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OBJECTIVEDisturbances in podocytes are typically associated with marked proteinuria, a hallmark of diabetic nephropathy. This study was conducted to investigate modulation of Notch-1 signaling in high glucose (HG)-stressed human podocytes and in a diabetic animal model.RESEARCH DESIGN AND METHODSExpression of the Notch signaling components was examined in HG-treated podocytes, human embryonic kidney cells (HEK293), and kidneys from diabetic animals by RT-qPCR, Western blot analysis, and immunohistochemical staining. The association between the Notch signaling, VEGF expression, and podocyte integrity was evaluated.RESULTSNotch-1 signaling was significantly activated in HG-cultured human podocytes and HEK293 cells and kidneys from diabetic animals. HG also augmented VEGF expression, decreasing nephrin expression and podocyte number—a critical event for the development of proteinuria in diabetic nephropathy. After use of pharmacological modulators or specific shRNA knockdown strategies, inhibition of Notch-1 signaling significantly abrogated VEGF activation and nephrin repression in HG-stressed cells and ameliorated proteinuria in the diabetic kidney.CONCLUSIONSOur findings suggest that upregulation of Notch-1 signaling in HG-treated renal podocytes induces VEGF expression and subsequent nephrin repression and apoptosis. Modulation of Notch-1 signaling may hold promise as a novel therapeutic strategy for the treatment of diabetic nephropathy.

This research examines empirically the relationship among social capital, entrepreneurial orientation, organizational resource, and entrepreneurial performance for new ventures. Data was collected by means of mailing questionnaire to new ventures in Taiwan, and a total of one hundred and four qualified observations were collected. The results obtained in this research indicate that there are significant relationships among social capital, entrepreneurial orientation, and organizational resources. Additionally, the influence of social capital, entrepreneurial orientation, and organizational resources on entrepreneurial performance is significant.The findings suggest that new ventures can speed up information diffusion and look for the opportunities of new technology, new product, niche market, and financial resources through expanding external business

In recent years, green energy has undergone a lot of development and has been the subject of many applications. Many research studies have focused on illumination with sunlight as a means of saving energy and creating healthy lighting. Natural light illumination systems have collecting, transmitting, and lighting elements. Today, most daylight collectors use dynamic concentrators; these include Sun tracking systems. However, this design is too expensive to be cost effective. To create a low-cost collector that can be easily installed on a large building, we have designed a static concentrator, which is prismatic and cascadable, to collect sunlight for indoor illumination. The transmission component uses a large number of optical fibers. Because optical fibers are expensive, this means that most of the cost for the system will be related to transmission. In this paper, we also use a prismatic structure to design an optical coupler for coupling n to 1. With the n-to-1 coupler, the number of optical fibers necessary can be greatly reduced. Although this new natural light illumination system can effectively guide collected sunlight and send it to the basement or to other indoor places for healthy lighting, previously there has been no way to manage the collected sunlight when lighting was not desired. To solve this problem, we have designed an optical switch and a beam splitter to control and separate the transmitted light. When replacing traditional sources, the lighting should have similar characteristics, such as intensity distribution and geometric parameters, to those of traditional artificial sources. We have designed, simulated, and optimized an illumination lightpipe with a dot pattern to redistribute the collected sunlight from the natural light illumination system such that it equals the qualities of a traditional lighting system. We also provide an active lighting module that provides lighting from the natural light illumination system or LED auxiliary sources, depending on circumstances. The system is controlled by a light detector. We used optical simulation tools to design and simulate the efficiency of the active module. Finally, we used the natural light illumination system to provide natural illumination for a traffic tunnel. This system will provide a great number of benefits for the people who use it.

BackgroundStromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells.ResultsHuman gastric cancer cell lines were exposed to doses of resistin; SDF-1 expression and secretion levels were then determined. Real-time polymerase chain reaction and western blotting analyses were performed to clarify molecular changes. Inhibition of Toll-like receptor 4 (TLR4) by a competitive antagonist inhibited resistin-induced SDF-1 expression. Pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that activation of the p38 mitogen-activated protein kinase (MAPK) pathway is critical for resistin-induced SDF-1 expression mediated by TLR4. The promoter activity and transcription factor enzyme-linked immunosorbent assay revealed that resistin induced expression of SDF-1 mediated by NF-κB in gastric cancer cells. Inhibition of p38 MARK activation blocked the SDF-1-induced expression and the SDF-1 promoter activity in the cancer gastric cells. Chromatin immunoprecipitation assay revealed that inhibition of p38 MARK activation also blocked the resistin-increased NF-κB-DNA-binding activity.ConclusionsResistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-κB may explain a new role of resistin in the link of obesity and gastric cancer.