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 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.

Understanding the potential key risk factors associated with teen driver crashes in the United States: a literature review

This article is a compilation of teen driver crash contributing factors typically extractable from the crash data collection system in the United States.Tremendous research effort has been undertaken over the decades to comprehend teen driver crash risks,as teen drivers continue to be over-involved in crashes even when accounting for the driving exposure.This article presents the contexts of crash factors related to operating conditions,roadway,vehicle,and driver and their unique influences on teen driver crashes in terms of estimated risk,prevalence,and estimated likelihood mainly from descriptive and analytical studies.The key variables are selected based on the number of studies that considered each risk factor for analysis.The understanding of crash factors could be translated into graduated driver licensing and other teen driver safety programs.While the discussions were grounded in crash studies carried out in the United States,the insights gleaned from these studies hold the potential to offer valuable guidance to other countries.For example,the insights and discussions can serve as a catalyst for the development and improvement of driver education programs tailored to address the specific requirements and difficulties confronted by their teenage drivers.

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.

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.

Infliximab vs adalimumab:Points to consider when selecting antitumor necrosis factor agents in pediatric patients with Crohn’s disease

Biologic agents with various mechanisms against Crohn’s disease(CD)have been released and are widely used in clinical practice.However,two anti-tumor necrosis factor(TNF)agents,infliximab(IFX)and adalimumab(ADL),are the only biologic agents approved by the Food and Drug Administration for pediatric CD currently.Therefore,in pediatric CD,the choice of biologic agents should be made more carefully to achieve the therapeutic goal.There are currently no headto-head trials of biologic agents in pediatric or adult CD.There is a lack of accumulated data for pediatric CD,which requires the extrapolation of adult data for the positioning of biologics in pediatric CD.From a pharmacokinetic point of view,IFX is more advantageous than ADL when the inflammatory burden is high,and ADL is expected to be advantageous over IFX in sustaining remission in the maintenance phase.Additionally,we reviewed the safety profile,immunogenicity,preference,and compliance between IFX and ADL and provide practical insights into the choice of anti-TNF therapy in pediatric CD.Careful evaluation of clinical indications and disease behavior is essential when prescribing anti-TNF agents.In addition,factors such as the efficacy of induction and maintenance of remission,safety profile,immunogenicity,patient preference,and compliance play an important role in evaluating and selecting treatment options.

Phyllosphere eukaryotic microalgal communities in rainforests:Drivers and diversity

Phyllosphere algae are common in tropical rainforests,forming visible biofilms or spots on plant leaf surfaces.However,knowledge of phyllosphere algal diversity and the environmental factors that drive that diversity is limited.The aim of this study is to identify the environmental factors that drive phyllosphere algal community composition and diversity in rainforests.For this purpose,we used single molecule real-time sequencing of full-length 18S rDNA to characterize the composition of phyllosphere microalgal communities growing on four host tree species(Ficus tikoua,Caryota mitis,Arenga pinnata,and Musa acuminata) common to three types of forest over four months at the Xishuangbanna Tropical Botanical Garden,Yunnan Province,China.Environmental 18S rDNA sequences revealed that the green algae orders Watanabeales and Trentepohliales were dominant in almost all algal communities and that phyllosphere algal species richness and biomass were lower in planted forest than in primeval and reserve rainforest.In addition,algal community composition differed significantly between planted forest and primeval rainforest.We also found that algal communities were affected by soluble reactive phosphorous,total nitrogen,and ammonium contents.Our findings indicate that algal community structure is significantly related to forest type and host tree species.Furthermore,this study is the first to identify environmental factors that affect phyllosphere algal communities,significantly contributing to future taxonomic research,especially for the green algae orders Watanabeales and Trentepohliales.This research also serves as an important reference for molecular diversity analysis of algae in other specific habitats,such as epiphytic algae and soil algae.

Influence of cultural factors on choice of childbirth place among women in Oyigbo Local Government Area,Rivers State,Nigeria

Objectives:This study aims to ascertain if cultural factors influence the childbirth place choice of women in Oyigbo.Materials and Methods:The study used a cross‑sectional study design using a self‑structured questionnaire as the instrument to collect data from 384 volunteers through simple random sampling,and these data were analyzed using frequency and percentage for descriptive statistics while Chi‑square was used for inferential statistics at 0.05 level of significance.Results:The influence of cultural factors such as family traditions(χ^(2)=12.56,P=0.006),beliefs(χ^(2)=70.66,P=0.000),lack of confidence in health facilities(χ^(2)=367.83,P=0.000),and the presence of male skilled birth attendants(χ^(2)=50.85,P=0.000)were statistically significant to the choice of childbirth place,while patriarchal system(χ^(2)=2.99,P=0.393)was not statistically significant to the choices of childbirth places of women in Oyigbo.Religion had a statistically significant influence on childbirth place(χ^(2)=125.46,P=0.000).Conclusion:This study shows that religious and cultural factors have a significant influence on the childbirth place choices of women in Oyigbo Local Government Area of Rivers State.

Overexpression of fibroblast growth factor 13 ameliorates amyloid-β-induced neuronal damage

Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear.In this study,we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β(Aβ_(1-42))-induced into bilateral hippocampus.We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13.The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats.After overexpression of fibroblast growth factor 13,learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved.Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione,superoxide dismutase,phosphatidylinositol-3-kinase,AKT and glycogen synthase kinase 3β,and anti-apoptotic factor BCL.Furthermore,fibroblast growth factor 13 overexpression decreased the number of apoptotic cells,expression of pro-apoptotic factor BAX,cleaved-caspase 3 and amyloid-βexpression,and levels of tau phosphorylation,malondialdehyde,reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats.The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002.These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3βsignaling pathway.

Scale and Associated Factors of Using Pyrethroid-Impregnated Mosquito Nets as Fishing Tools on Nokoué Lake within Sô-Ava Municipality in Benin, 2020

Background: In lacustrine communities, whether in Benin or elsewhere, populations use impregnated mosquito nets (IMNs) as fishing nets. This depletes the lake of its fishery resources, which in turn are contaminated by the pyrethroids impregnated in the nets. This study aims to determine the scale and factors associated with the use of pyrethroid-impregnated mosquito nets as fishing tools in the municipality of Sô-Ava in Benin. Methods: This is a cross-sectional and analytical study with two components. First, a quantitative component was made up of 280 volunteers who were interviewed in the seven districts of the city. Data collection was done in two phases: the first from September to October 2020, and the second in August 2022. Data were analyzed with Stata and logistic regression was used. Another qualitative component was made up of forty participants chosen by reasoned choice, of which 32 were split into four focus groups of eight members each, and the rest participated in semi-structured interviews. Triangulation of the different sources was used to analyze the data. Results: Around 67% of the population reported using impregnated mosquito nets as fishing tools and 33% exclusively for malaria. Seasonal fishermen (ORa = 2.03, CI = 1.35 - 4.97, P = 0.004) and years of professional experience (ORa = 1.53, CI = 1.00 - 2.05, P = 0.021) increase the risk of using these nets as fishing tools. The use of insecticide-treated mosquito nets against mosquitoes causes skin scratching and impairs breathing because of the impregnation products, as reported by respondents. Conclusion: A high prevalence of inappropriate use of impregnated mosquito nets in fishing practices is highlighted in this study. Interviews in the field revealed that nets are diverted for fishing purposes to increase the volume of catches. Consequently, it will be appropriate to assess the pyrethroid content in water and fishery products.

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.

A high resolution inversion method for fluid factor with dynamic dryrock V_(P)/V_(S) ratio squared

As an important indicator parameter of fluid identification,fluid factor has always been a concern for scholars.However,when predicting Russell fluid factor or effective pore-fluid bulk modulus,it is necessary to introduce a new rock skeleton parameter which is the dry-rock VP/VS ratio squared(DVRS).In the process of fluid factor calculation or inversion,the existing methods take this parameter as a static constant,which has been estimated in advance,and then apply it to the fluid factor calculation and inversion.The fluid identification analysis based on a portion of the Marmousi 2 model and numerical forward modeling test show that,taking the DVRS as a static constant will limit the identification ability of fluid factor and reduce the inversion accuracy.To solve the above problems,we proposed a new method to regard the DVRS as a dynamic variable varying with depth and lithology for the first time,then apply it to fluid factor calculation and inversion.Firstly,the exact Zoeppritz equations are rewritten into a new form containing the fluid factor and DVRS of upper and lower layers.Next,the new equations are applied to the four parameters simultaneous inversion based on the generalized nonlinear inversion(GNI)method.The testing results on a portion of the Marmousi 2 model and field data show that dynamic DVRS can significantly improve the fluid factor identification ability,effectively suppress illusion.Both synthetic and filed data tests also demonstrate that the GNI method based on Bayesian deterministic inversion(BDI)theory can successfully solve the above four parameter simultaneous inversion problem,and taking the dynamic DVRS as a target inversion parameter can effectively improve the inversion accuracy of fluid factor.All these results completely verified the feasibility and effectiveness of the proposed method.

Factors influencing quality of life in Chinese patients with dementia: a systematic review

Background:Dementia is a group of nervous system diseases characterized by progressive cognitive decline,leading to a loss of self-care ability and a decline in well-being.This places a significant burden on the global healthcare system,with Chinese patients accounting for approximately one-quarter of the world’s dementia cases.Therefore,it is crucial to identify factors that impact the quality of life(QOL)among elderly Chinese individuals with dementia.Method:To achieve this,we conducted a comprehensive search of several databases,including PubMed,Embase,Web of Science,the Cochrane Library,China National Knowledge Infrastructure,Wanfang Data,China VIP Database and China Biomedical Literature Database.We reviewed cross-sectional studies from the inception of these databases until March 27,2022.QOL outcomes were assessed using standardized scales in the studies included in this review.Results:The search yielded a total of 1,235 relevant articles,from which we finally included 21 cross-sectional studies and one longitudinal study after rigorous quality assessment.Among these,10 studies were classified as high quality,while 12 were classified as fair quality.Through our analysis,we identified 28 patient-rated QOL factors and 14 caregiver-rated QOL factors.These factors were categorized into three groups:patient,disease-related and caregiver.Factors commonly found to influence patient-rated QOL included age,education,marital status,depression,self-care ability,dementia severity,cognitive function,behavioral and psychological symptoms of dementia and caregiver burden.Similarly,factors commonly influencing caregiver-rated QOL included economic status,depression,self-care ability,dementia severity,cognitive function,behavioral and psychological symptoms of dementia and caregiving time.Conclusion:This review clarifies the factors that influence the QOL of Chinese individuals with dementia.When implementing interventions,it is crucial to consider the differences between patient-rated QOL and caregiver-proxy-rated QOL,as well as their respective influencing factors.

Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice

Hepatocellular carcinoma(HCC),a prevalent solid carcinoma of significant concern,is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes.The etiology and pathological progression of non-alcoholic steatohepatitis(NASH)-related HCC is multifactorial and multistage.However,no single animal model can accurately mimic the full NASH-related HCC pathological progression,posing considerable challenges to transition and mechanistic studies.Herein,a novel conditional inducible wild-type human HRAS overexpressed mouse model(HRAS-HCC)was established,demonstrating 100%morbidity and mortality within approximately one month under normal dietary and lifestyle conditions.Advanced symptoms of HCC such as ascites,thrombus,internal hemorrhage,jaundice,and lung metastasis were successfully replicated in mice.In-depth pathological features of NASH-related HCC were demonstrated by pathological staining,biochemical analyses,and typical marker gene detections.Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival,further confirming the accuracy and reliability of the model.Based on protein-protein interaction(PPI)network and RNA sequencing analyses,we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis,with subsequent progression to HCC.Collectively,our study successfully duplicated natural sequential progression in a single murine model over a very short period,providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.

基于无源均流的谐振式无桥型Boost LED驱动电源

传统Boost功率因数校正变换器的输出电压必须大于输入电压,在一定程度上限制了其在LED驱动电源中的应用。同时,传统LED驱动电源因输入端整流桥的存在而限制了自身效率的进一步提升。基于谐振式Boost功率因数校正变换器拓扑提出了一种无源均流型无桥Boost LED驱动电源,通过引入谐振式电容均流网络,实现了多路均流输出;通过整流桥的去除,进一步提升了系统的效率。最后,搭建了一台效率可达93.64%的140 W实验样机,验证了理论分析的正确性与可行性。

集体经营性建设用地入市农户满意度影响因素研究——基于Logistic-ISM模型的分析

农户满意程度可以反映政策改革成效,探究农户集体经营性建设用地入市满意度影响因素,有助于评价政策实施效果,同时对提升农村发展和农民幸福感也有一定的现实意义.采用问卷调查和访谈的方式,选取重庆市大足区作为研究区域,基于Logistic模型确定农户满意度的影响因素,结合ISM模型分析各影响因素之间的层次关系,对农民的政策实施满意度影响因素进行实证分析.研究结果显示:(1)针对入市实施效果,绝大部分农户持满意态度,不满意的地方集中在收益分配不及时和环境污染方面;(2)家中是否有村干部、生态环境变化情况、是否参与表决、分配公平性、入市实际收益、程序透明性、入市风险存在情况、对入市土地所有者的认知对入市农户满意度有显著影响.其中对入市土地所有者的认知、入市风险存在情况、入市实际收益为表层直接因素,中层间接因素有生态环境变化情况、是否参与表决、分配公平性以及程序透明性,家中是否有村干部为深层根源因素.应进一步完善土地产权制度,明晰入市到期后土地权属问题;健全监督管理机制,建立集体经营性建设用地入市单位的产业目录和准入标准制度;完善收益分配机制,制定集体土地入市指导性分配意见;将村集体负责人纳入政府基层领导队伍体系,提高程序透明性.