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Circulating tumor cells shielded with extracellular vesicle-derived CD45 evade T cell attack to enable metastasis

Signal Transduction and Targeted Therapy 2024年第5期9卷 2114-2131页

作者： Chuan Yang Xueping Wang Kenneth K.W.To Caimei Cui Min Luo Shaocong Wu Lamei Huang kai fu Can Pan Zeyu Liu Teng Fan Caibo Yang Fang Wang Liwu fu State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060P.R.China School of Pharmacy Faculty of MedicineThe Chinese University of Hong KongHong KongChina LABVIV Technology(Shenzhen)Co. LtdShenzhen 518057China

Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis.It remains elusive how CTCs evade immune surveillance and elimination by immune cells.In this study,we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle(EVs)-derived CD45(termed as CD45^(+)CTCs)that resisted T cell attack.A higher percentage of CD45^(+)CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients.Moreover,CD45^(+)tumor cells orchestrated an immunosuppressive milieu and CD45^(+)CTCs exhibited remarkably stronger metastatic potential than CD45−CTCs in vivo.Mechanistically,CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells,thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response.Together,these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis,providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

关键词： CD45 metastasis prevention

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Small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 905-952页

作者： Fang Wang kai fu Yujue Wang Can Pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu Kenneth Kin Wah To Chenglai Xia Jianye Zhang Zhi Shi Zeping Hu Min Huang Liwu fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer therapy.They induce long-term tumor regression and overall survival benefit in many types of cancer.With the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for immunotherapy.Small molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively investigated.Monotherapy of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor resistance.Here,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

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Pre-MASLD:Should it be defined separately?

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 1-3页

作者： Hang-kai Huang You-Ming Li Cheng-fu Xu Department of Gastroenterology Zhejiang Provincial Clinical Research Center for Digestive Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases,yet it has not received sufficient attention[1].Over the past two decades,the overall global prevalence of NAFLD has risen from 25%to 37%[2].The disease burden of NAFLD is fueled by the epidemic of obesity and diabetes[3].It is estimated that more than half of patients with diabetes have NAFLD.

关键词： NAFLD liver diseases

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Editorial:special topic on heterojunction in photocatalysts

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Science China Materials 2024年第2期67卷 379-381页

作者： Jiaguo Yu Xin Li Junwei fu kai Dai Laboratory of Solar fuel Faculty of Materials Science and ChemistryChina University of GeosciencesWuhan 430078China Institute of Biomass Engineering Key Laboratory of Energy Plants Resource and UtilizationMinistry of Agriculture and Rural AffairsSouth China Agricultural UniversityGuangzhou 510642China Hunan Joint International Research Center for Carbon Dioxide Resource Utilization State Key Laboratory of Powder MetallurgySchool of PhysicsCentral South UniversityChangsha 410083China Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation College of Physics and Electronic InformationHuaibei Normal UniversityHuaibei 235000China

To suppress the recombination of photogenerated electron and hole in single photocatalysts,an important method is to design heterojunction by combining two photocatalysts.This method has widely used to enhance the photocatalytic performance of the composites.At the begining,most people use type-Ⅱcharge carrier transfer mechanism to explain the emhanced activity of the composite semiconductors.

关键词： composite heterojunction method

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Exploring Trade-offs in Thermal Interface Materials:The Impact of Polymer-Filler Interfaces on Thermal Conductivity and Thixotropy

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Chinese Journal of Polymer Science 2024年第7期42卷 916-925,I0006页

作者： Bin Zhang Zheng-Li Dou Yong-Zheng Zhang Qiang fu kai Wu College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu610065China

Effective thermal transport across solid-solid interfaces which is essential in thermal interface materials(TIMs),necessitates both optimal thixotropy and high thermal conductivity.The role of filler surface modification,a fundamental aspect of TIM fabrication,in the influence of these properties is not fully understood.This study employs the use of a silane coupling agent(SCA)to modify alumina,integrating experimental approaches with molecular dynamics simulations,to elucidate the interface effects on thixotropy and thermal conductivity in polydimethylsiloxane(PDMS)-based TIMs.Our findings reveal that the variations of SCAs modify both interface binding energy and transition layer thickness.The interface binding energy restricts macromolecular segmental relaxation near the interface,hindering desirable thixotropy and bond line thickness.On the contrary,the thickness of the transition layer at the interface positively influences thermal conductivity,facilitating the transport of phonons between the polymer and filler.Consequently,selecting an optimal SCA allows a balance between traditionally conflicting goals of high thermal conductivity and minimal bond line thickness,achieving an impressively low interface thermal resistance of just 2.45-4.29 K·mm^(2)·W^(-1)at275.8 kPa.

关键词： Thermal interface material Surface modification Thermal conductivity Thixotropy Interface thermal resistance

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Graphitic carbon nitride nanosheets mitigate cadmium toxicity in Glycine max L.by promoting cadmium retention in root and improving photosynthetic performance

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Journal of Environmental Sciences 2024年第5期139卷 543-555页

作者： kai Xu Yunyu Guo Chenghua Xing Ronglong fu Bin Zou Rongchuan Liu Luyi Cai Jianfang Yan Xi-Lin Wu Miaozhen Cai College of Geography and Environmental Sciences Zhejiang Normal UniversityJinhua 321004China College of Agriculture Jinhua PolytechnicJinhua 321007China

Cadmium(Cd)pollution poses a serious threat to plant growth and yield.Nanomaterials have shown great application potential for alleviation of Cd toxicity to plants.In this study,we applied graphitic carbon nitride nanosheets(g-C_(3)N_(4)NSs)for alleviation of Cd-toxicity to soybean(Glycine max L.).The g-C_(3)N_(4)NSs supplementation significantly improved plant growth and reduced oxidative damage in the Cd-toxicated soybean seedlings through hydroponic culture.Particularly,the g-C_(3)N_(4)NSs dynamically regulated the root cell wall(RCW)components by increasing pectin content and modifying its demethylation via enhancing pectin methylesterase(PME)activity,therefore greatly enhanced stronger RCW-Cd retention(up to 82.8%)and reduced Cd migration to the shoot.Additionally,the g-C_(3)N_(4)NSs reversed the Cd-induced chlorosis,increased photosynthetic efficiency because of enhancement in F_v/F_mration,Y(Ⅱ)and sugars content.These results provide new insights into the alleviation of Cd toxicity to plants by g-C_(3)N_(4)NSs,and shed light on the application of low-cost and environmental-friendly carbon-based NMs for alleviating heavy metal toxicity to plants.

关键词： Cadmium Carbon nitride nanosheets Cell wall Pectin Pectin methylesterase Soybean

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Solid particle size characterization by a high-frequency collision response in pneumatic particulate flow

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Particuology 2024年第3期86卷 39-54页

作者： kai Wang Yichen Li Ziang Chang Min Qin Guangming fu Bangtang Yin Gang Wang jiaqi Tian School of Petroleum Engineering China University of Petroleum(East China)Qingdao266580China Key Laboratory of Unconventional Oil&Gas Development China University of Petroleum(East China)Ministry of EducationQingdao266580China National Engineering Research Center of Oil&Gas Drilling and Completion Technology Qingdao266580China Shock and Vibration of Engineering Materials and Structures Key Lab ofSichuan Province Southwest University of Science and TechnologyMianyang621000China

A novel triaxial vibration method is developed for the real-time characterization of the solid particle size distribution(PsD)in pneumatic particulate flow,which is critical for chemical industry.In this work,the particle-wall collision and friction behaviours were analysed by the time-domain statistical and timefrequency joint methods to narrow the high-frequency response range by the initial experiment of free fall for a single particle,interparticle,and multiple particles.Subsequently,verification experiments of PSD characterization in pneumatic flow were performed.First,the quantitative triaxial energy response model that considers the particle size,shape,and mass factors were established.Second,a good agreement of the particle number identification was found between the triaxial vibration energy and mean particle size of 150-550μm.Moreover,the performance with the best accuracy was focused on a range of 42-43 kHz in the x-axis and z-axis and 36.8-38.8 kHz in the y-axis.Finally,the individual particle energy was inversely analysed by the triaxial vibration response within the optimized frequency bands,and the PSD was characterized in real-time by a low error rate,that is,5.2% from the XZ-axis direction of sand(42-43 kHz)and 5.6% from the XYZ-axis of glass(30.9-33.9 kHz,46.2-47.2 kHz,38.3-41.3 kHz for each axis response).Therefore,this research complements the existing approaches for PsD characterization in particulate multiphase flow.

关键词： Solid particulate flow Triaxial vibration High-frequency response Particle wall Particle size distribution

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Multi-physical fields distribution in billet during helical electromagnetic stirring:A numerical simulation research

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China Foundry 2024年第1期21卷 51-59页

作者： Dong Pan Qing-tao Guo kai-lun Zhang fu-zhi Yu Yu-ying Li Yu-bao Xiao State Key Laboratory of Metal Materials for Marine Equipment and Application Anshan 114009LiaoningChina Ansteel Beijing Research Institute Co. Ltd.Beijing 102200China

Electromagnetic stirring is one of the widely applied techniques to modify the quality of casting billets.Different from conventional rotate stirring,the helical stirring is more professional in assisting multi-dimensional flow of molten metal and eliminating solidification defects.In this study,the single-winding helical stirring(SWHS)was introduced,offering advantages such as smaller volume and lower electromagnetic shielding compared to traditional helical stirring methods.Following a comprehensive numerical simulation,the stirring parameters of SWHS were adjusted to yoke inclination angle of 43°and frequency of 12 Hz.The higher electromagnetic force and flow velocity in drawing direction,as well as the lower temperature gradient induced by the SWHS,are positive factors for homogeneous solidification of billet.The experimental results on Al-8%Si alloy and 0.4%C-1.1%Mn steel demonstrate that compared to rotate stirring,the SWHS process can induce better billet quality and is more effective in accelerating the equiaxed expansion and reducing element segregation.The SWHS process can enhance the equiaxed ratio of the billet by 58.3%and reduce segregation degree of carbon element by 10.97%.Consequently,SWHS holds great promise as a potential approach for improving the quality of continuous casting billets.

关键词： billet electromagnetic stirring helical solidification element segregation numerical simulation

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Cationic engineered nanodiamonds for efficient antibacterial surface with strong wear resistance

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Nano Research 2024年第3期17卷 939-948页

作者： fu-Kui Li Wen-Bo Zhao Yong Wang Wen-Tao Huang Ya-Lun Ku Hang Liu Rui Guo Hui-Hui Yu kai-kai Liu Chong-Xin Shan Henan Key Laboratory of Diamond Optoelectronic Materials and Devices Key Laboratory of Materials PhysicsMinistry of Educationand School of Physics&MicroelectronicsZhengzhou UniversityZhengzhou 450052China

The spread of diseases caused by bacterial adhesion and immobilization in public places constitutes a serious threat to public health.Prevention of bacteria spread by the construction of an antibacterial surface takes precedence over post-infection treatment.Herein,we demonstrate an effective antibacterial surface with strong wear resistance by constructing cationic engineered nanodiamonds(C-NDs).The C-NDs with positive surface potentials interact effectively with bacteria through electrostatic interactions,where the C-NDs act on the phospholipid bilayer and lead to bacterial membrane collapse and rupture through hydrogen bonding and residual surface oxygen-containing reactive groups.In this case,bactericidal rate of 99.99%and bacterial biofilm inhibition rate of more than 80%can be achieved with the C-NDs concentration of 1 mg/mL.In addition,the C-NDs show outstanding antibacterial stability,retaining over 87%of the antibacterial effect after stimulation by adverse environments of heat,acid,and external abrasion.Therefore,an antibacterial surface with high wear resistance obtained by integrating C-NDs with commercial plastics has been demonstrated.The antibacterial surface with a mass fraction of 1 wt.%C-NDs improved abrasion resistance by 3981 times,with 99%killing of adherent bacteria.This work provides an effective strategy for highly efficient antibacterial wear-resistant surface,showing great practical applications in public health environments.

关键词： antibacterial surface cationic engineered nanodiamonds wear-resistant

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Effect of Ti Particles on the Microstructure and Mechanical Properties of AZ91 Magnesium Matrix Composites

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Acta Metallurgica Sinica(English Letters) 2024年第3期37卷 513-524页

作者： Lu Xiao Ting-Ting Liu Yue Chu Bo Song Jie Zhao Xian-Hua Chen kai-Hong Zheng fu-Sheng Pan College of Materials Science and Engineering Chongqing UniversityChongqing 400044China lntelligent Manufacturing and Automobile School Chongqing College of Electronic EngineeringChongqing 401331China School of Materials and Energy Southwest UniversityChongqing 400715China Science and Technology Research Institute of CNNC 404 Co.LTD Gansu 735100China Institute of New Materials Guangdong Academy of SciencesGuangzhou 510650China

Spherical micro-Ti particle(TiP)-reinforced AZ91 magnesium alloy composites were fabricated by semi-solid stirring assisted ultrasonic vibration,which were then subjected to hot extrusion.The microstructure results showed that the addition of Ti particles refined the grain size and decreased the texture intensity of the as-extruded AZ91 alloy.An Al3Ti phase with a thickness of 100 nm formed at the Ti/Mg interface,which had a non-coherent relationship with the magnesium matrix.The as-extruded 1 vol.%TiP/AZ91 composite exhibited the best comprehensive mechanical properties,with yield strength,ultimate tensile strength,and elongation at break of 366 MPa,456 MPa,and 14.6%,respectively,which were significantly higher than those of the AZ91 alloy.Therefore,the addition of Ti particles can improve the strength and ductility of the AZ91 alloy,demonstrating the value of magnesium matrix composites for commercial applications.

关键词： Magnesium matrix composites Ti particles Interface Mechanical properties

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