A 4D printed nanoengineered super bioactive hydrogel scaffold with programmable deformation for potential bifurcated vascular channel construction.

Four-dimensional (4D) printing of hydrogels enabled the fabrication of complex scaffold geometries out of static parts. Although current 4D fabrication strategies are promising for creating vascular parts such as tubes, developing branched networks or tubular junctions is still challenging. Here, for the first time, a 4D printing approach is employed to fabricate T-shaped perfusable bifurcation using an extrusion-based multi-material 3D printing process. An alginate/methylcellulose-based dual-component hydrogel system (with defined swelling behavior) is nanoengineered with carbonized alginate (∼100 nm) to introduce anti-oxidative, anti-inflammatory, and anti-thrombotic properties and shape-shifting properties. A computational model to predict shape deformations in the printed hydrogels with defined infill angles was designed and further validated experimentally. Shape deformations of the 3D-printed flat sheets were achieved by ionic cross-linking. An undisrupted perfusion of a dye solution through a T-junction with minimal leakage mimicking blood flow through vessels is also demonstrated. Moreover, human umbilical vein endothelial and fibroblast cells seeded with printed constructs show intact morphology and excellent cell viability. Overall, the developed strategy paves the way for manufacturing self-actuated vascular bifurcations with remarkable anti-thrombotic properties to potentially treat coronary artery diseases.

Cheminformatics approach to identify andrographolide derivatives as dual inhibitors of methyltransferases (nsp14 and nsp16) of SARS-CoV-2.

The Covid-19 pandemic outbreak has accelerated tremendous efforts to discover a therapeutic strategy that targets severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to control viral infection. Various viral proteins have been identified as potential drug targets, however, to date, no specific therapeutic cure is available against the SARS-CoV-2. To address this issue, the present work reports a systematic cheminformatic approach to identify the potent andrographolide derivatives that can target methyltransferases of SARS-CoV-2, i.e. nsp14 and nsp16 which are crucial for the replication of the virus and host immune evasion. A consensus of cheminformatics methodologies including virtual screening, molecular docking, ADMET profiling, molecular dynamics simulations, free-energy landscape analysis, molecular mechanics generalized born surface area (MM-GBSA), and density functional theory (DFT) was utilized. Our study reveals two new andrographolide derivatives (PubChem CID: 2734589 and 138968421) as natural bioactive molecules that can form stable complexes with both proteins via hydrophobic interactions, hydrogen bonds and electrostatic interactions. The toxicity analysis predicts class four toxicity for both compounds with LD50 value in the range of 500-700 mg/kg. MD simulation reveals the stable formation of the complex for both the compounds and their average trajectory values were found to be lower than the control inhibitor and protein alone. MMGBSA analysis corroborates the MD simulation result and showed the lowest energy for the compounds 2734589 and 138968421. The DFT and MEP analysis also predicts the better reactivity and stability of both the hit compounds. Overall, both andrographolide derivatives exhibit good potential as potent inhibitors for both nsp14 and nsp16 proteins, however, in-vitro and in vivo assessment would be required to prove their efficacy and safety in clinical settings. Moreover, the drug discovery strategy aiming at the dual target approach might serve as a useful model for inventing novel drug molecules for various other diseases.

Impacts of recent rainfall changes on agricultural productivity and water resources within the Southern Western Ghats of Kerala, India.

Significant changes in rainfall patterns are critical to agriculture, and the dependency of cropping systems on rainfall variability would engender appropriate farming practices and agriculture policies for a climate-resilient agriculture system. This study analyses the significance of rainfall variability on agriculture productivity in the Wayanad district of Kerala (India) using time series data on rainfall (1989-2019) and crop yield (2000-2019). The spatial variability of rainfall patterns reveals a dichotomy between the rain gauge stations in the northern and southern parts of the region. Despite the absence of statistically significant trends in the monthly, seasonal and annual rainfall, based on the Mann-Kendall trend analysis, an increase in the yield of many crops (e.g., winter paddy, banana) is evident, which emphasises the critical role of irrigation in driving the crop productivity. As an adaptation strategy to changing rainfall patterns, irrigation would meet the additional crop water requirement for sustainable agricultural production under the varying rainfall distributions. However, the increase in the area under irrigation in recent years has had significant implications for both surface water and groundwater resources. The conclusive findings suggest that the region requires climate-resilient agriculture, focusing on optimising irrigation and developing sustainable agriculture and water conservation strategies.