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| 1 | SLC1A1-mediated cellular and mitochondrial influx of R-2-hydroxyglutarate in vascular endothelial cells promotes tumor angiogenesis in IDH1-mutant solid tumors显示文摘Muta nt isocitrate dehydrog en ase 1(mlDH1)drives tumorigenesis via produci ng on cometabolite R-2-hydroxyglutarate(R-2-HG)across various tumor types.However,mlDHl in hibitors appear only effective in hematological tumors.The therapeutic ben efit in solid tumors remains elusive,likely due to the complex tumor microenvironment.In this study,we discover that R-2-HG produced by IDH1-mutant tumor cells is preferentially imported into vascular endothelial cells and remodels mitochondrial respiration to promote tumor angiogenesis,conferring a therapeutic vulnerability in IDH1-mutant solid tumors.Mechanistically,SLC1 Alz a Na'-depe ndent glutamate tran sporter that is prefere ntially expressed in en dothelial cells,facilitates the in flux of R-2-HG from the tumor microenvironment into the endothelial cells as well as the intracellular trafficking of R-2-HG from cytoplasm to mitochondria.R-2-HG hijacks SLC1A1 to promote mitochondrial Na^(+)/Ca^(2+)exchange,which activates the mitochondrial respiratory chain and fuels vascular en dothelial cell migratio n in tumor an giogenesis.SLC1A1 deficiency in mice abolishes mlDHl-promoted tumor an giogenesis as well as the therapeutic benefit of mlDHl in hibitor in solid tumors.Moreover,we report that HH2301,a newly discovered mlDHl inhibitor,shows promising efficacy in treating IDH1-mutant cholangiocarcinoma in preclinical models.Together,we identify a new role of SLC1A1 as a gatekeeper of R-2-HG-mediated crosstalk between IDH1-mutant tumor cells and vascular en dothelial cells,and dem on strate the therapeutic potential of mlDHl in hibitors in treating IDH1-muta nt solid tumors via disrupting R-2-HG-promoted tumor angiogenesis. | Xiaomin Wang Ziqi Chen Jun Xu Shuai Tang Nan An Lei Jiang Yixiang Zhang Shaoying Zhang Qingli Zhang Yanyan Shen Shijie Chen Xiaojing Lan Ting Wang Linhui Zhai Siyuwei Cao Siqi Guo Yingluo Liu Aiwei Bi Yuehong Chen Xiameng Gai Yichen Duan Ying Zheng Yixian Fu Yize Li Liang Yuan Linjiang Tong Kun Mo Mingcheng Wang Shu-Hai Lin Minjia Tan Cheng Luo Yi Chen Jia Liu Qiansen Zhang Leping Li Min Huang | 2022 | Cell Research2022，32，7： | 2 |
| 2 | A heuristic approximately duplicate records detection algorithm based on attributes analysis显示文摘 | Zhang Zhongnan He Ling Tan Yize | 2012 | International Journal of Digital Content Technology&its Applications2012，6，4： | 1 |
| 3 | Early exposure to sevoflurane inhibits Ca 2+ channels activity in hippocampal CA1 pyramidal neurons of developing rats显示文摘 | Aili Liu Yize Li Tao Tan Xin Tian | 2014 | Brain Research2014，，： | 1 |
| 4 | Amorphous calcium magnesium phosphate nanocomposites with superior osteogenic activity for bone regeneration显示文摘The seek of bioactive materials for promoting bone regeneration is a challenging and longterm task.Functionalization with inorganic metal ions or drug molecules is considered effective strategies to improve the bioactivity of various existing biomaterials.Herein,amorphous calcium magnesium phosphate(ACMP)nanoparticles and simvastatin(SIM)-loaded ACMP(ACMP/SIM)nanocomposites were developed via a simple co-precipitation strategy.The physiochemical property of ACMP/SIM was explored using transmission electron microscope(TEM),Fourier transform infrared spectroscopy(FTIR),powder X-ray diffraction(XRD)and highperformance liquid chromatograph(HPLC),and the role of Mg^(2+) in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure(XANES).After that,the transformation process of ACMP/SIM in simulated body fluid(SBF)was also tracked to simulate and explore the in vivo mineralization performance of materials.We find that ACMP/SIM releases ions of Ca^(2+),Mg^(2+)and PO_(4)^(3),when it is immersed in SBF at 37℃,and a phase transformation occurred during which the initially amorphous ACMP turns into self-assembled hydroxyapatite(HAP).Furthermore,ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells.For the in vivo studies,lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria.ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12weeks.The bioactive ACMP/SIM nanocomposites are promising as bone repair materials.Considering the facile preparation process and superior in vitro/vivo bioactivity,the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications. | Yingying Jiang Shuo Tan Jianping Hu Xin Chen Feng Chen Qianting Yao Zhi Zhou Xiansong Wang Zifei Zhou Yunshan Fan Junjian Liu Yize Lin Lijia Liu Shisheng He | 2021 | Regenerative Biomaterials2021，8，6： | 0 |
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