Dynamics of Advantageous Mutant Spread in Spatial Death-Birth and Birth-Death Moran Models

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.

Evolution and Prospects of Foundation Models: From Large Language Models to Large Multimodal Models

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.

The relationship between compartment models and their stochastic counterparts:A comparative study with examples of the COVID-19 epidemic modeling

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.

Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

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.

Exploiting fly models to investigate rare human neurological disorders

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.

Clinical Effect Observation of Constructing PERMA Model in Psychological Intervention for Patients with Chronic Cancer Pain

Background:The constructing PERMA model in psychological intervention was applied to patients with chronic cancer pain to provide data reference for reducing pain,fear of cancer recurrence,and improving the level of psychological capital.Aim:To explore the clinical effects of constructing PERMA model in psychological intervention for patients with chronic cancer pain.Methods:A total of 98 patients with chronic cancer pain admitted to our hospital from March 2021 to March 2023 were randomly divided into two groups,49 cases in each group.The control group received routine intervention,while the research group constructed PERMA model based on the routine intervention for psychological intervention.The pain severity,fear of cancer recurrence,psychological capital and quality of life before and after intervention were compared between the two groups.Results:After two months of intervention,the pain in the research group was milder than that in the control group(p<0.05).The scores and total scores of all dimensions of fear of cancer recurrence in the research group were lower than those in the control group(p<0.05).The scores and total scores of each dimension of psychological capital in the research group were higher than those in the control group(p<0.05).The scores of all dimensions of quality of life in the research group were higher than those in the control group(p<0.05).Conclusion:The PERMA model constructed in psychological interventions for patients with chronic cancer pain can assist analgesic medications to reduce pain and alleviate the fear of cancer recurrence,increase the level of psychological capital,and thus improve quality of life.

Effects of psychological intervention on negative emotions and psychological resilience in breast cancer patients after radical mastectomy

Breast cancer(BC)is the most common malignant tumor in women,and the treatment process not only results in physical pain but also significant psychological distress in patients.Psychological intervention(PI)has been recognized as an important approach in treating postoperative psychological disorders in BC patients.It has been proven that PI has a significant therapeutic effect on postoperative psychological disorders,improving patients'negative emotions,enhancing their psychological resilience,and effectively enhancing their quality of life and treatment compliance.

Effects of intensive psychological intervention on treatment compliance,psychological status,and quality of life of patients with epilepsy

BACKGROUND Epilepsy is a nervous system disease characterized by recurrent attacks,a long disease course,and an unfavorable prognosis.It is associated with an enduring therapeutic process,and finding a cure has been difficult.Patients with epilepsy are predisposed to adverse moods,such as resistance,anxiety,nervousness,and anxiety,which compromise treatment compliance and overall efficacy.AIM To explored the influence of intensive psychological intervention on treatment compliance,psychological status,and quality of life(QOL)of patients with epilepsy.METHODS The clinical data of 105 patients with epilepsy admitted between December 2019 and July 2023 were retrospectively analyzed,including those of 50 patients who underwent routine intervention(control group)and 55 who underwent intensive psychological intervention(research group).Treatment compliance,psychological status based on the Self-Rating Anxiety Scale(SAS)and Depression Scale Self-Rating Depression Scale(SDS)scores,hope level assessed using the Herth Hope Scale(HHS),psychological resilience evaluated using the Psychological Resilience Scale,and QOL determined using the QOL in Epilepsy-31 Inventory(QOLIE-31)were comparatively analyzed.RESULTS Treatment compliance in the research group was 85.5%,which is significantly better than the 68.0%of the control group.No notable intergroup differences in preinterventional SAS and SDS scores were identified(P>0.05);however,after the intervention,the SAS and SDS scores decreased significantly in the two groups,especially in the research group(P<0.05).The two groups also exhibited no significant differences in preinterventional HHS,Connor-Davidson Resilience Scale(CD-RISC),and QOLIE-31 scores(P>0.05).After 6 months of intervention,the research group showed evidently higher HHS,CD-RISC,tenacity,optimism,strength,and QOLIE-31 scores(P<0.05).CONCLUSION Intensive psychological intervention enhances treatment compliance,psychological status,and QOL of patients with epilepsy.

Progress of systematic psychological interventions in elderly patients with femoral fractures:A comprehensive review

This review aims to gain a deeper understanding of the psychological state of elderly patients with femoral fractures and provide more theoretical and practical support for clinical treatment and care.Through a literature analysis,we found that elderly patients with femoral fractures face various psychological issues such as anxiety,depression,sleep disorders,and social isolation.The application of systematic nursing interventions in clinical practice,including cognitivebehavioral therapy,mindfulness therapy,family therapy,art therapy,interpersonal therapy,emotion-focused therapy,and relaxation training,has yielded significant results.Systematic psychological interventions can improve the psychological state and quality of life of elderly patients with femoral fractures.Therefore,promoting the application and practice of systematic psychological interventions in the clinical care of elderly patients with fractures will provide more effective psychological services to a wider group of patients with fractures in the future.

Application of psychological intervention in intensive care unit nursing for patients with severe acute pancreatitis

BACKGROUND Severe acute pancreatitis(SAP)is a familiar critical disease in the intensive care unit(ICU)patients.Nursing staff are important spiritual pillars during the treatment of patients,and in addition to routine nursing,more attention needs be paid to the patient’s psychological changes.AIM To investigate the effects of psychological intervention in ICU patients with SAP.METHODS One hundred ICU patients with SAP were hospitalized in the authors’hospital between 2020 and 2023 were selected,and divided into observation and control groups per the hospitalization order.The control and observation groups received routine nursing and psychological interventions,respectively.Two groups are being compared,using the Self-rating Anxiety Scale(SAS),Self-Determination Scale(SDS),Acute Physiology and Chronic Health Evaluation(APACHE)Ⅱ,and 36-item Short Form Health Survey(SF-36)scores;nursing satisfaction of patients;ICU care duration;length of stay;hospitalization expenses;and the incidence of complications.RESULTS After nursing,the SDS,SAS,and APACHEⅡ scores in the experimental group were significantly lower than in the control group(P<0.05).The SF-36 scores in the observation group were significantly higher than those in the control group(P<0.05).The nursing satisfaction of patients in the experimental group was 94.5%,considerably higher than that of 75.6% in the control group(P<0.05).The ICU care duration,length of stay,and hospitalization expenses in the observation group were significantly lower than those in the control group,and the incidence of complications was lower(P<0.05).CONCLUSION For patients with SAP,the implementation of standardized psychological intervention measures can effectively alleviate adverse psychological conditions.

Analysis of the inflection points of height-diameter models

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.

Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs

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.

The Relationship Between Social Isolation, Psychological Resilience, and Psychological Well- Being Among Older People in the Community

Objective:To explore the relationship between social isolation,psychological resilience,and psychological well-being in community-dwelling older adults.Methods:A questionnaire survey was conducted with 265 community-dwelling older adults using the Social Isolation Scale for the Elderly(C-SIS),the 10-item Brief Psychological Resilience Scale,and the Comprehensive Happiness Questionnaire(MHQ).The results were statistically analyzed using SPSS 27.0.Results:The highest score on the Social Isolation Scale for Community Elderly was 23,with a mean entry score of 2.36±0.62.A score of 14 was the cut-off point,with scores of≤14 classified as social isolation.There were 136 cases with scores below 14,resulting in a social isolation incidence rate of 51.3%.The median(P50)psychological resilience score was 27,indicating a higher level of resilience.The total score on the Psychological Well-being Scale was 161,suggesting a moderate to slightly higher level of well-being.Social isolation had a direct negative effect on psychological well-being,while psychological resilience had a positive effect.Conclusion:Older adults should be supported in reducing the incidence of social isolation and increasing psychological resilience to enhance psychological well-being and promote successful aging.

Smaller & Smarter: Score-Driven Network Chaining of Smaller Language Models

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.

Research on the Status Quo of Psychological Crisis Among College Students in Ethnic Areas

The article discusses the significance of the research,and outlines the concepts of psychological crisis,its intervention,and psychological crisis among college students,as well as relevant theories on psychological crisis.The research mainly adopts case study and interview methods.Through scientific analysis of psychological crisis cases in four grades of X College in ethnic regions,it summarizes the current situation of crisis psychology among X College students,hoping to provide some first-hand data and research ideas for relevant researchers.

Animal models of amyotrophic lateral sclerosis： a comparison of model validity

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.

Psychological interventions for depression in children and adolescents:A bibliometric analysis

BACKGROUND Depression has gradually become a common psychological disorder among children and adolescents.Depression in children and adolescents affects their physical and mental development.Psychotherapy is considered to be one of the main treatment options for depressed children and adolescents.However,our understanding of the global performance and progress of psychological interventions for depression in children and adolescents(PIDCA)research is limited.AIM To identify collaborative research networks in this field and explore the current research status and hotspots through bibliometrics.METHODS Articles and reviews related to PIDCA from January 2010 to April 2023 were identified from the Web of Science Core Collection database.The Charticulator website,CiteSpace and VOSviewer software were used to visualize the trends in publications and citations,the collaborative research networks(countries,institutions,and authors),and the current research status and hotspots.RESULTS Until April 16,2023,1482 publications were identified.The number of documents published each year and citations had increased rapidly in this field.The United States had the highest productivity in this field.The most prolific institution was the University of London.Pim Cuijpers was the most prolific author.In the context of research related to PIDCA,both reference co-citation analysis and keywords co-occurrence analysis identified 10 research hotspots,including thirdwave cognitive behavior therapy,short-term psychoanalytic psychotherapy,cognitive behavioral analysis system of psychotherapy,family element in psychotherapy,modular treatment,mobile-health,emotion-regulation-based transdiagnostic intervention program,dementia risk in later life,predictors of the efficacy of psychological intervention,and risks of psychological intervention.CONCLUSION This bibliometric study provides a comprehensive overview of PIDCA from 2010 to present.Psychological intervention characterized as psychological-process-focused,short,family-involved,modular,internet-based,emotionregulation-based,and personalized may benefit more young people.

Association between Meeting 24-Hour Movement Guidelines and Psychological Features of Chinese Emerging Adults

Background:Emerging adulthood is a pivotal life stage,presenting significant psychological and social changes,such as decreased sociability,depression,and other mental health problems.Previous studies have associated these changes with an unhealthy lifestyle.The 24-h movement guidelines for healthy lifestyles have been developed to promote appropriate health behaviors and improve individual wellness.However,the relationship between adherence to the 24-h movement guidelines and different characteristics of Chinese emerging adults is yet to be explored.This cross-sectional study aimed to investigate the association between adherence to the 24-h movement guidelines and four characteristics(self-exploration,instability,possibilities,and responsibility)of Chinese emerging adults.Methods:Overall,1,510 Chinese emerging adults aged 18–29 years were included in this study.Each participant completed a self-administered questionnaire that included questions on adherence to the 24-h movement guidelines(physical activity,sedentary behavior,and sleep)and the inventory of dimensions of emerging adulthood.Multivariable logistic regression analysis was employed to investigate the associations between adherence to the 24-h movement guidelines and each of the four characteristics.Results:The proportion of participants who adhered to the 24-h movement guidelines was 31.72%.Multiple regression analysis revealed a significantly negative relationship between adhering to more guidelines and instability(β=−0.51,p<0.001).A statistically significant association was observed between instability and meeting only sedentary behavior(β=−1.27,95%confidence interval[CI]:[−2.32,−0.24],p=0.02),sedentary behavior+sleep(β=−1.30,95%CI:[−2.24,−0.35],p<0.01),and physical activity+sedentary behavior(β=−1.08,95%CI:[1.94,−0.21],p=0.02)guidelines.Further,positive and significant associations were observed between possibilities and meeting the guidelines for only physical activity(β=0.70,95%CI:[0.14,1.27),p=0.01),only sleep(β=0.61,95%CI:[0.01,1.21],p=0.04),physical activity+sedentary behavior(β=0.56,95%CI:[0.04,1.07),p=0.01),and physical activity+sleep(β=0.76,95%CI:[0.23,1.27],p=0.01).Conclusions:These findings suggest that adherence to the 24-h movement guidelines was associated with instability in Chinese emerging adults.Future studies are warranted to verify our findings to highlight the importance of maintaining a heath lifestyle to promote health in emerging adulthood.

Lipopolysaccharide mouse models for Parkinson's disease research:a critical appraisal

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.

Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

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.