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The low overall survival rate of patients with pancreatic cancer has driven research to seek a new therapeutic protocol. Radiotherapy (RT) is frequently an option in the neoadjuvant or palliative settings for pancreatic cancer treatment. This study explored the effect of RT protocols on the tumor microenvironment (TME) and their consequent impact on anti-programmed cell death ligand-1 (PD-L1) therapy. Using a murine orthotopic pancreatic tumor model, UN-KC-6141, RT-disturbed TME was examined by immunohistochemical staining. The results showed that ablative RT is more effective than fractionated RT at recruiting T cells. On the other hand, fractionated RT induces more myeloid-derived suppressor cell infiltration than ablative RT. The RT-disturbed TME presents a higher perfusion rate per vessel. The increase in vessel perfusion is associated with a higher amount of anti-PD-L1 antibody being delivered to the tumor. Animal survival is increased by anti-PD-L1 therapy after ablative RT, with 67% of treated animals surviving more than 30 days after tumor inoculation compared to a median survival time of 16.5 days for the control group. Splenocytes isolated from surviving animals were specifically cytotoxic for UN-KC-6141 cells. We conclude that the ablative RT-induced TME is more suited than conventional RT-induced TME to combination therapy with immune checkpoint blockade.  相似文献   
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Mobile Networks and Applications - Aiming at the problems of large data volume, long calculation time, and information feedback speed in traditional virtual augmented reality-based scenes, this...  相似文献   
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Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.  相似文献   
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Ce:Y3Al5O12 transparent ceramics (TCs) with appropriate emission light proportion and high thermal stability are significant to construct white light emitting diode devices with excellent chromaticity parameters. In this work, strategies of controlling crystal-field splitting around Ce3+ ion and doping orange-red emitting ion, were adopted to fabricate Ce:(Y,Tb)3(Al,Mn)5O12 TCs via vacuum sintering technique. Notably, 85.4 % of the room-temperature luminescence intensity of the TC was retained at 150 °C, and the color rendering index was as high as 79.8. Furthermore, a 12 nm red shift and a 16.2 % increase of full width at half maximum were achieved owing to the synergistic effects of Tb3+ and Mn2+ ions. By combining TCs with a 460 nm blue chip, a warm white light with a low correlated color temperature of 4155 K was acquired. Meanwhile, the action mechanism of Tb3+ ion and the energy transfer between Ce3+ and Mn2+ ions were verified in prepared TCs.  相似文献   
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Zhao  Kui  He  Fangmin  Meng  Jin  Wu  Hao  Zhang  Lei 《Wireless Networks》2021,27(3):1671-1681
Wireless Networks - In such mobile platforms as ships and aircraft, the detection and reconnaissance devices are near to the communication facilities. When working at the same time, they will...  相似文献   
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为探讨喷油方式对齿面温度的影响,以斜齿轮为研究对象,通过CFD仿真和试验研究不同喷油方式对斜齿轮齿面温度的影响。针对斜齿轮喷油润滑过程的特点,分析其齿面摩擦生热量,简化轮齿喷油润滑计算模型,并基于CFX进行齿面对流换热仿真研究,得到了不同喷油方式下的齿面温度;基于功率开放式斜齿轮试验平台,对不同喷油方式下的齿面温度进行了试验测量,与仿真计算结果进行对比分析。结果表明:在高速重载斜齿轮传动系统中,啮出侧喷油润滑的方式比啮入侧喷油润滑方式的冷却降温效果要好。  相似文献   
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