Berberine induces caspase-independent cell death in colon tumor cells through activation of apoptosis-inducing factor

Berberine, an isoquinoline alkaloid derived from plants, is a traditional medicine for treating bacterial diarrhea and intestinal parasite infections. Although berberine has recently been shown to suppress growth of several tumor cell lines, information regarding the effect of berberine on colon tumor growth is limited. Here, we investigated the mechanisms underlying the effects of berberine on regulating the fate of colon tumor cells, specifically the immorto Min mouse colonic epithelial (IMCE) cells carrying the Apcmin mutation, and of normal colon epithelial cells, namely young adult mouse colon (YAMC) epithelial cells. Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells. In contrast, YAMC cells were not sensitive to berberine-induced cell death. Berberine did not stimulate caspase activation, and PARP cleavage and berberine-induced cell death were not affected by a caspase inhibitor in IMCE cells. Rather, berberine stimulated a caspase-independent cell death mediator, apoptosis-inducing factor (AIF) release from mitochondria and nuclear translocation in a ROS production-dependent manner. Amelioration of berberine-stimulated ROS production or suppression of AIF expression blocked berberine-induced cell death and LDH release in IMCE cells. Furthermore, two targets of ROS production in cells, cathepsin B release from lysosomes and PARP activation were induced by berberine. Blockage of either of these pathways decreased berberine-induced AIF activation and cell death in IMCE cells. Thus, berberine-stimulated ROS production leads to cathepsin B release and PARP activation-dependent AIF activation, resulting in caspase-independent cell death in colon tumor cells. Notably, normal colon epithelial cells are less susceptible to berberine-induced cell death, which suggests the specific inhibitory effects of berberine on colon tumor cell growth

Berberine Induces Caspase-Independent Cell Death in Colon Tumor Cells through Activation of Apoptosis-Inducing Factor

Berberine, an isoquinoline alkaloid derived from plants, is a traditional medicine for treating bacterial diarrhea and intestinal parasite infections. Although berberine has recently been shown to suppress growth of several tumor cell lines, information regarding the effect of berberine on colon tumor growth is limited. Here, we investigated the mechanisms underlying the effects of berberine on regulating the fate of colon tumor cells, specifically the mouse immorto-Min colonic epithelial (IMCE) cells carrying the Apcmin mutation, and of normal colon epithelial cells, namely young adult mouse colonic epithelium (YAMC) cells. Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells. In contrast, YAMC cells were not sensitive to berberine-induced cell death. Berberine did not stimulate caspase activation, and PARP cleavage and berberine-induced cell death were not affected by a caspase inhibitor in IMCE cells. Rather, berberine stimulated a caspase-independent cell death mediator, apoptosis-inducing factor (AIF) release from mitochondria and nuclear translocation in a ROS production-dependent manner. Amelioration of berberine-stimulated ROS production or suppression of AIF expression blocked berberine-induced cell death and LDH release in IMCE cells. Furthermore, two targets of ROS production in cells, cathepsin B release from lysosomes and PARP activation were induced by berberine. Blockage of either of these pathways decreased berberine-induced AIF activation and cell death in IMCE cells. Thus, berberine-stimulated ROS production leads to cathepsin B release and PARP activation-dependent AIF activation, resulting in caspase-independent cell death in colon tumor cells. Notably, normal colon epithelial cells are less susceptible to berberine-induced cell death, which suggests the specific inhibitory effects of berberine on colon tumor cell growth

Implementation and Advancement of a Rural Residential Concentration Strategy in the Suburbs of Shanghai

Rural residential concentration was one of the important tasks of the “Three Concentrations” strategy implemented in the suburbs of Shanghai in the mid-1990s. The aims of this paper are to comprehensively evaluate the process, pattern and effects of residential concentration in the suburbs of Shanghai over the past 20 years, clarify the direction and focus of development, and propose suggestions for existing deficiencies. Based on remote sensing images and statistical data, the implementation and effects of the rural residential concentration strategy from 1990 to 2015 were analysed using landscape indexes and geospatial analysis. The results are as follows: (1) according to the changes in the landscape pattern and spatial structure, the trends in population concentration in the suburbs of Shanghai are obvious. (2) Before 1995, the trend of population diffusion was conspicuous. After 1995, the period of population diffusion gradually shifted to a period of population agglomeration. The rate of population concentration increased rapidly from 2000 to 2010 and then became moderate after 2010. (3) In 1990, most of the rural residential areas were distributed within 14–52 km of the city centre, the distribution of residential area in each ring was relatively uniform, and the overall distribution was scattered and uniform. By 2015, the rural population gradually converged in the inner suburbs, and the centralized distribution gradually changed to within 16–32 km of the city centre. (4) In 1990, most of the rural residential areas were located north-northwest, southeast, and southwest of the People’s Square. By 2015, the areas southwest and southeast of the People’s Square became the focus of rural residential distribution. These findings provide a useful reference for future rural planning and construction

A study of coupled incentive-based clearing mechanisms in electricity markets considering uncertainty risk

Promoting the construction of the electricity spot market and considering the market-oriented trading mode with joint participation of the generation side and load side and fair competition will be the trend of future development of the electricity spot market. The unit generation bidding strategy is adjusted by this paper based on incentive factors and an incentive-based clearing mechanism is designed for market coupling. To establish a coupled two-layer model of the power market, the upper layer of the heterogeneous generator bidding strategy modeling, the lower layer of the incentive-based market clearing mechanism modeling. On this basis, a spot market model is designed in which both the generation and user sides participate in peaking, and the peaking resources on the generation side and the user side are included in the market mechanism bidding. This paper’s clearing cost can save 854.42 yuan compared to the unified clearing mechanism in the bidding stage for clearing the total market electricity energy volume of 1000kW. The total carbon emissions are reduced by 5816.8 tons in a single day when compared to the single electric energy trading mechanism, which is based on the market-coupled incentive system. The market model proposed in the paper can effectively improve the level of new energy consumption and provide a useful reference for the design of the electricity market in regions with a high proportion of new energy

Analysis of Factors Influencing the Urban Carrying Capacity of the Shanghai Metropolis Based on a Multiscale Geographically Weighted Regression (MGWR) Model

With the rapid development of urban economy and the continuous expansion of urban scale, the limitations of urban carrying capacity begin to appear. For the sustainable development of the city, more and more scholars are paying attention to the research onurban carrying capacity. Basedon the continuous research of the authors’ research group over the past ten years, this paper uses a multiscale geographically weighted regression model and method to explore the impact of geographical location, floor area ratio, public transportation, residents’ consumption level, the density of high-tech enterprises, and the ecological environment on the carrying capacity of the Shanghai metropolis. The results show that (1) the impact of geographical location on the bearing capacity decreases from downtown to the outer areas and from the northeastern area to the southwestern area of Shanghai. (2) On the whole, the elasticity of the average floor area ratio to the urban carrying capacity is 0.52%. In different regions, most of the central urban areas have exceeded the optimal average plot ratio. With an increase in the average plot ratio, the urban carrying capacity presents a downward trend. Other sample areas generally did not reach the average optimal plot ratio, especially the southwestern area of Shanghai. With an increase in the average plot ratio, the urban carrying capacity of this area improved significantly. (3) The elasticity of public transportation convenience to the urban carrying capacity is 0.23%; that is, the average increase in the urban carrying capacity is 0.23% for every 1% increase in public transportation convenience. The elasticity of residents’ consumption level is −0.18%; in other words, every 1% increase in residents’ consumption level will reduce the urban carrying capacity by 0.18% on average. The elasticity of the density of high-tech enterprises is 0.08%; hence, when the density of high-tech enterprises increases by 1%, the urban carrying capacity increases by 0.08% on average. Lastly, the elasticity of the eco-environmental status index is 0.17%; that is, every 1% increase in the eco-environmental status index increases the urban carrying capacity by 0.17% on average

The Mechanical Mechanism and Influencing Factors of Ice Adhesion Strength on Ice-Phobic Coating

Ice accretion can cause problems on polar ships, ocean platforms, and in other marine industries. It is important to understand the interface debonding behavior between ice and the surface of equipment. In this work, we created a mechanical model to analyze the interface debonding behavior between a square-based ice cuboid and an elastic coating base, using contact mechanics and fracture mechanics. Three-dimensional (3D) finite element (FE) simulation was used to simulate the interface debonding for normal and shear separation. A bilinear cohesive zone model (CZM) was used to simulate the interface between the ice cuboid and the elastic coating. We investigated the effect of the elastic modulus E of an elastic film on the critical detachment force Fc for normal and shear separation. The results showed that Fc increases with an increase of the elastic modulus of the elastic film. When E exceeds a certain level, Fc achieves a constant value and then remains stable. Finally, a series of epoxy/polydimethylsiloxane (PDMS) interpenetrating polymer-network (IPN) gel coatings with different elastic moduli were prepared. The ice tensile and shear adhesion strengths (σice and τice) of the coatings were measured. The results were roughly consistent with the results of the numerical simulation when E < 1 MPa