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Precise delivery of obeticholic acid via nanoapproach for triggering natural killer T cell-mediated liver cancer immunotherapy

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2171-2182页

作者： Guofeng Ji Lushun Ma haochen yao Sheng Ma Xinghui Si Yalin Wang Xin Bao Lili Ma Fangfang Chen Chong Ma Leaf Huang Xuedong Fang Wantong Song Department of Gastrointestinal and Colorectal Surgery China-Japan Union Hospital of Jilin UniversityChangchun 130033China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of PharmacyUniversity of North Carolina at Chapel HillChapel HillNC 27599USA Key Laboratory of Zoonosis Chinese Ministry of EducationCollege of Basic Medical ScienceJilin UniversityChangchun 130021China Second Hospital of Shandong University Jinan 250000China Second Hospital of Jilin University Changchun 130041China Jilin Biomedical Polymers Engineering Laboratory Changchun 130022China State Key Laboratory of Inorganic Synthesis and Preparative Chemistry College of ChemistryJilin UniversityChangchun 130012China

Primary bile acids were reported to augment secretion of chemokine(C-X-C motif)ligand16(CXCL16)from liver sinusoidal endothelial cells(LSECs)and trigger natural killer T(NKT)cellbased immunotherapy for liver ***,abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer *** advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation,we proposed a strategy using nanoemulsion-loaded obeticholic acid(OCA),a clinically approved selective farnesoid X receptor(FXR)agonist,for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer *** OCA-nanoemulsion(OCA-NE)was prepared via ultrasonic emulsification method,with a diameter of 184 nm and good *** vivo biodistribution studies confirmed that the injected OCA-NE mainly accumulated in the liver and especially in LSECs and Kupffer *** a result,OCA-NE treatment significantly suppressed hepatic tumor growth in a murine orthotopic H22 tumor model,which performed much better than oral medication of free *** analysis revealed that the OCA-NE resulted in augmented secretion of CXCL16 and IFN-g,as well as increased NKT cell populations inside the ***,our research provides a new evidence for the antitumor effect of receptors for primary bile acids,and should inspire using nanotechnology for precisely manipulating LSECs for liver cancer therapy.

关键词： Obeticholic acid Farnesoid X receptor Nanoemulsion Liver sinusoidal endothelial cells Liver cancer

Epidemiologic and clinical characteristics of 42 deaths caused by SARS-CoV-2 infection in Wuhan, China: A retrospective study

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Biosafety and Health 2020年第3期2卷 164-168页

作者： Nan Zhang haochen yao Dong Zhang Jiahui Pan Ejun Peng Juanjuan Huang Yingli Zhang Xiaoming Xu Guobao Tian Hong Xu Guoqing Wang The First Hospital of Jilin University Changchun 130021China Department of Pathogenobiology The Key Laboratory of ZoonosisChinese Ministry of EducationCollege of Basic Medical ScienceJilin UniversityChangchun 130021China Tongji Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Sun Yat-sen University Zhongshan School of Medicine Guangzhou 510275China

This study described the epidemiologic and clinical characteristics of patients who died from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,and pointed out the potential risk factors associated with fatal *** data from 42 death cases due to SARS-CoV-2 infection at Tongji Hospital Affiliated to Huazhong University of Science and Technology,Wuhan,China was ***,clinical detection,laboratory findings,and treatments of the deceased were collected and *** average time between onset of symptoms and admission to the hospitals was 11±5 days of *** the deceased,60%were with *** of them were having fever and bilateral pneumonia on computed tomography,abnormal infection-related biomarkers,and renal *** blood coagulation parameters that appeared in more than half of them,were consistent with disseminated intravascular *** of the patients were treated in the *** on the fact that SARS-CoV-2 infection carries a risk of mortality,we may infer a few older male patients with underlying comorbidities are likely to have the increased *** consciousness level,markers of renal impairment and coagulation abnormalities may be poor prognostic factors.

关键词： SARS-CoV-2 COVID-19 Death cases Epidemiology Clinical characteristics Risk factors

Collector efficiency for hydrosol deep-bed filtration of non-Brownian particles at low and finite Reynolds numbers

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Particuology 2020年第6期18卷 124-133页

作者： haochen Li John Sansalone Engineering School of Sustainable Infrastructure and Environment(ESSIE) College of EngineeringUniversity of Florida217 BlackGainesvilleFL 32611USA

Aqueous filtration systems with granular media are increasingly implemented as a unit operation for the treatment of urban *** of these aqueous filtration systems are designed with coarse granular media and are therefore subject to finite granular Reynolds numbers(Reg).In contrast to the Reg conditions generated by such designs,current hydrosol filtration models,such as the yao and RT models,rely on a flow solution that is derived within the Stokes limit at low *** systems that are subject to these finite and higher Reg regimes,the collector efficiency has not been ***,in this study,we develop a 3D periodic porosity-compensated face-centered cubic sphere(PCFCC)computational fluid dynamics(CFD)model,with the surface interactions incorporated,to investigate the collector efficiency for Reg ranging from 0.01 to *** filtration induced by interception and sedimentation is examined for non-Brownian particlesfanging from 1 to 100 μm under favorable surface interactions for particle *** results from the CFD-based PCFCC model agreed well with those of the classical RT and yao models for Reg<*** on 3150 simulations from the PCFCC model,we developed a new correlation for vertical aqueous filtration based on a modified gravitation number,NG^*,for the initial deep-bed filtration efficiency at lower yet finite(0.01 to 20)*** proposed PCFCC model has low computational cost and is extensibile from vertical to horizontal filtration at low and finite Reg.

关键词： Deep-bed filtration Granular filtration Unit operations Stormwater Urban water Urban drainage

Reduction of mercury(Ⅱ)by electrons contained in carbon dots:An environmentally friendly cold vapor generation for mercury analysis

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Chinese Chemical Letters 2020年第10期31卷 2678-2682页

作者： Tao Chen yao Lin haochen Li Rui Yang Xiandeng Hou Baozhan Zheng Chengbin Zheng Key Laboratory of Green Chemistry and Technology Ministry of EducationCollege of ChemistrySichuan UniversityChengdu 610064China Chengdu No.7 High School Chengdu 610041China Analytical&Testing Center Sichuan UniversityChengdu 610064China

In this work,the reduction of mercury ions(Hg2+)to elemental mercury(Hg0)was easily achieved using highly reductive carbon dots(r-CDs),which synthesized from sucrose by a simple and cost-effective *** a careful mechanistic study,the reduction was probably accomplished with the large numbers of electrons contained in r-CDs rather than the oxidation of its functional ***,a3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay showed that the r-CDs were nontoxic to wildlife and human ***,the r-CDs were used as an alternative to toxic reductants(SnCl2 or NaBH4)for the sensitive and in situ determination of mercury by cold vapor gene ration(CVG)coupled to a miniature point discharge optical emission spectrometer(μPD-OES).Limit of detection of 0.05μg/L was obtained for Hg2+,with relative standard deviation(RSD)less than 5.4%at a concentration of 5μg/*** accuracy of r-CDs induced CVG-μPD-OES was validated by the determination of mercury in a certified reference material(DOLT-5,dogfish liver)and five natural water samples collected from different rivers and lakes in Chengdu City,Since r-CDs are nontoxic and prepared from abundant and inexpensive sucrose,the r-CDs induced CVG-μPD-OES retains the great potential for the inexpensive and enviro nmentally friendly field analysis of mercury in natural *** accuracy of the proposed method was validated by the analysis of a certified reference material and several water samples with satisfactory results.

关键词： Mercury analysis Reduction Carbon dots Cold vapor generation

Genomic Selection for Frogeye Leaf Spot Resistance in Soybean

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Journal of Northeast Agricultural University(English Edition) 2024年第1期31卷 11-19页

作者： yao Lanning Chen Yizhi Li haochen Zhang Yue Xia Mingyu Ning Shicheng Ning Hailong College of Arts and Sciences Northeast Agricultural UniversityHarbin 150030China College of Life Sciences Northeast Agricultural UniversityHarbin 150030China College of Economics and Management Northeast Agricultural UniversityHarbin 150030China College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150030China Key Laboratory of Soybean Biology Ministry of EducationKey Laboratory of Soybean Biology and Breeding/GeneticsMinistry of AgricultureCollege of AgricultureNortheast Agricultural UniversityHarbin 150030China Zhongnongfa Wudalianchi Agricultural Technology Co. LtdWudalianchi 164100HeilongjiangChina

Soybean frogeye leaf spot(FLS) disease is a global disease affecting soybean yield, especially in the soybean growing area of Heilongjiang Province. In order to realize genomic selection breeding for FLS resistance of soybean, least absolute shrinkage and selection operator(LASSO) regression and stepwise regression were combined, and a genomic selection model was established for 40 002 SNP markers covering soybean genome and relative lesion area of soybean FLS. As a result, 68 molecular markers controlling soybean FLS were detected accurately, and the phenotypic contribution rate of these markers reached 82.45%. In this study, a model was established, which could be used directly to evaluate the resistance of soybean FLS and to select excellent offspring. This research method could also provide ideas and methods for other plants to breeding in disease resistance.

关键词： LASSO regression stepwise regression genomic selection model soybean frogeye leaf spot(FLS)disease

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航空机电作动器神经网络快速终端滑模控制

航空学报 2021年第6期42卷 105-114页

作者：魏科鹏胡健姚建勇邢浩晨乐贵高南京理工大学机械工程学院南京210094

目前机电作动器由于具有干净、维护方便等优点,越来越受到航空业的青睐。航空机电作动器的特点是控制精度、稳定性和响应速度要求高,针对以上特点,提出了一种基于多层神经网络的快速终端滑模控制策略。为了提高航空作动器响应速度和跟... 详细信息

目前机电作动器由于具有干净、维护方便等优点,越来越受到航空业的青睐。航空机电作动器的特点是控制精度、稳定性和响应速度要求高,针对以上特点,提出了一种基于多层神经网络的快速终端滑模控制策略。为了提高航空作动器响应速度和跟踪精度,设计了快速终端滑模控制策略,不仅可以加快系统响应而且可以在无扰动情况下实现系统的有限时间稳定。针对系统参数不确定性和外部扰动,设计多层神经网络进行估计并通过前馈方法加以补偿。针对神经网络的重构误差,设计了非线性鲁棒项加以克服。利用李亚普洛夫稳定性定理证明了控制系统在有扰动情况下可以实现有界稳定。实验结果表明:所设计的控制器具有良好的参数自适应和抗干扰能力,同时具有更高的跟踪精度和更快的响应速度。

关键词：航空机电作动器快速终端滑模控制神经网络非线性控制模型不确定性

城创融合视角下从工业区到创新街区的更新路径与国际经验

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国际城市规划 2022年第5期37卷 90-97页

作者：周可斌师浩辰王世福刘垚华南理工大学建筑学院华南理工大学建筑设计研究院有限公司何镜堂建筑创作研究院城市规划设计与研究中心华南理工大学亚热带建筑科学国家重点实验室华南理工大学粤港澳大湾区规划创新研究中心广东工业大学建筑与城市规划学院

随着技术进步对城市经济社会发展逻辑的改变,量大面广的既有城市工业区在转型更新过程中呈现出功能和空间的创新转向特征。创新经济和创新活动的“城创融合”趋势催生了创新街区这一新的城市空间模式并产生了成功实践。笔者通过文献综... 详细信息

随着技术进步对城市经济社会发展逻辑的改变,量大面广的既有城市工业区在转型更新过程中呈现出功能和空间的创新转向特征。创新经济和创新活动的“城创融合”趋势催生了创新街区这一新的城市空间模式并产生了成功实践。笔者通过文献综述归纳总结创新街区的共性特征,提出基于创新街区理念的既有城市工业区更新的SANP概念模型,从创新空间、创新活动、创新网络与创新政策四个维度量化验证全球典型的工业区成功转型案例,并阐明如何采取具体举措来实现产业升级、空间提质与活力激发,为创新经济背景下我国大量既有城市工业区的转型与更新提供理论借鉴。

关键词：创新街区城市工业区转型更新 SANP框架

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钢管混凝土圆弧拱跨中与拱脚滑移性能的研究

煤炭学报 2018年第9期43卷 2461-2468页

作者：单仁亮张晓楠张磊白瑶张浩琛孙嵩陈宇翔中国矿业大学(北京)力学与建筑工程学院北京100083 中国新兴矿业化工总公司北京100039 中国科学院深海科学与工程研究所海南三亚572000

通过对6点均布加载条件下钢管混凝土圆弧拱跨中位置处位移和拱脚不同滑移量的监测,以及对钢管外壁和内部核心混凝土的应变、极限承载能力进行分析,同时通过内嵌一种无厚度黏聚力黏结单元的ABAQUS大型有限元软件建立混凝土损伤模型,对圆... 详细信息

通过对6点均布加载条件下钢管混凝土圆弧拱跨中位置处位移和拱脚不同滑移量的监测,以及对钢管外壁和内部核心混凝土的应变、极限承载能力进行分析,同时通过内嵌一种无厚度黏聚力黏结单元的ABAQUS大型有限元软件建立混凝土损伤模型,对圆弧拱抗弯过程进行全过程仿真三维数值模拟分析,较为准确的展示钢管核心混凝土受压破坏过程。实验和模拟分析结果表明:与两端固定相比,钢管混凝土圆弧拱试件在拱脚滑移的过程中,由于受到拉压弯三重作用发生了破坏,核心混凝土产生裂缝,随着荷载继续增加,裂缝的存在导致混凝土体积膨胀,进而使钢管发生鼓包。在一定的拱脚滑移量范围内,跨中截面核心混凝土底部受拉顶部受压,试件跨中与拱脚的弯矩急剧增加,钢管混凝土圆弧拱的承载力随着拱脚滑移量的增加而降低。通过室内试验和数值模拟,以及现场监测的结果分析可知,圆弧拱跨中下降的位移与两侧滑移量呈两倍关系。达到极限荷载后,圆弧拱试件中钢管对混凝土的套箍作用失效。

关键词： CFST拱抗弯实验 ABAQUS有限元模拟现场监测

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阿尔茨海默病药物研发最新进展

中国药科大学学报 2024年第6期55卷 816-825页

作者：穆峣赵慧敏刘昊晨柳晓泉中国药科大学代谢动力学研究中心南京211198

阿尔茨海默病(Alzheimer's disease,AD)是一种涉及到多种病理过程的神经退行性疾病,临床主要表现为记忆缺失和认知功能障碍。AD的病理过程复杂,发病机制尚不清楚,目前存在多种假说如β-淀粉样蛋白(β-amyloid,Aβ)沉积、Tau蛋白过度磷... 详细信息

阿尔茨海默病(Alzheimer's disease,AD)是一种涉及到多种病理过程的神经退行性疾病,临床主要表现为记忆缺失和认知功能障碍。AD的病理过程复杂,发病机制尚不清楚,目前存在多种假说如β-淀粉样蛋白(β-amyloid,Aβ)沉积、Tau蛋白过度磷酸化、神经炎症和神经元突触丢失等,研究人员以此为基础开展药物研发。2021年之前,美国食品药品监督管理局批准的药物均以调节神经递质为靶点,然而疗效非常有限。近几年来,两款抗Aβ单抗药物的获批给患者带来了一定的临床获益,但仍没能完全满足临床需求,AD药物研发仍亟待探索新的机制和靶点。目前针对AD的新机制和新靶标药物研发主要聚焦以下几个方向:抗Aβ药物、抗Tau蛋白药物、抗神经炎症免疫药物、改善线粒体功能药物、促进神经发生药物以及突触保护类药物。本文对这几个方向近10年来进入临床试验的AD新药进行概述,详细介绍了部分代表药物,并结合本课题组研究内容给出总结与展望。

关键词：阿尔茨海默病药物研发临床试验抗Aβ药物抗Tau蛋白药物抗神经炎症免疫药物