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Urban expansion caused numerous geological hazards, particularly in the mountainous areas. In this article, the unsaturated soil mechanics combined with a numerical method is applied to build the rainfall thresholds for the Xiangmi Lake slope in early warning. The drainage mechanism in soil slope under different rainfall conditions has been studied. Then, the actual rainfall data collected in the rainy season are taken as the rainfall condition to simulate the actual rainfall situation. The corresponding safety factor of the slope under the rainfall has been calculated and compared with the improved deformation tangential angle criterion for the slope safety prediction. The tangent angle can be used as the judgment basis to classify the early warning levels of a rainstorm, which helps to establish the early warning model of slope rainfall and guide the landslide early warning.

As there is growing evidence for the tumor microenvironment's role in tumorigenesis, we investigated the role of fibroblast-expressed kinases in triple-negative breast cancer (TNBC). Using a high-throughput kinome screen combined with 3D invasion assays, we identified fibroblast-expressed PIK3C[delta] (f- PIK3C[delta]) as a key regulator of cancer progression. Although PIK3C[delta] was expressed in primary fibroblasts derived from TNBC patients, it was barely detectable in breast cancer (BC) cell lines. Genetic and pharmacological gain- and loss-of-function experiments verified the contribution of f-PIK3C[delta] in TNBC cell invasion. Integrated secretomics and transcriptomics analyses revealed a paracrine mechanism via which f-PIK3C[delta] confers its protumorigenic effects. Inhibition of f-PIK3C[delta] promoted the secretion of factors, including PLGF and BDNF, that led to upregulation of NR4A1 in TNBC cells, where it acts as a tumor suppressor. Inhibition of PIK3C[delta] in an orthotopic BC mouse model reduced tumor growth only after inoculation with fibroblasts, indicating a role of f-PIK3C[delta] in cancer progression. Similar results were observed in the MMTV-PyMT transgenic BC mouse model, along with a decrease in tumor metastasis, emphasizing the potential immune-independent effects of PIK3C[delta] inhibition. Finally, analysis of BC patient cohorts and TCGA data sets identified f-PIK3C[delta] (protein and mRNA levels) as an independent prognostic factor for overall and disease-free survival, highlighting it as a therapeutic target for TNBC., Introduction Triple-negative breast cancer (TNBC; [ER.sup.-], [PR.sup.-], [HER2.sup.-]) represents a molecularly diverse and highly heterogeneous subtype of breast cancer (BC) (15%-20%) with a poor prognosis and high rates of recurrence [...]

Summary Carcinoma-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in tumor microenvironment that are critically involved in cancer progression. Here, we demonstrate that two cell-surface molecules, CD10 and GPR77, specifically define a CAF subset correlated with chemoresistance and poor survival in multiple cohorts of breast and lung cancer patients. CD10 + GPR77 + CAFs promote tumor formation and chemoresistance by providing a survival niche for cancer stem cells (CSCs). Mechanistically, CD10 + GPR77 + CAFs are driven by persistent NF-κB activation via p65 phosphorylation and acetylation, which is maintained by complement signaling via GPR77, a C5a receptor. Furthermore, CD10 + GPR77 + CAFs promote successful engraftment of patient-derived xenografts (PDXs), and targeting these CAFs with a neutralizing anti-GPR77 antibody abolishes tumor formation and restores tumor chemosensitivity. Our study reveals a functional CAF subset that can be defined and isolated by specific cell-surface markers and suggests that targeting the CD10 + GPR77 + CAF subset could be an effective therapeutic strategy against CSC-driven solid tumors. [ABSTRACT FROM AUTHOR]

Carcinoma-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in tumor microenvironment that are critically involved in cancer progression. Here, we demonstrate that two cell-surface molecules, CD10 and GPR77, specifically define a CAF subset correlated with chemoresistance and poor survival in multiple cohorts of breast and lung cancer patients. CD10 + GPR77 + CAFs promote tumor formation and chemoresistance by providing a survival niche for cancer stem cells (CSCs). Mechanistically, CD10 + GPR77 + CAFs are driven by persistent NF-κB activation via p65 phosphorylation and acetylation, which is maintained by complement signaling via GPR77, a C5a receptor. Furthermore, CD10 + GPR77 + CAFs promote successful engraftment of patient-derived xenografts (PDXs), and targeting these CAFs with a neutralizing anti-GPR77 antibody abolishes tumor formation and restores tumor chemosensitivity. Our study reveals a functional CAF subset that can be defined and isolated by specific cell-surface markers and suggests that targeting the CD10 + GPR77 + CAF subset could be an effective therapeutic strategy against CSC-driven solid tumors., (Copyright © 2018 Elsevier Inc. All rights reserved.)