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Endoplasmic reticulum stress,autophagy,neuroinflammation,and sigma 1 receptors as contributors to depression and its treatment

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Neural Regeneration Research 2024年第10期19卷 2202-2211页

作者： Chika Fujii Charles F.Zorumski Yukitoshi Izumi Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor family institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.

关键词： allopregnanolone fluvoxamine ketamine neurosteroids postpartum depression quercetin

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Glyphosate as a direct or indirect activator of pro-inflammatory signaling and cognitive impairment

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Neural Regeneration Research 2024年第10期19卷 2212-2218页

作者： Yukitoshi Izumi Kazuko A.O'Dell Charles F.Zorumski Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor family institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.

关键词： cognitive impairment glyphosate microglia neuroinflammation roundup toll-like receptor 4 zinc chelation

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Does topical vancomycin prevent fracture-related infections in closed fractures undergoing open reduction and internal fixation?A randomised controlled trial

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Chinese Journal of Traumatology 2024年第2期27卷 71-76页

作者： Mohit Gandhi Gopisankar Balaji Jagdish Menon Ruben Raj Thomas Department of Orthopaedics Jawaharlal Institute of Postgraduate Medical Education and ResearchPondicherryIndia Department of Preventive and social medicine Jawaharlal Institute of Postgraduate Medical Education and ResearchPondicherryIndia

Purpose:The role of topical vancomycin in fracture-related infection(FRI)is *** few studies have reported their efficacy in open and high-risk extremity *** study aimed to assess topical vancomycin's role in reducing FRI in closed fractures undergoing open surgical intervention with an ***:This prospective randomized cohort study was carried out between February 2021 to January *** with isolated closed fractures,who were planned for open reduction and internal fixation within 2 weeks from the time of injury were included for this *** data collected included age,gender,socioeconomic status,mechanism of injury,diagnosis,Tscherne classification,and time interval to take up for *** were randomized into the intervention and control groups using the block randomization *** control group received only systemic antibiotic prophylaxis,whereas the intervention group received topical application of vancomycin powder in the surgical wound alongside systemic antibiotic *** primary outcome measure was the incidence of FRI among these *** and radiological findings and culture reports(in cases with infection)were recorded during the post-operative period and at 6 weeks of *** relevant statistical calculations were done using STATA statistical/data analysis-parallel edition version 16.0(StataCorp LLC).The quantitative variables like age and duration of the surgery were assessed for normalcy by Shapiro-Wilk W *** independent samples t-test with equal variances was applied to the age ***'s exact test was used for the analysis of the primary outcome measure(presence of FRI following surgery),and"Risk of FRI"and"Risk difference"between the 2 groups was *** strength of the association between qualitative variables was assessed using the Fisher's exact and Chi-square tests,***:There were 88 patients included in this *** statistical si

关键词： Infections Antibiotics Vancomycin Fractures

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The Hierarchy of Distribution in Private Law

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social Sciences in China 2024年第2期45卷 29-48页

作者： Xie Hongfei institute of Law Chinese Academy of Social Sciences

In terms of the theory of the three hierarchies of distribution in economics,private law can be seen as embodying a 2.5th *** distribution confers equal objective rights on all private agents,who acquire subjective rights through de facto and de jure *** legal environment should be conducive to unleashing the energy and creativity of agents,supporting entrepreneurs,safeguarding competitive neutrality and promoting the mobility of factors of production in order to consolidate the material foundation of common *** changes the rules of primary distribution and is an inherent and rightful function of private *** equalizing the strengths and weaknesses of the interactions of private agents,redistribution is better able to promote self-determination and defend human dignity than public ***,it enables private law to achieve the national goals of enhancing social welfare and reducing confrontation in the operation of *** law lies between redistribution and tertiary distribution,occupying the 2.5th *** most typical expression is"interference liability,"i.e.,justified harm inflicted in cases of necessity(Aufopferungshaftung).This includes the expansion of the social liability of profitmaking legal persons,the expansion of tort liability,and the limitation of the return of *** law enables distributive justice to serve as a common basis for the various hierarchies of distribution,incorporating the different values of private law and weighting them differently depending on the *** justice can also help to transform all private law rules into laws of nature,thus highlighting the neutrality of private law.

关键词： private law primary distribution redistribution distributive justice corrective justice liability for justified harm inflicted in cases of necessity

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Exploring the impact of economic growth and energy consumption on SO2 emissions in China based on the Environmental Kuznets Curve hypothesis

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Petroleum Science 2024年第4期21卷 2892-2900页

作者： Bing-Jie Xu Yi-Fei Shen Hui Qiao Zhi Gao Faculty of Business City University of Macau Rural Development institute Chinese Academy of Social Sciences School of Marxism Shenzhen Polytechnic University

This study aims to analysis the influence of economic growth(EG) and energy consumption(EC) on sulfur dioxide emissions(SE) in China. Accordingly, this study explores the link between EG, EC, and SE for 30 provinces in China over the span of 2000-2019. This study also analyzes cross-sectional dependence tests, panel unit root tests, Westerlund panel cointegration tests, Dumitrescu-Hurlin(D-H) causality tests. According to the test results, there is an inverted U-shaped association between EG and SE,and the assumption of the Environmental Kuznets Curve(EKC) is verified. The signs of EG and EC in the fixed effect(FE) and random effect(RE) methods are in line with those in the dynamic ordinary least squares(DOLS), fully modified ordinary least squares(FMOLS) and autoregressive distributed lag(ARDL)estimators. Moreover, the results verified that EC can obviously positive impact the SE. To reduce SE in China, government and policymakers can improve air quality by developing cleaner energy sources and improving energy efficiency. This requires the comprehensive use of policies, regulations, economic incentives, and public participation to promote sustainable development.

关键词： SO 2 emissions Economic growth Energy consumption EKC China

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Whole-genome sequencing in medicinal plants:current progress and prospect

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Science China(Life Sciences) 2024年第2期67卷 258-273页

作者： Yifei Pei Liang Leng Wei Sun Baocai Liu Xue Feng Xiwen Li Shilin Chen institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China institute of Herbgenomics Chengdu University of Traditional Chinese MedicineChengdu 611137China Innovative institute of Chinese medicine and Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China institute of Agricultural Bioresource Fujian Academy of Agricultural SciencesFuzhou 350003China

Advancements in genomics have dramatically accelerated the research on medicinal plants,and the development of herbgenomics has promoted the“Project of 1K Medicinal Plant Genome”to decipher their genetic ***,it is difficult to obtain their high-quality whole genomes because of the prevalence of polyploidy and/or high genomic *** genomes of 123 medicinal plants were published until September *** published genome sequences were investigated in this review,covering their classification,research teams,ploidy,medicinal functions,and sequencing *** than 1,000 institutes or universities around the world and 50 countries are conducting research on medicinal plant *** species account for a majority of sequenced medicinal *** whole genomes of plants in the Poaceae family are the most *** 40%of the published papers studied species with tonifying,replenishing,and heat-cleaning medicinal *** plants are still in the process of domestication as compared with crops,thereby resulting in unclear genetic backgrounds and the lack of pure lines,thus making their genomes more difficult to *** addition,there is still no clear routine framework for a medicinal plant to obtain a high-quality whole ***,a clear and complete strategy has been originally proposed for creating a high-quality whole genome of medicinal ***,whole genome-based biological studies of medicinal plants,including breeding and biosynthesis,were *** also advocate that a research platform of model medicinal plants should be established to promote the genomics research of medicinal plants.

关键词： herbgenomics whole genome high throughput sequencing research strategy model species application

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Nociceptors and Macrophages in Bacterial Meningitis:Partners in Crime?

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Neuroscience Bulletin 2024年第3期40卷 418-420页

作者： Fang Gao Hongzhen Hu The Kimberly and Eric J.Waldman Department of Dermatology Icahn School of Medicine at Mount SinaiNew York NY10029USA The Nash family Department of Neuroscience Icahn School of Medicine at Mount SinaiNew York NY10029USA The Mark Lebwohl Center for Neuroinfammation and Sensation Icahn School of Medicine at Mount SinaiNew York NY10029USA Friedman Brain institute Icahn School of Medicine at Mount SinaiNew York NY10029USA

Bacterial meningitis is a serious and potentially life-threatening infection that affects the protective layers surrounding the brain and spinal cord,known as the *** types of bacteria,including Streptococcus pneumoniae,Neisseria meningitidis,and Haemophilus influenzae,can cause this *** populations,such as infants,children,immunocompromised adults,and the elderly,are particularly vulnerable to these *** of bacterial meningitis can manifest suddenly and may include high fever,severe and persistent headache,stiff neck,vomiting,sensitivity to light,and confusion or changes in mental state[1,2].Identifying these symptoms in infants can be more challenging and may lead to long-term disability or death[3].Despite the effectiveness of vaccines,it is crucial to understand how bacteria invade the brain and how our innate immune system responds to infection(Fig.1).

关键词： protective infection suddenly

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Discriminative explicit instance selection for implicit discourse relation classification

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Frontiers of Computer Science 2024年第4期18卷 129-138页

作者： Wei SONG Hongfei HAN Xu HAN Miaomiao CHENG Jiefu GONG Shijin WANG Ting LIU Information Engineering College Capital Normal UniversityBeijing 100048China iFLYTEK AI Research institute Hefei 230088China Research Center for social Computing and Information Retrieval Harbin Institute of TechnologyHarbin 150006China

Discourse relation classification is a fundamental task for discourse analysis,which is essential for understanding the structure and connection of *** discourse relation classification aims to determine the relationship between adjacent sentences and is very challenging because it lacks explicit discourse connectives as linguistic cues and sufficient annotated training *** this paper,we propose a discriminative instance selection method to construct synthetic implicit discourse relation data from easy-to-collect explicit discourse *** expanded instance consists of an argument pair and its sense *** introduce the argument pair type classification task,which aims to distinguish between implicit and explicit argument pairs and select the explicit argument pairs that are most similar to natural implicit argument pairs for data *** also propose a simple label-smoothing technique to assign robust sense labels for the selected argument *** evaluate our method on PDTB 2.0 and PDTB *** results show that our method can consistently improve the performance of the baseline model,and achieve competitive results with the state-of-the-art models.

关键词： discourse analysis PDTB discourse relation implicit discourse relation classification data expansion

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Effect of Diabetes Self-Management Education on Glycaemic Control in Sudanese Adults with Type 2 Diabetes

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Journal of Biosciences and medicines 2024年第3期12卷 316-327页

作者： Sahar Moawia Balla Elnour Tayseer Abdelmotalib Ahmed Taha Haiam Abdalla Wadatalla Ziryab Zainelabdin Mohamed Elmahdi Marwah Isam Abdulmajeed Mohammedahmed Rowa Abdelmonem Sidig Hamadto Nahla Yousif Osman Mohammed Saeed Omnia Mubarak Saad Abdallah Sulafa Abdelbagi Mustafa Ahmed Hanady Abdelhameed Ahmed Mohamed Sarah Khalil Fathi Khalil family medicine Health Gates Primary Care Riyadh SAU family medicine Dhaman Health Assurance Hospitals Company Kuwait KWT family medicine First Health Cluster Riyadh SAU Emergency Department Sheikh Khalifa Medical City Abudahbi ARE family medicine University of Medical Sciences and Technology Khartoum SDN family medicine Sudan Medical Specialization Board-Sudan Khartoum SDN family medicine Ultra Care Home Care Company Riyadh SAU medicine Department Health Gates Primary Care Riyadh SAU family medicine Mouwasat Hospital Madinah SAU

Research Background: The high prevalence of diabetes in Sudan, estimated at 16%, highlights the importance of effective health education in diabetes management. Diabetes self-management education has been identified as a crucial tool in enhancing the knowledge, attitudes, and abilities necessary for self-management among individuals with diabetes. Aim: To assess the impact of diabetes self-management education on medication adherence and glycemic control in Sudanese adults with type 2 diabetes before and 3 months after the DSME intervention. Method: The study was conducted in Sudan between September 2022 and March 2023, it was an interventional, one-group, pre- and post-test study that aimed to assess the impact of diabetes self-management education (DSME) on medication adherence and diabetes control in Sudanese adults with type 2 diabetes. The research was conducted in primary health care centers in six cities in Sudan and involved 244 participants. The data entry and statistical analysis were conducted using the Statistical Package for social Sciences version 27.0. A paired t test was used for analysis. Results: The study included 244 participants, 67% of whom were males. The age mean ± SD was 48.6 ± 9.3 years, and 85.3% of participants were married. Age at onset of diabetes mean ± SD was 40.60 ± 7.81 years;44.6% had diabetes for less than 5 years;and 84.1% had a positive family history of diabetes mellitus. The levels of poor, low, and partial adherence to medication decreased by 8.2%, 4%, and 20.6%, respectively, after the intervention. The levels of good and high medication regime adherence increased by 13% and 19.8%, respectively;BMI decreased by 1.1 ± 0.73 kg/m2 (p = 0.005). The fasting blood sugar decreased by 69 ± 32.9 mg/dl (p = 0.049), and the glycated hemoglobin decreased by 1.21 ± 0.28% (p = 0.001). Conclusions: The findings of this study reinforce the importance of patient education in improving glycemic control and enhancing self-management

关键词： Sudan Adherence Intervention Education Self-Management Diabetes

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Positive health:An integrated quantitative approach in patients with chronic gastrointestinal and hepato-pancreatico-biliary disorders

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World Journal of Gastroenterology 2024年第28期30卷 3418-3427页

作者： Anja H W M Lemlijn-Slenter Karolina AP Wijnands Gijs van der Hamsvoort Luuk P van Iperen Nico Wolter Angelique E de Rijk Ad AM Masclee Department of social medicine Faculty of HealthMedicine and Life sciencesCare and Public Health Research Institute Maastricht UniversityMaastricht 6200 MDLimburgNetherlands Division of Gastroenterology and Hepatology Department of Internal MedicineSchool of Nutrition and Translational Research in MetabolismMaastricht 6200 MDLimburgNetherlands social Medical Affairs Employee Insurance Agency(UWV)Heerlen 6400 ACLimburgNetherlands Department of Research Academic Knowledge Center Work and Health South-East Netherlands(AKAG-ZON)Heerlen 6400 ACLimburgNetherlands

BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of *** approach is especially relevant for patients with chronic *** gastrointestinal and hepatopancreatico-biliary(GI-HPB)disorders are among the top-6 of the most prevalent chronically affected organ *** impact of chronic GI-HPB disorders on individuals may be disproportionally high because:(1)The affected organ system frequently contributes to a malnourished state;and(2)persons with chronic GIHPB disorders are often younger than persons with chronic diseases in other organ *** To describe and quantify the dimensions of PH in patients with chronic GI-HPB *** Prospective,observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GIHPB disorder attending the Outpatient Department of the Maastricht University Medical *** questionnaires and data from patient files were used to quantify the six dimensions of *** consistency was tested with McDonald’s ***-order Pearson correlations and t-tests were used to assess associations and differences.A P value<0.05 was considered *** The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general *** quality of life,participation and daily functioning,GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems,but depressive symptoms(in 35%)and malnutrition(in 45%)were more frequent in patients with chronic GI-HPB *** scores between the six dimensions were only very weak to weak,forcing us to quantify each domain *** All six dimensions of PH are impaired in the GI-HPB *** and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.

关键词： Positive health Chronic gut disorders Gastrointestinal disorders Hepato-pancreatico-biliary disorders Integrated care

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