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These results provide the first genetic evidence supporting the central role of mitochondrial Complex I in I/R injury of mouse heart. The study also suggests that both forward and reverse electron flows underlie oxidative cardiomyocyte death during reperfusion.
Despite longstanding efforts to develop cytoprotective drugs against ischemia/reperfusion (IR) injuries, there remains no effective therapeutics to treat hypoxic injury. The failure of traditional strategies at solving this problem suggests the need for novel and unbiased approaches that can lead to previously unsuspected targets and lead compounds. Towards this end, we report here a unique small molecule screen in the nematode C. elegans for compounds that improve recovery when applied after the hypoxic insult, using a C. elegans strain engineered to have delayed cell non-autonomous death. In a screen of 2000 compounds, six were found to produce significant protection of C. elegans from delayed death. Four of the compounds were tested in an ex vivo mouse heart ischemia/reperfusion model and two, meclocycline and 3-amino-1,2,4-triazole, significantly reduced infarction size. Our work demonstrates the feasibility of this novel C. elegans screen to discover hypoxia protective drugs that are also protective in a mammalian model of hypoxic injury.
The detection ability of SO2 cameras has been improved effectively, while the calibration is still the main factor that limits their measurement accuracy. This paper presents a nonlinear calibration theory by considering the effect of light dilution due to the path radiance as well as the dependence of plume aerosol on scattering wavelength. This new spectral calibration method is used to retrieve the SO2 column density and emission rate of the Etna volcano. Results show that, compared with the DOAS calibration approach, the inversion error can be reduced by 13% if the new spectral calibration is adopted. The superiority of the proposed method will become more obvious for long-distance detection of optically thick plumes.
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