MicroRNA-10b (miR-10b) is a unique oncogenic miRNA that is highly expressed in all GBM subtypes, while absent in normal neuroglial cells of the brain. miR-10b inhibition strongly impairs proliferation and survival of cultured glioma cells, including glioma-initiating stem-like cells (GSC). Although several miR-10b targets have been identified previously, the common mechanism conferring the miR-10b-sustained viability of GSC is unknown. Here, we demonstrate that in heterogeneous GSC, miR-10b regulates cell cycle and alternative splicing, often through the non-canonical targeting via 5 0 UTRs of its target genes, including MBNL1-3, SART3, and RSRC1. We have further assessed the inhibition of miR-10b in intracranial human GSC-derived xenograft and murine GL261 allograft models in athymic and immunocompetent mice. Three delivery routes for the miR-10b antisense oligonucleotide inhibitors (ASO), direct intratumoral injections, continuous osmotic delivery, and systemic intravenous injections, have been explored. In all cases, the treatment with miR-10b ASO led to targets' derepression, and attenuated growth and progression of established intracranial GBM. No significant systemic toxicity was observed upon ASO administration by local or systemic routes. Our results indicate that miR-10b is a promising candidate for the development of targeted therapies against all GBM subtypes.

Using in silico analysis of The Cancer Genome Atlas (TCGA), we identified microRNAs associated with glioblastoma (GBM) survival, and predicted their functions in glioma growth and progression. Inhibition of two "risky" miRNAs, miR-148a and miR-31, in orthotopic xenograft GBM mouse models suppressed tumor growth and thereby prolonged animal survival. Intracranial tumors treated with uncomplexed miR-148a and miR-31 antagomirs exhibited reduced proliferation, stem cell depletion, and normalized tumor vasculature. Growth-promoting functions of these two miRNAs were, in part, mediated by the common target, the factor inhibiting hypoxia-inducible factor 1 (FIH1), and the downstream pathways involving hypoxia-inducible factor HIF1α and Notch signaling. Therefore, miR-31 and miR-148a regulate glioma growth by maintaining tumor stem cells and their niche, and providing the tumor a way to activate angiogenesis even in a normoxic environment. This is the first study that demonstrates intratumoral uptake and growth-inhibiting effects of uncomplexed antagomirs in orthotopic glioma.

PurposeTimely removal of formwork is one of the crucial aspects of construction management that directly influences the safety and quality of the structure as well as the economy of the project. Code recommendations in this regard are not widely practiced because of the difficulties in their implementations. Also, such code recommendations are not robust for all the possible construction conditions. The present paper proposes an IoT-enabled system that notifies the minimum striking time of vertical formwork based on a specified target compressive strength.Design/methodology/approachAn IoT device is proposed for the timely removal of vertical formwork by monitoring of early age concrete compressive strength in real-time. The maturity method is utilized for this purpose. The implementation of the proposed system is demonstrated on three concrete columns. The proposed system is found to be suitable for any construction condition.FindingsThe proposed system is a novel, cost-effective, IoT-enabled real-time monitoring system which includes features like cloud connectivity and remote monitoring. This system can be easily implemented at the site without any human intervention.Practical implicationsThe study explores the development of an IoT device for the timely removal of vertical formwork which will ensure quality, safety and productivity in concrete construction.Originality/valueThis paper is the first attempt to determine the minimum striking time of vertical formwork using IoT-based technology.