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.

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.

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.

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 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.

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.

Evaluating Partitioning Based Clustering Methods for Extended Non-negative Matrix Factorization (NMF)

Data is humongous today because of the extensive use of World WideWeb, Social Media and Intelligent Systems. This data can be very important anduseful if it is harnessed carefully and correctly. Useful information can beextracted from this massive data using the Data Mining process. The informationextracted can be used to make vital decisions in various industries. Clustering is avery popular Data Mining method which divides the data points into differentgroups such that all similar data points form a part of the same group. Clusteringmethods are of various types. Many parameters and indexes exist for the evaluationand comparison of these methods. In this paper, we have compared partitioningbased methods K-Means, Fuzzy C-Means (FCM), Partitioning AroundMedoids (PAM) and Clustering Large Application (CLARA) on secure perturbeddata. Comparison and identification has been done for the method which performsbetter for analyzing the data perturbed using Extended NMF on the basis of thevalues of various indexes like Dunn Index, Silhouette Index, Xie-Beni Indexand Davies-Bouldin Index.

帕金森病患者免疫球蛋白、Th9亚群水平变化及其与IGF-1、S-100B蛋白的相关性

目的:研究帕金森病(PD)患者免疫球蛋白(IgG、IgA和IgM)、辅助性T细胞亚群Th9水平变化及其与胰岛素生长因子-1(IGF-1)、S-100B蛋白的相关性。方法:选取2020年12月至2022年12月期间在河北省中医院确诊的108例PD患者,将其作为研究组,并根据患者病变程度分为轻度组(35例)、中度组(44例)和重度组(29例);另选108例健康成人作为对照组。对比研究组和对照组免疫球蛋白和Th9亚群水平,以及轻度组、中度组及重度组免疫球蛋白、Th9亚群、IGF-1和S-100B蛋白水平,采用Pearson相关性分析免疫球蛋白、Th9亚群和IGF-1、S-100B蛋白的相关性。采用Spearman相关性分析PD患者疾病程度和所有差异指标间的相关性。结果:研究组IgM水平较对照组低,且重度组低于中度组,中度组低于轻度组(P<0.05);研究组IgG、IgA、IL-9和Th9亚群水平较对照组高,且重度组高于中度组,中度组高于轻度组(P<0.05)。重度组IGF-1水平低于中度组,中度组低于轻度组;重度组S-100B蛋白水平高于中度组,中度组高于轻度组(P<0.05)。Pearson相关性分析结果显示,PD患者IgM水平与IGF-1水平呈正相关,与S-100B蛋白水平呈负相关;IgG、IgA、IL-9和Th9亚群水平均与IGF-1水平呈负相关,与S-100B蛋白水平呈正相关(P<0.05)。Spearman相关性分析结果显示,PD患者疾病程度与IgM、IGF-1水平呈负相关,与S-100B蛋白、IgG、IgA、IL-9和Th9亚群水平呈正相关(P<0.05)。结论:PD患者IgM水平降低,IgG、IgA、Th9亚群水平升高,且其水平变化与IGF-1、S-100B明显相关,可以用于评估病情的严重程度。

血清IL-18、CD64及SIRT3对重症肺炎患者多器官功能衰竭的预测价值

目的探讨血清白细胞介素-18(IL-18)、中性粒细胞分化抗原64(CD64)及沉默信息调节因子相关酶3(SIRT3)对重症肺炎患者多器官功能衰竭(MOFE)的预测价值。方法回顾性选取2020年8月至2022年8月新乡医学院第一附属医院收治的300例重症肺炎患者的临床资料,根据有无MOFE发生分为MOFE组90例和非MOFE组210例。比较两组患者的一般资料及血清IL-18、CD64及SIRT3水平,采用Logistic回归分析重症肺炎患者MOFE影响因素;采用受试者工作特征(ROC)曲线评价血清IL-18、CD64及SIRT3水平对重症肺炎患者MOFE发生的预测价值。结果MOFE组患者的年龄、慢阻肺所占比例、CPIS评分、APCHEⅡ评分明显高于非MOFE组,差异均有统计学意义(P<0.05);MOFE组患者的血清IL-18、CD64水平分别为(22.49±5.04)ng/L、(46.83±5.92)%,明显高于非MOFE组(16.46±3.59)ng/L、(39.06±4.26)%,SIRT3水平为(3.98±0.84)pg/mL,明显低于非MOFE组(4.82±1.25)pg/mL,差异均具有统计学意义(P<0.05);经Logistic回归分析结果显示,年龄、合并慢阻肺、血清IL-18、CD64及SIRT3均为重症肺炎患者MOFE发生的影响因素(P<0.05);血清IL-18、CD64及SIRT3水平预测重症肺炎患者MOFE发生的曲线下面积(AUC)分别为0.804、0.807、0.742,三指标联合预测MOFE发生的AUC为0.926,明显高于血清IL-18、CD64及SIRT3单独预测(Z=22.941、20.837、25.963,P<0.001),此时最佳敏感度、特异度分别为78.89%、91.43%。结论重症肺炎患者血清IL-18、CD64水平升高,SIRT3水平下降,均为MOFE发生的重要因素,联合检测三者水平有助于预测重症肺炎患者MOFE的发生。

启发式k-means聚类算法的改进研究

启发式k-means聚类算法通过在k-means第一次迭代后查看附近的集群来预测每个数据点可能会被划分到的集群子集,有效地加快了算法的运行速度。但由于启发式算法存在随机选择初始聚类中心以及无法有效识别数据集中离群点的缺陷,导致聚类结果的误差平方和较大并且轮廓系数偏小。针对这一问题,提出了CHk-means算法,该算法引入仔细播种方法,克服了启发式k-means算法随机选择初始聚类中心带来的局部最优解问题;该算法引入局部异常因子LOF算法对离群点进行检测,降低了离群点数据对聚类结果的影响。在多个数据集上对3种算法进行对比试验,结果表明CHk-means算法可有效降低聚类结果的误差平方和,增强聚类的轮廓系数,使聚类质量得到明显改善。

S-100β CysC和NF-κB对急性缺血性脑卒中患者静脉溶栓后出血转化的预测价值

目的 探讨急性缺血性脑卒中(AIS)外周血中S-100β、CysC和NF-κB水平对静脉溶栓后出血转化的影响及预测价值。方法 收集2019-03—2022-03接受溶栓治疗的AIS患者140例,根据溶栓后24 h是否发生出血转化(HT)将患者分为非HT组(n=112)和HT组(n=28)。比较2组一般临床资料,采用多因Logistic回归分析影响HT发生的危险因素,受试者工作特征(ROC)曲线评估S-100β、CysC和NF-κB预测HT发生的价值。结果 HT组与非HT组相比,患者年龄、发病至溶栓时间、房颤、TOAST分型、C反应蛋白、凝血酶原时间、S-100β、CysC、NF-κB、白质高信号和脑微出血等均有统计学差异(P<0.05)。Logistic多因素回归分析显示,房颤、S-100β、CysC和NF-κB为影响HT发生的危险因素。S-100β、CysC和NF-κB预测AIS患者静脉溶栓后出血转化的曲线下面积分别为0.915(0.902~0.923)、0.874(0.856~0.882)和0.789(0.771~0.796),均具有一定的预测价值。结论 S-100β、CysC和NF-κB为AIS患者静脉溶栓后HT发生的危险因素,对HT发生具有一定的预测价值。

Neurotrophic factor-based pharmacological approaches in neurological disorders

Aging is a physiological event dependent on multiple pathways that are linked to lifespan and processes leading to cognitive decline.This process represents the major risk factor for aging-related diseases such as Alzheimer’s disease,Parkinson’s disease,and ischemic stroke.The incidence of all these pathologies increases exponentially with age.Research on aging biology has currently focused on elucidating molecular mechanisms leading to the development of those pathologies.Cognitive deficit and neurodegeneration,common features of aging-related pathologies,are related to the alteration of the activity and levels of neurotrophic factors,such as brain-derived neurotrophic factor,nerve growth factor,and glial cell-derived neurotrophic factor.For this reason,treatments that modulate neurotrophin levels have acquired a great deal of interest in preventing neurodegeneration and promoting neural regeneration in several neurological diseases.Those treatments include both the direct administration of neurotrophic factors and the induced expression with viral vectors,neurotrophins’binding with biomaterials or other molecules to increase their bioavailability but also cell-based therapies.Considering neurotrophins’crucial role in aging pathologies,here we discuss the involvement of several neurotrophic factors in the most common brain aging-related diseases and the most recent therapeutic approaches that provide direct and sustained neurotrophic support.

Spatial Distribution Pattern and Influencing Factors of Physical Bookstores of Large Cities:A Case Study of Three National Central Cities in Western China

As cultural facilities,physical bookstore is an important part of urban infrastructure.Influenced by the development of social economy and the internet,physical bookstores also have become a combination of cultural space and tourism experience.In this case,it is necessary to explore the spatial characteristics and influencing factors of physical bookstores.This study uses Density-Based Spatial Clustering of Applications with Noise(DBSCAN),spatial analysis and geographical detectors to calculate the spatial distribution pattern and factors influencing physical bookstores in national central cities/municipality(hereafter using cities)in western China.Based on spatial data,population density,road density and other data,this study constructed a data set of the influencing factors of physical bookstores,consisting of 11 factors along 6 dimensions for 3 national central cities in western China.The results are as follows:first,the spatial distribution pattern of physical bookstores in Xi’an,Chengdu,and Chongqing is unbalanced.The spatial distribution of physical bookstores in Xi’an and Chongqing is from southwest to northeast and are relatively clustered,while those in Chengdu are relatively discrete.Second,the spatial distribution pattern of physical bookstores has been formed under the influence of different factors.The intensity and significance of influencing factors differ in the case cities.However,in general,the social factor,business factor,the density of research facilities,tourism factor and road density are the main driving factors in the three cities.There is a synergistic relationship between public libraries and physical bookstores.Third,the explanatory power becomes stronger after the interaction between various factors.In Xi’an and Chengdu,the density of communities and the density of research facilities have stronger explanatory power for the dependent variable after interacting with other factors.However,in Chongqing,the traffic factors have stronger explanatory power for the dependent variable after interacting with other factors.The results could provide a practical reference for the sustainable development of physical bookstores and encourage a love of reading among the public.

Joint Detection of Serum Vitamin D,Body Mass Index,and Tumor Necrosis Factor Alpha for the Diagnosis of Crohn’s Disease

Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.

AR、SKP2、SOX10、PD-L1及TIL表达在三阴性乳腺癌中的意义

目的:探索雄激素受体(androgen receptor,AR)、S期激酶相关蛋白2(S-phase kinase-associated protein 2,SKP2)、性别决定区Y相关的HMG盒含因子10(sry-related HMG box-containing factor 10,SOX10)、程序性死亡配体1(programmed death-ligand 1,PD-L1)及肿瘤浸润性淋巴细胞(tumor infiltrating lymphocyte,TIL)在三阴性乳腺癌(triple negative breast cancer,TNBC)表达与临床病理特征和预后的关系。方法:根据苏木精-伊红染色(hematoxylineosin, HE)染色切片评判109例TNBC瘤巢内TIL的比例,采用Leica Bond-Max全自动免疫组化仪检测TNBC组织中AR、SKP2、SOX10、PD-L1的表达。分析以上各生物指标与临床病理特征间的关系,并采用kaplan-Meier、Log-rank进行生存分析。结果:95例患者获得随访,中位随访时间为48个月,中位无病生存时间(disease-free survival, DFS)为42个月,中位总生存时间(overall survival, OS)48个月。在TNBC中,AR阳性表达与淋巴结转移阴性(P=0.009)、肿瘤最大径<2 cm(P=0.008)相关,TIL高表达与低级别TNBC相关(P=0.007),SKP2阳性表达与神经/脉管侵犯阳性(P=0.011)、高级别TNBC相关(P=0.002),SOX10阳性表达与淋巴结转移阳性(P=0.022)、高级别TNBC(P=0.005)相关,PD-L1阳性表达与淋巴结转移阳性(P=0.020)、神经/脉管侵犯阳性(P=0.006)、高级别TNBC(P=0.042)相关。生存分析显示,SKP2、SOX10阳性表达与更差的DFS(P=0.007、P<0.001)和OS(P=0.013、P<0.001)相关,TIL高表达与更好的DFS(P=0.016)及OS(P=0.004)相关。在生物表志物的联合表达中,AR+/SKP2-、AR+/SOX10-与更好的DFS(P=0.004、P<0.001)及OS(P=0.007、P=0.001)相关,SOX10+/低TIL、PD-L1+/低TIL与更差的DFS(P<0.001、P=0.008)及OS(P=0.001、P=0.002)相关,AR-/低TIL者具有更差的OS(P=0.014)。SKP2(HR=4.143,95%CI为1.578~10.875)、SOX10(HR=7.578,95%CI为2.067~27.782)的阳性表达是影响TNBC患者DFS的独立预后因子,SKP2(HR=3.758,95%CI为1.400~10.084)、SOX10(HR=5.131,95%CI为1.316~20.000)及TIL(HR=0.375,95%CI为0.154~0.917)的阳性表达是TNBC患者OS的独立预后因子(P均<0.05)。结论:在TNBC中,AR阳性、TIL高表达与具有更好预后的临床病理特征相关,SKP2、SOX10和PD-L1与具侵袭性的临床病理特征相关。SKP2、SOX10及TIL表达与TNBC预后相关,提示这些生物指标可能成为TNBC新的预后因子,同时它们也有可能成为潜在的治疗靶点。

基于SPSS分析的京津冀城市群空气质量综合评估

京津冀城市群空气质量反映地区污染治理健康绿色发展情况。科学的京津冀城市群空气质量评估对推动地区协同发展、节能减排、绿色发展起到指导作用。本文运用聚类分析和因子分析的统计技术方法,分析京津冀城市群空气质量的核心指标的特征和相关性,构建基于SPSS分析的更加科学有效的空气质量综合评估模式,给出对影响京津冀城市群空气质量核心污染源综合治理的结论和建议:经过治理后空气质量整体变优,污染治理成效显著;但是对O3污染的治理几乎没有效果,还需加强对VOCs的治理;使用AQI衡量城市整体空气污染情况并不全面。

Single-nuclei RNA sequencing uncovers heterogenous transcriptional signatures in Parkinson's disease associated with nuclear receptor-related factor 1 defect

Previous studies have found that deficiency in nuclear receptor-related factor 1(Nurr1),which participates in the development,differentiation,survival,and degeneration of dopaminergic neurons,is associated with Parkinson s disease,but the mechanism of action is perplexing.Here,we first asce rtained the repercussion of knocking down Nurr1 by pe rforming liquid chromatography coupled with tandem mass spectrometry.We found that 231 genes were highly expressed in dopaminergic neurons with Nurr1 deficiency,14 of which were linked to the Parkinson’s disease pathway based on Kyoto Encyclopedia of Genes and Genomes analysis.To better understand how Nurr1 deficiency autonomously invokes the decline of dopaminergic neurons and elicits Parkinson’s disease symptoms,we performed single-nuclei RNA sequencing in a Nurr1 LV-shRNA mouse model.The results revealed cellular heterogeneity in the substantia nigra and a number of activated genes,the preponderance of which encode components of the major histocompatibility Ⅱ complex.Cd74,H2-Ab1,H2-Aα,H2-Eb1,Lyz2,Mrc1,Slc6α3,Slc47α1,Ms4α4b,and Ptprc2 were the top 10 diffe rentially expressed genes.Immunofluorescence staining showed that,after Nurr1knockdown,the number of CD74-immunoreactive cells in mouse brain tissue was markedly increased.In addition,Cd74 expression was increased in a mouse model of Parkinson’s disease induced by treatment with 6-hydroxydopamine.Ta ken togethe r,our res ults suggest that Nurr1 deficiency results in an increase in Cd74 expression,thereby leading to the destruction of dopaminergic neuro ns.These findings provide a potential therapeutic target for the treatment of Parkinson’s disease.