MiR-196a-5p facilitates progression of estrogen-dependent endometrial cancer by regulating FOXO1

Background and Purpose. Estrogen-dependent endometrial cancer mainly occurs in younger pre-menopausal and post-menopausal women and threatens their health. Recently, microRNAs (miRNAs) have been considered as novel targets in endometrial cancer treatment. Therefore, we aimed to explore the effect of miRNA (miR)-196a-5p in estrogen-dependent endometrial cancer. Methods. 17β-estradiol (E2; 2.5, 5, 10 and 20 nM) was used to treat RL95-2, HEC-1B and ECC-1 cells followed by cell viability assessment using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The level of miR-196a-5p was measured by reverse transcription-quantitative PCR (RT-qPCR). We then transfected miR-196a-5p mimic/inhibitor and Forkhead box protein O1 (FOXO1) small interfering RNA (siRNA) into E2-treated cells. Apoptotic cells were measured by flow cytometry. Wound healing and Transwell assays were implemented to assess migration and invasion. Bioinformatics and luciferase reporter assays were applied to confirm the interaction between miR-196a-5p and FOXO1. Immunoblotting determined the levels of FOXO1, Bcl-2, Bax, Caspase 3. Results. E2 promoted cell viability and miR-196a-5p expression in RL95-2 and ECC-1 cells. miR-196a-5p mimic enhanced cell viability, migration and invasion but suppressed apoptosis and FOXO1, whilst miR-196a-5p inhibitor blocked these processes. In addition, miR-196a-5p upregulated Bcl-2, but down regulated Bax and Caspase 3 expression, an effect that was reversed by miR-196a-5p inhibitor. We determined that miR-196a-5p targeted FOXO1, and that si-FOXO1 blocked the effects of miR-196a-5p inhibitor on viability, apoptosis, migration and invasion of E2-treated RL95-2 and ECC-1 cells. Conclusions. Our findings suggested potential diagnostic and therapeutic applications for miR-196a-5p and its FOXO1 target in patients suffering from estrogen-dependent endometrial cancer

Three-dimensional laser scanning and numerical investigation on the influence of freeze-thaw and hang-wall mining on the instability of an open-pit slope

The instability of the open-pit slope and associated disasters of complex orebodies such as hanging-wall mining are the key problems to be solved urgently in the development of western resources. In this work, taking the hanging-wall mining in the open-pit mine of Hejing iron mine, for example, the disaster mechanism influenced by the coupling freeze-thaw and hanging-wall mining is systematically studied by 3D laser scanning and numerical simulation. Firstly, the rock mass structure information such as dip, dip angle, spacing, and equivalent trace length characteristics was obtained using 3D intelligent recognition technology. Then, numerical simulation is employed to reveal the influence of freeze-thaw and excavation sequences on the overall stability of the open-pit slope. The stress, displacement, plasticity zone, and maximum shear strain patterns are revealed in detail. The results show that the excavation engineering will lead to frequent increase and unloading of the internal stress of the rock mass, and the gradual increase of the goaf area will cause great damage to the rock mass. The slope failure mode is strongly impacted by freeze-thaw weathering and orebody excavation

A Closed-Loop Supply Chain Problem with Retailing and Recycling Competition

We investigate a durable product retailing and recycling problem in a closed-loop supply chain consisting of a single manufacturer and two competitive retailers, in which the manufacturer collects used products via retailers from the consumers and has sufficient channel power over the retailers to act as a Stackelberg leader; the retailers compete in retail products and recycling used products. In order to analyze the impact of retailing and recycling competitions on the profits of the manufacturer and the competitive retailers, two collection models (coordinated collection (Model C) and decentralized collection (Model D)) are established, respectively. Then, based on game theory, we derive the optimal retail price, the optimal repurchase price, and the optimal profits of the manufacturer and the retailers. The managerial insights demonstrate that more intense retailing competition induces the increase of the manufacturer's profits in both forward and reverse channels and retailers' profits in the forward channel and the decrease of retailers' profits in the reverse channel, while more intense recycling competition induces the decrease of the profits of the manufacturer and retailers in both forward and reverse channels. Finally, numerical examples are given to illustrate the effectiveness of the proposed models

Temperature Response of Respiration Across the Heterogeneous Landscape of the Alaskan Arctic Tundra

AbstractPredictions of the response of ecosystem respiration to warming in the Arctic are not well constrained, partly due to the considerable spatial heterogeneity of these permafrost‐dominated areas. Accurate calculations of in situ temperature sensitivities of respiration (Q10) are vital for the prediction of future Arctic emissions. To understand the impact of spatial heterogeneity on respiration rates and Q10, we compared respiration measured from automated chambers across the main local polygonized landscape forms (high and low centers, polygon rims, polygon troughs) to estimates from the flux‐partitioned net ecosystem exchange collected in an adjacent eddy covariance tower. Microtopographic type appears to be the most important variable explaining the variability in respiration rates, and low‐center polygons and polygon troughs show the greatest cumulative respiration rates, possibly linked to their deeper thaw depth and higher plant biomass. Regardless of the differences in absolute respiration rates, Q10 is surprisingly similar across all microtopographic features, possibly indicating a similar temperature limitation to decomposition across the landscape. Q10 was higher during the colder early summer and lower during the warmer peak growing season, consistent with an elevated temperature sensitivity under colder conditions. The respiration measured by the chambers and the estimates from the daytime flux‐partitioned eddy covariance data were within uncertainties during early and peak seasons but overestimated respiration later in the growing season. Overall, this study suggests that it is possible to simplify estimates of the temperature sensitivity of respiration across heterogeneous landscapes but that seasonal changes in Q10 should be incorporated into model simulations