Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting

Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin‐like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma

Ascl2 Knockdown Results in Tumor Growth Arrest by miRNA-302b-Related Inhibition of Colon Cancer Progenitor Cells

Background: Achaete scute-like 2 (Ascl2), a basic helix-loop-helix (bHLH) transcription factor, controls the fate of intestinal stem cells. However, the role of Ascl2 in colon cancer progenitor cells remains unknown. The cell line HT-29 (47.5–95 % of CD133 + population) and LS174T (0.45 % of CD133 + population) were chosen for functional evaluation of Ascl2 in colon cancer progenitor cells after gene knockdown by RNA interference. Methodology/Principal Findings: Immunohistochemistry demonstrated that Ascl2 was significantly increased in colorectal adenocarcinomas. Downregulation of Ascl2 using RNA interference in cultured colonic adenocarcinoma HT-29 and LS174T cells reduced cellular proliferation, colony-forming ability, invasion and migration in vitro, and resulted in the growth arrest of tumor xenografts in vivo. The Ascl2 protein level in CD133 + HT-29 cells was significantly higher than in CD133 2 HT-29 cells. Ascl2 blockade via shRNA interference in HT-29 cells (shRNA-Ascl2/HT-29 cells) resulted in 26.2 % of cells staining CD133 + compared with 54.7 % in control shRNA-Ctr/HT-29 cells. The levels of ‘stemness ’ associated genes, such as CD133, Sox2, Oct4, Lgr5, Bmi1, and C-myc, were significantly decreased in shRNA-Ascl2/HT-29 and shRNA-Ascl2/LS174T cells in vitro as well as in the corresponding tumor xenograft (CD133 was not performed in shRNA-Ascl2/LS174T cells). The shRNA-Ascl2/ HT-29 cells had inhibited abilities to form tumorspheres compared with control. The microRNA (miRNAs) microarrays, identified 26 up-regulated miRNAs and 58 down-regulated miRNAs in shRNA-Ascl2/HT-29 cells. Expression levels of let-7b

EQUILIBRIUM, KINETIC, AND THERMODYNAMIC STUDIES OF HAZARDOUS DYE NEUTRAL RED BIOSORPTION BY SPENT CORNCOB SUBSTRATE

This study focuses on the possible use of spent corncob substrate (SCS), an agricultural waste utilized after the cultivation of white rot fungus Pleurotus ostreatus, to adsorb the hazardous dye Neutral Red (NR) from aqueous solutions. Natural SCS was initially characterized by using a combination of Fourier Transform Infrared Spectrometry (FTIR) and Brunauer-Emmett-Teller (BET) techniques. A batch adsorption study was carried out with varied solution pH, adsorption time, temperature, and initial NR concentration. It was found that NR uptake was favorable over a pH range of 4.0 to 7.0, and the equilibrium adsorption capacity can be reached within about 180 min. The biosorption data were also calculated by the pseudo-second-order kinetic model and Langmuir isotherm model. The maximum adsorption capacity was 139.1, 140.0, and 143.3 mg g-1 at 20, 30, and 40 °C, respectively. Thermodynamic parameters showed that the adsorption was a spontaneous and endothermic process. The study highlighted a new pathway to develop potential low-cost biosorbent for the removal of dye pollutants from wastewater

Radium and Lead Radioisotopes Composition of Sediment and Its Biogeochemical Implication in Polymetallic Nodule Area of Clario-Clipperton Zone

Radioactivity levels of 210Pb and 226Ra were detected in a sediment core obtained using a multi-corer from the polymetallic nodule area inside the Clarion-Clipperton Zone (CCZ), a contract area of the China Ocean Mineral Resources Association (COMR) in the eastern Pacific Ocean. The profile of excess 210Pb (210Pbex) shows that the specific activity of 210Pbex has three parts with different distributions at depths of 0–16 cm (I), 17–36 cm (II), and 37–48 cm (III). When the I section of nonlocal mixing was excluded, using a steady-state diffusion mode, the bioturbation coefficients of the core were estimated to be 24.2 cm2/a at 17–36 cm deep and 5.9 cm2/a at 37–48 cm deep, which were greater compared to previously published results. This is most likely owing to bioturbations caused by various organism species in the two sections

Airborne crocidolite asbestos fibers in indoor and outdoor air in a rural area, China

Forty-eight air samples were collected in a rural area of China. The concentrations of asbestos fibers in the samples were determined by phase contrast microscopy and scanning electron microscopy in combination with energy-dispersion X-ray analysis. The mean concentrations of asbestos fibers in indoor and outdoor air samples were 0.0038 and 0.0037 f/mL, respectively. The fiber concentration was higher in areas in which outcrop crocidolite asbestos is present in the soil than in areas lacking this feature. Airborne asbestos fibers in the study area might be attributable to the weathering of natural outcrop crocidolite asbestos and the impact of human activities on crocidolite asbestos-containing soils. About 50% of the total asbestos fibers in both indoor and outdoor air samples were 5 to &le 10 m long. Scanning electron microscopy showed that the crocidolite asbestos fibers were mostly thinner than 0.25 m. At present, asbestos-containing soils are rarely used to produce asbestos stoves, pave roads, construct houses, or paint walls. However, asbestos fibers are continuously released into the air from these soils, due to natural weathering and human activities, and local residents are thus exposed to asbestos fibers throughout their lifetimes, and thus their health might be adversely affected by long-term inhalation of the fibers. Taiwan Association for Aerosol Research

Direct Generation of Human Neuronal Cells from Adult Astrocytes by Small Molecules

Astrocytes, due to the proximity to neuronal lineage and capability to proliferate, are ideal starting cells to regenerate neurons. Human fetal astrocytes have been successfully converted into neuronal cells by small molecules, which offered a broader range of further applications than transcription factor-mediated neuronal reprogramming. Here we report that human adult astrocytes could also be converted into neuronal cells by a different set of small molecules. These induced cells exhibited typical neuronal morphologies, expressed neuronal markers, and displayed neuronal electrophysiological properties. Genome-wide RNA-sequencing analysis showed that the global gene expression profile of induced neuronal cells resembled that of human embryonic stem cell-differentiated neurons. When transplanted into post-natal mouse brains, these induced neuronal cells could survive and become electrophysiologically mature. Altogether, our study provides a strategy to directly generate transgene-free neuronal cells from human adult astrocytes by small molecules