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Gefapixant,a Novel P2X3 Antagonist,Protects against Post Myocardial Infarction Cardiac Dysfunction and Remodeling Via Suppressing NLRP3 Inflammasome

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Current Medical Science 2023年第1期43卷 58-68页

作者： Yan-zhao WEI Shuang Yang Wei LI Yan-hong TANG Department of Cardiology Renmin Hospital of Wuhan UniversityWuhan430060China Cardiovascular Research Institute Wuhan UniversityWuhan430060China Hubei Key Laboratory of Cardiology Wuhan430060China Department of Cardiology Wuhan No.1 HospitalWuhan Hospital of Traditional Chinese and Western MedicineWuhan430022China

Objective The ATP responsive P2 purinergic receptors can be subdivided into metabotropic P2X family and ionotropic P2Y family.Among these,P2X3 is a type of P2X receptor which is specifically expressed on nerves,especially on pre-ganglionic sensory fibers.This study investigates whether gefapixant possesses the potential of inhibiting cardiac sympathetic hypersensitivity to protect against cardiac remodeling in the context of myocardial infarction.Methods The Sprague-Dawley rats were divided randomly into three groups:sham group-myocardial infarction group,and myocardial infarction with gefapixant treatment group.Myocardial infarction was induced by left anterior descending branch ligation.The gefapixant solution was intraperitoneally injected each time per day for 7 days and the appropriate dosage of gefapixant was determined according to the results of hematoxylin-eosin(HE)staining and myocardial injury biomarkers.Conditions of cardiac function were assessed by echocardiograph and cardiac fibrosis was evaluated by Western blotting and immunofluorescence staining of collagen I and collagen III.The sympathetic innervation was detected by norepinephrine concentration(pg/mL),in-vivo electrophysiology,and typical sympathetic biomarkers.Inflammatory cell infiltration was shown from immunofluorescence staining and pro-inflammatory signaling pathway activation was checked by immunohistology,quantitative realtime PCR(qPCR)and Western blotting.Results It was found that gefapixant injection of 10 mg/kg per day had the highest dosage-efficacy ratio.Furthermore,gefapixant treatment improved cardiac pump function as shown by increased LVEF and LVFS,and decreased LVIDd and LVIDs.The expression levels of collagen I and collagen III,and TNF-αwere all decreased by P2X3 inhibition.Mechanistically,the decreased activation of nucleotide-binding and oligomerization domain-like receptors family pyrin-domain-containing 3(NLRP3)inflammasome and subsequent cleavage of caspase-1 which modulated interleukin-1β(IL-1β)and IL-18 level in hear

关键词： myocardial infarction P2X3 inhibition gefapixant nucleotide-binding and oligomerization domain-like receptors family pyrin-domain-containing 3 inflammasome sympathetic nerve

The role of fibronectin in multiple sclerosis and the effect of drug delivery across the blood-brain barrier

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Neural Regeneration Research 2023年第10期18卷 2147-2155页

作者： shuang-shuang Wei Le Chen Feng-Yuan yang Si-Qi Wang Peng Wang Ningxia Key Laboratory of Craniocerebral Diseases School of Clinical MedicineNingxia Medical UniversityYinchuanNingxia Hui Autonomous RegionChina Ningxia Key Laboratory of Craniocerebral Diseases Ningxia Medical UniversityYinchuanNingxia Hui Autonomous RegionChina

Remyelination failure is one of the main characteristics of multiple sclerosis and is potentially correlated with disease progression.Previous research has shown that the extracellular matrix is associated with remyelination failure because remodeling of the matrix often fails in both chronic and progressive multiple sclerosis.Fibronectin aggregates are assembled and persistently exist in chronic multiple sclerosis,thus inhibiting remyelination.Although many advances have been made in the mechanisms and treatment of multiple sclerosis,it remains very difficult for drugs to reach pathological brain tissues;this is due to the complexity of brain structure and function,especially the existence of the blood-brain barrier.Therefore,herein,we review the effects of fibronectin aggregates on multiple sclerosis and the efficacy of different forms of drug delivery across the blood-brain barrier in the treatment of this disease.

关键词： blood-brain barrier brain delivery exosomes extracellular matrix fibronectin aggregates fibronectin intestinal flora multiple sclerosis remyelination failure remyelination

The Shock Response and Spall Mechanism of Mg-Al-Zn Alloy:Molecular Dynamics Study

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Acta Mechanica Solida Sinica 2022年第3期35卷 495-503页

作者： Xiaoyue yang shuang Xu Lisheng Liu Hubei Key Laboratory of Theory and Application of Advanced Materials Mechanics Wuhan University of TechnologyWuhan 430070China State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070China

Shock responses of Mg-Al-Zn alloy are investigated by the molecular dynamics(MD)method.The wave propagation,plastic deformation behavior and failure mechanism along the[0001]and[1010]orientations are analyzed.For both orientations,simulation results show that the shock wave has an obvious double-wave structure(plastic-elastic)under a piston velocity of 1200 m/s.A higher Hugoniot elastic limit(HEL)is observed for[0001]-oriented shock.When the shock pressure is along the[1010]direction,the distance between plastic and elastic waves is closer,and higher dislocation density and more twins are observed.Moreover,the spall strength for[1010]-oriented shock is predicted to be higher.In addition,the wave interactions,HEL and spall strength predicted for Mg-Al-Zn alloy are compared with the experimental results and MD simulation results of Mg single crystal in the literature.It is concluded that the shock performance of Mg-Al-Zn is better than that of Mg single crystal.

关键词： Mg-Al-Zn Shock compression Molecular dynamics Hugoniot elastic limit Spall strength

Access to enantioenriched molecules with diverse fluorinated tetrasubstituted stereocenters using hydroxy as a kinetic resolution auxiliary group

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Organic Chemistry Frontiers 2022年第4期9卷 1040-1047页

作者： Syeda Tazeen Zehra Shouang Lan Hao Zhang Jinggong Liu Shuang Yang Xinqiang Fang State Key Laboratory of Structural Chemistry and Key Laboratory of Coal to Ethylene Glycol and Its Related TechnologyCenter for Excellence in Molecular SynthesisFujian Institute of Research on the Structure of MatterUniversity of Chinese Academy of SciencesFuzhou 350100China Orthopedics Department Guangdong Provincial Hospital of Traditional Chinese MedicineThe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China

Developing a general method affording optically pure fully substituted carbon molecules bearing various fluorinated groups is highly important but very challenging.Here we show that using secondary OH as a kinetic resolution auxiliary group,a series of previously unavailable fluorinated fully substituted carbon molecules can be obtained with excellent enantioselectivities,thus providing an alternative complementary method that provides solutions to the limitations confronted by the known methods.

关键词： substituted auxiliary kinetic

Hybrid method for accurate multi-gravity-assist trajectory design using pseudostate theory and deep neural networks

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Science China(Technological Sciences) 2022年第3期65卷 595-610页

作者： yang Bin FENG JingLang HUANG XuXing LI shuang College of Astronautics Nanjing University of Aeronautics and AstronauticsNanjing 211106China Department of Mechanical&Aerospace Engineering University of StrathclydeGlasgow G11XJUK

This paper presents a novel hybrid method to design the continuous and accurate multi-gravity-assist trajectory for a high-fidelity dynamics.The gravitational perturbation of the primary body is considered during the gravity assistance.The pseudostate technique is applied to approximate the gravity-assisted trajectory,where the optimal sweepback duration is solved using a trained deep neural network.The major factors that affect the optimal sweepback duration of the approach and departure segments are investigated.The results show that the optimal sweepback duration of the approach segment only relies on the shape of the approach trajectory and is independent of the flight time.Then,a gravity-assisted trajectory patched strategy and a hybrid algorithm combining the particle swarm optimization and the sequential quadratic programming are developed to optimize the multi-gravity-assist trajectory.The proposed hybrid method is applied to the Europa orbiter mission.In comparison with the traditional patched conic method,this method demonstrates outstanding performance on accuracy and significantly reduces the computational time and complexity of the trajectory correction with the high-fidelity dynamics.

关键词： pseudostate theory multiple gravity assist deep neural network trajectory optimization Jovian system

Convex optimization of asteroid landing trajectories driven by solar radiation pressure

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Chinese Journal of Aeronautics 2022年第12期35卷 200-211页

作者： Chuanjun DONG Hongwei yang shuang LI Bo LI College of Astronautics Nanjing University of Aeronautics and AstronauticsNanjing 211106China Tianjin Key Laboratory of Microgravity and Hypogravity Environment Simulation Technology Tianjin 300458China Tianjin Institute of Aerospace Mechanical and Electrical Equipment Tianjin 300458China

High-area/mass ratio landers driven by Solar Radiation Pressure(SRP)have potential applications for future asteroid landing missions.This paper develops a new convex optimization-based method for planning trajectories driven by SRP.A Minimum Landing Error(MLE)control problem is formulated to enable planning SRP-controlled trajectories with different flight times.It is transformed into Second Order Cone Programming(SOCP)successfully by a series of different convexification technologies.A trust region constraint and a modified MLE objective function are used to guarantee the convergence performance of the optimization algorithm.Thereafter,the SRP-driven trajectory optimal control problem is converted equivalently into a sequence of convex optimal control problems that can be solved effectively.A set of numerical simulation results has verified the effectiveness and feasibility of the proposed optimization method.

关键词： Asteroids Convex optimization Optimal control Soft landing Solar radiation pressure Trajectory optimization

Research on the Flow and Heat Transfer Characteristics of a Water-Cooling Plate in a Heat Dissipation System

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Energy Engineering 2021年第6期118卷 1855-1867页

作者： Yukun Lv Zhuang Wei Quanzhi Ge Fan yang Shuang Yang Department of Energy Power and Mechanical EngineeringNorth China Electric Power UniversityBaoding071003China

The water-cooling heat dissipation technology can solve the heat dissipation and noise problems of the calculation plate.Therefore,the structural design of the water-cooling plate directly affects its flow and heat transfer characteristics,which restricts the promotion and application of the technology.To this end,the water-cooling plate of a heat dissipation system was taken as the research object,and its flow and heat transfer characteristics were numerical simulated and experimental studied.Through comparative analysis,the rationality of the numerical simulation method was verified.Based on this,three improved schemes of water-cooling plate structure were proposed and numerical simulation was carried out,and the optimal model was verified by experiments.The results of the study show that compared with the original water-cooling plate,the optimized water-cooling plate has increased internal flow velocity and distributes uniformly,increased heat transfer amount by 4.2%,and the average temperature of the calculation plate decreased by 5.3%.

关键词： Calculation plate water-cooling plate flow and heat transfer characteristics

On-board modeling of gravity fields of elongated asteroids using Hopfield neural networks

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Astrodynamics 2023年第1期7卷 101-114页

作者： Yingjie Zhao Hongwei yang shuang Li Yirong Zhou College of Astronautics Nanjing University of Aeronautics and AstronauticsNanjing 211106China College of Automation Engineering Nanjing University of Aeronautics and AstronauticsNanjing 211106China

To rapidly model the gravity field near elongated asteroids,an intelligent inversion method using Hopfield neural networks(HNNs)is proposed to estimate on-orbit simplified model parameters.First,based on a rotating mass dipole model,the gravitational field of asteroids is characterized using a few parameters.To solve all the parameters of this simplified model,a stepped parameter estimation model is constructed based on different gravity field models.Second,to overcome linearization difficulties caused by the coupling of the parameters to be estimated and the system state,a dynamic parameter linearization technique is proposed such that all terms except the parameter terms are known or available.Moreover,the Lyapunov function of the HNNs is matched to the problem of minimizing parameter estimation errors.Equilibrium values of the Lyapunov function areused as estimated values.The proposed method is applied to natural elongated asteroids 216 Kleopatra,951 Gaspra,and 433 Eros.Simulation results indicate that this method can estimate the simplified model parameters rapidly,and that the estimated simplified model provides a good approximation of the gravity field of elongated asteroids.

关键词： elongated asteroids simplified model Hopfield neural networks(HNNs) on-board learning gravity inversion

A Research on the Flow Characteristics of a Splitter-Based Water Cooling System for Computer Boards

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Fluid Dynamics & Materials Processing 2021年第4期17卷 833-844页

作者： Yukun Lv Quanzhi Ge Zhuang Wei Shuang Yang North China Electric Power University Baoding071003China

The splitter is an important component of water-based cooling systems used to extract heat from computer boards.In the present study,the flow characteristics of a 16-splitter structure were numerically simulated and compared with experimental results to verify the reliability of the numerical simulation method.Accordingly,the concept of splitter structural coefficients was proposed.Based on the results of this study,we recommend a selection range of 5≤k≤6 for the structure factor k of the splitter;after optimization,the maximum deviation of the splitter outlet flow was reduced from the original value of 100%to 8.3%.

关键词： Computing board cold-water splitter structure factor flow-transfer characteristics experimental study numerical simulation