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Decreased nicotinamide adenine dinucleotide (NAD+) levels accompany aging. CD38 is the main cellular NADase. Cyanidin-3-O-glucoside (C3G), a natural inhibitor of CD38, is a well-known drug that extends the human lifespan. We investigated mechanisms of CD38 in cell senescence and C3G in antiaging. Myocardial H9c2 cells were induced to senescence with D-gal. CD38 siRNA, C3G and UBCS039 (a chemical activator of Sirt6) inhibited D-gal-induced senescence by reducing reactive oxygen species, hexokinase 2 and SA--galactosidase levels. These activators also stimulated cell proliferation and telomerase reverse transcriptase levels, while OSS-128167 (a chemical inhibitor of Sirt6) and Sirt6 siRNA exacerbated the senescent process. H9c2 cells that underwent D-gal-induced cell senescence increased CD38 expression and decreased Sirt6 expression; CD38 siRNA and C3G decreased CD38 expression and increased Sirt6 expression, respectively; and Sirt6 siRNA stimulated cell senescence in the presence of C3G and CD38 siRNA. In D-gal-induced acute aging mice, CD38 and Sirt6 exhibited increased and decreased expression, respectively, in myocardial tissues, and C3G treatment decreased CD38 expression and increased Sirt6 expression in the tissues. C3G also reduced IL-1, IL-6, IL-17A, TNF-α levels and restored NAD+ and NK cell levels in the animals. We suggest that CD38 downregulates Sirt6 expression to promote cell senescence and C3G exerts an antiaging effect through CD38-Sirt6 signaling.

The developing terahertz wireless communication demands higher performance modulators. In this Letter, a mechanism of resonance mode transformation for a high-speed terahertz direct amplitude modulator with rather low insertion loss and high modulation depth is presented. By embedding an H-shaped resonance structure, which consists of a fin-line and two flip-flopped GaAs Schottky diodes, into the E-wall of a waveguide, the fed terahertz waves are modulated by the inductive-capacitive (LC) resonance transformation of the structure. Based on this mechanism, a modulator working in the frequency band around 140 GHz is fabricated and packaged. Thanks to the LC resonance transformation, the presented modulator exhibits a low insertion loss of 1.8 dB at 138 GHz, a large modulation depth higher than 99% at 148 GHz, and high modulation speeds up to 30 Gbps at 146 GHz. Accordingly, the presented mechanism paves a promising route to develop high performance terahertz direct modulators, which is of great significance for terahertz high-speed wireless communication.

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