Omecamtiv Mecarbil Enhances the Duty Ratio of Human ß-Cardiac Myosin Resulting in Increased Calcium Sensitivity and Slowed Force Development in Cardiac Muscle.

The small molecule drug omecamtiv mecarbil (OM) specifically targets cardiac muscle myosin and is known to enhance cardiac muscle performance, yet its impact on human cardiac myosin motor function is unclear. We expressed and purified human ß-cardiac myosin subfragment 1 (M2ß-S1) containing a C-terminal Avi tag. We demonstrate that the maximum actin-activated ATPase activity of M2ß-S1 is slowed more than 4-fold in the presence of OM, whereas the actin concentration required for half-maximal ATPase was reduced dramatically (30-fold). We find OM does not change the overall actin affinity. Transient kinetic experiments suggest that there are two kinetic pathways in the presence of OM. The dominant pathway results in a slow transition between actomyosin·ADP states and increases the time myosin is strongly bound to actin. However, OM also traps a population of myosin heads in a weak actin affinity state with slow product release. We demonstrate that OM can reduce the actin sliding velocity more than 100-fold in the in vitro motility assay. The ionic strength dependence of in vitro motility suggests the inhibition may be at least partially due to drag forces from weakly attached myosin heads. OM causes an increase in duty ratio examined in the motility assay. Experiments with permeabilized human myocardium demonstrate that OM increases calcium sensitivity and slows force development (ktr) in a concentration-dependent manner, whereas the maximally activated force is unchanged. We propose that OM increases the myosin duty ratio, which results in enhanced calcium sensitivity but slower force development in human myocardium.

Low-Temperature and High-Rate Rechargeable Aluminum Batteries Enabled by Ternary Eutectic Electrolytes.

Rechargeable aluminum batteries (RABs) have garnered extensive scientific attention as a promising alternative chemistry due to the inherent advantages associated with aluminum (Al) metal anodes, including their high theoretical capacities, cost-effectiveness, environmental friendliness, and inherent non-flammable properties. Nonetheless, the practical energy density of RABs is constrained by the electrolytes that support lower operational voltage windows. Herein, we report a ternary eutectic electrolyte composed of 1-ethyl-3-methylimidazolium chloride ([C2C1im]Cl):1-butyl-3-methylimidazolium chloride ([C4C1im]Cl):aluminum chloride (AlCl3) for the application of RABs. The electrolyte exhibits a high operational potential window (~3V vs. Al/Al3+ on SS 316) and high ionic conductivity (~8.3 mS.cm-1) while exhibiting only a low temperature glass transition at -65 oC suitable for all-climate conditions. Al||graphene nanoplatelets cell delivers a high capacity of ~117 mAh/g, and ~43 mAh/g at a very high current densities of 1A/g and 5A/g, respectively. The cells render a reversible capacity of 20 mAh/g at -20 oC and 17 mAh/g at -40 oC, indicating their suitability for operation under extreme environmental conditions. We comprehensively evaluated the design and optimization of carbon paper-based battery systems. The ternary eutectic electrolyte demonstrates exceptional electrochemical performance, thus signifying its substantial potential for utilization in high-performance energy storage systems in all climates.

A Secondary Al-CO2 Battery Enabled by Aluminum Iodide as a Homogeneous Redox Mediator.

As an emerging energy storage concept, Al-CO2 batteries have not yet been demonstrated as a rechargeable system that can deliver a high discharge voltage and a high capacity. In this work, we present a homogeneous redox mediator to access a rechargeable Al-CO2 battery with an ultralow overpotential of 0.05 V. In addition, the resulting rechargeable Al-CO2 cell can maintain a high discharge voltage of 1.12 V and delivers a high capacity of 9394 mAh/gcarbon. Nuclear magnetic resonance (NMR) analysis indicates that the discharge product is aluminum oxalate which can facilitate the reversible operation of Al-CO2 batteries. The rechargeable Al-CO2 battery system demonstrated here holds great promise as a low-cost and high-energy alternative for future grid energy storage applications. Meanwhile, the Al-CO2 battery system could facilitate capture and concentration of atmospheric CO2, ultimately benefiting both the energy and environmental sectors of society.