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A combined nanotherapeutic approach targeting farnesoid X receptor,ferroptosis,and fibrosis for nonalcoholic steatohepatitis treatment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2228-2246页

作者： Jiangtao Fu pingping Zhang Zhiguo Sun Guodong Lu Qi Cao Yiting Chen Wenbin Wu Jiabao Zhang Chunlin Zhuang Chunquan Sheng Jiajun xu Ying Lu Pei Wang The Center for Basic Research and Innovation of Medicine and Pharmacy(MOE) School of PharmacyNaval Medical UniversityShanghai 200433China National Demonstration Center for Experimental Pharmaceutical Education Naval Medical University/Second Military Medical UniversityShanghai 200433China Department of Diving and Hyperbaric Medicine Naval Special Medical CenterNaval Medical UniversityShanghai 200433China

Obeticholic acid(OCA),a farnesoid X receptor(FXR)agonist with favorable effects on fatty and glucose metabolism,has been considered the leading candidate drug for nonalcoholic steatohepatitis(NASH)treatment.However,its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major drawback.Ferroptosis,a newly recognized form of cell death characterized by uncontrolled lipid peroxidation,is involved in the progression of NASH.Nitric oxide(NO)is a versatile biological molecule that can degrade extracellular matrix.In this study,we developed a PEGylated thiolated hollow mesoporous silica nanoparticles(MSN)loaded with OCA,as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol(ONL@MSN).Biochemical analyses,histology,multiplexed flow cytometry,bulk-tissue RNA sequencing,and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle(ONL@MSN)in a mouse NASH model.Compared with the OCA-loaded nanoparticles(O@MSN),ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ferroptosis.ONL@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis,inhibition of immune response/lipid peroxidation,and correction of microbiota dysbiosis.These findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR,ferroptosis,and fibrosis.

关键词： Nonalcoholic steatohepatitis Nanotherapy Farnesoid X receptor Ferroptosis Fibrosis Obeticholic acid S-Nitrosothiol Liproxstatin-1

Exploration of sea anemone-inspired high-performance biomaterials with enhanced antioxidant activity

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Bioactive Materials 2022年第4期7卷 504-514页

作者： Lulu Wang Xiaokang Zhang pingping xu Jicheng Yan Yuzhong Zhang Hainan Su Chengjun Sun Qiang Lu Weizhi Liu Sars-Fang Centre MOE Key Laboratory of Marine Genetics and BreedingCollege of Marine Life SciencesOcean University of ChinaQingdao266003China Laboratory for Marine Biology and Biotechnology Pilot National Laboratory for Marine Science and TechnologyQingdao266071China State Key Laboratory of Microbial Technology Marine Biotechnology Research CenterShandong UniversityQingdao266237China Key Laboratory of Marine Eco-environmental Science and Technology Marine Bioresource and Environment Research CenterFirst Institute of OceanographyMinistry of Natural Resources(MNR)Qingdao266061China National Engineering Laboratory for Modern Silk Collaborative Innovation Center of Suzhou Nano Science and TechnologySoochow UniversitySuzhou215123China

Antioxidant biomaterials have attracted much attention in various biomedical fields because of their effective inhibition and elimination of reactive oxygen species(ROS)in pathological tissues.However,the difficulty in ensuring biocompatibility,biodegradability and bioavailability of antioxidant materials has limited their further development.Novel bioavailable antioxidant materials that are derived from natural resources are urgently needed.Here,an integrated multi-omics method was applied to fabricate antioxidant biomaterials.A key cysteine-rich thrombospondin-1 type Ⅰ repeat-like(TSRL)protein was efficiently discovered from among 1262 adhesive components and then used to create a recombinant protein with a yield of 500 mg L^(-1).The biocompatible TSRL protein was able to self-assemble into either a water-resistant coating through Ca^(2+)-mediated coordination or redox-responsive hydrogels with tunable physical properties.The TSRL-based hydrogels showed stronger 1,1-diphenyl-2-picrylhydrazyl(DPPH)radical scavenging rates than glutathione(GSH)and ascorbic acid(Aa)and protected cells against external oxidative stress significantly more effectively.When topically applied to mice skin,TSRL alleviated epidermal hyperplasia and suppressed the degradation of collagen and elastic fibers caused by ultraviolet radiation B(UVB)irradiation,confirming that it enhanced antioxidant activity in vivo.This is the first study to successfully characterize natural antioxidant biomaterials created from marine invertebrate adhesives,and the findings indicate the excellent prospects of these biomaterials for great applications in tissue regeneration and cosmeceuticals.

关键词： Sessile marine organisms Antioxidant biomaterials Water-resistant coatings Redox-responsive hydrogels Photoaging

Link QoS analysis of 5G-enabled V2V network based on vehicular cloud

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Science China(Information Sciences) 2018年第10期61卷 272-278页

作者： Guilu WU pingping xu National Mobile Communications Research Laboratory Southeast University

Dear editor,The fifth generation (5G) communication technologies, especially for millimeter wave (mm Wave)technology, have a huge application for satisfying different service requirements in vehicular networks, e.g., the vehicle-to-vehicle (V2V) network.In the mm Wave V2V network, a reliable link quality-of-service (Qo S) is particularly important because it brings reliable message transmissions for various service requirements. For a vehicular

关键词： Link QoS analysis of 5G-enabled V2V network based on vehicular cloud

协议企业储备模式下应急物资储备策略及供应链协调研究

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系统工程理论与实践 2024年第5期44卷 1589-1602页

作者：扈衷权郭珂欣徐金鹏冯平平西安电子科技大学经济与管理学院西安710126

为充分发挥应急物资协议企业储备模式的优越性,利用期权契约建立政企合作关系,在考虑企业可同时选用实物与生产能力这两种物资储备形式的情况下,给出企业在期权执行价格及灾害事件发生概率满足不同条件时的最优储备形式选择(单一实物储... 详细信息

为充分发挥应急物资协议企业储备模式的优越性,利用期权契约建立政企合作关系,在考虑企业可同时选用实物与生产能力这两种物资储备形式的情况下,给出企业在期权执行价格及灾害事件发生概率满足不同条件时的最优储备形式选择(单一实物储备,单一生产能力储备,实物储备+生产能力储备)及对应储备量,并在此基础上设计相应的供应链协调机制,分析相关因素对协调机制,储备策略及政企双方成本利润的影响.研究结果表明,所设计的协调机制具有较强的鲁棒性;当企业采取双储备形式时,较高的灾害事件发生概率会导致实物储备量增加及生产能力储备量降低,但物资现货市场采购价格的上升仅会导致生产能力储备量增加;无论企业采取何种储备形式,政企双方的成本利润均随灾害事件发生概率和物资现货市场采购价格的增加而上升,且权利金的降低会提升双方成本利润对相关因素变化反应的敏感性;随着灾害事件发生概率和物资现货市场采购价格的上升,企业储备模式的优越性将愈发显著.

关键词：应急物资储备政企合作实物储备生产能力储备供应链协调

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Joint relay selection and power control for robust cooperative multicast in mm Wave WPANs

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Science China(Information Sciences) 2016年第8期59卷 133-143页

作者： Hongyun CHU pingping xu Wei WANG Chencheng YANG National Mobile Communications Research Laboratory Southeast University Department of Electrical and Computer Engineering Purdue University

We propose an optimization algorithm for joint relay selection and source and relay power allocation under mixed line-of-sight(LoS) and non-Lo S path scenarios for both power saving and robustness enhancement of cooperative multicast in millimeter-wave wireless personal area networks. Our aims are to reduce power consumption and enhance the robustness of cooperative multicasts in millimeter-wave wireless personal area networks. First, we describe a novel beam training protocol that is capable of overhearing and information feedback to filter relay candidates with non-Lo S links and avoid selecting relays for transceivers with Lo S paths.Second, the joint relay selection and power allocation issue is formulated as an optimization problem with the objective of minimizing the maximum combined power consumption of the source and relay under maximum tolerable outage probabilities and transmit powers. By introducing relaxation and Lagrange multiplier methods,a closed-form expression for the joint relay selection and power allocation is obtained. Finally, simulation results indicate significant improvements in terms of both outage probability and power consumption over the conventional combined transmit power minimization algorithm.

关键词： millimeter-wave(mm Wave) cooperative multicast non-line-of-sight(non-LoS) relay selection power allocation

Plant above-ground biomass and litter quality drive soil microbial metabolic limitations during vegetation restoration of subtropical forests

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Soil Ecology Letters 2023年第2期5卷 103-115页

作者： Shuo Zhang Ying-Ping Wang Xi Fang Jinlei Chen Nannan Cao pingping xu Mengxiao Yu Xin Xiong Xiangping Tan Qi Deng Junhua Yan Key Laboratory of Vegetation Restoration and Management of Degraded Ecosystems South China Botanical GardenChinese Academy of SciencesGuangzhou 510650China University of Chinese Academy of Sciences Beijing 100049China CSIRO Oceans and Atmosphere PMB 1AspendaleVictoria 3195Australia Faculty of Life Science and Technology Central South University of Forestry and TechnologyChangsha 410004China

Changes in litter quality(carbon:nitrogen,C:N)and above-ground biomass(AGB)following vegetation restoration significantly impact soil physicochemical properties,yet their effects on soil microbial metabolic limitations remain unclear.We measured litter quality,AGB,soil physicochemical properties,and extracellular enzyme activity(EEA)along a vegetation restoration gradient(7,14,49,70 years,and nearly climax evergreen broadleaved forests)in southern China.We also evaluated soil microbial metabolic limitations by a vector analysis of the EEA.Results revealed the soil microbial metabolisms were co-limited by C and phosphorus(P).The microbial C limitation initially decreased(before 14 years)and then increased,while the microbial P limitation initially increased(before 49 years)and then decreased.Partial least squares path modeling(PLS-PM)showed that the microbial C limitation was mainly attributed to microbial C use efficiency induced by litter quality,suggesting that microorganisms may transfer cellular energy between microbial growth and Cacquiring enzyme production.The microbial P limitation was primarily correlated with AGB-driven change in soil elements and their stoichiometry,highlighting the importance of nutrient stoichiometry and balance in microbial metabolism.The shifts between microbial C and P limitations and the strong connections of plant–soil-microbe processes during vegetation restoration revealed here will provide us with helpful information for optimal management to achieve forest restoration success.

关键词： Extracellular enzymatic stoichiometry Microbial metabolic limitations Above-ground biomass Litter quality Vegetation restoration Subtropic

Performance analysis of AUL FeLAA and WiFi coexistence in the presence of Rayleigh fading channel and capture effect under unsaturated traffic conditions

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Science China(Information Sciences) 2019年第8期62卷 213-215页

作者： Wei WANG pingping xu Yuan ZHANG Hongyun CHU National Mobile Communications Research Laboratory Southeast University Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences

Dear editor,Recently, the 3rd generation partnership project(3GPP) release 15 has evolved the licensed assisted access (LAA) framework into the autonomous uplink (AUL) future enhanced LAA (FeLAA). The frame of the AUL FeLAA transmits autonomously and needs no scheduling grant. Significantly, how to coexist with WiFi in the unlicensed band is an

关键词： Performance analysis of AUL FeLAA and WiFi coexistence in the presence of Rayleigh fading channel and capture effect under unsaturated traffic conditions Rayleigh

Sparse array of sub-surface aided blockage-free multi-user mmWave communication systems

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Digital Communications and Networks 2020年第3期6卷 292-303页

作者： Weicong Chen Xi Yang Shi Jin pingping xu National Mobile Communications Research Laboratory Southeast UniversityNanjing210096P.R.China

Recently,Reconfigurable Intelligent Surfaces(RISs)have drawn intensive attention in the realization of the smart radio environment.However,existing works mainly consider the RIS as a whole uniform plane,which may be unrealistic to be installed on the facade of buildings when the RIS is extremely large.In contrast,this paper investigates a practical Sparse Array of Sub-surface(SAoS)deployment of the RIS for uplink multi-user millimeter Wave(mmWave)communication systems,in which the Mobile Stations(MSs)are distributed in the blind coverage area due to the blockage.In order to exploit the benefits of the sparse deployment,the correlation of the effective channel is firstly investigated.Then the approximation and lower bounds of the ergodic spectral efficiency are derived under frequency and spatial multiplexing scenarios,respectively.Based on the autocorrelation of the effective channel,we obtain an optimal reflect coefficient design as well as the deployment guidelines of RIS tiles.Moreover,the RIS tile scheduling algorithms are also proposed.Numerical results show that the ergodic spectral efficiency approximation matches well with the Monte Carlo result under frequency multiplexing scenarios,and the lower bound is tight under spatial multiplexing scenarios only when the effective channel is strongly correlated.On the basis of the RIS tile scheduling algorithm and the reflect coefficient design,the system performance can be significantly improved under frequency multiplexing scenarios.On the other hand,by deploying more sparse RIS tiles,we can increase the multiplexing gain under spatial multiplexing scenarios.

关键词： Sparse array Reconfigurable intelligent surface Multi-user Blockage-free mmWave

Energy-efficient cell-association bias adjustment algorithm for ultra-dense networks

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Science China(Information Sciences) 2018年第2期61卷 100-114页

作者： Wenxiang ZHU pingping xu Thi Oanh BUI Guilu WU Yan YANG National Mobile Communications Research Laboratory Southeast University Department of Electronic and Electrical Engineering Bengbu University

In recent years, energy efficiency has become an important topic, especially in the field of ultradense networks(UDNs). In this area, cell-association bias adjustment and small cell on/off are proposed to enhance the performance of energy efficiency in UDNs. This is done by changing the cell association relationship and turning off the extra small cells that have no users. However, the variety of cell association relationships and the switching on/off of the small cells may deteriorate some users’ data rates, leading to nonconformance to the users’ data rate requirement. Considering the discreteness and non-convexity of the energy efficiency optimization problem and the coupled relationship between cell association and scheduling during the optimization process, it is difficult to achieve an optimal cell-association bias. In this study, we optimize the network energy efficiency by adjusting the cell-association bias of small cells while satisfying the users’ data rate requirement. We propose an energy-efficient centralized Gibbs sampling based cell-association bias adjustment(CGSCA) algorithm. In CGSCA, global information such as channel state information, cell association information, and network load information need to be collected. Then, considering the overhead of the messages that are exchanged and the implementation complexity of CGSCA to obtain the global information in UDNs, we propose an energy-efficient distributed Gibbs sampling based cell-association bias adjustment(DGSCA) algorithm with a lower message-exchange overhead and implementation complexity.Using DGSCA, we derive the updated formulas for calculating the number of users in a cell and the users’ SINR. We analyze the implementation complexities(e.g., computation complexity and communication complexity) of the proposed two algorithms and other existing algorithms. We perform simulations, and the results show that CGSCA and DGSCA have faster convergence speed, as well as a higher performance gain of the energy efficiency and throughput compared

关键词： ultra-dense networks cell-association bias energy efficiency Gibbs sampling users’ data rate constraint