The first-generation chemical probes for species-selective fluorescence imaging of human senescence-associated β-galactosidase are developed.

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Previous evidence has revealed that increase in intracellular levels of calcium promotes cellular senescence. However, whether calcium channel blockers (CCBs) can slow aging and extend lifespan is still unknown. In this study, we showed that verapamil, an L-type calcium channel blocker, extended the Caenorhabditis elegans (C. elegans) lifespan and delayed senescence in human lung fibroblasts. Verapamil treatment also improved healthspan in C. elegans as reflected by several age-related physiological parameters, including locomotion, thrashing, age-associated vulval integrity, and osmotic stress resistance. We also found that verapamil acted on the α1 subunit of an L-type calcium channel in C. elegans. Moreover, verapamil extended worm lifespan by inhibiting calcineurin activity. Furthermore, verapamil significantly promoted autophagy as reflected by the expression levels of LGG-1/LC3 and the mRNA levels of autophagy-related genes. In addition, verapamil could not further induce autophagy when tax-6, calcineurin gene, was knocked down, indicating that verapamilinduced lifespan extension is mediated via promoting autophagy processes downstream of calcineurin. In summary, our study provided mechanistic insights into the anti-aging effect of verapamil in C. elegans.

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Combination drugs, characterized by high efficacy and few side effects, have received extensive attention from pharmaceutical companies and researchers for the treatment of complex diseases such as heart failure (HF). Traditional combination drug discovery depends on large-scale high-throughput experimental approaches that are time-consuming and costly. Herein we developed a novel, rapid, and potentially universal computer-guided combination drug-network-screening approach based on a set of databases and web services that are easy for individuals to obtain and operate, and we discovered for the first time that the menthol–allethrin combination screened by this approach exhibited a significant synergistic cardioprotective effect in vitro. Further mechanistic studies indicated that allethrin and menthol could synergistically block calcium channels. Allethrin bound to the central cavity of the voltage-dependent L-type calcium channel subunit alpha-1S (CACNA1S) lead to a conformational change in an allosteric site of CACNA1S, thereby enhancing the binding of menthol to this allosteric site. In summary, we reported a potentially universal computational approach to combination drug screening that has been used to discover a new combination of menthol–allethrin against HF in vitro, providing a new synergistic mechanism and prospective agent for HF treatment.

Aconitum episcopale Leveille is an important medicinal plant from the genus Aconitum L. of Ranunculaceae family and has been used as conventional medicine in Bai, Yi, and other ethnic groups of China. According to the available data and Ethno folk applications, A. episcopale is the only Aconitum species that has detoxifying and antialcoholic property. It can detoxify opium, especially the poisoning of Aconitum plants. Aconitum species have been widely used for their medicinal properties, and it is important to be noted that many of the species of this plant are reported to be toxic also. Distinguishing the species of this plant based on the morphology is a tough task and there are also no significant differences in the chemical composition. Therefore, before application of this plant for medicinal usage, it is very important to identify the species which could be life-threatening and exclude them. In this paper, the complete chloroplast (cp) genome sequence of A. episcopale was acquired by Illumina paired-end (PE) sequencing technology and compared with other species in the same family and genus. Herein, we report the complete cp genome of A. episcopale. The whole circular cp genome of A. episcopale has been found to be of 155,827 bp in size and contains a large single-copy region (LSC) of 86,452 bp, a small single-copy region (SSC) of 16,939 bp, and two inverted repeat regions (IRs) of 26,218 bp. The A. episcopale cp genome was found to be comprised of 132 genes, including 85 protein-coding genes (PCGs), 37 transfer RNA genes (tRNAs), eight ribosomal RNA genes (rRNAs), and two pseudogenes. A total of 20 genes contained introns, of which 14 genes contained a single intron and two genes had two introns. The chloroplast genome of A. episcopale contained 64 codons encoding 20 amino acids, with the number of codons encoding corresponding amino acids ranging from 22 to 1068. The Met and Trp amino acids have only one codon, and other amino acids had 2–6 codons. A total of 64 simple sequence repeats (SSRs) were identified, among which mononucleotide sequences accounted for the most. Phylogenetic analysis showed that A. episcopale is closely related with A. delavayi. Cumulatively the results of this study provided an essential theoretical basis for the molecular identification and phylogeny of A. episcopale.