EFFECT OF AUTOGENOUS SELF-HEALING ON HIGH TEMPERATURE EXPOSED ULTRA HIGH-PERFORMANCE CONCRETE

Mechanical properties of Ultra High-Performance Concrete (UHPC) degrade when exposed to elevated temperatures, even more than ordinary concretes due to its dense microstructure. Concerning, in particular, the special application of nuclear power plants, in which UHPC can find a promising use, concrete can be subjected to moderately high temperature (usually lower than 400 °C) along the working life, this making of interest the study on the influence and persistence of UHPC's innate self-healing capabilities over the thermal degradation. In this context, the paper focuses on an experimental study of UHPC recovery ability by autogenous self-healing after being exposed to high temperatures. The UHPC specimens have been made with hybrid fibers, that is, polypropylene and steel fibers, and have been pre-cracked up to a cumulative crack width of 0.3 mm under 4-point flexural test. The pre-cracked specimens have been exposed to a temperature of 200 °C or 400 °C, with a heating rate of 1 °C / minute from room temperature and kept at the target temperature for two hours, with a following slow cooling at a rate of <1 °C / minute. The specimens have been kept in the lab environment for 24 hours after reaching room temperature. Then they have been tested for residual flexural capacity or allowed to self-heal under water immersion for six months. The damage and healing evolution have been monitored periodically using ultra-sonic pulse velocity survey and digital microscope inspection. In spite of the thermal degradation, during the healing period UHPC showed a significant recovery in terms of strength assessed by ultrasonic pulse velocity tests

Exploring Toxins for Hunting SARS-CoV-2 Main Protease Inhibitors: Molecular Docking, Molecular Dynamics, Pharmacokinetic Properties, and Reactome Study

The main protease (Mpro) is a potential druggable target in SARS-CoV-2 replication. Herein, an in silico study was conducted to mine for Mpro inhibitors from toxin sources. A toxin and toxin-target database (T3DB) was virtually screened for inhibitor activity towards the Mpro enzyme utilizing molecular docking calculations. Promising toxins were subsequently characterized using a combination of molecular dynamics (MD) simulations and molecular mechanics-generalized Born surface area (MM-GBSA) binding energy estimations. According to the MM-GBSA binding energies over 200 ns MD simulations, three toxins—namely philanthotoxin (T3D2489), azaspiracid (T3D2672), and taziprinone (T3D2378)—demonstrated higher binding affinities against SARS-CoV-2 Mpro than the co-crystalized inhibitor XF7 with MM-GBSA binding energies of −58.9, −55.9, −50.1, and −43.7 kcal/mol, respectively. The molecular network analyses showed that philanthotoxin provides a ligand lead using the STRING database, which includes the biochemical top 20 signaling genes CTSB, CTSL, and CTSK. Ultimately, pathway enrichment analysis (PEA) and Reactome mining results revealed that philanthotoxin could prevent severe lung injury in COVID-19 patients through the remodeling of interleukins (IL-4 and IL-13) and the matrix metalloproteinases (MMPs). These findings have identified that philanthotoxin—a venom of the Egyptian solitary wasp—holds promise as a potential Mpro inhibitor and warrants further in vitro/in vivo validation

Exploring Natural Product Activity and Species Source Candidates for Hunting ABCB1 Transporter Inhibitors: An In Silico Drug Discovery Study

The P-glycoprotein (P-gp/ABCB1) is responsible for a xenobiotic efflux pump that shackles intracellular drug accumulation. Additionally, it is included in the dud of considerable antiviral and anticancer chemotherapies because of the multidrug resistance (MDR) phenomenon. In the search for prospective anticancer drugs that inhibit the ABCB1 transporter, the Natural Product Activity and Species Source (NPASS) database, containing >35,000 molecules, was explored for identifying ABCB1 inhibitors. The performance of AutoDock4.2.6 software to anticipate ABCB1 docking score and pose was first assessed according to available experimental data. The docking scores of the NPASS molecules were predicted against the ABCB1 transporter. Molecular dynamics (MD) simulations were conducted for molecules with docking scores lower than taxol, a reference inhibitor, pursued by molecular mechanics-generalized Born surface area (MM-GBSA) binding energy estimations. On the basis of MM-GBSA calculations, five compounds revealed promising binding affinities as ABCB1 inhibitors with ΔGbinding < −105.0 kcal/mol. The binding affinity and stability of the identified inhibitors were compared to the chemotherapeutic agent. Structural and energetical analyses unveiled great steadiness of the investigated inhibitors within the ABCB1 active site throughout 100 ns MD simulations. Conclusively, these findings point out that NPC104372, NPC475164, NPC2313, NPC197736, and NPC477344 hold guarantees as potential ABCB1 drug candidates and warrant further in vitro/in vivo tests