分类： 药物科学 >> 结构生物学 提交时间： 2024-04-17
摘要： The adenosine A3 receptor (A3AR) belongs to a subfamily of G protein-coupled receptors and is an important therapeutic target for conditions including inflammation and cancer. The clinical compounds CF101 and CF102 are potent and selective A3AR agonists, but the structural basis of their recognition was unknown. Here we present the cryogenic electron microscopy structures of the full-length human A3AR bound to CF101 and CF102 at 3.3-3.2 Å resolution in complex with heterotrimeric Gi protein. These agonists bind within the orthosteric pocket, with their adenine components engaging in conserved interactions while their substituted 3-iodobenzyl groups exhibit different orientations. Swapping extracellular loop 3 (ECL3) of A3AR onto other adenosine receptor subtypes enabled CF101/CF102 binding and receptor activaton, and mutations in key residues, including His3.37, Ser5.42 and Ser6.52 that form a unique subpocket in A3AR, abolished receptor activation, highlighting these structural elements are critical for ligand selectivity. Compared to inactive A2AAR, the A3AR structures reveal conserved mechanism of receptor activation, including an outward shift of TM6. These structures provide key insights into molecular recognition and signaling mechanisms of A3AR, which should aid rational design of subtype-selective ligands targeting this important class of adenosine receptors.
分类： 核科学技术 >> 辐射物理与技术 提交时间： 2024-04-11
Xian-Lin Yang
Chang-Lin Lan
Yu-Ting Wei
Yi Zhang
Gong Jiang
Bo Xie
Yu Liu
Hong-Tao Shen
Xiao-Jun Sun
摘要： Aluminum is the primary structural material in nuclear engineering, and its cross-section induced by 14 MeV neutrons is of great significance. To address the issue of insufficient accuracy for the 27Al(n,2n)26Al reaction cross-section, the activation method and accelerator mass spectrometry (AMS) technique were used to determine the 27Al(n,2n)26Al cross-section, which could be used as a D-T plasma ion temperature monitor in fusion reactors. At the China Academy of Engineering Physics (CAEP), neutron activation was performed using a K-400 neutron generator produced by the T(d,n)4He reaction. The 26Al/27Al isotope ratios were measured using the newly installed GYIG 1 MV AMS at the Institute of Geochemistry, Chinese Academy of Sciences. The neutron flux was monitored by measuring the activity of 92mNb produced by the 93Nb(n,2n)92mNb reaction. The measured results were compared with available data in the experimental nuclear reaction database, and the measured values showed a reasonable degree of consistency with partially available literature data. Thenewly acquired cross-sectional data at 12 neutron energy points through systematic measurements clarified the divergence, which has two different growth trends from the existing experimental values. The obtained results are also compared with the corresponding evaluated database, and the newly calculated excitation functions with TALYS-1.95 and EMPIRE-3.2 codes, the agreement with CENDL-3.2, TENDL-2021 and EMPIRE-3.2 results are generally acceptable. A substantial improvement in the knowledge of the 27Al(n,2n)26Al reaction excitation function was obtained in the present work, which will lay the foundation for the diagnosis of the fusion ion temperature, testing of the nuclear physics model, and evaluation of nuclear data, etc.
分类： 物理学 >> 核物理学 提交时间： 2016-08-30
Wei Hu
Jian Fang
Bo-Xiang Yu
Xuan Zhang
Li Zhou
Xiao Cai
Li-Jun Sun
Wan-Jin Liu
Lan Wang
Jun-Guang Lu
摘要： The liquid scintillator (LS) has been widely utilized in the past, running and future neutrino experiments, and requirement to the LS radio-purity is higher and higher. The water extraction is a powerful method to remove soluble radioactive nuclei, and a mini-extraction station has been constructed. To evaluate the extraction efficiency and optimize the operation parameters, a setup to load radioactivity to LS and a laboratory scale setup to measure radioactivity which use Bi^{212}-Po^{212}-Pb^{208} cascade decay are developed. Experiences from laboratory study will be useful to large scale water extraction plants design and the optimization of working in future.
分类： 物理学 >> 核物理学 提交时间： 2024-03-04
Fang-Lei Zou
Xiao-Jun Sun
Jing-Shang Zhang
Hai-Rui Guo
Yin-Lu Han
Rui-Rui Xu
Xi Tao
Ji-Min Wang
Xiao-Dong Sun
Yuan Tian
Tao Ye
Yong-Li Xu
Chun-Tian Liang
摘要： Based on the unified Hauser–Feshbach and exciton model, which can describe the particle emission processes between discrete energy levels with energy, angular momentum, and parity conservations, a statistical theory of light nucleus reaction (STLN) is developed to calculate the double-differential cross-sections of the outgoing neutron and light charged particles for the proton-induced 6Li reaction. A significant difference is observed between the p + 6Li and p + 7Li reactions owing to the discrepancies in the energy-level structures of the targets. The reaction channels, including sequential and simultaneous emission processes, are analyzed in detail. Taking the double-differential cross-sections of the outgoing proton as an example, the influence of contaminations (such as 1H, 7Li, 12C, and 16O) on the target is identified in terms of the kinetic energy of the first emitted particles. The optical potential parameters of the proton are obtained by fitting the elastic scattering differential cross-sections. The calculated total double-differential cross-sections of the outgoing proton and deuteron at Ep = 14 MeV agree well with the experimental data for different outgoing angles. Simultaneously, the mixed double differential cross-sections of 3He and α are in good agreement with the measurements. The agreement between the measured data and calculated results indicates that the two-body and three-body breakup reactions need to be considered, and the pre-equilibrium reaction mechanism dominates the reaction processes. Based on the STLN model, a PLUNF code for the p + 6Li reaction is developed to obtain an ENDF-6-formatted file of the double-differential cross-sections of the nucleon and light composite charged particles.
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