The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. https://www.selleckchem.com/products/17-AAG(Geldanamycin).html Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.The gradient-structure is ideal nanostructure for conversion-type anodes with drastic volume change. Here, we demonstrate an inorganic-organic competitive coating strategy for constructing gradient-structured ferroferric oxide-carbon nanospheres, in which the deposition of ferroferric oxide nanoparticles and polymerization of carbonaceous species are competitive and well controlled by the reaction thermodynamics. The synthesized gradient-structure with a uniform size of ~420 nm consists of the ferroferric oxide nanoparticles (4-8 nm) in carbon matrix, which are aggregated into the inner layer (~15 nm) with high-to-low component distribution from inside to out, and an amorphous carbon layer (~20 nm). As an anode material, the volume change of the gradient-structured ferroferric oxide-carbon nanospheres can be limited to ~22% with ~7% radial expansion, thus resulting in stable reversible specific capacities of ~750 mAh g-1 after ultra-long cycling of 10,000 cycles under ultra-fast rate of 10 A g-1. This unique inorganic-organic competitive coating strategy bring inspiration for nanostructure design of functional materials in energy storage.MicroRNAs (miRNAs) are emerging drivers in tumor progression, while the role of miR-503-3p in breast cancer (BC) remains largely unknown. We aimed to explore the impact of macrophage-derived exosomal miR-503-3p in the development of BC by regulating disheveled-associated binding antagonist of beta-catenin 2 (DACT2). miR-503-3p and DACT2 expression in BC tissues and cells was assessed, and the expression of Wnt/β-catenin signaling pathway-related proteins in BC cells was also evaluated. Macrophages were induced and exosomes were extracted. The screened BC cell lines were, respectively, treated with exosomes, miR-503-3p inhibitor/mimic or upregulated/inhibited DACT2, and then the phenotypes, glucose intake, oxygen consumption rate, and adenosine-triphosphate (ATP) level of BC cells were determined. Cell growth in vivo was also observed. MiR-503-3p was elevated, DACT2 was reduced, and Wnt/β-catenin signaling pathway was activated in BC cells. Macrophage-derived exosomes, upregulated miR-503-3p or inhibited DACT2 promoted malignant behaviors of BC cells, glucose intake, and activity of the Wnt/β-catenin signaling pathway, while repressed oxygen consumption rate and ATP level in BC cells. Reversely, reduced miR-503-3p or upregulated DACT2 exerted opposite effects. This study revealed that reduction of macrophage-derived exosomal miR-503-3p repressed glycolysis and promoted mitochondrial oxidative phosphorylation in BC by elevating DACT2 and inactivating Wnt/β-catenin signaling pathway. Our research may provide novel targets for BC treatment.Metasurfaces have provided unprecedented freedom for manipulating electromagnetic waves. In metasurface design, massive meta-atoms have to be optimized to produce the desired phase profiles, which is time-consuming and sometimes prohibitive. In this paper, we propose a fast accurate inverse method of designing functional metasurfaces based on transfer learning, which can generate metasurface patterns monolithically from input phase profiles for specific functions. A transfer learning network based on GoogLeNet-Inception-V3 can predict the phases of 28×8 meta-atoms with an accuracy of around 90%. This method is validated via functional metasurface design using the trained network. Metasurface patterns are generated monolithically for achieving two typical functionals, 2D focusing and abnormal reflection. Both simulation and experiment verify the high design accuracy. This method provides an inverse design paradigm for fast functional metasurface design, and can be readily used to establish a meta-atom library with full phase span.Studies along elevational gradients worldwide usually find the highest plant taxa richness in mid-elevation forest belts. Hence, an increase in upper elevation diversity is expected in the course of warming-related treeline rise. Here, we use a time-series approach to infer past taxa richness from sedimentary ancient DNA from the south-eastern Tibetan Plateau over the last ~18,000 years. We find the highest total plant taxa richness during the cool phase after glacier retreat when the area contained extensive and diverse alpine habitats (14-10 ka); followed by a decline when forests expanded during the warm early- to mid-Holocene (10-3.6 ka). Livestock grazing since 3.6 ka promoted plant taxa richness only weakly. Based on these inferred dependencies, our simulation yields a substantive decrease in plant taxa richness in response to warming-related alpine habitat loss over the next centuries. Accordingly, efforts of Tibetan biodiversity conservation should include conclusions from palaeoecological evidence.Metabolic reprogramming is a hallmark of malignancy. Testes-specific protease 50 (TSP50), a newly identified oncogene, has been shown to play an important role in tumorigenesis. However, its role in tumor cell metabolism remains unclear. To investigate this issue, LC-MS/MS was employed to identify TSP50-binding proteins and pyruvate kinase M2 isoform (PKM2), a known key enzyme of aerobic glycolysis, was identified as a novel binding partner of TSP50. Further studies suggested that TSP50 promoted aerobic glycolysis in HCC cells by maintaining low pyruvate kinase activity of the PKM2. Mechanistically, TSP50 promoted the Warburg effect by increasing PKM2 K433 acetylation level and PKM2 acetylation site (K433R) mutation remarkably abrogated the TSP50-induced aerobic glycolysis, cell proliferation in vitro and tumor formation in vivo. Our findings indicate that TSP50-mediated low PKM2 pyruvate kinase activity is an important determinant for Warburg effect in HCC cells and provide a mechanistic link between TSP50 and tumor metabolism.