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Tumor microenvironment reprogramming by nanomedicine to enhance the effect of tumor immunotherapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 1-37页

作者： yu Huang Hui fan Huihui Ti School of Chinese Materia Medica Guangdong Pharmaceutical UniversityGuangzhou 510006China Guangdong Province Precise Medicine Big Date of Traditional Chinese Medicine Engineering Technology Research Center Guangdong Pharmaceutical UniversityGuangzhou 510006China School of Pharmacy Guangdong Pharmaceutical UniversityGuangzhou 510006China

With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.

关键词： Tumor immunotherapy Tumor micr oenvir onment Nanomedicine Tumor repr ogramming

Design,synthesis,and biological evaluation of 1,2,4-triazole derivatives as potent antitubercular agents

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Chinese Chemical Letters 2024年第3期35卷 326-331页

作者： yu Wen Shichun Lun yuxue Jiao wei Zhang Tianyu Hu Ting Liu fan Yang Jie Tang Bing Zhang William R.Bishai Li-fang yu Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China Center for Tuberculosis Research Department of MedicineDivision of Infectious DiseaseJohns Hopkins School of MedicineBaltimoreMD21231-1044United States Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Shanghai Key Laboratory of Green Chemistry and Chemical Process School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China

Inhibition of mycobacterial membrane protein large 3(MmpL3)thereby affecting the mycolic acid biosynthetic pathway has been proven to be an effective strategy for developing antitubercular *** on the X-ray crystal structure of MmpL3 inhibitor complexes,a series of novel 1,2,4-triazole derivatives were designed,synthesized and evaluated antitubercular activity against Mtb strain *** structure–activity relationship exploration resulted in the identification of compounds 21 and 28,which possess potent antitubercular activity against Mtb strain H37Rv[minimum inhibitory concentration(MIC)=0.03–0.13μg/mL]and the clinical isolates of multidrug resistance(MDR)and extensive drug resistance(XDR)tuberculosis(MIC=0.06–1.0μg/mL).Moreover,compounds 21 and 28 showed neglectable cytotoxicity(IC_(50)≥32μg/mL)to the mammalian Vero cells and favorable physicochemical and pharmacokinetic properties according to the in silico absorption,distribution,metabolism and excretion(ADME)***,the potential target of representative 1,2,4-triazole 28 was identified to be MmpL3 using a microscale thermophoresis(MST)assay.

关键词： Tuberculosis MDR and XDR-TB MmpL3 inhibitor 1 2 4-Triazole Structure-based drug design

A Study on the Performances of Solar Air Collectors Having a Hemispherical Dimple on the Absorber Plate

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Fluid Dynamics & Materials Processing 2024年第5期20卷 939-955页

作者： Shuilian Li fan Zeng Xinli wei School of Architecture and Environmental Engineering Zhengzhou Technical CollegeZhengzhou450121China School of Mechanical and Power Engineering Zhengzhou UniversityZhengzhou450001China

In order to increase the efficiency of solar air collectors,a new variant with a protrusion is proposed in this study,and its performances are analyzed from two points of view,namely,in terms of optics and thermodynamics *** comparing and analyzing the light paths of the protrusion and the dimple,it can be concluded that when sunlight shines on the dimple,it is reflected and absorbed multiple times,whereas for the sunlight shining on the protrusion,there is no secondary reflection or absorption of *** the lighting area and the properties of the surfaces are the same,the absorption rate of the dimple is 10.3 percentage points higher than that of the *** the range of Reynolds number from 3000 to 11000,numerical simulations about the effects of the relative height(e/Dh=0.033–0.1)and relative spacing(p/e=4.5–8.5)of protrusions on air heat transfer and flow resistance show that,in terms of comprehensive evaluation coefficient(PF),the best relative height is 0.085,when the relative spacing is 5.A correlation of Nu and f with Re,e/Dh and p/e is obtained by linear regression of the results,in order to provide a useful reference for the design and optimization of this kind of solar air collector.

关键词： Heat transfer hemispherical protrusion dimple solar air collector correlation

Plant RNA-binding proteins:Phase separation dynamics and functional mechanisms underlying plant development and stress responses

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Molecular Plant 2024年第4期17卷 531-551页

作者： Sheng fan yu Zhang Shaobo Zhu Lisha Shen Temasek Life Sciences Laboratory 1 Research LinkNational University of Singapore1 Research LinkSingapore 117604Singapore Department of Biological Sciences National University of Singapore14 Science Drive 4Singapore 117543Singapore

RNA-binding proteins(RBPs)accompany RNA from synthesis to decay,mediating every aspect of RNA metabolism and impacting diverse cellular and developmental processes in *** RBPs undergo phase separation along with their bound RNA to form and function in dynamic membraneless biomolecular condensates for spatiotemporal coordination or regulation of RNA *** evidence suggests that phase-separating RBPs with RNA-binding domains and intrinsically disordered regions play important roles in plant development and stress ***,we summarize the current knowledge about how dynamic partitioning of RBPs into condensates controls plant development and enables sensing of experimental changes to confer growth plasticity under stress conditions,with a focus on the dynamics and functional mechanisms of RBP-rich nuclear condensates and cytoplasmic granules in mediating RNA *** also discuss roles of multiple factors,such as environmental signals,protein modifications,and N6-methyladenosine RNA methylation,in modulating the phase separation behaviors of RBPs,and highlight the prospects and challenges for future research on phase-separating RBPs in crops.

关键词： RNA-binding proteins phase separation biomolecular condensates RNA metabolism development stress resilience

Simultaneous enhancement of red luminescence and thermal stability of a novel red phosphor:A Li+-Eu3+ co-occupied site strategy in BaAl2Ge2O8 lattices

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Journal of Rare Earths 2024年第10期42卷 1846-1854页

作者： wei Zhang Changjian Wang Xusheng Qiao Xianping fan State Key Laboratory of Silicon Materials School of Materials Science and EngineeringZhejiang University Ocean Academy Zhejiang University

The rapid development of phosphor-converted white light emitting diodes（pc-WLEDs） requires new red phosphors with efficient and thermally stable luminescence for high-quality warm-white ***,it is still a challenge to discover red phosphors with facile synthesis,high internal quantum efficiency（IQE）,excellent thermal stability and high color ***,a novel red-emitting Eu3+activated barium dialuminum digermanate（BaAl2Ge3O8,EAGO） phosphor showing strong red emission at 610 nm was *** IQE is improved from 32.91% to 78.84% by employing a charge compensation *** lithium-ion co-dop ed BAGO:Eu3+phosphor exhibits a nearly twofold increase in integral photoluminescence（PL） intensity and the high color purity reaches 94.17%.Impressively,the PL intensity of the BAGO:Eu3+,Li+phosphor drops by only 2.6% at 150℃ of that at room ***,the pc-WLED using the red BAGO:Eu3+,Li+phosphor exhibits white light with the chromaticity coordinate of（0.3515,0.3495）,a high color-rendering index of 92 and a low correlated color temperature of 4746 *** these results manifest that BAGO:Eu3+,Li+phosphor is a suitable red phosphor for nearultraviolet（NUV） chip-based pc-WLEDs.

关键词： Red phosphor Charge compensation High quantum efficiency Excellent thermal stability Rare earths

Vibration Control of the Rail Grinding Vehicle with Abrasive Belt Based on Structural Optimization and Lightweight Design

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Chinese Journal of Mechanical Engineering 2024年第3期37卷 311-337页

作者： Wengang fan Shuai Zhang Zhiwei Wu Yi Liu Jiangnan yu School of Mechanical Electronic and Control EngineeringBeijing Jiaotong UniversityBeijing 100044China Key Laboratory of Vehicle Advanced Manufacturing Measuring and Control TechnologyMinistry of EducationBeijing 100044China China Railway Materials Operation and Maintenance Technology Co. LtdBeijing 100036China

As a new grinding and maintenance technology,rail belt grinding shows significant advantages in many applications The dynamic characteristics of the rail belt grinding vehicle largely determines its grinding performance and service *** order to explore the vibration control method of the rail grinding vehicle with abrasive belt,the vibration response changes in structural optimization and lightweight design are respectively analyzed through transient response and random vibration simulations in this ***,the transient response simulation analysis of the rail grinding vehicle with abrasive belt is carried out under operating conditions and non-operating ***,the vibration control of the grinding vehicle is implemented by setting vibration isolation elements,optimizing the structure,and increasing ***,in order to further explore the dynamic characteristics of the rail grinding vehicle,the random vibration simulation analysis of the grinding vehicle is carried out under the condition of the horizontal irregularity of the American AAR6 ***,by replacing the Q235 steel frame material with 7075 aluminum alloy and LA43M magnesium alloy,both vibration control and lightweight design can be achieved *** results of transient dynamic response analysis show that the acceleration of most positions in the two working conditions exceeds the standard value in GB/T 17426-1998 *** optimizing the structure of the grinding vehicle in three ways,the average vibration acceleration of the whole car is reduced by about 55.1%from 15.6 m/s^(2) to 7.0 m/s^(2).The results of random vibration analysis show that the grinding vehicle with Q235 steel frame does not meet the safety conditions of 3σ.By changing frame material,the maximum vibration stress of the vehicle can be reduced from 240.7 MPa to 160.0 MPa and the weight of the grinding vehicle is reduced by about 21.7%from 1500 kg to 1175 *** modal analysis results indic

关键词： Vibration control Dynamic characteristics Structural optimization Lightweight design Modal analysis

Fourth-order phase-field modeling for brittle fracture in piezoelectric materials

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Applied Mathematics and Mechanics(English Edition) 2024年第5期45卷 837-856页

作者： yu TAN fan PENG Chang LIU Daiming PENG Xiangyu LI State Key Laboratory of Geohazard Prevention and Geoenvironment Protection Chengdu University of TechnologyChengdu 610059China College of Science Chang'an UniversityXi'an 710064China Applied Mechanics and Structure Safety Key Laboratory of Sichuan Province School of Mechanics and Aerospace EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Failure analyses of piezoelectric structures and devices are of engineering and scientific *** this paper,a fourth-order phase-field fracture model for piezoelectric solids is developed based on the Hamilton *** typical electric boundary conditions are involved in the present model to characterize the fracture behaviors in various physical situations.A staggered algorithm is used to simulate the crack *** polynomial splines over hierarchical T-meshes(PHT-splines)are adopted as the basis function,which owns the *** numerical simulations are performed to study the influence of the electric boundary conditions and the applied electric field on the fracture behaviors of piezoelectric *** electric boundary conditions may influence crack paths and fracture loads *** present research may be helpful for the reliability evaluation of the piezoelectric structure in the future applications.

关键词： isogeometric analysis(IGA) brittle fracture fourth-order phase-field model piezoelectric solid

Investigation of electrostatically tunable adhesion and instability of flying head slider

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Friction 2024年第3期12卷 462-473页

作者： fan ZHANG yu WANG yueqiang HU Mingquan ZHANG Baotong LI School of Mechanical Engineering Xi’an Jiaotong UniversityXi’an 710049China National Engineering Research Center for High Efficiency Grinding College of Mechanical and Vehicle EngineeringHunan UniversityChangsha 410082China

The interfacial adhesion between microstructures is inevitable in a micro-electro-mechanical system(e.g.,hard disk drive(HDD)),which may lead to complicated microtribodynamics *** research has investigated the effect of surface potential on the interfacial adhesion and microtribodynamics of the head–disk interface(HDI)in an HDD.A dynamic continuum surface force model,where the electrowetting is considered,is proposed to evaluate the interfacial interaction,and then employed into a two-degree-of-freedom(2DOF)model to theoretically analyze the potential influence mechanism on the *** results confirm that the elimination of potential can effectively repress the adhesion retention,which is further proved by the measured slider response with a laser Doppler vibrometer(LDV).Moreover,the effect of the potential on the adhesion-induced instability is also analyzed through the phase *** tells that the critical stable flying height can be lowered with the elimination of potential.

关键词： electric field(EF) retention instability adhesion

Solvation strategies in various electrolytes for advanced zinc metal anode

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Journal of Energy Chemistry 2024年第7期94卷 740-757页

作者： Zhenxu Wang Lichong Bai Hongguang fan Yanpeng Wang wei Liu School of Materials Science and Engineering Ocean University of ChinaQingdao 266100ShandongChina

Aqueous zinc-ion batteries(AZIBs),known for their high safety,low cost,and environmental friendliness,have a wide range of potential applications in large-scale energy storage ***,the notorious dendrite growth and severe side reactions on the anode have significantly hindered their further practical *** studies have shown that the solvation chemistry in the electrolyte is not only closely related to the barriers to the commercialization of AZIBs,but have also sparked a number of valuable ideas to address the challenges of ***,we systematically summarize and discuss the regulatory mechanisms of solvation chemistry in various types of electrolytes and the influence of the solvation environment on battery *** challenges and future directions for solvation strategies based on the electrolyte environment are proposed to improve their performance and expand their application in AZIBs.

关键词： Solvation strategy Electrolyte Aqueous zinc-ion batteries Zinc dendrite