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Safety, pharmacokinetics, and biomarkers of F-652, a recombinant human interleukin-22 dimer, in healthy subjects

Cellular & Molecular Immunology 2019年第5期16卷 473-482页

作者： kai-yang tang Jason Lickliter Zhi-Hua Huang Zong-Shu Xian Han-yang Chen Cheng Huang Chong Xiao Yu-Peng Wang Ying Tan Lin-Feng Xu Yu-Liang Huang Xiao-Qiang Yan Generon(Shanghai)Corporation Ltd. Zhangjiang Hi-Tech ParkShanghaiChina Nucleus Network MelbourneVICAustralia

F-652 is a recombinant fusion protein consisting of two human interleukin-22(IL-22)molecules linked to an immunoglobulin constant region(IgG 2-Fc).IL-22 plays critical roles in promoting tissue repair and suppressing bacterial *** safety,pharmacokinetics(PK),tolerability,and biomarkers of F-652 were evaluated following a single dose in healthy male volunteers in a randomized,double-blind,placebo-controlled *** single-dose subcutaneous(SC)injection of F-652 at 2.0µg/kg into healthy subjects,six out of six subjects experienced delayed injection site reactions,which presented as erythematous and/or discoid eczematous lesions 10 to 17 days post-dosing.F-652 was then administered to the healthy subjects via an intravenous(IV)infusion at 2.0,10,30,and 45µg/*** severe adverse event(SAE)was observed during the *** the IV-dosed cohorts,eye and skin treatment emergent adverse events(TEAEs)were observed in the 30 and 45µg/kg cohorts.F-652 IV dosing resulted in linear increases in C max and AUC(0–t),and the T 1/2 ranged from 39.4 to 206h in the *** IV injection of F-652 induced dose-dependent increases in serum marker serum amyloid A,C-reactive protein,and FIB,and decreased serum *** serum levels of 36 common pro-inflammatory cytokines/chemokines were not altered by the treatment of F-652 at 45μg/*** conclusion,IV administration of F-652 to healthy male volunteers is safe and well-tolerated and demonstrates favorable PK and pharmacodynamic *** results warrant further clinical development of F-652 to treat inflammatory diseases.

关键词： Interleukin-22 F-652 Pharmacokinetics Pharmacodynamics Safety

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Repetitive traumatic brain injury–induced complement C1–related inflammation impairs long-term hippocampal neurogenesis

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Neural Regeneration Research 2025年第3期20卷 821-835页

作者： Jing Wang Bing Zhang Lanfang Li Xiaomei tang Jinyu Zeng Yige Song Chao Xu kai Zhao Guoqiang Liu Youming Lu Xinyan Li kai Shu Department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Neurosurgery Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Pathophysiology School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Institute for Brain Research Wuhan Center of Brain ScienceHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Graduate Student Chongqing Medical UniversityChongqingChina Department of Basic Medicine School of Medical ScienceHubei University for NationalitiesEnshiHubei ProvinceChina Department of Anatomy School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive ***,the mechanism underlying this neurogenesis impairment remains *** this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain *** results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and *** with repetitive traumatic brain injuryalso showed deficits in spatial memory ***,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was *** inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological *** findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

关键词： complement C1 dendrite dentate gyrus hippocampus neural stem cell neurogenesis neuroinflammation neurological function neuron traumatic brain injury

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A novel flexible nerve guidance conduit promotes nerve regeneration while providing excellent mechanical properties

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Neural Regeneration Research 2025年第7期20卷 2084-2094页

作者： Tong Li Quhan Cheng Jingai Zhang Boxin Liu Yu Shi Haoxue Wang Lijie Huang Su Zhang Ruixin Zhang Song Wang Guangxu Lu Peifu tang Zhongyang Liu kai Wang Department of Orthopedics the Fourth Medical Center of Chinese PLA General HospitalBeijingChina Department of Training and Sports Medicine Characteristic Medical Center of Chinese People’s Armed Police ForceTianjinChina Medical School of Chinese PLA BeijingChina Key Laboratory of Bioactive Materials for the Ministry of Education College of Life SciencesNankai UniversityTianjinChina Department of Orthopedics Tianjin HospitalTianjinChina Department of Rehabilitation Medicine Er Quan Hospital of PAPWuxiJiangsu ProvinceChina

Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor *** an alternative,nerve guidance conduits may be *** ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve *** designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align ***,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber *** presence of aligned fibers on the inner surface can promote the extension of nerve cells along the *** helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide *** novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.

关键词： aligned fibers anti-kinking helical fibers nerve guidance conduit nerve regeneration peripheral nerve injury topological guidance

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Motion Planning for Autonomous Driving with Real Traffic Data Validation

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Chinese Journal of Mechanical Engineering 2024年第1期37卷 74-86页

作者： Wenbo Chu kai yang Shen Li Xiaolin tang Western China Science City Innovation Center of Intelligent and Connected Vehicle Chongqing 400044China College of Mechanical and Vehicle Engineering Chongqing UniversityChongqing 400044China School of Civil Engineering Tsinghua UniversityBeijing 100084China

Accurate trajectory prediction of surrounding road users is the fundamental input for motion planning,which enables safe autonomous driving on public *** this paper,a safe motion planning approach is proposed based on the deep learning-based trajectory prediction *** begin with,a trajectory prediction model is established based on the graph neural network(GNN)that is trained utilizing the INTERACTION ***,the validated trajectory prediction model is used to predict the future trajectories of surrounding road users,including pedestrians and *** addition,a GNN prediction model-enabled motion planner is developed based on the model predictive control ***,two driving scenarios are extracted from the INTERACTION dataset to validate and evaluate the effectiveness of the proposed motion planning approach,i.e.,merging and roundabout *** results demonstrate that the proposed method can lower the risk and improve driving safety compared with the baseline method.

关键词： Trajectory prediction Graph neural network Motion planning INTERACTION dataset

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Path Planning and Tracking Control for Parking via Soft Actor-Critic Under Non-Ideal Scenarios

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IEEE/CAA Journal of Automatica Sinica 2024年第1期11卷 181-195页

作者： Xiaolin tang Yuyou yang Teng Liu Xianke Lin kai yang Shen Li IEEE the College of Mechanical and Vehicle Engineering Chongqing UniversityChongqing 400044China the Clinical Research Center and Medical Pathology Center Chongqing University Three Gorges HospitalChongqing UniversityWanzhou 404000 the Department of Automotive and Mechatronics Engineering Ontario Tech UniversityOshawa ON LIG OC5Canada the School of Civil Engineering Tsinghua UniversityBeijing 100084China

Parking in a small parking lot within limited space poses a difficult task. It often leads to deviations between the final parking posture and the target posture. These deviations can lead to partial occupancy of adjacent parking lots, which poses a safety threat to vehicles parked in these parking lots. However, previous studies have not addressed this issue. In this paper, we aim to evaluate the impact of parking deviation of existing vehicles next to the target parking lot(PDEVNTPL) on the automatic ego vehicle(AEV) parking, in terms of safety, comfort, accuracy, and efficiency of parking. A segmented parking training framework(SPTF) based on soft actor-critic(SAC) is proposed to improve parking performance. In the proposed method, the SAC algorithm incorporates strategy entropy into the objective function, to enable the AEV to learn parking strategies based on a more comprehensive understanding of the environment. Additionally, the SPTF simplifies complex parking tasks to maintain the high performance of deep reinforcement learning(DRL). The experimental results reveal that the PDEVNTPL has a detrimental influence on the AEV parking in terms of safety, accuracy, and comfort, leading to reductions of more than 27%, 54%, and 26%respectively. However, the SAC-based SPTF effectively mitigates this impact, resulting in a considerable increase in the parking success rate from 71% to 93%. Furthermore, the heading angle deviation is significantly reduced from 2.25 degrees to 0.43degrees.

关键词： Automatic parking control strategy parking deviation(APS) soft actor-critic(SAC)

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人脐带间充质干细胞条件培养基及外泌体对肝癌细胞增殖、迁移、侵袭和凋亡的影响

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中国组织工程研究 2025年第7期29卷 1350-1355页

作者：金凯唐婷李美乐谢裕安广西中医药大学研究生院广西壮族自治区南宁市530002 广西壮族自治区妇幼保健院广西壮族自治区南宁市530002 广西出生缺陷及干细胞生物样本库重点实验室广西壮族自治区南宁市530002

背景:间充质干细胞可通过分泌含细胞因子、生长因子和外泌体的细胞外囊泡调节肿瘤微环境,对肿瘤细胞生物学行为进行精准调控。目的:研究人脐带间充质干细胞条件培养基及外泌体对肝癌细胞生物学特性的影响。方法:收集人脐带间充质干细胞... 详细信息

背景:间充质干细胞可通过分泌含细胞因子、生长因子和外泌体的细胞外囊泡调节肿瘤微环境,对肿瘤细胞生物学行为进行精准调控。目的:研究人脐带间充质干细胞条件培养基及外泌体对肝癌细胞生物学特性的影响。方法:收集人脐带间充质干细胞培养上清,通过高速离心并过滤获得人脐带间充质干细胞条件培养基;收集人脐带间充质干细胞培养上清,通过超高速梯度离心法提取人脐带间充质干细胞外泌体。使用PKH26标记人脐带间充质干细胞外泌体,与肝癌细胞MHCC97-H共培养,荧光显微镜观察MHCC97-H细胞摄取外泌体情况。通过CCK-8增殖实验、Transwell迁移和侵袭实验以及流式凋亡实验评估人脐带间充质干细胞条件培养基、人脐带间充质干细胞外泌体对肝癌细胞生物学功能的影响。结果与结论:(1)人脐带间充质干细胞外泌体可被MHCC97-H细胞摄取且主要分布于细胞质中;(2)人脐带间充质干细胞条件培养基处理后,MHCC97-H细胞的增殖、迁移和侵袭能力显著增强(P<0.001,P<0.05,P<0.01),凋亡能力显著下降(P<0.001);而人脐带间充质干细胞外泌体处理后,MHCC97-H细胞的增殖能力下降(P<0.001),迁移、侵袭及凋亡能力显著增强(P<0.001);(3)结果表明,人脐带间充质干细胞条件培养基具有促进MHCC97-H细胞增殖、迁移、侵袭和抑制凋亡的能力;而人脐带间充质干细胞外泌体则具有促进MHCC97-H细胞迁移、侵袭及凋亡和抑制增殖的能力。

关键词：肝癌人脐带间充质干细胞外泌体条件培养基增殖迁移侵袭凋亡

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Driving Environment Uncertainty-Aware Motion Planning for Autonomous Vehicles

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Chinese Journal of Mechanical Engineering 2022年第5期35卷 301-314页

作者： Xiaolin tang kai yang Hong Wang Wenhao Yu Xin yang Teng Liu Jun Li College of Mechanical and Vehicle Engineering Chongqing UniversityChongqing 400044China Tsinghua Intelligent Vehicle Design and Safety Research Institute Tsinghua UniversityBeijing 100084China

Autonomous vehicles require safe motion planning in uncertain environments,which are largely caused by surrounding *** this paper,a driving environment uncertainty-aware motion planning framework is proposed to lower the risk of position uncertainty of surrounding vehicles with considering the risk of ***,a 4-degree of freedom vehicle dynamics model,and a rollover risk index are ***,the uncertainty of surrounding vehicles’position is processed and propagated based on the Extended Kalman Filter ***,the uncertainty potential field is established to handle the position uncertainty of autonomous *** addition,the model predictive controller is designed as the motion planning framework which accounts for the rollover risk,the position uncertainty of the surrounding vehicles,and vehicle dynamic constraints of autonomous ***,two edge cases,the cut-in scenario,and merging scenario are ***,the safety,effectiveness,and real-time performance of the proposed motion planning framework are demonstrated by employing a hardware-in-the-loop experiment bench.

关键词： Position uncertainty Rollover prevention Autonomous vehicles Motion planning Model predictive control

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Reflection and Refraction of Waves Across an Interface of Two-phase Flow

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Acta Mathematicae Applicatae Sinica 2021年第1期37卷 137-147页

作者： kai HU Hui KAN Chun-lei tang Xiao-zhou yang School of Mathematics and Statistics Southwest UniversityChongqing 400715China Wuhan Institute of Physics and Mathematics Chinese Academy of SciencesWuhan 430071China

We investigate a hyperbolic system of one-dimensional isothermal fluid with liquid-vapor phase *** refraction-reflection phenomena are intensively analyzed when elementary waves travel across the two-phase *** apply the characteristic method and hodograph transform of Riemann to reduce the nonlinear PDEs to a concise *** for the case of incident rarefaction wave,reduced linear equations are convenient to solve by Laplace *** an integral formula in wave interaction region is derived in this paper,instead of the hypergeometric functions solutions for non-isothermal polytropic *** is also observed that when incident waves travel from the vapor phase to the liquid phase,the refracted waves must be accelerated and move forward.

关键词： p-system two-phase fluid Hodograph transform Volterra equation

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Comparative Study of Trajectory Tracking Control for Automated Vehicles via Model Predictive Control and Robust H-infinity State Feedback Control

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Chinese Journal of Mechanical Engineering 2021年第4期34卷 168-181页

作者： kai yang Xiaolin tang Yechen Qin Yanjun Huang Hong Wang Huayan Pu College of Mechanical and Vehicle Engineering Chongqing UniversityChongqing 400000China School of Mechanical Engineering Beijing Institute of TechnologyBeijing 100080China School of Automotive Studies Tongji UniversityShanghai 201804China School of Vehicle and Mobility Tsinghua UniversityBeijing 100080China

A comparative study of model predictive control(MPC)schemes and robust Hstate feedback control(RSC)method for trajectory tracking is proposed in this *** main objective of this paper is to compare MPC and RSC controllers’performance in tracking predefined trajectory under different *** controller is designed based on the simple longitudinal-yaw-lateral motions of a single-track vehicle with a linear tire,which is an approximation of the more realistic model of a vehicle with double-track motion with a non-linear tire *** is designed on the basis of the same method as adopted for the MPC controller to achieve a fair ***,three test cases are built in CarSim-Simulink joint ***,the verification test is used to test the tracking accuracy of MPC and RSC controller under well road ***,the double lane change test with low road adhesion is designed to find the maximum velocity that both controllers can carry out while guaranteeing ***,an extreme curve test is built where the road adhesion changes suddenly,in order to test the performance of both controllers under extreme ***,the advantages and disadvantages of MPC and RSC under different scenarios are also discussed.

关键词： Trajectory tracking Automated vehicles Model predictive control Robust H∞state feedback control

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A thermodynamic description of the Si-rich Si-Fe system

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Acta Metallurgica Sinica(English Letters) 2012年第4期25卷 249-255页

作者： kai tang Merete tangstad SINTEF Materials and Chemistry N-7465 Trondheim Norway Department of Materials and Technology Norwegian University of Science and Technology TrondheimNorway

Phase equilibria in the Si-rich domain of the Si-Fe system have been reassessed based on the recent DTA experimental results. Thermodynamic properties of liquid phase have been reassessed using the associated solution model. The properties of DIA- MOND_A4 mixture phase have been added in order to evaluate the phase equilibria for the pure silicon materials. The assessed system is able to reproduce the experi- mental values in the whole composition range of the Si-Fe system.

关键词： Si-Fe Thermodynamic Assessment Phase equilibrium DTA

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