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Jian Ren,Xiao Xiao,Li Ruofei,Lv Cheng,Zhang Yu,Leiming Wang,Tao Hong,Hongqi Zhang,Wang Yibo 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Cavernous malformations (CMs) invading the central nervous system occur in ~0.16–0.4% of the general population, often resulting in hemorrhages and focal neurological deficits. Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of CMs in humans. Herein, we performed single-cell RNA sequencing (scRNA-seq) analysis on unselected viable cells from twelve human CM samples and three control samples. A total of 112,670 high-quality cells were clustered into 11 major cell types, which shared a number of common features in CMs harboring different genetic mutations. A new EC subpopulation marked with PLVAP was uniquely identified in lesions. The cellular ligand‒receptor network revealed that the PLVAP-positive EC subcluster was the strongest contributor to the ANGPT and VEGF signaling pathways in all cell types. The PI3K/AKT/mTOR pathway was strongly activated in the PLVAP-positive subcluster even in non-PIK3CA mutation carriers. Moreover, endothelial-to-mesenchymal transition (EndMT) cells were identified for the first time in CMs at the single-cell level, which was accompanied by strong immune activation. The transcription factor SPI1 was predicted to be a novel key driver of EndMT, which was confirmed by in vitro and in vivo studies. A specific fibroblast-like phenotype was more prevalent in lesion smooth muscle cells, hinting at the role of vessel reconstructions and repairs in CMs, and we also confirmed that TWIST1 could induce SMC phenotypic switching in vitro and in vivo. Our results provide novel insights into the pathomechanism decryption and further precise therapy of CMs.
Experimental study of the association between sandstone size effect and strain rate effect
Siming Kao,Guang-Ming Zhao,Wensong Xu,Xiang Cheng,Chunliang Dong,Ruofei Zhang 대한기계학회 2020 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.34 No.9
The association between sandstone size effect and strain rate effect were investigated experimentally with a split Hopkinson pressure bar (SHPB) system. The sandstone samples with Φ50 mm and different lengths were loaded under the constant ratio of punch velocity to sample length to study their size effects. Sandstone samples with constant length of 25 mm were taken as the reference to study their strain rate effects. Results indicate that, under the same velocity of the punch, strain rate of each sandstone sample is inversely proportional sample length; dynamic strength of sandstone increases with the strain rate and the length to diameter ratio (L/D), and presents a quadratic curvilinear relation with strain rate while presenting a cubic curvilinear relation with sample L/D; the reasonable L/D of Φ50 mm sandstone samples ranges from 0.5 to 0.8; that dissipated energy can present a fixed proportional relation with punch kinetic energy is unrelated to sample length.