Krüppel-like factor 8 (KLF8) regulates critical gene transcription associated with different types of cancer. A novel paradigm in tumor biology suggests that the initiation and progression of osteosarcoma (OS) are driven by osteosarcoma stem cell-like cells (OSCs), but the role and underlying mechanisms of KLF8 in OSCs are poorly elucidated. In this study, an obviously increased level of KLF8 is shown in 9 out of 10 primary OS tissues and is associated with the poor progressionfree interval. Significantly, KLF8 expression in CD133+ OSCs is higher than that in CD133-counterparts. By knocking down KLF8 in CD133+ OSCs, we show that si-KLF8-OSCs can hardly form compact spheres. In the meantime, infection with si-KLF8 in CD133+ OSCs results in the downregulation of OCT4 and SOX2; increased adriamycin (ADM) sensitivity; and decreased tumorigenic potential in vivo. Mechanisms study demonstrates that KLF8 directly binds the miR-429 promoter region and regulates its expression transcriptionally. Furthermore, we indicate that miR-429 directly targets SOX2 to mediate cancer stem cell-like features in CD133+ OSCs. In the clinic, miR-429 levels are negatively associated with KLF8 levels in OS, suggesting that an elevated KLF8/miR-429 ratio may have clinical value as a predictive biomarker. In conclusion, targeting the KLF8-miR-429-SOX2 signaling pathway may provide an effective therapeutic approach to suppress the initiation and progression of OS.

Low temperature combustion was developed using a four-cylinder light vehicle diesel engine. Operating conditions considered were 1600 rpm, 1bar and 3bar IMEP. Both EGR and split injection strategy were optimized in order to obtain the lowest BSFC accompanied with a low level of emissions. It was found that a late injection strategy with high levels of EGR rate was required for simultaneous reduction of NOx and soot. However, the fuel consumption remains higher than the conventional combustion regime. Thus, the optimization study of injection parameters to improve the trade-off between NOx and soot emissions while maintaining good fuel efficiency was performed. Several injection pressures were tested. The results showed that as injection pressure increased, NOx emissions increased slightly, soot initially decreased sharply, but further increase of injection pressure on soot was not obvious at low temperature atmosphere, and might lead to increased BSFC. Next, split injection strategy was adopted, optimized pilot injection conditions for minimizing fuel consumption were found at late pilot injection timing with big injection quantity, but little amount of pilot injection could make better comprehensive performance of diesel engine. Through multi-parameter collaborative optimization, the emission reduction path was proposed at operating condition of partial load. Low NOx and soot emissions could be obtained with slightly increase of fuel consumption.

No abstract