Human umbilical vein endothelial cells (HUVECs) have played a major role as a model system for the study of the regulation of endothelial cell function and the role of the endothelium in the response of the blood vessel wall to stretch, shear forces, and the development of atherosclerotic plaques and angiogenesis. Here, we use HUVECs and human microvascular endothelial cells to study the role of the HMG-CoA reductase inhibitor, simvastatin, and the small GTP-binding protein Rho in the regulation of angiogenesis. Simvastatin inhibited angiogenesis in response to FGF-2 in the corneal pocket assay of the mouse and in vascular endothelial growth factor (VEGF)-stimulated angiogenesis in the chick chorioallontoic membrane. Furthermore, simvastatin inhibited VEGF-stimulated tube formation by human dermal microvascular endothelial cells and the formation of honeycomb-like structures by HUVECs. The effect was dose-dependent and was not secondary to apoptosis. Geranylgeranyl-pyrophosphate (GGPP), a product of the cholesterol metabolic pathway that serves as a substrate for the posttranslational lipidation of RhoA, was required for membrane localization, but not farnesylpyrophosphate (FPP), the substrate for the lipidation of Ras. Furthermore, GGTI, a specific inhibitor of GGPP, mimicked the effect of simvastatin of tube formation and the formation of honeycombs whereas FTI, a specific inhibitor of the farnesylation of Ras, had no effect. Adenoviral expression of a DN-RhoA mutant mimicked the effect of simvastatin on tube formation and the formation of honeycombs, whereas a dominant activating mutant of RhoA reversed the effect of simvastatin on tube formation. Finally, simvastatin interfered with the membrane localization of RhoA with a dose-dependence similar to that for the inhibition of tube formation. Simvastatin also inhibited the VEGFstimulated phosphorylation of the VEGF receptor KDR, and the tyrosine kinase FAK, which plays a role in cell migration. These data demonstrate that simvastatin interfered with angiogenesis via the inhibition of RhoA. Data supporting a role for angiogenesis in the development and growth of atherosclerotic plaques suggest that this antiangiogenic effect of Statins might prevent the progression of atherosclerosis via the inhibition of plaque angiogenesis.

SummaryBackgroundAs one of only a handful of countries that have achieved both Millennium Development Goals (MDGs) 4 and 5, China has substantially lowered maternal mortality in the past two decades. Little is known, however, about the levels and trends of maternal mortality at the county level in China.MethodsUsing a national registration system of maternal mortality at the county level, we estimated the maternal mortality ratios for 2852 counties in China between 1996 and 2015. We used a state-of-the-art Bayesian small-area estimation hierarchical model with latent Gaussian layers to account for space and time correlations among neighbouring counties. Estimates at the county level were then scaled to be consistent with country-level estimates of maternal mortality for China, which were separately estimated from multiple data sources. We also assessed maternal mortality ratios among ethnic minorities in China and computed Gini coefficients of inequality of maternal mortality ratios at the country and provincial levels.FindingsChina as a country has experienced fast decline in maternal mortality ratios, from 108·7 per 100 000 livebirths in 1996 to 21·8 per 100 000 livebirths in 2015, with an annualised rate of decline of 8·5% per year, which is much faster than the target pace in MDG 5. However, we found substantial heterogeneity in levels and trends at the county level. In 1996, the range of maternal mortality ratios by county was 16·8 per 100 000 livebirths in Shantou, Guangdong, to 3510·3 per 100 000 livebirths in Zanda County, Tibet. Almost all counties showed remarkable decline in maternal mortality ratios in the two decades regardless of those in 1996. The annualised rate of decline across counties from 1996 to 2015 ranges from 4·4% to 12·9%, and 2838 (99·5%) of the 2852 counties had achieved the MDG 5 pace of decline. Decline accelerated between 2005 and 2015 compared with between 1996 and 2005. In 2015, the lowest county-level maternal mortality ratio was 3·4 per 100 000 livebirths in Nanhu District, Zhejiang Province. The highest was still in Zanda County, Tibet, but the fall to 830·5 per 100 000 livebirths was only 76·3%. 26 ethnic groups had population majorities in at least one county in China, and all had achieved declines in maternal mortality ratios in line with the pace of MDG 5. Intercounty Gini coefficients for maternal mortality ratio have declined at the national level in China, indicating improved equality, whereas trends in inequality at the provincial level varied.InterpretationIn the past two decades, maternal mortality ratios have reduced rapidly and universally across China at the county level. Fast improvement in maternal mortality ratios is possible even in less economically developed places with resource constraints. This finding has important implications for improving maternal mortality ratios in developing countries in the Sustainable Development Goal era.FundingNational Health and Family Planning Commission of the People's Republic of China, China Medical Board, WHO, University of ...

A novel hepatitis B virus (HBV) strain (W29) was isolated from serum samples in the northwest of China. Phylogenetic and distance analyses indicate that this strain is grouped with a series of distinct strains discovered in Vietnam and Laos that have been proposed to be a new genotype I. TreeOrderScan and GroupScan methods were used to study the intergenotype recombination of this special group. Recombination plots and tree maps of W29 and these putative genotype I strains exhibit distinct characteristics that are unexpected in typical genotype C strains of HBV. The amino acids of P gene, S gene, X gene, and C gene of all genotypes (including subtypes) were compared, and eight unique sites were found in genotype I. In vitro and in vivo experiments were also conducted to determine phenotypic characteristics between W29 and other representative strains of different genotypes obtained from China. Secretion of HBsAg in Huh7 cells is uniformly abundant among genotypes A, B, C, and I (W29), but not genotype D. HBeAg secretion is low in genotype I (W29), whose level is close to genotype A and much lower than genotypes B, C, and D. Results from the acute hydrodynamic injection mouse model also exhibit a similar pattern. From an overview of the results, the viral markers of W29 (I1) in Huh7 cells and mice had a more similar level to genotype A than genotype C, although the latter was closer to W29 in distance analysis. All evidence suggests that W29, together with other related strains found in Vietnam and Laos, should be classified into a new genotype.

Background The MYB transcription factor family is one of the largest transcriptional factor families in plants and plays a multifaceted role in plant growth and development. However, MYB transcription factors involved in pathogen resistance in apple remain poorly understood. Results We identified a new MYB family member from apple, and named it MdMYB30. MdMYB30 was localized to the nucleus, and was highly expressed in young apple leaves. Transcription of MdMYB30 was induced by abiotic stressors, such as polyethylene glycol and abscisic acid. Scanning electron microscopy and gas chromatograph–mass spectrometry analyses demonstrated that ectopically expressing MdMYB30 in Arabidopsis changed the wax content, the number of wax crystals, and the transcription of wax-related genes. MdMYB30 bound to the MdKCS1 promoter to activate its expression and regulate wax biosynthesis. MdMYB30 also contributed to plant surface properties and increased resistance to the bacterial strain Pst DC3000. Furthermore, a virus-based transformation in apple fruits and transgenic apple calli demonstrated that MdMYB30 increased resistance to Botryosphaeria dothidea . Our findings suggest that MdMYB30 plays a vital role in the accumulation of cuticular wax and enhances disease resistance in apple. Conclusions MdMYB30 bound to the MdKCS1 gene promoter to activate its transcription and regulate cuticular wax content and composition, which influenced the surface properties and expression of pathogenesis-related genes to resistance against pathogens. MdMYB30 appears to be a crucial element in the formation of the plant cuticle and confers apple with a tolerance to pathogens. Electronic supplementary material The online version of this article (10.1186/s12870-019-1918-4) contains supplementary material, which is available to authorized users.

A colorimetric assay for convenient detection of miRNA and RNase H activity was established in a homogeneous and label-free manner based on conformational and colorimetric changes of a polythiophene derivative (PMNT) in the duplex of DNA/PMNT and triplex of DNA/miRNA/PMNT.

Embryo transfer (ET) is an important procedure for assisted reproduction. However, the relatively lower success rate of ET hampers its application potential. In this study we aimed to elucidate the effects of extracellular vesicles derived from donor oviduct fluid (EDOF) on embryo development after ET. Extracellular vesicles from the oviduct were isolated and purified using ultracentrifugation and identified using transmission electron microscopy, NanoSight, bicinchoninic acid (BCA) protein assay and western blotting. The results revealed that extracellular vesicles were present in donor oviduct fluid in higher concentrations (P < 0.05) and contained more proteins (P < 0.05) than extracellular vesicles derived from recipient oviduct fluid (EROF). EDOF or EROF were supplemented in an ET medium (ETM) and the results showed that EDOF significantly improved birth rate via resisting apoptosis and promoting differentiation. In conclusion, our study indicated that there are differences in EDOF and EROF and that supplementing EDOF to ETM can improve the efficiency of ET; improved ET efficiency promotes the use of gene editing and benefits assisted reproductive technology and animal welfare.

The debate between cap-and-trade and carbon tax, two major carbon emission reduction mechanisms to deal with global warming, has been going on for years unsettled. The strategy to implement one of them or both is by far mainly addressed at the national level, and there is a need to customize the policy-making for different sectors, especially the emerging remanufacturing industry that has the great potential to reduce material and energy consumptions. Based on a closed-loop supply chain model, this study analyzes the tradeoffs between carbon tax and cap-and-trade with a series of numerical studies. While keeping carbon emissions under control, cap-and-trade demonstrates a better fit to remanufacturing: its performances on manufacturer profit, social welfare, and consumer surplus surpass carbon tax' in nine, eight, and six out of nine groups respectively. Only when the carbon quota level is too high, the cap-and-trade is possible to lose. In addition, this study examines two government-to-enterprise-subsidy (G-toE -S) strategies, direct subsidy and policy bias, and find both helpful but almost no difference in their impacts. The findings yield useful insights into the industry-wise design of carbon emission reduction mechanisms for remanufacturing and similar sectors.

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