We used a template-assisted approach to develop synthetic antimicrobial peptides, which differ from naturally occurring antimicrobial peptides that can compromise host natural defenses. Previous researches have demonstrated that symmetrical distribution patterns of amino acids contribute to the antimicrobial activity of natural peptides. However, there is little research describing such design ideas for synthetic α-helical peptides. Therefore, here, we established a centrosymmetric α-helical sequence template (y + hhh + y)n (h, hydrophobic amino acid; +, cationic amino acid; y, Gly or hydrophobic amino acid), which contributed to amphipathicity, and a series of centrosymmetric peptides was designed with pairs of small amino acids (Ala and Gly), which were utilized to modulate the biological activity. The centrosymmetric peptides with 3 repeat units exhibited strong antimicrobial activity; in particular, the Gly-rich centrosymmetric peptide GG3 showed stronger selectivity for gram-negative bacteria without hemolysis. Furthermore, beyond our expectation, fluorescence spectroscopy and electron microscopy analyses indicated that the GG3, which possessed poor α-helix conformation, dramatically exhibited marked membrane destruction via inducing bacterial membrane permeabilization, pore formation and disruption, even bound DNA to further exert antimicrobial activity. Collectively, the Gly-rich centrosymmetric peptide GG3 was an ideal candidate for commercialization as a clinical therapeutic to treat gram-negative bacterial infections.

Previous studies of grapes and tomatoes have shown that the abundance of phosphoenolpyruvate carboxykinase (PEPCK) increases in their flesh at the start of ripening, and that this coincides with a decrease in its citrate and/or malate content. Thus, PEPCK might function in the catabolism of organic acid anions during the ripening of these fruits. In the present study, the abundance of PEPCK was determined in the flesh of blueberries, raspberries, red currants, and strawberries at different stages of their development. In addition, changes in the amounts of citrate, malate, soluble sugars, isocitrate lyase, NADP-malic enzyme, phosphoenolpyruvate carboxylase, and pyruvate, orthophosphate dikinase in the flesh were determined. PEPCK was not detected in strawberry flesh, in which there was no dissimilation of malate or citrate. In the flesh of the other fruits, the abundance of PEPCK increased during ripening to an amount that was similar to that in grapes and tomatoes. In the flesh of blueberries and red currants, PEPCK was most abundant when there was dissimilation of malate. In the flesh of raspberries, PEPCK was most abundant when there was dissimilation of malate and citrate. These results are consistent with PEPCK playing a role in the dissimilation of citrate and/or malate in the flesh of these fruits during ripening. However, PEPCK was also present in the flesh of blueberries, raspberries, and red currants when there was no dissimilation of malate or citrate, and this raises the possibility that PEPCK might have additional functions. Dissection of blueberries provided evidence that both PEPCK and phosphoenolpyruvate carboxylase were present in the same cells, and possible functions for this are discussed.

In Chinese patients with Crohn's disease, abdominal pain is the most common clinical presentation, and the most common phenotypes are age 17 to 40 years at diagnosis, ileocolonic disease location, and inflammatory disease behavior. More than one-third of patients require surgery at a median of 4 years after onset of symptoms. Stricturing, penetrating disease, and smoking are associated with an increased risk of requiring bowel resection.

Hepatitis C virus (HCV)-related research has been hampered by the lack of appropriate small-animal models. It has been reported that tree shrews, or tupaias (Tupaia belangeri), can be infected with serum-derived HCV. However, these reports do not firmly establish the tupaia as a reliable model of HCV infection. Human CD81, scavenger receptor class B type I (SR-BI), claudin 1 (CLDN1), and occludin (OCLN) are considered essential receptors or coreceptors for HCV cell entry. In the present study, the roles of these tupaia orthologs in HCV infection were assessed. Both CD81 and SR-BI of tupaia were found to be able to bind with HCV envelope protein 2 (E2). In comparison with human CD81, tupaia CD81 exhibited stronger binding activity with E2 and increased HCV pseudoparticle ( Hepatitis C virus (HCV) is a major cause of liver disease. A total of 170 million individuals worldwide are estimated to be infected with HCV and are at risk of developing cirrhosis and hepatocellular carcinoma (32,33). Unfortunately, there is presently no effective HCV vaccine available, and current treatments are far from satisfactory (22, 28). The development of antiviral therapies and effective vaccines has been hampered greatly by the lack of a convenient small-animal model. Chimpanzees (Pan troglodytes) are the only nonhuman primate host serving as an HCV infection model. However, experiments using chimpanzees are both expensive and ethically problematic. To date, three small-animal models of HCV infection have been reported: the immunotolerized rat model, Trimera mouse model, and uPA/SCID mouse model (16,25,39). However, these models are difficult to prepare, and the abnormal immune status of each greatly limits their application.The tree shrew or tupaia (Tupaia belangeri) is a small, squirrel-like mammal that is closely related to primates (6). Since the 1980s, tupaias have been used as an animal model of various infectious agents and their associated diseases. Tupaia has been shown to be susceptible to a variety of human viruses, including herpes simplex virus and hepatitis B virus (HBV) (9,38). Early in 1998 it was reported that inoculation with HCV RNA-positive serum could lead to short-term viremia and the appearance of anti-HCV IgG in tupaia (40). Furthermore, primary tupaia hepatocytes (PTHs) can be infected in vitro with serum derived from chronic hepatitis C patients (2, 18, 21, 36), although it is not clear whether the viral RNA measured is due to de novo production and/or from the virus inoculum. Recently, independent observations showed that inoculating tupaia with hepatitis C patient serum or viral particles reconstituted from full-length HCV cDNA caused mild hepatitis and intermittent viremia (1). However, these reports do not firmly establish the tupaia as a reliable model of HCV replication and pathogenesis. Importantly, patient sera often exhibit very weak infectivity (15,36). Although these results show promise, additional work has to be conducted to evaluate the value of pursuing the tupaia system in HCV research.The e...