Coupled influence of tectonics, climate, and surface processes on landscape evolution in southwestern North America.

The Cenozoic landscape evolution in southwestern North America is ascribed to crustal isostasy, dynamic topography, or lithosphere tectonics, but their relative contributions remain controversial. Here we reconstruct landscape history since the late Eocene by investigating the interplay between mantle convection, lithosphere dynamics, climate, and surface processes using fully coupled four-dimensional numerical models. Our quantified depth-dependent strain rate and stress history within the lithosphere, under the influence of gravitational collapse and sub-lithospheric mantle flow, show that high gravitational potential energy of a mountain chain relative to a lower Colorado Plateau can explain extension directions and stress magnitudes in the belt of metamorphic core complexes during topographic collapse. Profound lithospheric weakening through heating and partial melting, following slab rollback, promoted this extensional collapse. Landscape evolution guided northeast drainage onto the Colorado Plateau during the late Eocene-late Oligocene, south-southwest drainage reversal during the late Oligocene-middle Miocene, and southwest drainage following the late Miocene.

[Study on mechanism of curcumol against liver fibrosis based on autophagy and apoptosis of hepatic stellate cells].

The present study clarified the molecular mechanism of curcumol against liver fibrosis based on its effects on the autopha-gy and apoptosis of hepatic stellate cells. The hepatic stellate cells were divided into a blank control group, a transforming growth factor-ß1(TGF-ß1)(10 ng·mL~(-1)) group, and low-(12.5 mg·L~(-1)), medium-(25 mg·L~(-1)), and high-dose(50 mg·L~(-1)) curcumol groups. The effect of curcumol on the viability of hepatic stellate cells induced by TGF-ß1 was detected by the MTT assay kit. The apo-ptosis in each group was determined by flow cytometry. Real-time fluorescence-based quantitative PCR(RT-PCR) was employed for the detection of mRNA expression of α-smooth muscle actin(α-SMA), type Ⅰ collagen(collagen Ⅰ), and type Ⅲ collagen(collagen Ⅲ). Western blot was used to detect the protein expression of p62, microtubule-associated protein 1 light chain 3(LC3), beclin1, B cell lymphoma 2(Bcl-2), and Bcl-2-associated X protein(Bax). Transmission electron microscopy(TEM) was used to observe cell morphology and autophagosome formation in each group. The autophagic flux was observed after cell infection with adenovirus under double fluorescence labeling. The cell viability assay revealed that compared with the TGF-ß1 group, the curcumol groups showed significantly decreased cell viability. The apoptosis assay showed that the apoptosis rates of the curcumol groups were significantly higher than that of the TGF-ß1 group. RT-PCR indicated that the mRNA expression of α-SMA, collagenⅠ, and collagen Ⅲ in the curcumol groups was significantly lower than that of the TGF-ß1 group. Western blot showed that the expression of p62, LC3, beclin1, Bcl-2, and Bax in the curcumol groups was significantly different from that in the TGF-ß1 group. As demonstrated by TEM, compared with the TGF-ß1 group, the curcumol groups showed significantly increased autophagosomes. The detection of autophagic flow by the adenovirus under double fluorescence labeling showed that autolysosomes in the curcumol groups were significantly increased compared with those in the TGF-ß1 group. Curcumol can induce the autophagy and apoptosis of hepatic stellate cells, which may be one of its anti-liver fibrosis mechanisms.