The production of artemisinin, the most effective antimalarial compound, is limited to Artemisia annua. Enzymes involved in artemisinin biosynthesis include amorpha-4,11-diene synthase (ADS), amorpha-4,11-diene 12-monooxygenase (CYP71AV1) and artemisinic aldehyde Δ(11)13 reductase (DBR2). Although artemisinin and its specific intermediates are not detected in other Artemisia species, we reported previously that CYP71AV1 and DBR2 homologs were expressed in some non-artemisinin-producing Artemisia plants. These homologous enzymes showed similar functions to their counterparts in A. annua and can convert fed intermediates into the following products along the artemisinin biosynthesis in planta These findings suggested a partial artemisinin-producing ability in those species. In this study, we examined genes highly homologous to ADS, the first committed gene in the pathway, in 13 Artemisia species. We detected ADS homologs in A. absinthium, A. kurramensis and A. maritima. We analyzed the enzymatic functions of all of the ADS homologs after obtaining their cDNA. We found that the ADS homolog from A. absinthium exhibited novel activity in the cyclization of farnesyl pyrophosphate (FPP) to koidzumiol, a rare natural sesquiterpenoid. Those from A. kurramensis and A. maritima showed similar, but novel, activities in the cyclization of FPP to (+)-α-bisabolol. The unique functions of the novel sesquiterpene synthases highly homologous to ADS found in this study could provide insight into the molecular basis of the exceptional artemisinin-producing ability in A. annua.
The temporal and spatial distributions of a magnetically driven shunting arc plasma were obtained using time-resolved probe measurement. A shunting arc was produced using a carbon rod and accelerated along a pair of rail electrodes by a Lorenz force. The pulse current for driving and maintaining the plasma was supplied from a 20 µF capacitor charged by a dc power supply. Double and single probes were employed to obtain the ion density of the shunting arc plasma. An ion density of 1 × 1019 m−3 was obtained at a distance of 50 mm from the carbon rod 15 µs after applying voltage. The ion density decreased to 2.0 × 1018 m−3 with increasing distance from 50 to 150 mm. The ion density changed with the energy inputted into the plasma.
Accumulation of senescent cells is promoted in various organs as aging, and it also contributes to the progression of age-related disorders. Recent reports have demonstrated the elimination of senescent cells, so-called "senolysis" ameliorated various age-related disorders including cardiovascular diseases. However, there is currently no senolytic drug available in clinical settings. Here, we found a novel senolytic drug (termed “seno-7284”) from those already used in clinical setting and it exhibited senolytic effect in murine models of type 2 diabetes, atherosclerosis and progeroid aging. Conducting senescence-associated beta-galactosidase staining(SA-beta gal), we found that administrating seno-7284 for one week significantly reduced the accumulation of senescent cells in viscerala dipose tissue of diabetic mice induced by fed high-fat diet(Figure). This drug also ameliorated systemic glucose metabolism and adipose tissue inflammation without a reduction of body weight. Further analysis including RNA-seq analysis suggested seno-7284 stimulates the endogenous senolytic function of NK cells and CD8+ T cells via the Cxcl9-Cxcr3 axis. We also found administrating seno-7284 for two weeks also reduced the accumulation of senescent cells and atherosclerotic lesions in the aorta of western-diet-fed ApoE knock out mice. Surprisingly, this drug significantly improved the lifespan of Zmpste24 KO progeroid aging mice. Correctively, our results indicate that seno-7284 mediates its senolytic effect through the recruitment of lymphocytes. Senolytics would become a promising therapy for aging and age-related cardiometabolic disorders.
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