The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

Efficient Clustering Network Based on Matrix Factorization

Contrastive learning is a significant research direction in the field of deep learning.However,existing data augmentation methods often lead to issues such as semantic drift in generated views while the complexity of model pre-training limits further improvement in the performance of existing methods.To address these challenges,we propose the Efficient Clustering Network based on Matrix Factorization(ECN-MF).Specifically,we design a batched low-rank Singular Value Decomposition(SVD)algorithm for data augmentation to eliminate redundant information and uncover major patterns of variation and key information in the data.Additionally,we design a Mutual Information-Enhanced Clustering Module(MI-ECM)to accelerate the training process by leveraging a simple architecture to bring samples from the same cluster closer while pushing samples from other clusters apart.Extensive experiments on six datasets demonstrate that ECN-MF exhibits more effective performance compared to state-of-the-art algorithms.

Characteristics and demographic factors of traditional Chinese medicine constitution types among elderly individuals in China:A national multistage cluster random study Author links open overlay panel

Objective:To reveal the distribution characteristics and demographic factors of traditional Chinese medicine(TCM)constitution among elderly individuals in China.Methods: Elderly individuals from seven regions in China were selected as samples in this study using a multistage cluster random sampling method.The basic information questionnaire and Constitution in Chinese Medicine Questionnaire(Elderly Edition)were used.Descriptive statistical analysis,chi-squared tests,and binary logistic regression analysis were used.Results: The single balanced constitution(BC)accounted for 23.9%.The results of the major TCM constitution types showed that BC(43.2%)accounted for the largest proportion and unbalanced constitutions ranged from 0.9%to 15.7%.East China region(odds ratio[OR]=2.097;95%confidence interval[CI],1.912 to 2.301),married status(OR=1.341;95%CI,1.235 to 1.457),and managers(OR=1.254;95%CI,1.044 to 1.505)were significantly associated with BC.Age>70 years was associated with qi-deficiency constitution and blood stasis constitution(BSC).Female sex was significantly associated with yang-deficiency constitution(OR=1.646;95%CI,1.52 to 1.782).Southwest region was significantly associated with phlegm-dampness constitution(OR=1.809;95%CI,1.569 to 2.086).North China region was significantly associated with inherited special constitution(OR=2.521;95%CI,1.569 to 4.05).South China region(OR=2.741;95%CI,1.997 to 1.3.763),Central China region(OR=8.889;95%CI,6.676 to 11.835),senior middle school education(OR=2.442;95%CI,1.932 to 3.088),and managers(OR=1.804;95%CI,1.21 to 2.69)were significantly associated with BSC.Conclusions: This study defined the distribution characteristics and demographic factors of TCM constitution in the elderly population.Adjusting and improving unbalanced constitutions,which are correlated with diseases,can help promote healthy aging through the scientific management of these demographic factors.

IMPACTS ON THE EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN ISCHEMIC BRAIN TISSUE TREATED WITH CLUSTER PUNC-TURE ON SCALP ACUPOINTS IN RATS

Objective To probe into the impacts on the expression of vascular endothelial growth factor （VEGF） in ischemic brain tissue treated with cluster puncture on scalp acupoints in rats, Methods 128 rats were randomized into pseudo-operation group, model group, scalp-needling group and cluster-needling group, In scalp-needling group, penetration method was used on the focal side from Bǎihuì （百会 GV20） to Qǔbīn （曲鬓 GB7）, and in cluster-needling group, penetration method was used on both sides from GV20 to GB7, and a common needling on GV 20. Needles were punctured 2 mm in depth, constantly rotated for 10min, retained for 2 h. Immunohistrochemical method was applied to determine VEGF expression and microvessel density （MVD）. Results With the intervention of cluster puncture on scalp acupoints, VEGF： expressions on every time-spot after ischemia were enhanced apparently, superior to those in scalp-needling group. On the three time-spots of the 7^th, 14^th and 21^st days, MVD was increased after cluster puncture on scale acupoints, superior to those in scalp-needling group. Conclusion Cluster puncture on scalp acupoints up-regulated VEGF expression and promoted regeneration of microvessel.

Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.

Interplay between microglia and environmental risk factors in Alzheimer's disease

Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.

Health risk assessment of trace metal(loid)s in agricultural soils based on Monte Carlo simulation coupled with positive matrix factorization model in Chongqing, southwest China

This study aimed to investigate the pollution characteristics, source apportionment, and health risks associated with trace metal(loid)s(TMs) in the major agricultural producing areas in Chongqing, China. We analyzed the source apportionment and assessed the health risk of TMs in agricultural soils by using positive matrix factorization(PMF) model and health risk assessment(HRA) model based on Monte Carlo simulation. Meanwhile, we combined PMF and HRA models to explore the health risks of TMs in agricultural soils by different pollution sources to determine the priority control factors. Results showed that the average contents of cadmium(Cd), arsenic (As), lead(Pb), chromium(Cr), copper(Cu), nickel(Ni), and zinc(Zn) in the soil were found to be 0.26, 5.93, 27.14, 61.32, 23.81, 32.45, and 78.65 mg/kg, respectively. Spatial analysis and source apportionment analysis revealed that urban and industrial sources, agricultural sources, and natural sources accounted for 33.0%, 27.7%, and 39.3% of TM accumulation in the soil, respectively. In the HRA model based on Monte Carlo simulation, noncarcinogenic risks were deemed negligible(hazard index <1), the carcinogenic risks were at acceptable level(10^(-6)<total carcinogenic risk ≤ 10^(-4)), with higher risks observed for children compared to adults. The relationship between TMs, their sources, and health risks indicated that urban and industrial sources were primarily associated with As, contributing to 75.1% of carcinogenic risks and 55.7% of non-carcinogenic risks, making them the primary control factors. Meanwhile, agricultural sources were primarily linked to Cd and Pb, contributing to 13.1% of carcinogenic risks and 21.8% of non-carcinogenic risks, designating them as secondary control factors.

Prevalence and Risk Factors of Stroke in Inpatients with Type 2 Diabetes Mellitus in China

Objective The prevalence and the cluster characteristics of risk factors of stroke were assessed in a Chinese diabetic population.Methods Clinical data of 30693 inpatients who were diagnosed with type 2 diabetes mellitus(T2DM)and admitted between 2013 and 2018 were retrospectively analyzed.The age-standardized prevalence of stroke was estimated using the 2010 Chinese population census data,and risk factors were analyzed by multiple imputation and regression.Results The crude and standardized prevalence rates of stroke in patients with T2DM were 34.4%and 21.5%,respectively,and 85.2%of the stroke patients had ischemic stroke.Nearly half of the patients who experienced stroke had clusters of more than 4 risk factors.Compared with no-risk-factor clustering,the risk of stroke significantly increased 3-4 times in the presence of more than 4 risk-factor clusters(P<0.001).Hypertension was the most common major risk factor for ischemic stroke[odds ratio(OR),2.34;95%confidence interval(CI),2.18-2.50]and hemorrhagic stroke(OR,3.68;95%CI 2.95-4.59;P<0.001).Moreover,a 1-standard-deviation increase in fasting blood glucose(FBG)was significantly negatively correlated with ischemic stroke risk,and the same change in FBG was significantly associated with an 8%increased risk of hemorrhagic stroke.Conclusion The prevalence of stroke in patients with T2DM is rather high,and the clustering of risk factors is associated with the development of stroke in T2DM patients.Risk factors differ in different stroke subtypes.Identifying risk factors for a specific high-risk group is necessary.

Heat-inducible SlWRKY3 confers thermotolerance by activating the SlGRXS1 gene cluster in tomato

High temperature stress is one of the major environmental factors that affect the growth and development of plants. Although WRKY transcription factors play a critical role in stress responses, there are few studies on the regulation of heat stress by WRKY transcription factors,especially in tomato. Here, we identified a group I WRKY transcription factor, SlWRKY3, involved in thermotolerance in tomato. First, SlWRKY3 was induced and upregulated under heat stress. Accordingly, overexpression of SlWRKY3 led to an increase, whereas knock-out of SlWRKY3 resulted in decreased tolerance to heat stress. Overexpression of SlWRKY3 accumulated less reactive oxygen species(ROS), whereas knock-out of SlWRKY3 accumulated more ROS under heat stress. This indicated that SlWRKY3 positively regulates heat stress in tomato. In addition,SlWRKY3 activated the expression of a range of abiotic stress-responsive genes involved in ROS scavenging, such as a SlGRXS1 gene cluster.Further analysis showed that SlWRKY3 can bind to the promoters of the SlGRXS1 gene cluster and activate their expression. Collectively, these results imply that SlWRKY3 is a positive regulator of thermotolerance through direct binding to the promoters of the SlGRXS1 gene cluster and activating their expression and ROS scavenging.

Examining the Use of Scott’s Formula and Link Expiration Time Metric for Vehicular Clustering

Implementing machine learning algorithms in the non-conducive environment of the vehicular network requires some adaptations due to the high computational complexity of these algorithms.K-clustering algorithms are simplistic,with fast performance and relative accuracy.However,their implementation depends on the initial selection of clusters number(K),the initial clusters’centers,and the clustering metric.This paper investigated using Scott’s histogram formula to estimate the K number and the Link Expiration Time(LET)as a clustering metric.Realistic traffic flows were considered for three maps,namely Highway,Traffic Light junction,and Roundabout junction,to study the effect of road layout on estimating the K number.A fast version of the PAM algorithm was used for clustering with a modification to reduce time complexity.The Affinity propagation algorithm sets the baseline for the estimated K number,and the Medoid Silhouette method is used to quantify the clustering.OMNET++,Veins,and SUMO were used to simulate the traffic,while the related algorithms were implemented in Python.The Scott’s formula estimation of the K number only matched the baseline when the road layout was simple.Moreover,the clustering algorithm required one iteration on average to converge when used with LET.

Evaluation and classification of residential greenbelt quality based on factor analysis & clustering analysis:An example of Xinxiang City,China

Five factors expressing greenbelt quality and one factor expressing quantity were adopted for evaluation of the residential greenbelt, and the AHP （Analytical Hierarchy Process） method was used to determine the value of factors. Thirty residential areas were selected as the samples. Two principal components were extracted and their expression was constructed by method of factor anlysis, therefore, quality evaluation of residential greenbelt was obtained. The accuracy of the function and implement quality classification toward the residential greenbelts in Xinxiang City were validated by clustering analysis method. The results showed that the greenbelt quality of fourteen residential areas was higher than the average level, of which eleven were newly-built residential areas. The 30 residential areas were classified into three types according to their greenbelt features and their formation by clustering analysis method. Finally rational proposal basing on aforesaid evaluating results was proposed for construction and renewal of residential greenbelt, upon which directive basis was provided for construction and renewal of residential greenbelt.

Exercise and exerkine upregulation:Brain-derived neurotrophic factor as a potential non-pharmacological therapeutic strategy for Parkinson’s disease

Physical activity and exercise have several beneficial roles in enhancing both physiological and psychological well-being of an individual.In addition to aiding the regulation of aerobic and anaerobic metabolism,exercise can stimulate the synthesis of exerkine hormones in the circulatory system.Among several exerkines that have been investigated for their therapeutic potential,Brain-derived neurotrophic factor(BDNF)is considered the most promising candidate,especially in the management of neurodegenerative diseases.Owing to the ability of physical activity to enhance BDNF synthesis,several experimental studies conducted so far have validated this hypothesis and produced satisfactory results at the pre-clinical level.This review highlights some of the recent animal model studies that have evaluated the efficiency of exercise in enhancing BDNF synthesis and promoting neuroprotective effects.Further,this review focuses on understanding the therapeutic benefits of exercise-induced exerkine synthesis as a non-pharmacological strategy in Parkinson’s disease(PD).Regarding physical activity and exerkine induction,the neuromuscular electrical stimulation(NMES)strategy could be considered as an alternate treatment modality for patients affected with PD.

Prevalence and risk factors of depression among patients with perianal fistulizing Crohn’s disease

BACKGROUND Psychological distress,especially depression,associated with perianal fistulizing Crohn’s disease(PFCD)is widespread and refractory.However,there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.AIM To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.METHODS The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff.Depressive symptoms,life quality,and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9,Inflammatory Bowel Disease Patient Quality of Life Questionnaire(IBDQ),and Inflammatory Bowel Disease(IBD)Fatigue Patient Self-assessment Scale.The basic demographic information,overall disease features,perianal clinical information,and laboratory inflammation indicators were also gathered.Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.RESULTS A total of 123 patients with PFCD were involved,and 56.91%were suffering from depression.According to multivariate logistic regression analysis,Perianal Disease Activity Index(PDAI)score[odds ratio(OR)=0.69,95%confidence interval(CI):0.50 to 0.95],IBDQ score(OR=0.93,95%CI:0.88 to 0.97),modified Van Assche index(OR=1.24,95%CI:1.01 to 1.53),and IBD Fatigue score(OR=1.72,95%CI:1.23 to 2.42)were independent risk factors of depression-related prevalence among patients with PFCD(P<0.05).Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index(βvalue=0.166,95%CI:0.02 to 0.31)and decreasing IBDQ score(βvalue=-0.116,95%CI:-0.14 to-0.09)were independently associated with the severity of depression(P<0.05).CONCLUSION Depressive symptoms in PFCD patients have significantly high prevalence.PDAI score,modified Van Assche index,quality of life,and fatigue severity were the main independent risk factors.

Epidemiological Aspects of Obesity, Overweight and Cardiovascular Risk Factors at Associes in Semi-Urban Areas (Case of Sébikotane)

Introduction: Obesity and overweight are a public health problem. The general objective was to determine the epidemiological aspects of obesity, overweight and associated risk factors in a semi-urban environment. Patients and Methods: This was a cross-sectional, descriptive study conducted on November 28 and 29, 2023 in Sébikotane. It focused on volunteers for screening for chronic non-communicable diseases. Epidemiological and clinical data were evaluated. Results: One hundred and twenty-nine cases of obesity were recorded (28%). Two hundred and eighty-two cases were overweight or obese (61.3%). The mean age was 49.55 years, with a standard deviation of 12.41 years. The age group [40 - 49 years] was the most representative, with 85 cases (30.1%), and the majority were female, with 264 cases (93.6%). Primary education was the most common, with 75 cases (46.3%). Grade 1 obesity concerned ninety-seven cases (75.2%), and diabetes was present in thirty cases (23%). Hypertension was present in ninety-five cases (33.7%). Obesity was more marked in the age group [40 - 49 years] with 45 cases (36%). Conclusion: Obesity and overweight are a major cause of morbidity and mortality. The development and implementation of a prevention and management program is essential.

Surgical and non-surgical risk factors affecting the insufficiency of ileocolic anastomosis after first-time surgery in Crohn’s disease patients

BACKGROUND Crohn's disease(CD)often necessitates surgical intervention,particularly when it manifests in the terminal ileum and ileocecal valve.Despite undergoing radical surgery,a subset of patients experiences recurrent inflammation at the anasto-motic site,necessitating further medical attention.AIM To investigate the risk factors associated with anastomotic insufficiency following ileocecal resection in CD patients.METHODS This study enrolled 77 patients who underwent open ileocolic resection with pri-mary stapled anastomosis.Patients were stratified into two groups:Group I co-mprised individuals without anastomotic insufficiency,while Group II included patients exhibiting advanced anastomotic destruction observed endoscopically or those requiring additional surgery during the follow-up period.Surgical and non-surgical factors potentially influencing anastomotic failure were evaluated in both cohorts.RESULTS Anastomotic insufficiency was detected in 12 patients(15.6%),with a mean time interval of 30 months between the initial surgery and recurrence.The predomi-nant reasons for re-intervention included stenosis and excessive perianastomotic lesions.Factors associated with a heightened risk of anastomotic failure encompassed prolonged postoperative obstruction,anastomotic bleeding,and clinically confirmed micro-leakage.Additionally,patients in Group II exhibited preoperative malnutrition and early recurrence of symptoms related to CD.CONCLUSION Successful surgical outcomes hinge on the attainment of a fully functional anastomosis,optimal metabolic status,and clinical remission of the underlying disease.Vigilant endoscopic surveillance following primary resection facilitates the timely identification of anastomotic failure,thereby enabling noninvasive interventions.

Influencing factors and preventive measures of infectious complications after intestinal resection for Crohn’s disease

The incidence of Crohn’s disease(CD)has increased in recent years,with most patients requiring intestinal resection.Complications after intestinal resection for CD can lead to poor prognosis and recurrence,among which infectious complic-ations are the most common.This study aimed to investigate the common risk factors,including medications,preoperative nutritional status,surgery-related factors,microorganisms,lesion location and type,and so forth,causing infectious complications after intestinal resection for CD,and to propose corresponding preventive measures.The findings provided guidance for identifying suscept-ibility factors and the early intervention and prevention of infectious complic-ations after intestinal resection for CD in clinical practice.

Research on Competitiveness of County Economy Based on Factor Analysis and Cluster Analysis——Taking 88 Counties in Guizhou as Samples

17 indices are selected,such as the growth rate of total regional output value,the proportion of tertiary industry in GDP,per capita financial expenditure,and soil erosion rate of Guizhou Province in 2009.According to the relevant indices data of statistical yearbook and governmental website,by using the method of factor analysis and the method of cluster analysis,we assess the competitiveness of county economy in 88 counties of Guizhou Province.The results show that the competitiveness of county economy in Guizhou Province is impacted by factors of location and economic foundation.In addition,the resources environment,economic structure,economic developmental speed and other factors also impact the competitiveness of county economy in Guizhou Province.Based on these,in the light of the developmental characteristics of different counties in conjunction with different developmental advantages in different regions,we should adopt different developmental strategies according to local conditions,which is significant to rapid,healthy and sustainable development of county economy in Guizhou Province.

Analysis of the Current Situation, Influential Factors, and Countermeasures of Rural E-commerce Development

The development of rural e-commerce is becoming an important driver for the transformation of China’s rural economy,and with the rapid development of information technology and the upgrading of the agricultural industry,rural e-commerce is showing a vigorous momentum of development.Traditionally,agricultural products are mainly sold through traditional farmers’markets,which are subjected to geography and channel limitations,resulting in inefficient circulation of agricultural products.This paper analyzes the definition,the status quo,as well as the influencing factors of rural e-commerce development.On this basis,countermeasures for the advancement of rural e-commerce development are put forward.

The Heterogeneity and Its Influencing Factors of Soil Nutrients in Peak-Cluster Depression Areas of Karst Region

By selecting a typical peak-cluster depression area of karst region in Southwest China, we evaluated the effect of land use types and topographic factors on soil nutrients. Grid and line sampling methods were used to sample soil in depression and slope lands respectively, and classical statistical tools were applied to analyze the spatial variability character of soil organic carbon （SOC）, total nitrogen （TN）, total phosphorus （TP）, total potassium （TK）, available nitrogen （AN）, available phosphorus （AP）, available potassium （AK）, pH, and C/N. It was found that land use type was the dominant factor that effected the spatial heterogeneity of SOC, TN, TP, TK, AN, and AP. The content of SOC, TN, and AN decreased with the increase of land use intensity. Due to high fertilizer input, TP and AP in tillage fields were higher than those in the other land use types. TK had no obvious change trend among various land use types. Topographic factors had a significant effect on SOC, TN, TP, AN, AP, AK, and pH. Habitat factor was the dominant factor that effected AK. Altitude factor was the dominant factor for pH. However, all of these factors had no significant effect on C/N. Tillage practice had important effect on soil nutrients loss and soil degradation in the fragile karst ecosystem, and the input of organic manure should be increased in this region.

Factor and Cluster Analysis on the Competitiveness of Agri-food Processing Industry in China

This paper establishes 13 evaluation indicators for the competitiveness of agri-food processing industry,uses factor analysis to evaluate the competitiveness of agri-food processing industry in 31 provinces(cities,autonomous regions)of China,and does cluster analysis to divide these regions into several categories according to the difference in competitiveness,in order to understand the level of competitiveness of agri-food processing industry in China.