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Direct-acting antiviral agents (DAAs) are known to interfere with various intracellular stages of the hepatitis C virus (HCV) life cycle and have demonstrated efficacy in treating HCV infection. However, DAA monotherapy can lead to drug resistance due to mutations. This paper explores the impact of DAA therapy on HCV dynamics using a multiscale age-structured partial differential equation (PDE) model that incorporates intracellular viral RNA replication within infected cells and two strains of viruses representing a drug-sensitive strain and a drug-resistant mutant variant, respectively. We derived an equivalent ordinary differential equation (ODE) model from the PDE model to simplify mathematical analysis and numerical simulations. We studied the dynamics of the two virus strains before treatment and investigated the impact of mutations on the evolution kinetics of drug-sensitive and drug-resistant viruses, as well as the competition between the two strains during treatment. We also explored the role of DAAs in blocking HCV RNA replication and releasing new virus particles from cells. During treatment, mutations do not significantly influence the dynamics of various virus strains; however, they can generate low-level HCV that may be completely inhibited due to their poor fitness. The fitness of the mutant strain compared to the drug-sensitive strain determines which strain dominates the virus population. We also investigated the prevalence and drug resistance evolution of HCV variants during DAA treatment. 

A close correlation between lithofacies and organofacies in meter-scale high-order cycles composed of lacustrine sediments enables comparison and refinement of lithofacies-defined cyclostratigraphy. Four lithofacies and four organofacies have been identified in fluctuating profundal high-order cycles in the lower-Permian Lucaogou Formation, southern Bogda Mountains, NW China. The four lithofacies include interbedded and interlaminated coarse siltstone and very fine sandstone, black shale, wackestone and dolostone, and calcareous and dolomitic shales. Four distinctive organofacies have been identified, on the basis of geochemical composition of organic matter and specific biomarker proxies related to organic matter types, rather than to depositional conditions and thermal maturity. The four organofacies are associated with the four lithofacies in the meter-scale high-order cycles, suggesting litho- and organo-facies may be genetically linked and may have been controlled by lake contraction and extension. The study shows that the lithofacies-derived and environment-defined high-order cycles can be delineated and substantiated by geochemical proxies-defined organofacies. This study also demonstrates that a holistic approach combining litho- and organic geochemical data is useful in reconstruction of meter-scale lacustrine cycles in a half-graben. 

Consumption in industrialized regions contributes to land-use change and greenhouse gas emissions in low-income regions.