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[Display omitted] • The SAR profiles of 1,4-naphthoquinones for activating XO were first investigated. • Introduction of electron-donor/acceptor units in the A/B ring improved the effect. • The effect was well predicted using the HOMO-LUMO gap and the binding free energy. • The risk of 1,4-naphthoquinones was evaluated with kinetic data and in vivo exposure. Oral intake of 1,4-naphthoquinones could be a potential risk factor for hyperuricemia and gout via activation of xanthine oxidase (XO). Herein, 1,4-naphthoquinones derived from food and food-borne pollutants were selected to investigate the structure and activity relationship (SAR) and the relative mechanism for activating XO in liver S9 fractions from humans (HLS9) and rats (RLS9). The SAR analysis showed that introduction of electron-donating substituents on the benzene ring or electron-withdrawing substituents on the quinone ring improved the XO-activating effect of 1,4-naphthoquinones. Different activation potential and kinetics behaviors were observed for activating XO by 1,4-naphthoquinones in HLS9/RLS9. Molecular docking simulation and density functional theory calculations showed a good correlation between -LogEC 50 and docking free energy or HOMO-LUMO energy gap. The risk of exposure to the 1,4-naphthoquinones was evaluated and discussed. Our findings are helpful to guide diet management in clinic and avoid adverse events attributable to exposure to food-derived 1,4-naphthoquinones. [ABSTRACT FROM AUTHOR]

This study aimed to develop a novel and practical fluorescent method for GSH detection in complex biological samples. To this end, a series of coumarin-based fluorescent probes was designed and synthesized using various aliphatic halogens as the sensing group. By using a new evaluation method of GSH/Cys/Hcy coexisting conditions, the probe with chloropropionate (CBF3) showed a high selectivity, excellent sensitivity, good stability for GSH detection. The reaction mechanism is proposed as nucleophilic substitution/cyclization and intramolecular charge transfer (ICT), which was confirmed by LC-MS and NMR analysis, as well as density functional theory calculations. In addition, CBF3 was demonstrated to be competent not only for the quantitative detection of GSH in real serum samples, but also for sensing GSH changes in different oxidative stress models in living cells and nematodes. This study showed a practical strategy for constructing GSH-specific fluorescent probes, and provided a sensitive tool for real-time sensing of GSH in real biological samples. The findings would greatly facilitate further investigations on GSH-associated clinical diagnosis and biomedical studies. Image 1 • A novel SN 2 -triggered and ICT-based fluorescent probe was developed for sensing GSH. • The reaction mechanism was confirmed by experimental and theoretical investigations. • The probe selectively responded to GSH in the GSH/Cys/Hcy coexisting conditions. • The probe exhibited a low detection limit of 9.2 nM. • The probe could monitor GSH in real serum sample, and in living cells and nematodes. [ABSTRACT FROM AUTHOR]

Improving the detection reliability of biosensors is essential but challenging. The dual-signal self-checking function is useful for the development of reliable biosensors; however, it inevitably increases the complexity of the sensing system. Thus, biosensors with intrinsic self-checking functions that do not require additional chemicals, specific sensor assemblies, and/or instruments are highly desirable. Herein, integrating the ability of fluorescence detection and photodegradation by carbon nitride nanosheets (CNNS), a biosensor with a self-checking function for sensitive telomerase activity detection was constructed. Acriflavine (AF) was screened from various dyes to form the most effective CNNS-AF donor-acceptor (D-A) interfaces by experiments and density functional theory (DFT) calculations, considering spectral match, electrostatic interaction, and non-covalent stacking. As a result, the proposed fluorescence biosensor not only showed highly sensitive detection of telomerase activity but also had an internal self-checking function by photodegradation of AF via continuous excitation and measurement of recovered fluorescence. This study sheds light on CNNS-based D-A interfaces with synergistic fluorescence detection and photocatalysis-induced self-checking properties for future clinical diagnosis with high sensitivity and reliability. • A biosensor with an intrinsic self-checking function for sensitive telomerase activity detection was constructed. • The self-checking function did not require additional chemicals, specific sensor assemblies, and/or instruments. • Carbon nitride-acriflavine was selected as the most effective donor-acceptor pair by experiments and DFT calculations. • Donor-acceptor fluorescent sensing and photocatalyst-based self-checking was coupled using carbon nitrides of multi-roles. [ABSTRACT FROM AUTHOR]