not exercise.Conversely,flies that exercised for 30 min passed marginally more trials on a learning and memory assay using an aversive stimulus than flies that did not exercise,whereas both groups performed better than flies subjected to the more intense exercise condition.Conclusion:These results suggest a hormetic effect of exercise regarding memory performance.Finally,flies fed a low dose of dietary EA(0.24 mg/mL)lived significantly longer than flies fed the control diet or higher concentrations of EA,again suggesting a hormetic effect of EA on longevity.
基金Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01 and 2023-PT330-01Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-034National Natural Science Foundation of China,Grant/Award Number:82161138027。
文摘Background:Alzheimer's disease(AD)represents the most prevalent neurodegenerative disorder,with mitochondrial dysfunction being observed in both AD patients and mouse models.Nonetheless,further investigation is required to elucidate the pathogenic genes associated with AD and to develop early diagnostic methodologies centered on mitochondrial function.Methods:In this study,the dataset GSE132903 was retrieved from the GEO database,encompassing both non-demented(ND)control and AD samples.Through the combination of differential expression gene analysis,weighted gene co-expression network analysis,and intersection with mitochondrial database gene sets,four hub genes associated with AD were identified.These four hub genes were subsequently validated in APP/PS1 and 5xFAD mouse models using molecular biology techniques.Results:The hub genes identified through bioinformatics analysis include SYNJ2BP,VDAC1,NUBPL,and COX19.Within the GSE132903 dataset,the expression levels of SYNJ2BP,NUBPL,and COX19 were significantly elevated in the AD group compared to the non-demented(ND)group,whereas VDAC1 expression was reduced in the AD group relative to the ND group.Furthermore,in the hippocampus of APP/PS1 and 5xFAD mouse models,the expression patterns of SYNJ2BP and NUBPL were consistent with the bioinformatics analysis results.Conclusion:Hub genes identified here through bioinformatics and molecular biology may help early diagnosis of AD patients and may also help build new AD models to explore its pathogenesis.
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
基金Tianmin Tianyuan Boutique Vegetable Industry Technology Service Station(Grant No.2024120011003081)Development of Environmental Monitoring and Traceability System for Wuqing Agricultural Production Areas(Grant No.2024120011001866)。
文摘Tomato is a major economic crop worldwide,and diseases on tomato leaves can significantly reduce both yield and quality.Traditional manual inspection is inefficient and highly subjective,making it difficult to meet the requirements of early disease identification in complex natural environments.To address this issue,this study proposes an improved YOLO11-based model,YOLO-SPDNet(Scale Sequence Fusion,Position-Channel Attention,and Dual Enhancement Network).The model integrates the SEAM(Self-Ensembling Attention Mechanism)semantic enhancement module,the MLCA(Mixed Local Channel Attention)lightweight attention mechanism,and the SPA(Scale-Position-Detail Awareness)module composed of SSFF(Scale Sequence Feature Fusion),TFE(Triple Feature Encoding),and CPAM(Channel and Position Attention Mechanism).These enhancements strengthen fine-grained lesion detection while maintaining model lightweightness.Experimental results show that YOLO-SPDNet achieves an accuracy of 91.8%,a recall of 86.5%,and an mAP@0.5 of 90.6%on the test set,with a computational complexity of 12.5 GFLOPs.Furthermore,the model reaches a real-time inference speed of 987 FPS,making it suitable for deployment on mobile agricultural terminals and online monitoring systems.Comparative analysis and ablation studies further validate the reliability and practical applicability of the proposed model in complex natural scenes.
基金Supported by the National Key Specialty of Traditional Chinese Medicine(Spleen and Stomach Diseases),No.0500004National Natural Science Foundation of China,No.82205104 and No.82104850+1 种基金Hospital Capability Enhancement Project of Xiyuan Hospital,CACMS,No.XYZX0303-07the Fundamental Research Funds for the Central Public Welfare Research Institutes,Excellent Young Scientists Training Program of China Academy of Chinese Medical Sciences,No.ZZ16-YQ-002.
文摘BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.
基金2024 Medical Science Research Project Plan of Hebei Province:Research on the Rehabilitation Effect of Combined Exercise Intervention Based on a Hospital-Community-Family Model for Elderly Patients with Chronic Diseases(Project No.:20240083)Youth Science and Technology Project of the Hebei Provincial Health Department:Research on the Standardization Level of Self-Management in Patients with Diabetic Foot and Related Factors Affecting Wound Healing(Project No.:20190002)。
文摘Objective:To explore the application effect of combined exercise intervention based on the hospital-community-family model on intrinsic capacity in elderly patients with diabetes mellitus complicated by chronic kidney disease.Methods:Using convenience sampling,100 elderly patients with diabetes mellitus complicated by chronic kidney disease who received treatment in the endocrinology department of a tertiary A-level hospital from May 2024 to May 2025 were selected as the study subjects.They were randomly divided into an experimental group(50 cases)and a control group(50 cases)using a random number table method.The control group received routine health education and telephone follow-up,while the experimental group,in addition to the control group’s interventions,underwent combined exercise intervention based on the hospital-community-family model.Remote medical guidance was utilized to monitor and study the application effect of exercise intervention on intrinsic capacity in elderly patients with diabetes mellitus complicated by chronic kidney disease.Fasting blood glucose,2-hour postprandial blood glucose,glomerular filtration rate,6-minute walk distance,and scores in five dimensions of intrinsic capacity(exercise,cognition,psychology,vitality,and sensation)were measured before the intervention,at 4 weeks of intervention,and at 12 weeks of intervention for both groups.Results:Before the exercise intervention,there were no statistically significant differences(p>0.05)between the two groups in terms of fasting blood glucose,2-hour postprandial blood glucose,glomerular filtration rate,6-minute walk distance,and scores across five dimensions of intrinsic capacity:mobility,cognition,psychology,vitality,and sensation.After 12 weeks of intervention,the experimental group demonstrated significantly higher scores than the control group in glomerular filtration rate,6-minute walk distance,and the dimensions of mobility,cognition,and vitality within intrinsic capacity,with all differences being statistically significant(p<0.05).Conversely,the experimental group showed significantly lower scores than the control group in fasting blood glucose,2-hour postprandial blood glucose,and the psychological dimension of intrinsic capacity,with these differences also being statistically significant(p<0.05).Conclusion:Continuous nursing care utilizing telemedicine based on a hospital-community-family model combined with exercise intervention can effectively enhance exercise tolerance and intrinsic capacity in elderly patients with diabetes mellitus complicated by chronic kidney disease,thereby improving their quality of life.The effectiveness of the intervention is positively correlated with the duration of the intervention.
文摘Background: Social determinants of health (SDOH) significantly influence diseases with environmental components, like vector-borne parasitic diseases. This study aims to examine how these factors influence vector-borne parasitic diseases (VBPDs) transmission in Chad and provide recommendations for policy improvements. Methods: The study adopts the WHO Conceptual Framework of SDOH to compare two regions in Southern Chad: Kouh-Est, which has an ongoing vector control program, and Grand-Sido, which lacks such a program. The study includes both nomadic and sedentary populations to provide a comprehensive understanding of the SDOH influencing VBPDs. Households were randomly selected. Data on sociodemographic characteristics, literacy, knowledge of VBPDs and protective measures, and access to education and health facilities were collected. Results: A total of 202 households from 17 villages, including 820 participants, were surveyed. Agriculture, livestock, and fishing were the main occupations, involving 84.1% of participants. Literacy was low, with 36.7% non-educated, 47.7% completing primary school, 14.5% secondary school, and only 0.3% reaching tertiary education. Most villages lacked schools beyond the primary level, and nomadic populations were significantly less educated than sedentary ones (p Conclusion: Educational deficiencies, lack of protective measures against vectors, inadequate healthcare resources, and lifestyle conditions aggravated by poor road infrastructure, limited transportation, and economic constraints contribute to worsened VBPDs outcomes in these rural populations. Addressing these systemic issues in the surveyed communities is essential for improving health equity and VBPDs outcomes in these regions specifically and in similar populations settings more broadly.
文摘This paper proposes a vector-borne plant disease model with discontinuous treatment strategies. Constructing Lyapunov function and applying non-smooth theory to analyze discontinuous differential equations, the basic reproductive number R0 is proved, which determines whether the plant disease will be extinct or not. If R0 R0 > 1 , there exists a unique endemic equilibrium which is globally stable. The numerical simulations are provided to verify our theoretical results, which indicate that after infective individuals reach some level, strengthening treatment measures is proved to be beneficial in controlling disease transmission.
文摘Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequences to livestock sector. Animal and human movements have a fundamental impact on RVF transmission. In recent years, there has been a growing interest in the use of mathematics and agent based models to represent and analyze the dynamic of RFV transmission. However, no previous study has taken into consideration animal herds’ mobility and precipitation factors to understand the disease spread. This limitation underlines the necessity to use computational model approach based on multi-agent system in the study of vector-borne diseases transmission and diffusion. In this paper, a multi-agent system combining conceptual model expressiveness is used to study animal herds’ mobility and the precipitation parameter impact on the Rift Valley Fever outbreak in Ferlo Barkedji in Northern Senegal. Simulation scenarios with various parameters, including rain quality, hosts, vectors, camp dispersal around ponds, etc., are unrolled. The different results we have obtained show that the evolution of the number of infected hosts and infected vectors depend on the degree of animal herds’ mobility and on precipitations. Our model provides a framework that permits predicting the spread of the disease associated with the mobility of animal herds.
基金the Begum Rokeya University,Rangpur,and the United Arab Emirates University,UAE for partially supporting this work。
文摘Rice is one of the most important staple crops globally.Rice plant diseases can severely reduce crop yields and,in extreme cases,lead to total production loss.Early diagnosis enables timely intervention,mitigates disease severity,supports effective treatment strategies,and reduces reliance on excessive pesticide use.Traditional machine learning approaches have been applied for automated rice disease diagnosis;however,these methods depend heavily on manual image preprocessing and handcrafted feature extraction,which are labor-intensive and time-consuming and often require domain expertise.Recently,end-to-end deep learning(DL) models have been introduced for this task,but they often lack robustness and generalizability across diverse datasets.To address these limitations,we propose a novel end-toend training framework for convolutional neural network(CNN) and attention-based model ensembles(E2ETCA).This framework integrates features from two state-of-the-art(SOTA) CNN models,Inception V3 and DenseNet-201,and an attention-based vision transformer(ViT) model.The fused features are passed through an additional fully connected layer with softmax activation for final classification.The entire process is trained end-to-end,enhancing its suitability for realworld deployment.Furthermore,we extract and analyze the learned features using a support vector machine(SVM),a traditional machine learning classifier,to provide comparative insights.We evaluate the proposed E2ETCA framework on three publicly available datasets,the Mendeley Rice Leaf Disease Image Samples dataset,the Kaggle Rice Diseases Image dataset,the Bangladesh Rice Research Institute dataset,and a combined version of all three.Using standard evaluation metrics(accuracy,precision,recall,and F1-score),our framework demonstrates superior performance compared to existing SOTA methods in rice disease diagnosis,with potential applicability to other agricultural disease detection tasks.
文摘Cynomolgus macaques,a species of Old World primate native to southeastern and eastern Asia and the island of Mauritius,are one of the most important nonhuman primate models for infectious disease.Although the closely related rhesus macaque is classified into subspecies based on geographic origin,no such subdivision exists for cynomolgus macaques,and they continue to be used interchangeably in infectious disease research,reducing the comparability of data produced from these studies.Research into the population genetics of cynomolgus macaques has found significant differences between macaques native to different areas,including their genetic diversity,with macaques from insular populations such as Mauritius and the Philippines exhibiting highly restricted heterozygosity compared to mainland populations native to Indonesia or Cambodia.In the context of infectious disease studies,research into pathogens,including Ebola virus,Crimean-Congo hemorrhagic fever virus,and Mycobacterium tuberculosis have found differences in study outcomes,survival times,and immune cell responses between different populations of macaques.This review provides an overview of the differences between cynomolgus macaque populations in the context of genetic diversity,and in response to infection,and highlights the need for clear reporting of geographic origin of primates used in research.This will improve data comparison between studies and help to further refine this important animal model.
基金supported by the Elderly Health Research Project of Jiangsu Province,No.LKM2023043(to XZ).
文摘Alterations in RNA methylation may affect the initiation and development of Alzheimer’s disease.However,the exact nature of the relationship between RNA methylation and Alzheimer’s disease remains unclear.In this study,RNA methylation levels were analyzed by bulk transcriptomic and single-cell RNA sequencing.The expression levels of RNA methylation regulators were confirmed using molecular biology techniques.Co-expression network analysis was used to identify relevant long non-coding RNAs.Molecular subtypes related to RNA methylation were classified,and variations in clinical characteristics,biological behavior,and immune signatures between subtypes were assessed.Machine learning approaches were applied to identify methylation-associated long non-coding RNAs,which were used to construct a risk model and nomogram for Alzheimer’s disease.Potential therapeutic agents for different risk groups were predicted,and in vitro experiments were conducted to identify key RNA methylation events.Single-cell analysis demonstrated enhanced RNA methylation in patients with Alzheimer’s disease,particularly within T cells,B cells,and NK cells.Quantitative reverse transcription-polymerase chain reaction and western blot confirmed alterations in RNA methylation regulators in neurons treated with amyloid-βoligomers in vitro.This evidence supported the classification of patients with Alzheimer’s disease into heterogeneous subtypes.Specifically,subtype 1 was identified as the immune-active subtype,while subtype 2 was characterized by a metabolic phenotype.Machine learning algorithms identified five significant methylation-associated long non-coding RNAs-LINC01007,MAP4K3-DT,MIR302CHG,VAC14-AS1,and TGFB2-OT1-that accurately predict clinical outcomes for patients with Alzheimer’s disease.These patients were classified into low-and high-risk categories;the latter group displayed higher immune infiltration,upregulated immune regulatory gene expression,and elevated immune scores and responded better to treatment with arachidonic-trifluoroethane.These findings suggest that dysregulated RNA methylation alters the immune microenvironment in Alzheimer’s disease and is closely associated with its progression.This phenomenon provides novel insights into potential therapeutic strategies for Alzheimer’s disease that target RNA methylation.
基金supported by OHSU Neurology Foundation Funds and NIH Grant R01NS119226 to IM.
文摘Oxidative stress has long been implicated as a driving force in neurodegenerative disease,with studies of human brain tissue and animal models revealing its important role.Parkinson’s disease(PD),in particular,highlights the selective vulnerability of neurons to the insults of reactive oxygen species.The motor symptoms of PD are caused by degeneration of dopamine neurons in the substantia nigra.These neurons experience increased oxidative stress due in part to highly active mitochondria that support their high bioenergetic demand and the generation of reactive oxygen species by dopamine metabolism(Watanabe et al.,2024).
基金supported by the Sichuan Provincial Cadre Health Research Project(ZH2024-101)the Key Natural Science Foundation of Sichuan Province(No.2025 ZNSFSC0053)。
文摘BACKGROUND Solid fuel use for cooking and heating is a major environmental risk factor,yet its association with new-onset heart disease(HD)remains unclear.The aim of this study was to investigate the relationship between solid fuel exposure and new-onset HD in a large cohort.METHODS Multivariable logistic regression models assessed associations between cooking/heating fuel types(coal,crop residue/wood,liquefied petroleum gas,natural gas,and others)and new-onset HD.Subgroup analyses explored effect modification by age,sex,education,smoking,alcohol use,and region.RESULTS A prospective cohort study included 5915 participants,with 781 participants(13.2%)developing new-onset HD.Coal use for cooking showed an initial association with new-onset HD risk(OR=1.41,95%CI:1.06–1.86,P=0.02),which attenuated after full adjustment(OR=1.28,95%CI:0.96–1.72,P=0.10).Coal use for heating demonstrated robust associations across all models(OR=1.86,95%CI:1.42–2.43,P<0.001).Crop residue/wood burning for heating was also significant(Model 2:OR=1.40,95%CI:1.06–1.86,P=0.02).Subgroup analyses revealed stronger associations among females,non-smokers,non-drinkers,and less-educated participants.Geographic stratification showed significant associations in southern but not northern regions.CONCLUSIONS Solid fuel use,particularly coal for heating,is associated with increased new-onset HD risk.Reducing solid fuel exposure is crucial for HD prevention in low-resource settings.
基金supported by the National Research Foundation of Korea (NRF)funded by the Ministry of Science,ICT&Future Planning (2022R1A2C2006229,2022R1A6A3A01086868)Korea Dementia Research Project through the Korea Dementia Research Center (KDRC)funded by the Ministry of Health&Welfare and Ministry of Science and ICT,Republic of Korea (RS-2024-00345328)KIST Institutional Grant (2E32851)。
文摘Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.
基金National Institutes of Health,No.R01AG057555(to PI,L.Xie,co-l,MEFP,PAS,PR)。
文摘Alzheimer s disease is a neurodegenerative disorder that leads to progressive memory loss,cognitive decline,and behavioral changes.Des pite ongoing research,its exa ct causes and effective treatments remain elusive.Traditional approaches have focused on symptom management,but breakthroughs in bioinformatics and high-thro ughput drug screening are offering new pathways to potential therapies.This review highlights our recent effo rts to identify novel drug candidates for Alzheimer's disease by leve raging computational methods and la rge-scale biological datasets.Our work introduces two key innovations in Alzheimer's disease research:addressing sex-specific diffe rences and leve raging drug repurposing for accelerated treatment discove ry.By combining sex-stratified preclinical data with machine learning and in vivo validation,we improve translational relevance and support precision medicine.Using the TgF344-AD rat model,which mimics human Alzheimer's disease spatial memory deficits and pathology,we explored the efficacy of various US Food and Drug Administrationapproved and investigational drugs.These included ibudilast,timapiprant,RG2833,diazoxide/dibenzoylmethane(combined),and BT-11,which targeted key Alzheimer's disease-related molecular pathways such as amyloid-beta plaques,Ta u tangles,and neuroinflammation.These drugs,at various stages of development,offer hope for not only managing symptoms but also addressing the underlying mechanisms of Alzheimer's disease.This review underscores the need for a multifaceted approach to Alzheimer's disease treatment,combining symptom relief with disease modification.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Degree and Postgraduate Education Teaching Reform Project of Jiangxi Province(No.JXYJG-2020-026).
文摘AIM:To assess the possibility of using different large language models(LLMs)in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surface diseases:ChatGPT-4,ChatGPT-3.5,Claude 2,PaLM2,and SenseNova.METHODS:A group of experienced ophthalmology professors were asked to develop a 100-question singlechoice question on ocular surface diseases designed to assess the performance of LLMs and human participants in answering ophthalmology specialty exam questions.The exam includes questions on the following topics:keratitis disease(20 questions),keratoconus,keratomalaciac,corneal dystrophy,corneal degeneration,erosive corneal ulcers,and corneal lesions associated with systemic diseases(20 questions),conjunctivitis disease(20 questions),trachoma,pterygoid and conjunctival tumor diseases(20 questions),and dry eye disease(20 questions).Then the total score of each LLMs and compared their mean score,mean correlation,variance,and confidence were calculated.RESULTS:GPT-4 exhibited the highest performance in terms of LLMs.Comparing the average scores of the LLMs group with the four human groups,chief physician,attending physician,regular trainee,and graduate student,it was found that except for ChatGPT-4,the total score of the rest of the LLMs is lower than that of the graduate student group,which had the lowest score in the human group.Both ChatGPT-4 and PaLM2 were more likely to give exact and correct answers,giving very little chance of an incorrect answer.ChatGPT-4 showed higher credibility when answering questions,with a success rate of 59%,but gave the wrong answer to the question 28% of the time.CONCLUSION:GPT-4 model exhibits excellent performance in both answer relevance and confidence.PaLM2 shows a positive correlation(up to 0.8)in terms of answer accuracy during the exam.In terms of answer confidence,PaLM2 is second only to GPT4 and surpasses Claude 2,SenseNova,and GPT-3.5.Despite the fact that ocular surface disease is a highly specialized discipline,GPT-4 still exhibits superior performance,suggesting that its potential and ability to be applied in this field is enormous,perhaps with the potential to be a valuable resource for medical students and clinicians in the future.
