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A new dimeric C-glycoside polyketide chrysomycin F (1), along with four new monomeric compounds, chrysomycins G (2), H (3), I (4), J (5), as well as three known analogues, chrysomycins A (6), B (7), and C (8), were isolated and characterised from a strain of Streptomyces sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis. Chrysomycin F contains two diastereomers, whose structures were further elucidated by a biomimetic [2 + 2] photodimerisation of chrysomycin A. Chrysomycins B and C showed potent anti-tuberculosis activity against both wild-type Mycobacterium tuberculosis and a number of clinically isolated MDR M. tuberculosis strains. [ABSTRACT FROM AUTHOR]

Vagal nerve stimulation (VNS) has a meaningful basis as a potentially effective treatment for heart failure with reduced ejection fraction. There is an ongoing VNS randomized study, and four studies are completed. However, relatively little is known about the effect of acetylcholine (ACh) on repolarization in human ventricular cardiomyocytes, as well as the effect of ACh on the rapid component of the delayed rectifier K+ current (IKr). Here, we investigated the effect of ACh on the action potential parameters in human ventricular preparations and on IKr in human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Using standard microelectrode technique, we demonstrated that ACh (5 µM) significantly increased the action potential duration in human left ventricular myocardial slices. ACh (5 µM) also prolonged repolarization in a human Purkinje fiber and a papillary muscle. Optical mapping revealed that ACh increased the action potential duration in human left ventricular myocardial slices and that the effect was dose-dependent. Perforated patch clamp experiments demonstrated action potential prolongation and a significant decrease in IKr by ACh (5 µM) in hiPSC-CMs. Computer simulations of the electrical activity of a human ventricular cardiomyocyte showed an increase in action potential duration upon implementation of the experimentally observed ACh-induced changes in the fully activated conductance and steady-state activation of IKr. Our findings support the hypothesis that ACh can influence the repolarization in human ventricular cardiomyocytes by at least changes in IKr. [ABSTRACT FROM AUTHOR]

Recently developed optically transparent microelectrode technology provides a promising approach for simultaneous high-resolution electrical and optical biointerfacing with tissues in vivo and in vitro. A critically unmet need is designing high-performance stretchable platforms for conformal biointerfacing with mechanically active organs. Here, we report silver nanowire (Ag NW) stretchable transparent microelectrodes and interconnects that exhibit excellent electrical and electrochemical performance, high optical transparency, superior mechanical robustness and durability by a simple selective-patterning process. The fabrication method allows the direct integration of Ag NW networks on elastomeric substrates. The resulting Ag NW interface exhibits a low sheet resistance (Rsh) of 1.52–4.35 Ω sq−1, an advantageous normalized electrochemical impedance of 3.78–6.04 Ω cm2, a high optical transparency of 61.3–80.5% at 550 nm and a stretchability of 40%. The microelectrode arrays (MEAs) fabricated with this approach exhibit uniform electrochemical performance across all channels. Studies on mice demonstrate that both pristine and stretched Ag NW microelectrodes can achieve high-fidelity electrophysiological monitoring of cardiac activity with/without co-localized optogenetic pacing. Together, these results pave the way for developing stretchable and transparent metal nanowire networks for high-resolution opto-electric biointerfacing with mechanically active organs, such as the heart. [ABSTRACT FROM AUTHOR]