MiR-126 enhances cisplatin chemosensitivity in hepatocellular carcinoma cells by targeting IRS1

Purpose: To investigate the potential role of miR-126 in regulating the proliferation and cisplatin chemosensitivity of human hepatocellular carcinoma (HCC) cells.Methods: The expression of miR-126 was evaluated using clinical HCC specimens. MiR-126-mediated downregulation of Insulin Receptor Substrate 1 (IRS1) was determined by qRT-PCR, western blot and luciferase reporter assay. Cell Counting Kit-8 (CCK8) and colony formation assays were performed to examine the proliferation of HCC cells.Results: Decreased expression of miR126 was found in HCC tumors and was correlated with poor survival in HCC patients. In HCC cells, miR-126 targeted IRS1 for downregulation, through which miR- 126 suppressed the growth of HCC cells and desensitized HCC cells to cisplatin treatment.Conclusion: MiR-126a impairs the proliferation and cisplatin chemoresistance of HCC cells by targeting IRS1.Keywords: miR-126, IRS1, HCC, cisplatin, chemosensitivit

Tensile stress development and critical behavior of a flexible barrier

A DEM numerical approach is employed to illustrate the critical stress development of a three-supporting cable flexible barrier under a large scale stony debris movement impact. A proper linear parallel bond is applied to build the flexible barrier model. Critical state is presented by lowering the tensile resistance of the flexible barrier and steepening the channel slope. The tensile stress of the supporting cables is primarily studied. Results mainly indicate that the particle-structure contact is essential to the stress development. The bottom cable always exhibits larger tensile stress due to the massive collision and compressive force of particles and the tensile force exerted by the vertical cable-net joint system. On the other hand, the intermediate cable receives lower collision and compressive force, resulting in smaller tensile stress. The bottom cable indicating numerous direct particle-structure contact part performs brittle failure, which is analogous to the concentrated load feedbacks. The loading of the intermediate one reaches ductile failure, reflecting the desirable effect of dispersing loads. This study suggests that practical engineering should try to avoid massive boulder impact or reinforce the bottom cable in order to improve the hazard prevention design

Enhanced heating rate of black carbon above planetary boundary layer over megacities in summertime

The fast development of a secondary aerosol layer was observed over megacities in eastern Asia during summertime. Within three hours, from midday to early afternoon, the contribution of secondary aerosols above the planetary boundary layer (PBL) increased by a factor of 3-5, and the coatings on the black carbon (BC) also increased and enhanced its absorption efficiency by 50%. This tended to result from the intensive actinic flux received above the PBL which promoted the photochemical reactions. The absorption of BC could be further amplified by the strong reflection of solar radiation over the cloud top across the PBL. This enhanced heating effect of BC introduced by combined processes (intensive solar radiation, secondary formation and cloud reflection) may considerably increase the temperature inversion above the PBL. This mechanism should be considered when evaluating the radiative impact of BC, especially for the polluted regions receiving strong solar radiation

Exosomes Released from Mycoplasma Infected Tumor Cells Activate Inhibitory B Cells

Mycoplasmas cause numerous human diseases and are common opportunistic pathogens in cancer patients and immunocompromised individuals. Mycoplasma infection elicits various host immune responses. Here we demonstrate that mycoplasma-infected tumor cells release exosomes (myco+ exosomes) that specifically activate splenic B cells and induce splenocytes cytokine production. Induction of cytokines, including the proinflammatory IFN-γ and the anti-inflammatory IL-10, was largely dependent on the presence of B cells. B cells were the major IL-10 producers. In splenocytes from B cell deficient μMT mice, induction of IFN-γ+ T cells by myco+ exosomes was greatly increased compared with wild type splenocytes. In addition, anti-CD3-stimulated T cell proliferation was greatly inhibited in the presence of myco+ exosome-treated B cells. Also, anti-CD3-stimulated T cell signaling was impaired by myco+ exosome treatment. Proteomic analysis identified mycoplasma proteins in exosomes that potentially contribute to the effects. Our results demonstrate that mycoplasma-infected tumor cells release exosomes carrying mycoplasma components that preferentially activate B cells, which in turn, are able to inhibit T cell activity. These results suggest that mycoplasmas infecting tumor cells can exploit the exosome pathway to disseminate their own components and modulate the activity of immune cells, in particular, activate B cells with inhibitory activity

Tensile stress development and critical behavior of a flexible barrier

A DEM numerical approach is employed to illustrate the critical stress development of a three-supporting cable flexible barrier under a large scale stony debris movement impact. A proper linear parallel bond is applied to build the flexible barrier model. Critical state is presented by lowering the tensile resistance of the flexible barrier and steepening the channel slope. The tensile stress of the supporting cables is primarily studied. Results mainly indicate that the particle-structure contact is essential to the stress development. The bottom cable always exhibits larger tensile stress due to the massive collision and compressive force of particles and the tensile force exerted by the vertical cable-net joint system. On the other hand, the intermediate cable receives lower collision and compressive force, resulting in smaller tensile stress. The bottom cable indicating numerous direct particle-structure contact part performs brittle failure, which is analogous to the concentrated load feedbacks. The loading of the intermediate one reaches ductile failure, reflecting the desirable effect of dispersing loads. This study suggests that practical engineering should try to avoid massive boulder impact or reinforce the bottom cable in order to improve the hazard prevention design

Numerical Investigation of Key Structural Parameters for Middle-Buried Rubber Waterstops

Leakage at the lining joints of mountain tunnels is frequent. According to the waterproofing mechanism of waterstops, it is known that the deformation of middle-buried rubber waterstops under stress in typical operating conditions determines their waterproof performance. In addition to the deformation of the adjacent lining concrete, the structural parameters of waterstops are the main factors influencing their deformation under stress. This study combines the common structural components of middle-buried waterstops and considers the bond strength between waterstops and the concrete. A localized numerical model of the lining joint is constructed to explore the impact of geometric parameters, such as hole size, number and position of waterstop ribs, and length and thickness of wing plates on the stress-induced deformation and waterproof performance of the waterstops. The effective mechanisms of different components are revealed, and recommended structural parameters are proposed to further optimize the design of middle-buried rubber waterstops

Characteristics of Direct Shear and Particle Breakage of Pebble Gravel Materials

Particle size is an important factor affecting the Thermal-Hydraulic-Mechanical (THM) coupling behavior of graveled rock mass, especially for the shear mechanical properties. In this study, three groups of the particle size range and nine particle grading samples are designed for a large-scale direct shear test. The relationships between shear stress and shear displacement, shear strength, stress ratio, shear strength parameters, and particle breakage of pebble gravel are analyzed. The influence of particle size range and grade on the strength and particle breakage of gravel material is discussed. Results show evident particle breakage in the process of direct shear, and the degree of fragmentation is controlled by the normal load and the particle size distribution of the sample. The shear strength of the sample is no longer applicable to Mohr-Coulomb strength theory because of particle breakage that is more in line with the power function relationship. Shear strength of pebble gravel material has scale effect, and a corresponding relationship model between friction coefficient f of material and characteristic particle size of the sample is proposed

Evaluating cellular uptake of gold nanoparticles in HL-7702 and HepG2 cells for plasmonic photothermal therapy

A novel method is proposed for quantifying the Raman intensity as a function of gold mass in a single cell based on the Raman mapping and inductively coupled plasma-mass spectrometry techniques. And a high-efficiency plasmonic photothermal therapy has also been achieved by adjusting the laser wavelength, laser power and exposure time, resulting in most of the HL-7702 cells survive, whereas most of the HepG2 cells get damaged