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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]

Bioelectronic devices that allow simultaneous accurate monitoring and control of the spatiotemporal patterns of cardiac activity provide an effective means to understand the mechanisms and optimize therapeutic strategies for heart disease. Optogenetics is a promising technology for cardiac research due to its advantages such as cell‐type selectivity and high space‐time resolution, but its efficacy is limited by the insufficient number of modulation channels and lack of simultaneous spatiotemporal mapping capabilities in current implantable cardiac optogenetics tools available for in vivo investigations. Here, soft implantable electro‐optical cardiac devices integrating multilayered highly uniform arrays of transparent microelectrodes and multicolor light‐emitting diodes in thin, flexible platforms are designed for mechanically compliant high‐content high‐precision electrical mapping and single‐/multi‐site optogenetics and electrical stimulation without light‐induced artifacts. Systematic benchtop characterizations, together with ex vivo and in vivo evaluations on healthy and diseased small animal hearts and human cardiac slices demonstrate their functionalities in real‐time spatiotemporal mapping and control of cardiac rhythm and function, with broad applications in basic and ultimately clinical cardiology. [ABSTRACT FROM AUTHOR]

Investigation of the complex relationships and dependencies of multiple cellular processes that govern cardiac physiology and pathophysiology requires simultaneous dynamic assessment of multiple parameters. In this study, we introduce triple-parametric optical mapping to simultaneously image metabolism, electrical excitation, and calcium signaling from the same field of view and demonstrate its application in the field of drug testing and cardiovascular research. We applied this metabolism-excitation-contraction coupling (MECC) methodology to test the effects of blebbistatin, 4-aminopyridine and verapamil on cardiac physiology. While blebbistatin and 4-aminopyridine alter multiple aspects of cardiac function suggesting off-target effects, the effects of verapamil were on-target and it altered only one of ten tested parameters. Triple-parametric optical mapping was also applied during ischemia and reperfusion; and we identified that metabolic changes precede the effects of ischemia on cardiac electrophysiology. Simultaneous triple-parametric optical mapping of transmembrane potential, intracellular calcium, and metabolic markers for cardiac physiology shows that metabolic changes precede the effects of ischemia on cardiac electrophysiology. [ABSTRACT FROM AUTHOR]

Fluorescent imaging with voltage- or calcium-sensitive dyes, known as optical mapping, is one of the indispensable modern techniques to study cardiac or neural electrophysiology, unsurpassed by temporal and spatial resolution. High-speed CMOS cameras capable of optical registration of action potential propagation are in general very costly. We present a complete solution priced below US$1,000 (including camera and lens) at the moment of publication with an open-source image acquisition and processing software. We demonstrate that the iDS UI-3130CP rev.2 camera we used in this study is capable of 200x200 977 frames per second (FPS) action potential recordings from rodent hearts, with the signal-to-noise-ratio of a conditioned signal of 16 ± 10. A comparison with a specialized MiCAM Ultimate-L camera has shown that signal-to-noise ratio (SNR) while lower is sufficient for accurate measurements of AP waveform, conduction velocity (± 0.04 m/s) and action potential duration (± 7ms) in mouse and rat hearts. We used 4-aminopyridine to prolong the action potential duration in mouse heart, thus demonstrating that the proposed system is adequate for pharmacological studies. [ABSTRACT FROM AUTHOR]

Transparent microelectrodes have recently emerged as a promising approach for crosstalk‐free multifunctional electrical and optical biointerfacing. High‐performance flexible platforms that allow seamless integration with soft tissue systems for such applications are urgently needed. Here, silver nanowires (Ag NWs)‐based transparent microelectrode arrays (MEAs) and interconnects are designed to meet this demand. The nanowire networks exhibit a high optical transparency >90.0% at 550 nm, and superior mechanical stability up to 100,000 bending cycles at 5 mm radius. The Ag NWs microelectrodes preserve low normalized electrochemical impedance of 3.4–15 Ω cm2 at 1 kHz, and the interconnects demonstrate excellent sheet resistance (Rsh) of 4.1–25 Ω sq−1. In vivo histological analysis reveals that the Ag NWs structures are biocompatible. Studies on Langendorff‐perfused mouse and rat hearts demonstrate that the Ag NWs MEAs enable high‐fidelity real‐time monitoring of heart rhythm during co‐localized optogenetic pacing and optical mapping. This proof‐of‐concept work illustrates that the solution‐processed, transparent, and flexible Ag NWs structures are a promising candidate for the next‐generation of large‐area multifunctional biointerfaces for interrogating complex biological systems in basic and translational research. [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]

Bioelectronics, electrophysiology, metal nanowires, optical mapping, optogenetics, transparent microelectrodes Microelectrode Arrays: Flexible and Transparent Metal Nanowire Microelectrode Arrays and Interconnects for Electrophysiology, Optogenetics, and Optical Mapping (Adv. Keywords: bioelectronics; electrophysiology; metal nanowires; optical mapping; optogenetics; transparent microelectrodes EN bioelectronics electrophysiology metal nanowires optical mapping optogenetics transparent microelectrodes 1 1 1 07/07/21 20210701 NES 210701 In article number 2100225, Igor R. Efimov, Luyao Lu, and co-workers develop flexible and transparent metal nanowire-based microelectrode arrays (MEAs) and interconnects from a simple solution-processing approach. [Extracted from the article]

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]