Sporadic E(Es)layers in the ionosphere are characterized by intense plasma irregularities in the E region at altitudes of 90-130 km.Because they can significantly influence radio communications and navigation systems,...Sporadic E(Es)layers in the ionosphere are characterized by intense plasma irregularities in the E region at altitudes of 90-130 km.Because they can significantly influence radio communications and navigation systems,accurate forecasting of Es layers is crucial for ensuring the precision and dependability of navigation satellite systems.In this study,we present Es predictions made by an empirical model and by a deep learning model,and analyze their differences comprehensively by comparing the model predictions to satellite RO measurements and ground-based ionosonde observations.The deep learning model exhibited significantly better performance,as indicated by its high coefficient of correlation(r=0.87)with RO observations and predictions,than did the empirical model(r=0.53).This study highlights the importance of integrating artificial intelligence technology into ionosphere modelling generally,and into predicting Es layer occurrences and characteristics,in particular.展开更多
Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
Large-scale Language Models(LLMs)have achieved significant breakthroughs in Natural Language Processing(NLP),driven by the pre-training and fine-tuning paradigm.While this approach allows models to specialize in speci...Large-scale Language Models(LLMs)have achieved significant breakthroughs in Natural Language Processing(NLP),driven by the pre-training and fine-tuning paradigm.While this approach allows models to specialize in specific tasks with reduced training costs,the substantial memory requirements during fine-tuning present a barrier to broader deployment.Parameter-Efficient Fine-Tuning(PEFT)techniques,such as Low-Rank Adaptation(LoRA),and parameter quantization methods have emerged as solutions to address these challenges by optimizing memory usage and computational efficiency.Among these,QLoRA,which combines PEFT and quantization,has demonstrated notable success in reducing memory footprints during fine-tuning,prompting the development of various QLoRA variants.Despite these advancements,the quantitative impact of key variables on the fine-tuning performance of quantized LLMs remains underexplored.This study presents a comprehensive analysis of these key variables,focusing on their influence across different layer types and depths within LLM architectures.Our investigation uncovers several critical findings:(1)Larger layers,such as MLP layers,can maintain performance despite reductions in adapter rank,while smaller layers,like self-attention layers,aremore sensitive to such changes;(2)The effectiveness of balancing factors depends more on specific values rather than layer type or depth;(3)In quantization-aware fine-tuning,larger layers can effectively utilize smaller adapters,whereas smaller layers struggle to do so.These insights suggest that layer type is a more significant determinant of fine-tuning success than layer depth when optimizing quantized LLMs.Moreover,for the same discount of trainable parameters,reducing the trainable parameters in a larger layer is more effective in preserving fine-tuning accuracy than in a smaller one.This study provides valuable guidance for more efficient fine-tuning strategies and opens avenues for further research into optimizing LLM fine-tuning in resource-constrained environments.展开更多
Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein functio...Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.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
Understanding the anisotropic creep behaviors of shale under direct shearing is a challenging issue.In this context,we conducted shear-creep and steady-creep tests on shale with five bedding orientations (i.e.0°,...Understanding the anisotropic creep behaviors of shale under direct shearing is a challenging issue.In this context,we conducted shear-creep and steady-creep tests on shale with five bedding orientations (i.e.0°,30°,45°,60°,and 90°),under multiple levels of direct shearing for the first time.The results show that the anisotropic creep of shale exhibits a significant stress-dependent behavior.Under a low shear stress,the creep compliance of shale increases linearly with the logarithm of time at all bedding orientations,and the increase depends on the bedding orientation and creep time.Under high shear stress conditions,the creep compliance of shale is minimal when the bedding orientation is 0°,and the steady-creep rate of shale increases significantly with increasing bedding orientations of 30°,45°,60°,and 90°.The stress-strain values corresponding to the inception of the accelerated creep stage show an increasing and then decreasing trend with the bedding orientation.A semilogarithmic model that could reflect the stress dependence of the steady-creep rate while considering the hardening and damage process is proposed.The model minimizes the deviation of the calculated steady-state creep rate from the observed value and reveals the behavior of the bedding orientation's influence on the steady-creep rate.The applicability of the five classical empirical creep models is quantitatively evaluated.It shows that the logarithmic model can well explain the experimental creep strain and creep rate,and it can accurately predict long-term shear creep deformation.Based on an improved logarithmic model,the variations in creep parameters with shear stress and bedding orientations are discussed.With abovementioned findings,a mathematical method for constructing an anisotropic shear creep model of shale is proposed,which can characterize the nonlinear dependence of the anisotropic shear creep behavior of shale on the bedding orientation.展开更多
Since the 1950s,when the Turing Test was introduced,there has been notable progress in machine language intelligence.Language modeling,crucial for AI development,has evolved from statistical to neural models over the ...Since the 1950s,when the Turing Test was introduced,there has been notable progress in machine language intelligence.Language modeling,crucial for AI development,has evolved from statistical to neural models over the last two decades.Recently,transformer-based Pre-trained Language Models(PLM)have excelled in Natural Language Processing(NLP)tasks by leveraging large-scale training corpora.Increasing the scale of these models enhances performance significantly,introducing abilities like context learning that smaller models lack.The advancement in Large Language Models,exemplified by the development of ChatGPT,has made significant impacts both academically and industrially,capturing widespread societal interest.This survey provides an overview of the development and prospects from Large Language Models(LLM)to Large Multimodal Models(LMM).It first discusses the contributions and technological advancements of LLMs in the field of natural language processing,especially in text generation and language understanding.Then,it turns to the discussion of LMMs,which integrates various data modalities such as text,images,and sound,demonstrating advanced capabilities in understanding and generating cross-modal content,paving new pathways for the adaptability and flexibility of AI systems.Finally,the survey highlights the prospects of LMMs in terms of technological development and application potential,while also pointing out challenges in data integration,cross-modal understanding accuracy,providing a comprehensive perspective on the latest developments in this field.展开更多
Deterministic compartment models(CMs)and stochastic models,including stochastic CMs and agent-based models,are widely utilized in epidemic modeling.However,the relationship between CMs and their corresponding stochast...Deterministic compartment models(CMs)and stochastic models,including stochastic CMs and agent-based models,are widely utilized in epidemic modeling.However,the relationship between CMs and their corresponding stochastic models is not well understood.The present study aimed to address this gap by conducting a comparative study using the susceptible,exposed,infectious,and recovered(SEIR)model and its extended CMs from the coronavirus disease 2019 modeling literature.We demonstrated the equivalence of the numerical solution of CMs using the Euler scheme and their stochastic counterparts through theoretical analysis and simulations.Based on this equivalence,we proposed an efficient model calibration method that could replicate the exact solution of CMs in the corresponding stochastic models through parameter adjustment.The advancement in calibration techniques enhanced the accuracy of stochastic modeling in capturing the dynamics of epidemics.However,it should be noted that discrete-time stochastic models cannot perfectly reproduce the exact solution of continuous-time CMs.Additionally,we proposed a new stochastic compartment and agent mixed model as an alternative to agent-based models for large-scale population simulations with a limited number of agents.This model offered a balance between computational efficiency and accuracy.The results of this research contributed to the comparison and unification of deterministic CMs and stochastic models in epidemic modeling.Furthermore,the results had implications for the development of hybrid models that integrated the strengths of both frameworks.Overall,the present study has provided valuable epidemic modeling techniques and their practical applications for understanding and controlling the spread of infectious diseases.展开更多
Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(...Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.展开更多
Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse ...Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.展开更多
Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poo...Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.展开更多
Both the attribution of historical change and future projections of droughts rely heavily on climate modeling. However,reasonable drought simulations have remained a challenge, and the related performances of the curr...Both the attribution of historical change and future projections of droughts rely heavily on climate modeling. However,reasonable drought simulations have remained a challenge, and the related performances of the current state-of-the-art Coupled Model Intercomparison Project phase 6(CMIP6) models remain unknown. Here, both the strengths and weaknesses of CMIP6 models in simulating droughts and corresponding hydrothermal conditions in drylands are assessed.While the general patterns of simulated meteorological elements in drylands resemble the observations, the annual precipitation is overestimated by ~33%(with a model spread of 2.3%–77.2%), along with an underestimation of potential evapotranspiration(PET) by ~32%(17.5%–47.2%). The water deficit condition, measured by the difference between precipitation and PET, is 50%(29.1%–71.7%) weaker than observations. The CMIP6 models show weaknesses in capturing the climate mean drought characteristics in drylands, particularly with the occurrence and duration largely underestimated in the hyperarid Afro-Asian areas. Nonetheless, the drought-associated meteorological anomalies, including reduced precipitation, warmer temperatures, higher evaporative demand, and increased water deficit conditions, are reasonably reproduced. The simulated magnitude of precipitation(water deficit) associated with dryland droughts is overestimated by 28%(24%) compared to observations. The observed increasing trends in drought fractional area,occurrence, and corresponding meteorological anomalies during 1980–2014 are reasonably reproduced. Still, the increase in drought characteristics, associated precipitation and water deficit are obviously underestimated after the late 1990s,especially for mild and moderate droughts, indicative of a weaker response of dryland drought changes to global warming in CMIP6 models. Our results suggest that it is imperative to employ bias correction approaches in drought-related studies over drylands by using CMIP6 outputs.展开更多
BACKGROUND Study on influencing factors of gastric retention before endoscopic retrograde cholangiopancreatography(ERCP)background:With the wide application of ERCP,the risk of preoperative gastric retention affects t...BACKGROUND Study on influencing factors of gastric retention before endoscopic retrograde cholangiopancreatography(ERCP)background:With the wide application of ERCP,the risk of preoperative gastric retention affects the smooth progress of the operation.The study found that female,biliary and pancreatic malignant tumor,digestive tract obstruction and other factors are closely related to gastric retention,so the establishment of predictive model is very important to reduce the risk of operation.METHODS A retrospective analysis was conducted on 190 patients admitted to our hospital for ERCP preparation between January 2020 and February 2024.Patient baseline clinical data were collected using an electronic medical record system.Patients were randomly matched in a 1:4 ratio with data from 190 patients during the same period to establish a validation group(n=38)and a modeling group(n=152).Patients in the modeling group were divided into the gastric retention group(n=52)and non-gastric retention group(n=100)based on whether gastric retention occurred preoperatively.General data of patients in the validation group and identify factors influencing preoperative gastric retention in ERCP patients.A predictive model for preoperative gastric retention in ERCP patients was constructed,and calibration curves were used for validation.The receiver operating characteristic(ROC)curve was analyzed to evaluate the predictive value of the model.RESULTS We found no statistically significant difference in general data between the validation group and modeling group(P>0.05).The comparison of age,body mass index,hypertension,and diabetes between the two groups showed no statistically significant difference(P>0.05).However,we noted statistically significant differences in gender,primary disease,jaundice,opioid use,and gastrointestinal obstruction between the two groups(P<0.05).Mul-tivariate logistic regression analysis showed that gender,primary disease,jaundice,opioid use,and gastrointestinal obstruction were independent factors influencing preoperative gastric retention in ERCP patients(P<0.05).The results of logistic regression analysis revealed that gender,primary disease,jaundice,opioid use,and gastroin-testinal obstruction were included in the predictive model for preoperative gastric retention in ERCP patients.The calibration curves in the training set and validation set showed a slope close to 1,indicating good consistency between the predicted risk and actual risk.The ROC analysis results showed that the area under the curve(AUC)of the predictive model for preoperative gastric retention in ERCP patients in the training set was 0.901 with a standard error of 0.023(95%CI:0.8264-0.9567),and the optimal cutoff value was 0.71,with a sensitivity of 87.5 and specificity of 84.2.In the validation set,the AUC of the predictive model was 0.842 with a standard error of 0.013(95%CI:0.8061-0.9216),and the optimal cutoff value was 0.56,with a sensitivity of 56.2 and specificity of 100.0.CONCLUSION Gender,primary disease,jaundice,opioid use,and gastrointestinal obstruction are factors influencing preoperative gastric retention in ERCP patients.A predictive model established based on these factors has high predictive value.展开更多
The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole...The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole organism.Consequently,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.This review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection.Differences among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of COVID-19.To effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities.Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.展开更多
The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent year...The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.展开更多
Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly inve...Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.展开更多
Accurate soil moisture(SM)prediction is critical for understanding hydrological processes.Physics-based(PB)models exhibit large uncertainties in SM predictions arising from uncertain parameterizations and insufficient...Accurate soil moisture(SM)prediction is critical for understanding hydrological processes.Physics-based(PB)models exhibit large uncertainties in SM predictions arising from uncertain parameterizations and insufficient representation of land-surface processes.In addition to PB models,deep learning(DL)models have been widely used in SM predictions recently.However,few pure DL models have notably high success rates due to lacking physical information.Thus,we developed hybrid models to effectively integrate the outputs of PB models into DL models to improve SM predictions.To this end,we first developed a hybrid model based on the attention mechanism to take advantage of PB models at each forecast time scale(attention model).We further built an ensemble model that combined the advantages of different hybrid schemes(ensemble model).We utilized SM forecasts from the Global Forecast System to enhance the convolutional long short-term memory(ConvLSTM)model for 1–16 days of SM predictions.The performances of the proposed hybrid models were investigated and compared with two existing hybrid models.The results showed that the attention model could leverage benefits of PB models and achieved the best predictability of drought events among the different hybrid models.Moreover,the ensemble model performed best among all hybrid models at all forecast time scales and different soil conditions.It is highlighted that the ensemble model outperformed the pure DL model over 79.5%of in situ stations for 16-day predictions.These findings suggest that our proposed hybrid models can adequately exploit the benefits of PB model outputs to aid DL models in making SM predictions.展开更多
Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and e...Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.展开更多
BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are p...BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are pivotal in identifying the most suitable transplant candidates.Traditionally,scoring systems like the model for end-stage liver disease have been instrumental in this process.Nevertheless,the landscape of prognostication is undergoing a transformation with the integration of machine learning(ML)and artificial intelligence models.AIM To assess the utility of ML models in prognostication for LT,comparing their performance and reliability to established traditional scoring systems.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines,we conducted a thorough and standardized literature search using the PubMed/MEDLINE database.Our search imposed no restrictions on publication year,age,or gender.Exclusion criteria encompassed non-English studies,review articles,case reports,conference papers,studies with missing data,or those exhibiting evident methodological flaws.RESULTS Our search yielded a total of 64 articles,with 23 meeting the inclusion criteria.Among the selected studies,60.8%originated from the United States and China combined.Only one pediatric study met the criteria.Notably,91%of the studies were published within the past five years.ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values(ranging from 0.6 to 1)across all studies,surpassing the performance of traditional scoring systems.Random forest exhibited superior predictive capabilities for 90-d mortality following LT,sepsis,and acute kidney injury(AKI).In contrast,gradient boosting excelled in predicting the risk of graft-versus-host disease,pneumonia,and AKI.CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT,marking a significant evolution in the field of prognostication.展开更多
Spiking neural network(SNN),widely known as the third-generation neural network,has been frequently investigated due to its excellent spatiotemporal information processing capability,high biological plausibility,and l...Spiking neural network(SNN),widely known as the third-generation neural network,has been frequently investigated due to its excellent spatiotemporal information processing capability,high biological plausibility,and low energy consumption characteristics.Analogous to the working mechanism of human brain,the SNN system transmits information through the spiking action of neurons.Therefore,artificial neurons are critical building blocks for constructing SNN in hardware.Memristors are drawing growing attention due to low consumption,high speed,and nonlinearity characteristics,which are recently introduced to mimic the functions of biological neurons.Researchers have proposed multifarious memristive materials including organic materials,inorganic materials,or even two-dimensional materials.Taking advantage of the unique electrical behavior of these materials,several neuron models are successfully implemented,such as Hodgkin–Huxley model,leaky integrate-and-fire model and integrate-and-fire model.In this review,the recent reports of artificial neurons based on memristive devices are discussed.In addition,we highlight the models and applications through combining artificial neuronal devices with sensors or other electronic devices.Finally,the future challenges and outlooks of memristor-based artificial neurons are discussed,and the development of hardware implementation of brain-like intelligence system based on SNN is also prospected.展开更多
基金supported by the Project of Stable Support for Youth Team in Basic Research Field,CAS(grant No.YSBR-018)the National Natural Science Foundation of China(grant Nos.42188101,42130204)+4 种基金the B-type Strategic Priority Program of CAS(grant no.XDB41000000)the National Natural Science Foundation of China(NSFC)Distinguished Overseas Young Talents Program,Innovation Program for Quantum Science and Technology(2021ZD0300301)the Open Research Project of Large Research Infrastructures of CAS-“Study on the interaction between low/mid-latitude atmosphere and ionosphere based on the Chinese Meridian Project”.The project was supported also by the National Key Laboratory of Deep Space Exploration(Grant No.NKLDSE2023A002)the Open Fund of Anhui Provincial Key Laboratory of Intelligent Underground Detection(Grant No.APKLIUD23KF01)the China National Space Administration(CNSA)pre-research Project on Civil Aerospace Technologies No.D010305,D010301.
文摘Sporadic E(Es)layers in the ionosphere are characterized by intense plasma irregularities in the E region at altitudes of 90-130 km.Because they can significantly influence radio communications and navigation systems,accurate forecasting of Es layers is crucial for ensuring the precision and dependability of navigation satellite systems.In this study,we present Es predictions made by an empirical model and by a deep learning model,and analyze their differences comprehensively by comparing the model predictions to satellite RO measurements and ground-based ionosonde observations.The deep learning model exhibited significantly better performance,as indicated by its high coefficient of correlation(r=0.87)with RO observations and predictions,than did the empirical model(r=0.53).This study highlights the importance of integrating artificial intelligence technology into ionosphere modelling generally,and into predicting Es layer occurrences and characteristics,in particular.
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
基金supported by the National Key R&D Program of China(No.2021YFB0301200)National Natural Science Foundation of China(No.62025208).
文摘Large-scale Language Models(LLMs)have achieved significant breakthroughs in Natural Language Processing(NLP),driven by the pre-training and fine-tuning paradigm.While this approach allows models to specialize in specific tasks with reduced training costs,the substantial memory requirements during fine-tuning present a barrier to broader deployment.Parameter-Efficient Fine-Tuning(PEFT)techniques,such as Low-Rank Adaptation(LoRA),and parameter quantization methods have emerged as solutions to address these challenges by optimizing memory usage and computational efficiency.Among these,QLoRA,which combines PEFT and quantization,has demonstrated notable success in reducing memory footprints during fine-tuning,prompting the development of various QLoRA variants.Despite these advancements,the quantitative impact of key variables on the fine-tuning performance of quantized LLMs remains underexplored.This study presents a comprehensive analysis of these key variables,focusing on their influence across different layer types and depths within LLM architectures.Our investigation uncovers several critical findings:(1)Larger layers,such as MLP layers,can maintain performance despite reductions in adapter rank,while smaller layers,like self-attention layers,aremore sensitive to such changes;(2)The effectiveness of balancing factors depends more on specific values rather than layer type or depth;(3)In quantization-aware fine-tuning,larger layers can effectively utilize smaller adapters,whereas smaller layers struggle to do so.These insights suggest that layer type is a more significant determinant of fine-tuning success than layer depth when optimizing quantized LLMs.Moreover,for the same discount of trainable parameters,reducing the trainable parameters in a larger layer is more effective in preserving fine-tuning accuracy than in a smaller one.This study provides valuable guidance for more efficient fine-tuning strategies and opens avenues for further research into optimizing LLM fine-tuning in resource-constrained environments.
基金supported by Warren Alpert Foundation and Houston Methodist Academic Institute Laboratory Operating Fund(to HLC).
文摘Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.
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funded by the National Natural Science Foundation of China(Grant Nos.U22A20166 and 12172230)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515012654)+1 种基金funded by the National Natural Science Foundation of China(Grant Nos.U22A20166 and 12172230)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515012654)。
文摘Understanding the anisotropic creep behaviors of shale under direct shearing is a challenging issue.In this context,we conducted shear-creep and steady-creep tests on shale with five bedding orientations (i.e.0°,30°,45°,60°,and 90°),under multiple levels of direct shearing for the first time.The results show that the anisotropic creep of shale exhibits a significant stress-dependent behavior.Under a low shear stress,the creep compliance of shale increases linearly with the logarithm of time at all bedding orientations,and the increase depends on the bedding orientation and creep time.Under high shear stress conditions,the creep compliance of shale is minimal when the bedding orientation is 0°,and the steady-creep rate of shale increases significantly with increasing bedding orientations of 30°,45°,60°,and 90°.The stress-strain values corresponding to the inception of the accelerated creep stage show an increasing and then decreasing trend with the bedding orientation.A semilogarithmic model that could reflect the stress dependence of the steady-creep rate while considering the hardening and damage process is proposed.The model minimizes the deviation of the calculated steady-state creep rate from the observed value and reveals the behavior of the bedding orientation's influence on the steady-creep rate.The applicability of the five classical empirical creep models is quantitatively evaluated.It shows that the logarithmic model can well explain the experimental creep strain and creep rate,and it can accurately predict long-term shear creep deformation.Based on an improved logarithmic model,the variations in creep parameters with shear stress and bedding orientations are discussed.With abovementioned findings,a mathematical method for constructing an anisotropic shear creep model of shale is proposed,which can characterize the nonlinear dependence of the anisotropic shear creep behavior of shale on the bedding orientation.
基金We acknowledge funding from NSFC Grant 62306283.
文摘Since the 1950s,when the Turing Test was introduced,there has been notable progress in machine language intelligence.Language modeling,crucial for AI development,has evolved from statistical to neural models over the last two decades.Recently,transformer-based Pre-trained Language Models(PLM)have excelled in Natural Language Processing(NLP)tasks by leveraging large-scale training corpora.Increasing the scale of these models enhances performance significantly,introducing abilities like context learning that smaller models lack.The advancement in Large Language Models,exemplified by the development of ChatGPT,has made significant impacts both academically and industrially,capturing widespread societal interest.This survey provides an overview of the development and prospects from Large Language Models(LLM)to Large Multimodal Models(LMM).It first discusses the contributions and technological advancements of LLMs in the field of natural language processing,especially in text generation and language understanding.Then,it turns to the discussion of LMMs,which integrates various data modalities such as text,images,and sound,demonstrating advanced capabilities in understanding and generating cross-modal content,paving new pathways for the adaptability and flexibility of AI systems.Finally,the survey highlights the prospects of LMMs in terms of technological development and application potential,while also pointing out challenges in data integration,cross-modal understanding accuracy,providing a comprehensive perspective on the latest developments in this field.
基金supported by the National Natural Science Foundation of China(Grant Nos.82173620 to Yang Zhao and 82041024 to Feng Chen)partially supported by the Bill&Melinda Gates Foundation(Grant No.INV-006371 to Feng Chen)Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Deterministic compartment models(CMs)and stochastic models,including stochastic CMs and agent-based models,are widely utilized in epidemic modeling.However,the relationship between CMs and their corresponding stochastic models is not well understood.The present study aimed to address this gap by conducting a comparative study using the susceptible,exposed,infectious,and recovered(SEIR)model and its extended CMs from the coronavirus disease 2019 modeling literature.We demonstrated the equivalence of the numerical solution of CMs using the Euler scheme and their stochastic counterparts through theoretical analysis and simulations.Based on this equivalence,we proposed an efficient model calibration method that could replicate the exact solution of CMs in the corresponding stochastic models through parameter adjustment.The advancement in calibration techniques enhanced the accuracy of stochastic modeling in capturing the dynamics of epidemics.However,it should be noted that discrete-time stochastic models cannot perfectly reproduce the exact solution of continuous-time CMs.Additionally,we proposed a new stochastic compartment and agent mixed model as an alternative to agent-based models for large-scale population simulations with a limited number of agents.This model offered a balance between computational efficiency and accuracy.The results of this research contributed to the comparison and unification of deterministic CMs and stochastic models in epidemic modeling.Furthermore,the results had implications for the development of hybrid models that integrated the strengths of both frameworks.Overall,the present study has provided valuable epidemic modeling techniques and their practical applications for understanding and controlling the spread of infectious diseases.
基金supported by the National Key Research and Development Program of China (2021YFF0702201)National Natural Science Foundation of China (81873736,31872779,81830032)+2 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006,2018B030337001,2021A1515012526)Natural Science Foundation of Guangdong Province (2021A1515012526,2022A1515012651)。
文摘Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.
文摘Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.
基金supported by the Cutting Edge Development Fund of Advanced Medical Research Institute(GYY2023QY01)the China Postdoctoral Science Foundation(certificate number:2023M732093)。
文摘Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.
基金supported by Ministry of Science and Technology of China (Grant No. 2018YFA0606501)National Natural Science Foundation of China (Grant No. 42075037)+1 种基金Key Laboratory Open Research Program of Xinjiang Science and Technology Department (Grant No. 2022D04009)the National Key Scientific and Technological Infrastructure project “Earth System Numerical Simulation Facility” (EarthLab)。
文摘Both the attribution of historical change and future projections of droughts rely heavily on climate modeling. However,reasonable drought simulations have remained a challenge, and the related performances of the current state-of-the-art Coupled Model Intercomparison Project phase 6(CMIP6) models remain unknown. Here, both the strengths and weaknesses of CMIP6 models in simulating droughts and corresponding hydrothermal conditions in drylands are assessed.While the general patterns of simulated meteorological elements in drylands resemble the observations, the annual precipitation is overestimated by ~33%(with a model spread of 2.3%–77.2%), along with an underestimation of potential evapotranspiration(PET) by ~32%(17.5%–47.2%). The water deficit condition, measured by the difference between precipitation and PET, is 50%(29.1%–71.7%) weaker than observations. The CMIP6 models show weaknesses in capturing the climate mean drought characteristics in drylands, particularly with the occurrence and duration largely underestimated in the hyperarid Afro-Asian areas. Nonetheless, the drought-associated meteorological anomalies, including reduced precipitation, warmer temperatures, higher evaporative demand, and increased water deficit conditions, are reasonably reproduced. The simulated magnitude of precipitation(water deficit) associated with dryland droughts is overestimated by 28%(24%) compared to observations. The observed increasing trends in drought fractional area,occurrence, and corresponding meteorological anomalies during 1980–2014 are reasonably reproduced. Still, the increase in drought characteristics, associated precipitation and water deficit are obviously underestimated after the late 1990s,especially for mild and moderate droughts, indicative of a weaker response of dryland drought changes to global warming in CMIP6 models. Our results suggest that it is imperative to employ bias correction approaches in drought-related studies over drylands by using CMIP6 outputs.
文摘BACKGROUND Study on influencing factors of gastric retention before endoscopic retrograde cholangiopancreatography(ERCP)background:With the wide application of ERCP,the risk of preoperative gastric retention affects the smooth progress of the operation.The study found that female,biliary and pancreatic malignant tumor,digestive tract obstruction and other factors are closely related to gastric retention,so the establishment of predictive model is very important to reduce the risk of operation.METHODS A retrospective analysis was conducted on 190 patients admitted to our hospital for ERCP preparation between January 2020 and February 2024.Patient baseline clinical data were collected using an electronic medical record system.Patients were randomly matched in a 1:4 ratio with data from 190 patients during the same period to establish a validation group(n=38)and a modeling group(n=152).Patients in the modeling group were divided into the gastric retention group(n=52)and non-gastric retention group(n=100)based on whether gastric retention occurred preoperatively.General data of patients in the validation group and identify factors influencing preoperative gastric retention in ERCP patients.A predictive model for preoperative gastric retention in ERCP patients was constructed,and calibration curves were used for validation.The receiver operating characteristic(ROC)curve was analyzed to evaluate the predictive value of the model.RESULTS We found no statistically significant difference in general data between the validation group and modeling group(P>0.05).The comparison of age,body mass index,hypertension,and diabetes between the two groups showed no statistically significant difference(P>0.05).However,we noted statistically significant differences in gender,primary disease,jaundice,opioid use,and gastrointestinal obstruction between the two groups(P<0.05).Mul-tivariate logistic regression analysis showed that gender,primary disease,jaundice,opioid use,and gastrointestinal obstruction were independent factors influencing preoperative gastric retention in ERCP patients(P<0.05).The results of logistic regression analysis revealed that gender,primary disease,jaundice,opioid use,and gastroin-testinal obstruction were included in the predictive model for preoperative gastric retention in ERCP patients.The calibration curves in the training set and validation set showed a slope close to 1,indicating good consistency between the predicted risk and actual risk.The ROC analysis results showed that the area under the curve(AUC)of the predictive model for preoperative gastric retention in ERCP patients in the training set was 0.901 with a standard error of 0.023(95%CI:0.8264-0.9567),and the optimal cutoff value was 0.71,with a sensitivity of 87.5 and specificity of 84.2.In the validation set,the AUC of the predictive model was 0.842 with a standard error of 0.013(95%CI:0.8061-0.9216),and the optimal cutoff value was 0.56,with a sensitivity of 56.2 and specificity of 100.0.CONCLUSION Gender,primary disease,jaundice,opioid use,and gastrointestinal obstruction are factors influencing preoperative gastric retention in ERCP patients.A predictive model established based on these factors has high predictive value.
基金National Key Research and Development Program of China(2022YFC2303700,2021YFC2301300)Yunnan Key Research and Development Program(202303AC100026)+2 种基金National Natural Science Foundation of China(82302002,82341069)Yunnan Fundamental Research Project(202201AS070047)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0490000)。
文摘The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole organism.Consequently,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.This review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection.Differences among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of COVID-19.To effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities.Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.
基金supported by the STI2030-Major Projects(2021ZD0200900 to Y.G.Y.)"Light of West China" Program of the Chinese Academy of Sciences(xbzg-zdsys-202302 to Y.G.Y.)
文摘The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.
基金supported by the National Key Research and Development Program of China (2021YFA0805300,2021YFA0805200)National Natural Science Foundation of China (32170981,82371874,82394422,82171244,82071421,82271902)+1 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006,2018B030337001)。
文摘Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.
基金supported by the Natural Science Foundation of China(Grant Nos.42088101 and 42205149)Zhongwang WEI was supported by the Natural Science Foundation of China(Grant No.42075158)+1 种基金Wei SHANGGUAN was supported by the Natural Science Foundation of China(Grant No.41975122)Yonggen ZHANG was supported by the National Natural Science Foundation of Tianjin(Grant No.20JCQNJC01660).
文摘Accurate soil moisture(SM)prediction is critical for understanding hydrological processes.Physics-based(PB)models exhibit large uncertainties in SM predictions arising from uncertain parameterizations and insufficient representation of land-surface processes.In addition to PB models,deep learning(DL)models have been widely used in SM predictions recently.However,few pure DL models have notably high success rates due to lacking physical information.Thus,we developed hybrid models to effectively integrate the outputs of PB models into DL models to improve SM predictions.To this end,we first developed a hybrid model based on the attention mechanism to take advantage of PB models at each forecast time scale(attention model).We further built an ensemble model that combined the advantages of different hybrid schemes(ensemble model).We utilized SM forecasts from the Global Forecast System to enhance the convolutional long short-term memory(ConvLSTM)model for 1–16 days of SM predictions.The performances of the proposed hybrid models were investigated and compared with two existing hybrid models.The results showed that the attention model could leverage benefits of PB models and achieved the best predictability of drought events among the different hybrid models.Moreover,the ensemble model performed best among all hybrid models at all forecast time scales and different soil conditions.It is highlighted that the ensemble model outperformed the pure DL model over 79.5%of in situ stations for 16-day predictions.These findings suggest that our proposed hybrid models can adequately exploit the benefits of PB model outputs to aid DL models in making SM predictions.
基金supported by the National Key Research and Development Program of China (2021YFA0805902,2022YFF0710703)National Natural Science Foundation of China (32201257)+1 种基金Science and Technology Innovation Project of Xiongan New Area (2022XAGG0121)Young Elite Scientists Sponsorship Program by the China Association for Science and Technology (2019QNRC001)。
文摘Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.
文摘BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are pivotal in identifying the most suitable transplant candidates.Traditionally,scoring systems like the model for end-stage liver disease have been instrumental in this process.Nevertheless,the landscape of prognostication is undergoing a transformation with the integration of machine learning(ML)and artificial intelligence models.AIM To assess the utility of ML models in prognostication for LT,comparing their performance and reliability to established traditional scoring systems.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines,we conducted a thorough and standardized literature search using the PubMed/MEDLINE database.Our search imposed no restrictions on publication year,age,or gender.Exclusion criteria encompassed non-English studies,review articles,case reports,conference papers,studies with missing data,or those exhibiting evident methodological flaws.RESULTS Our search yielded a total of 64 articles,with 23 meeting the inclusion criteria.Among the selected studies,60.8%originated from the United States and China combined.Only one pediatric study met the criteria.Notably,91%of the studies were published within the past five years.ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values(ranging from 0.6 to 1)across all studies,surpassing the performance of traditional scoring systems.Random forest exhibited superior predictive capabilities for 90-d mortality following LT,sepsis,and acute kidney injury(AKI).In contrast,gradient boosting excelled in predicting the risk of graft-versus-host disease,pneumonia,and AKI.CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT,marking a significant evolution in the field of prognostication.
基金supported financially by the fund from the Ministry of Science and Technology of China(Grant No.2019YFB2205100)the National Science Fund for Distinguished Young Scholars(No.52025022)+3 种基金the National Nature Science Foundation of China(Grant Nos.U19A2091,62004016,51732003,52072065,1197407252272140 and 52372137)the‘111’Project(Grant No.B13013)the Fundamental Research Funds for the Central Universities(Nos.2412023YQ004 and 2412022QD036)the funding from Jilin Province(Grant Nos.20210201062GX,20220502002GH,20230402072GH,20230101017JC and 20210509045RQ)。
文摘Spiking neural network(SNN),widely known as the third-generation neural network,has been frequently investigated due to its excellent spatiotemporal information processing capability,high biological plausibility,and low energy consumption characteristics.Analogous to the working mechanism of human brain,the SNN system transmits information through the spiking action of neurons.Therefore,artificial neurons are critical building blocks for constructing SNN in hardware.Memristors are drawing growing attention due to low consumption,high speed,and nonlinearity characteristics,which are recently introduced to mimic the functions of biological neurons.Researchers have proposed multifarious memristive materials including organic materials,inorganic materials,or even two-dimensional materials.Taking advantage of the unique electrical behavior of these materials,several neuron models are successfully implemented,such as Hodgkin–Huxley model,leaky integrate-and-fire model and integrate-and-fire model.In this review,the recent reports of artificial neurons based on memristive devices are discussed.In addition,we highlight the models and applications through combining artificial neuronal devices with sensors or other electronic devices.Finally,the future challenges and outlooks of memristor-based artificial neurons are discussed,and the development of hardware implementation of brain-like intelligence system based on SNN is also prospected.