Regioselective Synthesis of Potential Non-Quinonoid Prodrugs of Plasmodione: Antiparasitic Properties Against Two Hemoglobin-Feeding Parasites and Drug Metabolism Studies.

Ψ-1,4-naphthoquinones (Ψ-NQ) are non-quinoid compounds in which aromaticity-found in 1,4-naphthoquinones-is broken by the introduction of an angular methyl at C-4a or -8a. This series was designed to act as prodrugs of 1,4-naphthoquinones in an oxidative environment. Furthermore, from a medicinal chemistry point of view, the loss of planarity of the scaffold might lead to an improved solubility and circumvent the bad reputation of quinones in the pharmaceutical industry.

O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts.

Tissue injury causes activation of mesenchymal lineage cells into wound-repairing myofibroblasts (MFs), whose uncontrolled activity ultimately leads to fibrosis. Although this process is triggered by deep metabolic and transcriptional reprogramming, functional links between these two key events are not yet understood. Here, we report that the metabolic sensor post-translational modification O-linked β-D-N-acetylglucosaminylation (O-GlcNAcylation) is increased and required for myofibroblastic activation.

Ionic Liquid Crystals Based on Loop-Shaped Copper(I) Complexes.

This paper describes the synthesis and characterization of liquid crystals based on loop-shaped cationic copper(I) complexes of a multidentate ligand. Their synthesis involves the one-pot reaction of an alkyloxy-decorated pyridine-aldehyde unit with a diamine (2,2'-(ethylenedioxy)bis(ethylamine)) spacer to form in situ a pyridine-imine quadridentate-N-donor ligand, L, which is able to chelate a copper(I) center associated with various noncoordinating anions. All of these compounds were characterized by NMR, IR, and electronic absorption spectroscopy, and more particularly by X-ray diffraction and mass spectroscopy, enabling unambiguous assignment of the [ML] mononuclear nature of the cationic components.

Solution and Solvent-Free Stopper Exchange Reactions for the Preparation of Pillar[5]arene-Containing [2] and [3]Rotaxanes.

Invited for the cover of this issue are the group of Iwona and Jean-François Nierengarten from the University of Strasbourg (LIMA, UMR 7042, CNRS) and collaborators from the University of Carthage and the IPHC (University of Strasbourg and CNRS, UMR 7178). The image illustrates the fast motions of a pillar[5]arene subunit along the axle of a rotaxane, reminiscent of those of a guitarist's hand along the neck allowing him to use random parts of a scale with certain sweet spots when improvising a solo. Read the full text of the article at 10.

Honey Bee Larval Hemolymph as a Source of Key Nutrients and Proteins Offers a Promising Medium for Artificial Rearing.

, a major ectoparasite of the Western honey bee , is a widespread pest that damages colonies in the Northern Hemisphere. Throughout their lifecycle, females feed on almost every developmental stage of their host, from the last larval instar to the adult. The parasite is thought to feed on hemolymph and fat body, although its exact diet and nutritional requirements are poorly known.

Synthesis and Photochemical Properties of Fluorescent Metabolites Generated from Fluorinated Benzoylmenadiones in Living Cells.

This work describes the reactivity and properties of fluorinated derivatives ( and ) of plasmodione () and its metabolite, the plasmodione oxide (). Introduction of a fluorine atom on the 2-methyl group markedly alters the redox properties of the 1,4-naphthoquinone electrophore, making the compound highly oxidizing and particularly photoreactive. A fruitful set of analytical methods (electrochemistry, absorption and emission spectrophotometry, and HRMS-ESI) have been used to highlight the products resulting from UV photoirradiation in the absence or presence of selected nucleophiles.

Bioactivated and PEG-Protected Circa 2 nm Gold Nanoparticles for in Cell Labelling and Cryo-Electron Microscopy.

Advances in cryo-electron microscopy (EM) enable imaging of protein assemblies within mammalian cells in a near native state when samples are preserved by cryogenic vitrification. To accompany this progress, specialized EM labelling protocols must be developed. Gold nanoparticles (AuNPs) of 2 nm are synthesized and functionalized to bind selected intracellular targets inside living human cells and to be detected in vitreous sections.

Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis.

Tissue injury triggers activation of mesenchymal lineage cells into wound-repairing myofibroblasts, whose unrestrained activity leads to fibrosis. Although this process is largely controlled at the transcriptional level, whether the main transcription factors involved have all been identified has remained elusive. Here, we report multi-omics analyses unraveling Basonuclin 2 (BNC2) as a myofibroblast identity transcription factor.

Upconversion in a d-f [RuYb] Supramolecular Assembly.

We have prepared a hetero-tetrametallic assembly consisting of three ytterbium ions coordinated to a central [Ru(bpm)] (bpm = 2,2'-bipyrimidine) motif. Irradiation into the absorption band of the peripheral ytterbium ions at 980 nm engenders emission of the MLCT state of the central [Ru(bpm)] core at 636 nm, which represents the first example of f → d molecular upconversion (UC). Time-resolved measurements reveal a slow rise of the UC emission, which was modeled with a mathematical treatment of the observed kinetics according to a cooperative photosensitization mechanism using a virtual Yb centered doubly excited state followed by energy transfer to the Ru centered MLCT state.

Vancomycin-decorated microbubbles as a theranostic agent for Staphylococcus aureus biofilms.

Bacterial biofilms are a huge burden on our healthcare systems worldwide. The lack of specificity in diagnostic and treatment possibilities result in difficult-to-treat and persistent infections. The aim of this in vitro study was to investigate if microbubbles targeted specifically to bacteria in biofilms could be used both for diagnosis as well for sonobactericide treatment and demonstrate their theranostic potential for biofilm infection management.

Catestatin in innate immunity and Cateslytin-derived peptides against superbugs.

Chromogranin A (CgA) is the precursor of several antimicrobial peptides, such as Catestatin (Cts, bovine CgA344-364), initially described as a potent inhibitor of catecholamines. This peptide displays direct antimicrobial activities and contributes to immune system regulation. The aim of the present study is to investigate a designed peptide based on Cts to fight infections against superbugs and more particularly Staphylococcus aureus.

Iron Stearate Structures: An Original Tool for Nanoparticles Design.

Iron carboxylates are widely used as iron precursors in the thermal decomposition process or considered as in situ formed intermediate precursors. Their molecular and three-dimensional (3D)-structural nature has been shown to affect the shape, size, and composition of the resulting iron oxide nanoparticles (NPs). Among carboxylate precursors, stearates are particularly attractive because of their higher stability to aging and hydration and they are used as additives in many applications.

Evaluation of a Pediatric Obesity Management Toolkit for Health Care Professionals: A Quasi-Experimental Study.

Health care professionals (HCPs) play a critical role in helping to address weight-related issues with pediatric patients, yet often feel ill-equipped to discuss/manage this complex and sensitive health issue. Using the five As ("Ask, Assess, Advise, Agree, and Assist") of Pediatric Obesity Management, we created a series of educational videos and evaluated the content, quality (acceptability, engagement), and impact of these videos on HCPs' self-efficacy, knowledge, and change in practice when addressing weight-related issues with pediatric patients and their families using questionnaires. HCPs ( = 65) participated in a baseline assessment and 4-6 month follow-up ( = 54).

Music Community, Improvisation, and Social Technologies in COVID-Era Música Huasteca.

This article examines two interrelated aspects of Mexican regional music response to the coronavirus crisis in the música huasteca community: the growth of interactive huapango livestreams as a preexisting but newly significant space for informal community gathering and cultural participation at the onset of the coronavirus pandemic, and the composition of original verses by son huasteco performers addressing the pandemic. Both the livestreams and the newly created coronavirus disease (COVID) verses reflect critical improvisatory approaches to the pandemic in música huasteca. The interactive livestreams signaled an community infrastructure facilitated by social media and an emerging community space fostered by Do-It-Yourself (DIY) activists.

A Class of Valuable (Pro-)Activity-Based Protein Profiling Probes: Application to the Redox-Active Antiplasmodial Agent, Plasmodione.

Plasmodione () is a potent antimalarial redox-active drug acting at low nM range concentrations on different malaria parasite stages. In this study, in order to determine the precise protein interactome in parasites, we developed a class of (pro-)activity-based protein profiling probes (ABPP) as precursors of photoreactive benzophenone-like probes based on the skeleton of metabolites () generated in a cascade of redox reactions. Under UV-photoirradiation, we clearly demonstrate that benzylic oxidation of 3-benzylmenadione produces the 3-benzoylmenadione probe , allowing investigation of the proof-of-concept of the ABPP strategy with 3-benzoylmenadiones -.

Supramolecular Polymerization of Triarylamine-Based Macrocycles into Electroactive Nanotubes.

A -symmetric triarylamine-based macrocycle (i.e., hexaaza[1]paracyclophane), decorated with six lateral amide functions, is synthesized by a convergent and modular strategy.

The box C/D snoRNP assembly factor Bcd1 interacts with the histone chaperone Rtt106 and controls its transcription dependent activity.

Biogenesis of eukaryotic box C/D small nucleolar ribonucleoproteins initiates co-transcriptionally and requires the action of the assembly machinery including the Hsp90/R2TP complex, the Rsa1p:Hit1p heterodimer and the Bcd1 protein. We present genetic interactions between the Rsa1p-encoding gene and genes involved in chromatin organization including RTT106 that codes for the H3-H4 histone chaperone Rtt106p controlling H3K56ac deposition. We show that Bcd1p binds Rtt106p and controls its transcription-dependent recruitment by reducing its association with RNA polymerase II, modulating H3K56ac levels at gene body.

Careful conversations: an educational video to support parents in communicating about weight with their children.

Background: Parents may struggle to initiate healthy weight-related conversations with their children. Educational videos may be an effective tool for improving parents' knowledge and self-efficacy on this topic. The aim of this pilot study was to develop an educational video to assist parents in weight-related conversations with their child, and to assess changes in parents' self-efficacy on this topic.

Talking About Weight With Families-Helping Health Care Professionals Start the Conversation: A Nonrandomized Controlled Trial.

Health care professionals (HCPs) and trainees feel ill-equipped to discuss weight-related issues with children and their families. A whiteboard video for HCPs and trainees outlining strategies to communicate about weight was developed and evaluated. Seventy HCPs, including 15 trainees, participated in the baseline assessment and 39 repeated measures 4 to 6 months later.

VHH characterization. Comparison of recombinant with chemically synthesized anti-HER2 VHH.

In the continuous exploration of the VHH chemistry, biochemistry and therapeutic future use, we investigated two different production strategies of this small antibody-like protein, using an anti-HER2 VHH as a model. The total chemical synthesis of the 125 amino-acid peptide was performed with reasonable yield, even if optimization will be necessary to upgrade this kind of production. In parallel, we expressed the same sequence in two different hosts: Escherichia coli and Pichia pastoris.