Mg, Al, Cl, and F Walk into a Coin-Cell… Electrolyte Solutions and Strategies for Rechargeable Magnesium-ion Batteries

Effective grid-level collection of renewable resources such as wind or solar will require energy storage systems with high capacity, affordable, and safe battery electrochemistries. Research into novel battery technologies may ultimately prove rewarding in the ability to successfully combat both the variable availability of energy resources as well as the variable geographic and temporal demand for power. Magnesium-ion batteries (MIBs) offer a high volumetric energy density, and could supplement existing technologies. To this end, a series of magnesium dialkoxides were synthesized and characterized for use in magnesium ion electrolytes. We found a series of compounds that display considerably improved characteristics compared to previously investigated dialkoxides on the basis of Coulombic efficiency, anodic stability limit, conductivity, and solubility. Electrolyte performance is dependent on various electrolyte properties such as Lewis acid concentration, solvent environment, electrolytic conditioning, and ligand electrochemical characteristics. The electrodeposited magnesium from these systems was analyzed for both morphology and purity. Magnesium dialkoxides are extremely promising candidates for magnesium-ion technologies. Indeed, as proof of principle, the compounds investigated were shown to be compatible with a Mo6S8 cathode in a functioning MIB. The easy manipulation of these dialkoxide precursor compounds, compared to commonly investigated Grignard reagents, is a practical benefit. Our improved understanding of ligand and environment modification and their effects on the resulting electrochemistry is integral for the development of novel magnesium-ion electrolytes. The strategies employed in this work to increase the electrochemical properties of these electrolytes could prove useful in the improvement of other classes of magnesium electrolytes. The development of a highly efficient electrolyte system for the creation of an environmentally friendly and affordable MIB could revolutionize the applications of large-capacity rechargeable energy storage

A Fluorinated Alkoxyaluminate Electrolyte for Magnesium-Ion Batteries

The lack of electrolytes that simultaneously possess high Coulombic efficiency, conductivity, and voltage stability has hindered the deployment of rechargeable magnesium-ion batteries. With few exceptions, the tenacious oxide layer on magnesium metal has limited the scope of research to halide ion-based electrolytes, which help activate the electrode surface but also limit the working voltage window considerably. Herein, we demonstrate a new class of magnesium electrolytes based on fluoroalkoxyaluminate anions synthesized via a facile and scalable method and its incorporation in a full battery cell. Mixtures of magnesium and aluminum fluoroalkoxides in ethereal solvents result in solutions that can reversibly deposit magnesium metal with near unit efficiency in addition to achieving suitable oxidative stabilities (>3.5 V vs Mg/Mg²⁺ on glassy carbon and gold) and conductivities (>6 mS cm^–1)

Efficient viral transduction in mouse inner ear hair cells with utricle injection and AAV9-PHP.B

Viral delivery of exogenous coding sequences into the inner ear has the potential for therapeutic benefit for patients suffering genetic or acquired hearing loss. To devise improved strategies for viral delivery, we investigated two injection techniques, round window membrane injection or a novel utricle injection method, for their ability to safely and efficiently transduce sensory hair cells and neurons of the mouse inner ear. In addition, we evaluated three synthetic AAV vectors (Anc80L65, AAV9-PHP.B, AAV2.7m8) encoding enhanced green fluorescent protein (eGFP) and three promoters (Cmv, Synapsin, Gfap) for their ability to transduce and drive expression in desired cell types. We found the utricle injection method with AAV9-PHP.B and a Cmv promoter was the most efficient combination for driving robust eGFP expression in both inner and outer hair cells. We found eGFP expression levels rose over 3-5 days post-injection, a viral dose of 1.5 x 10(9) gc yielded half maximal eGFP expression and that the utricle injection method yielded transduced hair cells even when delivered as late as postnatal day 16. Sensory transduction and auditory thresholds were unaltered in injected mice relative to uninjected wild-type controls. Vestibular end organs were also transduced without affecting balance behavior. The Synapsin promoter and the Gfap promoter drove strong eGFP expression in inner ear neurons and supporting cells, respectively. We conclude the AAV9-PHP.B vector and the utricle injection method are well-suited for delivery of exogenous gene constructs into inner ears of mouse models of auditory and vestibular dysfunction. (C) 2020 The Authors. Published by Elsevier B.V

Mapping oto-pharyngeal development in a human inner ear organoid model

Inner ear development requires the coordination of cell types from distinct epithelial, mesenchymal and neuronal lineages. Although we have learned much from animal models, many details about human inner ear development remain elusive. We recently developed an in vitro model of human inner ear organogenesis using pluripotent stem cells in a 3D culture, fostering the growth of a sensorineural circuit, including hair cells and neurons. Despite previously characterizing some cell types, many remain undefined. This study aimed to chart the in vitro development timeline of the inner ear organoid to understand the mechanisms at play. Using single-cell RNA sequencing at ten stages during the first 36 days of differentiation, we tracked the evolution from pluripotency to various ear cell types after exposure to specific signaling modulators. Our findings showcase gene expression that influences differentiation, identifying a plethora of ectodermal and mesenchymal cell types. We also discern aspects of the organoid model consistent with in vivo development, while highlighting potential discrepancies. Our study establishes the Inner ear Organoid Developmental Atlas (IODA), offering deeper insights into human biology and improving inner ear tissue differentiation

Allele-specific gene editing prevents deafness in a model of dominant progressive hearing loss

Since most dominant human mutations are single nucleotide substitutions(1,2), we explored gene editing strategies to disrupt dominant mutations efficiently and selectively without affecting wild-type alleles. However, single nucleotide discrimination can be difficult to achieve(3) because commonly used endonucleases, such as Streptococcus pyogenes Cas9 (SpCas9), can tolerate up to seven mismatches between guide RNA (gRNA) and target DNA. Furthermore, the protospacer-adjacent motif (PAM) in some Cas9 enzymes can tolerate mismatches with the target DNA(3,4). To circumvent these limitations, we screened 14 Cas9/gRNA combinations for specific and efficient disruption of a nucleotide substitution that causes the dominant progressive hearing loss, DFNA36. As a model for DFNA36, we used Beethoven mice(5), which harbor a point mutation in Tmc1, a gene required for hearing that encodes a pore-forming subunit of mechanosensory transduction channels in inner-ear hair cells(6). We identified a PAM variant of Staphylococcus aureus Cas9 (SaCas9-KKH) that selectively and efficiently disrupted the mutant allele, but not the wild-type Tmc1/ TMC1 allele, in Beethoven mice and in a DFNA36 human cell line. Adeno-associated virus (AAV)-mediated SaCas9-KKH delivery prevented deafness in Beethoven mice up to one year post injection. Analysis of current ClinVar entries revealed that similar to 21% of dominant human mutations could be targeted using a similar approach