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Development of small molecule drugs targeting immune checkpoints

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Cancer Biology & Medicine 2024年第5期21卷 382-399页

作者： Luoyi Chen Xinchen Zhao Xiaowei liu yujie Ouyang Chuan Xu Ying Shi Department of Oncology Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of MedicineUniversity of Electronic Science and Technology of China Institute for Breast Health Medicine State Key Laboratory of Biotherapy West China Hospital Sichuan University Acupuncture and Massage College Chengdu University of Traditional Chinese Medicine

Immune checkpoint inhibitors(ICIs) are used to relieve and refuel anti-tumor immunity by blocking the interaction, transcription, and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints. Thousands of small molecule drugs or biological materials, especially antibody-based ICIs, are actively being studied and antibodies are currently widely used. Limitations, such as anti-tumor efficacy, poor membrane permeability, and unneglected tolerance issues of antibody-based ICIs, remain evident but are thought to be overcome by small molecule drugs. Recent structural studies have broadened the scope of candidate immune checkpoint molecules, as well as innovative chemical inhibitors. By way of comparison, small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features. Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions, including immune regulation, anti-angiogenesis, and cell cycle regulation. In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins, which will lay the foundation for further exploration.

关键词： CD47 Immune checkpoints programmed death protein 1 signal-regulatory protein α small molecule drugs

Iron single-atom/clusters catalysts derived from iron-rich Enteromorpha after urea-saturation for Fenton-like reaction

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Chinese Chemical Letters 2024年第3期35卷 149-152页

作者： yujie Zhang Siyi liu Dongdong Chen Xing Xu School of Environmental Science and Engineering Shandong UniversityQingdao 266237China

Fabrication of single atom catalysts(SACs)by a green and gentle method is important for their practical Fenton-like use.In this work,a high effective iron-based catalyst was prepared from the iron-rich Enteromorpha for NPX degradation via peroxymonosulfate(PMS).Both Fe-SACs and iron-clusters was fabricated from the intrinsic iron element in Enteromorpha after the urea saturation.The Fe-SACs/clusters can achieve 100%of NPX oxidation within 20 min with the k_(obs)of 0.282 min^(-1).Quenching tests indicated that the radical pathways were not dominated in the catalytic systems,and strong electron transfer process can be induced in the Fe-SACs/clusters+PMS system by using the NPX as electron donor and FeSACs/clusters/PMS^*complexes as electron acceptor.This result was consistent with the phenomenon observed in the galvanic oxidation system.In addition,the Fe-SACs/clusters was deposited onto the ceramic membrane(CM)by the spraying-crosslinking process to form a Fe-SACs/clusters@CM,which showed an effective and continuous NPX degradation in a heterogeneous PMS system.

关键词： SACs Iron Clusters Fenton-like reaction Enteromorpha

Preparation,characterization and antioxidant activity analysis of three Maillard glycosylated bone collagen hydrolysates from chicken,porcine and bovine

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Food Science and Human Wellness 2024年第4期13卷 2002-2013页

作者： Liwei Qi Hongru Zhang yujie Guo Hong liu Chunhui Zhang Key Laboratory of Agro-Products Processing Ministry of Agriculture and Rural AffairsInstitute of Food Science and TechnologyChinese Academy of Agricultural SciencesBeijing 100193China Laboratory of Biomass and Green Technologies University of Liege-Gembloux Agro-Bio TechPassage des déportés 2Gembloux B-5030Belgium

Bone collagen hydrolysates(peptides)derived from byproduct of animal product processing have been used to produce commercially valuable products due to their potential antioxidant activity.Maillard glycosylated reaction is considered as a promising method to enhance the antioxidant activity of peptides.Hence,this research aims at investigating the Maillard glycosylation activity and antioxidant activity of bone collagen hydrolysates from different sources.In this study,3 glycosylated bone collagen hydrolysates were prepared and characterized,and cytotoxicity and antioxidant activity were analyzed and evaluated.The free amino groups loss,browning intensity,and fluorescence intensity of G-Cbcp(glycosylated chicken bone collagen hydrolysates(peptides))were the heaviest,followed by G-Pbcp(glycosylated porcine bone collagen hydrolysates(peptides))and G-Bbcp(glycosylated bovine bone collagen hydrolysates(peptides)).The results of amino acid analysis showed that amino acid composition of different bone collagen hydrolysates was significantly different and the amino acid decreased to different degrees after Maillard glycosylated reaction,which may lead to differences in Maillard glycosylated reaction activity.Furthermore,the 3 glycosylated hydrolysates showed no significant cytotoxicity.The results showed that glycosylation process significantly increased the antioxidant activity of bone collagen hydrolysates,and G-Cbcp showed the strongest antioxidant activity,followed by G-Pbcp and G-Bbcp.Therefore,compared with the bone collagen hydrolysates,3 glycosylated hydrolysates showed significant characteristic and structural changes,and higher antioxidant activity.

关键词： Bone collagen hydrolysates Glycosylation reaction Antioxidant activity

Characterizing structure of cross-disciplinary impact of global disciplines:A perspective of the Hierarchy of Science

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Journal of Data and Information Science 2024年第1期9卷 53-81页

作者： Ruolan liu Jin Mao Gang Li yujie Cao Center for Studies of Information Resources Wuhan UniversityWuhan 430072China School of Information Management Wuhan UniversityWuhan 430072China School of Information Management Central China Normal University 430072WuhanChina

Purpose:Interdisciplinary fields have become the driving force of modern science and a significant source of scientific innovation.However,there is still a paucity of analysis about the essential characteristics of disciplines’cross-disciplinary impact.Design/methodology/approach:In this study,we define cross-disciplinary impact on one discipline as its impact to other disciplines,and refer to a three-dimensional framework of variety-balance-disparity to characterize the structure of cross-disciplinary impact.The variety of cross-disciplinary impact of the discipline was defined as the proportion of the high cross-disciplinary impact publications,and the balance and disparity of cross-disciplinary impact were measured as well.To demonstrate the cross-disciplinary impact of the disciplines in science,we chose Microsoft Academic Graph(MAG)as the data source,and investigated the relationship between disciplines’cross-disciplinary impact and their positions in the Hierarchy of Science(HOS).Findings:Analytical results show that there is a significant correlation between the ranking of cross-disciplinary impact and the HOS structure,and that the discipline exerts a greater cross-disciplinary impact on its neighboring disciplines.Several bibliometric features that measure the hardness of a discipline,including the number of references,the number of cited disciplines,the citation distribution,and the Price index have a significant positive effect on the variety of cross-disciplinary impact.The number of references,the number of cited disciplines,and the citation distribution have significant positive and negative effects on balance and disparity,respectively.It is concluded that the less hard the discipline,the greater the cross-disciplinary impact,the higher balance and the lower disparity of cross-disciplinary impact.Research limitations:In the empirical analysis of HOS,we only included five broad disciplines.This study also has some biases caused by the data source and applied regression models.Practical implications:

关键词： Interdisciplinary research cross-disciplinary Scientific impact Soft science Hard science Citation

Analysis and Optimization of Transient Mode Switching Behavior for Power Split Hybrid Electric Vehicle with Clutch Collaboration

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Automotive Innovation 2024年第1期7卷 150-165页

作者： Dehua Shi Sheng liu yujie Shen Shaohua Wang Chaochun Yuan Long Chen Automotive Engineering Research Institute Jiangsu UniversityZhenjiang 212013China Jiangsu Province Engineering Research Center of Electric Drive System and Intelligent Control for Alternative Vehicles Zhenjiang 212013China

The power split hybrid electric vehicle(HEV)adopts a power coupling configuration featuring dual planetary gearsets and multiple clutches,enabling diverse operational modes through clutch engagement and disengagement.The multi-clutch configuration usually involves the collaboration of two clutches during the transient mode switching process,thereby substantially elevating control complexity.This study focuses on power split HEVs that integrate multi-clutch mechanisms and investigates how different clutch collaboration manners impact the characteristics of transient mode switching.The powertrain model for the power-split HEV is established utilizing matrix-based methodologies.Through the formulation of clutch torque curves and clutch collaboration models,this research systematically explores the effects of clutch engagement timing and the duration of clutch slipping state on transient mode switching behaviors.Building upon this analysis,an optimization problem for control parameters pertaining to the two collaborative clutches is formulated.The simulated annealing algorithm is employed to optimize these control parameters.Simulation results demonstrate that the clutch collaboration manners have a great influence on the transient mode switching performance.Compared with the pre-calibrated benchmark and the optimal solution derived by the genetic algorithm,the maximal longitudinal jerk and clutch slipping work during the transient mode switching process is reduced obviously with the optimal control parameters derived by the simulated annealing algorithm.The study provides valuable insights for the dynamic coordinated control of the power-split HEVs featuring complex clutch collaboration mechanisms.

关键词： Power split hybrid electric vehicle Transient mode switching Clutch collaboration Simulated annealing Powertrain model

Design and Performance Analysis of HMDV Dynamic Inertial Suspension Based on Active Disturbance Rejection Control

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Computer Modeling in Engineering & Sciences 2024年第8期140卷 1485-1506页

作者： Xiaofeng Yang Wei Wang yujie Shen Changning liu Tianyi Zhang School of Automotive and Traffic Engineering Jiangsu UniversityZhenjiang212013China Automotive Engineering Research Institute Jiangsu UniversityZhenjiang212013China Chongqing Key Laboratory of Urban Rail Transit System Integration and Control Chongqing400074China State Key Laboratory of Advanced Design and Manufacturing Technology for Vehicle Hunan universityChangsha410082China

This paper addresses the impact of vertical vibration negative effects,unbalanced radial forces generated by the static eccentricity of the hub motor,and road excitation on the suspension performance of Hub Motor Driven Vehicle(HMDV).A dynamic inertial suspension based on Active Disturbance Rejection Control(ADRC)is proposed,combining the vertical dynamic characteristics of dynamic inertial suspension with the features of ADRC,which distinguishes between internal and external disturbances and arranges the transition process.Firstly,a simulation model of the static eccentricity of the hub motor is established to simulate the unbalanced radial electromagnetic force generated under static eccentricity.A quarter-vehicle model of an HMDV with a controllable dynamic inertial suspension is then constructed.Subsequently,the passive suspension model is studied under different grades of road excitation,and the impact mechanism of suspension performance at speeds of 0–20 m/s is analyzed.Next,the three main components within the ADRC controller are designed for the second-order controlled system,and optimization algorithms are used to optimize its internal parameters.Finally,the performance of the traditional passive suspension,the PID-based controllable dynamic inertial suspension,and the ADRC-based controllable dynamic inertial suspension are analyzed under different road inputs.Simulation results show that,under sinusoidal road input,the ADRC-based controllable dynamic inertial suspension exhibits a 52.3%reduction in the low-frequency resonance peak in the vehicle body acceleration gain diagram compared to the traditional passive suspension,with significant performance optimization in the high-frequency range.Under random road input,the ADRC-based controllable dynamic inertial suspension achieves a 29.53%reduction in the root mean square value of vehicle body acceleration and a 14.87%reduction in dynamic tire load.This indicates that the designed controllable dynamic inertial suspension possesses excellent vibration isola

关键词： HMDV static eccentricity ADRC dynamic inertial suspension road excitation

Enhanced electrochemical oxidation of perfluorooctanoic acid on Ti/SnO_(2)-Sb electrode by surface morphology regulation

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Chinese Chemical Letters 2024年第3期35卷 140-143页

作者： Kaiqiang Hou Genwang Zhu yujie Feng Yanming liu Xie Quan Key Laboratory of Industrial Ecology and Environmental Engineering(Ministry of Education China)School of Environmental Science and TechnologyDalian University of TechnologyDalian 116024China State Key Laboratory of Urban Water Resource and Environment School of EnvironmentHarbin Institute of TechnologyHarbin 150090China

Electrochemical oxidation is an effective method to degrade persistent organic pollutants.However,due to the limited catalytic activity of traditional thin film electrodes,the anodic oxidation process is slow and usually requires high energy consumption.Herein,Ti/SnO_(2)-Sb electrode with regulated surface structure was reported to enhance the performance for electrochemical oxidation of persistent organic pollutants.The electrode deposited with SnO_(2)-Sb nanoneedles(Ti/N-SnO_(2)-Sb)showed higher oxidation activity.Its kinetic constant for perfluorooctanoic acid(PFOA)oxidation was 2.0 h^(-1)and the total organic carbon removal rate was 81.7%(4 h)at a relatively low current density of 6 mA/cm^2.Compared with Ti/SnO_(2)-Sb thin film and nanoparticles,Ti/N-SnO_(2)-Sb significantly improved the electrochemical active area and·OH yield,and simultaneously reduced the electron transfer resistance,which enabled it to oxidize PFOA more rapidly even at a lower potential.This work provides a new strategy for promoting the electrochemical oxidation performance.

关键词： Electrochemical oxidation Nanoneedle SnO_(2)-Sb Perfluoroalkyl compounds Electrochemical degradation Persistent organic pollutants

COF-based membranes for liquid phase separation:Preparation,mechanism and perspective

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Journal of Environmental Sciences 2024年第7期141卷 63-89页

作者： yujie Zhao He Gu Yilun Zhou CaimeiWen Xiaolu liu Suhua Wang Zhongshan Chen Hui Yang Xiangke Wang College of Environmental Science and Engineering North China Electric Power UniversityBeijing 102206China School of Environmental Science and Engineering Guangdong University of Petrochemical TechnologyMaoming 525000China

Covalent organic frameworks(COFs)are a new kind of crystalline porous materials composed of organic molecules connected by covalent bonds,processes the characteristics of low density,large specific surface area,adjustable pore size and structure,and easy to functionalize,which have been widely used in the field of membrane separation technology.Recently,there are more and more researches focusing on the preparation methods,separation application,and mechanism of COF membranes,which need to be further summarized and compared.In this review,we primarily summarized several conventional preparation methods,such as two-phase interfacial polymerization,in-situ growth on substrate,unidirectional diffusion method,layer-by-layer assembly method,mixed matrix membranes,and so on.The advantages and disadvantages of each method are briefly summarized.The application potential of COF membrane in liquid separation are introduced from four aspects:dyeing wastewater treatment,heavy metal removal,seawater desalination and oil-water separation.Then,the mechanisms including pore structure,hydrophilic/hydrophobic,electrostatic repulsion/attraction and Donnan effect are introduced.For the efficient removal of different kind of pollutions,researchers can select different ligands to construct membranes with specific pore size,hydrophily,salt or organic rejection ability and functional group.The ideas for the design and preparation of COF membranes are introduced.Finally,the future direction and challenges of the next generation of COF membranes in the field of separation are prospected.

关键词： Covalent organic frameworks Membrane materials Liquid phase separation Separation mechanism

Artemisia argyi extract subfraction exerts an antifungal effect against dermatophytes by disrupting mitochondrial morphology and function

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Chinese Journal of Natural Medicines 2024年第1期22卷 47-61页

作者： CHEN Le ZHU Yunyun GUO Chaowei GUO yujie ZHAO Lu MIAO Yuhuan DU Hongzhi liu Dahui College of Pharmacy Hubei University of Chinese MedicineWuhan 430065China National Resource Center for Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China College of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China

Artemisia argyi(A.argyi),a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia,has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties.Despite its widespread use,scientific evidence validating the antifungal efficacy of A.argyi water extract(AAWE)against dermatophytes,particularly Trichophyton rubrum,Trichophyton mentagrophytes,and Microsporum gypseum,remains limited.This study aimed to substantiate the scientific basis of the folkloric use of A.argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes.The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species.The subfraction AAWE6,isolated using D101 macroporous resin,emerged as the most potent subfraction.The minimum inhibitory concentrations(MICs)of AAWE6 against T.rubrum,M.gypseum,and T.mentagrophytes were 312.5,312.5,and 625μg·mL−1,respectively.Transmission electron microscopy(TEM)results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T.rubrum,creating breaches(“small holes”),and disrupt the internal mitochondrial structure(“granary”).Furthermore,transcriptome data,quantitative real-time PCR(RT-qPCR),and biochemical assays corroborated the severe disruption of mitochondrial function,evidenced by inhibited tricarboxylic acid(TCA)cycle and energy metabolism.Additionally,chemical characterization and molecular docking analyses identified flavonoids,primarily eupatilin(131.16±4.52 mg·g^(−1))and jaceosidin(4.17±0.18 mg·g^(−1)),as the active components of AAWE6.In conclusion,the subfraction AAWE6 from A.argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function.This research validates the traditional use of A.argyi and provides scientific support for its antidermatophytic applicati

关键词： Artemisia argyi Dermatophyte Antifungal activity Mitochondrial structure Mitochondrial function Transcriptome analysis