We report direct observation of an unexpected anisotropic swelling of Si nanowires during lithiation against either a solid electrolyte with a lithium counter-electrode or a liquid electrolyte with a ...LiCoO2 counter-electrode. Such anisotropic expansion is attributed to the interfacial processes of accommodating large volumetric strains at the lithiation reaction front that depend sensitively on the crystallographic orientation. This anisotropic swelling results in lithiated Si nanowires with a remarkable dumbbell-shaped cross section, which develops due to plastic flow and an ensuing necking instability that is induced by the tensile hoop stress buildup in the lithiated shell. The plasticity-driven morphological instabilities often lead to fracture in lithiated nanowires, now captured in video. These results provide important insight into the battery degradation mechanisms.
In lithium-ion batteries, the electrochemical reaction between the electrodes and lithium is a critical process that controls the capacity, cyclability and reliability of the battery. Despite ...intensive study, the atomistic mechanism of the electrochemical reactions occurring in these solid-state electrodes remains unclear. Here, we show that in situ transmission electron microscopy can be used to study the dynamic lithiation process of single-crystal silicon with atomic resolution. We observe a sharp interface (~1 nm thick) between the crystalline silicon and an amorphous Li(x)Si alloy. The lithiation kinetics are controlled by the migration of the interface, which occurs through a ledge mechanism involving the lateral movement of ledges on the close-packed {111} atomic planes. Such ledge flow processes produce the amorphous Li(x)Si alloy through layer-by-layer peeling of the {111} atomic facets, resulting in the orientation-dependent mobility of the interfaces.
Retaining the high energy density of rechargeable lithium ion batteries depends critically on the cycle stability of microstructures in electrode materials. We report the reversible formation of ...nanoporosity in individual germanium nanowires during lithiation–delithiation cycling by in situ transmission electron microscopy. Upon lithium insertion, the initial crystalline Ge underwent a two-step phase transformation process: forming the intermediate amorphous Li x Ge and final crystalline Li15Ge4 phases. Nanopores developed only during delithiation, involving the aggregation of vacancies produced by lithium extraction, similar to the formation of porous metals in dealloying. A delithiation front was observed to separate a dense nanowire segment of crystalline Li15Ge4 with a porous spongelike segment composed of interconnected ligaments of amorphous Ge. This front sweeps along the wire with a logarithmic time law. Intriguingly, the porous nanowires exhibited fast lithiation/delithiation rates and excellent mechanical robustness, attributed to the high rate of lithium diffusion and the porous network structure for facile stress relaxation, respectively. These results suggest that Ge, which can develop a reversible nanoporous network structure, is a promising anode material for lithium ion batteries with superior energy capacity, rate performance, and cycle stability.
Age-dependent memory impairment is known to occur in several organisms, including Drosophila, mouse and human. However, the fundamental cellular mechanisms that underlie these impairments are still ...poorly understood, effectively hampering the development of pharmacological strategies to treat the condition. Polyamines are among the substances found to decrease with age in the human brain. We found that levels of polyamines (spermidine, putrescine) decreased in aging fruit flies, concomitant with declining memory abilities. Simple spermidine feeding not only restored juvenile polyamine levels, but also suppressed age-induced memory impairment. Ornithine decarboxylase-1, the rate-limiting enzyme for de novo polyamine synthesis, also protected olfactory memories in aged flies when expressed specifically in Kenyon cells, which are crucial for olfactory memory formation. Spermidine-fed flies showed enhanced autophagy (a form of cellular self-digestion), and genetic deficits in the autophagic machinery prevented spermidine-mediated rescue of memory impairments. Our findings indicate that autophagy is critical for suppression of memory impairments by spermidine and that polyamines, which are endogenously present, are candidates for pharmacological intervention.
Using advanced in situ transmission electron microscopy, we show that the addition of a carbon coating combined with heavy doping leads to record-high charging rates in silicon nanowires. The carbon ...coating and phosphorus doping each resulted in a 2 to 3 orders of magnitude increase in electrical conductivity of the nanowires that, in turn, resulted in a 1 order of magnitude increase in charging rate. In addition, electrochemical solid-state amorphization (ESA) and inverse ESA were directly observed and characterized during a two-step phase transformation process during lithiation: crystalline silicon (Si) transforming to amorphous lithium–silicon (Li x Si) which transforms to crystalline Li15Si4 (capacity 3579 mAh·g–1). The ultrafast charging rate is attributed to the nanoscale diffusion length and the improved electron and ion transport. These results provide important insight in how to use Si as a high energy density and high power density anode in lithium ion batteries for electrical vehicle and other electronic power source applications.
Hepatitis E virus (HEV), a small, non-enveloped RNA virus in the family Hepeviridae, is associated with endemic and epidemic acute viral hepatitis in developing countries. Our 3.5-Å structure of a ...HEV-like particle (VLP) shows that each capsid protein contains 3 linear domains that form distinct structural elements: S, the continuous capsid; P1, 3-fold protrusions; and P2, 2-fold spikes. The S domain adopts a jelly-roll fold commonly observed in small RNA viruses. The P1 and P2 domains both adopt β-barrel folds. Each domain possesses a potential polysaccharide-binding site that may function in cell-receptor binding. Sugar binding to P1 at the capsid protein interface may lead to capsid disassembly and cell entry. Structural modeling indicates that native T = 3 capsid contains flat dimers, with less curvature than those of T = 1 VLP. Our findings significantly advance the understanding of HEV molecular biology and have application to the development of vaccines and antiviral medications.
The lower limit of metal hydride nanoconfinement is demonstrated through the coordination of a molecular hydride species to binding sites inside the pores of a metal–organic framework (MOF). ...Magnesium borohydride, which has a high hydrogen capacity, is incorporated into the pores of UiO-67bpy (Zr6O4(OH)4(bpydc)6 with bpydc2– = 2,2′-bipyridine-5,5′-dicarboxylate) by solvent impregnation. The MOF retained its long-range order, and transmission electron microscopy and elemental mapping confirmed the retention of the crystal morphology and revealed a homogeneous distribution of the hydride within the MOF host. Notably, the B-, N-, and Mg-edge XAS data confirm the coordination of Mg(II) to the N atoms of the chelating bipyridine groups. In situ 11B MAS NMR studies helped elucidate the reaction mechanism and revealed that complete hydrogen release from Mg(BH4)2 occurs as low as 200 °C. Sieverts and thermogravimetric measurements indicate an increase in the rate of hydrogen release, with the onset of hydrogen desorption as low as 120 °C, which is approximately 150 °C lower than that of the bulk material. Furthermore, density functional theory calculations support the improved dehydrogenation properties and confirm the drastically lower activation energy for B–H bond dissociation.
Controlling the transport of lithium (Li) ions and their reaction with electrodes is central in the design of Li-ion batteries for achieving high capacity, high rate, and long lifetime. The ...flexibility in composition and structure enabled by tailoring electrodes at the nanoscale could drastically change the ionic transport and help meet new levels of Li-ion battery performance. Here, we demonstrate that radial heterostructuring can completely suppress the commonly observed surface insertion of Li ions in all reported nanoscale systems to date and to exclusively induce axial lithiation along the ⟨111⟩ direction in a layer-by-layer fashion. The new lithiation behavior is achieved through the deposition of a conformal, epitaxial, and ultrathin silicon (Si) shell on germanium (Ge) nanowires, which creates an effective chemical potential barrier for Li ion diffusion through and reaction at the nanowire surface, allowing only axial lithiation and volume expansion. These results demonstrate for the first time that interface and bandgap engineering of electrochemical reactions can be utilized to control the nanoscale ionic transport/insertion paths and thus may be a new tool to define the electrochemical reactions in Li-ion batteries.
Purpose
After single oral dosing of the glycine reuptake transporter (GlyT1) inhibitor, iclepertin (BI 425809), a single major circulating metabolite, M530a, was identified. However, upon multiple ...dosing, a second major metabolite, M232, was observed with exposure levels ~ twofold higher than M530a. Studies were conducted to characterize the metabolic pathways and enzymes responsible for formation of both major human metabolites.
Methods
In vitro
studies were conducted with human and recombinant enzyme sources and enzyme-selective inhibitors. The production of iclepertin metabolites was monitored by LC–MS/MS.
Results
Iclepertin undergoes rapid oxidation to a putative carbinolamide that spontaneously opens to an aldehyde, M528, which then undergoes reduction by carbonyl reductase to the primary alcohol, M530a. However, the carbinolamide can also undergo a much slower oxidation by CYP3A to form an unstable imide metabolite, M526, that is subsequently hydrolyzed by a plasma amidase to form M232. This difference in rate of metabolism of the carbinolamine explains why high levels of the M232 metabolite were not observed
in vitro
and in single dose studies in humans, but were observed in longer-term multiple dose studies.
Conclusions
The long half-life iclepertin metabolite M232 is formed from a common carbinolamine intermediate, that is also a precursor of M530a. However, the formation of M232 occurs much more slowly, likely contributing to its extensive exposure
in vivo
. These results highlight the need to employ adequate clinical study sampling periods and rigorous characterization of unexpected metabolites, especially when such metabolites are categorized as major, thus requiring safety assessment.
In humans, disruption of nonsense-mediated decay (NMD) has been associated with neurodevelopmental disorders (NDDs) such as autism spectrum disorder and intellectual disability. However, the ...mechanism by which deficient NMD leads to neurodevelopmental dysfunction remains unknown, preventing development of targeted therapies. Here we identified novel protein-coding UPF2 (UP-Frameshift 2) variants in humans with NDD, including speech and language deficits. In parallel, we found that mice lacking Upf2 in the forebrain (Upf2 fb-KO mice) show impaired NMD, memory deficits, abnormal long-term potentiation (LTP), and social and communication deficits. Surprisingly, Upf2 fb-KO mice exhibit elevated expression of immune genes and brain inflammation. More importantly, treatment with two FDA-approved anti-inflammatory drugs reduced brain inflammation, restored LTP and long-term memory, and reversed social and communication deficits. Collectively, our findings indicate that impaired UPF2-dependent NMD leads to neurodevelopmental dysfunction and suggest that anti-inflammatory agents may prove effective for treatment of disorders with impaired NMD.
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•Humans carrying novel variants in UPF2 exhibit speech and language deficits•Upf2-deficient mice and flies have impaired NMD and exhibit behavioral deficits•Inhibition of Upf2-dependent NMD triggers immune activation in mice•Reduction of brain inflammation reverses synaptic and behavioral deficits
Johnson et al. discovered that genetic ablation of Upf2-mediated NMD triggers an aberrant immune response and leads to memory, synaptic plasticity, social, and vocal communication deficits. These behavioral and neurophysiological abnormalities were reversed by FDA-approved agents that dampen brain inflammation.