CDO/CO3O4 NANOCOMPOSITE AS AN EFFICIENT ELECTROCATALYST FOR OXYGEN EVOLUTION REACTION IN ALKALINE MEDIA

Electrochemical water splitting is one of the promising way to enhance energy with less outflow. In this regard different electrocatalysts have been reported for Oxygen evolution reaction (OER) to get alternative of noble metal based electrocatalysts. In this work, we have introduced Cadmium-oxide/Cobalt-oxide (CdO/Co3O4) nanocomposite by co-precipitation chemical strategy with impressive OER performance in alkaline medium. Almost 310 mV overpotential value is required to achieve 10 mA/cm2 current density with Tafel slope value of 62 mV/Dec. The as synthesized nanocomposite has stability of 6h as its longer electrochemical performance

A Tale of Two Transmitters: Serotonin and Histamine as In Vivo Biomarkers of Chronic Stress in Mice

Background: Stress-induced mental illnesses (mediated by neuroinflammation) pose one of the world’s most urgent public health challenges. A reliable in vivo chemical biomarker of stress would significantly improve the clinical communities’ diagnostic and therapeutic approaches to illnesses like depression.Methods: Male and female C57BL/6J mice underwent a chronic stress paradigm. We paired innovative in vivo serotonin and histamine voltammetric measurement technologies, behavioral testing, and cutting-edge mathematical methods to correlate chemistry to stress and behavior.Results: Inflammation-induced increases in hypothalamic histamine were co-measured with decreased in vivo extracellular hippocampal serotonin in mice that underwent a chronic stress paradigm, regardless of behavioral phenotype. In animals with depression phenotypes, correlations were found between serotonin and the extent of behavioral indices of depression. We created a high accuracy algorithm that could predict whether animals had been exposed to stress or not based solely on the serotonin measurement. We next developed a model of serotonin and histamine modulation, which predicted that stress-induced neuroinflammation increases histaminergic activity, serving to inhibit serotonin. Finally, we created a mathematical index of stress, Si and predicted that during chronic stress, where Si is high, simultaneously increasing serotonin and decreasing histamine is the most effective chemical strategy to restoring serotonin to pre-stress levels. When we pursued this idea pharmacologically, our experiments were nearly identical to the model’s predictions.Conclusions: This work shines the light on two biomarkers of chronic stress, histamine and serotonin, and implies that both may be important in our future investigations of the pathology and treatment of inflammation-induced depression.

Cuticular Hydrocarbon Profile of Parasitic Beetles, Aethina tumida (Coleoptera: Nitidulidae)

Cuticular hydrocarbons (CHCs) cover insects’ bodies and play important roles in chemical communication, including nestmate recognition, for social insects. To enter colonies of a social host species, parasites may acquire host-specific CHCs or covertly maintain their own CHC profile by lowering its quantity. However, the chemical profile of small hive beetles (SHBs), Aethina tumida, which are parasites of honey bee, Apis mellifera, colonies, and other bee nests, is currently unknown. Here, adults of SHB and honey bee host workers were collected from the same field colonies and their CHC profiles were analysed using GC-MS. The chemical profiles of field-sampled SHBs were also compared with those of host-naive beetles reared in the laboratory. Laboratory-reared SHBs differed in their CHC profiles from field-sampled ones, which showed a more similar, but ten-fold lower, generic host CHC profile compared to host workers. While the data confirm colony-specific CHCs of honey bee workers, the profile of field-collected SHBs was not colony-specific. Adult SHBs often commute between different host colonies, thereby possibly preventing the acquisition of a colony-specific CHC profiles. An ester was exclusive to both groups of SHBs and might constitute an intraspecific recognition cue. Our data suggest that SHBs do not use any finely tuned chemical strategy to conceal their presence inside host colonies and instead probably rely on their hard exoskeleton and defence behaviours.

Natural Product-based Hybrids as Potential Candidates for the Treatment of Cancer: Focus on Curcumin and Resveratrol

One of the main current strategies for cancer treatment is represented by combination chemotherapy. More recently, this strategy shifted to the “hybrid strategy”, namely the designing of a new molecular entity containing two or more biologically active molecules and having superior features compared with the individual components. Moreover, the term “hybrid” has further extended to innovative drug delivery systems based on biocompatible nanomaterials and able to deliver one or more drugs to specific tissues or cells. At the same time, there is an increased interest in plant-derived polyphenols used as antitumoral drugs. The present review reports the most recent and intriguing research advances in the development of hybrids based on the polyphenols curcumin and resveratrol, which are known to act as multifunctional agents. We focused on two issues that are particularly interesting for the innovative chemical strategy involved in their development. On one hand, the pharmacophoric groups of these compounds have been used for the synthesis of new hybrid molecules. On the other hand, these polyphenols have been introduced into hybrid nanomaterials based on gold nanoparticles, which have many potential applications for both drug delivery and theranostics in chemotherapy.

Chemical profiling of DNA G-quadruplex-interacting proteins in live cells

DNA–protein interactions regulate critical biological processes. Identifying proteins that bind to specific, functional genomic loci is essential to understand the underlying regulatory mechanisms on a molecular level. Here we describe a co-binding-mediated protein profiling (CMPP) strategy to investigate the interactome of DNA G-quadruplexes (G4s) in native chromatin. CMPP involves cell-permeable, functionalized G4-ligand probes that bind endogenous G4s and subsequently crosslink to co-binding G4-interacting proteins in situ. We first showed the robustness of CMPP by proximity labelling of a G4 binding protein in vitro. Employing this approach in live cells, we then identified hundreds of putative G4-interacting proteins from various functional classes. Next, we confirmed a high G4-binding affinity and selectivity for several newly discovered G4 interactors in vitro, and we validated direct G4 interactions for a functionally important candidate in cellular chromatin using an independent approach. Our studies provide a chemical strategy to map protein interactions of specific nucleic acid features in living cells.

A chemical strategy toward novel brain-penetrant EZH2 inhibitors

Aberrant gene-silencing through dysregulation of polycomb protein activity has emerged as an important oncogenic mechanism in cancer, implicating polycomb proteins as important therapeutic targets. Recently, an inhibitor targeting EZH2, the methyltransferase component of PRC2, received FDA approval following promising clinical responses in cancer patients. However, the current array of EZH2 inhibitors have poor brain-penetrance limiting their use in patients with CNS malignancies, a number of which have been shown to be sensitive to EZH2 inhibition. To address this need, we have identified a chemical strategy, based on computational modeling of pyridone-containing EZH2 inhibitor scaffolds, to minimize P-glycoprotein activity and here we report the first brain-penetrant EZH2 inhibitor, TDI-6118 (compound 5). Additionally, in the course of our attempts to optimize this compound we discovered TDI-011904 (compound 21); a novel, highly-potent, and peripherally active EZH2 inhibitor based on a 7 member ring structure.

Metallated Anticancer Peptides: An Expanded Mechanism that Encompasses Physical and Chemical Bilayer Disruption

In the search for novel broad-spectrum therapeutics to fight chronic infections, inflammation, and cancer, host defense peptides (HDPs) have garnered increasing interest. Characterizing their biologically-active conformations and minimum motifs for function represents a requisite step to developing them into efficacious and safe therapeutics. Here, we demonstrate that metallating HDPs is an effective chemical strategy to improve their cytotoxicity on cancer cells. Mechanistically, we find that the metallated peptides not only physically but also chemically damage lipid membranes. Our testing ground features piscidins 1 and 3 (P1/3), two amphipathic, histidine-rich, membrane-interacting, and cell-penetrating HDPs that are α-helical bound to membranes. To investigate their membrane location, permeabilization effects, and lipid-oxidation capability, we employ neutron reflectometry, impedance spectroscopy, neutron diffraction, and UV spectroscopy. While P1-apo is more potent than P3-apo, metallation boosts their cytotoxicities by up to two-and seven-fold, respectively. Remarkably, P3 is particularly effective at inserting its metallated motif in bilayers, causing water crevices in the hydrocarbon region and placing Cu 2+ near the double bonds of the acyl chains, as needed to oxidize them. This study points at a new paradigm where metallating HDPs to expand their mechanistic reach could be explored to design more potent peptide-based anticancer therapeutics.

A Universal Chemical Method for Rational Design of Protein-based Nanoreactors

Self-assembly of a monomeric protease to form a multi-subunit protein complex “proteasome” enables targeted protein degradation in living cells. The naturally occurring proteasomes serve as an inspiration and blueprint for the design of artificial protein-based nanoreactors. Here we disclose a general chemical strategy for the design of proteasome-like nanoreactors. Micelle-assisted protein labeling (MAPLab) technology along with the N-terminal bioconjugation strategy is utilized for the synthesis of a well-defined monodisperse self-assembling semi-synthetic protease. The designer protein is programmed to self-assemble into a proteasome-like nanostructure which preserves the functional properties of native protease.