Ribosylated metabolites, especially modified nucleosides, have been extensively evaluated as cancer-related biomarkers. Boronate adsorbents are considered to be promising materials for extracting them from complex matrices. However, the enrichment of ribosylated metabolites in low abundance is still a challenge due to the limited capacity and selectivity of the existing boronate adsorbents. In this study, a novel type of magnetic nanoparticles named Fe 3 O 4 @ SiO 2 @PEI-FPBA was synthesized by grafting polyethyleneimine (PEI) onto the surface of Fe 3 O 4 @SiO 2 before modification by boronate groups. The high density of the amino groups on the PEI chains supplied a large number of binding sites for boronate groups. Thus, the adsorption capacity (1.34 ± 0.024 mg/g) of the nanoparticles, which is 6-to 7-fold higher than that of analogous materials, was greatly improved. The unreacted secondary amines and tertiary amines of the PEI enhanced the aqueous solubility of the nanoparticles, which could efficiently reduce nonspecific adsorption. The nanoparticles were able to capture 1,2 cis-diol nucleosides from 1000-fold interferences. Moreover, the flexible chains of PEI were favorable for effective enrichment and quick equilibration (<2 min). Finally, 60 ribose conjugates were enriched from human urine using the nanoparticles. Among them, 43 were identified to be nucleosides and other ribosylated metabolites. Nine low abundance modified nucleosides were detected for the first time. In conclusion, Fe 3 O 4 @SiO 2 @PEI-FPBA is an attractive candidate material for the highly selective enrichment of 1,2-cis-diol compounds.R ibonucleic acids (RNA) play crucial roles in many fundamental bioprocesses, and modifications in their bases or ribose are closely correlated with bioactivity. 1 Ribonucleosides as end products directly reflect the degradation rate of the RNA. Due to the lack of phosphorylases in cells, modified nucleosides cannot be reused as normal nucleosides for RNA synthesis and are thus excreted from the cell into the biofluids. 2 In tumor cells, the impaired tRNA metabolism usually leads to abnormal levels of modified nucleosides. 3 Therefore, modified nucleosides have been extensively studied in the search for cancer-related biomarkers. 4−6 Previous research has focused mainly on the detection of several common modified nucleosides in urine through chromatography or capillary electrophoresis coupled with mass spectrometry (MS) or UV detection. 7−11 Detection of potentially unknown modified nucleosides is significant for discovering new cancer biomarkers. However, the low concentrations and serious matrix interferences in the biological samples set great obstacles for their detection. Therefore, appropriate pretreatment approaches are necessary for the comprehensive analysis of nucleosides.Online solid phase extraction (SPE) purification by aprotic boronic acid chromatography (ApBAC) encounters an incompatibility issue between the loading solvents and the separation solvents. 12,13 For offline purif...

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The rate of behavioural decline in the ageing population is remarkably variable among individuals. Despite the considerable interest in studying natural variation in ageing rate to identify factors that control healthy ageing, no such factor has yet been found. Here we report a genetic basis for variation in ageing rates in Caenorhabditis elegans. We find that C. elegans isolates show diverse lifespan and age-related declines in virility, pharyngeal pumping, and locomotion. DNA polymorphisms in a novel peptide-coding gene, named regulatory-gene-for-behavioural-ageing-1 (rgba-1), and the neuropeptide receptor gene npr-28 influence the rate of age-related decline of worm mating behaviour; these two genes might have been subjected to recent selective sweeps. Glia-derived RGBA-1 activates NPR-28 signalling, which acts in serotonergic and dopaminergic neurons to accelerate behavioural deterioration. This signalling involves the SIR-2.1-dependent activation of the mitochondrial unfolded protein response, a pathway that modulates ageing. Thus, natural variation in neuropeptide-mediated glia-neuron signalling modulates the rate of ageing in C. elegans.