Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α.

Spatiotemporal regulation of tumor immunity remains largely unexplored. Here we identify a vascular niche that controls alternative macrophage activation in glioblastoma (GBM). We show that tumor-promoting macrophages are spatially proximate to GBM-associated endothelial cells (ECs), permissive for angiocrine-induced macrophage polarization. We identify ECs as one of the major sources for interleukin-6 (IL-6) expression in GBM microenvironment. Furthermore, we reveal that colony-stimulating factor-1 and angiocrine IL-6 induce robust arginase-1 expression and macrophage alternative activation, mediated through peroxisome proliferator-activated receptor-γ-dependent transcriptional activation of hypoxia-inducible factor-2α. Finally, utilizing a genetic murine GBM model, we show that EC-specific knockout of IL-6 inhibits macrophage alternative activation and improves survival in the GBM-bearing mice. These findings illustrate a vascular niche-dependent mechanism for alternative macrophage activation and cancer progression, and suggest that targeting endothelial IL-6 may offer a selective and efficient therapeutic strategy for GBM, and possibly other solid malignant tumors

Effect of Micelle Encapsulation on Toxicity of CdSe/ZnS and Mn-Doped ZnSe Quantum Dots

The optical properties of quantum dots (QD) make them excellent candidates for bioimaging, biosensing, and therapeutic applications. However, conventional QDs are comprised of heavy metals (e.g., cadmium) that pose toxicity challenges in biological systems. Synthesising QDs without heavy metals or introducing thick surface coatings, e.g., by encapsulation in micelles, can reduce toxicity. Here, we examined the toxicity of micelle encapsulated tetrapod-shaped Mn-doped ZnSe QDs, comparing them to 3-mercaptopropionic acid (MPA)-capped Mn-doped ZnSe QDs prepared by ligand exchange and commercial CdSe/ZnS QD systems that were either capped with MPA or encapsulated in micelles. HepG2 cell treatment with MPA-coated CdSe/ZnS QDs resulted in a dose-dependent reduction of viability (MTT assay, treatment at 0–25 μg/mL). Surprisingly, no reactive oxygen species (ROS) or apoptotic signaling was observed, despite evidence of apoptotic behavior in flow cytometry. CdSe/ZnS QD micelles showed minimal toxicity at doses up to 25 μg/mL, suggesting that thicker protective polymer layers reduce cytotoxicity. Despite their shape, neither MPA- nor micelle-coated Mn-doped ZnSe QDs displayed a statistically significant toxicity response over the doses investigated, suggesting these materials as good candidates for bioimaging applications

Recent Progress in Sensing and Computing Techniques for Human Activity Recognition and Motion Analysis

The recent scientific and technical advances in Internet of Things (IoT) based pervasive sensing and computing have created opportunities for the continuous monitoring of human activities for different purposes. The topic of human activity recognition (HAR) and motion analysis, due to its potentiality in human–machine interaction (HMI), medical care, sports analysis, physical rehabilitation, assisted daily living (ADL), children and elderly care, has recently gained increasing attention. The emergence of some novel sensing devices featuring miniature size, a light weight, and wireless data transmission, the availability of wireless communication infrastructure, the progress of machine learning and deep learning algorithms, and the widespread IoT applications has promised new opportunities for a significant progress in this particular field. Motivated by a great demand for HAR-related applications and the lack of a timely report of the recent contributions to knowledge in this area, this investigation aims to provide a comprehensive survey and in-depth analysis of the recent advances in the diverse techniques and methods of human activity recognition and motion analysis. The focus of this investigation falls on the fundamental theories, the innovative applications with their underlying sensing techniques, data fusion and processing, and human activity classification methods. Based on the state-of-the-art, the technical challenges are identified, and future perspectives on the future rich, sensing, intelligent IoT world are given in order to provide a reference for the research and practices in the related fields