In Silico Investigation of Potential Src Kinase Ligands from Traditional Chinese Medicine

Src kinase is an attractive target for drug development based on its established relationship with cancer and possible link to hypertension. The suitability of traditional Chinese medicine (TCM) compounds as potential drug ligands for further biological evaluation was investigated using structure-based, ligand-based, and molecular dynamics (MD) analysis. Isopraeroside IV, 9alpha-hydroxyfraxinellone-9-O-beta-D-glucoside (9HFG) and aurantiamide were the top three TCM candidates identified from docking. Hydrogen bonds and hydrophobic interactions were the primary forces governing docking stability. Their stability with Src kinase under a dynamic state was further validated through MD and torsion angle analysis. Complexes formed by TCM candidates have lower total energy estimates than the control Sacaratinib. Four quantitative-structural activity relationship (QSAR) in silico verifications consistently suggested that the TCM candidates have bioactive properties. Docking conformations of 9HFG and aurantiamide in the Src kinase ATP binding site suggest potential inhibitor-like characteristics, including competitive binding at the ATP binding site (Lys295) and stabilization of the catalytic cleft integrity. The TCM candidates have significantly lower ligand internal energies and are estimated to form more stable complexes with Src kinase than Saracatinib. Structure-based and ligand-based analysis support the drug-like potential of 9HFG and aurantiamide and binding mechanisms reveal the tendency of these two candidates to compete for the ATP binding site

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

CO-OPETITION STRATEGY FROM THE PATENT ANALYSIS PERSPECTIVE: THE CASE OF THE STENT MARKET

Information about technological innovation and its evolutionary path can be explored by patent analysis. Therefore, for those firms which are dependant on large investments and a high business performance, such as stent manufacturers, integrating patent information with business strategy is the critical issue. The competition between stent manufactures is intensifying because of increasing global volume demand and improving technological performance. From a resource-based view, adopting a co-opetition strategy is essential for firms to keep sustainable competitive advantage. Over the last decade, patent rights have become a major tool of the co-opetition strategy. This study analyzes patent data from the USPTO during 1984 to 2005 and constructs patent information indicators to verify the process of technology evolution. On these grounds, we can understand the relative technological position and technological strength of the major manufacturers in this industry and also inspect their changes of position and business scope to examine the relationship between each firm's technology strategy and business strategy.patent strategy, co-opetition strategy, stent

Genetic Studies of Hypertrophic Cardiomyopathy in Singaporeans Identify Variants in TNNI3 and TNNT2 That Are Common in Chinese Patients

10.1161/CIRCGEN.119.002823CIRCULATION-GENOMIC AND PRECISION MEDICINE135424-43