Elucidation of the mechanism of action for drug candidates is fundamental to drug development, and it is strongly facilitated by metabolomics. Herein, we developed an imaging metabolomics method based on air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) under ambient conditions. This method was subsequently applied to simultaneously profile a novel anti-insomnia drug candidate, N(6)-(4-hydroxybenzyl)-adenosine (NHBA), and various endogenous metabolites in rat whole-body tissue sections after the administration of NHBA. The principal component analysis (PCA) represented by an intuitive color-coding scheme based on hyperspectral imaging revealed in situ molecular profiling alterations in response to stimulation of NHBA, which are in a very low intensity and hidden in massive interferential peaks. We found that the abundance of six endogenous metabolites changed after drug administration. The spatiotemporal distribution indicated that five altered molecules—including neurotransmitter γ-aminobutyric acid, neurotransmitter precursors choline and glycerophosphocholine, energy metabolism-related molecules adenosine (an endogenous sleep factor), and creatine—are closely associated with insomnia or other neurological disorders. These findings not only provide insights into a deep understanding on the mechanism of action of NHBA, but also demonstrate that the AFADESI-MSI-based imaging metabolomics is a powerful technique to investigate the molecular mechanism of drug action, especially for drug candidates with multitarget or undefined target in the preclinical study stage.

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We introduce a structural approach to study Lagrangian submanifolds of the complex hyperquadric in arbitrary dimension by using its family of non-integrable almost product structures. In particular, we define local angle functions encoding the geometry of the Lagrangian submanifold at hand. We prove that these functions are constant in the special case that the Lagrangian immersion is the Gauss map of an isoparametric hypersurface of a sphere and give the relation with the constant principal curvatures of the hypersurface. We also use our techniques to classify all minimal Lagrangian submanifolds of the complex hyperquadric which have constant sectional curvatures and all minimal Lagrangian submanifolds for which all, respectively all but one, local angle functions coincide.2010 Mathematics Subject Classification. Primary 53C42, 53D12; Secondary 53B25.