TLR/WNT: A Novel Relationship in Immunomodulation of Lung Cancer

The most frequent cause of death by cancer worldwide is lung cancer, and the 5-year survival rate is still very poor for patients with advanced stage. Understanding the crosstalk between the signaling pathways that are involved in disease, especially in metastasis, is crucial to developing new targeted therapies. Toll-like receptors (TLRs) are master regulators of the immune responses, and their dysregulation in lung cancer is linked to immune escape and promotes tumor malignancy by facilitating angiogenesis and proliferation. On the other hand, over-activation of the WNT signaling pathway has been reported in lung cancer and is also associated with tumor metastasis via induction of Epithelial-to-mesenchymal-transition (EMT)-like processes. An interaction between both TLRs and the WNT pathway was discovered recently as it was found that the TLR pathway can be activated by WNT ligands in the tumor microenvironment; however, the implications of such interactions in the context of lung cancer have not been discussed yet. Here, we offer an overview of the interaction of TLR-WNT in the lung and its potential implications and role in the oncogenic process.     

NGF Modulates Cholesterol Metabolism and Stimulates ApoE Secretion in Glial Cells Conferring Neuroprotection against Oxidative Stress

Cholesterol plays a crucial role in the brain, where its metabolism is particularly regulated by astrocytic activity. Indeed, adult neurons suppress their own cholesterol biosynthesis and import this sterol through ApoE-rich particles secreted from astrocytes. Recent evidence suggests that nerve growth factor (NGF) may exert neurotrophic activity by influencing cell metabolism. Nevertheless, the effect of NGF on glial cholesterol homeostasis has still not been elucidated. Thus, the aim of this project is to assess whether NGF could influence cholesterol metabolism in glial cells. To reach this objective, the U373 astrocyte-derived cell line was used as an experimental model. Immunoblot and ELISA analysis showed that proteins and enzymes belonging to the cholesterol metabolism network were increased upon NGF treatment in glial cells. Furthermore, NGF significantly increased ApoE secretion and the amount of extracellular cholesterol in the culture medium. Co-culture and U373-conditioned medium experiments demonstrated that NGF treatment efficiently counteracted rotenone-mediated cytotoxicity in N1E-115 neuronal cells. Conversely, neuroprotection mediated by NGF treatment was suppressed when N1E-115 were co-cultured with ApoE-silenced U373 cells. Taken together, these data suggest that NGF controls cholesterol homeostasis in glial cells. More importantly, NGF exerts neuroprotection against oxidative stress, which is likely associated with the induction of glial ApoE secretion.     

The Hermite radial basis function control volume method for multi-zones problems; A non-overlapping domain decomposition algorithm

In this paper a non-overlapping non-iterative multi-domain formulation for the control volume Hermite radial basis functions (CV-HRBF) method is proposed, where the local Hermitian RBF meshless collocation method is used to satisfy a physical matching condition at the sub-domain boundaries. In addition, the robustness of the Hermite interpolation is exploited even further to apply multiple flux continuities for those cases where more than two sub-domains converge in the same point. The algorithm is first validated in one-dimensional advection diffusion problems for which an analytical solution is known. Its accuracy is compared with a classic CV approach and a local radial basis function collocation method (LRBFCM). More general applications in two and three-dimensional domains are then considered. A heat transfer problem in strongly heterogeneous materials, and a groundwater flow problem in presence of geological layers characterised by different hydraulic conductivity, are taken as engineering applications to test the capabilities of the CV-HRBF method to handle multi-zone problems. Finally, the transport of a single species is simulated in a one-dimensional channel consisting of two adjacent zones that feature different Peclet numbers.     

Fabrication and characterization of PEDOT nanowires based on self-assembled peptide nanotube lithography

In this article we demonstrate the use of self-assembled peptide nanotube structures as masking material in a rapid, mild and low cost fabrication of polymerized p-toluenesulfonate doped poly(3,4-ethylenedioxythiophene) (PEDOT:TsO) nanowire device. In this new fabrication approach the PEDOT:TsO nanowire avoids all contact with any organic solvents otherwise traditionally used in clean room fabrication. This can be achieved due to the intriguing properties of the self-assembled peptide nanotubes utilized as a dry etching mask for the patterning of the PEDOT:TsO nanowire. The peptide nanotubes, despite remaining stable during the reactive ion etching procedure, can be dissolved rapidly in water afterwards. The fabricated PEDOT:TsO nanowire devices exhibit excellent electrical characteristics. Finally, the potential of PEDOT:TsO nanowires as temperature sensors has been demonstrated and the high resolution of the sensor was illustrated.     

Laser-produced plasma light source for extreme ultraviolet lithography

Pulsed Nd:YAG lasers have been developed to achieve high peak power and high pulse repetition rate. These systems are being used as drivers for laser-produced plasmas which efficiently convert the 1064-nm laser output to extreme ultraviolet (EUV) light at 13.5 nm for future microlithography systems. The requirements for laser-produced plasma EUV light sources and their integration in lithography tools for high-volume manufacturing are reviewed to establish the key design issues for high-power lasers and plasma targets. Xenon has been identified as a leading target material to realize the goals of intense EUV emission and clean operation. Recent progress in high-power diode-pumped Nd:YAG lasers and xenon targets for EUV generation is reviewed, showing that laser-produced plasma sources meet the needs for current EUV lithography development tools. Future directions to meet EUV source requirements for high-volume manufacturing tools are discussed.     

Evidence of Oxygen Ferromagnetism in ZnO Based Materials

Discoveries of room‐temperature ferromagnetism (RTFM) in semiconductors hold great promise in future spintronics technologies. Unfortunately, this ferromagnetism remains poorly understood and the debate concerning the nature, carrier‐mediated versus defect‐mediated, of this ferromagnetism in semiconducting oxides is still open. Here, by using X‐ray absorption (XAS) and X‐ray magnetic circular dichroism (XMCD), it is demonstrated that the oxygen ions have a ferromagnetic response in different ZnO‐based compounds showing RTFM behavior: ZnO nanoparticles capped with organic molecules and ZnO/ZnS heterostructures. These results demonstrate the intrinsic occurrence of RTFM in these systems, and point out that it is not related to the metallic cation but it relays on the conduction band of the semiconductor.     

miRNA Expression Profiling in Subcutaneous Adipose Tissue of Monozygotic Twins Discordant for HIV Infection: Validation of Differentially Expressed miRNA and Bioinformatic Analysis

Combined AntiRetroviral Treatments (cARTs) used for HIV infection may result in varied metabolic complications, which in some cases, may be related to patient genetic factors, particularly microRNAs. The use of monozygotic twins, differing only for HIV infection, presents a unique and powerful model for the controlled analysis of potential alterations of miRNAs regulation consequent to cART treatment. Profiling of 2578 mature miRNA in the subcutaneous (SC) adipose tissue and plasma of monozygotic twins was investigated by the GeneChip^® miRNA 4.1 array. Real-time PCR and ddPCR experiments were performed in order to validate differentially expressed miRNAs. Target genes of deregulated miRNAs were predicted by the miRDB database (prediction score > 70) and enrichment analysis was carried out with g:Profiler. Processes in SC adipose tissue most greatly affected by miRNA up-regulation included (i) macromolecular metabolic processes, (ii) regulation of neurogenesis, and (iii) protein phosphorylation. Furthermore, KEGG analysis revealed miRNA up-regulation involvement in (i) insulin signaling pathways, (ii) neurotrophin signaling pathways, and (iii) pancreatic cancer. By contrast, miRNA up-regulation in plasma was involved in (i) melanoma, (ii) p53 signaling pathways, and (iii) focal adhesion. Our findings suggest a mechanism that may increase the predisposition of HIV⁺ patients to insulin resistance and cancer.     

Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast–Keratinocyte Interaction in a 3D Co-Culture Model

Microgravity impairs tissue organization and critical pathways involved in the cell–microenvironment interplay, where fibroblasts have a critical role. We exposed dermal fibroblasts to simulated microgravity by means of a Random Positioning Machine (RPM), a device that reproduces conditions of weightlessness. Molecular and structural changes were analyzed and compared to control samples growing in a normal gravity field. Simulated microgravity impairs fibroblast conversion into myofibroblast and inhibits their migratory properties. Consequently, the normal interplay between fibroblasts and keratinocytes were remarkably altered in 3D co-culture experiments, giving rise to several ultra-structural abnormalities. Such phenotypic changes are associated with down-regulation of α-SMA that translocate in the nucleoplasm, altogether with the concomitant modification of the actin-vinculin apparatus. Noticeably, the stress associated with weightlessness induced oxidative damage, which seemed to concur with such modifications. These findings disclose new opportunities to establish antioxidant strategies that counteract the microgravity-induced disruptive effects on fibroblasts and tissue organization.     

聚氨酯胶粘剂水解问题的有效解决途径

聚合物有几种主要的降解机理:热降解、化学物降解、氧化降解、微生物降解以及水解降解。其中,水解是缩聚反应生成的聚合物最致命的弱点,聚氨酯粘合剂也不例外。水解使聚合物的力学性能在一段时间后丧失殆尽,严重影响了其使用性能和应用范围。碳化二亚胺(Stabaxol~(?))是为解决酯类聚合物水解问题而研制的高效抗水解剂。文章描述了碳化二亚胺抗水解剂在聚酯型聚氨酯粘合剂中的水解保护机理及效果。