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991.
    
Blockade of the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction is currently the focus in the field of cancer immunotherapy, and so far, several monoclonal antibodies (mAbs) have achieved encouraging outcomes in cancer treatment. Despite this achievement, mAbs-based therapies are struggling with limitations including poor tissue and tumor penetration, long half-life time, poor oral bioavailability, and expensive production costs, which prompted a shift towards the development of the small-molecule inhibitors of PD-1/PD-L1 pathways. Even though many small-molecule inhibitors targeting PD-1/PD-L1 interaction have been reported, their development lags behind the corresponding mAb, partly due to the challenges of developing drug-like small molecules. Herein, we report the discovery of a series of novel inhibitors targeting PD-1/PD-L1 interaction via structural simplification strategy by using BMS-1058 as a starting point. Among them, compound A9 stands out as the most promising candidate with excellent PD-L1 inhibitory activity (IC50 = 0.93 nM, LE = 0.43) and high binding affinity to hPD-L1 (KD = 3.64 nM, LE = 0.40). Furthermore, A9 can significantly promote the production of IFN-γ in a dose-dependent manner by rescuing PD-L1 mediated T-cell inhibition in Hep3B/OS-8/hPD-L1 and CD3-positive T cells co-culture assay. Taken together, these results suggest that A9 is a promising inhibitor of PD-1/PD-L1 interaction and is worthy for further study.  相似文献   
992.
效用水平不可精确度量的一类博弈设计   总被引:2,自引:0,他引:2  
一类博弈的支付或效用水平难以用准确的数量给出,而且效用水平优劣的衡量很大程度上取决于参与者由获取的信息及经验形成的主观判断。对于这一类问题,文章尝试引入相对隶属度反映效用水平,并用于有限博弈  相似文献   
993.
通过文献研究和实践调查分析,构造企业制造战略检测量表,用偏最小二乘回归法来确定影响企业绩效的制造战略可观测项目,进一步分析制造战略与企业绩效的正相关关系,为企业制造战略竞争重点要素的识别和管理提供定量依据.  相似文献   
994.
ERB-1 zeolite emerges as a key bridging material for crafting heteroatom-containing MWW for versatile catalytic applications.In this study,we developed a solvent-free strategy facilitated by high-temperature condition and seed assistance,streamlining the synthesis of ERB-1 zeolite.This novel approach not only significantly reduces the growth time to 12 h compared to the conventional 168-h hydrothermal synthesis but also enhances product yield while minimizing waste generation.Benefiting from the platelet seeds and the grinding force,a distinct non-classical growth pathway,involving nanoparticle attachment,epitaxial growth,anisotropic assembly,and crystallization,was observed in the solvent-free synthesis.Through heteroatom substitution,pillared Sn-MWW was successfully prepared,exhibiting remarkable stability and catalytic performance in the Bayer-Villiger oxidation reaction of 2-adamantanone.Our findings present a simple and cost-effective way for rapid synthesis of MWW zeolite,with implications extending to diverse catalytic applications.  相似文献   
995.
An efficient synthesis of timosaponin AIII (TAIII) and five structurally modified analogs via a one-pot sequential glycosylation strategy is described. A partially protected D-galactopyranosyl thioglycoside was employed for regioselective glycosylation to facilitate the target synthesis. The antitumor activities of the synthetic saponins against human epithelial cervical cancer cell (HeLa) were preliminarily evaluated by means of CCK-8 assay. An L-rhamnosyl analog was discovered to display stronger inhibitory activity (IC50 3.3 μM) than TAIII (IC50 10.7 μM) to HeLa cell. Supplemental materials are available for this article. Go to the publisher's online edition of Journal of Carbohydrate Chemistry to view the free supplemental file.  相似文献   
996.
综述了改进催化抗体催化效率的可能方法 ,包括较好的半抗原、广泛的筛选、工程化及选择优化等  相似文献   
997.
Since the appearance of monolithic silica, much work has been done describing the properties of monolithic silica columns. Meanwhile the transferability of analytical methods from conventional to monolithic silica columns has been intensively investigated [1-5]. RP HPLC method development strategies for conventional columns should be updated or scaled to meet the higher performing monolithic column technology. Because of the high permeability of monolithic silica columns it should be possible to decrease the time for method development by applying high isocratic flow rates. Here we suggest a clear strategy for method development using monolithic columns. The strategy will be applicable for various sample compositions, e. g., acidic, basic, or neutral. The applicability of monolithic columns for especially complex separations of basic mixtures without the need of using a highly basic mobile phase that harms the column will be pointed out in this work. This work will describe in detail the actual method development process. For better understanding of our strategy, the influence of flow rate, column length, mobile phase composition, pH, and temperature will be discussed. Details about the application of a flow program will be mentioned.  相似文献   
998.
文章在分析传统物理实验教学方法优缺点的基础上,明确提出了"先行组织者"教学策略的概念及理论,接着以具体的实验为例,研究了"先行组织者"教学策略在大学基础物理实验中的实践应用,并调查分析了"先行组织者"教学策略的正确运用对学习者的认知结构和学习效果的积极影响.结果显示,恰当、适时地应用"先行组织者"教学策略能够有效加强学生对实验知识的全面掌握,培养学生科学的创新思维,促进基础物理实验教学的变革和发展.  相似文献   
999.
For the Optical Burst Switched (OBS) System, a new resource reservation strategy TAW+ is presented in the Intra-Domain Network Statue Model (INSM). By promptly using the control signal channel to update the INSM, better decisions are made in selecting optical path and assigning wavelength at each OBS network edge node, which can make the node to avoid reserving those being used link resources. Besides, a time slot is introduced to detect the latent collision, which not only can achieve the goal in preventing the forthcoming collision effectively, but also can better support multi-priority QoS. Furthermore, Virtual Configuration Table (VCT) at the network core node is further proposed to resolve collisions without bandwidth wastage. The analysis and simulation results verify the feasibility of the proposed strategy in the OBS network, show the enhancing of the network state awareness capability at edge node in lack of the optical conversion capability and optical buffer, and improve the effect on the data burst drop probability and QoS supports.  相似文献   
1000.
A mixed strategy of the exit selection in a pedestrian evacuation simulation with multi-exits is constructed by fusing the distance-based and time-based strategies through a cognitive coefficient, in order to reduce the evacuation imbalance caused by the asymmetry of exits or pedestrian layout, to find a critical density to distinguish whether the strategy of exit selection takes effect or not, and to analyze the exit selection results with different cognitive coefficients. The strategy of exit selection is embedded in the computation of the shortest estimated distance in a dynamic parameter model, in which the concept of a jam area layer and the procedure of step-by-step expending are introduced. Simulation results indicate the characteristics of evacuation time gradually varying against cognitive coefficient and the effectiveness of reducing evacuation imbalance caused by the asymmetry of pedestrian or exit layout. It is found that there is a critical density to distinguish whether a pedestrian jam occurs in the evacuation and whether an exit selection strategy is in effect. It is also shown that the strategy of exit selection has no effect on the evacuation process in the no-effect phase with a low density, and that evacuation time and exit selection are dependent on the cognitive coefficient and pedestrian initial density in the in-effect phase with a high density.  相似文献   
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