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Cell reprogramming therapy for Parkinson’s disease

Neural Regeneration Research 2024年第11期19卷 2444-2455页

作者： Wenjing Dong Shuyi Liu Shangang Li zhengbo wang State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan ProvinceChina Yunnan Key Laboratory of Primate Biomedical Research KunmingYunnan ProvinceChina

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars *** studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s *** initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical ***,ethical issues and tumor formation were limitations of its clinical *** pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell *** widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor *** induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s ***,there are also ethical concerns and the risk of tumor formation that need to be *** review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical *** review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo *** findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.

关键词： animal models astrocytes autologous cell reprogramming cell therapy direct lineage reprogramming dopaminergic neurons induced pluripotent stem cells non-human primates Parkinson’s disease

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COMPASS time synchronization and dissemination—Toward centimetre positioning accuracy

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Science China(Physics,Mechanics & Astronomy) 2014年第9期57卷 1788-1804页

作者： wang zhengbo ZHAO Lu wang ShiGuang ZHANG JianWei wang Bo wang LiJun NIM-THU Joint Institute for Measurement Science(JMI) Tsinghua University Department of Physics Tsinghua University Department of Applied Physics School of Physics and Nuclear Energy Engineering Beihang University Department of Precision Instruments & Mechanology Tsinghua University

In this paper we investigate methods to achieve highly accurate time synchronization among the satellites of the COMPASS global navigation satellite system(GNSS).Owing to the special design of COMPASS which implements several geo-stationary satellites(GEO),time synchronization can be highly accurate via microwave links between ground stations to the GEO *** as space-borne relay stations,the GEO satellites can further disseminate time and frequency signals to other satellites such as the inclined geo-synchronous(IGSO)and mid-earth orbit(MEO)satellites within the *** is shown that,because of the accuracy in clock synchronization,the theoretical accuracy of COMPASS positioning and navigation will surpass that of the *** addition,the COMPASS system can function with its entire positioning,navigation,and time-dissemination services even without the ground link,thus making it much more robust and *** further show that time dissemination using the COMPASS-GEO satellites to earth-fixed stations can achieve very high accuracy,to reach 100 ps in time dissemination and 3 cm in positioning accuracy,*** this paper,we also analyze two feasible synchronization *** special and general relativistic effects related to COMPASS clocks frequency and time shifts are *** conclude that COMPASS can reach centimeter-level positioning accuracy and discuss potential applications.

关键词： GNSS time and frequency Global Navigation Satellite System GNSS time synchronization time dissemination atomic clock phase locked loop relativity Geo-stationary satellites reference system

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Advances in the pathogenesis of Rett syndrome using cell models

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Animal Models and Experimental Medicine 2022年第6期5卷 532-541页

作者： Sijia Lu Yongchang Chen zhengbo wang State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingChina Yunnan Key Laboratory of Primate Biomedical Research KunmingChina

Rett syndrome(RTT)is a progressive neurodevelopmental disorder that occurs mainly in girls with a range of typical symptoms of autism spectrum ***2 protein loss-of-function in neural lineage cells is the main cause of RTT *** it is still hard to understand the mechanism of RTT on the basis of only clinical patients or animal models,cell models cultured in vitro play indispensable *** we reviewed the research progress in the pathogenesis of RTT at the cellular level,summarized the preclinical-research-related applications,and prospected potential future development.

关键词： cell models MeCP2 pathogenesis Rett syndrome

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Production calculation of the second and tertiary recovery combination reservoirs under chemical flooding

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Petroleum Exploration and Development 2021年第6期48卷 1403-1410页

作者： LIU Weidong wang Gaofeng LIAO Guangzhi wang Hongzhuang wang Zhengmao wang Qiang wang zhengbo State Key Laboratory of Enhanced Oil Recovery Beijing 100083China PetroChina Research Institute of Petroleum Exploration&Development Beijing 100083China PetroChina Exploration&Production Company Beijing 100007China

Based on the analysis of the production composition of reservoirs developed by the second&tertiary recovery combination(STRC),the relationship between the overall output of the STRC project and the production level during the blank water flooding stage is *** to the basic principle of reservoir engineering that the“recovery factor is equal to sweeping coefficient multiplied by oil displacement efficiency”,the formula for calculating the ultimate oil recovery factor of chemical combination flooding reservoir was *** dividing the reservoir into a series of grids according to differen-tial calculus thinking,the relationship between the ultimate recovery factor of a certain number of grids and the recovery de-gree of the reservoir was established,and then the variation law of oil production rate of the STRC reservoir was *** concept of“oil rate enlargement factor of chemical combination flooding”was defined,and a production calculation method of reservoir developed by STRC was put forward based on practical oilfield development *** study shows that the oil production enhancing effect of STRC increases evenly with the in crease of the ratio of STRC displacement efficiency to water displacement efficiency,and increases rapidly with the increase of the ratio of recovery degree at flooding mode conversion to the water displacement *** is more effective in increasing oil production of reservoir with high recovery *** practical tests of the alkali free binary flooding(polymer/surfactant)projects,the relative error of the oil production calculation method of STRC reservoir is about±10%,which meets the requirements of reservoir engineering.

关键词： chemical combination flooding second&tertiary recovery combination oil displacement efficiency oil rate en-largement factor of chemical flooding oil production calculation

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High-resolution frequency measurement of the ground-state hyperfine splitting of 113Cd+ ions

High-resolution frequency measurement of the ground-state hy...

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第四届中国卫星导航学术年会

作者： Shiguang wang Jianwei Zhang Kai Miao zhengbo wang Lijun wang Joint Institute for Measurement Science Tsinghua University Department of Physics Tsinghua University The state key lab of precision Measurement Technology and Instrument Department of Precision Instruments Tsinghua University

Time-keeping clock is one of the most important parts in COMPASS global navigation satellite system （GNSS） of China and the synchronization of these time-keeping clocks is the basis of GNSS. Recently, we have engaged in developing a transportable atomic clock based on 113Cd+ ions, which is potentially applied in the comparison of atomic clocks in different locations, including the time-keeping clocks at the ground stations of the COMPASS system. To operate a high precision microwave atomic clock, one has to measure its clock transition frequency precisely at zero external magnetic field. In this paper, the progress of the precision measurement of the ground-state hyperfine splitting of laser-cooled 113Cd+ ions is reported. In the previous experiment, the hyperfine splitting was measured to be 15 199 862 854.96（12） Hz, using Ramsey’s separated oscillation fields technique. Recently, by upgrading the ion trap apparatus, the control time sequence, and the magnetic field stabilization, we obtained a preliminary improved result of 15 199 862 855.013 Hz. This value is nearly one order of magnitude more accurate than the results obtained before.

关键词： microwave atomic clock ion trap hyperfine splitting 113Cd+ ions

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Progress Towards a Microwave Atomic Clock Based on the Laser-Cooled Cadmium Ions

Progress Towards a Microwave Atomic Clock Based on the Laser...

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第四届中国卫星导航学术年会

作者： Jianwei Zhang Shiguang wang Kai Miao zhengbo wang Lijun wang NIM-THU Joint Institute for Measurement Science(JMI) Tsinghua University Department of Precision Instruments and Mechanology Tsinghua University Department of Physics Tsinghua University

In the past decades, many groups in the world were engaged in building the microwave or optical frequency standards based on different trapped ions and achieved great improvements. A project aimed at a microwave atomic clock based on the laser-cooled 113Cd+ ions has been carried out since 2010 in our laboratory. The cadmium ion clock, a transportable clock with excellent frequency stability, is suitable in the comparison between the clocks located in different places, for example, to compare the time systems at different stations of the Compass system, or to examine the general relativity. A linear quadruple ion trap and the technique of laser cooling are applied in this clock. Meanwhile, the cadmium clock can be designed to be transportable which requires only one laser to accomplish the laser cooling, optical pump and optical detection. In this paper, we will report the detailed progress of this clock.

关键词： Microwave frequency standard Ion trap Cadmium ion Laser cooling

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基于肠脑轴传播α-突触核蛋白诱发帕金森病的研究进展

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生物工程学报 2022年第6期38卷 2120-2127页

作者：周佳文王正波昆明理工大学灵长类转化医学研究院云南昆明650500 省部共建非人灵长类生物医学国家重点实验室云南昆明650500 云南中科灵长类生物医学重点实验室云南昆明650500

帕金森病(Parkinson’s disease, PD)是最常见的神经退行性疾病,随着我国人口老龄化加剧,PD病人的增加将造成严重的经济和医疗负担。PD的典型病理特征是黑质致密部多巴胺能神经元的死亡以及多巴胺能神经元中异常聚集的淀粉样蛋白α-突... 详细信息

帕金森病(Parkinson’s disease, PD)是最常见的神经退行性疾病,随着我国人口老龄化加剧,PD病人的增加将造成严重的经济和医疗负担。PD的典型病理特征是黑质致密部多巴胺能神经元的死亡以及多巴胺能神经元中异常聚集的淀粉样蛋白α-突触核蛋白(α-synuclein,α-Syn)形成病理包涵体即路易小体(Lewy body)。研究发现路易小体不仅存在中枢神经系统中,也同样存在于外周神经系统。肠道内丰富的肠神经系统被称为“第二大脑”。肠脑轴的发现也证明α-Syn能在大脑和肠道进行双向传输。肠道中也存在着庞大的微生物群,这些微生物参与病理性α-Syn的形成和传输。因此文中基于肠脑轴探讨α-Syn在大脑和肠道的双向传输关系,尝试探索肠道微生物群对α-Syn异常聚集的影响。结合目前PD病人的研究和动物模型尤其是非人灵长类实验的研究,希望为PD疾病的筛查和诊断提供参考。

关键词：帕金森病 α-突触核蛋白肠脑轴肠道微生物动物模型

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多参数约束聚合物驱历史拟合方法

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石油勘探与开发 2010年第2期37卷 216-219,236页

作者：王正波王强叶银珠叶继根提高石油采收率国家重点实验室中国石油勘探开发研究院

聚合物驱数值模拟需要对大量物理化学现象进行描述,与水驱相比存在很强的特殊性。参考和借鉴水驱数值模拟历史拟合相关方法和聚合物驱油机理研究成果,筛选出聚合物的吸附量、残余阻力系数、聚合物溶液相对黏度、不可及孔隙体积、传导系... 详细信息

聚合物驱数值模拟需要对大量物理化学现象进行描述,与水驱相比存在很强的特殊性。参考和借鉴水驱数值模拟历史拟合相关方法和聚合物驱油机理研究成果,筛选出聚合物的吸附量、残余阻力系数、聚合物溶液相对黏度、不可及孔隙体积、传导系数、有效地层系数和表皮系数等7个影响聚驱效果的主要特征参数;在对这些参数开展较为详细的敏感性分析基础上,以多种现场实测资料作为约束条件,建立了一套较为系统、有效的多参数约束聚合物驱历史拟合方法。大庆某典型实际区块油藏数值模拟表明,聚合物驱历史拟合精度明显提高,单井含水拟合符合率达到75%。研究结果证明了该聚合物驱历史拟合方法的可行性和有效性。

关键词：聚合物驱三次采油历史拟合数值模拟敏感性分析

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A cynomolgus monkey with naturally occurring Parkinson's disease

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National Science Review 2021年第3期8卷 17-20页

作者： Hao Li Ling-Yan Su Lixin Yang Min Li Qianjin Liu Zhenhui Li Yan Hu Hongwei Li Shihao Wu Wenchao wang Yingzhou Hu zhengbo wang Joshua D.Rizak Baihui Huang Min Xu Jing Wu Long-Bao Lv Christoph W.Turck Yong Yin Yong-Gang Yao Bing Su Xintian Hu Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Shenzhen Key Laboratory for Molecular Biology of Neural Development Guangdong Provincial Key Laboratory of Brain Connectome and Behavior CAS Key Laboratory of Brain Connectome and Manipulation The Brain Cognition and Brain Disease Institute Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences China Kunming College of Life Science University of Chinese Academy of Sciences Institute of Neuroscience CAS Key Laboratory of Primate Neurobiology State Key Laboratory of NeuroscienceChinese Academy of Sciences National Resource Center for Non-Human Primates Kunming Primate Research Center and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) Kunming Institute of Zoology Chinese Academy of Sciences Max Planck Institute of Psychiatry Department of Translational Research in Psychiatry Department of Rehabilitation Medicine the Second People’s Hospital of Yunnan Province Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences KIZ–CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

Evidence for the existence of monkeys with spontaneous Parkinson’s disease (PD) has been lacking. Here,we screened macaque colonies at the Kunming Primate Research Center(Association for Assessment and Accreditation of Laboratory Animal Care(AAALAC) accredited), Kunming Institute of Zoology, Chinese Academy of Sciences, which has a large population of monkeys (>2400), to identify naturally occurring PD monkeys.

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非人灵长类帕金森动物模型中的行为学评估

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中国比较医学杂志 2023年第11期33卷 96-103页

作者：刘书一王正波昆明理工大学灵长类转化医学研究院省部共建非人灵长类生物医学国家重点实验室昆明650500 云南中科灵长类生物医学重点实验室昆明650500

帕金森病(Parkinson’s disease,PD)是一种神经退行性疾病,目前发病机制不明,患者会出现与疾病相关的运动和非运动症状。啮齿类动物模型只能部分精准模拟患者的症状,导致相关的临床前研究存在局限性,非人灵长类动物模型能够较好的弥补... 详细信息

帕金森病(Parkinson’s disease,PD)是一种神经退行性疾病,目前发病机制不明,患者会出现与疾病相关的运动和非运动症状。啮齿类动物模型只能部分精准模拟患者的症状,导致相关的临床前研究存在局限性,非人灵长类动物模型能够较好的弥补这种缺陷,对非人灵长类PD模型的运动和非运动症状的量化有利于发病机制和治疗的研究,本综述中总结了不同行为学量化方式,同时对比了不同方法之间的优劣性,为进行PD猴模型研究提供了行为学测试的参考。

关键词：帕金森病非人灵长类评分量表精细运动精神障碍认知障碍

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