CD8+ T Cell Senescence: Lights and Shadows in Viral Infections,Autoimmune Disorders and Cancer

CD8⁺ T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, they turn into memory lymphocytes, thus providing a long-term protection. During ageing, the thymic involution causes a reduction of circulating T cells and an enrichment of memory cells, partially explaining the lowering of the response towards novel antigens with implications in vaccine efficacy. Moreover, the persistent stimulation by several antigens throughout life favors the switching of CD8⁺ T cells towards a senescent phenotype contributing to a low-grade inflammation that is a major component of several ageing-related diseases. In genetically predisposed young people, an immunological stress caused by viral infections (e.g., HIV, CMV, SARS-CoV-2), autoimmune disorders or tumor microenvironment (TME) could mimic the ageing status with the consequent acceleration of T cell senescence. This, in turn, exacerbates the inflamed conditions with dramatic effects on the clinical progression of the disease. A better characterization of the phenotype as well as the functions of senescent CD8⁺ T cells can be pivotal to prevent age-related diseases, to improve vaccine strategies and, possibly, immunotherapies in autoimmune diseases and cancer.     

Melting behavior,crystallization kinetics and morphology of random copolyesters of poly(2‐hydroxyethoxybenzoate) with ε‐caprolactone

The melting behavior after isothermal crystallization and the crystallization kinetics of random poly(2‐hydroxyethoxybenzoate/ε‐caprolactone) copolymers rich in 2hydroxyethoxybenzoate units were investigated by means of differential scanning calorimetry and hot‐stage optical microscopy. The observed multiple endotherms, which are commonly displayed by polyesters, were found to be influenced both by crystallization temperature and composition. By applying the Hoffman‐Weeks method to the melting temperatures of isothermally crystallized samples, the equilibrium melting temperatures of the copolymers were obtained. Furthermore, isothemal crystallization kinetics was analyzed according to the Avrami treatment. Values of the exponent n close to 3 were obtained, independently of crystallization temperature and composition, in agreement with a crystallization process originating from predeterminated nuclei and characterized by three‐dimensional spherulitic growth. Space‐filling banded spherulites were observed by hot‐stage optical polarizing microscopy at all the crystallization temperatures explored, the band spacing being affected by both crystallization temperature and composition. As expected, the introduction of ε‐caprolactone comonomeric units in the polymer chain of PHEBA was found to decrease its crystallization rate.     

Processing and Properties of Ti(C,N)–WC-Based Materials

Two Ti(C,N)–WC powder mixtures, one containing 0.88 wt% Co and the other 6.2 wt% Ni + 2.9 wt% Co, were fabricated by different routes: pressureless and gas-pressure sintering in argon and nitrogen, and hot-pressing under vacuum. The microstructures of all the sintered samples consisted of grains with a core/rim structure, the core being Ti(C,N) and the rim (Ti,W)(C,N). An inner rim also was present at the core/rim interface. The more highly doped materials also had an intergranular Ni-Co-Ti-W binder phase. The compositions and cell parameters of the hard phases, as well as of the binder, were analyzed. The nitrogen partial pressure in the sintering furnace was the main factor that influenced grain growth and phase composition. In fact, sintering under argon enhanced grain growth and was accompanied by a lower tungsten content in the rim. The influence of the microstructure on some mechanical properties (hardness, flexural strength, toughness, and Young's modulus) also was investigated. Flexural-strength values up to 1550 MPa at room temperature and 1200 MPa at 800°C, and fracture-toughness values up to 8 MPa·m^1/2 were measured, depending on the starting composition and processing conditions.     

Self-assembled silver nanoislands formed on glass surface via out-diffusion for multiple usages in SERS applications

We demonstrate that silver nanoisland film self-assembled on the surface of silver-containing glass in the course of thermal processing in hydrogen is capable to detect 10⁻⁷ M concentration of rhodamine 6G in water using surface enhanced Raman spectroscopy (SERS) technique. The film can be multiply restored on the same glass substrate via annealing of the glass in hydrogen. We showed that the film can be self-assembled after as much as ten circles of the substrate cleaning followed by annealing. The proposed technique of the silver nanoisland film formation enables multiple usage of the same glass substrate in SERS experiments.     

Aromatic Linkers Unleash the Antiproliferative Potential of 3-Chloropiperidines Against Pancreatic Cancer Cells

In this study, we describe the synthesis and biological evaluation of a set of bis-3-chloropiperidines (B−CePs) containing rigid aromatic linker structures. A modification of the synthetic strategy also enabled the synthesis of a pilot tris-3-chloropiperidine (Tri-CeP) bearing three reactive meta-chloropiperidine moieties on the aromatic scaffold. A structure–reactivity relationship analysis of B−CePs suggests that the arrangement of the reactive units affects the DNA alkylating activity, while also revealing correlations between the electron density of the aromatic system and the reactivity with biologically relevant nucleophiles, both on isolated DNA and in cancer cells. Interestingly, all aromatic 3-chloropiperidines exhibited a marked cytotoxicity and tropism for 2D and 3D cultures of pancreatic cancer cells. Therefore, the new aromatic 3-chloropiperidines appear to be promising contenders for further development of mustard-based anticancer agents aimed at pancreatic cancers.     

Identification of a new oxidation/ dissolution mechanism for boria-accelerated SiC oxidation

Boria effects on accelerated SiC oxidation kinetics were investigated by conducting thermogravimetric analysis on SiC substrates coated with sol-gel derived borosilicate glass isothermally exposed to dry O₂ and argon at 800°C and 1200°C for 100 hours. Boria concentrations in the glass coatings were 0, 14-38, and 92-94 mol%, balance silica. Accelerated weight gain was observed for SiC exposures in dry O₂ at 800°C when boria concentrations were ≥ 92 mol%, corroborated by oxide thickness ranging from 3.5 to 10 µm. The oxide thickness predicted for pure SiC exposed to these conditions in the absence of boria is 0.15 µm. Microstructural analysis of SiC surfaces after oxide removal revealed that boria etched the underlying SiC substrate. Oxidation exposures at 1200°C in dry O₂ suppressed boria effects on accelerating SiC oxidation kinetics due to rapid boria volatilization coupled with the formation of a protective thermally grown silica scale. Accelerated weight gain or oxide growth did not occur with argon exposures at either temperature. A new mechanism for boria-accelerated SiC surface-reaction kinetics is presented based on evidence for boria etching of SiC.     

Structural properties of nanocomposites based on resole-type phenol-formaldehyde oligomers and detonation nanodiamonds

Using the methods of infrared spectroscopy (IRS) and X-ray photoelectron spectroscopy (XPS), it was shown that short-term high-energy machining of detonation nanodiamonds (DND) leads to structural changes in the crystal structure and functional composition of the surface layer on particles. The possibility of spontaneous formation for stable colloidal systems with a narrow size distribution of mechanically activated DND in phenol-formaldehyde oligomers (PFO) was established. By molecular spectroscopy it was revealed that π → π* interactions of the aromatic rings of PFO are caused by orientational phenomena as a result of hydrogen bonds between an activated DND surface and functional groups of PFO. The effect of DND concentration on the curing reaction parameters ofpsgr the phenol-formaldehyde oligomer was determined by differential scanning calorimetry (DSC). The concentration effect of mechanically activated nanodiamonds on the physical and mechanical characteristics of a composite material based on phenol-formaldehyde binder and polyamide paper (Nomex) was studied. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48582.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

The Anti-Inflammatory Properties of Mesenchymal Stem Cells in Epilepsy: Possible Treatments and Future Perspectives

Mesenchymal stem cells (MSCs) are multipotent adult cells with self-renewing capacities. MSCs display specific properties, such as the ability to repair damaged tissues, resulting in optimal candidates for cell therapy against degenerative diseases. In addition to the reparative functions of MSCs, growing evidence shows that these cells have potent immunomodulatory and anti-inflammatory properties. Therefore, MSCs are potential tools for treating inflammation-related neurological diseases, including epilepsy. In this regard, over the last decades, epilepsy has no longer been considered a purely neuronal pathology, since inflammatory events underlying the genesis of epilepsy have been demonstrated. This review assessed current knowledge on the use of MSCs in the treatment of epilepsy. Mostly, attention will be focused on the anti-inflammatory and immunological skills of MSCs. Understanding the mechanisms by which MSCs might modulate the severity of the disease will contribute to the development of new potential alternatives for both prophylaxis and treatment against epilepsy.