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Triple-negative breast cancer (TNBC) cells lack the expression of ER, PR and HER2. Thus, TNBC patients cannot benefit from hormone receptor-targeted therapy as non-TNBC patients, but can only receive chemotherapy as the systemic treatment and have a worse overall outcome. More effective therapeutic targets and combination therapy strategies are urgently needed to improve the treatment effectiveness. METHODS: We analyzed the expression levels of EZH2 and TET1 in TCGA and our own breast cancer patient cohort, and tested their correlation with patient survival. We used TNBC and non-TNBC cell lines and mouse xenograft tumor model to unveil novel EZH2 targets and investigated the effect of EZH2 inhibition or TET1 overexpression in cell proliferation and viability of TNBC cells. RESULTS: In TNBC cells, EZH2 decreases TET1 expression by H3K27me3 epigenetic regulation and subsequently suppresses anti-tumor p53 signaling pathway. Patients with high EZH2 and low TET1 presented the poorest survival outcome. Experimentally, targeting EZH2 in TNBC cells with specific inhibitor GSK343 or shRNA genetic approach could induce cell cycle arrest and senescence by elevating TET1 expression and p53 pathway activation. Using mouse xenograft model, we have tested a novel therapy strategy to combine GSK343 and chemotherapy drug Adriamycin and could show drastic and robust inhibition of TNBC tumor growth by synergistic induction of senescence and apoptosis. CONCLUSIONS: We postulate that the well-controlled dynamic pathway EZH2-H3K27me3-TET1 is a novel epigenetic co-regulator module and provide evidence regarding how to exploit it as a novel therapeutic target via its pivotal role in senescence and apoptosis control. Of clinical and therapeutic significance, the present study opens a new avenue for TNBC treatment by targeting the EZH2-H3K27me3-TET1 pathway that can modulate the epigenetic landscape.

Copyright © 2019 American Chemical Society. Upconversion nanoparticles (UCNPs) and MnO 2 hybrid theranostic nanoplatform (UCMn) is highly desired; however, the rational design of such UCMn hybrid nanomaterials is still a great challenge. Herein, a simple and versatile strategy for the in situ growth of MnO 2 on the surfaces of UCNPs was reported using a sacrificial template method to construct an ideal MnO 2 -disguised and tumor microenvironment-triggered architecture. Such sophisticated architecture not only achieves activatable magnetic resonance imaging and restorable upconversion luminescence (UCL) imaging with over 100-fold enhancement of UCL in vivo but also significantly improves the efficiency of chemodynamic therapy (CDT) by glutathione depletion- and cisplatin-activation-enhanced • OH generation simultaneously. Additionally, the synergetic effect of CDT and chemotherapy presents excellent therapeutic effect in vivo as compared to either CDT or chemotherapy alone. We believe that the ideal design of the MnO 2 -disguised upconversion hybrid nanocomposite will provide more revelations on the future research on nanoscale theranostic systems.

Technology and information are used in everywhere. Technology has massive impact on the society, but its stages are still early. Many applications were implemented for logistic and manufacturing process to personal usage. This paper focuses on the application of IoT on a personal level, which is home automation. The curtain are driven by a direct-current motor. The lights are operated according to the light sensor. Both of them are controlled by a touch sensitive smart mirror or voice activation. With the help of an online database management program and ESP8266 wireless devices, the communication between the microcontrollers was done successfully. System activity can be tracked via NETPIE. Results showed that curtain and lights were able to be controlled remotely via touch control and voice activation. Record of results are kept for future machine learning integration. In practice, benefits of IoT were demonstrated in order to bring down the barriers and create a pathway to mainstream adaptation of IoT smart devices.

In this paper, the Smoothed Particle Hydrodynamics method is used to simulate experimental shallow free surface turbulent flows over a rough bed made of regularly packed uniform spheres. The numerical program is based on the open source code SPHysics and significant improvement is made in the turbulence modelling and rough bed treatment within the code. A modified Sub-Particle-Scale eddy viscosity model is proposed to simulate the effect of turbulence transfer mechanisms in the highly-sheared free surface flow, and a drag force term is introduced into the momentum equation as a source term to account for the existence of the bed roughness. To validate the numerical model, a laboratory experiment is carried out to study shallow, turbulent flow behaviour under different flow conditions. The SPH simulations are then compared with the flow velocity, shear stress and turbulent intensity profiles measured via acoustic doppler velocimeters. Several issues with regard to the rough bed hydraulics are investigated, including the study of water surface behaviour and its interaction with the bulk flow.

In this paper a 3D incompressible Smoothed Particle Hydrodynamics (ISPH) erosion model\ud is proposed to simulate the scouring process behind a large vertical cylinder. The erosion\ud model is based on the turbidity water particle concept and the sediment motion is initiated\ud when the fluid bottom shear stress exceeds the critical value. The previous 2D SPH sediment\ud initiation model is expanded by combining the effects of both transverse and longitudinal\ud sloping beds in a practical 3D situation. To validate the developed model, a laboratory flume\ud experiment was carried out to study the clear water scouring around a vertical cylinder under\ud unidirectional current, in which high-speed video cameras were used for the real-time monitoring\ud of sediment movement. The 3D ISPH results are compared with the experimental data with good\ud agreement in terms of the scouring patterns and scales. Besides, the computed flow velocity field\ud suggests that both the horseshoe vortices and lee-wake flows around the cylinder have been\ud accurately simulated.\ud

In this review, we highlight recent research and current ideas on how to improve the efficiency of the light reactions of photosynthesis in crops. We note that the efficiency of photosynthesis is a balance between how much energy is used for growth and the energy wasted or spent protecting the photosynthetic machinery from photodamage. There are reasons to be optimistic about enhancing photosynthetic efficiency, but many appealing ideas are still on the drawing board. It is envisioned that the crops of the future will be extensively genetically modified to tailor them to specific natural or artificial environmental conditions.

Modern water management decisions are increasingly dependent on efficient numerical simulations of multiple scenarios with multi-models. In this paper, a service mode for the hydrodynamic simulation based on cloud computing is proposed, and the relevant frameworks of the Hydrologic/Hydraulic Modeling Platform (HydroMP) are designed and implemented. Various hydro-models can be integrated into HydroMP dynamically without the need of program recompiling, since it achieves the scheduling of computing resources to provide end users with the rapid computing capacity of concurrent scenario simulations in the form of a Web service. The present study focuses on the dynamic model integration, resource scheduling, system communication and data structure design. To use the present one-dimensional hydrodynamic cloud computing as a prototype, two integration methods (including the EXE integration and PIIM integration) are applied to construct the CE-QUAL-RIV1 and JPWSPC (Joint Point Water Stage Prediction and Correction) models, thereby to investigate real-time scheduling of the water transfer channels in the South-to-North Water Diversion (SNWD) project. The results showed that massive modeling scenarios by use of different hydrodynamic models, if submitted concurrently, can be processed simultaneously in the HydroMP. The data structure of the proposed framework can also be extended to two-dimensional and three-dimensional hydrodynamic situations.

The non-homogeneous debris flows, consisting of a wide range of grain size, bulk density and demonstrating non-uniform velocity distributions, are commonly modeled as the two-phase flow. In adopting such an approach, a critical grain diameter to separate the solid and liquid phase, within such debris flows, can be determined through the principles of minimum energy dissipation. In the current study, an improved analytical approach using the resistance formula of water flow and mass conservation law is presented to determine the velocity of the solid and liquid phases within a non-homogeneous debris flow, based on the derived critical grain diameter. Some of the dynamic parameters required in the analysis are validated against the experimental data of a non-homogeneous, two-phase debris flow measured from the Jiangjia gully, Yunnan Province of China. The results show that, for the majority of non-homogeneous debris flows tested, the liquid phase exhibits higher velocity than the solid phase. However, as the bulk density of the debris flow increases, the solid phase tends to have higher velocity than the liquid phase. These findings are shown to have important implications on the vertical grading patterns of the bed deposits in depositional areas. The observations from the field studies indicate that the non-homogeneous debris flows with bulk density being significantly lower, close to and significantly higher than the critical value seem to exhibit normal (i.e. bed-to-surface vertical fining), mixed, and inverse (bed-to-surface vertical coarsening) grading patterns in the alluvial fan deposits.

The smoothed particle hydrodynamics (SPH) method is a meshless numerical modeling technique. It has been applied in many different research fields in coastal engineering. Due to the drawback of its kernel approximation, however, the accuracy of SPH simulation results still needs to be improved in the prediction of violent wave impact. This paper compares several different forms of correction on the first-order derivative of ISPH formulation aiming to find one optimum kernel approximation. Based on four benchmark case analysis, we explored different kernel corrections and compared their accuracies. Furthermore, we applied them to one solitary wave and two dam-break flows with violent wave impact. The recommended method has been found to achieve much more promising results as compared with experimental data and other numerical approaches.