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Adhesion is a critical quality attribute and performance characteristic for transdermal and topical delivery systems (TDS). Regulatory agencies recommend in vivo skin adhesion studies to support the approval of TDS in both new drug applications and abbreviated new drug applications. The current assessment approach in such studies is based on the visual observation of the percent adhesion, defined as the ratio of the area of TDS attached to the skin to the total area of the TDS. Visually estimated percent adhesion by trained clinicians or trial participants creates variability and bias. In addition, trial participants are typically confined to clinical centers during the entire product wear period, which may lead to challenges when translating adhesion performance to the real world setting. In this work we propose to use artificial intelligence and mobile technologies to aid and automate the collection of photographic evidence and estimation of percent adhesion. We trained state-of-art deep learning models with advanced techniques and in-house curated data. Results indicate good performance from the trained models and the potential use of such models in clinical practice is further explored. [ABSTRACT FROM AUTHOR]

While Ni-rich cathodes have been widely adopted in high-energy lithium-ion batteries, there remains room for improvement regarding their cycle stability and safety. Herein, hexagonal boron nitride (h-BN) is demonstrated, for the first time, to be an effective surface modification additive for Ni-rich cathodes. The h-BN coated Ni-rich cathode, prepared via a rapid low-temperature post-calcination process, shows markedly improved cycle stability and safety with only a trace amount of h-BN being added (1 wt% relative to the cathode oxide). Systematic synchrotron post-mortem and operando X-ray analyses reveal that the improvements could be attributed to the anion-trapping ability of the B atoms in h-BN, which mitigates surface Ni-ion reduction and carbonate accumulation caused by electrolyte corrosion during both cycling and thermal runaway. Furthermore, the high thermal conductivity of h-BN contributes to efficient heat dissipation during the early stages of thermal runaway and therefore delays the onset temperature. This work identifies h-BN as well as the concept of "anion-trapping" as promising strategies for enhancing the cycle life and safety of Ni-rich cathodes and presents an industrially facile method to accomplish such applications. [ABSTRACT FROM AUTHOR]

Background: Huntington's disease (HD) is a neurodegenerative disease caused by CAG-repeat expansions (>36) in exon 1 of HTT, which dysregulates multiple cellular machineries. Translin-associated protein X (TRAX) is a scaffold protein with diverse functions, including suppressing the microRNA (miRNA)-mediated silencing by degrading pre-miRNA. To date, the role of TRAX in neurodegenerative diseases remains unknown.Objectives: We delineated the role of TRAX upregulation during HD progression.Methods: Expression of TRAX in the brains of humans and three mouse models with HD were analyzed by immunohistochemistry staining, western blot, and quantitative reverse transcription-polymerase chain reaction. Adeno-associated viruses harboring TRAX short hairpin RNA were intrastriatally injected into HD mice to downregulate TRAX. HD-like symptoms were analyzed by behavioral and biochemical assessments. The miRNA-sequencing and RNA-sequencing analyses were used to identify the TRAX- regulated miRNA-messenger RNA (mRNA) axis during HD progression. The identified gene targets were validated biochemically in mouse and human striatal cells.Results: We discovered that TRAX was upregulated in the brains of HD patients and three HD mouse models. Downregulation of TRAX enhanced 83 miRNAs (including miR-330-3p, miR-496a-3p) and subsequently changed the corresponding mRNA networks critical for HD pathogenesis (eg, DARPP-32 and brain-derived neurotrophic factor). Disruption of the TRAX-mediated miRNA-mRNA axis accelerated the progression of HD-like symptoms, including the degeneration of motor function, accumulation of mHTT aggregates, and shortened neurite outgrowth.Conclusions: We demonstrated that TRAX upregulation is authentic and protective in HD. Our study provides a novel layer of regulation for HD pathogenesis and may lead to the development of new therapeutic strategies for HD. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Composite cathodes consisting of a LiNi0.8Co0.1Mn0.1O2 (NCM) cathode and brittle Li3InCl6 (LIC) solid‐state electrolyte (SSE) are assessed for all‐solid‐state Li‐ion battery (ASSLIB) applications under a low stacking pressure (coin‐cell configuration: ≈2.0 MPa). Herein, an investigation is conducted to understand how the internal particle morphologies of the polycrystal (PC‐)/single‐crystal (SC‐) NCM cathode materials affect the internal cracking within the composite electrodes and thereby electrode performance. Extensive debonding between NCM and LIC takes place even at a very low current density (0.03C) with high voltage (4.4 V), but substantially narrower/shorter debonding gaps are observed for SC‐NCM as compared with PC‐NCM (wider/lengthier) due to their different particle sizes. High current rates (e.g., 0.1C) bring about greater strain rates in PC‐NCM particles, resulting in widespread microcracking along the grain boundaries between primary particles and consequently creating "dead zones" that are isolated from the ionic and electronic conduction pathways. Although SC‐NCM shows microcracking within the agglomerates, individual NCM crystals remain in close contact with the SSEs because of noticeably fewer grains in the agglomerations than in the PC‐NCM secondary particles. A low‐pressure SC‐NCM ASSLIB is demonstrated with good cycle stability comparable with that of a liquid‐electrolyte cell even under stressful currents. [ABSTRACT FROM AUTHOR]

The uniform and smaller-sized (~3 μm) LiNi0.8Co0.1Mn0.1O2 (SNCM) particles are prepared via a fast nucleation process of oxalate co-precipitation, followed by a two-step calcination procedure. It is found that the fast nucleation by vigorous agitation enables us to produce oxalate nuclei having a uniform size which then grow into micron-particles in less than a few minutes. The impacts of solution pH, precipitation time, calcination temperature, and surface modification with ZrO2 on the structural, morphological, and electrochemical properties of SNCM are systematically examined to identify the optimal synthetic conditions. A novel bimodal cathode design has been highlighted by using the combination of the SNCM particles and the conventional large (~10 μm) LiNi0.83Co0.12Mn0.05O2 (LNCM) particles to achieve the high volumetric energy density of cathode. The volumetric discharge capacity is found to be 526.6 mAh/cm3 for the bimodal cathode L80% + S20%, whereas the volumetric discharge capacity is found to be only 480.3 and 360.6 mAh/cm3 for L100% and S100% unimodal, respectively. Moreover, the optimal bi-modal cathode delivered higher specific energy (622.4 Wh/kg) and volumetric energy density (1622.6 Wh/L) than the L100% unimodal (596.1 Wh/kg and 1402.1 Wh/L) cathode after the 100th cycle. This study points to the promising utility of the SNCM material in Li-ion battery applications. [ABSTRACT FROM AUTHOR]

In Escherichia coli, ClpYQ (HslUV) is a two-component ATP-dependent protease in which ClpQ is the peptidase subunit and ClpY is the ATPase and the substrate-binding subunit. The ATP-dependent proteolysis is mediated by substrate recognition in the ClpYQ complex. ClpY has three domains, N, I, and C, and these domains are discrete and exhibit different binding preferences. In vivo, ClpYQ targets SulA, RcsA, RpoH, and TraJ molecules. In this study, ClpY was analyzed to identify the molecular determinants required for the binding of its natural protein substrates. Using yeast two-hybrid analysis, we showed that domain I of ClpY contains the residues responsible for recognition of its natural substrates, while domain C is necessary to engage ClpQ. Moreover, the specific residues that lie in the amino acid (aa) 137 to 150 (loop 1) and aa 175 to 209 (loop 2) double loops in domain I of ClpY were shown to be necessary for natural substrate interaction. Additionally, the two-hybrid system, together with random PCR mutagenesis, allowed the isolation of ClpY mutants that displayed a range of binding activities with SulA, including a mutant with no SulA binding trait. Subsequently, via methyl methanesulfonate tests and cpsB::lacZ assays with, e.g., SulA and RcsA as targets, we concluded that aa 175 to 209 of loop 2 are involved in the tethering of natural substrates, and it is likely that both loops, aa 137 to 150 and aa 175 to 209, of ClpY domain I may assist in the delivery of substrates into the inner core for ultimate degradation by ClpQ.