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Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension

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Bioactive Materials 2022年第2期7卷 494-504页

作者： Chen Wang Changyang Xing zhelong li Yunnan liu Qiaoying li Yixiao Wang Jiao Hu lijun Yuan Guodong Yang Department of Ultrasound Diagnostics Tangdu HospitalFourth Military Medical UniversityXi’an710038People’s Republic of China State Key Laboratory of Cancer Biology Fourth Military Medical UniversityXi’an710032People’s Republic of China Department of Biochemistry and Molecular Biology Fourth Military Medical UniversityXi’an710032People’s Republic of China

Arterial stiffness due to the vessel remodeling is closely linked to raised blood pressure,and its physiopathologic mechanism is still not fully understood.We here aimed to explore whether extracellular vesicle(EV)mediated intercellular communication between endothelium and smooth muscle cell contribute to the blood vessel remodeling under hypertension.We here revealed that the arterial endothelial cells robustly secreted EV,which in turn could be circulated and/or directly taken up by the subendothelial smooth muscle cells(SMC).Under hypertension,the EV secretion increased and the miRNA profile changed significantly mainly due to the raised mechanical force and subsequent enhanced reactive oxygen species generation.Among the miRNA cargos in the EV,miR-320d/423-5p were found increased most significantly.In vivo delivery of miR-320d/423-5p mimics via engineered EV increased their expression in arterial vessels,recapitulating the phenotype in hypertension.In contrast,therapeutic delivery of miR-320d/423-5p inhibitors via engineered EV alleviated the phenotype in spontaneous hypertension rat model.Together,we have found that the injured endothelium due to the raised mechanical force in hypertension contributes to the arterial wall remodeling via the secreted EV.Our study has not only provided novel insights on the mechanism of hypertension associated blood vessel wall remodeling,but also shed light on therapeutic intervention of hypertension associated vascular diseases.

关键词： Hypertension Extracellular vesicles Endothelial cell Smooth muscle cell Phenotype switch microRNA

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Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE^(-/-) mice

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Bioactive Materials 2022年第10期7卷 82-94页

作者： Tingting Wang Yan Dong li Yao Fan Lu Chenxi Wen Zhuo Wan li Fan zhelong li Te Bu Mengying Wei Xuekang Yang Yi Zhang Department of Equipment Division School of StomatologyFourth Military Medical UniversityXi’an710032People’s Republic of China Department of Burns and Cutaneous Surgery Xijing HospitalFourth Military Medical UniversityXi’an710032People’s Republic of China Department of Hematology Tangdu HospitalFourth Military Medical UniversityXi’an710038People’s Republic of China Department of Pathology Xi’an No.3 HospitalThe Affiliated Hospital of Northwest UniversityXi’an710018People’s Republic of China Department of Biochemistry and Molecular Biology Fourth Military Medical UniversityXi’an710032People’s Republic of China Department of Ultrasound Diagnostics Tangdu HospitalFourth Military Medical UniversityXi’an710038People’s Republic of China

Atherosclerosis is characterized by inflammation in the arterial wall,which is known to be exacerbated by diabetes.Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis.In this study,we showed that diabetes aggravated atherosclerosis in apolipoproteinE knockout(ApoE^(-/-))mice,in which increased expression of long-chain acyl-CoA synthetase 1(Acsl1)in macrophages played an important role.Knockdown of Acsl1 in macrophages(Mφ^(shAcsl1))reprogrammed macrophages to an anti-inflammatory phenotype,especially under hyperglycemic conditions.Injection of Mφ^(shAcsl1) reprogrammed macrophages into streptozotocin(STZ)-induced diabetic ApoE^(-/-) mice(ApoE^(-/-)+STZ)alleviated inflammation locally in the plaque,liver and spleen.Consistent with the reduction in inflammation,plaques became smaller and more stable after the adoptive transfer of reprogrammed macrophages.Taken together,our findings indicate that increased Acsl1 expression in macrophages play a key role in aggravated atherosclerosis of diabetic mice,possibly by promoting inflammation.Adoptive transfer of Acsl1 silenced macrophages may serve as a potential therapeutic strategy for atherosclerosis.

关键词： Atherosclerosis Diabetes Macrophage Acsl1 Adoptive transfer

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人体器官捐献中的死亡标准问题

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器官移植 2024年第3期15卷 359-366页

作者：杨顺良江哲龙吕立志李羽抒王栋中国人民解放军联勤保障部队第九〇〇医院泌尿外科福州350025 中国人民解放军联勤保障部队第九〇〇医院OPO 福州350025 中国人民解放军联勤保障部队第九〇〇医院肝胆外科福州350025 中国人民解放军联勤保障部队第九〇〇医院卫勤部福州350025

死亡后捐献是开展公民逝世后器官捐献工作最重要的伦理原则。新修订的《人体器官捐献和移植条例》未定义死亡,且回避了“是否承认脑死亡”这一关键性问题,器官捐献工作中可能存在一定的法律风险或损害捐献者权益的情况。死亡是人类生命... 详细信息

死亡后捐献是开展公民逝世后器官捐献工作最重要的伦理原则。新修订的《人体器官捐献和移植条例》未定义死亡,且回避了“是否承认脑死亡”这一关键性问题,器官捐献工作中可能存在一定的法律风险或损害捐献者权益的情况。死亡是人类生命过程最终无法避免的事实,任何时代都需要而且只能通过一些具体的标准来判定死亡。死亡标准的建立基础是人们所持有的死亡观,并受到生产力发展水平和其他社会因素制约。中西方死亡判定标准的认定上存在明显差异。为了规范器官捐献和移植工作,推进器官捐献高质量发展,必须坚持动机纯正原则,以知情同意为前提,尊重捐献者及其近亲属的死亡标准自主选择权,严格遵循死亡判定程序和操作规范,确保死亡认定的科学性、准确性和公正性。

关键词：器官捐献死亡标准脑死亡器官捐献心脏死亡器官捐献器官移植伦理知情同意自主选择

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HIF1α epigenetically repressed macrophages via CRISPR/Cas9-EZH2 system for enhanced cancer immunotherapy

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Bioactive Materials 2021年第9期6卷 2870-2880页

作者： Yan Dong Siyan Zhang Xiaotong Gao Dandan Yin Tingting Wang zhelong li Zhuo Wan Mengying Wei Ying Luo Guodong Yang li liu Department of Hematology Tangdu HospitalFourth Military Medical UniversityXi’an710038People’s Republic of China Department of Ultrasound Diagnostics Tangdu HospitalFourth Military Medical UniversityXi’an710038People’s Republic of China State Key Laboratory of Cancer Biology Fourth Military Medical UniversityXi’an710032People’s Republic of China Department of Biochemistry and Molecular Biology Fourth Military Medical UniversityXi’an710032People’s Republic of China Department of Pathophysiology Fourth Military Medical UniversityXi’an710032People’s Republic of China

Immune suppressive microenvironment in tumor emerges as the main obstacle for cancer immunotherapy.In this study,we identified that HIF1α was activated in the tumor associated macrophages and acted as an important factor for the immune suppressive microenvironment.Epigenetically silencing of Hif1αvia histone H3 methylation in the promoter region was achieved by CRISPR/dCas9-EZH2 system,in which histone H3 methylase EZH2 was recruited to the promoter region specifically.The Hif1αsilenced macrophage,namely HERM(Hif1αEpigenetically Repressed Macrophage)manifested as inheritable tumor suppressing phenotype.In the subcutaneous B16-F10 melanoma syngeneic model,intratumoral injection of HERMs reprogrammed the immune suppressive microenvironment to the active one,reducing tumor burden and prolonging overall survival.Additionally,HERMs therapy remarkably inhibited tumor angiogenesis.Together,our study has not only identified a promising cellular and molecular target for reverting immune suppressive microenvironment,but also provided a potent strategy for reprogramming tumor microenvironment via epigenetically reprogrammed macrophages.

关键词： Cancer immunotherapy Immune suppressive microenvironment Macrophage HIF1α CRISPR/dCas9 Epigenetically reprogrammed macrophage

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Calibration after bootstrap for accurate uncertainty quantification in regression models

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npj Computational Materials 2022年第1期8卷 1092-1100页

作者： Glenn Palmer Siqi Du Alexander Politowicz Joshua Paul Emory Xiyu Yang Anupraas Gautam Grishma Gupta zhelong li Ryan Jacobs Dane Morgan Department of Computer Sciences University of Wisconsin-MadisonMadisonWIUSA Department of Materials Science and Engineering University of Wisconsin-MadisonMadisonWIUSA

Obtaining accurate estimates of machine learning model uncertainties on newly predicted data is essential for understanding the accuracy of the model and whether its predictions can be trusted.A common approach to such uncertainty quantification is to estimate the variance from an ensemble of models,which are often generated by the generally applicable bootstrap method.In this work,we demonstrate that the direct bootstrap ensemble standard deviation is not an accurate estimate of uncertainty but that it can be simply calibrated to dramatically improve its accuracy.We demonstrate the effectiveness of this calibration method for both synthetic data and numerous physical datasets from the field of Materials Science and Engineering.The approach is motivated by applications in physical and biological science but is quite general and should be applicable for uncertainty quantification in a wide range of machine learning regression models.

关键词： ensemble applicable uncertainty

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基于流热耦合的表冷型转子线圈温度场仿真计算

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电机技术 2024年第1期 6-10页

作者：郦泽嵘徐国俊咸哲龙上海电气电站设备有限公司发电机厂 200240

文章以某空表冷发电机为研究对象,采用经典公式算法和计算流体动力学方法,对转子表面风摩损耗及转子线圈温升进行计算,并对不同方法得到的计算值与试验值进行对比分析。结果表明,低转速工况下两种方法得到的风摩损耗数值基本一致;采用... 详细信息

文章以某空表冷发电机为研究对象,采用经典公式算法和计算流体动力学方法,对转子表面风摩损耗及转子线圈温升进行计算,并对不同方法得到的计算值与试验值进行对比分析。结果表明,低转速工况下两种方法得到的风摩损耗数值基本一致;采用计算流体动力学方法得到的转子线圈温度更接近试验值。该计算方法可支撑发电机通风冷却系统的设计及优化。

关键词：空冷发电机转子线圈温度场流热耦合

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提高电动汽车接纳能力的配电网动态重构方法

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供用电 2024年第4期41卷 89-95页

作者：石立国李延真胡洋王者龙陈雷王长春国网山东省电力公司青岛供电公司山东青岛266000 天津相和电气科技有限公司天津300000

为提高配电网对电动汽车的接纳能力,提出一种考虑光伏出力、负荷及电动汽车充电功率不确定性的配电网动态重构方法。首先通过引入仿射数,对光伏出力、负荷及电动汽车充电功率不确定性进行描述。然后,以最大化电动汽车接纳能力为目标,建... 详细信息

为提高配电网对电动汽车的接纳能力,提出一种考虑光伏出力、负荷及电动汽车充电功率不确定性的配电网动态重构方法。首先通过引入仿射数,对光伏出力、负荷及电动汽车充电功率不确定性进行描述。然后,以最大化电动汽车接纳能力为目标,建立配电网动态重构模型,并通过改进郊狼算法进行求解,得到一天内24 h静态重构结果,并对重构结果相同的时段进行合并。最后,提出了基于欧氏距离的动态重构时段划分方法,将重构时段进行进一步合并,得到最终的动态重构时段。通过86节点配电网对所提重构方法进行仿真分析,结果表明,所提方法能够将电动汽车接纳能力提升21.16%,同时能够减少重构时段,降低开关的动作次数。

关键词：电动汽车接纳能力不确定性动态重构郊狼算法欧氏距离

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Efficient CRISPR/Cas9-mediated genome editing in sheepgrass(Leymus chinensis)

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Journal of Integrative Plant Biology 2023年第11期65卷 2416-2420页

作者： zhelong lin Lei Chen Shanjie Tang Mengjie Zhao Tong li Jia You Changqing You Boshu li Qinghua Zhao Dongmei Zhang Jianli Wang Zhongbao Shen Xianwei Song Shuaibin Zhang Xiaofeng Cao State Key Laboratory of Plant Genomics and National Center for Plant Gene Research Institute of Genetics and Developmental BiologyThe Chinese Academy of SciencesBeijing 100101China Institute of Forage and Grassland Sciences Heilongjiang Academy of Agricultural SciencesHarbin 150086China State Key Laboratory of Plant Cell and Chromosome Engineering Center for Genome EditingInstitute of Genetics and Developmental BiologyThe Chinese Academy of SciencesBeijing 100101China

The lack of genome editing platforms has hampered efforts to study and improve forage crops that can be grown on lands not suited to other crops.Here,we established efficient Agrobacterium-mediated clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated nuclease 9(Cas9)genome editing in a perennial,stress-tolerant forage grass,sheepgrass(Leymus chinensis).By screening for active single-guide RNAs(sg RNAs),accessions that regenerate well,suitable Agrobacterium strains,and optimal culture media,and co-expressing the morphogenic factor Ta WOX5,we achieved 11%transformation and 5.83%editing efficiency in sheepgrass.Knocking out Teosinte Branched1(TB1)significantly increased tiller number and biomass.This study opens avenues for studying gene function and breeding in sheepgrass.

关键词： Agrobacterium genetic transformation genome editing Lc TB1 sheepgrass

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基于能源设备的空-地立体化协同碳流分析研究

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微型电脑应用 2024年第5期40卷 53-55,59页

作者：刘继彦李延真公维帅鞠文杰王者龙王凌晨国网山东省电力公司山东济南250001 国网山东省电力公司青岛供电公司山东青岛266000 复旦大学信息科学与工程学院上海200438

为了有效确保二氧化碳含量监测的实时性、准确性和全面性,并探究影响二氧化碳含量的因素,设计基于能源设备的空-地立体化协同碳排放监测系统。搭建地面和空中两种二氧化碳监测环境,利用地面传感器获取排放口碳数据,利用无人机搭载传感... 详细信息

为了有效确保二氧化碳含量监测的实时性、准确性和全面性,并探究影响二氧化碳含量的因素,设计基于能源设备的空-地立体化协同碳排放监测系统。搭建地面和空中两种二氧化碳监测环境,利用地面传感器获取排放口碳数据,利用无人机搭载传感器获取空间内二氧化碳特征信息。通过Pearson相关系数法探究二氧化碳含量与环境因素之间的关联性,并融合空-地数据进行碳流分析。实验结果表明,该系统能较好地反映空间内二氧化碳含量的分布,具备较好的实时性、准确性和全面性。

关键词：碳排放二氧化碳传感器无人机空-地协同碳监测

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Electrodeposition of zinc-cobalt alloys from chloride bath

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材料保护 1992年第11期 4-8页

作者： Harbin Institute of Technology Zhang Jingshuang li Wenliang Yang zhelong An Maozhong Tu Zhenmi Wang Zuobin

Zinc-cobalt alloys have been electrodeposited from a ammonia-free mild acidic electrolyte based on potassium chloride. And the passivation of Zn-Co alloy was also investigated. The temperature, current density, pH and cobalt content of the bath, all effect the cobalt content of the alloy deposit. Control of cobalt concentration and temperature (or C.D) of the bath were best for requlating the alloy composition, the properties of Zn-Co coating are found to be superior to those of zinc deposit, and especially, the corrosion resistance of Zn-Co alloy increases remarkably.

关键词： Electrodeposition of zinc-cobalt alloys from chloride bath Zn

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