Background and objective: Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology. Methods: Children (aged 6-11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography-mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma-related genes. Results: We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P < 0.05 and fold-change >1.5 or <0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor-controlled or well-controlled asthma, and area under the curve values were >0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress-related biological progression of paediatric asthma. Conclusion: Metabolomic analysis of patient urine combined with network-biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma.We investigated metabolic profiles of paediatric asthma patients to identify asthma-specific biomarkers in urine. A combination of eight metabolites showed excellent discrimination across groups. Enrichment analysis identified complex biological processes associated with immunity, inflammation, oxidative stress and DNA damage. These approaches enabled discrimination between asthma stages and elucidate its mechanisms.

A stable 3D Tb -based metal-organic framework [Tb(BPDC) ]⋅(CH ) NH (DUT-101) was synthesized, and it is the first efficient dual-channel luminescence sensor for aqueous UO ions. DUT-101 contains an anionic three-dimensional framework and protonated dimethylamine molecules embedded within the channels. The intense green emission of DUT-101 could be highly selectively and sensitively quenched by UO ions even in the presence of other competing metal ions. A possible sensing mechanism was proposed based on both suppression of luminescence resonance energy transfer and enhancement of intermolecular electron transfer. Furthermore, visual green fluorescent test papers based on DUT-101 were fabricated and could be used to discriminate UO ions among various metal ions.

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Randependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation. Bone morphogenetic proteins (BMPs), first identified by their ability to induce bone formation in bone matrix (1), are signal molecules belonging to the transforming growth factor beta (TGF-␤) superfamily (2, 3). BMPs have critical roles in skeletal development by regulating osteoblast and chondrocyte differentiation (4), cartilage and bone formation, and limb development (5, 6). BMPs can determine the fate of mesenchymal stem cells by stimulating their differentiation into the chondroosteoblastic lineage and meanwhile blocking their differentiation into the myoblastic lineage (7). In response to BMP signals, critical osteogenic transcription factors such as Runx2 and Osterix are induced and drive efficient bone development (8). On the contrary, BMPs can inhibit myogenic differentiation by suppressing the expression of myogenic basic helixloop-helix (bHLH) transcriptional factors such as MyoD, myogenin, and Myf5 (9) and/or inducing the expression of Id (inhibitory of differentiation or inhibitor of DNA binding) proteins that block the DNA-binding ability of bHLH transcription factors.BMP ligands such as BMP2 or BMP4 can bind to type I and type II receptors on the cell surface. The type II receptors phosphorylate and activate the type I receptors, which in turn phosphorylate downstream receptor-regulated Smads (R-Smads), i.e., Smad1, Smad5, and Smad8 (Smad1/5/8) (10, 11). The activated phospho-R-Smads form complexes with Smad4 and translocate into the nucleus. The Smad complex acts as a transcriptional activator or repressor to regulate target gene expression (11-13).BMP signaling is precisely controlled during development. The level of R-Smads in the nucleus determines the duration and strength of TGF-␤ superfamily signaling. R-Smads undergo nucleocytoplasmic shuttling, regulated by nuclear transport and retention proteins (14,15). Ligand-induced phosphorylation of R-Smads facilitates dissocia...

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