Matrix-assisted laser desorption/ionization mass spectrometry has been considered an important tool for various biochemical analyses and proteomics research. Although addition of conventional matrix efficiently supports laser desorption/ionization of analytes with minimal fragmentation, it often results in high background interference and misinterpretation of the spatial distribution of biomolecules especially in low-mass regions. Here, we show design, systematic characterization, and application of graphene oxide/multiwalled carbon nanotube-based films fabricated on solid substrates as a new matrix-free laser desorption/ionization platform. We demonstrate that the graphene oxide/multiwalled carbon nanotube double layer provides many advantages as a laser desorption/ionization substrate, such as efficient desorption/ionization of analytes with minimum fragmentation, high salt tolerance, no sweet-spots for mass signal, excellent durability against mechanical and photoagitation and prolonged exposure to ambient conditions, and applicability to tissue imaging mass spectrometry. This platform will be widely used as an important tool for mass spectrometry-based biochemical analyses because of its outstanding performance, long-term stability, and cost effectiveness.

AimsThe association between relative muscle mass (RMM) and incidence of type 2 diabetes (T2DM) is largely unknown. We examined whether RMM predicted development of T2DM in an apparently young healthy population.MethodsThis cohort study was comprised of 113,913 men and 89,854 women, free of T2DM at baseline, who underwent a health checkup examination and were followed-up annually or biennially for an average of 2.9 years. We used skeletal muscle mass index (SMI) as an indicator of RMM. SMI (%) [total skeletal muscle mass (kg)/body weight (kg)×100] was estimated using a bioelectrical impedance analyzer. The study outcome was incident T2DM, defined as fasting serum glucose ≥126 mg/dL, HbA1C ≥6.5%, or use of medication for T2DM.ResultsDuring 589,098.8 person-years of follow-up, 4,264 individuals developed T2DM (incidence rate, 7.2 per 1000 person-years). Median age (range) at baseline was 39.1 years (18.1–87.1). RMM was negatively associated with incidence of T2DM in a dose-response manner. The multivariate-adjusted hazard ratios (95% CIs) for incident T2DM comparing quartiles 3, 2 and 1 of RMM to the highest quartile were 1.32 (1.14–1.52), 1.63 (1.42–1.86), and 2.21 (1.94–2.51), respectively, for males and 1.18 (0.88–1.58), 1.46 (1.11–1.91), and 1.96 (01.51–2.53) for females (P for trend <0.001; 0.011). This association was stronger in younger or premenopausal subjects.ConclusionsRMM was negatively associated with development of T2DM in a large sample of young and middle-aged Korean adults. Further research is required to determine whether preservation of muscle mass through intervention affects the risk of T2DM.

Phosphatidylinositol 3-kinase α (PI3Kα) is an important regulator of intracellular signaling pathways, controlling remarkably diverse arrays of physiological processes. Because the PI3K pathway is frequently up-regulated in human cancers, the inhibition of PI3Kα can be a promising approach to cancer therapy. In this study, we have designed and synthesized a new series of imidazo[1,2-a]pyridine derivatives as PI3Kα inhibitors through the fragment-growing strategy. By varying groups at the 3- and 6-positions of imidazo[1,2-a]pyridines, we studied the structure-activity relationships (SAR) profiles and identified a series of potent PI3Kα inhibitors. Representative derivatives showed good activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.

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