Molecular Networking and On-Tissue Chemical Derivatization for Enhanced Identification and Visualization of Steroid Glycosides by MALDI Mass Spectrometry Imaging.

Spatial metabolomics describes the spatially resolved analysis of interconnected pathways, biochemical reactions, and transport processes of small molecules in the spatial context of tissues and cells. However, a broad range of metabolite classes (e.g.

Detection of protein persulfidation in plants by the dimedone switch method.

Hydrogen sulfide (HS) is a well-known signaling molecule in both animals and plants, endogenously produced by cells, and involved in a wide variety of biological functions. In plants, HS regulates a wide range of essential aspects of plant life, including plant responses to numerous stresses and physiological processes as important as abscisic acid (ABA)-dependent stomatal movement, photosynthesis, and autophagy. The best studied molecular mechanism responsible of sulfide signaling is protein persulfidation, a post-translational modification of cysteine residues, where a thiol group (P-SH) is transformed into a persulfide group (P-SSH).

Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors.

The soluble epoxide hydrolase (sEH) has been suggested as a pharmacological target for the treatment of several diseases, including pain-related disorders. Herein, we report further medicinal chemistry around new benzohomoadamantane-based sEH inhibitors (sEHI) in order to improve the drug metabolism and pharmacokinetics properties of a previous hit. After an extensive in vitro screening cascade, molecular modeling, and in vivo pharmacokinetics studies, two candidates were evaluated in vivo in a murine model of capsaicin-induced allodynia.

Blood Culture Headspace Gas Analysis Enables Early Detection of Bacteremia in an Animal Model of Sepsis.

(1) Background: Automated blood culture headspace analysis for the detection of volatile organic compounds of microbial origin (mVOC) could be a non-invasive method for bedside rapid pathogen identification. We investigated whether analyzing the gaseous headspace of blood culture (BC) bottles through gas chromatography-ion mobility spectrometry (GC-IMS) enables differentiation of infected and non-infected; (2) Methods: BC were gained out of a rabbit model, with sepsis induced by intravenous administration of E. coli (EC group; n = 6) and control group (n = 6) receiving sterile LB medium intravenously.

Combinatorial Optimization of Activity-Based Probes for Acyl Protein Thioesterases 1 and 2.

Acyl protein thioesterases hydrolyze fatty acid thioesters on cysteine residues of proteins. The two protein depalmitoylases APT1 and APT2 have a very high degree of similarity and show substantial overlap in substrate utility. Potent, selective, and cell-permeable activity-based probes are needed to study the role of these enzymes.

Calibration by differentiation - Self-supervised calibration for X-ray microscopy using a differentiable cone-beam reconstruction operator.

High-resolution X-ray microscopy (XRM) is gaining interest for biological investigations of extremely small-scale structures. XRM imaging of bones in living mice could provide new insights into the emergence and treatment of osteoporosis by observing osteocyte lacunae, which are holes in the bone of few micrometres in size. Imaging living animals at that resolution, however, is extremely challenging and requires very sophisticated data processing converting the raw XRM detector output into reconstructed images.

Antiproliferative Properties of Lipophililic-Acid Chelating Fluoroquinolones and TriazoloFluoroquinolones with 7-dihaloanilinosubstitution.

Background: Incidence rates and prevalence of cancer are substantially high globally. New safe therapeutic drugs are endorsed to overcome the high toxicity and poor safety profile of clinical anticancer agents.

Objective: As antineoplastic Vosaroxin is a commercial fluoroquinolone (FQ), we hypothesize that superlative antiproliferation activity of lipophilic FQs/TFQs series correlates to their acidic groups and C8-C7 ethylene diamine Chelation Bridge along with bulky dual halogenations.

Correction: SuFEx-enabled, chemoselective synthesis of triflates, triflamides and triflimidates.

[This corrects the article DOI: 10.1039/D1SC06267K.].

Correction: Rapid synthesis of internal peptidyl α-ketoamides by on resin oxidation for the construction of rhomboid protease inhibitors.

[This corrects the article DOI: 10.1039/D0RA10614C.].

SuFEx-enabled, chemoselective synthesis of triflates, triflamides and triflimidates.

Sulfur(vi) Fluoride Exchange (SuFEx) chemistry has emerged as a next-generation click reaction, designed to assemble functional molecules quickly and modularly. Here, we report the generation of trifluoromethanesulfonyl fluoride (CFSOF) gas in a two chamber system, and its use as a new SuFEx handle to efficiently synthesize triflates and triflamides. This broadly tolerated protocol lends itself to peptide modification or to telescoping into coupling reactions.

Nitroxyl Delivered by Angeli's Salt Causes Short-Lasting Activation Followed by Long-Lasting Deactivation of Meningeal Afferents in Models of Headache Generation.

The role of TRPA1 receptor channels in meningeal nociception underlying the generation of headaches is still unclear. Activating as well as inhibitory effects of TRPA1 agonists have been reported in animal models of headache. The aim of the present study was to clarify the effect of the TRPA1 agonist nitroxyl (HNO) delivered by Angeli's salt in two rodent models of meningeal nociception.

Phosphinate esters as novel warheads for activity-based probes targeting serine proteases.

Activity-based protein profiling enables the specific detection of the active fraction of an enzyme and is of particular use for the profiling of proteases. The technique relies on a mechanism-based reaction between small molecule activity-based probes (ABPs) with the active enzyme. Here we report a set of new ABPs for serine proteases, specifically neutrophil serine proteases.

Stress-induced inflammation evoked by immunogenic cell death is blunted by the IRE1α kinase inhibitor KIRA6 through HSP60 targeting.

Mounting evidence indicates that immunogenic therapies engaging the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress favor proficient cancer cell-immune interactions, by stimulating the release of immunomodulatory/proinflammatory factors by stressed or dying cancer cells. UPR-driven transcription of proinflammatory cytokines/chemokines exert beneficial or detrimental effects on tumor growth and antitumor immunity, but the cell-autonomous machinery governing the cancer cell inflammatory output in response to immunogenic therapies remains poorly defined. Here, we profiled the transcriptome of cancer cells responding to immunogenic or weakly immunogenic treatments.

A laser-mediated photo-manipulative toolbox for generation and real-time monitoring of DNA lesions.

With the advancement of laser-based microscopy tools, it is now possible to explore mechano-kinetic processes occurring inside the cell. Here, we describe the advanced protocol for studying the DNA repair kinetics in real time using the laser to induce the DNA damage. This protocol can be used for inducing, testing, and studying the repair mechanisms associated with DNA double-strand breaks, interstrand cross-link repair, and single-strand break repair.

Small extracellular vesicles obtained from hypoxic mesenchymal stromal cells have unique characteristics that promote cerebral angiogenesis, brain remodeling and neurological recovery after focal cerebral ischemia in mice.

Obtained from the right cell-type, mesenchymal stromal cell (MSC)-derived small extracellular vesicles (sEVs) promote stroke recovery. Within this process, microvascular remodeling plays a central role. Herein, we evaluated the effects of MSC-sEVs on the proliferation, migration, and tube formation of human cerebral microvascular endothelial cells (hCMEC/D3) in vitro and on post-ischemic angiogenesis, brain remodeling and neurological recovery after middle cerebral artery occlusion (MCAO) in mice.

Fungal and host protein persulfidation are functionally correlated and modulate both virulence and antifungal response.

Aspergillus fumigatus is a human fungal pathogen that can cause devastating pulmonary infections, termed "aspergilloses," in individuals suffering immune imbalances or underlying lung conditions. As rapid adaptation to stress is crucial for the outcome of the host-pathogen interplay, here we investigated the role of the versatile posttranslational modification (PTM) persulfidation for both fungal virulence and antifungal host defense. We show that an A.

Lipidomic and in-gel analysis of maleic acid co-polymer nanodiscs reveals differences in composition of solubilized membranes.

Membrane proteins are key in a large number of physiological and pathological processes. Their study often involves a prior detergent solubilization step, which strips away the membrane and can jeopardize membrane protein integrity. A recent alternative to detergents encompasses maleic acid based copolymers (xMAs), which disrupt the lipid bilayer and form lipid protein nanodiscs (xMALPs) soluble in aqueous buffer.

Probes for Photoaffinity Labelling of Kinases.

Protein kinases, one of the largest enzyme superfamilies, regulate many physiological and pathological processes. They are drug targets for multiple human diseases, including various cancer types. Probes for the photoaffinity labelling of kinases are important research tools for the study of members of this enzyme superfamily.

Review: Miniature dielectric barrier discharge (DBD) in analytical atomic spectrometry.

The development of miniature, sensitive, high throughput, and in-situ analytical instruments has been becoming developing field of modern analytical chemistry. Due to its unique advantages such as easy operation, simple configuration, ambient working temperature and pressure, low power consumption, and miniature dimension, dielectric barrier discharge (DBD) has always been a hot topic in analytical chemistry. This review gives an overview of miniature DBD application in analytical atomic spectrometry, starting with an introduction to its geometrical configuration and ionization mechanisms.

Light Sheet Microscopy Using FITC-Albumin Followed by Immunohistochemistry of the Same Rehydrated Brains Reveals Ischemic Brain Injury and Early Microvascular Remodeling.

Until recently, the visualization of cerebral microvessels was hampered by the fact that only short segments of vessels could be evaluated in brain sections by histochemistry. These limitations have been overcome by light sheet microscopy, which allows the 3D analysis of microvasculature in cleared brains. A major limitation of light sheet microscopy is that antibodies do not sufficiently penetrate cleared brains.

Rapid synthesis of internal peptidyl α-ketoamides by on resin oxidation for the construction of rhomboid protease inhibitors.

Rhomboid proteases are intramembrane serine proteases, which are involved in a wide variety of biological processes and have been implied in various human diseases. Recently, peptidyl α-ketoamides have been reported as rhomboid inhibitors with high potency and selectivity - owing to their interaction with both the primed and non-primed site of the target protease. However, their synthesis has been performed by solution phase chemistry.

Tagged Benzoxazin-4-Ones as Novel Activity-Based Probes for Serine Proteases.

Activity-based probes (ABPs) are valuable chemical tools for profiling enzymes. They have been particularly useful in the study of proteases. ABPs rely on electrophilic scaffolds that covalently modify the target enzymes.

Bioorthogonal Reactions in Activity-Based Protein Profiling.

Activity-based protein profiling (ABPP) is a powerful technique to label and detect active enzyme species within cell lysates, cells, or whole animals. In the last two decades, a wide variety of applications and experimental read-out techniques have been pursued in order to increase our understanding of physiological and pathological processes, to identify novel drug targets, to evaluate selectivity of drugs, and to image probe targets in cells. Bioorthogonal chemistry has substantially contributed to the field of ABPP, as it allows the introduction of tags, which may be bulky or have unfavorable physicochemical properties, at a late stage in the experiment.