UU tests showed that the shear strength of undisturbed red clay was higher than that of remoulded red clay.Glioblastoma multiforme (GBM) is highly invasive, with a high recurrence rate and limited treatment options, and is the deadliest glioma. Exosomes (Exos) have attracted much attention in the diagnosis and treatment of GBM and are expected to address the severe limitations of biopsy conditions. Exos in the cerebrospinal fluid (CSF) have great potential in GBM dynamic monitoring and intervention strategies. Here, we evaluated the difference in the proteome information of Exos from the CSF (CSF-Exos) between GBM patients and low-grade glioma patients, and the correlations between GBM-CSF-Exos and immunosuppressive properties. Our results indicates that GBM-CSF-Exos contained a unique protein, LGALS9 ligand, which bound to the TIM3 receptor of dendritic cells (DCs) in the CSF to inhibit antigen recognition, processing and presentation by DCs, leading to failure of the cytotoxic T-cell-mediated antitumor immune response. Blocking the secretion of exosomal LGALS9 from GBM tumors could cause mice to exhibit sustained DC tumor antigen-presenting activity and long-lasting antitumor immunity. We concluded that GBM cell-derived exosomal LGALS9 acts as a major regulator of tumor progression by inhibiting DC antigen presentation and cytotoxic T-cell activation in the CSF and that loss of this inhibitory effect can lead to durable systemic antitumor immunity.Glioblastoma (GBM) is a highly aggressive tumor with poor prognosis. A small subpopulation of glioma stem cells (GSCs) has been implicated in radiation resistance and tumor recurrence. In this study we analyzed the expression of miRNAs associated with the functions of GSCs using miRNA microarray analysis of these cells compared with human neural stem cells. These analyses identified gene clusters associated with glioma cell invasiveness, axonal guidance, and TGF-β signaling. miR-504 was significantly downregulated in GSCs compared with NSCs, its expression was lower in GBM compared with normal brain specimens and further decreased in the mesenchymal glioma subtype. Overexpression of miR-504 in GSCs inhibited their self-renewal, migration and the expression of mesenchymal markers. The inhibitory effect of miR-504 was mediated by targeting Grb10 expression which acts as an oncogene in GSCs and GBM. Overexpression of exogenous miR-504 resulted also in its delivery to cocultured microglia by GSC-secreted extracellular vesicles (EVs) and in the abrogation of the GSC-induced polarization of microglia to M2 subtype. Finally, miR-504 overexpression prolonged the survival of mice harboring GSC-derived xenografts and decreased tumor growth. In summary, we identified miRNAs and potential target networks that play a role in the stemness and mesenchymal transition of GSCs and the miR-504/Grb10 pathway as an important regulator of this process. Overexpression of miR-504 exerted antitumor effects in GSCs as well as bystander effects on the polarization of microglia via delivery by EVs.Breast cancer is one of the most common female malignant cancers. Biorhythm disorder largely increases the risk of breast cancer. We aimed to investigate the biological functions and molecular mechanisms of circadian gene TIMELESS circadian regulator (TIM) in estrogen receptor (ER)-positive breast cancer and provide a new therapeutic target for breast cancer patients. Here, we explored that the expression of TIM was elevated in breast cancer, and high expression of TIM in cancer tissues was associated with poor prognosis, especially in the ER-positive breast cancer patients. In addition, we found that TIM promoted cell proliferation and enhanced mitochondrial respiration. TIM interacted with specificity protein 1 (Sp1) which contributes to upregulate the expression of alkaline ceramidase 2 (ACER2). Moreover, ACER2 is responsible for TIM-mediated promotive effects of cell growth and mitochondrial respiration. Collectively, our research unveiled a novel function of TIM in sphingolipid metabolism through interaction with Sp1. It provides a new theoretical explanation for the pathogenesis of breast cancer, and targeting TIM may serve as a potential therapeutic target for ER-positive breast cancer.Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis. Vacuolar protein sorting 34 (VPS34) is a member of the phosphatidylinositol-3-kinase lipid kinase family that controls the canonical autophagy pathway and vesicular trafficking.  https://www.selleckchem.com/products/BIBF1120.html  Using a recently developed specific inhibitor (VPS34-IN1), we found that VPS34 inhibition induces apoptosis in AML cells but not in normal CD34+ hematopoietic cells. Complete and acute inhibition of VPS34 was required for the antileukemic activity of VPS34-IN1. This inhibitor also has pleiotropic effects against various cellular functions related to class III PI3K in AML cells that may explain their survival impairment. VPS34-IN1 inhibits basal and L-asparaginase-induced autophagy in AML cells. A synergistic cell death activity of this drug was also demonstrated. VPS34-IN1 was additionally found to impair vesicular trafficking and mTORC1 signaling. From an unbiased approach based on phosphoproteomic analysis, we identified that VPS34-IN1 specifically inhibits STAT5 phosphorylation downstream of FLT3-ITD signaling in AML. The identification of the mechanisms controlling FLT3-ITD signaling by VPS34 represents an important insight into the oncogenesis of AML and could lead to new therapeutic strategies.MicroRNAs (miRNAs) and natural antisense transcripts (NATs) control many biological processes and have been broadly applied for genetic manipulation of eukaryotic gene expression. Still unclear, however, are whether and how NATs regulate miRNA production. Here, we report that the cis-NATs of MIR398 genes repress the processing of their pri-miRNAs. Through genome-wide analysis of RNA sequencing data, we identify cis-NATs of MIRNA genes in Arabidopsis and Brassica. In Arabidopsis, MIR398b and MIR398c are coexpressed in vascular tissues with their antisense genes NAT398b and NAT398c, respectively. Knock down of NAT398b and NAT398c promotes miR398 processing, resulting in stronger plant thermotolerance owing to silencing of miR398-targeted genes; in contrast, their overexpression activates NAT398b and NAT398c, causing poorer thermotolerance due to the upregulation of miR398-targeted genes. Unexpectedly, overexpression of MIR398b and MIR398c activates NAT398b and NAT398c. Taken together, these results suggest that NAT398b/c repress miR398 biogenesis and attenuate plant thermotolerance via a regulatory loop.