Fluoxazolevir is an aryloxazole-based entry inhibitor of hepatitis C virus (HCV). We show that fluoxazolevir inhibits fusion of HCV with hepatic cells by binding HCV envelope protein 1 to prevent fusion. Nine of ten fluoxazolevir resistance-associated substitutions are in envelope protein 1, and four are in a putative fusion peptide. Pharmacokinetic studies in mice, rats and dogs revealed that fluoxazolevir localizes to the liver. A 4-week intraperitoneal regimen of fluoxazolevir in humanized chimeric mice infected with HCV genotypes 1b, 2a or 3 resulted in a 2-log reduction in viraemia, without evidence of drug resistance. In comparison, daclatasvir, an approved HCV drug, suppressed more than 3 log of viraemia but is associated with the emergence of resistance-associated substitutions in mice. Combination therapy using fluoxazolevir and daclatasvir cleared HCV genotypes 1b and 3 in mice. Fluoxazolevir combined with glecaprevir and pibrentasvir was also effective in clearing multidrug-resistant HCV replication in mice. Fluoxazolevir may be promising as the next generation of combination drug cocktails for HCV treatment.Cellular metabolic reprogramming is an important mechanism by which cells rewire their metabolism to promote proliferation and cell growth. This process has been mostly studied in the context of tumorigenesis, but less is known about its relevance for nonpathological processes and how it affects whole-animal physiology. Here, we show that metabolic reprogramming in Drosophila female germline cells affects nutrient preferences of animals. Egg production depends on the upregulation of the activity of the pentose phosphate pathway in the germline, which also specifically increases the animal’s appetite for sugar, the key nutrient fuelling this metabolic pathway. We provide functional evidence that the germline alters sugar appetite by regulating the expression of the fat-body-secreted satiety factor Fit. Our findings demonstrate that the cellular metabolic program of a small set of cells is able to increase the animal’s preference for specific nutrients through inter-organ communication to promote specific metabolic and cellular outcomes.Optical tweezers have emerged as a powerful tool for the non-invasive trapping and manipulation of colloidal particles and biological cells1,2. However, the diffraction limit precludes the low-power trapping of nanometre-scale objects. Substantially increasing the laser power can provide enough trapping potential depth to trap nanoscale objects. Unfortunately, the substantial optical intensity required causes photo-toxicity and thermal stress in the trapped biological specimens3. Low-power near-field nano-optical tweezers comprising plasmonic nanoantennas and photonic crystal cavities have been explored for stable nanoscale object trapping4-13. However, the demonstrated approaches still require that the object is trapped at the high-light-intensity region. We report a new kind of optically controlled nanotweezers, called opto-thermo-electrohydrodynamic tweezers, that enable the trapping and dynamic manipulation of nanometre-scale objects at locations that are several micrometres away from the high-intensity laser focus. At the trapping locations, the nanoscale objects experience both negligible photothermal heating and light intensity. Opto-thermo-electrohydrodynamic tweezers employ a finite array of plasmonic nanoholes illuminated with light and an applied a.c. electric field to create the spatially varying electrohydrodynamic potential that can rapidly trap sub-10 nm biomolecules at femtomolar concentrations on demand. This non-invasive optical nanotweezing approach is expected to open new opportunities in nanoscience and life science by offering an unprecedented level of control of nano-sized objects, including photo-sensitive biological molecules.Epigenetic regulation involves changes in gene expression independent of DNA sequence variation that are inherited through cell division. In addition to a fundamental role in cell differentiation, some epigenetic changes can also be transmitted transgenerationally through meiosis. Epigenetic alterations (epimutations) could thus contribute to heritable variation within populations and be subject to evolutionary processes such as natural selection and drift. However, the rate at which epimutations arise and their typical persistence are unknown, making it difficult to evaluate their potential for evolutionary adaptation. Here, we perform a genome-wide study of epimutations in a metazoan organism. We use experimental evolution to characterize the rate, spectrum and stability of epimutations driven by small silencing RNAs in the model nematode Caenorhabditis elegans. We show that epimutations arise spontaneously at a rate approximately 25 times greater than DNA sequence changes and typically have short half-lives of two to three generations. Nevertheless, some epimutations last at least ten generations. Epimutations mediated by small RNAs may thus contribute to evolutionary processes over a short timescale but are unlikely to bring about long-term divergence in the absence of selection.The Green Revolution is credited with alleviating famine, mitigating poverty and driving aggregate economic growth since the 1960s. In Asia, high-input technology packages secured a tripling of rice output, with germplasm improvements providing benefits beyond US$4.3 billion yr-1. Here, we unveil the magnitude and macro-economic relevance of parallel nature-based contributions to productivity growth in non-rice crops over the period 1918-2018 (across 23 different Asia-Pacific geopolitical entities). We empirically demonstrate how biological control resolved invasive pest threats in multiple agricultural commodities, ensuring annually accruing (on-farm) benefits of US$14.6-19.5 billion yr-1. Scientifically guided biological control of 43 exotic invertebrate pests permitted 73-100% yield-loss recovery in critical food, feed and fibre crops including banana, breadfruit, cassava and coconut. Biological control thereby promoted rural growth and prosperity even in marginal, poorly endowed, non-rice environments. read more By placing agro-ecological innovations on equal footing with input-intensive measures, our work provides lessons for future efforts to mitigate invasive species, restore ecological resilience and sustainably raise output of global agrifood systems.