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With the escalation of global climate change and human activity, geohazards become increasingly frequent which cause severe casualties and property losses to local communities. To alleviate this situation and provide scientific guidance for risk reduction, it is imperative to address some of the basic questions related to geohazards, including: i) how to detect active geohazards (AGs) rapidly and automatically over a wide area; ii) how to determine the region with a high level of hazard activity; iii) what are the primary conditioning factors (CFs) of AGs; and iv) do factors operate independently or are they interconnected. To tackle these issues, we propose a universally applicable framework for wide area automated detection of AGs. The framework is based on multi-source Earth observations which capture surface deformation ranging from millimeters to meters. Our study has focused on the Hexi Corridor (HXC) in Gansu Province, China, covering an area of 210,000 km2 with a length of 1100 km. First, we construct an AGs database for the HXC with high automatic and rapid update capabilities, including a total of 4492 AGs (3652 active landslides and 840 land subsidence areas). Second, using the Geographic Detectors method, we determine the primary CFs including elevation, land surface temperature, and precipitation. We find that faults exert greater control over very slow-moving landslides, but are less effective over slow-moving landslides. Third, we analyzed the interactive effects of dual CFs on geohazard actives. Any interaction effect of dual CFs contributes to the bivariate enhancement of geohazard activity. This study significantly enhances the capabilities of the wide area automated detection of AGs, and provides a crucial dataset for hazard prediction and mitigation along the HXC.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) clinically reduce atherosclerosis and lower blood pressure. However, their impact on endothelial dysfunction in type 2 diabetes (T2D) remains unclear. In this study, we investigated the protective effect and underlying mechanism of the SGLT2 inhibitor dapagliflozin in diabetes. Methods: Vascular reactivity was measured to assess the vasoprotective effect of dapagliflozin in a mouse model of high glucose (HG)-induced T2D. Pulse wave velocity was measured to quantify arterial stiffness. Protein expression was assessed by western blotting and immunofluorescence, oxidative stress was evaluated using dihydroethidium, nitric oxide was evaluated using the Griess reaction, and cellular senescence was assessed based on senescence-associated beta-galactosidase (SA‐β‐gal) activity and the expression of senescence markers. Furthermore, the endothelial nitric oxide synthase (eNOS) acetylation status was determined and eNOS interactions with SIRT1 were evaluated by coimmunoprecipitation assays. Results: Dapagliflozin protected against impaired endothelium-dependent vasorelaxation and improved arterial stiffness in the mouse model of T2D; mouse aortas had significantly reduced levels of senescence activity and senescence-associated inflammatory factors. HG-induced increases in senescence activity, protein marker levels, and oxidative stress in vitro were all ameliorated by dapagliflozin. The decreases in eNOS phosphorylation and nitric oxide (NO) production in senescent endothelial cells were restored by dapagliflozin. SIRT1 expression was reduced in HG-induced senescent endothelial cells, and dapagliflozin restored SIRT1 expression. SIRT1 inhibition diminished the antisenescence effects of dapagliflozin. Coimmunoprecipitation showed that SIRT1 was physically associated with eNOS, suggesting that the effects of dapagliflozin are dependent on SIRT1 activation. Conclusion: These findings indicate that dapagliflozin protects against endothelial cell senescence by regulating SIRT1 signaling in diabetic mice.

Due to the complex diagenesis process, basalt usually contains defects in the form of amygdales formed by diagenetic bubbles, which affect its mechanical properties. In this study, a synthetic rock mass method (SRM) based on the combination of discrete fracture network (DFN) and finite-discrete element method (FDEM) is applied to characterizing the amygdaloidal basalt, and to systematically exploring the effects of the development characteristics of amygdales and sample sizes on the mechanical properties of basalt. The results show that with increasing amygdale content, the elastic modulus (E) increases linearly, while the uniaxial compressive strength (UCS) shows an exponential or logarithmic decay. When the orientation of amygdales is between 0° and 90°, basalt shows a relatively pronounced strength and stiffness anisotropy. Based on the analysis of the geometric and mechanical properties, the representative element volume (REV) size of amygdaloidal basalt blocks is determined to be 200 mm, and the mechanical properties obtained on this scale can be regarded as the properties of the equivalent continuum. The results of this research are of value to the understanding of the mechanical properties of amygdaloidal basalt, so as to guide the formulation of engineering design schemes more accurately.

Due to the large differences in physico-mechanical properties of composite strata, jamming, head sinking and other serious consequences occur frequently during tunnel boring machine (TBM) excavation. To analyse the stability of surrounding rocks in composite strata under the disturbance of TBM excavation, a geomechanical model test was carried out based on the Lanzhou water supply project. The evolution patterns and distribution characteristics of the strain, stress, and tunnel deformation and fracturing were analysed. The results showed that during TBM excavation in the horizontal composite formations (with upper soft and lower hard layers and with upper hard and lower soft layers), a significant difference in response to the surrounding rocks can be observed. As the strength ratio of the surrounding rocks decreases, the ratio of the maximum strain of the hard rock mass to that of the relatively soft rock mass gradually decreases. The radial stress of the relatively soft rock mass is smaller than that of the hard rock mass in both types of composite strata, indicating that the weak rock mass in the composite formation results in the difference in the mechanical behaviours of the surrounding rocks. The displacement field of the surrounding rocks obtained by the digital speckle correlation method (DSCM) and the macro-fracture morphology after tunnel excavation visually reflected the deformation difference of the composite rock mass. Finally, some suggestions and measures were provided for TBM excavation in composite strata, such as advance geological forecasting and effective monitoring of weak rock masses.

Cryptocrystalline basalt is one of the two major types of rocks exposed in the super large-scale underground powerhouse in Baihetan hydropower station in China. The rock of this type shows various site-specific mechanical responses (e.g. fragmentation, fracturing, and relaxation) during excavation. Using conventional triaxial testing facility MTS 815.03, we obtained the stress–strain curves, macroscopic failure characteristics, and strength characteristics of cryptocrystalline basalt. On this basis, evolution of crack initiation and propagation was explored using the finite-discrete element method (FDEM) to understand the failure mechanism of cryptocrystalline basalt. The test results showed that: (1) under different confining stresses, almost all the pre-peak stress–strain curves of cryptocrystalline basalt were linear and the post-peak stresses decreased rapidly; (2) the cryptocrystalline basalt showed a failure mode in a form of fragmentation under low and medium confining stresses while fragmentation-shear coupling failure dominated at high confining stresses; and (3) the initial strength ratio (σci/σf, where σci and σf are the crack initiation strength and peak strength, respectively) ranged from 0.45 to 0.55 and the damage strength ratio (σcd/σf, where σcd is the crack damage strength) exceeded 0.9. The stress–strain curve characteristics and failure modes of cryptocrystalline basalt could be reflected numerically. For this, FDEM simulation was employed to reveal the characteristics of cryptocrystalline basalt, including high σcd/σf values and rapid failure after σcd, with respect to the microscopic characteristics of mineral structures. The results showed that the fragmentation characteristics of cryptocrystalline basalt were closely related to the development of tensile cracks in rock samples prior to failure. Moreover, the decrease in degree of fragmentation with increasing confining stress was also correlated with the dominant effect of confining stress on the tensile cracks. Keywords: Baihetan hydropower station, Cryptocrystalline basalt, Deformation and failure characteristics, Characteristic strengths, Crack propagation evolution

Sirtuin type 1 (Sirt1) and protein kinase B (Akt2) are associated with development of obesity and inflammation, but the molecular mechanisms of Sirt1 and Akt2 interaction on adipose inflammation remain unclear. To explore these mechanisms, a mouse model was used. Mice were fed with a high-fat diet (HFD) for 8 weeks, with interventions of resveratrol (RES) or nicotinamide (NAM) during the last 15 days. The HFD reduced Sirt1 mRNA in adipose tissue and elevated interleukin-6 (IL-6) expression. RES reduced the adipose tissue weight, increased the Sirt1 mRNA level, and reduced both mRNA and protein levels of IL-6, MCP-1, inducible nitric oxide synthase, and TNF-α by inhibiting phosphorylation of Akt2 in adipose tissue. Additionally, macrophage type I marker genes were reduced while macrophage type II marker genes were elevated by RES addition. Moreover, activation of Akt2 signal by using insulin significantly blunted the inhibitory effect of RES on adipose inflammation. Immunoprecipitation assay demonstrated that RES enhances the protein-protein interaction between Sirt1 and Akt2, but NAM inhibits this interaction. Furthermore, Sirt1 significantly reduced the levels of raptor and inactivated mammalian target of rapamycin (mTOR)C1 signal by interacting with Akt2, and confirmed that RES attenuated adipose inflammation by inhibiting the mTOR/S6K1 pathway via rapamycin.

Forkhead box C2 (Foxc2) protein is a transcription factor in regulation of development, metabolism, and immunology. However, the regulatory mechanisms of Foxc2 on proliferation and apoptosis of preadipocytes are unclear. In this study, we found that high-fat-diet-induced obesity elevated the expression of Foxc2 and cyclin E after 6 weeks. Additionally, Foxc2 suppressed preadipocyte differentiation, increased cell counts and augmented G1-S transition of preadipocytes, along with the elevation of cyclin E expression and the reduction levels of p27 and p53. Furthermore, Foxc2 knockdown reduced early apoptotic cells with accompanying reduction of mitochondrial membrane potential and increased fragmentation of genomic DNA. We show that Foxc2 reduces the expression of Bax, caspase-9, and caspase-3 in both serum-starved and palmitic acid-induced cell apoptotic models, which confirms the anti-apoptotic role of Foxc2. Moreover, the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)C1 signaling pathway and the ERK/mTORC1 signaling pathway were activated along with preadipocyte proliferation in response to Foxc2 overexpression, whereas apoptosis marker genes were downregulated during this process. Those effects were blocked by the interference of Foxc2 or signal pathways specific inhibitors. These data collectively reveal that Foxc2 enhances proliferation of preadipocytes and inhibits apoptosis of preadipocytes by activating the Akt/mTORC1 and ERK/mTORC1 signaling pathways.