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Infiltration by monocytes of the central nervous system and its role in multiple sclerosis: reflections on therapeutic strategies

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Neural Regeneration Research 2025年第3期20卷 779-793页

作者： Guangyong Zhang Qing Yao Chubing Long Pengcheng Yi Jiali Song Luojia Wu wei wan Xiuqin Rao Yue Lin Gen wei Jun Ying Fuzhou Hua Department of Anesthesiology the Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina Key Laboratory of Anesthesiology of Jiangxi Province NanchangJiangxi ProvinceChina

Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.

关键词： blood–brain barrier macrophages monocytes multiple sclerosis neuroinflammation review therapy

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Health benefits from the rapid reduction in ambient exposure to air pollutants after China's clean air actions:progress in efficacy and geographic equality

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National Science Review 2024年第2期11卷 103-113页

作者： Tao Xue Ruohan wang Meng wang Yanying wang Dan Tong Xia Meng Conghong Huang Siqi Ai Fangzhou Li Jingyuan Cao Mingkun Tong Xueqiu Ni Hengyi Liu Jianyu Deng Hong Lu wei wan Jicheng Gong Shiqiu Zhang Tong Zhu Clean Air Asia Institute of Reproductive and Child Health National Health Commission Key Laboratory of Reproductive Health/Department of Epidemiology and Biostatistics Ministry of Education Key Laboratory of Epidemiology of Major Diseases(PKU) School of Public Health Peking University Health Science Centre State Environmental Protection Key Laboratory of Atmospheric Exposure and Health Risk Management and Center for Environment and Health Peking University Advanced Institute of Information Technology Peking University Department of Epidemiology and Environmental Health School of Public Health and Health ProfessionsUniversity at Buffalo State Key Joint Laboratory of Environment Simulation and Pollution Control College of Environmental Sciences and EngineeringPeking University Department of Earth System Science Tsinghua University School of Public Health Key Laboratory of Public Health Safety of the Ministry of Education and Key Laboratory of Health Technology Assessment of the Ministry of HealthFudan University College of Land Management Nanjing Agricultural University National&Local Joint Engineering Research Center for Rural Land Resources Use and Consolidation

Clean air actions （CAAs） in China have been linked to considerable benefits in public health.However,whether the beneficial effects of CAAs are equally distributed geographically is unknown.Using high-resolution maps of the distributions of major air pollutants (fine particulate matter[PM2.5]and ozone[O3]) and population,we aimed to track spatiotemporal changes in health impacts from,and geographic inequality embedded in,the reduced exposures to PM2.5and O3from 2013 to 2020.We used a method established by the Global Burden of Diseases Study.By analyzing the changes in loss of life expectancy（LLE） attributable to PM2.5and O3,we calculated the gain of life expectancy （GLE） to quantify the health benefits of the air-quality improvement.Finally,we assessed the geographic inequality embedded in the GLE using the Gini index （GI）.Based on risk assessments of PM2.5and O3,during the first stage of CAAs（2013 to 2017）,the mean GLE was 1.87 months.Half of the sum of the GLE was disproportionally distributed in about one quarter of the population exposed （GI 0.44）.During the second stage of CAAs（2017 to 2020）,the mean GLE increased to 3.94 months and geographic inequality decreased （GI 0.18）.According to our assessments,CAAs were enhanced,from the first to second stages,in terms of not only preventing premature mortality but also ameliorating health inequalities.The enhancements were related to increased sensitivity to the health effects of air pollution and synergic control of PM2.5and O3levels.Our findings will contribute to optimizing future CAAs.

关键词： clean air action public health inequality fine particulate matter ozone

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Mental retardation,seizures and language delay caused by new SETD1B mutations:Three case reports

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World Journal of Clinical Cases 2024年第2期12卷 383-391页

作者： Le Ding Li-wan wei Tai-Song Li Jing Chen Department of Neurology Children’s Hospital of Nanjing Medical UniversityNanjing 210000Jiangsu ProvinceChina Chigene(Beijing)Translational Medical Research Center Co.Ltd.Beijing 101111China

BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE SUMMARY This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation,epilepsy,and language delay resulting from a new mutation in the SETD1B gene.Three individuals with these symptoms were selected,and their clinical symptoms,gene test results,and treatment were analyzed.This article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment approach.Among the three patients(two females and one male,aged 8,4,and 1,respectively),all exhibited psychomotor retardation,attention deficit,and hyperactivity disorder,and two had epilepsy.Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child,although mental development remained somewhat delayed.Whole exome sequencing revealed new mutations in the SETD1B gene for all patients,specifically with c.5473C>T(p.Arg1825trp),c.4120C>T(p.Gln1374*,593),c.14_15insC(p.His5Hisfs*33).CONCLUSION Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language delay.Although the exact mechanism is not fully understood,interventions such as drug therapy,rehabilitation training,and family support can assist patients in managing their symptoms and enhancing their quality of life.Furthermore,genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance,informs families about genetic disease risks,and contributes to understanding disease pathogenesis and drug research and development.

关键词： Neurodevelopmental disorder Seizure SETD1B gene Whole-exome sequencing New mutation Case report

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Strengthened Initialization of Adaptive Cross-Generation Differential Evolution

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Computer Modeling in Engineering & Sciences 2022年第3期129卷 1495-1516页

作者： wei wan Gaige wang Junyu Dong Department of Computer Science of Technology Ocean University of ChinaQingdao266100China Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education Jilin UniversityChangchun130012China Guangxi Key Laboratory of Hybrid Computation and IC Design Analysis Guangxi University for NationalitiesNanning530006China

Adaptive Cross-Generation Differential Evolution(ACGDE)is a recently-introduced algorithm for solving multiobjective problems with remarkable performance compared to other evolutionary algorithms(EAs).However,its convergence and diversity are not satisfactory compared with the latest algorithms.In order to adapt to the current environment,ACGDE requires improvements in many aspects,such as its initialization and mutant operator.In this paper,an enhanced version is proposed,namely SIACGDE.It incorporates a strengthened initialization strategy and optimized parameters in contrast to its predecessor.These improvements make the direction of crossgeneration mutation more clearly and the ability of searching more efficiently.The experiments show that the new algorithm has better diversity and improves convergence to a certain extent.At the same time,SIACGDE outperforms other state-of-the-art algorithms on four metrics of 24 test problems.

关键词： Differential Evolution(DE) multi-objective optimization(MO) opposition-based learning parameter adaptation

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ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover

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Protein & Cell 2023年第9期14卷 653-667页

作者： Maomao Pu Wenhui Zheng Hongtao Zhang wei wan Chao Peng Xuebo Chen Xinchang Liu Zizhen Xu Tianhua Zhou Qiming Sun Dante Neculai wei Liu Metabolic Medicine Center International Institutes of Medicinethe Fourth Affiliated HospitalZhejiang University School of MedicineYiwu 322000China Joint Institute of Genetics and Genomics Medicine between Zhejiang University and University of Toronto Hangzhou 310058China National Center for Protein Science Shanghai Institute of Biochemistry and Cell BiologyShanghai Institutes of Biological SciencesChinese Academy of SciencesShanghai200031China

Lipophagy,the selective engulfment of lipid droplets(LDs)by autophagosomes for lysosomal degradation,is critical to lipid and energy homeostasis.Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes.This function of oRP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs.Upon lipophagy induction,ORP8 has increased localization on LDs and is phosphorylated by AMPK,thereby enhancing its affinity for LC3/GABARAPs.Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride.Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice,and Osbpl8 mice exhibit liver lipid clearance defects.Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.

关键词： ORP8 lipophagy lipid autophagy

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Salidroside Ameliorates Lung Injury Induced by PM_(2.5) by Regulating SIRT1-PGC-1αin Mice

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Biomedical and Environmental Sciences 2024年第4期37卷 367-376页

作者： LI Xiao Hong LIU Yu Mei SHAN Hui TAN Jin Feng ZHOU Jian SONG Yuan Jin LI Si Qi LIU Chen XU Dong Qun YU Li LI wan wei School of Public Health Shandong Second Medical UniversityWeifang 261053ShandongChina Key Laboratory of Health Inspection and Quarantine Weifang 261053ShandongChina weifang Environmental Monitoring Station Weifang 261042ShandongChina Department of Orthopedics The 80th Army Hospital of PLAWeifang 261000ShandongChina Environment and Health Related Product Safety Institute of Chinese Center for Disease Control and Prevention Beijing 100021China School of Basic Medicine Shandong Second Medical UniversityWeifang 261053ShandongChina

Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM_(2.5) in mice and illuminate the function of SIRT1-PGC-1ɑaxis.Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM_(2.5) group,SAL+PM_(2.5) group.On the first day,SAL was given by gavage,and on the second day,PM_(2.5) suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑproteins were detected by Western blotting.Results Exposure to PM_(2.5) leads to obvious morphological and pathologica changes in the lung of mice.PM_(2.5) caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM_(2.5) by activating the SIRT1-PGC-1α pathway.Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.

关键词： PM_(2.5) Salidroside Oxidative stress Inflammation Apoptosis SIRT1-PGC-1α

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求解高维优化问题的ITCSO算法

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控制与决策 2024年第2期39卷 449-457页

作者：张伟魏万峰黄卫民河南理工大学电气工程与自动化学院河南焦作454003

为提高竞争群优化(competitive swarm optimization,CSO)算法求解高维优化问题的寻优效率,提出一种改进的3重竞争群优化(improved triple competitive swarm optimization,ITCSO)算法.首先,采用3重竞争机制提高算法的寻优效率,同时,获胜粒子较好的收敛基础可以提高失败粒子的个体认知,明确粒子更新方向以提高粒子探索能力;然后,提出优败粒子向获胜子群学习的策略,增强算法的社会认知能力,减少算法评估次数,从而提高算法全局搜索能力;最后,提出获胜子群自竞争和劣败粒子基于获胜者变异的操作,增强粒子局部开发能力,避免算法陷入局部最优.为验证所提出算法的可行性,通过计算系统状态转移矩阵特征值和使用极限分析方法,给出稳定性和收敛性理论证明.采用几种基准测试函数验证所提出算法求解高维问题时的性能,并与其他算法进行对比.实验结果表明,ITCSO算法不仅有较高的寻优效率,且全局搜索和局部开发能力突出,更适用于高维问题的求解.

关键词：粒子群优化算法竞争群优化算法高维优化 3重竞争机制局部开发收敛性分析

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亚精胺抑制核糖体DNA转录

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科学通报 2024年第15期69卷 2072-2080页

作者：许银丰万伟湖南第一师范学院基础生物学实验室长沙410205 浙江大学医学院生物化学系杭州310058

核糖体是细胞内合成蛋白的唯一细胞器,主要由核糖体RNA(ribosomal RNA,rRNA)和核糖体蛋白组装形成.rDNA转录生成rRNA在细胞内的核仁处完成,是核糖体生物发生的重要限速步骤之一.在正常细胞内,核糖体DNA(ribosomal DNA,rDNA)的转录活性... 详细信息

核糖体是细胞内合成蛋白的唯一细胞器,主要由核糖体RNA(ribosomal RNA,rRNA)和核糖体蛋白组装形成.rDNA转录生成rRNA在细胞内的核仁处完成,是核糖体生物发生的重要限速步骤之一.在正常细胞内,核糖体DNA(ribosomal DNA,rDNA)的转录活性受到营养状态的严密调控.而在癌细胞内,癌基因的激活、抑癌基因的失活和生长相关信号通路的失调等多种不同的机制均可导致rDNA的转录绕过营养状态的控制.癌细胞内异常激活的rDNA转录是癌细胞快速生长、增殖的必要前提,也是癌细胞的共有特征之一.抑制癌细胞内异常激活的r DNA转录有望开发出新的抗癌药物.我们既往的研究揭示,肿瘤蛋白p53诱导核蛋白2(tumor protein p53 inducible nuclear protein 2,TP53INP2)的核仁定位是其促进rDNA转录的重要前提,可用来指示细胞内的rDNA转录活性.本研究发现,天然活性成分亚精胺可抑制TP53INP2的核仁定位,并显著降低细胞的rDNA转录活性.机制研究表明,亚精胺可抑制蛋白激酶雷帕霉素靶蛋白复合物1(mechanistic target of rapamycin complex 1,mTORC1)的必需亚基Raptor的乙酰化并降低细胞内m TORC1的活性,进而抑制r DNA的转录.功能研究揭示,亚精胺可显著抑制蛋白的合成和细胞的增殖.本研究提示,抑制细胞内的r DNA转录活性可能是亚精胺发挥抗癌作用的重要机制之一.

关键词：癌症 mTORC1 rDNA转录核糖体生物发生亚精胺

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New WHO global air quality guidelines help prevent premature deaths in China

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National Science Review 2022年第4期9卷 10-12页

作者： Tao Xue Guannan Geng Xia Meng Qingyang Xiao Yixuan Zheng Jicheng Gong Jun Liu wei wan Qiang Zhang Haidong Kan Shiqiu Zhang Tong Zhu Institute of Reproductive and Child Health/National Health Commission Key Laboratory of Reproductive Health and Department of Epidemiology and Biostatistics School of Public HealthPeking University State Key Joint Laboratory of Environmental Simulation and Pollution Control School of EnvironmentTsinghua University School of Public Health Key Laboratory of Public Health Safety of the Ministry of Educationand Key Laboratory of Health Technology Assessment of the Ministry of HealthFudan University Center of Air Quality Simulation and System Analysis Chinese Academy of Environmental Planning College of Environmental Sciences and Engineering Peking University School of Energy and Environmental Engineering University of Science and Technology Beijing Clean Air Asia Ministry of Education Key Laboratory for Earth System Modeling Department of Earth System ScienceTsinghua University

The air quality guidelines (AQGs) issued by the World Health Organization (WHO) in 2005 are key references for the National Ambient Air Quality Standards (NAAQSs) in China.On 22September 2021,the WHO issued new AQGs (NAQGs)[1],which propose more stringent targets to control exposure to multiple air pollutants,including fine particulate matter (PM2.5) and ozone (O3),to which,in 2019,451 million premature deaths,globally,were attributable [2].

关键词： OZONE EXPOSURE POLLUTION HEALTH PM2.5 ASSOCIATIONS MORTALITY

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Dark rearing maintains tyrosine hydroxylase expression in retinal amacrine cells following optic nerve transection

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Neural Regeneration Research 2012年第1期7卷 18-23页

作者： wei wan Zhenghai Liu Xiaosheng wang Xuegang Luo Department of Human Anatomy and Neurobiology Xiangya Medical College of Central South University Changsha 410013 Hunan Province China Department of Human Anatomy University of South China Hengyang 421001 Hunan Province China

The present study examined changes in retinal tyrosine hydroxylase （TH） expression in rats having undergone optic nerve transection and housed under a normal day/night cycle or in the dark. The aim was to investigate the effects of amacrine cells on axonal regeneration in retinal ganglion cells and on the synapses that transmit visual signals. The results revealed that retinal TH expression gradually decreased following optic nerve transection in rats housed under a normal day/night cycle reaching a minimum at 5 days. In contrast, retinal TH expression decreased to a minimum at 1 day following optic nerve transection in dark reared rats, gradually increasing afterward and reaching a normal level at 5 7 days. The number of TH-positive synaptic particles correlated with the TH levels indicating that dark rearing can help maintain TH expression during the synaptic degeneration stage （5 7 days after optic nerve injury） in retinal amacrine cells.

关键词： optic nerve transection tyrosine hydroxylase dark rearing amacrine cells peripheral nerve injury neural regeneration

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