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.

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%).

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.

The Reception Commemorating the 45th Anniversary of China-U.S.Diplomatic Ties Held in Beijing

On January 5,the Chinese People's Association for Friendship with Foreign Countries and the Chinese People's Institute of Foreign Affairs jointly hosted a reception commemorating the 45th anniversary of the establishment of diplomatic relationship between China and the United States in Beijing.Member of the Political Bureau of the CPC Central Committee and Foreign Minister Wang Yi attended the commemoration and delivered aspeech.David Meale,ChargédAffaires at the U.S.Embassy in China,addressed the reception.He extended on behalf of the U.S.side congratulations on the anniversary,expressing the readiness of the U.S.to implement the consensus reached by the two heads of state and promote the steady development of U.S.-China relations.More than 350 people from all walks of life of both countries attended the reception.

FREE SPEECH OR SINOPHOBIA? THE U.S. SENATE MUST DECIDE

The 100 men and women who make up the U.S.Senate will soon have an important choice.They will either affirm that the First Amendment matters or they will surrender to fear.The senators must decide whether to go along with their colleagues in the House of Representatives and require the popular social media app TikTok to be sold to an American company.If they do endorse the House vote,then ByteDance must divest itself of TikTok or see the app will be banned on U.S.-based social media platforms.

Cross-Cultural Adjustment and Coping:U.S.Students in Taiwan Residents Higher Education

The aim of this study was to investigate the adjustment problems of students from the United States enrolled in universities in the East,specifically in Taiwan,their problems related to cultural adaptation,and the process of adjustment to student life in Taiwan.Under investigation were cultural adjustment and coping skills as these students transitioned from West to East.Qualitative data were collected from interviews with participants and faculty members as well as participant observations.Results indicated that U.S.students found their own ways to acclimate to their new academic setting as well as to social relations,cross-cultural issues,and the linguistic environment in Taiwan to achieve effective adaptation.They made changes in themselves to cope with all situations they encountered.This study provides suggestions for international students abroad in Taiwan,for the Taiwan Residents government,and for universities or colleges in terms of what they should offer to current and future international students.

Digital Disparities:How Artificial Intelligence Can Facilitate Anti-Black Racism in the U.S.Healthcare Sector

This paper delves into the intricate interplay between artificial intelligence(AI)systems and the perpetuation of Anti-Black racism within the United States medical industry.Despite the promising potential of AI to enhance healthcare outcomes and reduce disparities,there is a growing concern that these technologies may inadvertently/advertently exacerbate existing racial inequalities.Focusing specifically on the experiences of Black patients,this research investigates how the following AI components:medical algorithms,machine learning,and natural learning processes are contributing to the unequal distribution of medical resources,diagnosis,and health care treatment of those classified as Black.Furthermore,this review employs a multidisciplinary approach,combining insights from computer science,medical ethics,and social justice theory to analyze the mechanisms through which AI systems may encode and reinforce racial biases.By dissecting the three primary components of AI,this paper aims to present a clear understanding of how these technologies work,how they intersect,and how they may inherently perpetuate harmful stereotypes resulting in negligent outcomes for Black patients.Furthermore,this paper explores the ethical implications of deploying AI in healthcare settings and calls for increased transparency,accountability,and diversity in the development and implementation of these technologies.Finally,it is important that I prefer the following paper with a clear and concise definition of what I refer to as Anti-Black racism throughout the text.Therefore,I assert the following:Anti-Black racism refers to prejudice,discrimination,or antagonism directed against individuals or communities of African descent based on their race.It involves the belief in the inherent superiority of one race over another and the systemic and institutional practices that perpetuate inequality and disadvantage for Black people.Furthermore,I proclaim that this form of racism can be manifested in various ways,such as unequal access to opportunities,resources,education,employment,and fair treatment within social,economic,and political systems.It is also pertinent to acknowledge that Anti-Black racism is deeply rooted in historical and societal structures throughout the U.S.borders and beyond,leading to systemic disadvantages and disparities that impact the well-being and life chances of Black individuals and communities.Addressing Anti-Black racism involves recognizing and challenging both individual attitudes and systemic structures that contribute to discrimination and inequality.Efforts to combat Anti-Black racism include promoting awareness,education,advocacy for policy changes,and fostering a culture of inclusivity and equality.

Investigation of factors influencing roof stability at a Western U.S.longwall coal mine

The coal mine roof rating(CMRR) was developed to bridge the gap between geological variation in underground coal mines and engineering design. The CMRR accounts for the compressive strength of the immediate roof, the shear strength and intensity of any discontinuities present, and the moisture sensitivity of the immediate roof. The CMRR has been widely used and validated in Eastern US coal mines, but it has seen limited application in the Western US. This study focuses on roof behavior at a Western coal mine(Mine A). Mine A shows significant lateral geological variation, along with localized faulting and a laterally extensive sandstone channel network. The CMRR is not used to predict roof instability at the mine. It is, therefore, hypothesized that there are other factors that are correlated with roof instability in underground coal mines that could potentially also be considered in conjunction with the CMRR.This hypothesis was tested by collecting 30 CMRR measurements at Mine A. At each measurement location, a binary record of the roof condition(stable or unstable) was made, and other parameters such as depth of cover, presence of faulting, and sandstone channels were also recorded. ANOVA tests showed that the CMRR values and the roof conditions were not strongly correlated, indicating that the CMRR input criteria are not fully predictive of roof stability at this mine. The CMRR values showed statistically significant correlations(p less than 0.05) with faulting as well as with location at an intersection. For areas that had previously experienced roof fall but were currently stable, faulting was correlated with roof condition(p less than 0.05) only when the condition was classified as unstable.

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.

How to Look at the U.S. Factor in China's Peripheral Security

Since the Obama Administration implements the Asia-Pacific rebalancing strategy,China’s security situation in the peripheral areas shows a downward trend,the specific demonstration of which is the complex factors in political relations

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.

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.