Synergistic effect of berberine and HMQ1611 impairs cell proliferation and migration by regulating Wnt signaling pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a biologically complex disease. Combination chemotherapy is a good strategy after surgery treatment. In this study, we report that berberine combined with HMQ1611 (BCH) had a good synergistic effect on the HCC. Our findings concluded that BCH showed good inhibition on the HCC proliferation and colony formation, which attributed to cell cycle arrest by BCH at G1 phase through impairing the expression of cyclinD1, cyclinE, and cdc2 and downregulated the phosphorylation of Akt, mTOR, and ERK. Moreover, BCH negatively regulated Wnt signaling pathway by upregulating the Axin and inhibiting the nuclear translocation of ß-catenin. BCH suppressed the phosphorylation of LRP5/6, GSK3ß, the expression of Wnt5a, Frizzled8, CK1, and APC, as well as the nucleus protein included MMP2, MMP3, MMP9, and c-myc. The above data of Wnt signaling regulators contributed to inhibition by BCH on cell migration. In vivo studies, BCH significantly suppressed the growth of SMMC-7721 xenograft tumors through downregulating Ki67 and ß-catenin, as well as upregulating Axin and p-ß-catenin. In conclusion, the results revealed that BCH exhibited potential antitumor activities against human liver cancer in vitro and in vivo, and the potential mechanism underlying these activities depended on the inhibition of the Wnt/ß-catenin signaling pathway.

[Effective components of traditional Chinese medicine for regulating TGF-Beta1/Smads signaling pathway in hepatic fibrosis].

Hepatic fibrosis is a liver damage healing response affected by a variety of factors; its formation is associated with multiple cytokines and a variety of signaling pathways. Transforming growth factor beta1( TGF-ß1) is one of the strongest fibrosis cytokines known,and involves almost all the key links in hepatic fibrosis. TGF-ß1/Smads signal pathway is the most classical pathway for TGF-ß1 to play its role in promoting fibrosis as well as one of the most important signaling pathways of hepatic fibrosis formation. Studies for the signal pathway have made a series of scientific research achievements in recently years. Traditional Chinese medicine has the advantages of " multiple ingredients,multiple targets and less side effects",and is widely used in the clinical treatment of hepatic fibrosis.Effective components of traditional Chinese medicine are monomer compounds,which are extracted and purified from traditional Chinese medicine. Nowadays,the molecular biology studies of effective traditional Chinese medicine have become a hotspot. Modern advanced technology and methods can be used to directly clarify the targets and the signaling pathways,reveal the mechanism of traditional Chinese medicine in treating diseases,and promote the modernization and international development of traditional Chinese medicine industry. This review summarized the structure,function and application of TGF-ß1/Smads signaling pathway in the progress of anti-hepatic fibrosis,and analyzed the action mode and possible mechanism of various effective components of traditional Chinese medicine in regulating TGF-ß1/Smads signaling pathway and intervening the treatment of hepatic fibrosis in the past five years,so as to put forward new ideas for innovating new targeted traditional Chinese medicine for hepatic fibrosis.

Tumour-originated exosomal miR-155 triggers cancer-associated cachexia to promote tumour progression.

Emerging evidence supports the pivotal roles of cancer-associated cachexia in breast cancer progression. However, the mediators and mechanisms that mediate cancer-induced cachexia remain unclear. Here, we show that breast cancer-derived exosomes alter adipocytes and muscle cells in terms of increased catabolism characterized by the release of metabolites. Likewise, tumour cells cocultivated with mature adipocytes or C2C12 exhibit an aggressive phenotype through inducing epithelial-mesenchymal transition. Mechanistically, we show that cancer cell-secreted miR-155 promotes beige/brown differentiation and remodel metabolism in resident adipocytes by downregulating the PPARγ expression, but does not significantly affect biological conversion in C2C12. In vitro the use of propranolol ameliorates tumour exosomes-associated cachectic wasting through upregulating the PPARγ expression. These results demonstrate that cancer-derived exosomes reprogram systemic energy metabolism and accelerate cancer-associated cachexia to facilitate tumour progression.

Preparation and Effect of CO2 Response Gel for Plugging Low-Permeability Reservoirs.

In order to solve the problem of gas channeling during CO2 flooding in low-permeability reservoirs, a novel CO2 responsive gel channeling system was prepared by using carrageenan, branched polyethylene imide and ethylenediamine under laboratory conditions. Based on the Box-Behnken response surface design method, the optimal synthesis concentration of the system was 0.5 wt% carrageenan, 2.5 wt% branchized polyethylenimide and 6.5 wt% ethylenediamine. The micromorphology of the system before and after response was characterized by scanning electron microscopy. The rheology and dehydration rate were tested under different conditions. The channeling performance and enhanced oil recovery effect of the gel system were simulated by a core displacement experiment. The experimental results show that the internal structure of the system changes from a disordered, smooth and loosely separated lamellae structure to a more uniform, complete and orderly three-dimensional network structure after exposure to CO2. The viscosity of the system was similar to aqueous solution before contact with CO2 and showed viscoelastic solid properties after contact with CO2. The experiment employing dehydration rates at different temperatures showed that the internal structure of the gel would change at a high temperature, but the gel system had a certain self-healing ability. The results of the displacement experiment show that the plugging rate of the gel system is stable at 85.32% after CO2 contact, and the recovery rate is increased by 17.06%, which provides an important guide for the development of low-permeability reservoirs.

Numerical Modeling of Foam Carrying Sand Transport in Multifactor Horizontal Wells.

The solution of wellbore multiphase flow models has an important position in oil-gas field development. However, the solution of multiphase flow models often involves a series of complicated situations such as interphase mass and energy transfer, surface problems, and so on. Foam carrying sand particles in the wellbore is a solid, liquid, and gas three-phase cylinder flow problem. To solve this problem, we developed a computational fluid dynamics-discrete element method model based on the traditional N-S equations to track the streamline of the foam fluid and sand particles in the wellbore. On this basis, we investigated the influence of three factors, i.e., foam and sand properties and wellbore parameters, on the sand carrying rate of foam. The results show that whether the sand mound at the bottom of wells that can be dispersed is mainly affected by the properties of foam. The location of sand deposition in the wellbore and the effectiveness of foam in sand transportation are mainly influenced by the wellbore parameters and sand properties.

Investigations of Water Transport in Shale Reservoir with Dual-Wettability by Using Monte Carlo Method.

How liquids transport in the shale system has been the focus because of fracturing fluid loss. In this study, a single-nanopore model is established for liquid transport in shale while considering the slip effect and effective viscosity of confined fluids. Then, the fractal Monte Carlo (FMC) model is proposed to upscale the single-pore model into shale porous media. The effects of different transport mechanisms, shale wettability, and pore characteristic parameters on confined liquid flow in shale rock are investigated. Results show that FMC permeabilities are 2-3 orders of magnitude larger than intrinsic and slip-corrected permeabilities in organic matter. However, the slip effect and effective viscosity have little influence on water flow in inorganic matter. With the contact angle of organic pore (θom) increasing and contact angle of inorganic pore (θin) decreasing, the effective permeability of the whole shale matrix grows in number. The enhancement factor in the situation of θom = 170° and θin = 20° is 4 orders of magnitude larger than the case of θom = 130° and θin = 40°, although the close effective macroscopic contact angle (θeff = 80°) occurs in these two cases, which indicates that shale microscopic wettability has a significant impact on the confined liquid transport. Moreover, with the increase of porosity and maximum pore diameters, shale permeability increases rapidly, but the enhancement factor has the opposite trend. Compared with the tiny impact of the variance of minimum inorganic pore diameters, minimum organic pore diameters have more significant impacts on liquid flow in shale systems, and the enhancement factor also rapidly increases up to 30 times for the case of 0.5 nm because of the strong slip effect.

Industrial Preparation of Self-Lubricating Polyurethane via Direct Fluorination with Gaseous Fluorine.

Fluorination modification is an effective way to improve the friction property of a polymer; however, current preparation of fluorine-containing polymers is limited by the high cost and complex synthesis. Here, an industrial fluorination strategy with gaseous fluorine (F2) to achieve fluorine enrichment on the surface of a polyurethane (PU) sheet was demonstrated. Benefiting from the high reactivity and strong diffusion of F2 gas, the as-prepared PU sample was characterized by the rich fluorinated surface with the slightly fluorinated bulk. As a result, the fluorinated PU combined the excellent mechanical properties of pristine PU with the unique function of the fluorine-containing polymer, where the fluorinated surface may function as a robust lubricating layer, contributing to remarkable promotion of friction property while maintaining the mechanical strength unchanged. The friction coefficient decreased to 0.5 at the dry condition and 0.1 at the wet condition from the initial value of 1 and 0.45 for the pristine PU sample. The surface manipulation via direct fluorination offers great opportunities to tailor the friction property while keeping the mechanical strength unchanged.

Polysaccharide from Gynura divaricata modulates the activities of intestinal disaccharidases in streptozotocin-induced diabetic rats.

During diabetes, structural and functional changes in the alimentary tract are known to take place resulting in an increased absorption of intestinal glucose and alterations in the activities of brush-border disaccharidases. To elucidate the effect of administrating polysaccharide from Gynura divaricata (PGD) on disaccharidase activities, the specific activities of intestinal disaccharidases, namely sucrase, maltase and lactase, were measured in streptozotocin-induced diabetic rats. Normal control and diabetic rats were treated by oral administration with PGD. Specific activities of intestinal disaccharidases were increased significantly during diabetes, and amelioration of the activities of sucrase and maltase during diabetes was clearly visible by the treatment with PGD. However, the increased activity of lactase during diabetes mellitus was remarkably alleviated by the administration of PGD only in the duodenum. Meanwhile, oral sucrose tolerance tests demonstrated that PGD alleviated the hyperglycaemia during diabetes mellitus, resulting from the amelioration in the activities of intestinal disaccharidases. The present investigation suggests that PGD exerted an anti-diabetic effect partly via inhibiting the increased intestinal disaccharidase activities of diabetic rats. This beneficial influence of administration of PGD on intestinal disaccharidases clearly indicates their helpful role in the management of diabetes.

Highly Stretchable and Conductive Carbon Fiber/Polyurethane Conductive Films Featuring Interlocking Interfaces.

Stretchable conductors are essential assembly units of next-generation flexible electronics, requiring excellent conductivity and stretchability simultaneously. However, poor interfacial adhesion between conductive fillers and polymer matrixes often triggers the relative slippage and dislocation of the conductive network, deteriorating the final conductivity. Herein, we constructed interlocking interfaces in a polyurethane (PU) conductive composite by introducing brush-like carbon fibers (CFs) with laterally grown zinc oxide nanowires (ZnO NWs). The ZnO NW-enabled construction of the functional interfaces integrated the CFs tightly with the polymer matrix to greatly improve the interfacial adhesion and suppress the sliding displacement of conductive fillers upon external load, contributing to excellent mechanical strength and conductive stability. Specifically, the combination of high mechanical strength (7.19 MPa) and stable conductivity (26.3 S/m under 100% strain, approaching 30 S/m of the initial conductivity) was demonstrated for the brush-like CF/PU film. Finally, the application potential of the novel stretchable conductor as a thermal therapy unit and connecting wire in a flexible circuit was explored successfully under complex dynamic deformations. Accordingly, this inspiring result creatively combines the interface geometry with conductive stability, and offers a facile and effective route to prepare excellent stretchable conductors, which can be easily applied to other conductive composites.

Exact electric field strength over the packed capillary electrochromatography column bed, theoretical considerations and practical determination.

On the basis of the experiments, it was proved that Ohm's law holds true in a capillary electrochromatography (CEC) column. By using the additivity of the potential drop over the packed and unpacked sections, the exact values of the electric field strength over the packed CEC column bed were determined experimentally. The ratio of the resistance of packed CEC column sections to that of an open capillary of the same length (Rp/Ro,Lp) were calculated. Some theoretical calculations were made to show how some structural parameters of particle lattice affect the resulting Rp/Ro,Lp value of the column bed formed accordingly. It is suggested that to correctly elucidate the EOF phenomenon in a CEC column, the potential drop over the packed and unpacked column sections, Ep and Eo, should be accounted for respectively, rather than using the average field strength over the total column length.