Deep-learning based bioactive therapeutic peptides generation and screening

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.

Medical prevention center for chronic diseases in the medical consortium of Wenling city / 中华医院管理杂志

" Medical prevention integration" is the practical need of the construction of healthy China and the focus of the construction of medical consortium in the future. Taking the practice of four chronic disease specific medical prevention centers of Wenling County medical consortium as an example, the authors analyzed their practices and experience in coordinating county advantageous resources, establishing organizational structure, and implementing chronic disease specific prevention and control based on informatization. The " medical prevention integration" system constructed by this mode optimized chronic disease service content, improved service capacity and service quality, and achieved in improving satisfaction. This mode could improve the effect and satisfaction of chronic disease management, improve the prevention and treatment efficiency of chronic diseases, and practice the whole cycle health management of chronic diseases.

Bipolar Plasma Kinetic Prostatectomy Combined with Holmium Laser Percutaneous Nephrolithotomy for Senior High Risk Patients with Benign Prostate Hyperplasia and Complicated Bladder Stone / 中国微创外科杂志

Objective To evaluated the role of transurethral plasmakinetic resection of the prostate ( TUPKRP ) in combination with percutaneous bladder channel lithotripsy with holmium laser in the treatment of benign prostate hyperplasia ( BPH) and bladder stone in senior patients . Methods Seventy-three patients treated during January 2009 to May 2014 were retrospectively reviewed.The patients aged 70-95 years old (mean, 85.6 years old).All of the patients were complicated with one or more diseases of the cardiovascular system .Ultrasound examinations prior to operation showed the sizes of prostates ranging 35-105 g, among which 58 cases showed middle prostatic lobe protruding into the bladder cavity .The sizes of the bladder stones ranged 1.5 -4.5 cm. Results The operations were successful in all the cases .The time of lithotripsy ranged 15-50 min (mean, 24 min), and the time of prostatectomy ranged 40 -135 min (mean, 70 min).No severe complications, such as major bleeding, transurethral resection syndrome, bladder perforation, residual stones, or severe infections, were observed.The urethral catheters were removed 3-5 days after operation, without urine leakage, dysuria, or urinary incontinence.Post-operation pathology of all the cases revealed BPH .The duration of hospitalization was 5-10 d (mean, 6 d).Three months after operation, the international prostate symptom scores were decreased from (23.5 ±5.1) points to (7.5 ±1.6) points (P<0.05), the quality of life (QOL) scores were decreased from (5.1 ± 0.5) points to (2.2 ±0.8) poins (P<0.05), the maximum flow rates (Qmax) were increased from (6.2 ±2.4) ml/s to (17.9 ± 4.2) ml/s (P<0.05), and residual urine volumes were decreased from (185.6 ±29.7) ml to (30.0 ±21.2) ml (P<0.05). Conclusion Transurethral plasmakinetic resection of the prostate in combination with percutaneous bladder channel lithotripsy with holmium laser is safe and effective for the treatment of benign prostate hyperplasia and bladder stone in senior patients .

A simple and fast detection method for bovine milk residues in foods: a 2-site monoclonal antibody immunochromatography assay.

UNLABELLED: The ingredient declaration on food labels assumes paramount importance in the protection of food-allergic consumers. China has not implemented Food allergen labeling. A gold immunochromatography assay (GICA) was developed using 2 monoclonal antibodies (mAb) against the milk allergen ß-lactoglobulin in this study. The GICA was specific for pure milk samples with a sensitivity of 0.2 ng/mL. Milk protein traces extracted from 110 food products were detected by this method. The labels of 106 were confirmed by our GICA method: 57 food samples originally labeled as containing milk were positive for ß-lactoglobulin and 49 food samples labeled as not containing milk were negative for ß-lactoglobulin. However, 3 food samples falsely labeled as containing milk were found to contain no ß-lactoglobulin whereas 1 food sample labeled as not containing milk actually contained ß-lactoglobulin. First, these negatives could be because of the addition of a casein fraction. Second, some countries demand that food manufacturers label all ingredients derived from milk as "containing milk" even though the ingredients contain no detectable milk protein by any method. Our GICA method could thus provide a fast and simple method for semiquantitatation of ß-lactoglobulin in foods. PRACTICAL APPLICATION: The present method provides a fast, simple, semiquantitative method for the determination of milk allergens in foods.

Gene cloning,prokaryotic vector constructing for the major allergen ovomucoid in Hen's egg white and its recombinant expression / 中国免疫学杂志

Objective:To clone and express the gene of ovomucoid,which is the main allevgen in egg white.Methods:Using total RNA of chicken oviduct as template,the gene of ovomucoid was amplified by RT-PCR.The homology was analyzed by comparision with the sequence in GeneBank.Subsequently,the PCR product of the ovomucoid gene was cloned into prokaryotic expressing vector pET-28a and was expressed by the challenge of IPTG.Results:The whole gene of ovomucoid,one of the main allergens in egg white,was successfully cloned.The cloned ORF sequence contains 633 bp,including stop codon,encods for 210 amino acids.Sequence analysis shows that the ovomucoid gene displays 99% nucleotide identities with the published sequences.The molecule weight of ovomucoid protein obtained was 21 kD.By the challenge of IPTG,SDS-PAGE analysis showed that the ovomucoid gene was overexpressed in E.coli BL21(DE3).Conclusion:The gene of ovomucoid is cloned and overexpressed in E.coli BL21(DE3).This study will be the basis for the further research.