Synthesis and Photophysical Properties of 4'-5' Disubstituted CinNapht Dyes Accessible through Double SNAr Late-Stage Functionalization.

This article describes the synthesis of a difluorinated CinNapht derivative in the 4' and 5' positions allowing the easy access to two new families of fluorophores by late-stage functionalization using SNAr. The first one comprises derivatives incorporating hindered aromatic amines in the 4' and 5' positions, which show red-emission in apolar solvents. The second one is obtained through the use of dinucleophiles.

A Naphthalimide Based "Turn-ON" Probe for Wash-Free Imaging of Lipid-Droplet in Living Cells With an Excellent Selectivity.

The impacts of dimethylation of 4-Amino-1,8-Naphthalimide (ANI) on its photophysical properties are reported. The resulting 4-DiMe-ANI displays completely different fluorescence properties, conferring it ability to selectively label lipid droplets in living cells. A comprehensive photophysical study revealed that this selectivity arises from an Internal Charge Transfer favored in lipophilic media to the detriment of a non-emissive TICT in more polar media.

CinNapht AIE(E)gens for selective imaging of lipid droplets.

This article describes the synthesis and photophysical properties of Aggregation-Induced Emission (enhancement) luminogens derivated from CinNaphts dyes. These fluorophores can be obtained in good yields in a single SNAr step of a fluorinated CinNapht derivative by incorporating hindered aromatic amines. They exhibit AIE(E) behavior associated with solid-state fluorescence covering an emission range from 563 to 722 nm.

Lanthanide-Based Probes for Imaging Detection of Enzyme Activities by NIR Luminescence, T1- and ParaCEST MRI.

Applying a single molecular probe to monitor enzymatic activities in multiple, complementary imaging modalities is highly desirable to ascertain detection and to avoid the complexity associated with the use of agents of different chemical entities. We demonstrate here the versatility of lanthanide (Ln) complexes with respect to their optical and magnetic properties and their potential for enzymatic detection in NIR luminescence, CEST and T1 MR imaging, controlled by the nature of the Ln ion, while using a unique chelator. Based on X-ray structural, photophysical, and solution NMR investigations of a family of Ln DO3A-pyridine model complexes, we could rationalize the luminescence (Eu, Yb), CEST (Yb) and relaxation (Gd) properties and their variations between carbamate and amine derivatives.

Visualization of an Endogenous Mitochondrial Azoreductase Activity under Normoxic Conditions Using a Naphthalimide Azo-Based Fluorogenic Probe.

In this paper, we demonstrate the existence of an endogenous mitochondrial azoreductase (AzoR) activity that can induce the cleavage of N═N double bonds of azobenzene compounds under normoxic conditions. To this end, 100% OFF-ON azo-based fluorogenic probes derived from 4-amino-1,8-naphthalimide fluorophores were synthesized and evaluated. The in vitro study conducted with other endogenous reducing agents of the cell, including reductases, demonstrated both the efficacy and the selectivity of the probe for AzoR.

Characteristics of patients with atrial fibrillation treated with direct oral anticoagulants and new insights into inappropriate dosing: results from the French National Prospective Registry: PAFF.

Aims: Since the introduction of direct oral anticoagulant (DOAC) for atrial fibrillation (AF) therapy, inappropriate and/or underdosing of these drugs has been a major clinical challenge. We evaluated the characteristics of patients with AF treated with inappropriate and low-dose DOACs.

Methods And Results: Patients with AF treated with inappropriate and low-dose DOACs from October 2021 to December 2021 were evaluated from the French National Prospective Registry (PAFF).

Pediatric hepatic hemangiomas: spectrum and prognostic significance of initial ultrasound findings.

Background: Hepatic hemangiomas may be associated with serious complications; however, it is unknown whether ultrasound (US) features can predict complications.

Objective: To analyze initial US features of hepatic hemangiomas predictive of complications.

Materials And Methods: This is a single-center retrospective cohort study of clinical, biological, and imaging data of infants with hepatic hemangioma between 2000 and 2018.

Partial Replacement of Synthetic Vitamin E by Polyphenols in Post-Weaning Piglets.

Vitamin E is an essential nutrient usually recommended in post-weaning piglets, when a decline in the serum vitamin E concentration is observed. Selected polyphenols have the potential to partially replace vitamin E in animal feed. The aim of this study was to investigate the effect of the dietary inclusion of some commercial polyphenol products (PPs) on the growth performance, antioxidant status and immunity of post-weaning piglets.

Unprecedented perspectives on the application of CinNapht fluorophores provided by a "late-stage" functionalization strategy.

A simple and easy-to-implement process based on a nucleophilic aromatic substitution reaction with a wide variety of nucleophiles on a fluorinated CinNapht is described. This process has the key advantage of introducing multiple functionalities at a very late stage, thus providing access to new applications including the synthesis of photostable and bioconjugatable large Stokes shift red emitting dyes and selective organelle imaging agents, as well as AIEE-based wash-free lipid droplet imaging in live cells with high signal-to-noise ratio. The synthesis of bench-stable CinNapht-F has been optimized and can be reproduced on a large scale, making it an easy-to-store starting material that can be used at will to prepare new molecular imaging tools.

Blood Purification with oXiris© in Critically Ill Children with Vasoplegic Shock.

Introduction: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. As such, circulating cytokines and danger- and pathogen-associated molecular patterns (such as endotoxins) are recognized as central in the pathogenesis of sepsis and organ dysfunction. Removing these compounds by extracorporeal blood filtration, commonly considered blood purification, may improve the septic patients' condition.

Clinical practice guidelines: management of severe bronchiolitis in infants under 12 months old admitted to a pediatric critical care unit.

Purpose: We present guidelines for the management of infants under 12 months of age with severe bronchiolitis with the aim of creating a series of pragmatic recommendations for a patient subgroup that is poorly individualized in national and international guidelines.

Methods: Twenty-five French-speaking experts, all members of the Groupe Francophone de Réanimation et Urgence Pédiatriques (French-speaking group of paediatric intensive and emergency care; GFRUP) (Algeria, Belgium, Canada, France, Switzerland), collaborated from 2021 to 2022 through teleconferences and face-to-face meetings. The guidelines cover five areas: (1) criteria for admission to a pediatric critical care unit, (2) environment and monitoring, (3) feeding and hydration, (4) ventilatory support and (5) adjuvant therapies.

Profiles of Fatty Acids, Polyphenols, Sterols, and Tocopherols and Scavenging Property of Mediterranean Oils: New Sources of Dietary Nutrients for the Prevention of Age-related Diseases.

The present study provides the fatty acid, tocopherol, phytosterol, and polyphenol profiles of some Mediterranean oils extracted from pumpkin, melon, and black cumin seed oils and those of dietary argan seed oil. Gas chromatography analysis revealed that oleic and linoleic acids were the most abundant fatty acids. Argan and melon seed oils exhibited the highest levels of oleic acid (47.

Cytotoxic and Antioxidant Activities of Imine Analogs of Trans-Resveratrol towards Murine Neuronal N2a Cells.

-resveratrol is a natural polyphenol showing numerous biological properties, especially anti-tumoral and antioxidant activity. Among numerous resveratrol derivatives, aza-stilbenes, which bear an imine bound, show interesting biological activities. In the present study, we synthesized a series of imine analogs of -resveratrol (seven aza-stilbenes) following an easy and low-cost procedure of green chemistry.

A comparative study of the effects of 3 testicular toxicants in cultures of seminiferous tubules of rats or of domestic cats (veterinary waste): An alternative method for reprotoxicology.

In response to the EU cosmetics directive regulation and REACH legislation which encourage cell culture methods in order to reduce or replace the use of animals in toxicology studies, we settled the culture of prepubertal domestic cat seminiferous tubules in our validated BioAlter® model, usually used with prepubertal rat, called here BioAlter®-rat, by opposition to BioAlter®-cat settled here. We carried out a comparative study on the effects of 3 testicular toxicants, 1,3-dinitrobenzene at 60 μM, 2-methoxyacetic acid at 2.5 mM and carbendazim at 50 nM or 500 nM in both BioAlter®-cat and BioAlter®-rat over a 3-week culture period.

"CinNapht" dyes: a new cinnoline/naphthalimide fused hybrid fluorophore. Synthesis, photo-physical study and use for bio-imaging.

Six-membered-diaza ring of cinnoline has been fused on naphthalimide dye to give a donor-acceptor system called CinNapht. This red shifted fluorophore, that can be synthesised in gram scale, exhibits a large Stoke shift and a fluorescence quantum yield up to 0.33.

Quantitative Flow Ratio Analysis by Paramedical Compared With Medical Users.

Objectives: We aimed to validate whether quantitative flow ratio (QFR) analysis could be performed by both medical and paramedical certified users. Therefore, we compared QFR values with conventional guidewire-based fractional flow reserve (FFR) as the reference using core laboratory analysis. QFR allows FFR calculation based on the coronary angiogram.

High-Relaxivity Molecular MRI Contrast Agent to Target Gb3-Expressing Cancer Cells.

Targeted contrast agents (CAs) can improve magnetic resonance imaging (MRI) for accurate cancer diagnosis. In this work, we used the Shiga toxin B-subunit (STxB) as a targeting agent, which binds to Gb3, a glycosphingolipid highly overexpressed on the surface of tumor cells. We developed STxB-targeted MRI probes from cyclic peptide scaffolds functionalized with six to nine monoamide DO3A[Gd(III)] chelates.

Evaluation of borinic acids as new, fast hydrogen peroxide-responsive triggers.

Hydrogen peroxide (HO) is responsible for numerous damages when overproduced, and its detection is crucial for a better understanding of HO-mediated signaling in physiological and pathological processes. For this purpose, various "off-on" small fluorescent probes relying on a boronate trigger have been prepared, and this design has also been involved in the development of HO-activated prodrugs or theranostic tools. However, this design suffers from slow kinetics, preventing activation by HO with a short response time.

Low concentrations of glyphosate alone affect the pubertal male rat meiotic step: An in vitro study.

Glyphosate is the most used herbicide in the world. Controversial studies exist on its effect on the male reproductive system. We used the validated BioAlter® model to test the effects of low concentrations of Glyphosate.

Myeloid phenotypes in severe COVID-19 predict secondary infection and mortality: a pilot study.

Background: De-regulated host response to severe coronavirus disease 2019 (COVID-19), directly referring to the concept of sepsis-associated immunological dysregulation, seems to be a strong signature of severe COVID-19. Myeloid cells phenotyping is well recognized to diagnose critical illness-induced immunodepression in sepsis and has not been well characterized in COVID-19. The aim of this study is to review phenotypic characteristics of myeloid cells and evaluate their relations with the occurrence of secondary infection and mortality in patients with COVID-19 admitted in an intensive care unit.

An in vitro bioassay to assess the potential global toxicity of waters on spermatogenesis: a pilot study.

Many toxicants are present in water as a mixture. Male infertility is one of the environmental impacts in developed countries. Using our rat seminiferous tubule culture model, we evaluated the effects of waters of different origins, on several parameters of the seminiferous epithelium.

Cardiovascular disorders in patients with congenital portosystemic shunts: 23 years of experience in a tertiary referral centre.

Background: Congenital portosystemic shunts are rare vascular malformations that may have an impact on the heart-lung system. Associated congenital and/or acquired heart diseases are poorly reported.

Aims: To analyse cardiovascular disorders within a large congenital portosystemic shunt population, and develop a diagnostic strategy.