In silico Investigation of Cyclosporine Conjugates as Potential Anti-angiogenic Agents via NFAT Inhibition
Calcineurin (CN) activation is a main cause of cancerous tumor formation, one of the leading causes of death globally. Cyclosporine-A (CsA) is a commercially available oral drug that inhibits CN activation; however, low bioavailability limits its use. Nine patented CsA conjugates are potential alternatives to CsA as they have improved cytotoxicities and bioavailabilities but unknown CN-binding affinity. This study aimed to identify the CNinhibition strength and bioavailability of CsA conjugates in silico drug-likeness evaluation via modified Lipinski’s Rule of Five was done on CsA, voclosporin, and CsA conjugates to test bioavailability. The binding affinities of bioavailable compounds were computed via docking to CN in five trials, and the binding affinities were compared. The Water-soluble, RVal, IIA, Alpha, and MeBmt 2 conjugates showed improved bioavailabilities compared to CsA as they passed the drug-likeness screening. After five trials of computational docking to CN, the IIA and RVal conjugates showed improved binding affinities at -15.8 kcal/mol and -15.2 kcal/mol, respectively, compared to CsA at -14.3 kcal/mol. Notably, IIA also showed an improved binding affinity compared to voclosporin at -15.5 kcal/mol. These results suggest that CsA conjugates may be better oral chemotherapeutic drugs than CsA.
Quantitative environmental DNA metabarcoding for the enumeration of Pacific salmon (Oncorhynchus spp.)
Understanding species abundance is critical to managing and conserving planetary biodiversity. Pacific salmon (Oncorhynchus spp.) are keystone species of cultural, economic, and ecological importance in Alaska and especially Southwest Alaska. Traditional methods of enumerating salmon such as weirs and visual surveys are often costly, time-intensive, and reliant on taxonomic expertise. Environmental DNA (eDNA), which identifies and quantifies species based on DNA they shed in their habitats, is a potential cost- and time- saving alternative. The relative ease of collecting eDNA samples also enables citizen scientist involvement, expanding research coverage. Currently, more research is required to define eDNA’s potential and limits. This project investigates whether quantitative eDNA metabarcoding can accurately quantify the abundances of six fish species: the five Pacific salmon species plus rainbow trout. Water samples were collected from eight creeks in the Wood River watershed of Southwest Alaska. eDNA metabarcoding and subsequent bioinformatics processing produced a read count for each species. These were compared to visual survey counts, taken to be the true counts for the purposes of this study. Data analyses showed a positive, linear relationship between visual survey count and eDNA count for sockeye salmon. The regressions were significant for both the early (p = 0.089) and late (p = 0.030) sampling dates when 𝛼 = 0.10. eDNA detections of non-sockeye species generally corresponded to visual survey observations of species presence or absence. Overall, the results of this study support eDNA’s potential to be an alternative or supplement to standard methods for the enumeration of fish species.
Silver nanoparticles-loaded titanium dioxide coating towards immobilized photocatalytic reactor for water decontamination and bacterial deactivation under natural sunlight irradiation
The environmental implications of rapid industrialization, including rising pollution, depleted resources, the effects of climate change brought on by global warming, and unrestrained groundwater extraction, are contributing to a growing water scarcity crisis [1-3]. The improvements in quality of life are largely attributable to the innovations in manufacturing technology made possible by the Industrial Revolution, but these innovations also pose risks to the natural world and human health [1-3]. The textile business uses a wide variety of raw materials, including natural fibers like cotton as well as synthetic and woolen fibers, and the chemical components of dyes are just one example. The annual output of synthetic dyes is around 700,000 tons, and there are over 10,000 different varieties available. As much as 200,000 tons of synthetic dyes are released into the environment every year due to the inefficient dyeing technique commonly employed in the textile industry. According to the World Bank, the processing of textiles for dyeing and finishing accounts for between 17 and 20 percent of industrial wastewater [1-3]. Textile wastewaters contain a high biological oxygen demand (BOD), chemical oxygen demand (COD), nitrogen, color, acidity, high suspended particles, high dissolved solids, surfactants, dyestuffs, heavy metals, and other soluble chemicals [3] due to the variety of dyes used to color textile items. In particular, water-soluble reactive and azo dyes are employed to obtain the required color. Ten to twenty percent of the dyes used end up in the effluents, where they might harm wildlife and the ecosystem (carcinogenic or mutagenic). Headaches, nausea, skin irritation, respiratory difficulties, and congenital deformities are only some of the health problems linked to exposure to textile wastewater. There are repercussions for aquatic ecology, environmental biodiversity, and the quality of receiving water bodies. New, low-cost, and highly effective water treatment methods are needed to deal with polluted wastewater. Adsorption and coagulation, two common water purification methods, just concentrate pollutants by shifting them to other phases; they do not "eliminate" or "destroy" them. Sedimentation, filtration, chemical oxidation, and biotechnology are all examples of conventional water treatment methods, but they all have their drawbacks. These include insufficient removal, high chemical reagent consumption, high treatment costs, long treatment times, and the creation of toxic secondary pollutants. New water treatment procedures are needed to improve the quality of treated effluent [1-3]. The use of semiconductor particles in photocatalysis is gaining appeal as a solution to global pollution problems due to its shown efficiency in degrading a wide variety of contaminants. Photocatalyst-coated surfaces-based reactors have proven to be practical for long-term operation over photocatalytic powder-based reactors (i.e., slurry-based reactors) [4-5]. As a promising photo-electrode and photocatalyst, titanium dioxide (TiO2) has enjoyed wider applicability in photocatalytic hydrogen generation, solar cells, and remediation of organic contaminants among other photo-catalytic applications [4-6]. TiO2 has been recognized as one of the low-cost, most effective, and fascinating photo-catalyst as a result of its interesting thermal and chemical stability, desirable electronic features, others, and environmental benignity [6-8]. Pristine TiO2 semiconductor is characterized by a wide band gap that can only utilize the UV part of the light spectrum with a wavelength of less than 385 nm, which is just 5% of the sunlight energy capacity. Spectrum usability extension to visible regions warrants further and extensive research study [8-10]. Additionally, the quickness of the recombination of photo-generated holes and electrons further restricts the practical applicability of the semiconductor [10-12]. It is highly desirable to develop a cost-effective scalable strategy to over these drawbacks toward sustainable development and a clean environment using only natural sunlight irradiation [5-11]. In addition, it is preferred to fabricate them as films rather than powders as photocatalytic immobilized reactors are more practical than powder-based reactors [4-8]. Dye sensitization, supports, magnetic separation, and surface modification by doping with non-metals, metals, and transition metals and coupling with other semiconductors have all been used to enhance the photocatalytic activity of TiO2 photocatalyst. Higher photonic efficiency can be attained through the synergistic fine-tuning of features such as physical, chemical, and electronic, and these composites and hybrid materials based on TiO2 are creating a big trend. Doping has been widely studied as a means of altering the surface of TiO2. Rare earth metals, noble metals, and transition metals are all discussed in the existing literature on the surface modification of TiO2 doped with cations [4-12]. In this study, for the first time, Ag nanoparticles loaded mesoporous TiO2 coating was prepared and applied as an immobilized photocatalytic reactor for water decontamination and bacterial deactivation under natural sunlight irradiation.