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Leucine-rich repeats containing G protein-coupled receptor 4 (LGR4) is a receptor that belongs to the superfamily of G protein-coupled receptors that can be activated by R-spondins (RSPOs), Norrin, circLGR4, and the ligand of the receptor activator of nuclear factor kappa-B (RANKL) ligands to regulate signaling pathways in normal and pathological processes. LGR4 is widely expressed in different tissues where it has multiple functions such as tissue development and maintenance. LGR4 mainly acts through the Wnt/β-catenin pathway to regulate proliferation, survival, and differentiation. In cancer, LGR4 participates in tumor progression, invasion, and metastasis. Furthermore, recent evidence reveals that LGR4 is essential for the regulation of the cancer stem cell population by controlling self-renewal and regulating stem cell properties. This review summarizes the function of LGR4 and its ligands in normal and malignant processes.  相似文献   
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Sustainable water resources management aims at increasing the efficient use of water and achieving food security. This work proposes a generalized novel spatial fuzzy strategic planning (SFSP) in combination with multi-criteria decision making (MCDM) and a conceptual agricultural water use model for determining sustainable agricultural water management strategies. The proposed framework is applied to an irrigation and drainage network in Iran, which constitutes a large-scale water resource system. A spatial strength, weakness, opportunity, and threat (SWOT) analysis of internal and external factors related to agricultural water management is applied in this work. Possible water management strategies were ranked with the MCDM approach that combines the Analytic Hierarchy Process (AHP) and the Fuzzy technique for order-preference by similarity to ideal solution (TOPSIS). The AHP estimates the criteria weights and the TOPSIS model prioritizes the agricultural water management strategies. The results of SWOT analysis show that the final scores of the internal and external factors are equal to 2.9 and 2.73, respectively. Accordingly, the most attractive strategic type is a SO (aggressive) strategy, and a combination of structural and non-structural strategies (SO, ST, and WO strategies) are the top-ranked ones. Proposed strategies for water supply and demand management are the development and rehabilitation of the physical structure of water resources system of irrigation network, improvement of operation management and maintenance of water resources system, wastewater management, and inter-basin water transfer within the irrigation network. The results indicate that the total annual volume of agricultural water under normal conditions is about 1.8 billion cubic meters, of which about 1707 million cubic meters (95%) issue from surface water sources and 90 million cubic meters (5%) from groundwater sources. The proposed model and the calculated results provide viable and effective solutions for the implementation of sustainable management of water resources and consumption in large-scale water resources systems.

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A simplified low-cost approach to experimentally determine transport parameters in mountain rivers is described, with an emphasis on the longitudinal dispersion coefficient (DL). The approach is based on a slug injection of table salt (NaCl) as a tracer and specific conductance readings at different locations downstream of the injection spot. Observed specific conductance readings are fit using the advection-dispersion equation with OTIS-P, yielding estimates of cross-sectional area and longitudinal dispersion coefficient for various stream reaches. Estimates of the DL are used to assess the accuracy of several empirical equations reported in the literature. This allowed the determination of complementary transport parameters related to transient storage zones. The empirical equations yielded rather high DL values, with some reaching up an order of magnitude higher to those obtained from tracer additions and OTIS-P. Overall, the proposed approach seems reliable and pertinent for river reaches of ca. 150 m in length.  相似文献   
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Water Resources Management - The water evaluation and planning (WEAP) approach and the invasive weed optimization algorithm (IWOA) are herein employed to determine the optimal operating policies in...  相似文献   
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The structural role of V in 28Li2O–72SiO2 (in mol%) lithium silicate glass doped with 0.5 mol% V2O5 was assessed using 29Si and 51V Nuclear Magnetic Resonance (NMR), Fourier-transform infrared (FTIR), and X-ray photoelectron (XPS) spectroscopy techniques. Despite the low amount of V2O5 used, the structural information obtained or deduced from the statistical analysis of the NMR data could explain the evolution of glass properties after V2O5 addition. The XPS results indicated that all vanadium exists in 5+ oxidation state. Both the 29Si NMR and FTIR data point toward an increase in the polymerization of the silicate network, caused by the V2O5 acting as network former, capable to form various tetrahedral units (for n = 0, 1, and 2) in the glasses. These units, which are similar to phosphate units, scavenge the Li+ ions and cause the silicate network to polymerize. However, in an overall balance, the entire glass network is depolymerized due to the additional nonbridging oxygens contributed by the vanadium polyhedra. The addition of vanadium causes the network to expand and increases the ionic conductivity.  相似文献   
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Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)-stop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a dose- and DNA sequence-dependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the G-quartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4′-(4,4′-(1,3-phenylene)bis(1H-1,2,3-triazole-4,1-diyl))bis(1-methylquinolin-1-ium) ( 1 d ) showed the greater activity. Importantly, dose–response curves show that 1 d is cytotoxic in the human colon cancer HT-29 cell line enriched in cancer stem-like cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells.  相似文献   
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Stem cells for regenerative medicine purposes offer therapeutic benefits, but disadvantages are still ill defined. The benefit of stem cells may be attributed to their secretion of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs), including exosomes. We present a novel cell-free stem cell-derived extract (CCM), formulated from human progenitor endothelial stem cells (hPESCs), characterized for biologically active factors using ELISA, nanoparticle tracking analysis and single particle interferometric reflectance imaging sensing. The effect on fibroblast proliferation and ability to induce stem cell migration was analyzed using Alamar Blue proliferation and Transwell migration assays, respectively. GFs including IGFBP 1, 2, 3, and 6, insulin, growth hormone, PDGF-AA, TGF-α, TGF-β1, VEGF, and the anti-inflammatory cytokine, IL-1RA were detected. Membrane enclosed particles within exosome size range and expressing exosome tetraspanins CD81 and CD9 were identified. CCM significantly increased cell proliferation and induced stem cell migration. Analysis of CCM revealed presence of GFs, CKs, and EVs, including exosomes. The presence of multiple factors including exosomes within one formulation, the ability to promote cell proliferation and induce stem cell migration may reduce inflammation and pain, and augment tissue repair.  相似文献   
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