Yanzheng Xie,Lei Xie,Ailan Chen,Shengnan Wu,Yuxiao Mo,Xiaoqiang Guo,Changchun Zeng,Xinan Huang,Jinyang He
AIDS , a serious fatal disease caused by the human immunodeficiency virus (HIV), is an epidemic disease for which no effective vaccine has been established. The current therapeutic interventions for AIDS have limited efficacy because they are unable to clear HIV infections and the continuous occurrence of resistant HIV strains. Therefore, the exploitation of new drugs to prevent the spread of AIDS remains a high priority. In this study, the effects of icariin and its metabolite anhydroicaritin on SIV/HIV replication were investigated. In CEM × 174 cells and PBMC cells, both icariin and anhydroicaritin can significantly inhibit HIV-1 or SIVmac251 replication. Furthermore, molecular docking studies revealed that icariin and anhydroicaritin can act on both HIV reverse transcriptase and protease but could not bind to integrase . Reverse transcriptase and protease inhibition biological assays showed that both icariin and anhydroicaritin could significantly inhibit only HIV reverse transcriptase. In summary, the two compounds can significantly inhibit HIV/SIV in vitro and their targets may be mainly involved with HIV reverse transcriptase.
Ba Fang,Liu Yushi,Liu Wan-Qiu,Tian Xintong,Li Jian
Serine integrases are emerging as one of the most powerful biological tools for synthetic biology. They have been widely used across genome engineering and genetic circuit design. However, developing serine integrase-based tools for directly/precisely manipulating synthetic biobricks is still missing. Here, we report SYMBIOSIS, a versatile method that can robustly manipulate DNA parts in vivo and in vitro. First, we propose a ‘keys match locks’ model to demonstrate that three orthogonal serine integrases are able to irreversibly and stably switch on seven synthetic biobricks with high accuracy in vivo. Then, we demonstrate that purified integrases can facilitate the assembly of ‘donor’ and ‘acceptor’ plasmids in vitro to construct composite plasmids. Finally, we use SYMBIOSIS to assemble different chromoprotein genes and create novel colored Escherichia coli. We anticipate that our SYMBIOSIS strategy will accelerate synthetic biobrick manipulation, genetic circuit design and multiple plasmid assembly for synthetic biology with broad potential applications.
Livestock manure has been identified as a significant hotspot for antibiotic resistance genes (ARGs). However, the impact of nanoscale zero-valent iron (nZVI) on the fate of ARGs during livestock manure composting remains poorly understood. Here, we investigated the evolution of ARGs in chicken manure compost exposed to 100 and 600 mg kg −1 nZVI. The results showed that nZVI addition reduced the concentration of some antibiotics such as doxycycline and sulfamethoxazole. Furthermore, nZVI addition decreased the abundances of most ARGs at the end of composting, but nZVI dosage did not have any significant effect. The abundances of the dominant ARGs ( sul1 and sul2 ) were significantly correlated to the class 1 integron-integrase gene ( intI1 ). A network analysis revealed that the genera Bacteroides , Bacillus , Corynebacterium , Thiopseudomonas and Pseudomonas were the main potential hosts for multiple ARGs, and the decreased abundance of these bacteria contributed to the removal of ARGs. Structural equation models demonstrated that the reduction in intI1 played a predominant role in ARG removal. The nZVI also had direct effects on the intI1 abundance. These findings suggest that the addition of nZVI is a promising strategy to minimize ARG release in chicken manure compost.
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