For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ~1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.
Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV. The present study evaluated the safety and efficacy of 30 mg clevudine once daily for 24 weeks and assessed the durable antiviral response for 24 weeks after cessation of dosing. A total of 243 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients were randomized (3:1) to receive clevudine 30 mg once daily (n ؍ 182) or placebo (n ؍ 61) for 24 weeks. Patients were followed for a further 24 weeks off therapy. Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log 10 copies/mL in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained off therapy, with 3.73 log 10 reduction at week 34 and 2.02 log 10 reduction at week 48. At week 24, 59.0% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (less than 300 copies/mL). The proportion of patients who achieved normalization of alanine aminotransferase (ALT) levels was 68.2% in the clevudine group and 17.5% in the placebo group at week 24 (P < 0.0001). ALT normalization in the clevudine group was well maintained during post-treatment follow-up period. The incidence of adverse events (AEs) was similar between the clevudine group and the placebo group. No resistance to clevudine was detected with 24 weeks of administration of drug. Conclusion: A 24-week clevudine therapy was well tolerated and showed potent and sustained antiviral effect without evidence of viral resistance during treatment period in HBeAg-positive chronic hepatitis B. (
Activation of hepatic stellate cells (HSC) results in their proliferation and in the secretion of extracellular matrix (ECM) proteins, which leads to hepatic fibrosis. microRNAs (miRNAs) have been shown to regulate various cell functions, such as proliferation, differentiation, and apoptosis. Hence, we have analyzed the miRNAs that were differentially expressed in HSC isolated from sham-operated and bile duct-ligated rats. Expression of two miRNAs, miRNA-150 and miRNA-194, was reduced in HSC isolated from fibrotic rats compared with sham-operated animals. These two miRNAs were overexpressed in LX-2 cells, and their ability to inhibit cell proliferation, the expression of smooth muscle alpha-actin (SMA), a marker for activation, and collagen type I, a marker for ECM secretion, was determined. Overexpression of these two miRNAs resulted in a significant inhibition of proliferation (P < 0.05) and reduced SMA and collagen I levels compared with either untreated cells or nonspecific miRNA-expressing cells. Next, the protein targets of these two miRNAs were found using bioinformatics approaches. C-myb was found to be a target for miRNA-150, and rac 1 was found to be one of the targets for miRNA-194. Therefore, we studied the expression of these two proteins by overexpressing these two miRNAs in LX-2 cells and found that overexpression of miRNA-150 and miRNA-194 resulted in a significant inhibition of c-myb and rac 1 expression, respectively. We conclude that both miRNA-150 and miRNA-194 inhibit HSC activation and ECM production, at least in part, via inhibition of c-myb and rac 1 expression.
BMAC injection significantly improved both knee pain and functions in the patients with degenerative arthritis of knee. Also, the injection would be more effective in early to moderate phases.
Room-temperature optoelectronic devices that operate at shortwave and midwave infrared wavelengths (1-8 μm) can be used for numerous applications 1-5 . To achieve the operating wavelength range needed for a given application, a combination of materials with different bandgaps (e.g. superlattice/heterostructure) 6,7 or the variation of semiconductor alloy composition during growth 8,9 is used; however, these approaches involve fabrication complexity and the operating range is fixed post-fabrication. Although wide-range, active, and reversible tunability of the operating wavelengths in optoelectronic devices after fabrication is a highly desirable feature, no such platform has been yet developed. Here, we demonstrate high-performance room-temperature infrared optoelectronics with actively variable spectra by presenting black phosphorus (bP) as an ideal candidate. Enabled by the * � � 𝐸𝐸 𝑔𝑔 𝑘𝑘 𝐵𝐵 𝑇𝑇 �� (2)where 𝑚𝑚 𝑒𝑒 * and 𝑚𝑚 ℎ * are the effective masses of electrons and holes, respectively, 𝑘𝑘 𝐵𝐵 is Boltzmann's constant, and 𝑇𝑇 is temperature 36,37 . Since 𝑚𝑚 𝑒𝑒 * and 𝑚𝑚 ℎ * in bP have similar values, the effective mass ratio (𝑚𝑚 𝑒𝑒 * /𝑚𝑚 ℎ * ) is much higher than that of other small bandgap semiconductors.According to equation (2), this results in suppressed Auger recombination (longer Auger lifetime), which leads to bP's theoretical QY limit being much higher than that of other small bandgap semiconductors in the high injection regime.
A 24-week clevudine therapy was well-tolerated and showed potent and sustained antiviral effect without evidence of viral resistance in e-CHB patients. However, treatment for longer than 24 weeks would be needed to achieve durable remission.
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