| 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 | Theory,technology and practice of shale gas three-dimensional development:A case study of Fuling shale gas field in Sichuan Basin,SW China显示文摘In the Jiaoshiba block of the Fuling shale gas field,the employed reserves and recovery factor by primary well pattern are low,no obvious barrier is found in the development layer series,and layered development is difficult.Based on the understanding of the main factors controlling shale gas enrichment and high production,the theory and technology of shale gas three-dimensional development,such as fine description and modeling of shale gas reservoir,optimization of three-dimensional development strategy,highly efficient drilling with dense well pattern,precision fracturing and real-time control,are discussed.Three-dimensional development refers to the application of optimal and fast drilling and volume fracturing technologies,depending upon the sedimentary characteristics,reservoir characteristics and sweet spot distribution of shale gas,to form'artificial gas reservoir'in a multidimensional space,so as to maximize the employed reserves,recovery factor and yield rate of shale gas development.In the research on shale gas three-dimensional development,the geological+engineering sweet spot description is fundamental,the collaborative optimization of natural fractures and artificial fractures is critical,and the improvement of speed and efficiency in drilling and fracturing engineering is the guarantee.Through the implementation of three-dimensional development,the overall recovery factor in the Jiaoshiba block has increased from 12.6%to 23.3%,providing an important support for the continuous and stable production of the Fuling shale gas field. | SUN Huanquan CAI Xunyu HU Degao LU Zhiyong ZHAO Peirong ZHENG Aiwei LI Jiqing WANG Haitao | 2023 | Petroleum Exploration and Development2023，50，3： | 1 |
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