Organofluorine Hydrazone Derivatives as Multifunctional Anti-Alzheimer's Agents with CK2 Inhibitory and Antioxidant Features

A set of novel hydrazone derivatives were synthesized and analyzed for their biological activities. The compounds were tested for their inhibitory effect on the phosphorylating activity of the protein kinase CK2, and their antioxidant activity was also determined in three commonly used assays. The hydrazones were evaluated for their radical scavenging against the DPPH, ABTS and peroxyl radicals. Several compounds have been identified as good antioxidants as well as potent protein kinase CK2 inhibitors. Most hydrazones containing a 4-N(CH₃)₂ residue or perfluorinated phenyl rings showed high activity in the radical-scavenging assays and possess nanomolar IC₅₀ values in the kinase assays.     

Ecological Planting Imperative: Functional Systems,Not Stylized Ecologies

The ability of landscape architectural projects to mitigate the worst effects of climate change will depend upon designed ecological systems. These systems will be built with plants. Despite the recognition of ecology as an essential driver of landscapes, the professionals of landscape architecture too often lack the knowledge and practical skills to create robust vegetative systems. New approaches and tools are required. This article outlines principles and methods for designing biodiverse plant systems for urban sites. Planting methods that increase species richness, functional diversity, and spatial complexity are emphasized as a way of developing more resilient plantings. Selecting species with similar evolutionary adaptions to stress, disturbance, and competition—as well as creating multi-layered compositions of diverse plant morphologies—allows designers to create compatible, long-lived plant mixes. To balance the increased visual complexity of diverse plant mixes, the article explores design techniques to make plantings more appealing to the public. The strategies explored here are based on the projects, experience, and research of Phyto Studio, a Washington, D.C. based studio. The methods build on work described in the author’s book, Planting in a Post-Wild World, an exploration of how to create designed plant communities.     

Discovery of GPR183 Agonists Based on an Antagonist Scaffold

The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca²⁺ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch.     

Ratiometric Detection of Glutathione Based on Disulfide Linkage Rupture between a FRET Coumarin Donor and a Rhodamine Acceptor

Abnormal levels of glutathione, a cellular antioxidant, can lead to a variety of diseases. We have constructed a near-infrared ratiometric fluorescent probe to detect glutathione concentrations in biological samples. The probe consists of a coumarin donor, which is connected through a disulfide-tethered linker to a rhodamine acceptor. Under the excitation of the coumarin donor at 405 nm, the probe shows weak visible fluorescence of the coumarin donor at 470 nm and strong near-infrared fluorescence of the rhodamine acceptor at 652 nm due to efficient Forster resonance energy transfer (FRET) from the donor to the acceptor. Glutathione breaks the disulfide bond through reduction, which results in a dramatic increase in coumarin fluorescence and a corresponding decrease in rhodamine fluorescence. The probe possesses excellent cell permeability, biocompatibility, and good ratiometric fluorescence responses to glutathione and cysteine with a self-calibration capability. The probe was utilized to ratiometrically visualize glutathione concentration alterations in HeLa cells and Drosophila melanogaster larvae.     

In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64Cu-PET/CT Imaging in Breast Cancer Model

An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2^Mal, has been synthesized and studied for in vivo ⁶⁴Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1^Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [⁶⁴Cu]Cu-GluCAB-2^Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [⁶⁴Cu]Cu-GluCAB-2^Mal and previous-generation [⁶⁴Cu]Cu-GluCAB-1^Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [⁶⁴Cu]Cu-GluCAB-2^Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [⁶⁴Cu]Cu-Glu-CAB-2^Mal.     

Effects of upholstery materials on the burning behavior of real‐scale residential upholstered furniture mock‐ups

Fire spread and growth on real‐scale four cushion mock‐ups of residential upholstered furniture (RUF) were investigated with the goal of identifying whether changes in five classes of materials (barrier, flexible polyurethane foam, polyester fiber wrap, upholstery fabric, and sewing thread), referred to as factors, resulted in statistically significant changes in burning behavior. A fractional factorial experimental design plus practical considerations yielded a test matrix with 20 material combinations. Experiments were repeated a minimum of two times. Measurements included fire spread rates derived from video recordings and heat release rates (HRRs). A total of 13 experimental parameters (3 based on the videos and 10 on the HRR results), referred to as responses, characterized the measurements. Statistical analyses based on Main Effects Plots (main effects) and Block Plots (main effects and factor interactions) were used. The results showed that three of the factors resulted in statistically significant effects on varying numbers of the 13 responses. The Barrier and Fabric factors had the strongest main effects with roughly comparable magnitudes. Foam was statistically significant for fewer of the responses and its overall strength was weaker than for Barrier and Fabric. No statistically significant main effects were identified for Wrap or Thread. Multiple two‐term interactions between factors were identified as being statistically significant. The Barrier*Fabric interaction resulted in the highest number of and strongest statistically significant effects. The existence of two‐term interactions means that it will be necessary to consider their effects in approaches designed to predict the burning behavior of RUF.     

An integrated dimensionality reduction and surrogate optimization approach for plant-wide chemical process operation

With liquefied natural gas becoming increasingly prevalent as a flexible source of energy, the design and optimization of industrial refrigeration cycles becomes even more important. In this article, we propose an integrated surrogate modeling and optimization framework to model and optimize the complex CryoMan Cascade refrigeration cycle. Dimensionality reduction techniques are used to reduce the large number of process decision variables which are subsequently supplied to an array of Gaussian processes, modeling both the process objective as well as feasibility constraints. Through iterative resampling of the rigorous model, this data-driven surrogate is continually refined and subsequently optimized. This approach was not only able to improve on the results of directly optimizing the process flow sheet but also located the set of optimal operating conditions in only 2 h as opposed to the original 3 weeks, facilitating its use in the operational optimization and enhanced process design of large-scale industrial chemical systems.     

Effect of nitrogen on the antibacterial behavior of oxynitride glasses

The main drawback of bioglasses is their restricted use in load bearing applications and the consequent need to develop stronger glassy materials. This has led to the consideration of oxynitride glasses for numerous biomedical applications. This paper investigated two different types of glasses at a constant cationic ratio, with and without nitrogen (a N containing and a N-free glass composition) to better understand the effect of N on the biological properties of glasses. The results revealed that the addition of N increased the glass transition temperature, isoelectric point (IEP) and slightly increased wettability. Moreover, compared to N including glass, N-free glass exhibited better anti-bacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), two key bacteria that infect implants. In summary, these in vitro results indicated that amine functional groups existing in N containing glasses which are missing in N-free glasses, caused a slight difference in wetting behavior and a more obvious change in isoelectric point and in bacterial response. N-free glasses exhibited better inhibitory results both against E. coli and S. aureus compared to N including glass suggesting that oxygen rich glasses should be further studied for their novel antibacterial properties.