Taking the Xinhe mine's structure, mine pressure, structural fissure, fault andfault displacement, the distance between fault and water inrush point, thickness of block,water pressure those geological factors whic...Taking the Xinhe mine's structure, mine pressure, structural fissure, fault andfault displacement, the distance between fault and water inrush point, thickness of block,water pressure those geological factors which influenced the water inrush as the independentvariable, based on these data of water inrush point and water uninrush point, usingthe method of quantification theory(Ⅰ,Ⅱ), it would quantitatively disposes the qualitativevariable, applied to calculation to evaluate the risk of Xinhe's water inrush.展开更多
By using the method of literature review, this paper introduces the popular theoretical models which have shown to better explain physical activity behaviors at a certain degree, summarizes the dominating theoretical ...By using the method of literature review, this paper introduces the popular theoretical models which have shown to better explain physical activity behaviors at a certain degree, summarizes the dominating theoretical models in the studies of physical activity behaviors of the elderly in China. In addition, shortcomings and future prospects are pointed out at the end.展开更多
To solve the disability of conventional model used in electrical leak location when measurement electrodes were buried under the liner, a new model of high voltage DC leak detection is developed. For single-liner land...To solve the disability of conventional model used in electrical leak location when measurement electrodes were buried under the liner, a new model of high voltage DC leak detection is developed. For single-liner landfill, the waste material layer, the geomembrane liner and the soil under the liner are simulated with infinite horizontal layers. The leak is regarded as two parts, one being negative current source at the entrance, and the other positive current source of the same size at the exit. Comparisons between the new theoretical model and conventional model show that conventional model is efficient in locating leaks in geomembane liner associating the dipole scanning above the liner but is ineffective when the measurement electrodes were buried under the liner. The new theoretical model data are in excellent agreement with experimental data not only above the liner but also under the liner.展开更多
The properties of nonadiabatic trapping models of the reaction NH+H -N+H, are investigated in a collinear model as \veil as a non-collinear thermal reaction on the basis of theintrinsic reaction coordinate (IRC) intbr...The properties of nonadiabatic trapping models of the reaction NH+H -N+H, are investigated in a collinear model as \veil as a non-collinear thermal reaction on the basis of theintrinsic reaction coordinate (IRC) intbrmation obtained by ah initio calculations at QCISD/631 IG** ie\el. Using the unitied statistical theory fornonadiabatic trapping models. the thermal rateconstants over the temperature range of 2000-3000K are computed which are in excellent agreementwith the experiment results.展开更多
Forming limit diagram (FLD) is an important performance index to describe the maximum limit of principal strains that can be sustained by sheet metals till to the onset of localized necking. It offers a convenient and...Forming limit diagram (FLD) is an important performance index to describe the maximum limit of principal strains that can be sustained by sheet metals till to the onset of localized necking. It offers a convenient and useful tool to predict the forming limit in the sheet metal forming processes. In the present study, FLD has been determined experimentally for Ti?6Al?4V alloy at 400 °C by conducting a Nakazima test with specimens of different widths. Additionally, for theoretical FLD prediction, various anisotropic yield criteria (Barlat 1989, Barlat 1996, Hill 1993) and different hardening models viz., Hollomon power law (HPL), Johnson?Cook (JC), modified Zerilli–Armstrong (m-ZA), modified Arrhenius (m-Arr) models have been developed. Theoretical FLDs have been determined using Marciniak and Kuczynski (M?K) theory incorporating the developed yield criteria and constitutive models. It has been observed that the effect of yield model is more pronounced than the effect of constitutive model for theoretical FLDs prediction. However, the value of thickness imperfection factor (f0) is solely dependent on hardening model. Hill (1993) yield criterion is best suited for FLD prediction in the right hand side region. Moreover, Barlat (1989) yield criterion is best suited for FLD prediction in left hand side region. Therefore, the proposed hybrid FLD in combination with Barlat (1989) and Hill (1993) yield models with m-Arr hardening model is in the best agreement with experimental FLD.展开更多
In order to explore how to extract more transport information from current fluctuation, a theoretical extraction scheme is presented in a single barrier structure based on exclusion models, which include counter-flows...In order to explore how to extract more transport information from current fluctuation, a theoretical extraction scheme is presented in a single barrier structure based on exclusion models, which include counter-flows model and tunnel model. The first four cumulants of these two exclusion models are computed in a single barrier structure, and their characteristics are obtained. A scheme with the help of the first three cumulants is devised to check a transport process to follow the counter-flows model, the tunnel model or neither of them. Time series generated by Monte Carlo techniques is adopted to validate the abstraction procedure, and the result is reasonable.展开更多
Cyclic loads generated by environmental factors,such as winds,waves,and trains,will likely lead to performance degradation in pile foundations,resulting in issues like permanent displacement accumulation and bearing c...Cyclic loads generated by environmental factors,such as winds,waves,and trains,will likely lead to performance degradation in pile foundations,resulting in issues like permanent displacement accumulation and bearing capacity attenuation.This paper presents a semi-analytical solution for predicting the axial cyclic behavior of piles in sands.The solution relies on two enhanced nonlinear load-transfer models considering stress-strain hysteresis and cyclic degradation in the pile-soil interaction.Model parameters are calibrated through cyclic shear tests of the sand-steel interface and laboratory geotechnical testing of sands.A novel aspect involves the meticulous formulation of the shaft loadtransfer function using an interface constitutive model,which inherently inherits the interface model’s advantages,such as capturing hysteresis,hardening,degradation,and particle breakage.The semi-analytical solution is computed numerically using the matrix displacement method,and the calculated values are validated through model tests performed on non-displacement and displacement piles in sands.The results demonstrate that the predicted values show excellent agreement with the measured values for both the static and cyclic responses of piles in sands.The displacement pile response,including factors such as bearing capacity,mobilized shaft resistance,and convergence rate of permanent settlement,exhibit improvements compared to non-displacement piles attributed to the soil squeezing effect.This methodology presents an innovative analytical framework,allowing for integrating cyclic interface models into the theoretical investigation of pile responses.展开更多
The spread of an advantageous mutation through a population is of fundamental interest in population genetics. While the classical Moran model is formulated for a well-mixed population, it has long been recognized tha...The spread of an advantageous mutation through a population is of fundamental interest in population genetics. While the classical Moran model is formulated for a well-mixed population, it has long been recognized that in real-world applications, the population usually has an explicit spatial structure which can significantly influence the dynamics. In the context of cancer initiation in epithelial tissue, several recent works have analyzed the dynamics of advantageous mutant spread on integer lattices, using the biased voter model from particle systems theory. In this spatial version of the Moran model, individuals first reproduce according to their fitness and then replace a neighboring individual. From a biological standpoint, the opposite dynamics, where individuals first die and are then replaced by a neighboring individual according to its fitness, are equally relevant. Here, we investigate this death-birth analogue of the biased voter model. We construct the process mathematically, derive the associated dual process, establish bounds on the survival probability of a single mutant, and prove that the process has an asymptotic shape. We also briefly discuss alternative birth-death and death-birth dynamics, depending on how the mutant fitness advantage affects the dynamics. We show that birth-death and death-birth formulations of the biased voter model are equivalent when fitness affects the former event of each update of the model, whereas the birth-death model is fundamentally different from the death-birth model when fitness affects the latter event.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
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
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
The inflection point is an important feature of sigmoidal height-diameter(H-D)models.It is often cited as one of the properties favoring sigmoidal model forms.However,there are very few studies analyzing the inflectio...The inflection point is an important feature of sigmoidal height-diameter(H-D)models.It is often cited as one of the properties favoring sigmoidal model forms.However,there are very few studies analyzing the inflection points of H-D models.The goals of this study were to theoretically and empirically examine the behaviors of inflection points of six common H-D models with a regional dataset.The six models were the Wykoff(WYK),Schumacher(SCH),Curtis(CUR),HossfeldⅣ(HOS),von Bertalanffy-Richards(VBR),and Gompertz(GPZ)models.The models were first fitted in their base forms with tree species as random effects and were then expanded to include functional traits and spatial distribution.The distributions of the estimated inflection points were similar between the two-parameter models WYK,SCH,and CUR,but were different between the threeparameter models HOS,VBR,and GPZ.GPZ produced some of the largest inflection points.HOS and VBR produced concave H-D curves without inflection points for 12.7%and 39.7%of the tree species.Evergreen species or decreasing shade tolerance resulted in larger inflection points.The trends in the estimated inflection points of HOS and VBR were entirely opposite across the landscape.Furthermore,HOS could produce concave H-D curves for portions of the landscape.Based on the studied behaviors,the choice between two-parameter models may not matter.We recommend comparing seve ral three-parameter model forms for consistency in estimated inflection points before deciding on one.Believing sigmoidal models to have inflection points does not necessarily mean that they will produce fitted curves with one.Our study highlights the need to integrate analysis of inflection points into modeling H-D relationships.展开更多
In this paper, the basic equations of beam-wave interaction for designing the 220 GHz folded waveguide (FW) backward wave oscillator (BWO) are described. On the whole, these equations are mainly classified into sm...In this paper, the basic equations of beam-wave interaction for designing the 220 GHz folded waveguide (FW) backward wave oscillator (BWO) are described. On the whole, these equations are mainly classified into small signal model (SSM), large signal model (LSM), and simplified small signal model (SSSM). Using these linear and nonlinear one-dimensional (1D) models, the oscillation characteristics of the FW BWO of a given configuration of slow wave struc- ture (SWS) can be calculated by numerical iteration algorithm, which is more time efficient than three-dimensional (3D) particle-in-cell (PIC) simulation. The SSSM expressed by analytical formulas is innovatively derived for determining the initial values of the FW SWS conveniently. The dispersion characteristics of the FW are obtained by equivalent circuit analysis. The space charge effect, the end reflection effect, the lossy wall effect, and the relativistic effect are all considered in our models to offer more accurate results. The design process of the FW BWO tube with output power of watt scale in a frequency range between 215 GHz and 225 GHz based on these 1D models is demonstrated. The 3D PIC method is adopted to verify the theoretical design results, which shows that they are in good agreement with each other.展开更多
Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders,and it is a rapidly growing global public health issue.It is characterized by hyperglycemia,a condition involving a high blood...Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders,and it is a rapidly growing global public health issue.It is characterized by hyperglycemia,a condition involving a high blood glucose level brought on by deficiencies in insulin secretion,decreased activity of insulin,or both.Prolonged effects of diabetes include cardiovascular problems,retinopathy,neuropathy,nephropathy,and vascular alterations in both macro-and micro-blood vessels.In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis,identifying targets,and reviewing novel treatment options and medications.Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences.The most popular in vivo studies involves the small animal models,such as rodent models,chemically induced diabetogens like streptozotocin and alloxan,and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals.Other models include virally induced models,diet/nutrition induced diabetic animals,surgically induced models or pancreatectomy models,and non-obese models.Large animals or non-rodent models like porcine(pig),canine(dog),nonhuman primate,and Zebrafish models are also outlined.The in vitro models discussed are murine and human beta-cell lines and pancreatic islets,human stem cells,and organoid cultures.The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition ofα-glucosidase activity.展开更多
With the continuous evolution and expanding applications of Large Language Models (LLMs), there has been a noticeable surge in the size of the emerging models. It is not solely the growth in model size, primarily meas...With the continuous evolution and expanding applications of Large Language Models (LLMs), there has been a noticeable surge in the size of the emerging models. It is not solely the growth in model size, primarily measured by the number of parameters, but also the subsequent escalation in computational demands, hardware and software prerequisites for training, all culminating in a substantial financial investment as well. In this paper, we present novel techniques like supervision, parallelization, and scoring functions to get better results out of chains of smaller language models, rather than relying solely on scaling up model size. Firstly, we propose an approach to quantify the performance of a Smaller Language Models (SLM) by introducing a corresponding supervisor model that incrementally corrects the encountered errors. Secondly, we propose an approach to utilize two smaller language models (in a network) performing the same task and retrieving the best relevant output from the two, ensuring peak performance for a specific task. Experimental evaluations establish the quantitative accuracy improvements on financial reasoning and arithmetic calculation tasks from utilizing techniques like supervisor models (in a network of model scenario), threshold scoring and parallel processing over a baseline study.展开更多
To control the power hierarchy design of lithium-ion battery(LIB)builtup sets for electric vehicles(EVs),we offer intensive theoretical and experimental sets of choice anode/cathode architectonics that can be modulate...To control the power hierarchy design of lithium-ion battery(LIB)builtup sets for electric vehicles(EVs),we offer intensive theoretical and experimental sets of choice anode/cathode architectonics that can be modulated in full-scale LIB built-up models.As primary structural tectonics,heterogeneous composite superstructures of full-cell-LIB(anode//cathode)electrodes were designed in closely packed flower agave rosettes TiO2@C(FRTO@C anode)and vertical-star-tower LiFePO4@C(VST@C cathode)building blocks to regulate the electron/ion movement in the three-dimensional axes and orientation pathways.The superpower hierarchy surfaces and multi-directional orientation components may create isosurface potential electrodes with mobile electron movements,in-to-out interplay electron dominances,and electron/charge cloud distributions.This study is the first to evaluate the hotkeys of choice anode/cathode architectonics to assemble different LIB-electrode platforms with high-mobility electron/ion flows and high-performance capacity functionalities.Density functional theory calculation revealed that the FRTO@C anode and VST-(i)@C cathode architectonics are a superior choice for the configuration of full-scale LIB built-up models.The integrated FRTO@C//VST-(i)@C full-scale LIB retains a huge discharge capacity(~94.2%),an average Coulombic efficiency of 99.85%after 2000 cycles at 1 C,and a high energy density of 127 Wh kg?1,thereby satisfying scale-up commercial EV requirements.展开更多
Animal models are necessary to investigate the pathogenic features underlying motor neuron degeneration and for therapeutic development in amyotrophic lateral sclerosis(ALS). Measures of model validity allow for a c...Animal models are necessary to investigate the pathogenic features underlying motor neuron degeneration and for therapeutic development in amyotrophic lateral sclerosis(ALS). Measures of model validity allow for a critical interpretation of results from each model and caution from over-interpretation of experimental models. Face and construct validity refer to the similarity in phenotype and the proposed causal factor to the human disease, respectively. More recently developed models are restricted by limited phenotype characterization, yet new models hold promise for novel disease insights, thus highlighting their importance. In this article, we evaluate the features of face and construct validity of our new zebrafish model of environmentally-induced motor neuron degeneration and discuss this in the context of current environmental and genetic ALS models, including C9 orf72, mutant Cu/Zn superoxide dismutase 1 and TAR DNA-binding protein 43 mouse and zebrafish models. In this mini-review, we discuss the pros and cons to validity criteria in each model. Our zebrafish model of environmentally-induced motor neuron degeneration displays convincing features of face validity with many hallmarks of ALS-like features, and weakness in construct validity. However, the value of this model may lie in its potential to be more representative of the pathogenic features underlying sporadic ALS cases, where environmental factors may be more likely to be involved in disease etiology than single dominant gene mutations. It may be necessary to compare findings between different strains and species modeling specific genes or environmental factors to confirm findings from ALS animal models and tease out arbitrary strain-and overexpression-specific effects.展开更多
Parkinson's disease,the most common movement disorder,has a strong neuroinflammatory aspect.This is evident by increased pro-inflammatory cytokines in the serum,and the presence of activated microglial cells,and i...Parkinson's disease,the most common movement disorder,has a strong neuroinflammatory aspect.This is evident by increased pro-inflammatory cytokines in the serum,and the presence of activated microglial cells,and inflammatory cytokines in the substantia nigra of post-mortem brains as well as cerebrospinal fluid of Parkinson's disease patients.The central and peripheral neuroinflammatory aspects of Parkinson's disease can be investigated in vivo via administration of the inflammagen lipopolysaccharide,a component of the cell wall of gram-negative bacteria.In this mini-review,we will critically evaluate different routes of lipopolysaccharide administration(including intranasal systemic and ste reotasic),their relevance to clinical Parkinson's disease as well as the recent findings in lipopolysaccharide mouse models.We will also share our own expe riences with systemic and intrastriatal lipopolysaccharide models in C57BL/6 mice and will discuss the usefulness of lipopolysaccharide mouse models for future research in the field.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
文摘Taking the Xinhe mine's structure, mine pressure, structural fissure, fault andfault displacement, the distance between fault and water inrush point, thickness of block,water pressure those geological factors which influenced the water inrush as the independentvariable, based on these data of water inrush point and water uninrush point, usingthe method of quantification theory(Ⅰ,Ⅱ), it would quantitatively disposes the qualitativevariable, applied to calculation to evaluate the risk of Xinhe's water inrush.
文摘By using the method of literature review, this paper introduces the popular theoretical models which have shown to better explain physical activity behaviors at a certain degree, summarizes the dominating theoretical models in the studies of physical activity behaviors of the elderly in China. In addition, shortcomings and future prospects are pointed out at the end.
基金Project supported by the National High-Technology Research and Development Program of China (Grant No. 863-2001AA644010)
文摘To solve the disability of conventional model used in electrical leak location when measurement electrodes were buried under the liner, a new model of high voltage DC leak detection is developed. For single-liner landfill, the waste material layer, the geomembrane liner and the soil under the liner are simulated with infinite horizontal layers. The leak is regarded as two parts, one being negative current source at the entrance, and the other positive current source of the same size at the exit. Comparisons between the new theoretical model and conventional model show that conventional model is efficient in locating leaks in geomembane liner associating the dipole scanning above the liner but is ineffective when the measurement electrodes were buried under the liner. The new theoretical model data are in excellent agreement with experimental data not only above the liner but also under the liner.
文摘The properties of nonadiabatic trapping models of the reaction NH+H -N+H, are investigated in a collinear model as \veil as a non-collinear thermal reaction on the basis of theintrinsic reaction coordinate (IRC) intbrmation obtained by ah initio calculations at QCISD/631 IG** ie\el. Using the unitied statistical theory fornonadiabatic trapping models. the thermal rateconstants over the temperature range of 2000-3000K are computed which are in excellent agreementwith the experiment results.
基金The financial support received for this research work from Department of Science and Technology (DST), Government of India, SERB-DST, SR/FTP/ETA0056/2011
文摘Forming limit diagram (FLD) is an important performance index to describe the maximum limit of principal strains that can be sustained by sheet metals till to the onset of localized necking. It offers a convenient and useful tool to predict the forming limit in the sheet metal forming processes. In the present study, FLD has been determined experimentally for Ti?6Al?4V alloy at 400 °C by conducting a Nakazima test with specimens of different widths. Additionally, for theoretical FLD prediction, various anisotropic yield criteria (Barlat 1989, Barlat 1996, Hill 1993) and different hardening models viz., Hollomon power law (HPL), Johnson?Cook (JC), modified Zerilli–Armstrong (m-ZA), modified Arrhenius (m-Arr) models have been developed. Theoretical FLDs have been determined using Marciniak and Kuczynski (M?K) theory incorporating the developed yield criteria and constitutive models. It has been observed that the effect of yield model is more pronounced than the effect of constitutive model for theoretical FLDs prediction. However, the value of thickness imperfection factor (f0) is solely dependent on hardening model. Hill (1993) yield criterion is best suited for FLD prediction in the right hand side region. Moreover, Barlat (1989) yield criterion is best suited for FLD prediction in left hand side region. Therefore, the proposed hybrid FLD in combination with Barlat (1989) and Hill (1993) yield models with m-Arr hardening model is in the best agreement with experimental FLD.
基金Project supported by the National Natural Science Foundation of China (Grant No. 60676053)Applied Material in Xi’an Innovation Funds,China (Grant No. XA-AM-200603)
文摘In order to explore how to extract more transport information from current fluctuation, a theoretical extraction scheme is presented in a single barrier structure based on exclusion models, which include counter-flows model and tunnel model. The first four cumulants of these two exclusion models are computed in a single barrier structure, and their characteristics are obtained. A scheme with the help of the first three cumulants is devised to check a transport process to follow the counter-flows model, the tunnel model or neither of them. Time series generated by Monte Carlo techniques is adopted to validate the abstraction procedure, and the result is reasonable.
基金the financial support provided by the National Natural Science Foundation of China(Grant No.42272310).
文摘Cyclic loads generated by environmental factors,such as winds,waves,and trains,will likely lead to performance degradation in pile foundations,resulting in issues like permanent displacement accumulation and bearing capacity attenuation.This paper presents a semi-analytical solution for predicting the axial cyclic behavior of piles in sands.The solution relies on two enhanced nonlinear load-transfer models considering stress-strain hysteresis and cyclic degradation in the pile-soil interaction.Model parameters are calibrated through cyclic shear tests of the sand-steel interface and laboratory geotechnical testing of sands.A novel aspect involves the meticulous formulation of the shaft loadtransfer function using an interface constitutive model,which inherently inherits the interface model’s advantages,such as capturing hysteresis,hardening,degradation,and particle breakage.The semi-analytical solution is computed numerically using the matrix displacement method,and the calculated values are validated through model tests performed on non-displacement and displacement piles in sands.The results demonstrate that the predicted values show excellent agreement with the measured values for both the static and cyclic responses of piles in sands.The displacement pile response,including factors such as bearing capacity,mobilized shaft resistance,and convergence rate of permanent settlement,exhibit improvements compared to non-displacement piles attributed to the soil squeezing effect.This methodology presents an innovative analytical framework,allowing for integrating cyclic interface models into the theoretical investigation of pile responses.
基金supported in part by the NIH grant R01CA241134supported in part by the NSF grant CMMI-1552764+3 种基金supported in part by the NSF grants DMS-1349724 and DMS-2052465supported in part by the NSF grant CCF-1740761supported in part by the U.S.-Norway Fulbright Foundation and the Research Council of Norway R&D Grant 309273supported in part by the Norwegian Centennial Chair grant and the Doctoral Dissertation Fellowship from the University of Minnesota.
文摘The spread of an advantageous mutation through a population is of fundamental interest in population genetics. While the classical Moran model is formulated for a well-mixed population, it has long been recognized that in real-world applications, the population usually has an explicit spatial structure which can significantly influence the dynamics. In the context of cancer initiation in epithelial tissue, several recent works have analyzed the dynamics of advantageous mutant spread on integer lattices, using the biased voter model from particle systems theory. In this spatial version of the Moran model, individuals first reproduce according to their fitness and then replace a neighboring individual. From a biological standpoint, the opposite dynamics, where individuals first die and are then replaced by a neighboring individual according to its fitness, are equally relevant. Here, we investigate this death-birth analogue of the biased voter model. We construct the process mathematically, derive the associated dual process, establish bounds on the survival probability of a single mutant, and prove that the process has an asymptotic shape. We also briefly discuss alternative birth-death and death-birth dynamics, depending on how the mutant fitness advantage affects the dynamics. We show that birth-death and death-birth formulations of the biased voter model are equivalent when fitness affects the former event of each update of the model, whereas the birth-death model is fundamentally different from the death-birth model when fitness affects the latter event.
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.
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 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.
文摘The inflection point is an important feature of sigmoidal height-diameter(H-D)models.It is often cited as one of the properties favoring sigmoidal model forms.However,there are very few studies analyzing the inflection points of H-D models.The goals of this study were to theoretically and empirically examine the behaviors of inflection points of six common H-D models with a regional dataset.The six models were the Wykoff(WYK),Schumacher(SCH),Curtis(CUR),HossfeldⅣ(HOS),von Bertalanffy-Richards(VBR),and Gompertz(GPZ)models.The models were first fitted in their base forms with tree species as random effects and were then expanded to include functional traits and spatial distribution.The distributions of the estimated inflection points were similar between the two-parameter models WYK,SCH,and CUR,but were different between the threeparameter models HOS,VBR,and GPZ.GPZ produced some of the largest inflection points.HOS and VBR produced concave H-D curves without inflection points for 12.7%and 39.7%of the tree species.Evergreen species or decreasing shade tolerance resulted in larger inflection points.The trends in the estimated inflection points of HOS and VBR were entirely opposite across the landscape.Furthermore,HOS could produce concave H-D curves for portions of the landscape.Based on the studied behaviors,the choice between two-parameter models may not matter.We recommend comparing seve ral three-parameter model forms for consistency in estimated inflection points before deciding on one.Believing sigmoidal models to have inflection points does not necessarily mean that they will produce fitted curves with one.Our study highlights the need to integrate analysis of inflection points into modeling H-D relationships.
基金Project supported by the Innovative Research Foundation of China Academy of Engineering Physics(Grant No.426050502-2)
文摘In this paper, the basic equations of beam-wave interaction for designing the 220 GHz folded waveguide (FW) backward wave oscillator (BWO) are described. On the whole, these equations are mainly classified into small signal model (SSM), large signal model (LSM), and simplified small signal model (SSSM). Using these linear and nonlinear one-dimensional (1D) models, the oscillation characteristics of the FW BWO of a given configuration of slow wave struc- ture (SWS) can be calculated by numerical iteration algorithm, which is more time efficient than three-dimensional (3D) particle-in-cell (PIC) simulation. The SSSM expressed by analytical formulas is innovatively derived for determining the initial values of the FW SWS conveniently. The dispersion characteristics of the FW are obtained by equivalent circuit analysis. The space charge effect, the end reflection effect, the lossy wall effect, and the relativistic effect are all considered in our models to offer more accurate results. The design process of the FW BWO tube with output power of watt scale in a frequency range between 215 GHz and 225 GHz based on these 1D models is demonstrated. The 3D PIC method is adopted to verify the theoretical design results, which shows that they are in good agreement with each other.
文摘Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders,and it is a rapidly growing global public health issue.It is characterized by hyperglycemia,a condition involving a high blood glucose level brought on by deficiencies in insulin secretion,decreased activity of insulin,or both.Prolonged effects of diabetes include cardiovascular problems,retinopathy,neuropathy,nephropathy,and vascular alterations in both macro-and micro-blood vessels.In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis,identifying targets,and reviewing novel treatment options and medications.Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences.The most popular in vivo studies involves the small animal models,such as rodent models,chemically induced diabetogens like streptozotocin and alloxan,and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals.Other models include virally induced models,diet/nutrition induced diabetic animals,surgically induced models or pancreatectomy models,and non-obese models.Large animals or non-rodent models like porcine(pig),canine(dog),nonhuman primate,and Zebrafish models are also outlined.The in vitro models discussed are murine and human beta-cell lines and pancreatic islets,human stem cells,and organoid cultures.The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition ofα-glucosidase activity.
文摘With the continuous evolution and expanding applications of Large Language Models (LLMs), there has been a noticeable surge in the size of the emerging models. It is not solely the growth in model size, primarily measured by the number of parameters, but also the subsequent escalation in computational demands, hardware and software prerequisites for training, all culminating in a substantial financial investment as well. In this paper, we present novel techniques like supervision, parallelization, and scoring functions to get better results out of chains of smaller language models, rather than relying solely on scaling up model size. Firstly, we propose an approach to quantify the performance of a Smaller Language Models (SLM) by introducing a corresponding supervisor model that incrementally corrects the encountered errors. Secondly, we propose an approach to utilize two smaller language models (in a network) performing the same task and retrieving the best relevant output from the two, ensuring peak performance for a specific task. Experimental evaluations establish the quantitative accuracy improvements on financial reasoning and arithmetic calculation tasks from utilizing techniques like supervisor models (in a network of model scenario), threshold scoring and parallel processing over a baseline study.
文摘To control the power hierarchy design of lithium-ion battery(LIB)builtup sets for electric vehicles(EVs),we offer intensive theoretical and experimental sets of choice anode/cathode architectonics that can be modulated in full-scale LIB built-up models.As primary structural tectonics,heterogeneous composite superstructures of full-cell-LIB(anode//cathode)electrodes were designed in closely packed flower agave rosettes TiO2@C(FRTO@C anode)and vertical-star-tower LiFePO4@C(VST@C cathode)building blocks to regulate the electron/ion movement in the three-dimensional axes and orientation pathways.The superpower hierarchy surfaces and multi-directional orientation components may create isosurface potential electrodes with mobile electron movements,in-to-out interplay electron dominances,and electron/charge cloud distributions.This study is the first to evaluate the hotkeys of choice anode/cathode architectonics to assemble different LIB-electrode platforms with high-mobility electron/ion flows and high-performance capacity functionalities.Density functional theory calculation revealed that the FRTO@C anode and VST-(i)@C cathode architectonics are a superior choice for the configuration of full-scale LIB built-up models.The integrated FRTO@C//VST-(i)@C full-scale LIB retains a huge discharge capacity(~94.2%),an average Coulombic efficiency of 99.85%after 2000 cycles at 1 C,and a high energy density of 127 Wh kg?1,thereby satisfying scale-up commercial EV requirements.
基金supported by a grant from Estate of Luther Allyn Shourds Dean,No.20R17162(to CAS)
文摘Animal models are necessary to investigate the pathogenic features underlying motor neuron degeneration and for therapeutic development in amyotrophic lateral sclerosis(ALS). Measures of model validity allow for a critical interpretation of results from each model and caution from over-interpretation of experimental models. Face and construct validity refer to the similarity in phenotype and the proposed causal factor to the human disease, respectively. More recently developed models are restricted by limited phenotype characterization, yet new models hold promise for novel disease insights, thus highlighting their importance. In this article, we evaluate the features of face and construct validity of our new zebrafish model of environmentally-induced motor neuron degeneration and discuss this in the context of current environmental and genetic ALS models, including C9 orf72, mutant Cu/Zn superoxide dismutase 1 and TAR DNA-binding protein 43 mouse and zebrafish models. In this mini-review, we discuss the pros and cons to validity criteria in each model. Our zebrafish model of environmentally-induced motor neuron degeneration displays convincing features of face validity with many hallmarks of ALS-like features, and weakness in construct validity. However, the value of this model may lie in its potential to be more representative of the pathogenic features underlying sporadic ALS cases, where environmental factors may be more likely to be involved in disease etiology than single dominant gene mutations. It may be necessary to compare findings between different strains and species modeling specific genes or environmental factors to confirm findings from ALS animal models and tease out arbitrary strain-and overexpression-specific effects.
文摘Parkinson's disease,the most common movement disorder,has a strong neuroinflammatory aspect.This is evident by increased pro-inflammatory cytokines in the serum,and the presence of activated microglial cells,and inflammatory cytokines in the substantia nigra of post-mortem brains as well as cerebrospinal fluid of Parkinson's disease patients.The central and peripheral neuroinflammatory aspects of Parkinson's disease can be investigated in vivo via administration of the inflammagen lipopolysaccharide,a component of the cell wall of gram-negative bacteria.In this mini-review,we will critically evaluate different routes of lipopolysaccharide administration(including intranasal systemic and ste reotasic),their relevance to clinical Parkinson's disease as well as the recent findings in lipopolysaccharide mouse models.We will also share our own expe riences with systemic and intrastriatal lipopolysaccharide models in C57BL/6 mice and will discuss the usefulness of lipopolysaccharide mouse models for future research in the field.
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.