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Interleukin (IL)-36α, IL-36β and IL-36γ are expressed highly in skin and are involved in the pathogenesis of psoriasis, while the antagonists IL-36Ra or IL-38, another potential IL-36 inhibitor, limit uncontrolled inflammation. The expression and role of IL-36 cytokines in rheumatoid arthritis (RA) and Crohn's disease (CD) is currently debated. Here, we observed that during imiquimod-induced mouse skin inflammation and in human psoriasis, expression of IL-36α, γ and IL-36Ra, but not IL-36β and IL-38 mRNA, was induced and correlated with IL-1β and T helper type 17 (Th17) cytokines (IL-17A, IL-22, IL-23, CCL20). In mice with collagen-induced arthritis and in the synovium of patients with RA, IL-36α, β, γ, IL-36Ra and IL-38 were all elevated and correlated with IL-1β, CCL3, CCL4 and macrophage colony-stimulating factor (M-CSF), but not with Th17 cytokines. In the colon of mice with dextran sulphate sodium-induced colitis and in patients with CD, only IL-36α, γ and IL-38 were induced at relatively low levels and correlated with IL-1β and IL-17A. We suggest that only a minor subgroup of patients with RA (17-29%) or CD (25%) had an elevated IL-36 agonists/antagonists ratio, versus 93% of patients with psoriasis. By immunohistochemistry, IL-36 cytokines were produced by various cell types in skin, synovium and colonic mucosa such as keratinocytes, CD68+ macrophages, dendritic/Langerhans cells and CD79α+ plasma cells. In primary cultures of monocytes or inflammatory macrophages (M1), IL-36β and IL-36Ra were produced constitutively, but IL-36α, γ and IL-38 were produced after lipopolysaccharide stimulation. These distinct expression profiles may help to explain why only subgroups of RA and CD patients have a potentially elevated IL-36 agonists/antagonists ratio. [ABSTRACT FROM AUTHOR]

Modeling proton-induced damage in biological systems, in particular in DNA building blocks, is of major concern in studies on cancer proton therapy. This is indeed an extremely complex process and analysis of the mechanism at the molecular level is of crucial interest. Such collision reactions of protons on biological targets induce different reactions: excitation and ionization of the biomolecule, fragmentation of the ionized species, and charge transfer from the projectile ion toward the biomolecular target. In order to have an insight into such mechanisms, we have performed a theoretical approach of two of the most important steps, the fragmentation and the charge transfer processes. For that purpose, we have considered collision of protons with isolated 2-deoxy-D-ribose by means of ab-initio molecular dynamics and quantum chemistry molecular methods. The conformation of the sugar moiety has been analyzed and appears to induce important effects, in particular different fragmentation patterns have been pointed out with regard to the conformation, and significant variations of the charge transfer cross sections have been exhibited. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

ATRP of methyl methacrylate catalyzed by Eosin Y, an inexpensive and an environmental benign dye, was performed in a continuous flow reactor made of FEP tubing and irradiated by visible light green LEDs. The reaction under flow conditions was significantly more rapid and controlled compared to that in batch giving 90% of polymerization after only 3 h of irradiation. The formed polymers in flow have M n measured by GPC and DOSY NMR in accordance with the theoretical values and show low dispersities (Ð < 1.5). The livingness of the polymers has been confirmed by LED on and LED off experiments and by the synthesis of block copolymers. The protocol described herein serves as a "proof of concept" of using Eosin Y as a photocatalyst for controlled polymerization and of using 1D and 2D NMR for polymer characterization. The protocol could be replicated in the future for other reversible-deactivation radical polymerizations., (Copyright © 2020 El Achi, Bakkour, Adhami, Molina, Penhoat, Azaroual, Chausset-Boissarie and Rolando.)

A novel extension of Meyer's lactamization is reported for the preparation of seven-membered ring lactams 1a-d incorporating a biaryl unit. The required keto-esters 2a-c were readily accessible via the Suzuki coupling reaction. A borylation-Suzuki coupling (BSC) sequence was successfully developed for the high-yielding preparation of keto-ester 2d. Cyclization of the resulting keto-esters 2a-d or keto-acids 5a,c,d in the presence of (R)-phenylglycinol afforded the desired lactams 1a-d in high yields (72-93%) and excellent diastereoselectivities (>95%). This methodology provides a facile stereoselective access to new axially chiral bridged biaryls.

To test a possible specific effect of carbon K-shell ionizations in DNA, survival curves for Chinese hamster V79 cells were measured for X irradiations at energies below and above the carbon K-shell ionization threshold. Specific values of the X-ray energies (250 and 340 eV) were chosen to ensure isoattenuation of the two kinds of radiation within the cell. An enhancement of lethality by a factor of about 2 was found for X rays at 340 eV compared to below the threshold at 250 eV. This may be attributed to the production of highly efficient carbon K-shell ionizations located on DNA. A model of X-ray lethality (Goodhead et al., Radiat. Prot. Dosim. 52, 217-223, 1994) was extended to allow for a possible lethal effect from clusters of reactive species induced by K-shell photoionizations (K-shell clusters). Within this model, the increase in lethality above the carbon K-shell threshold may be explained by a value of 2% for the lethal efficiency of K-shell clusters overlapping the DNA. An extrapolation to the lethal effect of more complex ion-induced K-shell ionizations indicates that K-shell ionization may be a major process in the biological effectiveness of heavy ions.