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iNKT cells account for a relevant fraction of effector T-cells in the intestine and are considered an attractive platform for cancer immunotherapy. Although iNKT cells are cytotoxic lymphocytes, their functional role in colorectal cancer (CRC) is still controversial, limiting their therapeutic use. Thus, we examined the immune cell composition and iNKT cell phenotype of CRC lesions in patients (n = 118) and different murine models. High-dimensional single-cell flow-cytometry, metagenomics, and RNA sequencing experiments revealed that iNKT cells are enriched in tumor lesions. The tumor-associated pathobiont Fusobacterium nucleatum induces IL-17 and Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in iNKT cells without affecting their cytotoxic capability but promoting iNKT-mediated recruitment of neutrophils with polymorphonuclear myeloid-derived suppressor cells-like phenotype and functions. The lack of iNKT cells reduced the tumor burden and recruitment of immune suppressive neutrophils. iNKT cells in-vivo activation with α-galactosylceramide restored their anti-tumor function, suggesting that iNKT cells can be modulated to overcome CRC-associated immune evasion. Tumor co-infiltration by iNKT cells and neutrophils correlates with negative clinical outcomes, highlighting the importance of iNKT cells in the pathophysiology of CRC. Our results reveal a functional plasticity of iNKT cells in CRC, suggesting a pivotal role of iNKT cells in shaping the tumor microenvironment, with relevant implications for treatment.

In the last years, bistable composite structures are finding interest in several aeronautical applications such as power harvesting devices or morphing applications on very small aircraft/drones, not needing servo-activated control systems. Residual stresses, developed upon cooling after curing, leads to warped the composite laminates. Several batches of unsymmetrical and unbalanced [0°/90°] laminates were cured in an autoclave according to a standard temperature cycle, following the pre-preg supplier suggested curing cycle. In order to increase the thermal stresses (and hence the bistability phenomenon), these laminates were removed from the autoclave immediately after the curing reaction and rapidly cooled down at room temperature not applying the indicated cool rate between 2 and 5 °C min−1. During storage at room temperature, thermal stresses changed over time, indicating that asymptotic stress relaxation occurs. The first part of this work looks at residual stress characterization of bistable composite plates measuring the changes of shape observed during room temperature annealing. Rectangular plates were produced and the bistable geometric shapes were accurately assessed using a laser scanner system over several days, in order to monitor the curvature changes due to stress relaxation. Then phenomenological viscoelastic predicting models were proposed for a quick estimate for the strain/stress relaxation phenomenon. The loss of bistability was demonstrated with the help of numerical simulation and experimental testing. The final goal was to gain a better knowledge of the relation between processing and final shape of bistable laminates, in order to make them suitable for application on small air vehicles.

The present paper is focused on the analysis of the adhesion integrity of Single Lap Joints (SLJ). The technique adopted for the monitoring is based on the employment of vibration signals generated and received by piezo sensors attached on the specimens surfaces on the two opposite sides of the adhesive. Undamaged joints, when subjected to harmonic excitation, behave linearly exhibiting a spectral response including just the excitation frequency. As soon as the adhesive fails, harmonic excitation induces a rich variety of spectral components in the joints response, including subharmonics and superharmonics. A new approach is presented based on the beating resulting from the superposition of harmonic waves. The interpretation of the spectral content of the joint response is based on an analytical model of the single lap joint with different amounts of debondings associated with a nonlinear behaviour. Local Defect Resonance (LDR) conditions are promoted with the consequent superposition of defect with main structure vibration. Analytical results are compared with experiments and Finite Elements (FE) simulations demonstrating the consistence of the formulation. An efficient method for the Structural Health Monitoring (SHM) of the bonded single lap joints is provided, able to correlate the joint vibrational response to the debonding extension through the analysis of the response spectral content.

In the present paper a method for the Structural Health Monitoring (SHM) of bonded lap joints is presented. This method is based on the interference of elastic waves generated by piezo sensors and travelling along thin bonded plates through the adhesion area. Tone bursts of different extension were generated and, when they encountered the debonded area, the wave speed changed. This affected the wave reflection at the boundary of the disbond and the subsequent interference of the reflected wave with the main wave travelling along the joint. Destructive interference conditions were promoted when the adhesive was partially debonded and this was related to the length of the disbond. In the present study numerical simulations based on finite elements were performed and compared with a simplified analytical model describing the Lamb waves propagation through the joint. The simulation results were subsequently compared with the experimental data and a good agreement was found: the proposed method was simple, straightforward and its application on thin single lap joints provided reliable results.

Functional RNAs, such as microRNAs, are emerging as innovative tools in the treatment of aggressive and incurable cancers. In this study, we explore the potential of silica dioxide nanoparticles (SiO2NPs) in the delivery of biologically active miRNAs. Focusing on the tumor-suppressor miR-34a, we evaluated miRNAs delivery by SiO2NPs into the mammary gland, using in vitro as well as in vivo model systems. We showed that silica nanoparticles can efficiently deliver miR-34a into normal and cancer epithelial cells grown in culture without major signs of toxicity. Delivered miRNA retained the ability to silence artificial as well endogenous targets and can reduce the growth of mammospheres in 3D culture. Finally, miR-34a delivery through intra-tumor administration of SiO2NPs leads to a reduced mammary tumor growth. In conclusion, our studies suggest that silica nanoparticles can mediate the delivery of miR-34a directly into mammary tumors while preserving its molecular and biological activity.

This work is concerned with the geometrical characterisation of bistable composite plates in order to investigate their curvatures interdependence. The main non linear feature of bistable asymmetric laminates concerns large deflection with small energy input. This is an aspect of particular interest for several applications. Accordingly, there is an increasing importance placed on accuracy/sensitivity of predicting techniques to model bistable deformation shapes. This paper presents a novel forecast model to map the surface profiles of bistable laminates. By Timoshenko and Ashwell approaches, an analytical model is developed to provide an interpretation of the bistable shapes, in terms of principal and anticlastic curvatures. The experimental data (via laser acquisitions), with analytical and Finite Element models, help to understand the relation between material properties, plate dimensions, stacking sequence, curing features of the composite laminates and the bistability phenomenon.

Summary Loss of p53 function is invariably associated with cancer. Its role in tumor growth was recently linked to its effects on cancer stem cells (CSCs), although the underlying molecular mechanisms remain unknown. Here, we show that c-myc is a transcriptional target of p53 in mammary stem cells (MaSCs) and is activated in breast tumors as a consequence of p53 loss. Constitutive Myc expression in normal mammary cells leads to increased frequency of MaSC symmetric divisions, extended MaSC replicative-potential, and MaSC-reprogramming of progenitors, whereas Myc activation in breast cancer is necessary and sufficient to maintain the expanding pool of CSCs. Concomitant p53 loss and Myc activation trigger the expression of 189 mitotic genes, which identify patients at high risk of mortality and relapse, independently of other risk factors. Altogether, deregulation of the p53:Myc axis in mammary tumors increases CSC content and plasticity and is a critical determinant of tumor growth and clinical aggressiveness., Graphical Abstract, Highlights • Myc is overexpressed and deregulated in breast tumors because of p53 signaling attenuation • Myc activation favors SC symmetric divisions and SC reprogramming of progenitors • Myc activation is necessary and sufficient to sustain the cancer SC phenotype • Expression of 189 mitotic p53:Myc targets identifies high-risk breast cancer patients, Santoro et al. demonstrate the existence of a regulatory axis instructed by the tumor-suppressor p53, executed by the Myc oncogene, and involving 189 p53:Myc targets. The authors show that activation of this axis maintains the expanding pool of cancer stem cells (SCs), thus promoting tumor growth, and predicts adverse prognosis.