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Targeting proprotein convertase subtilisin/kexin type 9(PCSK9):from bench to bedside

Signal Transduction and Targeted Therapy 2024年第2期9卷 509-557页

作者： Xuhui Bao Yongjun Liang Hanman Chang Tianji Cai Baijie Feng Konstantin Gordon Yuekun Zhu Hailian Shi yundong he Liyi Xie Institute of Therapeutic Cancer Vaccines Fudan University Pudong Medical CenterShanghaiChina Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghaiChina Department of Oncology Fudan University Pudong Medical CenterShanghaiChina Center for Clinical Research Fudan University Pudong Medical CenterShanghaiChina Clinical Research Center for Cell-based Immunotherapy Fudan UniversityShanghaiChina Department of Pathology Duke University Medical CenterDurhamNCUSA Center for Medical Research and Innovation Fudan University Pudong Medical CenterShanghaiChina Institute for Food Safety and health Illinois Institute of TechnologyChicagoILUSA Department of Sociology University of MacaoTaipaMacaoChina Medical Institute Peoples’Friendship University of RussiaMoscowRussia A.Tsyb Medical Radiological Research Center ObninskRussia Department of Colorectal Surgery The First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineZhangjiang Hi-tech ParkShanghaiChina Department of Radiation Oncology Fudan University Shanghai Cancer CenterShanghaiChina Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina

Proprotein convertase subtilisin/kexin type 9(PCSK9)has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases(CVD).This comprehensive review delineates the intricate roles and wide-ranging implications of PCSK9,extending beyond CVD to emphasize its significance in diverse physiological and pathological states,including liver diseases,infectious diseases,autoimmune disorders,and notably,*** exploration offers insights into the interaction between PCSK9 and low-density lipoprotein receptors(LDLRs),elucidating its substantial impact on cholesterol homeostasis and cardiovascular *** also details the evolution of PCSK9-targeted therapies,translating foundational bench discoveries into bedside applications for optimized patient *** advent and clinical approval of innovative PCSK9 inhibitory therapies(PCSK9-iTs),including three monoclonal antibodies(Evolocumab,Alirocumab,and Tafolecimab)and one small interfering RNA(siRNA,Inclisiran),have marked a significant breakthrough in cardiovascular *** therapies have demonstrated unparalleled efficacy in mitigating hypercholesterolemia,reducing cardiovascular risks,and have showcased profound value in clinical applications,offering novel therapeutic avenues and a promising future in personalized medicine for cardiovascular ***,emerging research,inclusive of our findings,unveils PCSK9’s potential role as a pivotal indicator for cancer prognosis and its prospective application as a transformative target for cancer *** review also highlights PCSK9’s aberrant expression in various cancer forms,its association with cancer prognosis,and its crucial roles in carcinogenesis and cancer *** conclusion,this synthesized review integrates existing knowledge and novel insights on PCSK9,providing a holistic perspective on its transformative impact in reshaping therapeutic paradigms acr

关键词： PCSK9 metabolism convert

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Remodeling the immune microenvironment for gastric cancer therapy through antagonism of prostaglandin E2 receptor 4

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Genes & Diseases 2024年第4期11卷 411-425页

作者： Mengmeng Guo Pan Hu Jiayi Xie Kefu Tang Shixiu Hu Jialiang Sun yundong he Jing Li Weiqiang Lu Huirong Liu Mingyao Liu Zhengfang Yi Shihong Peng Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghai 200241China Prenatal Diagnosis Center Department of Clinical LaboratoryChangning Maternity and Infant Health HospitalEast China Normal UniversityShanghai 200051China Key Laboratory of Acupuncture and Immunological Effects Shanghai University of Traditional Chinese MedicineShanghai 201203China Fengxian Hospital Affiliated to Southern Medical University Shanghai 201400China Shanghai Yuyao Biotech Co. Ltd.Shanghai 200241China

Gastric cancer is highly prevalent among digestive tract *** to the intri-cate nature of the gastric cancer immune microenvironment,there is currently no effective treatment available for advanced gastric ***,there is promising potential for immunotherapy targeting the prostaglandin E2 receptor subtype 4(EP4)in gastric *** our previous study,we identified a novel small molecule EP4 receptor antagonist called *** with YY001 alone demonstrated a significant reduction in gastric cancer growth and inhibited tumor metastasis to the lungs in a mouse ***,adminis-tration of YYo01 stimulated a robust immune response within the tumor microenvironment,characterized by increased infiltration of antigen-presenting cells,T cells,and M1 ***,our research revealed that YYo01 exhibited remarkable synergistic ef-fects when combined with the PD-1 antibody and the clinically targeted drug apatinib,rather than *** findings suggest that YYo01 holds great promise as a potential therapeutic strategy for gastric cancer,whether used as a standalone treatment or in combination with other drugs.

关键词： EP4 Immunomodulation Synergy Tumor microenvironment YY001

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Targeting signaling pathways in prostate cancer:mechanisms and clinical trials

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2337-2367页

作者： yundong he Weidong Xu Yu-Tian Xiao Haojie Huang Di Gu Shancheng Ren Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghaiChina Department of Urology Shanghai Changzheng HospitalShanghaiChina Department of Urology Shanghai Changhai HospitalShanghaiChina Department of Urology Mayo Clinic College of Medicine and ScienceRochesterMNUSA Department of Urology The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina

Prostate cancer(PCa)affects millions of men *** to advances in understanding genomic landscapes and biological functions,the treatment of PCa continues to ***,various new classes of agents,which include next-generation androgen receptor(AR)signaling inhibitors(abiraterone,enzalutamide,apalutamide,and darolutamide),bone-targeting agents(radium-223 chloride,zoledronic acid),and poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib,rucaparib,and talazoparib)have been developed to treat *** targeting other signaling pathways,including cyclin-dependent kinase(CDK)4/6,Ak strain transforming(AKT),wingless-type protein(WNT),and epigenetic marks,have successively entered clinical ***,prostate-specific membrane antigen(PSMA)targeting agents such as 177Lu-PSMA-617 are promising theranostics that could improve both diagnostic accuracy and therapeutic *** clinical studies with immune checkpoint inhibitors(ICIs)have shown limited benefits in PCa,whereas subgroups of PCa with mismatch repair(MMR)or CDK12 inactivation may benefit from ICIs *** this review,we summarized the targeted agents of PCa in clinical trials and their underlying mechanisms,and further discussed their limitations and future directions.

关键词： clinical mechanisms summarized

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多级特征融合的掩码自编码声纹识别方法

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福建电脑 2024年第10期40卷 23-27页

作者：林泽文郑景元何允栋余文敬徐翀杭州电子科技大学计算机学院杭州310018

基于AudioMAE的自监督声纹识别具有良好的泛化性且不需要大量标注数据,但在重构原始梅尔频谱图时,AudioMAE仅使用编码器最后一层的输出,而忽略了编码器浅层包含的特征信息。为了解决这个问题,本文提出一种多级特征融合策略,首先将浅层... 详细信息

基于AudioMAE的自监督声纹识别具有良好的泛化性且不需要大量标注数据,但在重构原始梅尔频谱图时,AudioMAE仅使用编码器最后一层的输出,而忽略了编码器浅层包含的特征信息。为了解决这个问题,本文提出一种多级特征融合策略,首先将浅层的特征经过投影层与最后一层特征进行对齐,然后使用动态权重策略融合不同层级的特征,最后将融合后的特征送到解码器进行重构。实验的结果显示,本文方法在top1分类准确率上达到了95.95%,在top5分类准确率上达到了98.44%,较原始的AudioMAE分别提升了0.68%和0.24%。

关键词：声纹识别自监督学习掩码自编码器多级特征融合

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低时延QC-LDPC编码在遥测系统中的应用

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遥测遥控 2024年第5期45卷 68-72页

作者：孙士捷何云东孙成张德超汤佳骏上海机电工程研究所上海201100

本文介绍了一种基于QC-LDPC编码的遥测系统应用方案,提出了编码码长与遥测帧长的联合设计方法,该设计方法对频谱资源、信道质量以及硬件能力进行综合考量,给出最优的设计方案。针对所采用的RU编码算法以及LLR BP译码算法,基于FPGA与AD9... 详细信息

本文介绍了一种基于QC-LDPC编码的遥测系统应用方案,提出了编码码长与遥测帧长的联合设计方法,该设计方法对频谱资源、信道质量以及硬件能力进行综合考量,给出最优的设计方案。针对所采用的RU编码算法以及LLR BP译码算法,基于FPGA与AD936X架构给出了遥测系统的硬件实现路线。按照技术路线对系统的编码增益进行了仿真计算,结合理论分析与仿真结果,可以看出所提出的遥测系统设计方法同时具备低时延和高增益的优势。该方法克服了传统遥测系统中信道编码延迟较大的问题,以极小的编码延时带来了约8 dB的编码增益,在未来的遥测系统中具备一定的应用价值。

关键词：遥测系统 QC-LDPC 置信传播算法

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Experimental and numerical study on dynamic mechanical behaviors of shale under true triaxial compression at high strain rate

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International Journal of Mining Science and Technology 2024年第2期34卷 149-165页

作者： Xiaoping Zhou Linyuan Han Jing Bi yundong Shou School of Civil Engineering Wuhan UniversityWuhan 430072China College of Civil Engineering Guizhou UniversityGuiyang 550025China

High-energy gas fracturing of shale is a novel,high efficacy and eco-friendly mining technique,which is a typical dynamic perturbing *** effectively extract shale gas,it is important to understand the dynamic mechanical properties of *** experiments on shale subjected to true triaxial compression at different strain rates are first conducted in this *** dynamic stress-strain curves,peak strain,peak stress and failure modes of shale are *** results of the study indicate that the intermediate principal stress and the minor principal stress have the significant influence on the dynamic mechanical behaviors,although this effect decreases as the strain rate *** characteristics of compression-shear failure primarily occur in shale subjected to triaxial compression at high strain rates,which distinguishes it from the fragmentation characteristics observed in shale under dynamic uniaxial ***,a numerical three-dimensional Split Hopkinson Pressure Bar(3D-SHPB),which is established by coupling PFC3D and FLAC3D methods,is validated to replicate the laboratory characteristics of *** dynamic mechanical characteristics of shale subjected to different confining stresses are systematically investigated by the coupling PFC3D and FLAC3D *** numerical results are in good agreement with the experimental data.

关键词： Dynamic behaviors True triaxial compression High strain rates Dynamic failure mechanism PFC3D-FLAC3D coupled method

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Blockchain-Enabled Federated Learning for Privacy-Preserving Non-IID Data Sharing in Industrial Internet

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Computers, Materials & Continua 2024年第8期80卷 1967-1983页

作者： Qiuyan Wang Haibing Dong Yongfei Huang Zenglei Liu yundong Gou School of Electrical and Information Engineering Hunan Institute of TechnologyHengyang421002China

Sharing data while protecting privacy in the industrial Internet is a significant *** machine learning methods require a combination of all data for training;however,this approach can be limited by data availability and privacy *** learning(FL)has gained considerable attention because it allows for decentralized training on multiple local ***,the training data collected by data providers are often non-independent and identically distributed(non-IID),resulting in poor FL *** paper proposes a privacy-preserving approach for sharing non-IID data in the industrial Internet using an FL approach based on blockchain *** overcome the problem of non-IID data leading to poor training accuracy,we propose dynamically updating the local model based on the divergence of the global and local *** approach can significantly improve the accuracy of FL training when there is relatively large *** addition,we design a dynamic gradient clipping algorithm to alleviate the influence of noise on the model accuracy to reduce potential privacy leakage caused by sharing model ***,we evaluate the performance of the proposed scheme using commonly used open-source image *** simulation results demonstrate that our method can significantly enhance the accuracy while protecting privacy and maintaining efficiency,thereby providing a new solution to data-sharing and privacy-protection challenges in the industrial Internet.

关键词： Federated learning data sharing non-IID data differential privacy blockchain

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电动汽车制动模式切换扭矩协调控制

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振动与冲击 2021年第10期40卷 304-314页

作者：杨阳何云东罗倡杨忠重庆大学机械传动国家重点实验室重庆400044 重庆大学汽车工程学院重庆400044 重庆长安汽车股份有限公司重庆400023

由于电液复合制动系统动态响应特性的差异,纯电动汽车在制动模式切换过程中会造成整车和系统部件的冲击度增大,影响汽车的行驶平顺性和系统部件的使用寿命。为减小制动模式切换过程中的整车冲击度和总制动力矩波动,采用比例积分微分控制... 详细信息

由于电液复合制动系统动态响应特性的差异,纯电动汽车在制动模式切换过程中会造成整车和系统部件的冲击度增大,影响汽车的行驶平顺性和系统部件的使用寿命。为减小制动模式切换过程中的整车冲击度和总制动力矩波动,采用比例积分微分控制PID和模糊控制相结合的组合控制算法对轮缸压力进行精确控制,在此基础上以纯液压制动时的动力学模型作为参考模型,控制电机制动力随参考模型输出的参考力矩变化,从而减小电机制动系统和液压制动系统的响应特性差异;在MATLAB/Simulink中搭建了电液复合制动系统和整车模型,验证了控制策略的有效性。仿真结果表明,与未协调控制时相比,所提出的控制策略使整车冲击度显著减小,改善了制动模式切换过程中的汽车行驶平顺性。

关键词：电动汽车电液复合制动系统模式切换扭矩协调控制冲击度

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Study on the influence of mechanism dispersion on transient recovery voltage distribution of modular DC vacuum circuit breakers

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High Voltage 2024年第2期9卷 346-355页

作者： Chongyang Huang Yongshuai Yin Shuxin Liu Hanwen Du Zengyu Shan yundong Cao Shurui Yang Key Laboratory of Special Electric Machines and High Voltage Apparatus in the Ministry of Education Shenyang University of TechnologyShenyangChina Shenyang Power Supply Company of State Grid Liaoning Electric Power Co. LtdShenyangChina Chifeng Power Supply Company of State Grid Mongolia Electric Power Co. LtdChifengChina

A simulation analysis and an experiment are carried out to investigate how the gap difference between the breaks of a direct current vacuum circuit breakers with multi-breaks(MB-DC VCB)caused by the mechanism dispersion of the breaker influences the distribution of TRV among the *** interruption model of MB-DC VCB,combining the continuous transition model,is established to analyse the rising rate of transient recovery voltage and the dielectric strength recovery speed of the breaks for MB-DC VCB under different gap difference *** on the experimental platform of dual break DC vacuum circuit breaker breaking,the correctness of the simulation model is verified on a DC VCB with the double-breaks interruption experimental ***,a model is applied to the non-synchronous interruption simulation of a DC VCB with *** relationship between the TRVs of the breaks under different gap difference conditions is analysed using the comparative analysis method,obtaining the maximum gap difference at the moment of breaking *** results of this study show that large-gap breaks have a higher TRV than small-gap breaks(the fracture of the action delay module),with double fractures reaching 1.4 times and triple fractures reaching a maximum of 1.52 times;the ability of small-gap breaks to withstand TRV is weak,giving rise to re-breakdown or even interruption failure;as the number of fractures increases,the maximum gap difference also *** the synchronous interruption ability of the MB-DC VCB is conducive to improving the interruption performance and interruption success rate of this type of a circuit breaker.

关键词： TRV transient distribution

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A strategy for strengthening chaotic mixing of dual shaft eccentric mixers by changing non-Newtonian fluids kinetic energy distribution

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Chinese Journal of Chemical Engineering 2024年第5期69卷 122-134页

作者： Songsong Wang Tong Meng Qian Zhang Changyuan Tao yundong Wang Zequan Li Zuohua Liu School of Chemistry and Chemical Engineering Chongqing UniversityChongqing 400044China State Key Laboratory of Coal Mine Disaster Dynamics and Control Chongqing 400044China Department of Chemical Engineering Tsinghua UniversityBeijing 100084China

Efficiently modulating the velocity distribution and flow pattern of non-Newtonian fluids is a critical challenge in the context of dual shaft eccentric mixers for process intensification,posing a significant barrier for the existing ***,this work reports a convenient strategy that changes the kinetic energy to controllably regulate the flow patterns from radial flow to axial *** showed that the desired velocity distribution and flow patterns could be effectively obtained by varying the number and structure of baffles to change kinetic energy,and a more uniform velocity distribution,which could not be reached normally in standard baffle dual shaft mixers,was easily ***,a comparative analysis of velocity and shear rate distributions is employed to elucidate the mechanism behind the generation of flow patterns in various dual-shaft eccentric ***,there is little difference in the power number of the laminar flow at the same Reynolds number,meaning that the baffle type has no effect on the power consumption,while the power number of both unbaffle and U-shaped baffle mixing systems decreases compared with the standard baffle mixing system in the transition ***,at the same rotational condition,the dimensionless mixing time of the U-shaped baffle mixing system is 15.3%and 7.9%shorter than that of the standard baffle and the unbaffle mixing system,respectively,which shows the advantage of the U-shaped baffle in stirring rate.

关键词： Dual shaft “U-shaped”baffle Flow pattern Mixing time Power demand

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