The Impact of the ‘Mis-Peptidome’ on HLA Class I-Mediated Diseases: Contribution of ERAP1 and ERAP2 and Effects on the Immune Response

The strong association with the Major Histocompatibility Complex (MHC) class I genes represents a shared trait for a group of autoimmune/autoinflammatory disorders having in common immunopathogenetic basis as well as clinical features. Accordingly, the main risk factors for Ankylosing Spondylitis (AS), prototype of the Spondyloarthropathies (SpA), the Behçet’s disease (BD), the Psoriasis (Ps) and the Birdshot Chorioretinopathy (BSCR) are HLA-B*27, HLA-B*51, HLA-C*06:02 and HLA-A*29:02, respectively. Despite the strength of the association, the HLA pathogenetic role in these diseases is far from being thoroughly understood. Furthermore, Genome-Wide Association Studies (GWAS) have highlighted other important susceptibility factors such as Endoplasmic Reticulum Aminopeptidase (ERAP) 1 and, less frequently, ERAP2 that refine the peptidome presented by HLA class I molecules to CD8⁺ T cells. Mass spectrometry analysis provided considerable knowledge of HLA-B*27, HLA-B*51, HLA-C*06:02 and HLA-A*29:02 immunopeptidome. However, the combined effect of several ERAP1 and ERAP2 allelic variants could generate an altered pool of peptides accounting for the “mis-immunopeptidome” that ranges from suboptimal to pathogenetic/harmful peptides able to induce non-canonical or autoreactive CD8⁺ T responses, activation of NK cells and/or garbling the classical functions of the HLA class I molecules. This review will focus on this class of epitopes as possible elicitors of atypical/harmful immune responses which can contribute to the pathogenesis of chronic inflammatory diseases.     

Gastric Adenocarcinomas and Signet-Ring Cell Carcinoma: Unraveling Gastric Cancer Complexity through Microbiome Analysis—Deepening Heterogeneity for a Personalized Therapy

Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. With the advances of the omic studies, a heterogeneous GC landscape has been revealed, with significant molecular diversity. Given the multifaceted nature of GC, identification of different patient subsets with prognostic and/or predictive outcomes is a key aspect to allow tailoring of specific treatments. Recently, the involvement of the microbiota in gastric carcinogenesis has been described. To deepen this aspect, we compared microbiota composition in signet-ring cell carcinoma (SRCC) and adenocarcinoma (ADC), two distinct GC subtypes. To this purpose, 10 ADC and 10 SRCC and their paired non-tumor (PNT) counterparts were evaluated for microbiota composition through 16S rRNA analysis. Weighted and unweighted UniFrac and Bray–Curtis dissimilarity showed significant community-level separation between ADC and SRCC. Through the LEfSe (linear discriminant analysis coupled with effect size) tool, we identified potential microbial biomarkers associated with GC subtypes. In particular, SRCCs were significantly enriched in the phyla Fusobacteria, Bacteroidetes, Patescibacteria, whereas in the ADC type, Proteobacteria and Acidobacteria phyla were found. Overall, our data add new insights into GC heterogeneity and may contribute to deepening the GC classification.     

Graphene nanoplatelets composite membranes for thermal comfort enhancement in performance textiles

The advent of 2D nanostructured materials as advanced fillers for polymer matrix composites has opened the doors to a plethora of new industrial applications requiring both electric and thermal management. Unique properties, in fact, can arise from accurate selection and processing of 2D fillers and their matrix. Here, we report an innovative family of nanocomposite membranes based on polyurethane (PU) and graphene nanoplatelets (GNPs), designed to improve thermal comfort in functional textiles. GNP particles were thoroughly characterized (through Raman, atomic force microscopy, high-resolution TEM, scanning electron microscope), and showed high crystallinity (I_D/I_G = 0.127), low thickness (D50 < 6–8 layers), and high lateral dimensions (D50 ≈ 3 μm). When GNPs were loaded (up to 10% wt/wt) into the PU matrix, their homogeneous dispersion resulted in an increase of the in-plane thermal conductivity of composite membranes up to 471%. The thermal dissipation of membranes, alone or coupled with cotton fabric, was further evaluated by means of an ad hoc system designed to simulate a human forearm. The results obtained provide a new strategy for the preparation of membranes suitable for technical textiles, with improved thermal comfort.     

Mechanical Cues Regulating Proangiogenic Potential of Human Mesenchymal Stem Cells through YAP‐Mediated Mechanosensing

Stem cells secrete trophic factors that induce angiogenesis. These soluble factors are promising candidates for stem cell–based therapies, especially for cardiovascular diseases. Mechanical stimuli and biophysical factors presented in the stem cell microenvironment play important roles in guiding their behaviors. However, the complex interplay and precise role of these cues in directing pro‐angiogenic signaling remain unclear. Here, a platform is designed using gelatin methacryloyl hydrogels with tunable rigidity and a dynamic mechanical compression bioreactor to evaluate the influence of matrix rigidity and mechanical stimuli on the secretion of pro‐angiogenic factors from human mesenchymal stem cells (hMSCs). Cells cultured in matrices mimicking mechanical elasticity of bone tissues in vivo show elevated secretion of vascular endothelial growth factor (VEGF), one of representative signaling proteins promoting angiogenesis, as well as increased vascularization of human umbilical vein endothelial cells (HUVECs) with a supplement of conditioned media from hMSCs cultured across different conditions. When hMSCs are cultured in matrices stimulated with a range of cyclic compressions, increased VEGF secretion is observed with increasing mechanical strains, which is also in line with the enhanced tubulogenesis of HUVECs. Moreover, it is demonstrated that matrix stiffness and cyclic compression modulate secretion of pro‐angiogenic molecules from hMSCs through yes‐associated protein activity.     

Direct ink writing of ceramic matrix composite structures

We present the development of an ink containing chopped fibers that is suitable for direct ink writing (DIW), enabling to obtain ceramic matrix composite (CMC) structures with complex shape. We take advantage of the unique formability opportunities provided by the use of a preceramic polymer as both polymeric binder and ceramic source. Inks suitable for the extrusion of fine filaments (<1 mm diameter) and containing a relatively high amount of fibers (>30 vol% for a nozzle diameter of 840 μm) were formulated. Despite some optimization of ink rheology still being needed, complex CMC structures with porosity of ~75% and compressive strength of ~4 MPa were successfully printed. The process is of particular interest for its ability to orient the fibers in the extrusion direction due to the shear stresses generated at the nozzle tip. This phenomenon was observed in the production of polymer matrix composites, but it is here employed for the first time for the production of ceramic matrix ones. The possibility to align high aspect ratio fillers using DIW opens the path to layer‐by‐layer design for optimizing the mechanical and microstructural properties within a printed object, and could potentially be extended to other types of fillers.     

Kinetics of 4-nitrophenol biodegradation in a sequencing batch reactor

In this paper, the biodegradation process of 4-nitrophenol (4NP) in a sequencing batch reactor has been investigated. Kinetic tests have been carried out on biomass grown on mixed substrate (4NP plus biogenic substrate) both in the presence of a biogenic substrate fraction in the feed and with 4NP as the sole carbon source. Removal kinetics for all tests is well described by the typical substrate inhibition pattern as predicted by the Haldane equation. In both sets, estimated kinetic parameters are very similar: no beneficial effect of the biogenic fraction is observed on the 4NP removal while increasing trend of 4NP maximum removal rate with the 4NP/COD(TOT) ratio in the feed has been observed. This finding has been modelled by estimating the fraction of the total biomass involved in 4NP biodegradation as a function of 4NP concentration in the feed. High removal rates, short acclimation times and good settling characteristics of produced sludge (observed during the whole working period) confirm the suitability of periodic systems in enhancing the bacterial potentialities for biodegradation of xenobiotic compounds.     

Transient measurement of phononic states with covariance-based stochastic spectroscopy

We present a novel approach to transient Raman spectroscopy, which combines stochastic probe pulses and a covariance-based detection to measure stimulated Raman...