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Coumarin hybrids have been designed and synthesized as an important new strategy in the field of medicinal chemistry. Coumarin core has been shown to form various compounds to combat several diseases including microbial, cancer, inflammatory, and neurodegenerative disorders. Recently, a number of coumarin-based drugs (e.g., coumadin, acenocoumarol, dicoumarol, phenprocoumon, and novobiocin) have been FDA-approved and are in the clinic, and several coumarin-containing compounds are in clinical trials. Our group classified coumarin-based hybrid compounds into groups showing shared biological activities and discussed their potential therapeutic targets. Graphical Abstract

Heterosis, or hybrid vigor, is exploited by breeders to produce elite high-yielding crop lines, but beneficial phenotypes are lost in subsequent generations owing to genetic segregation. Clonal propagation through seeds would enable self-propagation of F1 hybrids. Here we report a strategy to enable clonal reproduction of F1 rice hybrids through seeds. We fixed the heterozygosity of F1 hybrid rice by multiplex CRISPR–Cas9 genome editing of the REC8, PAIR1 and OSD1 meiotic genes to produce clonal diploid gametes and tetraploid seeds. Next, we demonstrated that editing the MATRILINEAL (MTL) gene (involved in fertilization) could induce formation of haploid seeds in hybrid rice. Finally, we combined fixation of heterozygosity and haploid induction by simultaneous editing of all four genes (REC8, PAIR1, OSD1 and MTL) in hybrid rice and obtained plants that could propagate clonally through seeds. Application of our method may enable self-propagation of a broad range of elite F1 hybrid crops.