Network analytics for drug repurposing in COVID-19.

To better understand the potential of drug repurposing in COVID-19, we analyzed control strategies over essential host factors for SARS-CoV-2 infection. We constructed comprehensive directed protein-protein interaction (PPI) networks integrating the top-ranked host factors, the drug target proteins and directed PPI data. We analyzed the networks to identify drug targets and combinations thereof that offer efficient control over the host factors. We validated our findings against clinical studies data and bioinformatics studies. Our method offers a new insight into the molecular details of the disease and into potentially new therapy targets for it. Our approach for drug repurposing is significant beyond COVID-19 and may be applied also to other diseases.

Twenty years of research on water management issues in the Danube Macro-region - past developments and future directions.

The Danube River-Danube Delta-Black Sea (DBS) region has witnessed major political, social and economic changes during the past three decades, which have profoundly affected the riverine, coastal and marine systems, their water management situation and the development of related research programmes. We reviewed the research activities in the DBS system of the past twenty years to determine the main funding bodies and to assess key research areas and how they varied over time and geographic region. As data basis we used a metadatabase filled with 478 projects addressing environmental and water management issues in the Danube River Basin, covering also the Danube Delta and the north-western Black Sea. As overall outcome extensive research efforts in the field of water management could be proven for the past two decades, despite the tumultuous times of political and economic transformations. One of the main findings was that EU funded projects played a key role for the development of transboundary research collaboration and were also the scientifically most productive one's. Historically, nutrient pollution was the main problem addressed, shifting to pollution in a broader sense and hydromorphological alterations in recent years. The newly arising challenges of climate change impacts and sediment management became important research questions in the last years, too. Most research was performed in the thematic field of navigation, followed by restoration and biodiversity issues. To meet all of the already identified and newly emerging challenges in the DBS System, cross-border and integrated (river-delta-sea) research activities are of major importance and have to be further promoted. We thus suggest drawing up a regional DBS Research Agenda linked to key challenges in water management to strengthen research collaboration and advance targeted scientific projects, an approach fostering also the scientific capacity in the region.

A novel dynamic layer-by-layer assembled nano-scale biointerface: functionality tests with platelet adhesion and aggregate morphology influenced by adenosine diphosphate.

An improved biointerface was developed, dynamic layer-by-layer self-assembly surface (d-LbL), and utilized as a biologically-active substrate for platelet adhesion and aggregation. Possible clinical applications for this research include improved anti-coagulation surfaces. This work demonstrated the functionality of d-LbL biointerfaces in the presence of platelet-rich-plasma (PRP) with the addition of 20 µM adenosine diphosphate (ADP), a thrombus activator. The surface morphology of the experimental control, plain PRP, was compared to PRP containing additional ADP (PRP + ADP) and resulted in an expected increase of platelet adhesions along the fibrinogen d-LbL substrate. The d-LbL process was used to coat glass slides with fibrinogen, Poly (sodium 4-styrene-sulfonate), and Poly (diallydimethlyammonium chloride). Slides were exposed to PRP under flow and static conditions with and without 20 µM of ADP. Fluorescence microscopy (FM), phase contrast microscopy (PCM), atomic force microscopy (AFM), and field emission-scanning electron microscopy (FE-SEM) were used to evaluate platelet adhesions under the influence of varied shear conditions. PCM images illustrated differences between the standard LbL and d-LbL substrates. FM images provided percent surface coverage values. For high-shear conditions, percent surface coverage values increased when using ADP whereas plain PRP exposure displayed no significant increase. AFM scans also displayed higher mean peak height values and unique surface characteristics for PRP + ADP as opposed to plain PRP. FE-SEM images revealed platelet adhesions along the biointerface and unique characteristics of the d-LbL surface. In conclusion, PRP + ADP was more effective at increasing platelet aggregation, especially under high shear conditions, providing further validation of the improved biointerface.