Aberrant expression of microRNA (miR)-1 has been observed in many human malignancies. However, the function and underlying mechanism of miR-1 remains elusive. To address the specific role of miR-1 in tumor glycolysis using the gain- or loss-of-function studies. Metabolic studies combined with gene expression analysis were performed in vitro and in vivo. We demonstrated aberrant expression of miR-1 in aerobic glycolysis, the Warburg effect, in cancer cells. MiR-1 suppressed aerobic glycolysis and tumor cell proliferation via inactivation of Smad3 and targeting HIF-1α, leading to reduce HK2 and MCT4 expression, which illustrated a novel pathway to mediate aerobic glycolysis in cancer cells. Overexpression of miR-1 mimics significantly decreased tumor glycolysis, including lactate production and glucose uptake, and cell proliferation, and these effects were reversed by ectopic expression of Smad3. Importantly, endogenous Smad3 regulated and interacted with HIF-1α, resulting in increasing activity of Smad3, and this interaction was dramatically abolished by addition of miR-1. We further demonstrated that Smad3 was central to the effects of miR-1 in colorectal cancer cells, establishing a previously unappreciated mechanism by which the miR-1/Smad3/HIF-1α axis facilitates the Warburg effect to promote cancer progression in vitro and in vivo. The results indicate that miR-1 may have an essential role as a tumor suppressor, suggesting its potential role in molecular therapy of patients with advanced colorectal cancer.

Background error modeling plays a key role in a variational data assimilation system. The National Meteorological Center (NMC) method has been widely used in variational data assimilation systems to generate a forecast error ensemble from which the climatological background error covariance can be modeled. In this paper, the characteristics of the background error modeling via the NMC method are investigated for the variational data assimilation system of the Weather Research and Forecasting (WRF-Var) Model. The background error statistics are extracted from short-term 3-km-resolution forecasts in June, July, and August 2012 over a limited-area domain. It is found 1) that background error variances vary from month to month and also have a feature of diurnal variations in the low-level atmosphere and 2) that u-and y-wind variances are underestimated and their autocorrelation length scales are overestimated when the default control variable option in WRF-Var is used. A new approach of control variable transform (CVT) is proposed to model the background error statistics based on the NMC method. The new approach is capable of extracting inhomogeneous and anisotropic climatological information from the forecast error ensemble obtained via the NMC method. Single observation assimilation experiments show that the proposed method not only has the merit of incorporating geographically dependent covariance information, but also is able to produce a multivariate analysis. The results from the data assimilaton and forecast study of a real convective case show that the use of the new CVT improves synoptic weather system and precipitation forecasts for up to 12 h.

This study examines precipitation climatology and interannual variability in two regions in the lower midlatitude Asia to the east and west of the Tibetan Plateau, one located in monsoonal East Asia (the M region) and the other in semiarid central Asia (the W region). The focus is on the 5-month summer half year (May–September) for the M region and the winter half year (December–April) for the W region, corresponding to their respective rainy seasons. The main mechanism of moisture transport for the M region is the summer lower-tropospheric southerly winds, whereas the winter midtropospheric westerly circulation between 25° and 45°N is responsible for conducting moisture fluxes to the W region. It is further discovered that the winter precipitation series are positively correlated between the two regions (r = 0.47). There is also a weak cross-seasonal correlation between the winter W region precipitation and summer M region precipitation (r = 0.27). Winter westerly circulation over the W region is influenced by both the east Atlantic–western Russia and the polar–Eurasia extratropical teleconnection patterns, while El Niño–Southern Oscillation influences regional circulation patterns in both regions through teleconnections via the Indo-Pacific warm pool convection in winter and its lagged impact on the western North Pacific anticyclone over the Philippine Sea. In the meantime, responses of the regional winter circulation in the M region to the upstream westerly circulation intensity cause the correlation in winter precipitation between the two regions. Such linkages form the basis of the concurrent and cross-seasonal correlations in precipitation between the two remote regions.

Using outputs from 10 CMIP5 models with fixed sea surface temperature, we investigate the fast response of the East Asian summer monsoon (EASM) and summer precipitation in East China to anthropogenic aerosols. To address this topic, we employ two commonly used EASM indices that can represent zonal and meridional land-sea thermal contrast, respectively. The results reveal that the notion of a weakened EASM in response to increased anthropogenic aerosols is a robust one, as well as decreased precipitation in East China. The ensemble mean of decreased precipitation in the aerosol run was about 6.6% in comparison to the CTL run and could be enlarged to 8.3% by excluding the experiments with the aerosol direct effect only. Convective precipitation was found to be the primary contributor (>80%) to the reduction of total precipitation. The combination of direct and indirect effects of aerosols can decrease solar radiation reaching the Earth’s surface and eventually modulate large-scale EASM circulation and suppress summer precipitation in East China. The uncertainties and discrepancies among the models highlight the complexity of interaction in aerosol-precipitation processes when investigating present and future changes of the EASM.