Angiopoietin-like protein 4 (ANGPTL4) has been associated with a variety of diseases. It is known as an endogenous inhibitor of lipoprotein lipase (LPL), and it modulates lipid deposition and energy homeostasis. ANGPTL4 is cleaved by unidentified protease(s), and the biological importance of this cleavage event is not fully understood with respect to its inhibitory effect on LPL activity. Here, we show that ANGPTL4 appears on the cell surface as the full-length form, where it can be released by heparin treatment in culture and in vivo. ANGPTL4 protein is then proteolytically cleaved into several forms by proprotein convertases (PCs). Several PCs, including furin, PC5/6, paired basic amino acid-cleaving enzyme 4, and PC7, are able to cleave human ANGPTL4 at a consensus site. PC-specific inhibitors block the processing of ANGPTL4. Blockage of ANGPTL4 cleavage reduces its inhibitory effects on LPL activity and decreases its ability to raise plasma triglyceride levels. In summary, the cleavage of ANGPTL4 by these PCs modulates its inhibitory effect on LPL activity.Angiopoietin-like protein 4 (ANGPTL4) is also known as hepatic fibrinogen/angiopoietin-related protein, fasting-induced adipose factor, peroxisome proliferator-activated receptors, and ␥-angiopoietin-related protein. It is one of the seven members of the ANGPTL family (ANGPTL1-7). Mainly produced in hepatocytes in humans and adipocytes in mice, ANGPTL4 exerts its biological effects by means of autocrine/ paracrine and endocrine processes. ANGPTL4 has been implicated in a variety of diseases, including cardiovascular disease (1, 2), cancer metastasis (3), obesity (4), diabetes (5), wound repair (6, 7), inflammation (8), and arthritis (9).ANGPTL4 is a fusion protein consisting of an N-terminal coiled-coil domain and a C-terminal fibrinogen-like domain.These two domains have been shown to have distinct biological functions (10). The N-terminal domain is responsible for the inhibitory effects on LPL, 4 converting the active form of LPL into an inactive form (11), and the C terminus mediates its antiangiogenic functions (12). Interestingly, these two domains are separated by a short linker that can be cleaved after secretion. The cleavage phenomenon has been shown to occur in humans as well as in rodents (13,14). Cleavage of ANGPTL4 appears to be tissue-dependent in humans; liver secretes cleaved ANGPTL4, whereas adipose tissue secretes the fulllength form (14).The physiological relevance of the proteolytic processing of ANGPTL4 is largely unknown. In a human study, treatment with fenofibrate, a potent peroxisome proliferator-activated receptor-␣ agonist, markedly increased plasma levels of cleaved ANGPTL4. On this basis, it was proposed that the cleaved form of ANGPTL4 may have specific functions (14). There is evidence that the antiangiogenic activity of ANGPTL4 is regulated by an interaction of its coiled-coil domain with heparan sulfate proteoglygans (HSPGs) (18). This may be due to an ability of the N-terminal domain to facilitate the interaction between t...

The structural, electronic and optical properties of the two-dimensional (2D) heterostructure of ZnO/GeC are calculated using hybrid density functional theory. The results suggest that the ZnO monolayer has a stable contact with the GeC monolayer. Biaxial strains can significantly tune the bandgaps and band alignments of the ZnO/GeC heterostructures and all the strained heterostructures are beneficial for absorbing visible light. The induced built-in electric field across the ZnO/GeC heterostructure interface can reduce photoinduced carrier recombination rates, which is favorable for enhancing the photocatalytic performance. In particular, the band edge positions of the ZnO/GeC heterostructures of biaxial strains of , 0, 2%, 4%, and 6% are thermodynamically favorable for overall water redox processes in the pH range of 6.9–12.4, 9.4–13.1, 12.1–14.0, 12.9–14.0, 12.5–14.0, 10.9–14.0 and 5.5–8.6. Our investigation exhibits an effective method to design 2D material based water-splitting photocatalysts.

Gene therapy has drawn significant interest in the past two decades since it provides a promising strategy to treat both genetic disorders and acquired diseases. However, the transfer of gene therapy to clinical applications is troubled with many difficulties, since many current systems are of toxicity, low transfection efficiency and low biodegradability. To address these challenges, we developed a dextran-peptide hybrid system as a safe and efficient vector for gene therapy and investigated the structure-function-cytotoxicity relationship of this dextran-peptide hybrid system. Dextrans (Dex10, Dex20, and Dex70) with different molecular weights (10, 20 and 70 kDa) were conjugated with a cationic peptide, R5H5, at various degrees of substitution. Gene expression and cytotoxicity mediated by this delivery system were evaluated against SKOV-3 human ovarian carcinoma cells and compared to 25 kDa branched poly(ethylenimine) (PEI). The results showed that Dex10-R5H5 and Dex20-R5H5 hybrids derived from low molecular weight dextrans induced higher gene expression and lower cytotoxicity than Dex70-R5H5 hybrid from higher molecular weight dextran. The best performance on gene expression was achieved by Dex10-R5H5 at 40% substitution of R5H5, which induced greater gene expression than PEI at a low N/P ratio of 5. Dex10-R5H5/DNA complexes at 40% substitution of R5H5 also showed much higher cell viability (93%) than PEI/DNA (66%) at the same N/P ratio. These results indicate that the Dex-R5H5 hybrid with the low molecular weight of dextran and the high degree of substitution of R5H5 is a very promising material for safe and efficient gene therapy.

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