Spatial metabolomics using mass-spectrometry imaging to decipher the impact of high red meat diet on the colon metabolome in rat.

Colorectal cancer (CRC) is the third most common cancer in the world with a higher prevalence in the developed countries, mainly caused by environmental and lifestyle factors such as diet, particularly red meat consumption. The metabolic impact of high red meat consumption on the epithelial part of the colon was investigated using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MSI), to specifically analyze the epithelial substructure. Ten colons from rats fed for 100 days high red or white meat diet were subjected to untargeted MSI analyses using two spatial resolutions (100 μm and 10 μm) to evaluate metabolite changes in the epithelial part and to visualize the distribution of metabolites of interest within the epithelium crypts.

Insights into posttranslational regulation of skeletal muscle contractile function by the acetyltransferases, p300 and CBP.

Mice with skeletal muscle-specific and inducible double knockout of the lysine acetyltransferases, p300 (E1A binding protein p300) and CBP (cAMP-response element-binding protein binding protein), referred to as i-mPCKO, demonstrate a dramatic loss of contractile function in skeletal muscle and ultimately die within 7 days. Given that many proteins involved in ATP generation and cross-bridge cycling are acetylated, we investigated whether these processes are dysregulated in skeletal muscle from i-mPCKO mice and, thus, whether they could underlie the rapid loss of muscle contractile function. Just 4-5 days after inducing knockout of p300 and CBP in skeletal muscle from adult i-mPCKO mice, there was ∼90% reduction in ex vivo contractile function in the extensor digitorum longus (EDL) and a ∼65% reduction in in vivo ankle dorsiflexion torque, as compared with wild type (WT; i.

Excess Intramyocellular Lipid Does Not Affect Muscle Fiber Biophysical Properties in Mice or People With Metabolically Abnormal Obesity.

Observational studies have shown correlations between intramyocellular lipid (IMCL) content and muscle strength and contractile function in people with metabolically abnormal obesity. However, a clear physiologic mechanism for this association is lacking, and causation is debated. We combined immunofluorescent confocal imaging with force measurements on permeabilized muscle fibers from metabolically normal and metabolically abnormal mice and people with metabolically normal (defined as normal fasting plasma glucose and glucose tolerance) and metabolically abnormal (defined as prediabetes and type 2 diabetes) overweight/obesity to evaluate relationships among myocellular lipid droplet characteristics (droplet size and density) and biophysical (active contractile and passive viscoelastic) properties.

Copper-Catalyzed Coupling between -Haloanilines and Lactams/Amides: Synthesis of Benzimidazoles and Telmisartan.

An efficient copper-catalyzed synthesis of (annelated) benzimidazoles is reported. This transformation is based on a simple and straightforward one-pot sequence involving a copper-catalyzed cross coupling between -haloanilines and lactams/amides followed by a subsequent cyclization under acidic conditions. A variety of (annelated) benzimidazoles could be easily obtained in high yields from readily available starting materials, and this procedure could be further applied to the synthesis of the antihypertensive blockbuster drug telmisartan.

Insights into post-translational regulation of skeletal muscle contractile function by the acetyltransferases, p300 and CBP.

Unlabelled: Mice with skeletal muscle-specific inducible double knockout of the lysine acetyltransferases, p300 (E1A binding protein p300) and CBP (cAMP-response element-binding protein binding protein), referred to as i-mPCKO, demonstrate a dramatic loss of contractile function in skeletal muscle and ultimately die within 7 days. Given that many proteins involved in ATP generation and cross-bridge cycling are acetylated, we investigated whether these processes are dysregulated in skeletal muscle from i-mPCKO mice and thus could underlie the rapid loss of muscle contractile function. Just 4-5 days after inducing knockout of p300 and CBP in skeletal muscle from adult i-mPCKO mice, there was ∼90% reduction in contractile function in the extensor digitorum longus (EDL) and a ∼65% reduction in ankle dorsiflexion torque, as compared to wildtype (WT; i.

Translation, validity and reliability of the pain attitudes and beliefs scale for physiotherapists in French.

Background: The Pain Attitudes and Beliefs Scale for Physiotherapists (PABS-PT) questionnaire evaluates manual therapists' biomedical and biopsychosocial beliefs regarding the management of chronic low back pain. Its usage in clinical settings is an important step in the implementation of national guidelines and policies to improve patient management.

Objectives: The objective of this study was to translate the PABS-PT questionnaire into French, to adapt it culturally, and to conduct a psychometric analysis.

Prevalence and risk factors of the use of physical restraint and impact of a decision support tool: A before-and-after study.

Background: Physical restraint is frequently used in intensive care units to prevent patients' life-threatening removal of indwelling devices. In France, their use is poorly studied. Therefore, to evaluate the need for physical restraint, we have designed and implemented a decision support tool.

Metabolic Reprogramming of Macrophages upon In Vitro Incubation with Aluminum-Based Adjuvant.

Aluminum-based adjuvants have been extensively used in vaccines. Despite their widespread use, the mechanism behind the immune stimulation properties of these adjuvants is not fully understood. Needless to say, extending the knowledge of the immune-stimulating properties of aluminum-based adjuvants is of utmost importance in the development of new, safer, and efficient vaccines.

Evaluation of dried-blood spots and a hematocrit-independent procedure in lysosomal diseases screening using multiplexed tandem mass spectrometry assays.

Background: Dried blood spots (DBS) are widely used as a non-invasive sampling method, especially in newborn screening (NBS). Despite its numerous advantages, conventional DBS might be limited by the hematocrit effect when analyzing a punch, depending on its position in the blood spot. This effect could be avoided using hematocrit-independent sampling devices such as the hemaPEN®.

Large-Scale Interlaboratory DI-FT-ICR MS Comparability Study Employing Various Systems.

Ultrahigh resolution mass spectrometry (UHR-MS) coupled with direct infusion (DI) electrospray ionization offers a fast solution for accurate untargeted profiling. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers have been shown to produce a wealth of insights into complex chemical systems because they enable unambiguous molecular formula assignment even if the vast majority of signals is of unknown identity. Interlaboratory comparisons are required to apply this type of instrumentation in quality control (for food industry or pharmaceuticals), large-scale environmental studies, or clinical diagnostics.

Identification of risk loci for primary aldosteronism in genome-wide association studies.

Primary aldosteronism affects up to 10% of hypertensive patients and is responsible for treatment resistance and increased cardiovascular risk. Here we perform a genome-wide association study in a discovery cohort of 562 cases and 950 controls and identify three main loci on chromosomes 1, 13 and X; associations on chromosome 1 and 13 are replicated in a second cohort and confirmed by a meta-analysis involving 1162 cases and 3296 controls. The association on chromosome 13 is specific to men and stronger in bilateral adrenal hyperplasia than aldosterone producing adenoma.

A rapid and quantitative reversed-phase HPLC-DAD/ELSD method for lipids involved in nanoparticle formulations.

Lipid nanoparticles (LNPs) have shown great success as drug delivery systems, especially for mRNA vaccines, as those developed during the Covid-19 pandemics. Lipid analysis is critical to monitor the formulation process and control the quality of LNPs. The present study is focused on the development and validation of a high-performance liquid chromatography - diode array detector -evaporative light scattering detector (HPLC-DAD/ELSD) based method for the simultaneous quantification of 7 lipids, illustrating the main components of LNPs: ionizable lipids, the neutral co-lipid cholesterol, phospholipids, hydrophilic polymer-lipids for colloidal stability (e.

Design - a new way to look at old molecules.

We discuss how design enriches molecular science, particularly structural biology and bioinformatics. We present two use cases, one in academic practice and the other to design for outreach. The first case targets the representation of ion channels and their dynamic properties.

Imaging Matrix-Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry of oxaliplatin derivatives in human tissue sections.

Mass Spectrometry Imaging is an effective technology that allows to determine the in-situ distribution of endogen and/or exogen small molecules. It is a rapidly emerging approach for visualizing drugs and their metabolites within biological tissues. Matrix-Assisted Laser Desorption Ionization (MALDI) Mass Spectrometry Imaging (MSI) coupled to high resolving power analyzer (e.

Integrative Metabolomics Reveals Deep Tissue and Systemic Metabolic Remodeling in Glioblastoma.

(1) Background: Glioblastoma is the most common malignant brain tumor in adults. Its etiology remains unknown in most cases. Glioblastoma pathogenesis consists of a progressive infiltration of the white matter by tumoral cells leading to progressive neurological deficit, epilepsy, and/or intracranial hypertension.

An analytical study of lipid-oligonucleotide aggregation properties.

Lipid-oligonucleotides (LON) attract great interest as supramolecular scaffolds to improve the intracellular delivery of nucleic acids. Analytical characterization of LON assemblies is critical to formulation development, understanding in-vivo performance, as well as quality control. For this study, we selected LONs featuring different modifications on both oligonucleotide (with or without a G4 prone sequence) and lipid (mono or bis-alkyl chain covalently attached to the oligonucleotide sequence).

Hydrogenation of fluorinated molecules: an overview.

The review aims at providing an overview on the developments made in hydrogenation reactions of molecules having various fluorinated groups (F, CF3, CF2H, CF2Rf). Indeed, the hydrogenation of fluorine-containing molecules is a straightforward and atom-economical way to access challenging (chiral) fluorinated scaffolds. This promising field is still in its infancy and milestones are expected in the coming years.

Muscle metabolic remodelling patterns in Duchenne muscular dystrophy revealed by ultra-high-resolution mass spectrometry imaging.

Duchenne muscular dystrophy (DMD) is a common and severe X-linked myopathy, characterized by muscle degeneration due to altered or absent dystrophin. DMD has no effective cure, and the underlying molecular mechanisms remain incompletely understood. The aim of this study is to investigate the metabolic changes in DMD using mass spectrometry-based imaging.

Green reversed-phase HPLC development strategy: Application to artesunate and amodiaquine analysis.

A green analytical chemistry strategy is described to develop a reversed-phase high-performance liquid chromatography method for amodiaquine and artesunate analysis using ethanol-based mobile phases. This method development was particularly challenging due to the basicity of amodiaquine and low UV absorption of artesunate, leading to peak asymmetry and detection issues, respectively. UV detection concern was even more challenging due to the baseline drift observed with ethanol in gradient mode.

Physical, Modular and Articulated Interface for Interactive Molecular Manipulation.

Rational drug design is an approach based on detailed knowledge of molecular interactions and dynamic of bio-molecules. This approach involves designing new digital and interactive tools including classical desktop interaction devices as well as advanced ones such as haptic arms or virtual reality devices. These approaches however struggle to deal with flexibility of bio-molecules by simultaneously steering the numerous degrees of freedom.

Analysis of lipid-oligonucleotide conjugates by cyclodextrin-modified capillary zone electrophoresis.

Lipid-oligonucleotide (LONs) based bioconjugates represent an emerging class of therapeutic agents, allowing the delivery of therapeutic oligonucleotide sequences. The LON development requests accurate and efficient analytical methods. In this contribution, LON analysis methods were developed in cyclodextrin-modified capillary zone electrophoresis (CD-CZE).

Development of a green HPLC method for the analysis of artesunate and amodiaquine impurities using Quality by Design.

Greening analytical methods has become of great interest in the field of pharmaceutical analysis to protect both the operators' health and the environment. In this work, an innovative methodology combining Quality-by-Design (QbD) and Green Chemistry principles was followed to develop a single, green and robust RP-HPLC method for the quantitative analysis of impurities of both artesunate and amodiaquine drugs. Ethanol was selected as the best ecofriendly alternative solvent in substitution to the commonly used organic solvents such as acetonitrile and methanol.

Direct Access to Highly Enantioenriched α-Branched Acrylonitriles through a One-Pot Sequential Asymmetric Michael Addition/Retro-Dieckmann/Retro-Michael Fragmentation Cascade.

A highly enantioselective synthesis of α-branched acrylonitriles is reported featuring a one-pot sequential asymmetric Michael addition/retro-Dieckmann/retro-Michael fragmentation cascade. The method, which relies on a solid, bench-stable, and commercially available acrylonitrile surrogate, is practical, scalable, and highly versatile and provides a direct access to a wide range of enantioenriched nitrile-containing building blocks. Most importantly, the method offers a new tool to incorporate an acrylonitrile moiety in an asymmetric fashion.

Green Analytical Methods of Antimalarial Artemether-Lumefantrine Analysis for Falsification Detection Using a Low-Cost Handled NIR Spectrometer with DD-SIMCA and Drug Quantification by HPLC.

Two green analytical approaches have been developed for the analysis of antimalarial fixed dose tablets of artemether and lumefantrine for quality control. The first approach consisted of investigating the qualitative performance of a low-cost handheld near-infrared spectrometer in combination with the principal component analysis as an exploratory tool to identify trends, similarities, and differences between pharmaceutical samples, before applying the data driven soft independent modeling of class analogy (DD-SIMCA) as a one-class classifier for proper drug falsification detection with 100% of both sensitivity and specificity in the studied cases. Despite its limited spectral range and low resolution, the handheld device allowed detecting falsified drugs with no active pharmaceutical ingredient and identifying specifically a pharmaceutical tablet brand name.