RESUMO
Many bioactive peptides demonstrated therapeutic effects over-complicated diseases, such as antiviral, antibacterial, anticancer, etc. Similar to the generating de novo chemical compounds, with the accumulated bioactive peptides as a training set, it is possible to generate abundant potential bioactive peptides with deep learning. Such techniques would be significant for drug development since peptides are much easier and cheaper to synthesize than compounds. However, there are very few deep learning-based peptide generating models. Here, we have created an LSTM model (named LSTM_Pep) to generate de novo peptides and finetune learning to generate de novo peptides with certain potential therapeutic effects. Remarkably, the Antimicrobial Peptide Database has fully utilized in this work to generate various kinds of potential active de novo peptide. We proposed a pipeline for screening those generated peptides for a given target, and use Main protease of SARS-COV-2 as concept-of-proof example. Moreover, we have developed a deep learning-based protein-peptide prediction model (named DeepPep) for fast screening the generated peptides for the given targets. Together with the generating model, we have demonstrated iteratively finetune training, generating and screening peptides for higher predicted binding affinity peptides can be achieved. Our work sheds light on to the development of deep learning-based methods and pipelines to effectively generating and getting bioactive peptides with a specific therapeutic effect, and showcases how artificial intelligence can help discover de novo bioactive peptides that can bind to a particular target.
RESUMO
OBJECTIVE: To observe the time distribution characteristic of silica nanoparticles in rats after one-time intratracheal infusion. METHODS: Specific pathogen free male Wistar rats were randomly divided into one control group and7 experimental groups according to different time of intratracheal infusion( 1,3,5,7,14,21 and 28 days),6 rats in each group. The experiment groups were intratracheally instilled with 1. 0 mL silica nanoparticle suspension( mass concentration 50. 00 g/L). The control group was not given any treatment. Rats were sacrificed and their organ tissue samples such as serum,lung,spleen,liver and kidney were collected at different time points. The silicon levels of tissues were determined by inductively coupled plasma optical-emission spectrometry. The histology of rat's lungs was observed by optical microscope and the location of silica in lungs was observed by polarization microscope. RESULTS: After exposure to silica nanoparticles for 1-7 days,the changes of rats' lung tissue was mainly exudative inflammation. The changes of lung was proliferative inflammatory lesions after 14-28 days of exposure to silica nanoparticles. The visible nodules of cells were observed in the lung tissue in 28 days experiment group. The distribution of silica nanoparticles was observed obviously in the lung tissues of rats of 1 day experiment group under the polarizing microscopy. The tendency decreased with the increase of observation time. Silica nanoparticles were rarely seen 21 and 28 days after intratracheal infusion in rats. The silicon levels of serum,lung and spleen tissues reached the peak in 1 day after silica nanoparticles instillation,then dropped in 3-7 days( serum) or 3-14 days( lung and spleen tissues) and went back to that of the control group's. The level of silicon in the livers and kidneys of rats in the experimental groups showed no significant increase in the level of 1-5 day after the instillation( P > 0. 05),and showed significant increase in the level of 7 day( P < 0. 05). The level reached its peak on time points of 14 and 21 days after the instillation,and subsequently decreased,and didn't returned to normal till the 28 th day. The silicon levels of the lungs,spleens,livers and kidneys were all higher in rats than that of serum( P < 0. 05). The silicon levels of the lungs and spleens were higher than that of the livers and kidneys after instillation for1-5 days( P < 0. 05). The silicon levels of the lungs and spleens were both lower than that of the livers and kidneys after instillation for 14-28 days( P < 0. 05). CONCLUSION: Silica nanoparticles can cause lung injury when instilled intratracheally in rats. After instillation,silica nanoparticles were mainly distributed in the lungs and spleens after 1-5 days and distributed in the livers and kidneys after 14-28 days.
