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

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

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Intracellular transport dynamics revealed by single-particle tracking

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Biophysics Reports 2021年第5期7卷 413-427页

作者： Ming-Li Zhang hui-Ying ti Peng-Ye Wang hui Li School of Systems Science Beijing Normal University Beijing National Laboratory for Condensed Matter Physics and Laboratory of Soft Matter Physics Institute of Physics Chinese Academy of Sciences School of Physical Sciences University of Chinese Academy of Sciences Songshan Lake Materials Laboratory

Intracellular transport is the basis for the transfer of matter, energy, and information in cells and is critical to many cellular functions. Within the nonequilibrium environment of living cells, the transport behaviours are far from the traditional motion in liquid but are more complex and active. With the advantage of high spatial and temporal resolution, the single-particle tracking(SPT) method is widely utilized and has achieved great advances in revealing intracellular transport dynamics. This review describes intracellular transport from a physical perspective and classifies it into two modes: diffusive motion and directed motion. The biological functions and physical mechanisms for these two transport modes are introduced. Next, we review the principle of SPT and its advances in two aspects of intracellular transport. Finally, we discuss the prospect of near infrared SPT in exploring the in vivo intracellular transport dynamics.

关键词： Intracellular transport Single-particle tracking (SPT) Diffusive motion Directed motion Near infrared SPT Dynamics

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Hamiltonian Gromov–Witten Invariants on C^n+1 with S^1-action

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Acta Mathematica Sinica,English Series 2016年第3期32卷 309-330页

作者： ti Yao LI Bo hui CHEN Department of Mathematics Sichuan University Chengdu 610064 P. R. China School of Mathematical Sciences Chongqing Normal University Chongqing 401331 P. R. China Department of Mathematics and Yangtze Mathematical Center Sichuan University Chengdu 610064 P. R. China

Consider a Hamiltonian action of S1 on （Cn^n＋1,ωstd）, we shown that the Hamiltonian Gromov-Witten invariants of it are well-defined. After computing the Hamiltonian Gromov-Witten invariants of it, we construct a ring homomorphism from HS1,CR（X, R） to the small orbifold quantum cohomology of X//rS^1 and obtain a simpler formula of the Gromov-Witten invariants for weighted projective space.

关键词： Hamiltonian Gromov-Witten invariants orbifold Gromov-Witten invariants weighted projective space

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Cemented vertebra and adjacent vertebra refractured in a chronic kidney disease-mineral and bone disorder patient: A case report

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World Journal of Clinical Cases 2024年第10期12卷 1804-1809页

作者： ti-Dong Zhang Shuai Cao hui-Yong Ren Yu-Min Li Yi-Ming Yuan Department of Orthopedics Civil Aviation General HospitalBeijing 100123China

BACKGROUND Although percutaneous vertebral augmentation(PVA)is a commonly used procedure for treating vertebral compression fracture(VCF),the risk of vertebral refracture should be considered.Chronic kidney disease-mineral and bone disorder(CKD-MBD)is a systemic disease of mineral and bone metabolism.It is associated with an increased risk of fracture.Few studies have reported the use of PVA in patients with CKD-MBD.We herein report a rare case wherein the cemented vertebra and the adjacent vertebra refractured simultaneously in a CKD-MBD patient after PVA.CASE SUMMARY A 74-year-old man suffered from low back pain after taking a fall about 3 wk ago.According to physical examination,imaging and laboratory findings,diagnoses of T12 VCF,CKD-MBD,and chronic kidney disease stage 5 were established.He then received percutaneous vertebroplasty at T12 vertebra.Fourteen weeks later,he presented with T12 and L1 vertebral refractures caused by lumbar sprain.Once again,he was given PVA which was optimized for the refractured vertebrae.Although the short-term postoperative effect was satisfactory,he reported chronic low back pain again at the 3-month follow-up.CONCLUSION It is necessary that patients with CKD-MBD who have received PVA are aware of the adverse effects of CKD-MBD.It may increase the risk of vertebral refracture.Furthermore,the PVA surgical technique needs to be optimized according to the condition of the patient.The medium-and long-term effects of PVA remain uncertain in patients with CKD-MBD.

关键词： Chronic kidney disease-mineral and bone disorder Percutaneous vertebral augmentation Vertebral compression fracture Vertebral refracture Cemented vertebra Adjacent vertebra Case report

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Probing cell membrane integrity using a histone-targeting protein nanocage displaying precisely positioned fluorophores

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Nano Research 2023年第1期16卷 894-904页

作者： ti Fang Chaoqun Li Ao Liang hui Zhang Fan Zhang Xian-En Zhang Yi-Yu Yang Feng Li Guangzhou Women and Children’s Medical Center Guangzhou Medical UniversityGuangzhou 510120China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China Faculty of Synthetic Biology Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Cell membrane integrity is fundamental to the normal activities of cells and is involved in both acute and chronic pathologies.Here,we report a probe for analyzing cell membrane integrity developed from a 9 nm-sized protein nanocage named Dps via fluorophore conjugation with high spatial precision to avoid self-quenching.The probe cannot enter normal live cells but can accumulate in dead or live cells with damaged membranes,which,interestingly,leads to weak cytoplasmic and strong nuclear staining.This differential staining is found attributed to the high affinity of Dps for histones rather than DNA,providing a staining mechanism different from those of known membrane exclusion probes(MEPs).Moreover,the Dps nanoprobe is larger in size and thus applies a more stringent criterion for identifying severe membrane damage than currently available MEPs.This study shows the potential of Dps as a new bioimaging platform for biological and medical analyses.

关键词： protein engineering fluorescent probes nanoparticles cell membrane damage ferritin superfamily

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Influence of varying forms of bionic units on repairing remaining quenching surface of gray cast iron

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Journal of Iron and Steel Research(International) 2021年第2期28卷 201-210页

作者： hui Li Li Feng Hong Zhou Peng Zhang ti Zhou Qi Sui Lu-quan Ren Key Laboratory of Automobile Materials(Jilin University) Ministry of EducationChangchun 130025JilinChina School of Material Science and Engineering Jilin UniversityChangchun 130025JilinChina School of Mechanical and Aerospace Engineering Jilin UniversityChangchun 130025JilinChina Key Laboratory of Terrain Machinery Bionics Engineering(Jilin University) Ministry of EducationChangchun 130025JilinChina

In order to repair and reuse remaining quenching surface(RQS)divided into severely worn surface(SWun-S)and mildly worn surface(MWun-S)of abandoned gray cast iron guide rail,inspired by the bionic theory,varying forms of bionic units such as spot(Sp-S),striation(St-S),and reticulation(Re-S)were fabricated on RQS of gray cast iron through laser processing technology.Firstly,the microstructure,phase composition,and microhardness of bionic units and RQS were analyzed by optical microscopy as well as X-ray diffraction instrument and scanning electron microscopy,respectively.Secondly,the oil lubrication wear experiment was performed on homemade line reciprocating wear machine.The results demonstrated that the bionic units had a significant effect on improving wear resistance of RQS of abandoned guide rail due to the microstructure and higher hardness.In addition,the weight loss ratios of MWun-S,Sp-S,St-S,and Re-S samples were decreased by 36.72%,36.78%,62.26%,and 80.39%,respectively,compared with that of SWun-S sample.The mechanism of wear resistance enhancement was also discussed.

关键词： Repairing Laser bionic unit Remaining quenching surface Gray cast iron

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Characteristics of SEN clogging and adhesive behavior of oxide inclusion during continuous casting of ti-stabilized ultra-pure ferritic stainless steels

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Journal of Iron and Steel Research(International) 2023年第10期30卷 1939-1951页

作者： Xue-feng Bai Yan-hui Sun hui-bin Wu Collaborative Innovation Center of Steel Technology University of Science and Technology BeijingBeijing100083China

Submerged entry nozzle(SEN)clogging during continuous casting of ti-stabilized ultra-pure ferritic stainless(ti-UPFS)steels was systematically investigated via cross-sectional analysis and acid dissolution treatment.The SEN deposit profile was characterized as occurring in three major layers:(1)an eroded refractory layer;(2)an initial adhesive layer comprised an Al_(2)O_(3)-ZrO_(2) composite sub-layer and a dense Al_(2)O_(3)-based deposit sub-layer;and(3)a porous multiphase deposit layer mainly consisting of MgO·Al_(2)O_(3),CaO-Al_(2)O_(3),and CaO-tiOx.The MgO·Al_(2)O_(3)-rich inclusions did not adhere directly to the eroded refractory but were entrapped during the deposit growth.Results of inclusion characterization in the tundish revealed that the MgO·Al2O3-rich particles present in the tundish served as the primary source of clogging deposits.Furthermore,a novel cavity-induced adhesion model by circular approximation was established to explain the effects of complex inclusion characteristics and refractory material type on adhesion force.A high number of small MgO·Al_(2)O_(3) inclusions were expected to accelerate the buildup of clogging deposits.Improving the modification of MgO·Al_(2)O_(3)-rich inclusions in the size range of 2-4μm by Ca treatment was crucial to minimizing the risk of SEN clogging during the continuous casting of ti-UPFS steels.

关键词： ti-stabilized ultra-pure ferritic stainless steel Submerged entry nozzle clogging MgO·Al_(2)O_(3)-rich inclusion Adhesion Continuous casting

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Sheng Jiang San, traditional multi-herb formulation, exerts anti-influenza effects in vitro and in vivo via neuraminidaseinhibition and immune regulation

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中国药理学与毒理学杂志 2019年第9期33卷 738-739页

作者： ZHANG tian-bo XIAO Meng-jie Chun-Kwok WONG Ka-Pun CHRIS MOK ZHAO Xin TI Hui-hui Pang-Chui SHAW State Key Laboratory of Respiratory Disease Guangdong Provincial Key Laboratory of Molecular Target&Clinical PharmacologySchool of Pharmaceutical Sciences and The Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina The School of Life Sciences The Chinese University of Hong KongHong KongChina School of Public Health Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina

OBJECtiVE Sheng Jiang San(SJS),a multi-herb formulation,is used in treating high fever,thirsty and anxiety in ancient China and it is sometimes used to treat seasonal influenza in modern.However,there is no evidencebased investigation and mechanism research to support SJS′s anti-influenza efficacy.This study aims to investigate the anti-influenza effect of SJS and its possible mechanisms.METHODS In this study,we examined the inhibitory effect of SJS against different influenza viruses on Madin-Darby canine kidney cells.Influenza virus infected BALB/c mice were employed as in vivo model to evaluate the efficacy.Mice challenged with A/PR/8/34(H1N1)were orally administrated SJS 1 g·kg^-1 daily for seven days and monitored for 14 d.The survival rate,body mass changes,lung index,lung viral load,histopathologic changes and immune-regulation of the mice were measured.The underlying anti-influenza virus mechanisms were studied by a series of biological assays in vitro to determine if hemagglutinin,ribonucleoprotein complex or nerauminidase were targets of SJS.RESULTS SJS exerted a broad spectrum of inhibitory effects on multiple influenza strains in a dose-dependent manner.And IC50 of SJS against A/WSN/33(H1N1)was lower than 35 mg·L^-1.SJS also protected 50%of mice from influenza virus PR8 infection.The lung index and the lung viral load of SJS treated mice were signifi⁃cantly decrease compared with untreated mice.SJS 2 g·L^-1 inhibited 80%of neuraminidase enzymatic activity.SJS also up-regulated TNF-αand IFN-αand down-regulated IL-2 of influenza virus induced mice.CONCLUSION SJS is a useful formulation for treating influenza virus infection.

关键词： Sheng Jiang San anti-influenza activity neuraminidase inhibition immuno-regulation

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Effects of embedding direct reduction followed by magnetic separation on recovering titanium and iron of beach titanomagnetite concentrate

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Journal of Iron and Steel Research(International) 2017年第2期24卷 156-164页

作者： Chao Geng ti-chang Sun You-wen Ma Cheng-yan Xu hui-fen Yang School of Civil and Environmental Engineering University of Science and Technology Beijing Beijing 100083 China

Embedding direct reduction followed by magnetic separation was conducted to fully recover iron and titanium separately from beach titanomagnetite （TTM）. The influences of reduction conditions, such as molar ratio of C to Fe, reduction time, and reduction temperature, were studied. The results showed that the TTM concentrate was reduced to iron and iron-titanium oxides, depending on the reduction time, and the reduction sequence at 1 200℃ was suggested as follows ： Fe2.75 ti0.25O4→Fe2tiO4→FetiO3→Feti2O5. The reduction temperature played a considerable role in the reduction of TTM concentrates. Increasing temperature from 1 100 to 1 200℃ was beneficial to recovering titanium and iron, whereas the results deteriorated as temperature increased further. The results of X-ray diffraction and scanning electron microscopy analyses showed that low temperature （≤1100℃） was unfavorable for the gasification of reductant, resulting in insufficient reducing atmosphere in the reduction process. The molten phase was formed at high temperatures of 1250-1 300℃, which accelerated the migration rate of metallic particles and suppressed the diffusion of reduction gas, resulting in poor reduction. The optimum conditions for reducing TTM concentrate are as follows： molar ratio of C to Fe of 1.68, reduction time of 150 min, and reduction temperature of 1 200℃. Under these conditions, direct reduction iron powder, assaying 90.28 mass% TFe and 1.73 mass% tiO2 with iron recovery of 90.85%, and titanium concentrate, assaying 46.24 mass% tiO2 with tiO2 recovery of 91.15%, were obtained.

关键词： titanomagnetite concentrate Direct reduction Reduction condition Direct reduction iron powder Magnetic separation

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Dairy Consumption and Associations with Nutritional Status of Chinese Children and Adolescents

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Biomedical and Environmental Sciences 2019年第6期32卷 393-405页

作者： XU Pei Pei YANG ti ti XU Juan LI Li CAO Wei GAN Qian HU Xiao Qi PAN hui ZHAO Wen Hua ZHANG Qian National Institute for Nutrition and Health Chinese Center for Disease Control and Prevention

Objective This study aimed to describe frequency and quantity of total dairy consumption of Chinese children and adolescents and explore the associations between dairy consumption and nutrition status, including stunting, wasting, overweight, and obesity. Methods Participants included 28,250 children and adolescents aged 6-17 years old. A food frequency questionnaire(FFQ) including 100 kinds of food was used to collect information about frequency and quantity of dairy consumption. Determination of stunting was with a height cutoff value for age and gender, and determination for wasting, overweight, and obesity was with BMI for age and gender. Results Of the total sample, 36.1% of children aged 6-17 reported consuming dairy food more than once per day(≥ 1/day). The average total dairy intake of all the participants was 126.7 g/day. For boys, dairy consumption had an inverse correlation with stunting and wasting after controlling for confounders. For girls, dairy consumption was negatively associated with stunting and obesity after controlling for confounders as above. Conclusion Dairy consumption in Chinese children and adolescents was relatively lower than that in developed countries, and was negatively associated with stunting and wasting for boys and with stunting and obesity for girls.

关键词： Dairy consumption Children and adolescents Nutrition status Association China

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