Nucleotide sequences from a total of 421 HEV isolates were retrieved from Genbank and analysed. Phylogenetically, HEV was classified into four major genotypes. Genotype 1 was more conserved and classified into five subtypes. The number of genotype 2 sequences was limited but can be classified into two subtypes. Genotypes 3 and 4 were extremely diverse and can be subdivided into ten and seven subtypes. Geographically, genotype 1 was isolated from tropical and several subtropical countries in Asia and Africa, and genotype 2 was from Mexico, Nigeria, and Chad; whereas genotype 3 was identified almost worldwide including Asia, Europe, Oceania, North and South America. In contrast, genotype 4 was found exclusively in Asia. It is speculated that genotype 3 originated in the western hemisphere and was imported to several Asian countries such as Japan, Korea and Taiwan, while genotype 4 has been indigenous and likely restricted to Asia. Genotypes 3 and 4 were not only identified in swine but also in wild animals such as boar and a deer. Furthermore, in most areas where genotypes 3 and 4 were characterised, sequences from both humans and animals were highly conserved, indicating they originated from the same infectious sources. Based upon nucleotide differences from five phylogenies, it is proposed that five, two, ten and seven subtypes for HEV genotypes 1, 2, 3 and 4 be designated alphabetised subtypes. Accordingly, a total of 24 subtypes (1a, 1b, 1c, 1d, 1e, 2a, 2b, 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 4a, 4b, 4c, 4d, 4e, 4f and 4g) were given.

The hepatitis C virus (HCV), which currently infects an estimated 3% of people worldwide, has been present in some human populations for several centuries, notably HCV genotypes 1 and 2 in West Africa and genotype 6 in Southeast Asia. Here we use newly developed methods of sequence analysis to conduct the first comprehensive investigation of the epidemic and evolutionary history of HCV in Asia. Our analysis includes new HCV core (n ‫؍‬ 16) and NS5B (n ‫؍‬ 14) gene sequences, obtained from serum samples of jaundiced patients from Laos. These exceptionally diverse isolates were analyzed in conjunction with all available reference strains using phylogenetic and Bayesian coalescent methods. We performed statistical tests of phylogeographic structure and applied a recently developed "relaxed molecular clock" approach to HCV for the first time, which indicated an unexpectedly high degree of rate variation. Our results reveal a >1,000-year-long development of genotype 6 in Asia, characterized by substantial phylogeographic structure and two distinct phases of epidemic history, before and during the 20th century. We conclude that HCV lineages representing preexisting and spatially restricted strains were involved in multiple, independent local epidemics during the 20th century. Our analysis explains the generation and maintenance of HCV diversity in Asia and could provide a template for further investigations of HCV spread in other regions.

Sustained cardiac hypertrophy represents one of the most common causes leading to cardiac failure. There is emerging evidence to implicate the involvement of NF-B in the development of cardiac hypertrophy. However, several critical questions remain unanswered. We tested the use of soluble epoxide hydrolase (sEH) inhibitors as a means to enhance the biological activities of epoxyeicosatrienoic acids (EETs) to treat cardiac hypertrophy. sEH catalyzes the conversion of EETs to form the corresponding dihydroxyeicosatrienoic acids. Previous data have suggested that EETs may inhibit the activation of NF-B-mediated gene transcription. We directly demonstrate the beneficial effects of several potent sEH inhibitors (sEHIs) in cardiac hypertrophy. Specifically, we show that sEHIs can prevent the development of cardiac hypertrophy using a murine model of pressureinduced cardiac hypertrophy. In addition, sEHIs reverse the preestablished cardiac hypertrophy caused by chronic pressure overload. We further demonstrate that these compounds potently block the NF-B activation in cardiac myocytes. Moreover, by using in vivo electrophysiologic recordings, our study shows a beneficial effect of the compounds in the prevention of cardiac arrhythmias that occur in association with cardiac hypertrophy. We conclude that the use of sEHIs to increase the level of the endogenous lipid epoxides such as EETs may represent a viable and completely unexplored avenue to reduce cardiac hypertrophy by blocking NF-B activation.epoxyeicosatrienoic acids ͉ NF-B

To determine hepatitis C virus (HCV) genotype distribution in China, a total of 148 HCV RNA positive serum samples were collected from nine geographic areas and subjected to RT-PCR followed by direct DNA sequencing and phylogenetic analysis of the core, E1, and NS5B regions. HCV was genotyped in 139 (93.9%) samples. Among them subtype 1b was the most predominant [66% (92/139)] followed by 2a [14% (19/139)]. Of 92 subtype 1b isolates, 35 (38%) and 30 (33%) formed two clusters, designated groups A and B. Group A was prevalent throughout China, while group B was predominant in the central and southern regions. In three cities in the Pearl River Delta, subtype 6a replaced 2a as the second most predominant subtype, and in Kunming (southwest) multiple HCV genotypes/subtypes were present. New variants of HCV genotype 6 were discovered in three samples from Kunming and one in Guangzhou in the Pearl River Delta.