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CCL9/CCR1 axis-driven chemotactic nanovesicles for attenuating metastasis of SMAD4-deficient colorectal cancer by trapping TGF-β

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3711-3729页

作者： Boning Niu tianyi tian Lu Wang Yinmei tian tian tian Yuanyuan Guo Hu Zhou Zhiping Zhang Tongji School of Pharmacy Huazhong University of Science and TechnologyWuhan 430030China Department of Oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pharmacy Liyuan HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China School of Pharmaceutical Sciences Fujian Provincial Key Laboratory of Innovative Drug Target ResearchHigh Throughput Drug Screening PlatformXiamen UniversityXiamen 361102China National Engineering Research Center for Nanomedicine Huazhong University of Science and TechnologyWuhan 430030China Hubei Engineering Research Centre for Novel Drug Delivery System Huazhong University of Science and TechnologyWuhan 430030China

SMAD4 deficiency in colorectal cancer(CRC)is highly correlated with liver metastasis and high mortality,yet there are few effective precision therapies ***,we show that CCR1^(+)-granulocytic myeloid-derived suppressor cells(G-MDSCs)are highly infiltrated in SMAD4-deficient CRC via CCL15/CCR1 and CCL9/CCR1 axis in clinical specimens and mouse models,*** excessive TGF-β,secreted by tumor-infiltrated CCR1^(+)-G-MDSCs,suppresses the immune response of cytotoxic T lymphocytes(CTLs),thus facilitating ***,we develop engineered nanovesicles displaying CCR1 and TGFBR2 molecules(C/T-NVs)to chemotactically target the tumor driven by CCL9/CCR1 axis and trap TGF-βthrough TGF-β-TGFBR2 specific *** C/T-NVs counteract CCR1^(+)-G-MDSC infiltration through competitive responding CCL9/CCR1 axis.C/T-NVs-induced intratumoral TGF-βexhaustion alleviates the TGF-β-suppressed immune response of ***,C/T-NVs attenuate liver metastasis of SMAD4-deficient *** further exploration,high expression of programmed cell death ligand-1(PD-L1)is observed in clinical specimens of SMAD4-deficient *** C/T-NVs with anti-PD-L1 antibody(aPD-L1)induces tertiary lymphoid structure formation with sustained activation of CTLs,CXCL13^(+)-CD4^(+)T,CXCR5^(+)-CD20^(+)B cells,and enhanced secretion of cytotoxic cytokine interleukin-21 and IFN-γaround tumors,thus eradicating metastatic *** strategy elicits pleiotropic antimetastatic immunity,paving the way for nanovesicle-mediated precision immunotherapy in SMAD4-deficient CRC.

关键词： SMAD4-deficient CRC Metastasis G-MDSCs TGF-β CCR1 TGFBR2

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Capturing metal clusters at the strong-interaction region to reverse Ostwald ripening

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Science China Materials 2024年第4期67卷 1363-1364页

作者： Shuheng tian Ding Ma Beijing National Laboratory for Molecular Sciences New Cornerstone Science LaboratoryCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China

High-temperature interactions induce sintering of metal nanoparticles(NPs) on heterogeneous catalyst surfaces, leading to reduced surface area and active site loss through Ostwald ripening [1]. This irreversible deactivation necessitates costly catalyst replacement, notably impacting metals like copper in hydrogenation and reforming reactions [2].

关键词： catalyst reforming irreversible

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DeepSI:A Sensitive-Driven Testing Samples Generation Method of Whitebox CNN Model for Edge Computing

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Tsinghua Science and Technology 2024年第3期29卷 784-794页

作者： Zhichao Lian Fengjun tian School of Cyber Science and Engineering Nanjing University of Science and TechnologyNanjing 210094China

In recent years,Deep Learning(DL)technique has been widely used in Internet of Things(IoT)and Industrial Internet of Things(IIoT)for edge computing,and achieved good *** more and more studies have shown the vulnerability of neural ***,it is important to test the robustness and vulnerability of neural *** specifically,inspired by layer-wise relevance propagation and neural network verification,we propose a novel measurement of sensitive neurons and important neurons,and propose a novel neuron coverage criterion for robustness *** on the novel criterion,we design a novel testing sample generation method,named DeepSI,which involves definitions of sensitive neurons and important ***,we construct sensitive-decision paths of the neural network through selecting sensitive neurons and important ***,we verify our idea by setting up several experiments,then results show our proposed method achieves superior performances.

关键词： neuron sensitivity Layer-wise Relevance Propagation(LRP) neural network verification deeplearning testing

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Frequency Domain Fatigue Evaluation on SCR Girth-Weld Based on Structural Stress

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China Ocean Engineering 2024年第2期38卷 255-270页

作者： ZHANG Long ZHAO tian-feng College of Safety and Ocean Engineering China University of Petroleum(Beijing)Beijing 102249China

The Steel Catenary Riser(SCR)is a vital component for transporting oil and gas from the seabed to the floating *** harsh environmental conditions and complex platform motion make the SCR’s girth-weld prone to fatigue *** structural stress fatigue theory and Master S-N curve method provide accurate predictions for the fatigue damage on the welded joints,which demonstrate significant potential and compatibility in multi-axial and random fatigue ***,we propose a new frequency fatigue model subjected to welded joints of SCR under multiaxial stress,which fully integrates the mesh-insensitive structural stress and frequency domain random process and transforms the conventional welding fatigue technique of SCR into a spectrum analysis technique utilizing structural ***,a full-scale FE model of SCR with welds is established to obtain the modal structural stress of the girth weld and the frequency response function(FRF)of modal coordinate,and a biaxial fatigue evaluation about the girth weld of the SCR can be achieved by taking the effects of multi-load correlation and pipe-soil interaction into *** research results indicate that the frequency-domain fatigue results are aligned with the time-domain results,meeting the fatigue evaluation requirements of the SCR.

关键词： SCR girth weld random vibration self(cross)power spectrum structural stress method biaxial fatigue damage

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Frost heaving and crack initiation characteristics of tunnel rock mass in cold regions under low-temperature degradation

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Journal of Mountain Science 2024年第8期21卷 2844-2854页

作者： CHEN Wenhua XIANG tian School of Civil Engineering Beijing Jiaotong UniversityBeijing 202303China

Water freezing in rock fractures causes volumetric expansion and fracture development through frost *** study introduces a novel analytical model to investigate how uneven freezing force and surrounding rock pressure influence fracture initiation,based on mass conservation,elasticity,and water-ice phase transition principles.A model for rock fracture initiation considering freezing temperature,uneven freezing expansion,in-situ stress,and lateral pressure was proposed based on fracture *** for stress intensity factors were developed and validated using the phase field *** effects of rock elastic modulus anisotropy and critical fracture energy density on fracture initiation were also *** results show that the values of KI and KII exhibit an upward trend as the freezing temperature,uneven expansion,in-situ stress,and lateral pressure *** uneven freezing expansion has the most significant influence on KI and KII values among these *** the uneven freezing expansion coefficient increases to 0.5,the fracture initiation mode shifts from tensile fracture to shear *** the lateral pressure coefficient increases to 1,the fracture initiation mode shifts from tensile fracture to shear *** elastic modulus anisotropy causes fractures to propagate in a clockwise direction,forming a'butterfly'*** fracture energy density an isotropy causes counterclockwise deviation in propagation direction,resulting in branching paths and an'H'-shaped pattern.

关键词： Rock fractures Fracture water Uneven freezing expansion Phase field method Initiation angle Anisotropy

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Polyelectrolyte Complexes and Coacervates Formed by De novo-Designed Peptides and Oligonucleotide

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Chinese Journal of Polymer Science 2024年第9期42卷 1333-1340,I0007页

作者： tian-Hao Ren De-Hai Liang Beijing National Laboratory for Molecular Sciences Department of Polymer Science and Engineering and the Key Laboratory of Polymer Chemistry and Physics of the Ministry of EducationCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing100871China

The liquid-liquid phase separation of biopolymers in living cells contains multiple interactions and occurs in a dynamic *** the regulation mechanism is still a *** this work,we designed a series of peptides(XXLY)_(6)SSSGSS and studied their complexation and coacervation behavior with single-stranded ***“X”and“Y”are varied to combine known amounts of charged and non-charged amino acids,together with the introduction of secondary structures and pH *** show that the electrostatic interaction,which is described as charge density,controls both the strength of complexation and the degree of chain relaxation,and thus determines the growth and size of the *** hydrophobic interaction is prominent when the charges are ***,the secondary structures of peptides exhibit profound effect on the morphology of the phases,such as solid phase to liquid phase *** study gains insight into the phase separation under physiological *** is also helpful to create coacervates with desirable structures and functions.

关键词： Polyelectrolyte complex Coacervate Peptides Secondary structure Electrostatic interaction

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Numerical investigation on characteristics of interfacial wave of liquid film in gas-liquid two-phase flow using OpenFOAM

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Chinese Journal of Aeronautics 2024年第2期37卷 233-248页

作者： Xiaoqi MA Yueshe WANG Jiaming tian State Key Laboratory of Multiphase Flow in Power Engineering Xi’an Jiaotong UniversityXi’an 710049China

Liquid film cooling as an advanced cooling technology is widely used in space *** operation of liquid film along the rocket combustion inner wall is crucial for thermal protection of rocket *** stability of liquid film is mainly determined by the characteristics of interfacial wave,which is rarely investigated right *** to improve the stability of thin film has become a hot *** view of this,an advanced model based on the conventional Volume of Fluid(VOF)model is adopted to investigate the characteristics of interfacial wave in gas-liquid flow by using OpenFOAM,and the mechanism of formation and development of wave is revealed intuitively through numerical *** effects from gas velocity,surface tension and dynamic viscosity of liquid(three factors)on the wave are studied *** can be found that the gas velocity is critical to the formation and development of wave,and four modes of droplets generation are illustrated in this ***,a gas vortex near the gas-liquid interface can induce formation of wave easily,so changing the gas vortex state can regulate formation and development of ***’s more,the change rules of three factors influencing on the interfacial wave are obtained,and the surface tension has a negative effect on the formation and development of wave only when the surface tension coefficient is above the critical value,whereas the dynamic viscosity has a positive effect in this ***,the maximum height and maximum slope angle of wave will level off as the gas velocity ***,the maximum slope angle of wave is usually no more than 38°,no matter what happens to the three factors.

关键词： Interfacial wave Gas-liquid Two-phase flow VOF model OpenFOAM

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Prediction of ball-on-plate friction and wear by ANN with data-driven optimization

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Friction 2024年第6期12卷 1235-1249页

作者： Alexander KOVALEV Yu tian Yonggang MENG State Key Laboratory of Tribology in Advanced Equipment Tsinghua UniversityBeijing 100084China

For training artificial neural network(ANN),big data either generated by machine or measured from experiments are used as input to"learn"the unspecified functions defining the *** experimental data are fed directly into the optimizer allowing training to be performed according to a predefined loss *** predict sliding friction and wear at mixed lubrication conditions,in this study a specific ANN structure was so designed that deep learning algorithms and data-driven optimization models can be *** ball-on-plate friction and wear data were analyzed using the specific training procedure to optimize the weights and biases incorporated into the neural layers of the ANN,and only two independent experimental data sets were used during the ANN optimization *** the training procedure,the ANN is capable to predict the contact and hydrodynamic pressure by adapting the output data according to the tribological condition implemented in the optimization algorithm.

关键词： machine learning deep learning artificial neural network mixed lubrication

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Interface property of dissimilar Ti-6Al-4V/AA1050 composite laminate made by non-equal channel lateral co-extrusion and heat treatment

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Defence Technology（防务技术） 2024年第3期33卷 197-208页

作者： Juan Liao Mengmeng tian Xin Xue School of Mechanical Engineering and Automation Fuzhou UniversityFuzhou 350116China

The purpose of this paper is to examine the effect of processing parameters and subsequent heat treatments on the microstructures and bonding strengths of Ti-6Al-4V/AA1050 laminations formed via a non-equal channel lateral co-extrusion *** microstructural evolution and growth mechanism in the diffusion layer were discussed further to optimize the bonding quality by appropriately adjusting process *** electron microscopes(SEM),energy dispersive spectrometer(EDS),and X-ray diffraction(XRD)were used to characterize interfacial diffusion *** shear test was used to determine the mechanical properties of the interfacial diffusion *** experimental results indicate that it is possible to co-extrusion Ti-6Al-4V/AA1050 compound profiles using non-equal channel lateral *** heat treatment processes affect the thickness of the diffusion *** the temperature and time of heat treatment increase,the thickness of the reaction layers increases ***,the shear strength of the Ti-6Al-4V/AA1050 composite interface is proportional to the diffusion layer *** is observed that a medium interface thickness results in superior mechanical performance when compared to neither a greater nor a lesser interface *** characterization of all heat treatments reveals that the only intermetallic compound observed in the diffusion layers is TiAl_(3).Due to the inter-diffusion of Ti and Al atoms,the TiAl_(3) layer grows primarily at AA1050/TiAl_(3) interfaces.

关键词： Shear strength Co-extrusion Heat treatment Microstructure Intermetallic compounds

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A new method for evaluating the firing precision of multiple launch rocket system based on Bayesian theory

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Defence Technology（防务技术） 2024年第2期32卷 232-241页

作者： Yunfei Miao Guoping Wang Wei tian College of Mechanical and Electrical Engineering Nanjing University of Aeronautics and AstronauticsNanjingJiangsuChina Institute of Launch Dynamics Nanjing University of Science and TechnologyNanjingJiangsuChina

How to effectively evaluate the firing precision of weapon equipment at low cost is one of the core contents of improving the test level of weapon system.A new method to evaluate the firing precision of the MLRS considering the credibility of simulation system based on Bayesian theory is proposed in this *** of all,a comprehensive index system for the credibility of the simulation system of the firing precision of the MLRS is constructed combined with the group analytic hierarchy process.A modified method for determining the comprehensive weight of the index is established to improve the rationality of the index weight *** Bayesian posterior estimation formula of firing precision considering prior information is derived in the form of mixed prior distribution,and the rationality of prior information used in estimation model is discussed *** the simulation tests,the different evaluation methods are compared to validate the effectiveness of the proposed ***,the experimental results show that the effectiveness of estimation method for firing precision is improved by more than 25%.

关键词： Multiple launch rocket system Bayesian theory Simulation credibility Mixed prior distribution Firing precision

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