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| 1 | Small molecule inhibitors reveal allosteric regulation of USP14 via steric blockade显示文摘The ubiquitin system is important for drug discovery,and the discovery of selective small-molecule inhibitors of deubiquitinating enzymes (DUBs) remains an active yet extremely challenging task. With a few exceptions,previously developed inhibitors have been found to bind the evolutionarily conserved catalytic centers of DUBs,resulting in poor selectivity. The small molecule IU1 was the first-ever specific inhibitor identified and exhibited surprisingly excellent selectivity for USP14 over other DUBs. However,the molecular mechanism for this selectivity was elusive. Herein,we report the high-resolution co-crystal structures of the catalytic domain of USP14 bound to IU1 and three IU1 derivatives. All the structures of these complexes indicate that IU1 and its analogs bind to a previously unknown steric binding site in USP14,thus blocking the access of the C-terminus of ubiquitin to the active site of USP14 and abrogating USP14 activity. Importantly,this steric site in USP14 is very unique,as suggested by structural alignments of USP14 with several known DUB X-ray structures. These results,in conjunction with biochemical characterization,Indicate a coherent steric blockade mechanism for U5P14 inhibition by compounds of the IU series. In light of the recent report of steric blockade of USP7 by FT671,this work suggests a potential generally applicable allosteric mechanism for the regulation of DUBs via steric blockade,as showcased by our discovery of IU1-248 which is 10-fold more potent than IU1. | Yiwei Wang Yuxuan Jiang Shan Ding Jiawang Li Ningjing Song Yujing Ren Danning Hong Cai Wu Bin Li Feng Wang Wei He Jiawei Wang Ziqing Mei | 2018 | Cell Research2018，28，12： | 15 |
| 2 | Biodegradation behavior of magnesium and ZK60 alloy in artificial urine and rat models显示文摘In this work, the biodegradable and histocompatibility properties of pure Mg and ZK60 alloy wereinvestigated as new temporary implants for urinary applications. The corrosion mechanism in artificialurine was proposed using electrochemical impedance spectroscopy and potentiodynamic polarizationtests. The corrosion potential of pure magnesium and ZK60 alloy were -1820 and -1561 mV, respectively,and the corrosion current densities were 59.66 ± 6.41 and 41.94 ± 0.53 μA cm^-2, respectively. Thein vitro degradation rates for pure Mg and ZK60 alloy in artificial urine were 0.382 and 1.023 mm/y,respectively, determined from immersion tests. The ZK60 alloy degraded faster than the pure Mg in bothartificial urine and in rat bladders (the implants of both samples are ø 3 mm × 5 mm). Histocompatibilityevaluations showed good histocompatibility for the pure Mg and ZK60 alloy during the 3 weeks postimplantationin rat bladders, and no harm was observed in the bladder, liver and kidney tissues. Theresults provide key information on the degradation properties and corrosion mechanism of pure Mg andZK60 alloy in the urinary system. | Shiying Zhang Yanze Bi Jianye Li Zhenguo Wang Jingmin Yan Jiawang Song Haibo Sheng Heqing Guo Yan Li | 2017 | Bioactive Materials2017，2，2： | 4 |
| 3 | Static mechanics analysis of no bumping no vibration welding structure with double-inclined surface for high-speed & heavy-load CWR显示文摘It is known from our former theoretical analysis that the single-inclined welding surface which is inclined towards the transverse direction of the rail can only eliminate vertical bumping, and the single-inclined welding surface which is inclined towards the vertical direction of the rail can only eliminate lateral vibration. In this paper, we put forward a welding structure of double-inclined welding surface to eliminate the vertical bumping and lateral vibration at the same time, and analyze the stress state of continuous welded rail (CWR) by combining geometrical azimuth. Furthermore, the increase of bearing capacity of CWR with the double-inclined welding surface is theoretically analyzed. | SONG YuQuan WANG MingHui SONG JiaWang | 2011 | Science China(Technological Sciences)2011，54，3： | 1 |
| 4 | Mechanical analysis of temperature impact on stability during superplastic tensile deformation显示文摘Based on state equation that stress is the function of strain, strain-rate and temperature, the paper establishes the differential constitutive equation used for analyzing load-stability and the variational constitutive equation used for analyzing geometry-stability during superplastic tensile deformation, which contain strain hardening index, strain-rate sensitivity index, temperature sensitivity index introducted for the first time and temperature undulation index introducted for the first time in the paper. And then, based on the universal condition of plastic elementary theory, the paper analyzes load-stability and geometry-stability under continuously rising temperature and under the non-uniform temperature along the axes of specimen respectively. The results prove the impact of continuously rising speed and non-uniform value of temperature on deformation stability is that the faster temperature rises and the more non-uniform temperature is, the smaller the corresponding uniform strain of load-stability and geometry-stability are; strain hardening index is the necessary condition of stability during superplastic tensile deformation, and geometry-instability will not happen when load-instability occurs, but happen when uniform deformation has lasted after load-instability; in the superplastic temperature field, constant temperature is not necessary condition of superplasticitiy, but during the deformation, the slower temperature rises and the more uniform temperature is, the more stable deformation is. | SONG Yuquan GUAN Zhiping WANG Minghui SONG Jiawang | 2006 | Science China(Technological Sciences)2006，49，6： | 0 |
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