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A Small-Molecule Drug for the Self-Checking of Mitophagy

Angewandte Chemie 2025年第10期137卷

作者： Ms. Yanan Gao Mr. Qingjie Bai Ms. Youxiao Ren Dr. Xintian Shao Mr. Mengrui Zhang Dr. Luling Wu Prof. Simon E. Lewis Prof. Tony D. James Prof. Xiaoyuan Chen Prof. Qixin Chen State Key Laboratory of Advanced Drug Delivery and Release Systems School of Pharmaceutical Sciences Neck-Shoulder and Lumbocrural Pain Hospital Medical Science and Technology Innovation Center Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong 250117 PR China Department of Chemistry University of Bath Bath BA2 7AY U.K. School of Chemistry and Chemical Engineering Henan Normal University Xinxiang 453007 People's Republic of China Departments of Diagnostic Radiology Chemical and Biomolecular Engineering and Biomedical Engineering Yong Loo Lin School of Medicine and College of Design and Engineering National University of Singapore Singapore 119074 Singapore Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117599 Singapore Nanomedicine Translational Research Program Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore Theranostics Center of Excellence (TCE) Yong Loo Lin School of Medicine National University of Singapore 11 Biopolis Way Helios Singapore 138667 Institute of Molecular and Cell Biology Agency for Science Technology and Research (A*STAR) 61 Biopolis Drive Proteos Singapore 138673 Singapore Department of Pharmacy and Pharmaceutical Sciences National University of Singapore Lower Kent Ridge Road 4 Science Drive 2 117544 Singapore

Mitophagy, particularly in the context of drugs that disrupt mitochondrial membrane potential (MMP), represents a critical focus in pharmacology. However, the discovery and evaluation of MMP-disrupting drugs are often hampered using commercially available marker molecules that target similar or identical zones. These markers can significantly interfere with, obscure, or amplify the functional effects of MMP-targeting drugs, frequently leading to clinical failures. In response to this challenge, we propose a “one-two punch” drug design strategy that integrates both target-zone drug functionality and non-target zone biological reporting within a single small-molecule drug. We have developed a novel proof-of-concept mitophagy self-check drug ( MitoSC ) that exhibits dual-color and dual-localization properties. The functional component of this system is a variable MitoSC that disrupts mitochondrial membrane potential (MMP) homeostasis, thereby inducing mitophagy. Upon activation, this component transforms into a blue-fluorescent monomer ( MitoSC-fun ) specifically within the mitochondrial target zone. Concurrently, the biological reporting component is represented by a red-fluorescent monomer ( MitoSC-rep ) that localizes to lysosomes, the non-target zone. As mitophagy progresses, the fluorescent signals from MitoSC-rep (lysosomes) and MitoSC-fun (mitochondria) converge, enabling real-time monitoring of the mitophagic process. This strategy combines potent drug functionality with robust biological reporting, thereby minimizing interference and eliminating the complexities associated with external detection. Our findings underscore the potential of a single-molecule drug to exert target-zone specific actions while simultaneously providing non-target zone self-checking, offering a new perspective for drug design.

关键词： Mitochondria Lysosomes Subcellular dynamics Dual localization Self-checking drug

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Pickup Manipulator design and Its Kinematics Simulation 2

Pickup Manipulator Design and Its Kinematics Simulation

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2018 2nd International Symposium on Resource Exploration and Environmental science, REES 2018

作者： Zhang, Zhongdang Zhang, Zhaoqiang Ma, Shitai Zhou, Haibo Tianjin University of Technology Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent Control Tianjin300384 China National Demonstration Center for Experimental Mechanical and Electrical Engineering Education Tianjin300384 China

In order to improve the flexibility of the pickup manipulator and solve the problem of picking up small sports balls in training ground such as golfing, tennis, and table tennis, a 5-DOF pickup manipulator structure is designed. According to the pickup task requirements of the manipulator, through theoretical calculations, the 86HS series stepping motor is selected as the driving motors of the front end joints. Based on this, the stepping motor control system is designed to realize the closed-loop control of the manipulator. Then the manipulator model is built using D-H method, the inverse kinematics solution is calculated, and the analysis of kinematic theory is conducted. Finally, the targeted pickup point is selected to carry out case simulation analysis of the manipulator, the motion law of the manipulator is verified to be reasonable and the task of picking up small sports balls is completed. © Published under licence by IOP Publishing Ltd.

关键词： Manipulators

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A design of hardware-in-the-loop real-time simulation for large-scale complex electromechanical system

A design of hardware-in-the-loop real-time simulation for la...

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CSAA/IET International Conference on Aircraft Utility systems, AUS 2018

作者： Liu, Zhentian Wang, Guangsen Lin, Chengmei Wang, Zhiwei Li, Jing National Key Laboratory of Science and Technology on Vessel Integrated Power System Naval Univ. of Engineering Wuhan China Wuhan Marine Machinery Co. Ltd Wuhan China

ISBN: (纸本)9781785617911

The more electric aircraft (MEA), belonging to the large-scale complex electromechanical system (LSCES), always has a large-scale complex structure, of which the design, testing, and evaluation may be a challenging task. In order to analyze the impact of various factors on the system performance and reduce the potential risk, it is advantageous to establish a hardware-inthe-loop (HIL) real-time simulation platform for MEA. From this purpose, some key processes are suggested to clear the way for an efficient and accurate design. First, the principles of system partitioning and high-performance communication network are presented for distributed parallel computation. Then, algorithms are discussed and compared aiming to compensate intersimulation time-step switching error caused by high-frequency switches which are widely used in MEA. Finally, an automation test method based on Monte Carlo (MC) and Genetic Algorithm (GA) methodology is proposed. In the experimental part, a permanent magnet synchronous motor (PMSM) in HIL mode is presented to demonstrate the practicality, with the results of the offline and real-time simulation compared. In short, this paper provides a guidance for establishing an HIL platform for LSCES. © 2018 IET Conference Publications. All rights reserved.

关键词： Genetic algorithms

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Multi-objective Optimization of Non-uniform Beam for Minimum Weight and Sound Radiation

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Transactions of Tianjin University 2017年第4期23卷 380-393页

作者： Furui Xiong Mengxin He Yousef Naranjani Qian Ding Jianqiao Sun Science and Technology on Reactor System Design Technology Laboratory Nuclear Power Institute of China School of Mechanical Engineering Tianjin University School of Engineering University of California Merced

A multi-objective optimization of non-uniform beams is presented for minimum radiated sound power and weight. The transfer matrix method is used to compute the structural and acoustic responses of a non-uniform beam accurately and efficiently. The multi-objective particle swarm optimization technique is applied to search the Pareto optimal solutions that represent various compromises between weight and sound radiation. Several constraints are imposed, which substantially reduce the volume fraction of feasible solutions in the design space. Two non-uniform beams with different boundary conditions are studied to demonstrate the multi-objective optimal designs of the structure. © 2017, Tianjin University and Springer-Verlag Berlin Heidelberg.

关键词： Acoustic generators Acoustic properties Acoustic wave propagation Acoustic wave scattering Optimal systems Pareto principle Particle swarm optimization (PSO) Transfer matrix method

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Why To Model Remote Sensing Measurements In 3d? Recent Advances In Dart: Atmosphere, Topography, Large Landscape, Chlorophyll Fluorescence And Satellite Image Inversion

Why To Model Remote Sensing Measurements In 3d? Recent Advan...

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International Conference on Advanced Technologies for Signal and Image Processing (ATSIP)

作者： J.P. Gastellu-Etchegorry Y. Wang O. Regaieg T. Yin Z. Malenovsky Z. Zhen X. Yang Z. Tao L. Landier A. Al Bitar Deschamps N. Lauret J. Guilleux E. Chavanon B. Cao J. Qi A. Kallel Z. Mitraka N. Chrysoulakis B. Cook D. Morton Université de Toulouse CESBIO - UPS CNES CNRS IRD Toulouse France Earth System Science Interdisciplinary Center University of Maryland College Park MD 20740-3823 USA School of Technology Environments and Design University of Tasmania Hobart Australia College of Geo-Exploration Science and Technology Jilin University Changchun China Chinese Academy of Sciences Institute of Remote Sensing and Digital Earth Beijing China Key Laboratory of Geographical Information Science East China Normal University Shanghai China CNES 18 Av. Belin Toulouse France Beijing Forestry University Beijing China CRNS ATMS Sfax Tunisia Foundation for Research and Technology Hellas (FORTH) Heraklion Greece NASA Goddard Space Flight Center Greenbelt USA

ISBN: (数字)9781728175133

ISBN: (纸本)9781728175140

Remote sensing (RS) dedicated to the study of land surfaces benefits from more and more advanced sensors. However, the interpretation of RS data is often is often inaccurate due to the complexity of the observed land surfaces. Therefore, RS models, in particular physical models, that simulate RS observations of the three-dimensional (3D) landscapes are critical to correctly interpret RS data. DART is one of the most comprehensive 3D models of Earthatmosphere optical radiative transfer (RT), from ultraviolet (UV) to thermal infrared (TIR). It simulates the optical signal of proximal, aerial and satellite imaging spectrometers and laser scanners, the 3D RB and solar-induced chlorophyll fluorescence (SIF) signal, for any urban or natural landscape and any experimental or instrument configuration. It is freely available for research and teaching activities (***). After illustrating three significant sources of inaccuracy in RS interpretation, five recent DART advances are presented: RT in the atmosphere and topography, fast RS image simulation of large landscapes, SIF modelling, and satellite image inversion.

关键词： Atmospheric modeling Three-dimensional displays Reflectivity Surface topography Sun Forestry Solid modeling

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The fuzzy adaptive PID control of brushless DC motor

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Journal of Physics: Conference Series 2020年第5期1507卷

作者： H Q Yin W J Yi C C Li K J Wang J T Wu National Key Laboratory of Transient Physics Nanjing University of Science and Technology Nanjing 210094 China Beijing Institute of Astronautical System Engineering Beijing 100076 China

Brushless direct current motor (BLDCM) is a complicated system with multivariable, nonlinear and strong coupled. The present work devotes to design a fuzzy adaptive PID algorithm based on the speed loop so that it could crack the traditional PID problems which include bad parameter setting, poor adaptability, imprecise control and weak anti-interference so on. In this paper, the mathematical model and operating characteristics of BLDCM are analyzed. Then, the simulation platform is built by MATLAB/Simulink. Finally, the control effects of PI, PID and fuzzy adaptive PID are compared and analyzed. The results indicate that the fuzzy adaptive PID is better robustness, faster response, smaller overshoot and more stable operation than others.

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Effect of tungsten on creep properties of martensitic 9Cr steel

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IOP Conference Series: Materials science and Engineering 2020年第1期838卷

作者： F Y Hu S J Zhang J J Shen Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent Control School of Mechanical Engineering Tianjin University of Technology China National Demonstration Center for Experimental Mechanical and Electrical Engineering Education (Tianjin University of Technology) China

The effects of tungsten on the creep behavior and microstructure of tempered martensite 9Cr steel with different W concentrations ranging from 0–2.5 wt% were studied. The matrix consisted of tempered lath martensite structure and M23C6 located along the grain boundary or inside the grain. As the W concentration increased, the number of M23C6 increased while the particle size decreased. Also, with the increasing W concentration, the minimum creep rate and elongation decreased while the time to rupture increased. The rise in W concentration led to the refinement of M23C6, which enhanced the creep strength but reduced the creep plasticity.

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Federated learning with differential privacy: Algorithms and performance analysis

arXiv

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arXiv 2019年

作者： Wei, Kang Li, Jun Ding, Ming Ma, Chuan Yang, Howard H. Farhad, Farokhi Jin, Shi Quek, Tony Q. S. Poor, H. Vincent School of Electrical and Optical Engineering Nanjing University of Science and Technology Nanjing210094 China Data61 Csiro SydneyNSW2015 Australia Singapore University of Technology and Design Information System Technology and Design Pillar Singapore National Mobile Communications Research Laboratory Southeast University Nanjing210096 China Department of Electrical Engineering Princeton University PrincetonNJ08544 United States

Federated learning (FL), as a manner of distributed machine learning, is capable of significantly preserving clients' private data from being exposed to external adversaries. Nevertheless, private information can still be divulged by analyzing on the differences of uploaded parameters from clients, e.g., weights trained in deep neural networks. In this paper, to effectively prevent information leakage, we propose a novel framework based on the concept of differential privacy (DP), in which artificial noises are added to the parameters at the clients side before aggregating, namely, noising before model aggregation FL (NbAFL). First, we prove that the NbAFL can satisfy DP under distinct protection levels by properly adapting different variances of artificial noises. Then we develop a theoretical convergence bound of the loss function of the trained FL model in the NbAFL. Specifically, the theoretical bound reveals the following three key properties: 1) There is a tradeoff between the convergence performance and privacy protection levels, i.e., a better convergence performance leads to a lower protection level;2) Given a fixed privacy protection level, increasing the number N of overall clients participating in FL can improve the convergence performance;3) There is an optimal number of maximum aggregation times (communication rounds) in terms of convergence performance for a given protection level. Furthermore, we propose a K-random scheduling strategy, where K (1 Copyright © 2019, The Authors. All rights reserved.

关键词： Deep neural networks

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Structural design and strength analysis of multi-ring packed flywheel with heavy metal alloy segments

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IOP Conference Series: Materials science and Engineering 2019年第1期657卷

作者： L Jiang W Zhang C W Wu L P Zhang Y X Zhang Z Y Liu National Key Laboratory of Science and Technology on Reactor System Design Technology Nuclear Power Institute of China Chengdu 610041 China State Key Laboratory of Structural Analysis for Industrial Equipment Dalian University of Technology Dalian 116024 China

Flywheel, as a kinetic energy storage and conversion device, has promising applications due to its high efficiency, no pollution and long lifetime. In particular, with a three-layer structure packed with heavy metal alloy middle layer, a flywheel can achieve both a large rotational inertia and a high energy density. To guarantee structural strength safety of this type of multi-ring packed flywheel operating at high temperature, structural and thermal stress analysis for a flywheel with a tungsten alloy layer sandwiched between two stainless steel layers is carried out using finite element method (FEM). Based on plane stress assumption, flywheel stress characteristic along radius under assembly force, centrifugal force and thermal loading is demonstrated. The results show that, the rise of temperature causes inconsistent thermal expansion between neighbouring layers and results in a large thermal stress. Particularly, a high circumferential tensile stress occurs in the middle layer. It is also found that, the segments of the middle tungsten alloy layer can efficiently relieve the inconsistent thermal expansion and lower the thermal stress. Moreover, the number of segments significantly influences the efficiency of thermal stress releasing and the reserved gap between adjacent segments significantly improves the contact pressure between inner hub and tungsten alloy layer. This work may provide reference for structural design of the multi-ring packed flywheels under thermal loading.

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Research on homoclinic orbits and homoclinic bifurcation motion in a typical triple-well potential vibration system 25

Research on homoclinic orbits and homoclinic bifurcation mot...

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25th International Congress on Sound and Vibration 2018: Hiroshima Calling, ICSV 2018

作者： Feng, Jingjing Zhang, Wei Lui, Haiying Hu, Wenhua Beijing University of Technology College of Mechanical Engineering Beijing Key Laboratory on Nonlinear Vibrations and Strength of Mechanical Structures Beijing China Tianjin University of Technology School of Mechanical Engineering Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent Control Tianjin China Tianjin University of Technology National Demonstration Center for Experimental Mechanical and Electrical Engineering Education Tianjin China

ISBN: (纸本)9781510868458

The pull-in phenomenon is an important sign of instable movement for electrostatic micro-resonators. In present paper, the problems of homoclinic orbits and homoclinic bifurcation motion in a typical triple-well potential system with non-Z2 symmetric and higher-order nonlinear terms are studied, which is used to describe corresponding nonlinear dynamical behaviors of pull-in and complex vibration phenomena in typical micro-resonator. For the complexity between the equilibrium points and the phase space curves in triple-well potential system, the non-Z2 symmetric homoclinic orbits that are corresponding to the pull-in phenomenon are discussed under a certain energy input condition. Because the fact of the air damping in the actual micro-resonator cannot be ignored, the autonomous system containing the damping terms is studied directly. The further improved Padé approximation method can be applied to directly obtain analytical expressions of special homoclinic orbits with completely non-Z2 symmetry in corresponding conservative system, which contain not only the conventional Z2 symmetric nonlinear terms, but also the non-Z2 symmetric and higher-order nonlinear terms. In addition, the phase diagrams and bifurcation parameter curves of homoclinic orbit in corresponding autonomous system are obtained when the homoclinic bifurcation occurs. The present method is valid by comparing with the phase diagrams of homoclinic orbits from numerical method. Copyright © (2018) by International Institute of Acoustics & *** rights reserved.

关键词： Numerical methods

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