Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.

Gossypium barbadense genome sequence provides insight into the evolution of extra-long staple fiber and specialized metabolites.

Of the two cultivated species of allopolyploid cotton, Gossypium barbadense produces extra-long fibers for the production of superior textiles. We sequenced its genome (AD)2 and performed a comparative analysis. We identified three bursts of retrotransposons from 20 million years ago (Mya) and a genome-wide uneven pseudogenization peak at 11-20 Mya, which likely contributed to genomic divergences. Among the 2,483 genes preferentially expressed in fiber, a cell elongation regulator, PRE1, is strikingly At biased and fiber specific, echoing the A-genome origin of spinnable fiber. The expansion of the PRE members implies a genetic factor that underlies fiber elongation. Mature cotton fiber consists of nearly pure cellulose. G. barbadense and G. hirsutum contain 29 and 30 cellulose synthase (CesA) genes, respectively; whereas most of these genes (>25) are expressed in fiber, genes for secondary cell wall biosynthesis exhibited a delayed and higher degree of up-regulation in G. barbadense compared with G. hirsutum, conferring an extended elongation stage and highly active secondary wall deposition during extra-long fiber development. The rapid diversification of sesquiterpene synthase genes in the gossypol pathway exemplifies the chemical diversity of lineage-specific secondary metabolites. The G. barbadense genome advances our understanding of allopolyploidy, which will help improve cotton fiber quality.

The concentrations, distribution and sources of PAHs in agricultural soils and vegetables from Shunde, Guangdong, China.

The concentrations, distribution and sources of 16 polycyclic aromatic hydrocarbons (PAHs) were determined in 30 agricultural soil and 16 vegetable samples collected from subtropical Shunde area, an important manufacturing center in China. The total PAHs ranged from 33.7 to 350 microg/kg in soils, and 82 to 1,258 microg/kg in vegetables. The most abundant individual PAHs are phenanthrene, fluoranthene, chrysene, pyrene and benzo(b)fluoranthene for soil samples, and anthracene, naphthalene, phenanthrene, pyrene and chrysene for vegetable samples. Average vegetable-soil ratios of total PAHs were 2.20 for leafy vegetables and 1.27 for fruity vegetables. Total PAHs in vegetable samples are not significantly correlated to those in corresponding soil samples. Principal component analyses were conducted to distinguish samples on basis of their distribution in each town, soil type and vegetable specie. Relatively abundant soil PAHs were found in town Jun'an, Beijiao, Chencun, Lecong and Ronggui, while abundant vegetable PAHs were observed in town Jun'an, Lecong, Xingtan, Daliang and Chenchun. The highest level of total PAHs were found in vegetable soil, followed by pond sediment and "stacked soil" on pond banks. The PAHs contents in leafy vegetables are higher than those in fruity vegetables. Some PAH compound ratios suggest the PAHs derived from incomplete combustion of petroleum, coal and refuse from power generation and ceramic manufacturing, and paint spraying on furniture, as well as sewage irrigation from textile industries. Soil PAHs contents have significant logarithmic correlation with total organic carbon, which demonstrates the importance of soil organic matter as sorbent to prevent losses of PAHs.