The chemokine CXCL12 and its G-protein-coupled receptor CXCR4 control the migration, invasiveness and metastasis of breast cancer cells. Binding of CXCL12 to CXCR4 triggers activation of heterotrimeric Gi proteins that regulate actin polymerization and migration. However, the pathways linking chemokine G-protein-coupled receptor/Gi signalling to actin polymerization and cancer cell migration are not known. Here we show that CXCL12 stimulation promotes interaction between Gαi2 and ELMO1. Gi signalling and ELMO1 are both required for CXCL12-mediated actin polymerization, migration and invasion of breast cancer cells. CXCL12 triggers a Gαi2-dependent membrane translocation of ELMO1, which associates with Dock180 to activate small G-proteins Rac1 and Rac2. In vivo, ELMO1 expression is associated with lymph node and distant metastasis, and knocking down ELMO1 impairs metastasis to the lung. Our findings indicate that a chemokine-controlled pathway, consisting of Gαi2, ELMO1/Dock180, Rac1 and Rac2, regulates the actin cytoskeleton during breast cancer metastasis.

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Functional trait composition of plant communities has been proposed as a helpful key for understanding the mechanisms of biodiversity effects on ecosystem functioning. In this study, we applied a step-wise modeling procedure to test the relative effects of taxonomic diversity, functional identity, and functional diversity on macrophytes community productivity along water depth gradient. We sampled 42 plots and 1513 individual plants and measured 16 functional traits and abundance of 17 macrophyte species. Results showed that there was a significant decrease in taxonomic diversity, functional identity (i.e., stem dry mass content, leaf [C] and leaf [N]), and functional diversity (i.e., floating leaf, mean Julian flowering date and rooting depth) with increasing water depth. For the multiple-trait functional diversity (FD) indices, functional richness decreased, while functional divergence increased with water depth gradient. Macrophyte community productivity was strongly determined by functional trait composition within community, but not significantly affected by taxonomic diversity. Community-weighted means (CWM) showed a two times higher explanatory power relative to FD indices in determining variations in community productivity. For nine of sixteen traits, CWM and FD showed significant correlations with community productivity, although the strength and direction of those relations depended on selected trait. Furthermore, functional composition in a community affected productivity through either additive or opposite effects of CWM and FD, depending on the particular traits being considered. Our results suggested both mechanisms of mass ratio and niche complementarity can operate simultaneously on variations in community productivity, and considering both CWM and FD would lead to a more profound understanding of traits–productivity relationships.

SUMMARY1. Trait-based approaches provide a framework for integrating the distribution of functional traits associated with ecological strategies into the responses of plant community dynamics along environmental gradients. We used a trait-based approach to unravel the processes governing macrophyte community assembly along a water depth gradient. We sampled 42 plots and 1513 individual plants and measured 12 functional traits and abundance of 17 macrophyte species. 2. The results showed significant evidences of habitat filtering (i.e. a significant reduction in the range and variance of trait values) and of niche differentiation (i.e. trait values distributed more evenly than expected), both of which affected the functional responses of macrophyte communities associated with different sets of traits in significant different patterns along the gradient. 3. Habitat filtering effects increased significantly for specific leaf area and leaf carbon content along the gradient. Niche differentiation effects increased significantly for leaf dry mass content, but decreased for ramet size, shoot height and leaf carbon content with increasing water depth, implying that the relative strength of biotic competition in a specific functional niche would vary with water depth. 4. Intraspecific trait variability promoted significantly the detection of habitat filtering effects on stem diameter, lamina thickness and stem dry mass content, and niche differentiation effects on specific leaf area, leaf dry mass content, shoot height, stem diameter, stem dry mass content and ramet size. 5. Community assembly processes shape the functional trait distribution within communities along environmental gradients through hierarchical effects of habitat filtering and niche differentiation. Our study highlights that niche differentiation plays a structuring role in macrophyte community assembly and that intraspecific trait variability is an important factor influencing macrophyte community dynamics.

A high incidence of tumor recurrence and metastasis has been reported in breast cancer patients; nevertheless, the underlying molecular mechanisms are largely unknown. Epithelial–mesenchymal transition (EMT), which is induced by transforming growth factor-β (TGF-β), has been implicated in tumorigenesis and breast cancer metastasis. EMT events are now directly associated with tumor metastasis, and this progress is dependent on the inflammatory microenvironment. Cytosolic phospholipase A2α (cPLA2α) has been shown to participate in a series of biological processes including inflammation and cancer development. However, the role and molecular mechanism of cPLA2α in breast cancer EMT and metastasis remain enigmatic. In this study, we found that cPLA2α was commonly overexpressed in most human breast cancer tissues and significantly correlated with a poor prognosis for human breast cancer. Functional studies demonstrated that cPLA2α overexpression was significantly associated with elevated migration and invasion in MDA-MB-231 and T47D cells. Conversely, reduced cPLA2α expression strongly attenuated metastasis and the EMT program of MDA-MB-231 cells. Further study found that knockdown of cPLA2α in MDA-MB-231 cells inhibited TGF-β-induced EMT through the PI3K/Akt signaling pathway. Animal experiments revealed that cPLA2α downregulation in MDA-MB-231 cells markedly restrained tumorigenesis and metastasis in vivo. This study indicates the potential role of cPLA2α in breast cancer metastasis and indicates that this molecule is a promising therapeutic target for breast cancer.

Allometric scaling models describing sizedependent biological relationships are important for understanding the adaptive responses of plants to environmental variation. In this study, allometric analysis was used to investigate the biomass allocation and morphology of three submerged macrophytes (Potamogeton maackianus, Potamogeton malaianus and Vallisneria natans) in response to water depth (1.0 and 2.5 m) in an in situ experiment. The three macrophytes exhibited different allometric strategies associated with distinct adjustments in morphology and biomass allocation in response to varying water depths. In deeper water, after accounting for the effects of plant size, P. maackianus and P. malaianus tended to enhance light harvesting by allocating more biomass to the stem, increasing shoot height and specific leaf area. V. natans tended to allocate more biomass to the leaf than to the basal stem (rosette), showing a higher leaf mass ratio and shoot height in deeper water. The three species decreased biomass allocation to roots as water depth increased. The main effect of water depth treatments was reduced light availability, which induced plastic shoot or leaf elongation. This shows that macrophytes have evolved responses to light limitation similar to those of terrestrial plants.

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Metabolomic analysis has been used to characterize the effects and mechanisms of drugs for nonalcoholic fatty liver disease (NAFLD) at the metabolic level. Nuciferine is an active component derived from folium nelumbinis and has been demonstrated to have beneficial effects on a highfat diet (HFD) induced hepatic steatosis model. However, the effect of the altered metabolites of nuciferine on NAFLD has not yet been elucidated. In this study, we established a NAFLD rat model using HFD and treated with nuciferine. The lipid content levels, pro-inflammatory cytokines, and oxidative stress were investigated to access the therapeutic effects of nuciferine. Additionally, the metabolic regulatory mechanisms of nuciferine on NAFLD were analyzed using untargeted metabolomics. Gene expression of the key enzymes related to the changed metabolic pathways following nuciferine intervention was also investigated. The results showed that nuciferine treatment significantly reduced the body weight, levels of lipids, and liver enzymes in the blood and improved the hepatic steatosis in the NAFLD rat model. Nuciferine treatment also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the levels of methane dicarboxylic aldehyde (MDA) in the liver. Nuciferine treatment decreased the serum levels of interleukin (IL)-6, IL-1b, and tumor necrosis factor-alpha (TNF-a) and upregulated the gene expression of IL-6, IL-1b, and TNF-a in the liver. Metabolomic analysis indicated a metabolism disorder in the NAFLD rat model reflected in a dysfunction of the glycerophospholipid, linoleic acid, alpha-linolenic acid, arginine and proline metabolism. Conversely, treatment with nuciferine improved the metabolic disorder in the NAFLD rat model. Nuciferine treatment also regulated the gene expression of key enzymes related to the glycerophospholipid, linoleic acid, and alpha-linolenic acid metabolism pathways in the liver. In conclusion, our study demonstrated an amelioration of the metabolic disorders following nuciferine treatment in NAFLD rat model. Our study contributes to the understanding of the effects and mechanisms of drugs for complex diseases using metabolomic analysis and experimental approaches.