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Development of pharmacological immunoregulatory anticancer therapeutics:current mechanistic studies and clinical opportunities

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2477-2526页

作者： Nanhao Yin Xintong li Xuanwei Zhang Shaolong xue Yu Cao Gabriele Niedermann you Lu Jianxin xue Division of Thoracic Tumor Multimodality Treatment Cancer Center&State Key Laboratory of Biotherapyand The National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.37Guoxue LaneChengdu 610041 SichuanPR China Department of Gynecology and Obstetrics West China Second University HospitalSichuan UniversityNo.20Section 3South Renmin RoadChengdu 610041 SichuanPR China Department of Emergency Medicine Laboratory of Emergency MedicineWest China HospitalSichuan UniversityNo.37Guoxue LaneChengdu 610041 SichuanPR China Institute of Disaster Medicine&Institute of Emergency Medicine Sichuan UniversityNo.17Gaopeng AvenueChengdu 610041 SichuanPR China Department of Radiation Oncology Medical Center—University of FreiburgFaculty of MedicineUniversity of FreiburgGerman Cancer Consortium(DKTK)Partner Site DKTK-FreiburgRobert-Koch-Strasse 379106 FreiburgGermany Laboratory of Clinical Cell Therapy West China HospitalSichuan UniversityNo.2222Xinchuan RoadChengdu 610041 SichuanPR China

Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment,but challenges related to resistance and toxicity still *** to the advancement of immuno-oncology,an increasing number of novel immunoregulatory targets and mechanisms are being revealed,with relevant therapies promising to improve clinical immunotherapy in the foreseeable ***,comprehending the larger picture is *** this review,we analyze and summarize the current landscape of preclinical and translational mechanistic research,drug development,and clinical trials that brought about next-generation pharmacological immunoregulatory anti-cancer agents and drug candidates beyond classical immune checkpoint *** with further clarification of cancer immunobiology and advances in antibody engineering,agents targeting additional inhibitory immune checkpoints,including LAG-3,TIM-3,TIGIT,CD47,and B7 family members are becoming an important part of cancer immunotherapy research and discovery,as are structurally and functionally optimized novel anti-PD-(L)1 and anti-CTLA-4 agents and agonists of co-stimulatory molecules of T *** by bispecific T cell engagers,newly emerging bi-specific and multi-specific antibodies targeting immunoregulatory molecules can provide considerable clinical ***-generation agents also include immune epigenetic drugs and cytokine-based *** therapies,cancer vaccines,and oncolytic viruses are not covered in this *** comprehensive review might aid in further development and the fastest possible clinical adoption of effective immuno-oncology modalities for the benefit of patients.

关键词： clinical immuno landscape

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Effects of cerium salts on corrosion behaviors of Si–Zr hybrid sol–gel coatings

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Chinese Journal of Aeronautics 2015年第2期28卷 600-608页

作者： Yu Mei liu Yuxing liu Jianhua li Songmei xue Bing Zhang you Yin Xiaolin School of Materials Science and Engineering Beihang University

The present work examines the effects of cerium salts on corrosion behaviors of Si-Zr hybrid sol-gel coatings. The Si-Zr hybrid sol-gel coatings on a 2A l2 aluminum substrate were pre- pared through hydrolysis and condensation of glycidoxypropyl-trimethoxy-silane （GTMS） and zirconium（IV） n-propoxide （TPOZ）. Used as inhibitors for corrosion, three types of cerium salts （Co（NO3）3, CeCl3, and Ce（CH3COO）3） were doped into the sol-gel coatings. Fourier transform infrared （FTIR） and scanning electron microscopy （SEM） were employed to investigate the structures and morphologies of various coatings, and the corrosion resistances of the coatings were evaluated by electrochemical methods and neutral salt spray tests. Experimental results indicate that the addition of cerium salts can hinder the process of corrosion due to their self-healing abili- ties. Furthermore, the sol-gel coating doped with Ce（CH3COO）3 has the best corrosion resistance because of the promotions of hydrolysis and condensation provided by CH3COO-.

关键词： Cerium salts Corrosion resistance Hybrid coating Inhibitor

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Methylprednisolone inhibits activated CD4^+ T cell survival promoted by toll-like receptor ligands

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Hepatobiliary & Pancreatic Diseases International 2010年第4期9卷 376-383页

作者： Lu, you-Sheng Pu, li-Yong li, Xiang-Cheng Wang, xue-Hao Nanjing Med Univ Affiliated Hosp 1 Liver Transplantat Ctr Peoples Hosp Jiangsu Prov Nanjing 210029 Peoples R China

BACKGROUND: Methylprednisolone (MP) can affect the survival of CD4(+) T lymphocytes and plays an important role in adaptive immune responses; however, its mechanism of action is not clear. Recent studies have shown that toll-like receptors (TLRs) on CD4(+) T cells can directly modulate adaptive immune responses by affecting the survival and proliferation of activated CD4(+) T cells. This study aimed to investigate the relationship between MP, TLRs and activated CD4(+) T cells. METHODS: We separated and purified CD4(+) T cells from mice, activated them in vitro, and co-cultured them with TLR ligands, MP or inhibitors of nuclear factor-kappa B (NF-kappa B) and activator protein 1 (AP-1). We then assessed CD4(+) T cell survival and proliferation and the expression of NF-kappa B and AP-1. RESULTS: Activated CD4(+) T cells showed increased TLR-3 and TLR-9 mRNA expression, but polyinosinic-polycytidylic acid (poly I:C) and MP had no effect on the expression of these mRNAs. Still, poly I:C and CpG oligodeoxynucleotides (CpG DNA) increased the survival of activated CD4(+) T cells, whereas MP reduced the survival of activated CD4(+) T cells and could inhibit the survival effects of poly I:C and CpG DNA. The NF-kappa B essential modifier-binding domain (NBD) inhibited the survival of activated CD4(+) T cells induced by poly I:C and CpG DNA, but the AP-1 inhibitor crucumin did not have the same effect. The increased expression of NF-kappa B induced by poly I:C and CpG DNA in activated CD4(+) T cells could be inhibited by MP, but the same was not true for the increased expression of AP-1 induced by poly I:C and CpG DNA. Finally, the proliferation of activated CD4(+) T cells was not affected by poly I:C or MP. CONCLUSION: The survival of activated CD4(+) T cells is promoted by TLR ligands, but this effect is inhibited by MP.

关键词： methylprednisolone toll-like receptor CD4(+) T lymphocytes NF-kappa B

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内蒙古达来诺尔湖湖泊沉积物中敏感粒度组分沉积环境及地层分析

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沉积与特提斯地质 2016年第3期36卷 77-82页

作者：于瑞雪李畅游李文宝甄志磊赵胜男张帅内蒙古农业大学水利与土木建筑工程学院内蒙古呼和浩特010018 中国中铁投资集团安徽安庆246000

对达来诺尔湖北岸岸边（DL-0）、湖中心（DL-1）和湖南岸（DL-2）3个点的岩心沉积物进行了详细的岩性分析、粒度分析和粒度参数垂向分布序列分析。对沉积环境变化较为敏感的粒度组分的分析发现 DL-0与 DL-1和 DL-2井岩心沉积物敏感粒度... 详细信息

对达来诺尔湖北岸岸边（DL-0）、湖中心（DL-1）和湖南岸（DL-2）3个点的岩心沉积物进行了详细的岩性分析、粒度分析和粒度参数垂向分布序列分析。对沉积环境变化较为敏感的粒度组分的分析发现 DL-0与 DL-1和 DL-2井岩心沉积物敏感粒度组分的峰值有较大差别，其粒度分布范围相差较大，表明湖北岸岸边、湖中心和湖南岸的沉积物来源和沉积环境的时空差异。敏感粒度组分含量随深度变化的初步分析表明，湖北岸岸边（DL-0）和湖中心（DL-1）两个点的沉积环境较为稳定；而位于湖南岸（DL-2）点的沉积环境变化比较大，包含了5个明显的沉积波动旋回，并对达来诺尔湖由北至南进行了沉积地层分析。在达来诺尔湖水下1.5m 内主要是粒径0-200μm 的颗粒，岩性为粘土、粉砂和砂，以粘土和粉砂为主，随着深度的增加，黏土含量增大，粉砂和砂含量减小。

关键词：达来诺尔湖沉积环境粒度分析地层分析

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Room-temperature vertical ferroelectricity in rhenium diselenide induced by interlayer sliding

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Frontiers of physics 2023年第5期18卷 143-151页

作者： Fang li Jun Fu Mingzhu xue you li Hualing Zeng Erjun Kan Ting Hu Yi Wan MIIT Key Laboratory of Semiconductor Microstructure and Quantum Sensing and Department of Applied PhysicsNanjing University of Science and TechnologyNanjing 210094China International Center for Quantum Design of Functional Materials(ICQD) Hefei National Laboratory for Physical Sciences at the Microscaleand Department of PhysicsUniversity of Science and Technology of ChinaHefei 230026China State Key Laboratory for Artificial Microstructure&Mesoscopic Physics School of PhysicsPeking UniversityBeijing 100871China

One variety of ferroelectricity that results from lateral relative movements between the adjacent atomic layers is referred to as sliding ferroelectricity,which generates an interfacial charge transfer and hence a polarization *** mechanism of sliding ferroelectricity existent in van der Waals crystals is quite distinct from the conventional ferroelectric switching mechanisms mediated by ion *** creates new possibilities for the design of two-dimensional(2D)ferroelectrics since it can be achieved even in non-polar *** 2D ferroelectrics can be widely employed for practical implementations,however,there is still significant work to be done on several fronts,such as exploring ferroelectricity possibly in more potential 2D ***,we report the experimental observation of room-temperature robust vertical ferroelectricity in layered semiconducting rhenium diselenide(ReSe_(2)),a representative member of the transition metal dichalcogenides material family,based on a combined research of nanoscale piezoresponse and second harmonic generation *** no such ferroelectric behavior was seen in 1L ReSe_(2),2L ReSe_(2)exhibits vertical ferroelectricity at ambient *** on density-functional theory calculations,we deduce that the microscopic origin of ferroelectricity for ReSe_(2)is uncompensated vertical charge transfer that is dependent on in-plane translation and switchable upon interlayer *** findings have important ramifications for the ongoing development of sliding ferroelectricity since the semiconducting properties and low switching barrier of ReSe2 open up the fascinating potential for functional nanoelectronics applications.

关键词： rhenium diselenide transition metal dichalcogenides vertical ferroelectricity sliding ferroelectricity

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Major physiological adjustments in freezing-tolerant grey tiger longicorn beetle(Xylotrechus rusticus) during overwintering period

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Journal of Forestry Research 2014年第3期25卷 653-659页

作者： Jue-wen li Juan Shi Yu xue Hong-bo Mao you-qing Luo Beijing Key Laboratory of Forest Pest Control Beijing Forestry University College of Forestry Northeast Forestry University Forestry Administration of Acheng District

1Xylotrechus rusticus （linnaeus） is one of the most destruc-tive woodborers in northeast China;it damages poplar and is listed as a domestic forestry quarantine pest. Overwintering larvae were collected during October 2012 and March 2013 in Harbin, China, to quantify indi-cators related to the insect’s overwintering strategy and the major cryo-protectants. The supercooling points （SCPs）, which ranged from-14.7＆#176;C to -2.9＆#176;C, were higher than the lethal temperatures of LT50 （-33.64＆#176;C） and LT99 （-40.17＆#176;C） after 24 h exposure. , also the minimum mean daily temperature （-24.5＆#176;C） and mean monthly temperature （-18.0＆#176;C） at the sampling site in January during 2008-2012. Thus, X. rusticus is a typical freezing-tolerant insect. Glycerol serves as a major cryoprotectant for overwintering larvae , because it was the only polyol accumulated during the winter and it also had a significant negative correlation with the SCP （p=0.033, R=0.907）. The glycogen and lipid are major sources of ener-gy and their levels decreased substantially in the middle of overwintering, when glycogen had a significant correlation with the SCP （p= 0.006, R=0.971） whereas the lipid contents did not. Moreover, inter-conversions between glycerol and glycogen, as well as mannose and glycogen, were suggested by their negative correlations. The water content did not change obviously during the winter and was not correlated with the SCP. The free amino acids in the hemolymph and the total protein contents of the bodies of larvae changed significantly during winter, although both had no correlations with the SCP.

关键词： cold hardiness cryoprotectant freezing tolerant physiological variation Xylotrechus rusticus.

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Semisolid Slurry Preparation of Die Steel with High Chromium Content

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Journal of Iron and Steel Research International 2004年第5期11卷 8-12页

作者： MAO Wei-min ZHAO Ai-min ZHANG li-juan ZHONG xue-you University of Science and Technology Beijing

The control model of laminar cooling system for hot strip, including air-cooling model, water-cooling model, temperature distribution model along thickness direction, feedforward control model, feedback control model and self-learning model, was introduced. PID arithmetic and Smith predictor controller were applied to feedback control. The sample of model parameter classification was given. The calculation process was shown by flow chart. The model has been proved to be simple, effective and of high precision.

关键词： hot strip laminar cooling control model Smith predictor

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The small and large subunits of carbamoyl-phosphate synthase exhibit diverse contributions to pathogenicity in Xanthomonas citri ***

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Journal of Integrative Agriculture 2015年第7期14卷 1338-1347页

作者： GUO Jing SONG xue ZOU li-fang ZOU Hua-song CHEN Gong-you School of Agriculture and Biology Shanghai Jiao Tong University

Carbamoyl-phosphate synthase plays a vital role in the carbon and nitrogen metabolism cycles. In Xanthomonas citrisubsp. citri, carA and carB encode the small and large subunits of carbamoyl-phosphate synthase, respectively. The deletion mutation of the coding regions revealed that carA did not affect any of the phenotypes, while carB played multiple roles in pathogenicity. The deletion of carB rendered the loss of pathogenicity in host plants and the ability to induce a hyper- sensitive reaction in the non-hosts. Quantitative reverse transcription-PCR assays indicated that 11 hrp genes coding the type Ill secretion system were suppressed when interacting with citrus plants. The mutation in carB also affected bacterial utilization of several carbon and nitrogen resources in minimal medium MMX and extracellular enzyme activities. These data demonstrated that only the large subunit of carbamoyl-phosphate synthase was essential for canker development by X. citri subsp, citri.

关键词： Xanthomonas citri subsp citri carbamoyl-phosphate synthase pathogenicity citrus canker hrp gene

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Single-shot phase-shifting digital holography with a photon-sieve-filtering telescope

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Chinese Physics B 2019年第8期28卷 156-159页

作者： you li Yao-Cun li Jun-Yong Zhang Yan-li Zhang xue-Mei li Key Laboratory of High Power Laser and Physics Shanghai Institute of Optics and Fine MechanicsChinese Academy of SciencesShanghai 201800China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China School of Mathematics Physics & Information ScienceZhejiang Ocean UniversityZhoushan 316022China

A method of single-shot phase-shifting digital holography with a photon-sieve-filtering telescope is *** copy images with different phases are first generated by use of a monofocal photon-sieve filter in Kepler telescope,and then interfere with the reference plane wave by a beam *** hologram is captured by a charge-coupled device(CCD)in one single *** complex-valued amplitude of the test object can be reconstructed by three-step phase-shifting interferometry through three frames of extracted sub-interferograms from the single-exposure *** principle and simulation experiments are carried out and verified the validity of our proposed *** method can be applied for snapshot imaging and three-dimensional object construction.

关键词： digital holography phase shift diffractive lenses frequency filtering

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Distribution behavior of inclusions in compact-strip-produced martensitic steel and its influence on mechanical properties

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Journal of Materials Science & Technology 2023年第11期142卷 98-111页

作者： Jing Wang Peng xue Laiqi Zhang li you Xiaodong Zhu Shuize Wang Yong Zhong Xinping Mao State Key Laboratory for Advanced Metals and Materials University of Science and Technology BeijingBeijing 100083China Shanghai Key Laboratory of Materials Laser Processing and Modification School of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai 200240China Research Institute Baoshan Iron&Steel Co.LtdShanghai 201999China Beijing Advanced Innovation Center for Materials Genome Engineering University of Science and Technology BeijingBeijing 100083China

The distribution behavior of inclusions in martensitic steel produced by compact strip production process(CSP-MS)and its influence on mechanical properties were systematically *** inclusions in the CSP-MS specimen are mainly composed of spherical Al_(2)O_(3)-CaO-CaS,MnS with high aspect ratio and small-sized TiN,whereas many coarse cuboidal TiN inclusions do exist in conventional martensitic steel(Con-MS).The high inclusion density of the CSP-MS specimen resulted in lower total elongation and impact toughness,and the MnS inclusions with high aspect ratio led to significantly stronger mechanical anisotropy than that for Con-MS *** in-situ tensile results indicated that when the fracture direction is parallel to MnS direction,the microcracks induced by MnS inclusions tend to propagate into the matrix,leading to the formation of valley-like features,which significantly deteriorate the properties such as the total elongation and impact *** microcracks caused by TiN inclusions are sharper than those caused by spherical Al_(2)O_(3)-CaO-CaS inclusions,and are easy to propagate into the *** work is expected to guide the optimization of the mechanical properties of martensitic steels produced by CSP process and provide a theoretical basis for the CSP process design.

关键词： Martensitic steel Compact strip production Inclusion distribution behavior Mechanical properties In-situ tensile test

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