At present,treatments for Alzheimer's disease can temporarily relieve symptoms but cannot prevent the decline of cognitive ability and other neurodegenerative changes.Dendrobium nobile Lindl alkaloid is the main a...At present,treatments for Alzheimer's disease can temporarily relieve symptoms but cannot prevent the decline of cognitive ability and other neurodegenerative changes.Dendrobium nobile Lindl alkaloid is the main active component of Dendrobium nobile Lindl.Dendrobium nobile Lindl alkaloid has been shown to resist aging,prolong life span,and exhibit immunomodulatory effects in animals.This review summarizes the mechanisms behind the neuroprotective effects reported in Alzheimer's disease animal models.The neuroprotective effects of Dendrobium nobile Lindl alkaloid have not been studied in patients.The mechanisms by which Dendrobium nobile Lindl alkaloid has been reported to improve cognitive dysfunction in Alzheimer's disease animal models may be associated with extracellular amyloid plaque production,regulation of tau protein hyperphosphorylation,inhibition of neuroinflammation and neuronal apoptosis,activation of autophagy,and enhanced synaptic connections.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
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
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
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
BACKGROUND Inflammatory bowel disease(IBD)is a global health burden that affects millions of individuals worldwide,necessitating extensive patient education.Large language models(LLMs)hold promise for addressing patie...BACKGROUND Inflammatory bowel disease(IBD)is a global health burden that affects millions of individuals worldwide,necessitating extensive patient education.Large language models(LLMs)hold promise for addressing patient information needs.However,LLM use to deliver accurate and comprehensible IBD-related medical information has yet to be thoroughly investigated.AIM To assess the utility of three LLMs(ChatGPT-4.0,Claude-3-Opus,and Gemini-1.5-Pro)as a reference point for patients with IBD.METHODS In this comparative study,two gastroenterology experts generated 15 IBD-related questions that reflected common patient concerns.These questions were used to evaluate the performance of the three LLMs.The answers provided by each model were independently assessed by three IBD-related medical experts using a Likert scale focusing on accuracy,comprehensibility,and correlation.Simultaneously,three patients were invited to evaluate the comprehensibility of their answers.Finally,a readability assessment was performed.RESULTS Overall,each of the LLMs achieved satisfactory levels of accuracy,comprehensibility,and completeness when answering IBD-related questions,although their performance varies.All of the investigated models demonstrated strengths in providing basic disease information such as IBD definition as well as its common symptoms and diagnostic methods.Nevertheless,when dealing with more complex medical advice,such as medication side effects,dietary adjustments,and complication risks,the quality of answers was inconsistent between the LLMs.Notably,Claude-3-Opus generated answers with better readability than the other two models.CONCLUSION LLMs have the potential as educational tools for patients with IBD;however,there are discrepancies between the models.Further optimization and the development of specialized models are necessary to ensure the accuracy and safety of the information provided.展开更多
Background and Aims:Metabolic dysfunction-associated steatotic liver disease(MASLD)represents an escalating healthcare burden across the Middle East and North Africa(MENA)region;however,system-level preparedness remai...Background and Aims:Metabolic dysfunction-associated steatotic liver disease(MASLD)represents an escalating healthcare burden across the Middle East and North Africa(MENA)region;however,system-level preparedness remains largely undefined.This study aimed to assess existing models of care,clinical infrastructure,policy frameworks,and provider perspectives across 17 MENA countries.Methods:A cross-sectional,mixed-methods survey was distributed to clinicians from MASLD-related specialties across the region.A total of 130 experts(87.2%response rate)from academic,public,and private sectors in 17 countries participated.The questionnaire addressed national policies,diagnostic and therapeutic practices,referral pathways,multidisciplinary team(MDT)integration,and patient/public engagement.Quantitative responses were analyzed descriptively,while qualitative inputs underwent thematic analysis.Results:Only 35.4%of respondents confirmed the presence of national clinical guidelines for MASLD,and 73.1%reported the absence of a national strategy.Structured referral pathways were reported by 39.2%of participants,and only 31.5%believed the current model adequately addresses MASLD.While 60%supported MDT approaches,implementation remained inconsistent.Limited access to transient elastography was reported by 26.2%of providers.Public education efforts were minimal:22.3%reported no available tools,and 87.7%indicated the absence of patient-reported outcomes data.Nearly half(47.7%)cited poor patient adherence,attributed to low awareness,financial barriers,and lack of follow-up.Conclusions:Significant policy,structural,and educational gaps persist in MASLD care across the MENA region.To address this rising burden,countries must adopt integrated national strategies,expand access to non-invasive diagnostic tests,institutionalize MDT care,and invest in both public and provider education as essential pillars of system-wide preparedness.展开更多
BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relation...BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration,particularly the involvement of Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis.Experimental mouse models have been used to explore how P.gingivalis products contribute to neuroinflammatory and degenerative processes.However,a comprehensive synthesis of these findings is lacking.This systematic review evaluates the role of P.gingivalisderived factors in triggering Alzheimer's-like pathology,with an emphasis on bacterial products and host immune responses.We hypothesize that P.gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.AIM To link gingival P.gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.METHODS This systematic review followed the 2020 PRISMA guidelines.A comprehensive search was conducted in five databases(PubMed,Scopus,ScienceDirect,Sage,SpringerLink)for original studies between 2014 and 2024.Studies included mouse models to evaluate the effect of P.gingivalis or its products on Alzheimer's-like pathologies.Exclusion criteria were in vitro,human,or review studies.Twenty-three studies met the inclusion criteria.Bacterial components and activated host factors were extracted,categorized,and analyzed using narrative synthesis and descriptive statistics.RESULTS In 24 studies,lipopolysaccharides(54.84%)and gingipains(25.81%)were the most frequently reported P.gingivalis products.These factors activated toll-like receptors(TLR2/TLR4),microglia,and astrocytes,increasing levels of interleukin 1 beta,tumor necrosis factor-alpha,and other proinflammatory cytokines.The host response includedβ-amyloid accumulation,Tau hyperphosphorylation,and changes in blood-brain barrier permeability.Glial cells were the most frequently mentioned host factors(n=15),followed by proteins(n=13)and cytokines(n=11).These interactions promoted cognitive impairment,synaptic dysfunction,and neurodegeneration in mouse models,supporting a role for P.gingivalis in Alzheimer's-like pathology.CONCLUSION P.gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models,supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.展开更多
Ischemic heart disease(IHD)remains a leading contributor to cardiovascular disease(CVD)worldwide.Despite advances in diagnostic and therapeutic approaches,translational research demands robust large animal models to b...Ischemic heart disease(IHD)remains a leading contributor to cardiovascular disease(CVD)worldwide.Despite advances in diagnostic and therapeutic approaches,translational research demands robust large animal models to bridge the gap between experimental interventions and clinical application.Among these,porcine models have gained prominence due to their anatomical,physiological,immunological,and genomic similarities to humans.This review provides a comprehensive overview of current methodologies for establishing porcine IHD models,critically assesses emerging rehabilitative strategies,and outlines innovative therapeutic technologies,with the goal of guiding model selection and fostering the development of novel treatment strategies.展开更多
The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although v...The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although various models have been employed to establish ALD models over the past few decades,most successful cases are associated with high mortality rates,operational difficulties,and incompatibility formation mechanism compared to human ALD.However,the ALD models established by oral administration that simulate human drinking behavior often fail to induce significant liver damage.Therefore,it is imperative to explore simple and effective modes of oral administration for establishing ALD models consistent with the pathophysiological process of human ALD.Herein,we summarized the pathogenesis of ALD and discussed several issues related to construct ALD models with rodents(mainly mice and rats)by oral administration,including animal selection,animal feeding,alcohol intervention,and evaluation criteria.The purpose of this review is to provide a standardized and efficient formula for ALD modeling,so as to facilitate efficacy evaluation and mechanism analysis of food bioactive ingredients in ALD.展开更多
AIM:To assess the performance of five distinct large language models(LLMs;ChatGPT-3.5,ChatGPT-4,PaLM2,Claude 2,and SenseNova)in comparison to two human cohorts(a group of funduscopic disease experts and a group of oph...AIM:To assess the performance of five distinct large language models(LLMs;ChatGPT-3.5,ChatGPT-4,PaLM2,Claude 2,and SenseNova)in comparison to two human cohorts(a group of funduscopic disease experts and a group of ophthalmologists)on the specialized subject of funduscopic disease.METHODS:Five distinct LLMs and two distinct human groups independently completed a 100-item funduscopic disease test.The performance of these entities was assessed by comparing their average scores,response stability,and answer confidence,thereby establishing a basis for evaluation.RESULTS:Among all the LLMs,ChatGPT-4 and PaLM2 exhibited the most substantial average correlation.Additionally,ChatGPT-4 achieved the highest average score and demonstrated the utmost confidence during the exam.In comparison to human cohorts,ChatGPT-4 exhibited comparable performance to ophthalmologists,albeit falling short of the expertise demonstrated by funduscopic disease specialists.CONCLUSION:The study provides evidence of the exceptional performance of ChatGPT-4 in the domain of funduscopic disease.With continued enhancements,validated LLMs have the potential to yield unforeseen advantages in enhancing healthcare for both patients and physicians.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohe...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohepatitis,which is characterized by inflammation,hepatocyte injury,and fibrosis,increasing the risk of cirrhosis and liver failure.Recent studies suggest that neutrophil extracellular traps(NETs)and extracellular DNA(ecDNA)contribute to liver inflammation and fibrogenesis.However,their role in MASLD pathogenesis remains incompletely understood.AIM To investigate the dynamics of circulating NETs and ecDNA as potential biomarkers of liver injury in MASLD.METHODS Using three complementary mouse models,thioacetamide(TAA)-induced fibrosis,choline-deficient L-amino acid-defined(CDAA)diet-induced metabolic dysfunction-associated steatohepatitis,and cafeteria(CAF)diet-induced MASLD,we assessed the association between NET-related markers and liver damage.Blood samples were collected biweekly to analyze ecDNA and NET markers,including myeloperoxidase(MPO)and MPO-DNA complexes,using ELISA and real-time PCR.Liver histopathology was assessed for inflammation,fibrosis,and neutrophil infiltration.RESULTS The TAA and CDAA models exhibited significant liver injury,characterized by increased plasma alanine aminotransferase and aspartate aminotransferase levels,hepatocellular damage,and fibrosis.Elevated circulating NET markers(MPO and ecDNA)were observed in these models,with a strong correlation between NET formation and liver pathology.The CAF diet model induced steatosis but failed to elicit significant liver fibrosis or an increase in NET markers,suggesting that NETosis is associated with more severe liver damage.Notably,ecDNA and MPO levels correlated with neutrophil infiltration and fibrosis scores,indicating their potential as biomarkers of MASLD progression.CONCLUSION NETosis and ecDNA levels reflect liver injury severity in MASLD.NET markers and liver fibrosis were strongly associated in TAA and CDAA models,whereas CAF model showed minimal NET involvement.展开更多
In vitro liver disease modelling,a rapidly evolving field,has become a multidimensional endeavour aimed at more precisely and effectively recapitulating the complexity of hepatic pathophysiology.This review systematic...In vitro liver disease modelling,a rapidly evolving field,has become a multidimensional endeavour aimed at more precisely and effectively recapitulating the complexity of hepatic pathophysiology.This review systematically outlines the essential structural and cellular components of the liver as foundational elements for model design.Emphasising pathophysiological states rather than disease hallmarks,we discuss key liver injury paradigms,including hepatic steatosis,drug-induced hepatotoxicity,fibrogenesis,tumourigenesis and cholestatic injury.Each section integrates cellular mechanisms with model development strategies,highlighting advances in co-culture systems,multicellular organoids and liver-on-a-chip platforms.Although challenges persist,emerging platforms are increasingly capable of capturing multicellular crosstalk,structural heterogeneity and injury-response dynamics.Moving forward,model utility will depend not only on structural mimicry but on the ability to produce biologically meaningful outputs under experimentally controlled conditions.展开更多
This article evaluates the transformative potential of large language models(LLMs)as patient education tools for managing inflammatory bowel disease.The discussion highlights their ability to deliver nuanced and perso...This article evaluates the transformative potential of large language models(LLMs)as patient education tools for managing inflammatory bowel disease.The discussion highlights their ability to deliver nuanced and personalized infor-mation,addressing limitations in traditional educational materials.Key consider-ations include the necessity for domain-specific fine-tuning to enhance accuracy,the adoption of robust evaluation metrics beyond readability,and the integration of LLMs with clinical decision support systems to improve real-time patient education.Ethical and accessibility challenges,such as algorithmic bias,data privacy,and digital literacy,are also examined.Recommendations emphasize the importance of interdisciplinary collaboration to optimize LLM integration,en-suring equitable access and improved patient outcomes.By advancing LLM technology,healthcare can empower patients with accurate and personalized information,enhancing engagement and disease management.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
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
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
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
Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human disea...Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human diseases, some of these mouse models do not replicate important disease symptoms or pathology. Pigs are more similar to humans than mice in anatomy, physiology, and genome. Thus, pigs are considered to be better animal models to mimic some human diseases. This review describes genetically modified pigs that have been used to model various diseases including neurological, cardiovascular, and diabetic disorders. We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases,展开更多
基金supported by Shijingshan’s Tutor Studio of Pharmacology,No.GZS-2016-07(to JSS)the Construction of National First Class Pharmacy Disciplineb,No.GESR-2017-85(to JSS)+1 种基金the Master Start Foundation of Zunyi Medical University,No.F-839(to DDL)a grant from Guizhou Chinese Medicine Administration,No.QZYY-2018-025(to DDL)。
文摘At present,treatments for Alzheimer's disease can temporarily relieve symptoms but cannot prevent the decline of cognitive ability and other neurodegenerative changes.Dendrobium nobile Lindl alkaloid is the main active component of Dendrobium nobile Lindl.Dendrobium nobile Lindl alkaloid has been shown to resist aging,prolong life span,and exhibit immunomodulatory effects in animals.This review summarizes the mechanisms behind the neuroprotective effects reported in Alzheimer's disease animal models.The neuroprotective effects of Dendrobium nobile Lindl alkaloid have not been studied in patients.The mechanisms by which Dendrobium nobile Lindl alkaloid has been reported to improve cognitive dysfunction in Alzheimer's disease animal models may be associated with extracellular amyloid plaque production,regulation of tau protein hyperphosphorylation,inhibition of neuroinflammation and neuronal apoptosis,activation of autophagy,and enhanced synaptic connections.
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 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.
基金Supported by the China Health Promotion Foundation Young Doctors'Research Foundation for Inflammatory Bowel Disease,the Taishan Scholars Program of Shandong Province,China,No.tsqn202306343National Natural Science Foundation of China,No.82270578.
文摘BACKGROUND Inflammatory bowel disease(IBD)is a global health burden that affects millions of individuals worldwide,necessitating extensive patient education.Large language models(LLMs)hold promise for addressing patient information needs.However,LLM use to deliver accurate and comprehensible IBD-related medical information has yet to be thoroughly investigated.AIM To assess the utility of three LLMs(ChatGPT-4.0,Claude-3-Opus,and Gemini-1.5-Pro)as a reference point for patients with IBD.METHODS In this comparative study,two gastroenterology experts generated 15 IBD-related questions that reflected common patient concerns.These questions were used to evaluate the performance of the three LLMs.The answers provided by each model were independently assessed by three IBD-related medical experts using a Likert scale focusing on accuracy,comprehensibility,and correlation.Simultaneously,three patients were invited to evaluate the comprehensibility of their answers.Finally,a readability assessment was performed.RESULTS Overall,each of the LLMs achieved satisfactory levels of accuracy,comprehensibility,and completeness when answering IBD-related questions,although their performance varies.All of the investigated models demonstrated strengths in providing basic disease information such as IBD definition as well as its common symptoms and diagnostic methods.Nevertheless,when dealing with more complex medical advice,such as medication side effects,dietary adjustments,and complication risks,the quality of answers was inconsistent between the LLMs.Notably,Claude-3-Opus generated answers with better readability than the other two models.CONCLUSION LLMs have the potential as educational tools for patients with IBD;however,there are discrepancies between the models.Further optimization and the development of specialized models are necessary to ensure the accuracy and safety of the information provided.
文摘Background and Aims:Metabolic dysfunction-associated steatotic liver disease(MASLD)represents an escalating healthcare burden across the Middle East and North Africa(MENA)region;however,system-level preparedness remains largely undefined.This study aimed to assess existing models of care,clinical infrastructure,policy frameworks,and provider perspectives across 17 MENA countries.Methods:A cross-sectional,mixed-methods survey was distributed to clinicians from MASLD-related specialties across the region.A total of 130 experts(87.2%response rate)from academic,public,and private sectors in 17 countries participated.The questionnaire addressed national policies,diagnostic and therapeutic practices,referral pathways,multidisciplinary team(MDT)integration,and patient/public engagement.Quantitative responses were analyzed descriptively,while qualitative inputs underwent thematic analysis.Results:Only 35.4%of respondents confirmed the presence of national clinical guidelines for MASLD,and 73.1%reported the absence of a national strategy.Structured referral pathways were reported by 39.2%of participants,and only 31.5%believed the current model adequately addresses MASLD.While 60%supported MDT approaches,implementation remained inconsistent.Limited access to transient elastography was reported by 26.2%of providers.Public education efforts were minimal:22.3%reported no available tools,and 87.7%indicated the absence of patient-reported outcomes data.Nearly half(47.7%)cited poor patient adherence,attributed to low awareness,financial barriers,and lack of follow-up.Conclusions:Significant policy,structural,and educational gaps persist in MASLD care across the MENA region.To address this rising burden,countries must adopt integrated national strategies,expand access to non-invasive diagnostic tests,institutionalize MDT care,and invest in both public and provider education as essential pillars of system-wide preparedness.
文摘BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration,particularly the involvement of Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis.Experimental mouse models have been used to explore how P.gingivalis products contribute to neuroinflammatory and degenerative processes.However,a comprehensive synthesis of these findings is lacking.This systematic review evaluates the role of P.gingivalisderived factors in triggering Alzheimer's-like pathology,with an emphasis on bacterial products and host immune responses.We hypothesize that P.gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.AIM To link gingival P.gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.METHODS This systematic review followed the 2020 PRISMA guidelines.A comprehensive search was conducted in five databases(PubMed,Scopus,ScienceDirect,Sage,SpringerLink)for original studies between 2014 and 2024.Studies included mouse models to evaluate the effect of P.gingivalis or its products on Alzheimer's-like pathologies.Exclusion criteria were in vitro,human,or review studies.Twenty-three studies met the inclusion criteria.Bacterial components and activated host factors were extracted,categorized,and analyzed using narrative synthesis and descriptive statistics.RESULTS In 24 studies,lipopolysaccharides(54.84%)and gingipains(25.81%)were the most frequently reported P.gingivalis products.These factors activated toll-like receptors(TLR2/TLR4),microglia,and astrocytes,increasing levels of interleukin 1 beta,tumor necrosis factor-alpha,and other proinflammatory cytokines.The host response includedβ-amyloid accumulation,Tau hyperphosphorylation,and changes in blood-brain barrier permeability.Glial cells were the most frequently mentioned host factors(n=15),followed by proteins(n=13)and cytokines(n=11).These interactions promoted cognitive impairment,synaptic dysfunction,and neurodegeneration in mouse models,supporting a role for P.gingivalis in Alzheimer's-like pathology.CONCLUSION P.gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models,supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.
基金supported by the National Key R&D Program of China(2023YFC3603800,2023YFC3603801)National Natural Science Foundation of China(82202793,82172534,82372574)+3 种基金Natural Science Foundation of Sichuan Province(2023NSFSC1999,2023NSFSC1495)Young and Middle-Aged Leading Talent Cultivation Project of Sichuan University(JH20231160)Noncommunicable Chronic Diseases-National Science and Technology Major Project(2024ZD0526000)1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC21038)。
文摘Ischemic heart disease(IHD)remains a leading contributor to cardiovascular disease(CVD)worldwide.Despite advances in diagnostic and therapeutic approaches,translational research demands robust large animal models to bridge the gap between experimental interventions and clinical application.Among these,porcine models have gained prominence due to their anatomical,physiological,immunological,and genomic similarities to humans.This review provides a comprehensive overview of current methodologies for establishing porcine IHD models,critically assesses emerging rehabilitative strategies,and outlines innovative therapeutic technologies,with the goal of guiding model selection and fostering the development of novel treatment strategies.
基金supported by the National Natural Science Foundation of China(32430083).
文摘The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although various models have been employed to establish ALD models over the past few decades,most successful cases are associated with high mortality rates,operational difficulties,and incompatibility formation mechanism compared to human ALD.However,the ALD models established by oral administration that simulate human drinking behavior often fail to induce significant liver damage.Therefore,it is imperative to explore simple and effective modes of oral administration for establishing ALD models consistent with the pathophysiological process of human ALD.Herein,we summarized the pathogenesis of ALD and discussed several issues related to construct ALD models with rodents(mainly mice and rats)by oral administration,including animal selection,animal feeding,alcohol intervention,and evaluation criteria.The purpose of this review is to provide a standardized and efficient formula for ALD modeling,so as to facilitate efficacy evaluation and mechanism analysis of food bioactive ingredients in ALD.
基金Supported by National Natural Science Foundation of China(No.82160195)Science and Technology Project of Jiangxi Provincial Department of Education(No.GJJ200169)+1 种基金Science and Technology Project of Jiangxi Province Health Commission of Traditional Chinese Medicine(No.2020A0087)Science and Technology Project of Jiangxi Health Commission(No.202130210).
文摘AIM:To assess the performance of five distinct large language models(LLMs;ChatGPT-3.5,ChatGPT-4,PaLM2,Claude 2,and SenseNova)in comparison to two human cohorts(a group of funduscopic disease experts and a group of ophthalmologists)on the specialized subject of funduscopic disease.METHODS:Five distinct LLMs and two distinct human groups independently completed a 100-item funduscopic disease test.The performance of these entities was assessed by comparing their average scores,response stability,and answer confidence,thereby establishing a basis for evaluation.RESULTS:Among all the LLMs,ChatGPT-4 and PaLM2 exhibited the most substantial average correlation.Additionally,ChatGPT-4 achieved the highest average score and demonstrated the utmost confidence during the exam.In comparison to human cohorts,ChatGPT-4 exhibited comparable performance to ophthalmologists,albeit falling short of the expertise demonstrated by funduscopic disease specialists.CONCLUSION:The study provides evidence of the exceptional performance of ChatGPT-4 in the domain of funduscopic disease.With continued enhancements,validated LLMs have the potential to yield unforeseen advantages in enhancing healthcare for both patients and physicians.
基金Supported by Slovak Research and Development Agency,No.APVV-21-0370Ministry of Education,Science,Research and Sport of the Slovak Republic,No.VEGA 1/0706/25 and No.VEGA 1/0341/23.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohepatitis,which is characterized by inflammation,hepatocyte injury,and fibrosis,increasing the risk of cirrhosis and liver failure.Recent studies suggest that neutrophil extracellular traps(NETs)and extracellular DNA(ecDNA)contribute to liver inflammation and fibrogenesis.However,their role in MASLD pathogenesis remains incompletely understood.AIM To investigate the dynamics of circulating NETs and ecDNA as potential biomarkers of liver injury in MASLD.METHODS Using three complementary mouse models,thioacetamide(TAA)-induced fibrosis,choline-deficient L-amino acid-defined(CDAA)diet-induced metabolic dysfunction-associated steatohepatitis,and cafeteria(CAF)diet-induced MASLD,we assessed the association between NET-related markers and liver damage.Blood samples were collected biweekly to analyze ecDNA and NET markers,including myeloperoxidase(MPO)and MPO-DNA complexes,using ELISA and real-time PCR.Liver histopathology was assessed for inflammation,fibrosis,and neutrophil infiltration.RESULTS The TAA and CDAA models exhibited significant liver injury,characterized by increased plasma alanine aminotransferase and aspartate aminotransferase levels,hepatocellular damage,and fibrosis.Elevated circulating NET markers(MPO and ecDNA)were observed in these models,with a strong correlation between NET formation and liver pathology.The CAF diet model induced steatosis but failed to elicit significant liver fibrosis or an increase in NET markers,suggesting that NETosis is associated with more severe liver damage.Notably,ecDNA and MPO levels correlated with neutrophil infiltration and fibrosis scores,indicating their potential as biomarkers of MASLD progression.CONCLUSION NETosis and ecDNA levels reflect liver injury severity in MASLD.NET markers and liver fibrosis were strongly associated in TAA and CDAA models,whereas CAF model showed minimal NET involvement.
基金supported by the German Research Foundation(DFG Ta434/8-1,CRC/TR 412 Project-ID 535081457 and SFB1382,Project-ID 403224013 and ID 556479455).
文摘In vitro liver disease modelling,a rapidly evolving field,has become a multidimensional endeavour aimed at more precisely and effectively recapitulating the complexity of hepatic pathophysiology.This review systematically outlines the essential structural and cellular components of the liver as foundational elements for model design.Emphasising pathophysiological states rather than disease hallmarks,we discuss key liver injury paradigms,including hepatic steatosis,drug-induced hepatotoxicity,fibrogenesis,tumourigenesis and cholestatic injury.Each section integrates cellular mechanisms with model development strategies,highlighting advances in co-culture systems,multicellular organoids and liver-on-a-chip platforms.Although challenges persist,emerging platforms are increasingly capable of capturing multicellular crosstalk,structural heterogeneity and injury-response dynamics.Moving forward,model utility will depend not only on structural mimicry but on the ability to produce biologically meaningful outputs under experimentally controlled conditions.
文摘This article evaluates the transformative potential of large language models(LLMs)as patient education tools for managing inflammatory bowel disease.The discussion highlights their ability to deliver nuanced and personalized infor-mation,addressing limitations in traditional educational materials.Key consider-ations include the necessity for domain-specific fine-tuning to enhance accuracy,the adoption of robust evaluation metrics beyond readability,and the integration of LLMs with clinical decision support systems to improve real-time patient education.Ethical and accessibility challenges,such as algorithmic bias,data privacy,and digital literacy,are also examined.Recommendations emphasize the importance of interdisciplinary collaboration to optimize LLM integration,en-suring equitable access and improved patient outcomes.By advancing LLM technology,healthcare can empower patients with accurate and personalized information,enhancing engagement and disease management.
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.
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.
基金supported by the grants from the National Basic Research Program of China(973 Program) awarded to N.L.(No.2011CBA01000) and L.L.(No. 2011CB944203)
文摘Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human diseases, some of these mouse models do not replicate important disease symptoms or pathology. Pigs are more similar to humans than mice in anatomy, physiology, and genome. Thus, pigs are considered to be better animal models to mimic some human diseases. This review describes genetically modified pigs that have been used to model various diseases including neurological, cardiovascular, and diabetic disorders. We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases,
