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.

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.

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.

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.

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.

教育硕士产教融合“U-G-S&E”育人模式探析

产教融合是教育与产业的深度合作,我国产教融合的政策经历了从职业教育到普通教育的发展。产教融合符合教育硕士人才培养的逻辑,“U-G-S&E”育人模式以高校为主导,政府提供政策引导和资金支持,中小学和企业协同参与教育硕士的培养。通过实践探索发现,“U-G-S&E”模式可以更好地激发学生提升职业能力的动力,助力学生职业生涯规划和就业,提升以赛赋能的效果,帮助高校校内导师、中小学和企业的校外导师加深对教育链、人才链与产业链、创新链有机衔接的理解,助力孵化本地企业参与遴选国家产教融合型企业,推动本地企业更好的融入国家现代教育体系建设。

U-G-S模式下现代大学附属学校建设的路径思考

U-G-S(大学-政府-学校)三方联动是上海师范大学近年来建设现代大学附属学校的主要模式,上海师范大学、各区政府与中小学校高效协同合作,发挥各方优势,主动服务上海市政府建设“五个新城”的城市战略,办老百姓家门口的好学校。大学附属学校分为挂牌学校和新建学校两种类型,研究从内在机制、实践路径和建设成效三个方面对两类学校的变革发展进行深度剖析,以期为大学附属学校建设提供宝贵经验。

U-G-S协同推进创新人才早期培养的国际经验与启示

本文选取美国、澳大利亚、新加坡等创新人才机制相对成熟的国家,探究其创新人才多主体早期培育项目经验,分析、归纳得出主要培养路径有四:首先,“丰富和加速”是主要培养手段,以高阶课程助力超前学习、以缩短学制促进加速学习、以暑期项目丰富课程学习;其次,以信息技术搭建资优教育平台,扩展资源网络渠道,推进创新人才培养的机会均等;再次,注重教育体系衔接,以大中小衔接体系为创新人才接续培养枢纽,确保培养质量;最后,以分类培养理念创新人才和技术创新人才为目标,建立针对性培养体系。据此,本文提出改进我国创新人才早期培养U-G-S协作机制的建议:加强政策顶层设计、扶持校企联合、增强创新人才网络资源建设、推进校本创新人才培养项目建设等。

“U-S”合作中高校教师与中小学教师的跨界知识互动探究

对于“U-S”合作情境中高校教师与中小学教师如何进行知识互动这一重要问题,鲜有实证研究涉及。通过对高校与中小学合作的多个案例进行质性研究,发现高校教师与中小学教师的知识互动存在三种不同的模式:一是高校教师主导下的知识迁移模式,二是内化与重构后的知识转化模式,三是基于研究伙伴关系的知识生产模式。基于此,自我定位与地位关系、知识互动的聚焦性和持续性、卷入程度及跨界互动能力,是影响高校教师与中小学教师知识互动效果的重要因素。

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.

基于CLUE-S模型的浙江省土地利用结构变化趋势分析

土地利用格局变化及未来发展情景对省域土地合理规划和生物多样性保护具有重要意义。以东部典型区域浙江省为例,根据浙江省2013和2018年两期精度500 m×500 m土地利用数据、浙江省陆地国家公园、国家级自然保护区数据,分别设置了土地利用结构和经济社会发展速率维持现状的情景、自然保护地体系建立情景和城市扩张情景。选取高程、坡度、人口等11种影响因素作为驱动因子,采用CLUE-S模型拟合浙江省2018年的土地利用覆被格局并判断拟合精度,进而模拟出三种情景下研究区2030年的土地利用格局演变。结果表明:1)Logistic二元回归分析结果ROC值均大于0.699,表明所选驱动因子对土地利用类型的解释能力较为准确。2)Kappa系数高达0.9460,表明模型能够准确的模拟浙江省土地利用分布格局;3)与2018年浙江省土地利用情况相比,2030年在不同情景下土地利用面积与空间分布均发生了一定的变化,土地利用结构和经济社会发展维持现状情景下建设用地持续扩张,建设用地面积增加16575 hm^(2),显著增加的区域主要位于杭州市郊和温州市郊。自然保护地体系建立情景下,林地、水域分别增加了15625、1600 hm^(2),耕地、草地和建设用地分别减少了1550、1700和13975 hm^(2),空间上都呈现均匀变化。城市扩张情景下,建设用地面积迅速增加145800 hm^(2),增加部分多数位于原有建设用地的外围。三种情景对比下,自然保护地体系建立情景是浙江省2030年最适宜的土地利用土地覆被格局。2030年浙江省在自然保护地体系建立情景下生态空间的面积最大,为6741925 hm^(2),年均增加速度为0.0192%。

Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?

Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and maturation.Its cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and urine.There is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic neuropathy.Whether p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open question.In this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases.We also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.

师范生U-G-S培养模式实践探索与路径优化——基于“优师计划”背景

师范生U-G-S培养模式实践已取得诸多成效,如多方配合助力师范生培养,促进区域均衡,提升基层教学水平等。但师范生U-G-S培养模式在实践中也存在突出问题,如高校一方主导、其他方参与度低,难以高效协同,培育方案与实际岗位需求存在适配偏差等。剖析“优师计划”对优化师范生U-G-S培养模式的启发,探索以当地政府为统筹、师范院校为关键、中小学校为导向、师范生为主体的“四位一体”优化路径,有助于提高师范生培育成效。

内蒙古根河三道桥铅锌银矿床C-H-O-S同位素和U-Pb定年研究及其意义

内蒙古根河三道桥大型铅锌银矿床位于大兴安岭得尔布干成矿带中北段,矿体主要呈脉状赋存于火山岩地层中。氢氧同位素研究表明,成矿期石英和绢云母的δD值变化范围为-149.1‰~-156.7‰,δ^(18)OH_(2)O值变化范围为-13.6‰~3.4‰;成矿后期石英δD值变化范围为-131.9‰~-147.7‰,δ^(18)OH_(2)O值变化范围为-16.5‰~-18.2‰。碳同位素分析结果表明,与矿化有关的方解石δ^(13)C值变化范围为-1.8‰~-3.1‰,δ^(18)O值变化范围为5.3‰~8.6‰。原位S同位素分析结果表明,硫化物的δ^(34)S值变化范围为2.3‰~5.6‰,与其西南侧下护林矽卡岩型铅锌银矿床中的硫化物的δ^(34)S值(1.2‰~5.9‰)基本一致。上述同位素组成特征指示成矿物质主要来源于岩浆热液,在上升到地壳浅部时有一定量的大气降水混入。锆石U-Pb年代学研究表明,矿化的闪长玢岩脉年龄为(136.0±0.7)Ma(MSWD=0.44);未矿化、穿切硫化物微细脉的闪长玢岩脉的锆石U-Pb年龄为(120.8±0.6)Ma(MSWD=0.49)。结合前人相关研究进展,认为三道桥铅锌银矿床形成于136.0~120.8 Ma期间(早白垩世),为伸展构造背景下与浅成侵入岩有关的中温热液型铅锌银矿床。

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.

全程·融合·协同:教育硕士U-G-S协同培养模式的创新实践研究

教育硕士是职前教师培养的重要对象,是高素质研究型教师队伍的重要来源。教育硕士U-G-S协同培养是我国教师队伍建设政策的主旨所向,更是卓越教育硕士培养的现实所需。以J大学教育硕士为研究样本,以利益相关者理论为理论基础,厘清U-G-S协同培养模式中各利益主体之间的互动关系及利益诉求,形成U-G-S协同培养模式的运行程序,并依据“计划、行动、观察、反思”的步骤开展行动实践。研究结果显示,U-G-S协同培养模式在导师团队建设、人才素养提升、研究成果产出等多方面取得显著成效。

Commentary on "Association of daily sitting time and leisure-time physical activity with body fat among U.S.adults"

In their study,association of daily sitting time and leisure-time physical activity (LTPA) with body fat among U.S.Adults,Liao et al.^(1) analyzed data from the 2011-2018 National Health and Examination Survey to examine associations between h/day sitting,meeting (or not meeting) the U.S.Physical Activity Guidelines of≥150 min/week of moderate-and vigorous-intensity LTPA,and combinations of sitting time and LTPA on totaland trunk percent body fat (BF%).