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您的检索式：作者名="Dai Chunxi"
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| 1 | A unique hyperdynamic dimer interface permits small molecule perturbation of the melanoma oncoprotein MITF for melanoma therapy显示文摘Microphthalmia transcription factor(MITF)regulates melanocyte development and is the“lineage-specific survival”oncogene of melanoma.MITF is essential for melanoma initiation,progression,and relapse and has been considered an important therapeutic target;however,direct inhibition of MITF through small molecules is considered impossible,due to the absence of a ligand-binding pocket for drug design.Here,our structural analyses show that the structure of MITF is hyperdynamic because of its out-of-register leucine zipper with a 3-residue insertion.The dynamic MITF is highly vulnerable to dimer-disrupting mutations,as we observed that MITF loss-of-function mutations in human Waardenburg syndrome type 2 A are frequently located on the dimer interface and disrupt the dimer forming ability accordingly.These observations suggest a unique opportunity to inhibit MITF with small molecules capable of disrupting the MITF dimer.From a high throughput screening against 654,650 compounds,we discovered compound TT-012,which specifically binds to dynamic MITF and destroys the latter’s dimer formation and DNA-binding ability.Using chromatin immunoprecipitation assay and RNA sequencing,we showed that TT-012 inhibits the transcriptional activity of MITF in B16F10 melanoma cells.In addition,TT-012 inhibits the growth of high-MITF melanoma cells,and inhibits the tumor growth and metastasis with tolerable toxicity to liver and immune cells in animal models.Together,this study demonstrates a unique hyperdynamic dimer interface in melanoma oncoprotein MITF,and reveals a novel approach to therapeutically suppress MITF activity. | Zaizhou Liu Kaige Chen Jun Dai Peng Xu Wei Sun Wanlin Liu Zhixin Zhao Steven P.Bennett Peifeng Li Tiancheng Ma Yuqi Lin Akinori Kawakami Jing Yu Fei Wang Chunxi Wang Miao Li Peter Chase Peter Hodder Timothy P.Spicer Louis Scampavia Chunyang Cao Lifeng Pan Jiajia Dong Yong Chen Biao Yu Min Guo Pengfei Fang David E.Fisher Jing Wang | 2023 | Cell Research2023，33，1： | 0 |
| 2 | Simulation and experiment of starting transient flow field of the hydrostatic bearing based on dynamic mesh method显示文摘A new method is developed to assess and analyze the dynamic performance of hydrostatic bearing oil film by using an amulets-layer dynamic mesh technique. It is implemented using C Language to compile the UDF program of a single oil film of the hydrostatic bearing. The effects of key lubrication parameters of the hydrostatic bearing are evaluated and analyzed under various working conditions,i.e. under no-load,a load of 40 t,a full load of 160 t,and the rotation speed of 1r/min,2r/min,4r/min,8r/min,16r/min,32r/min. The transient data of oil film bearing capacity under different load and rotation speed are acquired for a total of 18 working conditions during the oil film thickness changing. It allows the effective prediction of dynamic performance of large size hydrostatic bearing. Experiments on hydrostatic bearing oil film have been performed and the results were used to define the boundary conditions for the numerical simulations and validate the developed numerical model. The results showed that the oil film thickness became thinner with the increase of the operating time of the hydrostatic bearing,both the oil film rigidity and the oil cavity pressure increased significantly,and the increase of the bearing capacity was inversely proportional to the cube of the change of the film thickness. Meanwhile,the effect of the load condition on carrying capacity of large size static bearing was more important than the speed condition. The error between the simulation value and the experimental value was 4.25%. | 张艳芹 Kong Xiangbin Guo Lili Yu Xiaodong Dai Chunxi Shao Junpeng | 2017 | High Technology Letters2017，23，3： | 0 |
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