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Novel Pt(IV) complex OAP2 induces STING activation and pyroptosis via mitochondrial membrane remodeling for synergistic chemo-immunotherapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1742-1758页

作者： Renming Fan Ruizhuo Lin Shuo zhang Aohua deng Yongrui hai Junyan Zhuang Yang Liu Maosheng Cheng Gaofei Wei Institute of Medical Research Northwestern Polytechnical UniversityXi'an 710072China Research&Development Institute of Northwestern Polytechnical University in Shenzhen Shenzhen 518057China Key Laboratory of Structure-Based Drug Design and Discovery Ministry of EducationSchool of Pharmaceutical EngineeringShenyang Pharmaceutical UniversityShenyang 110016China

Mitochondrial membrane remodeling can trigger the release of mitochondrial DNA (mtDNA), leading to the activation of cellular oxidative stress and immune responses. While the role of mitochondrial membrane remodeling in promoting inflammation in hepatocytes is well-established, its effects on tumors have remained unclear. In this study, we designed a novel Pt(IV) complex, OAP2, which is composed of oxaliplatin (Oxa) and acetaminophen (APAP), to enhance its anti-tumor effects and amplify the immune response. Our findings demonstrate that OAP2 induces nuclear DNA damage, resulting in the production of nuclear DNA. Additionally, OAP2 downregulates the expression of mitochondrial Sam50, to promote mitochondrial membrane remodeling and trigger mtDNA secretion, leading to double-stranded DNA accumulation and ultimately synergistically activating the intracellular cGAS-STING pathway. The mitochondrial membrane remodeling induced by OAP2 overcomes the limitations of Oxa in activating the STING pathway and simultaneously promotes gasdermin-D-mediated cell pyroptosis. OAP2 also promotes dendritic cell maturation and enhances the quantity and efficacy of cytotoxic T cells, thereby inhibiting cancer cell proliferation and metastasis. Briefly, our study introduces the first novel small-molecule inhibitor that regulates mitochondrial membrane remodeling for active immunotherapy in anti-tumor research, which may provide a creative idea for targeting organelle in anti-tumor therapy.

关键词： Anti-tumor drug Prodrug Platinum Chemo-immunotherapy Mitochondrial membrane modeling STING Pyroptosis mtDNA

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Development of a high-repetition-rate lumped-inductance kicker magnet prototype for the beam switchyard of SHINE

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Nuclear Science and Techniques 2024年第2期35卷 20-31页

作者： Yong-Fang Liu Rui-Ping Wang Jin Tong Bo zhang Si Chen Qi-Bing Yuan hai-Xiao deng Ming Gu Bo Liu Shanghai Advanced Research Institute Chinese Academy of SciencesShanghai 201412People’s Republic of China

The Shanghai high-repetition-rate X-ray free-electron laser and extreme light facility(SHINE)operates at a maximum repetition rate of 1 *** magnets are key components that distribute electron bunches into three different undulator lines in a bunch-by-bunch *** kicker field width must be less than the time interval between bunches.A lumpedinductance kicker prototype was developed using a vacuum chamber with a single-turn *** full magnetic field strength was 0.005 *** paper presents the requirements,design considerations,design parameters,magnetic field calculations,and measurements of the kicker *** relevant experimental results are also *** pulse width of the magnetic field was approximately 600 ns,and the maximum operation repetition rate was 1 *** developed kicker satisfies the requirements for the SHINE ***,numerous recommendations for the future optimization of kicker magnets are provided.

关键词： X-ray free-electron laser Kicker magnet Beam switchyard High repetition rate Ni-Zn ferrites

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Dynamics of a Reaction-diffusion-ODE System in a Heterogeneous Media

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Acta Mathematicae Applicatae Sinica 2024年第2期40卷 275-301页

作者： Cong-hui zhang hai-feng zhang Mei-rong zhang School of Science Beijing University of Civil Engineering and ArchitectureBeijing 102616China Institute of Applied System Analysis Jiangsu UniversityZhenjiang 212013China Department of Mathematical Sciences Tsinghua UniversityBeijing 100084China

The existence and stability of stationary solutions for a reaction-diffusion-ODE system are investigated in this *** first show that there exist both continuous and discontinuous stationary *** a good understanding of the stability of discontinuous stationary solutions is gained under an appropriate *** addition,we demonstrate the influences of the diffusion coefficient on stationary *** results we obtained are based on the super-/sub-solution method and the generalized mountain pass ***,some numerical simulations are given to illustrate the theoretical results.

关键词： reaction-diffusion-ODE system discontinuous stationary solutions stability asymptotic behavior monotone solutions

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Discovery of the choristodere Hyphalosaurus baitaigouensis from the Lower Cretaceous Jiufotang Formation of western Liaoning,China and its paleobiogeographic significance

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Journal of Palaeogeography 2024年第3期13卷 547-562页

作者： Li-Jun zhang Shu-An Ji hai-Chun zhang South China Sea Culture Museum Hainan Tropical Ocean UniversitySanya 572022Hainan ProvinceChina Key Laboratory of Stratigraphy and Paleontology Ministry of Natural ResourcesInstitute of GeologyChinese Academy of Geological SciencesBeijing 100037China State Key Laboratory of Palaeobiology and Stratigraphy Nanjing Institute of Geology and Palaeontology and Center for Excellence in Life and PaleoenvironmentChinese Academy of SciencesNanjing 210008Jiangsu ProvinceChina

The water-living reptile genus Hyphalosaurus was previously discovered in the Lower Cretaceous Yixian Formation bearing the middle Jehol Biota in western Liaoning,*** complete skeletons of Hyphalosaurus are reported for the first time from the Jiufotang Formation bearing the late Jehol Biota at two sites in western *** show the typical characteristics of Hyphalosaurus baitaigouensis in terms of the contact between some cranial bones and the number of cervical and dorsal vertebrae,and therefore are assigned to *** discovery extends the stratigraphic range of this species from the Yixian Formation to the overlying Jiufotang *** paper further briefly compares the main characteristics of the two skeletons,summarizes the temporal and spatial distribution of Hyphalosaurus,and discusses the palaeogeographic evolution of western Liaoning at the middle and late Jehol Biota stages based on the aquatic habits of Hyphalosaurus and the geological background of western *** analytical results show that the volcanic downwarped lakes,with distinct geographical divisions in western Liaoning during the deposition of the Yixian Formation,had not completely disappeared till the deposition of the Jiufotang *** palaeo-lake in the Fuxin-Yixian Basin underwent the process of generation,expansion and shrinkage during the depositional period of the Yixian Formation and finally merged into a large *** palaeo-Dalinghe River,which connected the main basins in western Liaoning during the depositional period of the Jiufotang Formation,was formed simultaneously.

关键词： Western liaoning Jehol biota Jiufotang formation Hyphalosaurus baitaigouensis Palaeobiogeography

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Performance Improvement of Two-Phase Steam Ejector based on CFD Techniques,Response Surface Methodology and Genetic Algorithm

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Journal of Thermal Science 2024年第2期33卷 675-695页

作者： zhang Hao ZHAO Hongxia zhang Xiuao ZENG Hongxuan deng Jianqiang School of Energy and Power Engineering Shandong UniversityJi’nan250061China School of Chemical Engineering and Technology Xi’an Jiaotong UniversityXi’an710049China

The steam ejector is a crucial component in the waste heat recovery *** performance determines the amount of recovered heat and system ***,poor ejector performance has always been the main bottleneck for system ***,this study proposes an optimization methodology to improve the steam ejector's performance by utilizing computational fluid dynamics(CFD) techniques,response surface methodology(RSM),and genetic algorithm(GA).Firstly,a homogeneous equilibrium model(HEM) was established to simulate the two-phase flow in the steam ***,the orthogonal test was presented to the screening of the key decision variables that have a significant impact on the entrainment ratio(ER).Next,the RSM was used to fit a response surface regression model(RSRM).Meanwhile,the effect of the interaction of geometric parameters on the performance of the steam ejector was ***,GA was employed to solve the RSRM's global optimal ER *** results show that the RSRM exhibits a good fit for ER(R^(2)=0.997).After RSM and GA optimization,the maximum ejector efficiency is 27.94%,which is 48.38% higher than the initial ejector of 18.83%.Furthermore,the optimized ejector efficiency is increased by 46.4% on average under off-design ***,the results reveal that the combination of CFD,RSM,and GA presents excellent reliability and feasibility in the optimization design of a two-phase steam ejector.

关键词： two-phase steam ejector optimization methodology CFD techniques response surface methodology genetic algorithm homogeneous equilibrium model

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Learning topological defects formation with neural networks in a quantum phase transition

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Communications in Theoretical Physics 2024年第5期76卷 68-76页

作者： Han-Qing Shi hai-Qing zhang Center for Gravitational Physics Department of Space ScienceBeihang UniversityBeijing 100191China Peng Huanwu Collaborative Center for Research and Education Beihang UniversityBeijing 100191China

Neural networks possess formidable representational power,rendering them invaluable in solving complex quantum many-body *** they excel at analyzing static solutions,nonequilibrium processes,including critical dynamics during a quantum phase transition,pose a greater challenge for neural *** address this,we utilize neural networks and machine learning algorithms to investigate time evolutions,universal statistics,and correlations of topological defects in a one-dimensional transverse-field quantum Ising ***,our analysis involves computing the energy of the system during a quantum phase transition following a linear quench of the transverse magnetic field *** excitation energies satisfy a power-law relation to the quench rate,indicating a proportional relationship between the excitation energy and the kink ***,we establish a universal power-law relationship between the first three cumulants of the kink numbers and the quench rate,indicating a binomial distribution of the ***,the normalized kink-kink correlations are also investigated and it is found that the numerical values are consistent with the analytic formula.

关键词： neural networks machine learning transverse-field quantum Ising model kibble-zurek mechanism

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Derivation of Expanded Isospectral-Nonisospectral Integrable Hierarchies via the Column-vector Loop Algebra

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Acta Mathematicae Applicatae Sinica 2024年第3期40卷 778-800页

作者： hai-feng WANG Yu-feng zhang School of Science Jimei UniversityXiamen 361021China School of Mathematics China University of Mining and TechnologyXuzhou 221116China

A scheme for generating nonisospectral integrable hierarchies is *** on the method,we deduce a nonisospectral hierarchy of soliton equations by considering a linear spectral *** follows that the corresponding expanded isospectral and nonisospectral integrable hierarchies are deduced based on a 6 dimensional complex linear space ■.By reducing these integrable hierarchies,we obtain the expanded isospectral and nonisospectral derivative nonlinear Schr?dinger *** using the trace identity,the biHamiltonian structure of these two hierarchies are also ***,some symmetries and conserved quantities of the resulting hierarchy are discussed.

关键词： expanded isospectral-nonisospectral integrable hierarchies column-vector loop algebra bi-Hamiltonian structure symmetry

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Design optimization of a hexapod vibration isolation system for electro-optical payload

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Chinese Journal of Aeronautics 2024年第2期37卷 330-342页

作者： Jing LI Weipeng LI Xiaoyan zhang hai HUANG School of Astronautics Beihang UniversityBeijing 100191China

The electro-optical payloads on mobile platforms generally suffer undesirable vibrations generated by maneuvers and *** vibrations are in six degrees of freedom and cause line-of-sight jitters,resulting in image blurring and loss of tracking *** this paper,a Hexapod Vibration Isolation System(HVIS)is proposed and optimized to solve this *** optimization aims to centralize and minimize the natural frequencies of HVIS,for expanding the vibration isolation bandwidth and improving the vibration isolation in the higher frequency *** that the design space for HVIS is limited and interfered with the frames of the mobile platform,a non-collision algorithm is proposed and applied in the optimization to obtain the feasible optimal *** optimization result shows that the natural frequency bandwidth has been reduced by 42.9%,and the maximum natural frequency is reduced by 30.2%.The prototypes of initial and optimal designs are manufactured and *** simulated and experimental results demonstrate the validity of the optimization,and the optimal design provides a maximum of 15 dB more isolation in rotation direction than the initial design.

关键词： Electro-optical payload Vibrations Isolation system Hexapod Optimization Non-collision design

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An artificial intelligence approach for particle transport velocity prediction in horizontal flows

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颗粒学报（英文版） 2024年第9期92卷 234-250页

作者： Haoyu Chen Zhiguo Wang hai Huang Jun zhang College of Petroleum Engineering Xi'an Shiyou UniversityXi'an710065China Shaanxi Key Laboratory of Carbon Dioxide Sequestration and Enhanced Oil Recovery Xi'an710065China College of New Energy Xi'an Shiyou UniversityXi'an710065China Engineering Research Center of Smart Energy and Carbon Neutral in Oil&Gas Field Universities of Shaanxi ProvinceChina College of Petroleum Engineering Xi'an Shiyou UniversityXi'an710065China The Erosion/Corrosion Research Center The University of TulsaOK74104United States

Particle entrainment is an inevitable phenomenon in pipeline systems,especially during the develop-ment and extraction phases of oil and gas *** predicting the critical velocity for particle transport is a key focus for implementing effective sand control *** work presents a semi-supervised learning-deep hybrid kernel extreme learning machine(SSL-DHKELM)model for predicting the critical velocity,which integrates multiple machine learning theories including the deep learning approach,which is adept at advanced feature ***,the SSL framework enhances the model's capabilities when data availability is *** improved slime mould algorithm is also employed to optimize the model's *** proposed model has high accuracy on both the sample dataset and out-of-sample *** trained with only 10％of the data,the model's error still did not increase ***,this model achieves superior predictive accuracy compared to existing mechanistic models,demonstrating its impressive performance and robustness.

关键词： Critical velocity Deep learning Extreme learning machine Particle transport Semi-supervised learning

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Synthesis of multifunctional additives for solid propellants:Structure,properties and mechanism

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Defence Technology（防务技术） 2024年第3期33卷 308-316页

作者： Pingan zhang Lina Sun Jianmin Yuan Jianru deng College of Chemistry and Chemical Engineering Hunan UniversityChangsha 410082PR China College of Material Science and Engineering Hunan UniversityChangsha 410082PR China Hu Bei Sanjiang Aerospace Jianghe Chemical Technology Co. LtdYichang 444200PR China

To simplify the composite propellant formulation and address the current issue of the single-functionality present in existing additives,the multi-cyano,amine-based polybutadiene(AEHTPB-CN)was prepared based on AEHTPB by adopting appropriate synthesis *** replacing 10% of HTPB binder in the propellant formulation,it can effectively enhance the interfacial bond strength between the propellant binder matrix and solid fillers(AP(ammonium perchlorate)and RDX(cyclotrimethylene-trinitramine)),the mechanical properties of the HTPB/AP/RDX/Al propellant were superior to blank control propellant with an improvement of 35.4% in tensile strength,62.0% enhancement in elongation at break,and reduce the propellant burn rate by 10.7% with any energy *** function mechanism of AEHTPB-CN was systematically elucidated through experiments and computer simulation *** results show that the tertiary amine group in AEHTPB-CN can react with AP to form ammonium ionic bonds,and the hydroxyl and cyano groups can form hydrogen bonding interactions with AP,which enables AEHTPB-CN to be firmly adsorbed on the AP surface through chemical and physical *** RDX,the interfacial bonding effect of AEHTPB-CN is attributed to their ability to form C-H···N≡C weak hydrogen bonding interaction between the cyano group and RDX methylene group.

关键词： Hydroxyl-terminated polybutadiene(HTPB) HTPB propellant Chemical modification Bonding agent Mechanism

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