MODIS-Derived Spatiotemporal Changes of Major Lake Surface Areas in Arid Xinjiang, China, 2000–2014

Inland water bodies, which are critical freshwater resources for arid and semi-arid areas, are very sensitive to climate change and human disturbance. In this paper, we derived a time series of major lake surface areas across Xinjiang Uygur Autonomous Region (XUAR), China, based on an eight-day MODIS time series in 500 m resolution from 2000 to 2014. A classification approach based on water index and dynamic threshold selection was first developed to accommodate varied spectral features of water pixels at different temporal steps. The overall classification accuracy for a MODIS-derived water body is 97% compared to a water body derived using Landsat imagery. Then, monthly composites of water bodies were derived for the months of April, July, and September to identify seasonal patterns and inter-annual dynamics of 10 major lakes (\u3e100 km2) in XUAR. Our results indicate that the changing trends of surface area of major lakes varied across the region. The surface areas of the Ebinur and Bosten Lakes showed a significant shrinking trend. The Ulungur-Jili Lake remained relatively stable during the entire period. For mountain lakes, the Barkol Lake showed a decreasing trend in April and July, but the Sayram Lake showed a significant expanding trend in September. The four plateau lakes exhibited significant expanding trends in all three seasons except for Arkatag Lake in July. The shrinking of major lakes reflects severe anthropogenic impacts due to agricultural and industrial needs, in addition to the impact of climate change. The pattern of lake changes across the XUAR can provide insight into the impact of climate change and human activities on regional water resources in this arid and semi-arid region

Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice

Background/Aims: Activation of the Wnt/β-catenin signalling pathway has been widely investigated in bone biology and shown to promote bone formation. However, its specific effects on osteoclast differentiation have not been fully elucidated. Our study aimed to identify the role of β-catenin in osteoclastogenesis and bone homeostasis. Methods: In the present study, exon 3 in the β-catenin gene (Ctnnb1) allele encoding phosphorylation target serine/threonine residues was flanked by floxP sequences. We generated mice exhibiting conditional β-catenin activation (Ctsk-Cre;Ctnnb1flox(exon3)/+, designated CA-β-catenin) by crossing Ctnnb1flox(exon3)/flox(exon3) mice with osteoclast-specific Ctsk-Cre mice. Bone growth and bone mass were analysed by micro-computed tomography (micro-CT) and histomorphometry. To further examine osteoclast activity, osteoclasts were induced from bone marrow monocytes (BMMs) isolated from CA-β-catenin and Control mice in vitro. Osteoclast differentiation was detected by tartrate-resistant acid phosphatase (TRAP) staining, immunofluorescence staining and reverse transcription-quantitative PCR (RT–qPCR) analysis. Results: Growth retardation and low bone mass were observed in CA-β-catenin mice. Compared to controls, CA-β-catenin mice had significantly reduced trabecular bone numbers under growth plates as well as thinner cortical bones. Moreover, increased TRAP-positive osteoclasts were observed on the surfaces of trabecular bones and cortical bones in the CA-β-catenin mice; consistent results were observed in vitro. In the CA-β-catenin group, excessive numbers of osteoclasts were induced from BMMs, accompanied by the increased expression of osteoclast-associated marker genes. Conclusion: These results indicated that the constitutive activation of β-catenin in osteoclasts promotes osteoclast formation, resulting in bone loss

Enantioselective Synthesis of Biaryl Atropisomers via Pd/Norbornene-Catalyzed Three-Component Cross-Couplings

Three-component cross-coupling cocatalyzed by palladium and norbornene is reported for the synthesis of biaryl atropisomers. This domino reaction gave optimal yield and enantioselectivity with a P,C-type ligand bearing axial chirality and P chiral center. The process showed advantages over traditional cross-coupling because of its step economy and its compatibility with readily available <i>ortho</i>-substituted aryl halides, which could, therefore, be used instead of continuously trisubstituted aryl halides

Enantioselective Synthesis of Biaryl Atropisomers via Pd/Norbornene-Catalyzed Three-Component Cross-Couplings

Three-component cross-coupling cocatalyzed by palladium and norbornene is reported for the synthesis of biaryl atropisomers. This domino reaction gave optimal yield and enantioselectivity with a P,C-type ligand bearing axial chirality and P chiral center. The process showed advantages over traditional cross-coupling because of its step economy and its compatibility with readily available <i>ortho</i>-substituted aryl halides, which could, therefore, be used instead of continuously trisubstituted aryl halides

Ibrutinib Inhibits Angiogenesis and Tumorigenesis in a BTK-Independent Manner

BTK inhibitor (BTKi) Ibrutinib carries an increased bleeding risk compared to more selective BTKis Acalabrutinib and Zanubrutinib, however, its impact on vascular endothelium remains unknown. In this study, we found that Ibrutinib induced stronger cytotoxic effect on endothelial cells than Zanubrutinib, however, Acalabrutinib cytotoxicity was extremely weak. RNA-seq, followed by KEGG analysis and quantitative RT-PCR validation, was conducted to identify the differential apoptotic target genes of BTKis, leading to their distinct cytotoxic effects on endothelial cells, which showed that Ibrutinib and Zanubrutinib dramatically modulated the expression of critical apoptotic genes, GADD45B, FOS, and BCL2A1, among which FOS and GADD45B were upregulated more significantly by Ibrutinib than Zanubrutinib, however, Acalabrutinib downregulated BCL2A1 moderately and was not able to modulate the expression of FOS and GADD45B. Next, we performed in vitro angiogenesis assays and found that Ibrutinib was more able to induce endothelial dysfunction than Zanubrutinib via stimulating more BMP4 expression, however, Acalabrutinib had no such effect. Especially, the capacity of Ibrutinib to induce endothelial dysfunction can be antagonized by targeting BMP4. Accordingly, Ibrutinib, as an angiogenesis inhibitor, inhibited ovarian and breast cancer progression in vivo. Collectively, our findings addressed a novel molecular basis underlying Ibrutinib-induced endothelial cell dysfunction and suggested the potential application of Ibrutinib to treat angiogenesis-dependent cancers

Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling

Background/Aims: Osteopontin (OPN) is an Extracellular Matrix (ECM) molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. Methods: The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Counting Kit-8 (CCK-8), Wound scratch assay and transwell. Western blots were employed to detect the expression of Matrix metalloproteinase-2 (MMP-2) and epithelial-mesenchymal transition (EMT)-related factors in HEC-1A cells treated with rhOPN. Results: rhOPN promotes cell proliferation, migration and invasion in HEC-1A cells. rhOPN influenced EMT-related factors and MMP-2 expression in HEC-1A cells. rhOPN promoted HEC-1A cells migration, invasion and EMT through protein kinase B (PKB/AKT) and Extracellular regulated protein kinases (ERK1/2) signaling pathway. Conclusions: These results may open up a novel therapeutic strategy for endometrial cancer: namely, rhOPN have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer

Stress-inducible Protein-1 promotes metastasis of gastric cancer via Wnt/β-catenin signaling pathway

Abstract Background Stress-Inducible Protein-1 (STIP1) is a co-chaperone that associates directly with heat shock proteins, and regulates motility of various types of cancer. In the present study, we investigated the role of STIP1 on metastasis of gastric cancer (GC). Methods In vivo metastatic experimental model was employed to investigate the effect of STIP1 on metastasis of GC cells. Loss-of-function and gain-of-function experiments were performed to examine the role of STIP1 on metastasis of GC cells. Western blot, immunofluorescence staining, migration and invasion assays, microarray and KEGG pathway analysis were applied to explore the underlying mechanism. Results In current study, we demonstrated that STIP1 promoted lung metastasis of GC cells in vivo. Furthermore, STIP1 significantly enhanced migration and invasion abilities of GC cells. In contrast, knock-down of STIP1 yielded the opposite effects on these phenotypes in vitro. STIP1 promoted tumor metastasis through inducing epithelial-to-mesenchymal transition in GC cells. Mechanistically, STIP1 promoted GC metastasis via up-regulation of targeted genes in Wnt/β-catenin signaling pathway, including c-Myc and Cyclin D1, and accompanied with nuclear translocation of β-catenin. Conclusions Our findings indicate that elevated expression of STIP1 exhibited a metastasis-promoting effect in GC cells through activation of Wnt/β-catenin signaling pathway. STIP1 may be served as a potential therapeutic target for preventing GC metastasis