Persistent hepatitis C virus infection in vitro: coevolution of virus and host.

The virological and cellular consequences of persistent hepatitis C virus (HCV) infection have been elusive due to the absence of the requisite experimental systems. Here, we report the establishment and the characteristics of persistent in vitro infection of human hepatoma-derived cells by a recently described HCV genotype 2a infectious molecular clone. Persistent in vitro infection was characterized by the selection of viral variants that displayed accelerated expansion kinetics, higher peak titers, and increased buoyant densities. Sequencing analysis revealed the selection of a single adaptive mutation in the HCV E2 envelope protein that was largely responsible for the variant phenotype. In parallel, as the virus became more aggressive, cells that were resistant to infection emerged, displaying escape mechanisms operative at the level of viral entry, HCV RNA replication, or both. Collectively, these results reveal the existence of coevolutionary events during persistent HCV infection that favor survival of both virus and host

(Diethyl ether){1-[2-(1-methyl-1H-imidazol-2-yl-κN 3)-1,1-diphenyl­ethyl]-(1,2,3,3a,7a-η)-inden­yl}lithium(I)

In the title compound, [Li(C27H23N2)(C4H10O)], the Li atom possesses a nearly planar trigonal coordination environment (assuming the cyclo­penta­dienyl ring of the indenyl group occupies one coordination place). The diethyl ether ligand adopts a nearly planar W-type conformation

Estimating household air pollution exposures and health impacts from space heating in rural China

Exposure to and the related burden of diseases caused by pollution from solid fuel cooking, known as household air pollution (HAP), has been incorporated in the assessment of the Global Burden of Diseases (GBD) project. In contrast, HAP from space heating using solid fuels, prevalent in countries at middle or high altitudes, is less studied and missing from the GBD assessment. China is an ideal example to estimate the bias of exposure and burden of diseases assessment when space heating is neglected, considering its remarkably changing demands for heating from the north to the south and a large solid-fuel-dependent rural population. In this study, based on a meta-analysis of 27 field measurement studies in rural China, we derive the indoor PM2.5 (fine particulate matter with an aerodynamic diameter smaller than 2.5 μm) concentration for both the heating and non-heating seasons. Combining this dataset with time-activity patterns and percentage of households using solid fuels, we assess the population-weighted annual mean exposure to PM2.5 (PWE) and the health impacts associated with HAP in mainland rural China by county for the year 2010. We find that ignoring heating impacts leads to an underestimation in PWE estimates by 38 μg/m3 for the nationwide rural population (16 to 40 as interquartile range) with substantial negative bias in northern provinces. Correspondingly, premature deaths and disability-adjusted life years will be underestimated by approximately 30 × 103 and 60 × 104 in 2010, respectively. Our study poses the need for incorporating heating effects into HAP risk assessments in China as well as globally

Distinguishing Emission-Associated Ambient Air PM2.5 Concentrations and Meteorological Factor-Induced Fluctuations

Although PM2.5 (particulate matter with aerodynamic diameters less than 2.5 μm) in the air originates from emissions, its concentrations are often affected by confounding meteorological effects. Therefore, direct comparisons of PM2.5 concentrations made across two periods, which are commonly used by environmental protection administrations to measure the effectiveness of mitigation efforts, can be misleading. Here, we developed a two-step method to distinguish the significance of emissions and meteorological factors and assess the effectiveness of emission mitigation efforts. We modeled ambient PM2.5 concentrations from 1980 to 2014 based on three conditional scenarios: realistic conditions, fixed emissions, and fixed meteorology. The differences found between the model outputs were analyzed to quantify the relative contributions of emissions and meteorological factors. Emission-related gridded PM2.5 concentrations excluding the meteorological effects were predicted using multivariate regression models, whereas meteorological confounding effects on PM2.5 fluctuations were characterized by probabilistic functions. When the regression models and probabilistic functions were combined, fluctuations in the PM2.5 concentrations induced by emissions and meteorological factors were quantified for all model grid cells and regions. The method was then applied to assess the historical and future trends of PM2.5 concentrations and potential fluctuations on global, national, and city scales. The proposed method may thus be used to assess the effectiveness of mitigation actions

Impacts of air pollutants from rural Chinese households under the rapid residential energy transition

Rural residential energy consumption in China is experiencing a rapid transition towards clean energy, nevertheless, solid fuel combustion remains an important emission source. Here we quantitatively evaluate the contribution of rural residential emissions to PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 μm) and the impacts on health and climate. The clean energy transitions result in remarkable reductions in the contributions to ambient PM2.5, avoiding 130,000 (90,000-160,000) premature deaths associated with PM2.5 exposure. The climate forcing associated with this sector declines from 0.057 ± 0.016 W/m2 in 1992 to 0.031 ± 0.008 W/m2 in 2012. Despite this, the large remaining quantities of solid fuels still contributed 14 ± 10 μg/m3 to population-weighted PM2.5 in 2012, which comprises 21 ± 14% of the overall population-weighted PM2.5 from all sources. Rural residential emissions affect not only rural but urban air quality, and the impacts are highly seasonal and location dependent

Extensive beam test study of prototype MRPCs for the T0 detector at the CSR external-target experiment

The CSR External-target Experiment (CEE) will be the first large-scale nuclear physics experiment device at the Cooling Storage Ring (CSR) of the Heavy-Ion Research Facility in Lanzhou (HIRFL) in China. A new T0 detector has been proposed to measure the multiplicity, angular distribution and timing information of charged particles produced in heavy-ion collisions at the target region. Multi-gap resistive plate chamber (MRPC) technology was chosen as part of the construction of the T0 detector, which provides precision event collision times (T0) and collision geometry information. The prototype was tested with hadron and heavy-ion beams to study its performance. By comparing the experimental results with a Monte Carlo simulation, the time resolution of the MRPCs are found to be $\sim$ 50 ps or better. The timing performance of the T0 detector, including both detector and readout electronics, we found to fulfil the requirements of the CEE.Comment: 12 pages, 36 figure

Substantial transition to clean household energy mix in rural China

The household energy mix has significant impacts on human health and climate, as it contributes greatly to many health- and climate-relevant air pollutants. Compared to the well-established urban energy statistical system, the rural household energy statistical system is incomplete and is often associated with high biases. Via a nationwide investigation, this study revealed high contributions to energy supply from coal and biomass fuels in the rural household energy sector, while electricity comprised ∼20%. Stacking (the use of multiple sources of energy) is significant, and the average number of energy types was 2.8 per household. Compared to 2012, the consumption of biomass and coals in 2017 decreased by 45% and 12%, respectively, while the gas consumption amount increased by 204%. Increased gas and decreased coal consumptions were mainly in cooking, while decreased biomass was in both cooking (41%) and heating (59%). The time-sharing fraction of electricity and gases (E&G) for daily cooking grew, reaching 69% in 2017, but for space heating, traditional solid fuels were still dominant, with the national average shared fraction of E&G being only 20%. The non-uniform spatial distribution and the non-linear increase in the fraction of E&G indicated challenges to achieving universal access to modern cooking energy by 2030, particularly in less-developed rural and mountainous areas. In some non-typical heating zones, the increased share of E&G for heating was significant and largely driven by income growth, but in typical heating zones, the time-sharing fraction was <5% and was not significantly increased, except in areas with policy intervention. The intervention policy not only led to dramatic increases in the clean energy fraction for heating but also accelerated the clean cooking transition. Higher income, higher education, younger age, less energy/stove stacking and smaller family size positively impacted the clean energy transition

The calcimimetic R-568 induces apoptotic cell death in prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Increased serum level of parathyroid hormone (PTH) was found in metastatic prostate cancers. Calcimimetic R-568 was reported to reduce PTH expression, to suppress cell proliferation and to induce apoptosis in parathyroid cells. In this study, we investigated the effect of R-568 on cellular survival of prostate cancer cells.</p> <p>Methods</p> <p>Prostate cancer cell lines LNCaP and PC-3 were used in this study. Cellular survival was determined with MTT, trypan blue exclusion and fluorescent Live/Death assays. Western blot assay was utilized to assess apoptotic events induced by R-568 treatment. JC-1 staining was used to evaluate mitochondrial membrane potential.</p> <p>Results</p> <p>In cultured prostate cancer LNCaP and PC-3 cells, R-568 treatment significantly reduced cellular survival in a dose- and time-dependent manner. R-568-induced cell death was an apoptotic event, as evidenced by caspase-3 processing and PARP cleavage, as well as JC-1 color change in mitochondria. Knocking down calcium sensing receptor (CaSR) significantly reduced R-568-induced cytotoxicity. Enforced expression of Bcl-xL gene abolished R-568-induced cell death, while loss of Bcl-xL expression led to increased cell death in R-568-treated LNCaP cells,.</p> <p>Conclusion</p> <p>Taken together, our data demonstrated that calcimimetic R-568 triggers an intrinsic mitochondria-related apoptotic pathway, which is dependent on the CaSR and is modulated by Bcl-xL anti-apoptotic pathway.</p