Activity

Dietary compounds play an important role in the prevention and treatment of many cancers, although their specific molecular mechanism is not yet known. selleck chemicals llc In the present study, thirty dietary agents were analyzed on nine drug targets through in silico studies. However, nine dietary scaffolds, such as silibinin, flavopiridol, oleandrin, ursolic acid, α-boswellic acid, β-boswellic acid, triterpenoid, guggulsterone, and oleanolic acid potentially bound to the cavity of PI3K-α, PKC-η, H-Ras, and Ras with the highest binding energy. Particularly, the compounds silibinin and flavopiridol have been shown to have broad spectrum anticancer activity. Interestingly, flavopiridol was embedded in the pockets of PI3K-α and PKC-η as bound crystal inhibitors in two different conformations and showed significant interactions with ATP binding pocket residues. However, complex-based pharmacophore modeling achieved two vital pharmacophoric features namely, two H-bond acceptors for PI3K-α, while three are hydrophobic, one cat-donor and one H-bond donor and acceptor for PKC-η, respectively. The database screening with the ChemBridge core library explored potential hits on a valid pharmacophore query. Therefore, to optimize perspective lead compounds from the hits, which were subjected to various constraints such as docking, MM/GBVI, Lipinski rule of five, ADMET and toxicity properties. Henceforth, the top ligands were sorted out and examined for vital interactions with key residues, arguably the top three promising lead compounds for PI3K-α, while seven for PKC-η, exhibiting binding energy from – 11.5 to – 8.5 kcal mol-1. Therefore, these scaffolds could be helpful in the development of novel class of effective anticancer agents.Urban greening is an effective mitigation option for climate change in urban areas. In this contribution, a European Union (EU)-wide assessment is presented to quantify the benefits of urban greening in terms of availability of green water, reduction of cooling costs and CO2 sequestration from the atmosphere, for different climatic scenarios. Results show that greening of 35% of the EU’s urban surface (i.e. more than 26,000 km2) would avoid up to 55.8 Mtons year-1 CO2 equivalent of greenhouse gas emissions, reducing energy demand for the cooling of buildings in summer by up to 92 TWh per year, with a net present value (NPV) of more than 364 billion Euro. It would also transpire about 10 km3 year-1 of rain water, turning into “green” water about 17.5% of the “blue” water that is now urban runoff, helping reduce pollution of the receiving water bodies and urban flooding. The greening of urban surfaces would decrease their summer temperature by 2.5-6 °C, with a mitigation of the urban heat island effect estimated to have a NPV of 221 billion Euro over a period of 40 years. The monetized benefits cover less than half of the estimated costs of greening, having a NPV of 1323 billion Euro on the same period. Net of the monetized benefits, the cost of greening 26,000 km2 of urban surfaces in Europe is estimated around 60 Euro year-1 per European urban resident. The additional benefits of urban greening related to biodiversity, water quality, health, wellbeing and other aspects, although not monetized in this study, might be worth such extra cost. When this is the case, urban greening represents a multifunctional, no-regret, cost-effective solution.Purine rich element binding protein A (Purα), encoded by the Purα gene, is an important transcriptional regulator that binds to DNA and RNA and is involved in processes such as DNA replication and RNA translation. Purα also plays an important role in the nervous system. To identify the function of Pura, we performed RNA sequence (RNA-seq) analysis of Purɑ-KO mouse hippocampal neuron cell line (HT22) to analyze the effect of Purα deletion on neuronal expression profiles. And combined with ChIP-seq analysis to explore the mechanism of Purα on gene regulation. In the end, totaly 656 differentially expressed genes between HT22 and Purα-KO HT22 cells have been found, which include 7 Alzheimer’s disease (AD)-related genes and 5 Aβ clearance related genes. 47 genes were regulated by Purα directly, the evidence based on CHIP-seq, which include Insr, Mapt, Vldlr, Jag1, etc. Our study provides the important informations of Purα in neuro-development. The possible regulative effects of Purα on AD-related genes consist inthe direct and indirect pathways of Purα in the pathogenesis of AD.Automatic recognition of unique characteristics of an object can provide a powerful solution to verify its authenticity and safety. It can mitigate the growth of one of the largest underground industries-that of counterfeit goods-flowing through the global supply chain. In this article, we propose the novel concept of material biometrics, in which the intrinsic chemical properties of structural materials are used to generate unique identifiers for authenticating individual products. For this purpose, the objects to be protected are modified via programmable additive manufacturing of built-in chemical “tags” that generate signatures depending on their chemical composition, quantity, and location. We report a material biometrics-enabled manufacturing flow in which plastic objects are protected using spatially-distributed tags that are optically invisible and difficult to clone. The resulting multi-bit signatures have high entropy and can be non-invasively detected for product authentication using [Formula see text]Cl nuclear quadrupole resonance (NQR) spectroscopy.The rate coefficients for OH + CH3OH and OH + CH3OH (+ X) (X = NH3, H2O) reactions were calculated using microcanonical, and canonical variational transition state theory (CVT) between 200 and 400 K based on potential energy surface constructed using CCSD(T)//M06-2X/6-311++G(3df,3pd). The results show that OH + CH3OH is dominated by the hydrogen atoms abstraction from CH3 position in both free and ammonia/water catalyzed ones. This result is in consistent with previous experimental and theoretical studies. The calculated rate coefficient for the OH + CH3OH (8.8 × 10-13 cm3 molecule-1 s-1), for OH + CH3OH (+ NH3) [1.9 × 10-21 cm3 molecule-1 s-1] and for OH + CH3OH (+ H2O) [8.1 × 10-16 cm3 molecule-1 s-1] at 300 K. The rate coefficient is at least 8 order magnitude [for OH + CH3OH(+ NH3) reaction] and 3 orders magnitude [OH + CH3OH (+ H2O)] are smaller than free OH + CH3OH reaction. Our calculations predict that the catalytic effect of single ammonia and water molecule on OH + CH3OH reaction has no effect under tropospheric conditions because the dominated ammonia and water-assisted reaction depends on ammonia and water concentration, respectively.