Burkerowe1094

Developing high-performance solid electrolytes that are operable at room temperature is one of the toughest challenges related to all-solid-state fluoride-ion batteries (FIBs). In this study, tetragonal β-Pb0.78Sn1.22F4, a promising solid electrolyte material for mild-temperature applications, was modified through annealing under various atmospheres using thin-film models. The annealed samples exhibited preferential growth and enhanced ionic conductivities. The rate-determining factor for electrode/electrolyte interface reactions in all-solid-state FIBs was also investigated by comparing β-Pb0.78Sn1.22F4 with representative fluoride-ion- and lithium-ion-conductive materials, namely, LaF3, CeF3, and Li7La3Zr2O12. The overall rate constant of the interfacial reaction, k0, which included both mass and charge transfers, was determined using chronoamperometric measurements and Allen-Hickling simulations. Arrhenius-type correlations between k0 and temperature indicated that activation energies calculated from k0 and ionic conductivities (σion) were highly consistent. The results indicated that the mass transfer (electrolyte-side fluoride-ion conduction) should be the rate-determining process at the electrode/electrolyte interface. β-Pb0.78Sn1.22F4, with a large σion value, had a larger k0 value than Li7La3Zr2O12. Therefore, it is hoped that the development of high-conductivity solid electrolytes can lead to all-solid-state FIBs with superior rate capabilities similar to those of all-solid-state Li-ion batteries.The dynamics near the surface of glasses can be much faster than in the bulk. We studied the surface dynamics of a Pt-based metallic glass using electron correlation microscopy with sub-nanometer resolution. Our studies show an ∼20 K suppression of the glass transition temperature at the surface. The enhancement in surface dynamics is suppressed by coating the metallic glass with a thin layer of amorphous carbon. Parallel molecular dynamics simulations on Ni80P20 show a similar temperature suppression of the surface glass transition temperature and that the enhanced surface dynamics are arrested by a capping layer that chemically binds to the glass surface. Mobility in the near-surface region occurs via atomic caging and hopping, with a strong correlation between slow dynamics and high cage-breaking barriers and stringlike cooperative motion. Surface and bulk dynamics collapse together as a function of temperature rescaled by their respective glass transition temperatures.ConspectusWithout question, natural products have provided the lion share of leads, if not drugs themselves, for the treatment of bacterial infections. The bacterial arms race, fueled by selection and survival pressures has delivered a natural arsenal of small molecules targeting the most essential of life processes. Antibiotics that target these critical intracellular processes face the formidable defense of both penetrating a bacterial cell membrane and avoiding efflux to exert their effect. These challenges are especially effective in Gram-negative (Gram-(-)) bacteria, which have a double membrane structure and efficient efflux systems from the combination of outer-membrane porins and inner membrane proton pumps. In this landscape of offense and defense, our clinically used antibiotics have only successfully targeted three intracellular processes for therapeutic intervention in Gram-(-) bacteria dihydrofolate biosynthesis, transcription, and translation. Not surprisingly, such critical survival machinery ilass of antibiotics capable of selectively targeting the ribosomal P-site.In this study, we have focused on the structure-based design of the inhibitors of one of the two SARS-CoV-2 methyltransferases (MTases), nsp14. This MTase catalyzes the transfer of the methyl group from S-adenosyl-l-methionine (SAM) to cap the guanosine triphosphate moiety of the newly synthesized viral RNA, yielding the methylated capped RNA and S-adenosyl-l-homocysteine (SAH). As the crystal structure of SARS-CoV-2 nsp14 is unknown, we have taken advantage of its high homology to SARS-CoV nsp14 and prepared its homology model, which has allowed us to identify novel SAH derivatives modified at the adenine nucleobase as inhibitors of this important viral target. We have synthesized and tested the designed compounds in vitro and shown that these derivatives exert unprecedented inhibitory activity against this crucial enzyme. The docking studies nicely explain the contribution of an aromatic part attached by a linker to the position 7 of the 7-deaza analogues of SAH.Few matrices have the potential to be universally applicable for imaging vast endogenous compounds ranging from micro to macromolecules. In this article, we present hydralazine (HZN) as a versatile and universal matrix for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) of a wide range of endogenous compounds between 50.0 and 20,000.0 Da. this website HZN was prepared from its hydrochloride by alkalizing HZN·HCl with ammonia to enhance the optical absorptivity at the preferred MALDI UV laser wavelength. To further improve its performance for MALDI MS, HZN was doped with NH4OH or TFA, resulting in matrix superior performance for imaging biologically relevant compounds in the negative and positive-ion modes, respectively. The analyte-matrix interaction was also enhanced by the optimized matrix solvent and the deposition amount. Compared with conventional matrices such as 2,5-dihydroxybenzoic acid, α-cyano-4-hydroxycinnamic acid, and 9-aminoacridine (9-AA), the HZN matrix provided higher sensitivity, broader molecular coverage, and improved signal intensities. Its broad acquisition range makes it versatile for imaging small molecular metabolites and lipids, as well as proteins. In addition, HZN was applied successfully for the visualization of tissue-specific distributions and changes of small molecules, lipids, and proteins in the kidney and liver sections of obese ob/ob and diabetic db/db mice. The use of the HZN matrix shows great potential application in the field of pathological research.Chloride channels regulate cell volume by an efflux of chloride ions in response to osmotic stresses. These have been shown to play a role in cancer invasion. However, their function in cancer metastasis remains unclear. As the internal environment of the human body is rarely exposed to osmotic stress, we presumed that Cl- efflux in cancer cells is induced by mechanical stress caused by their crowded environment and invasion of their narrow interstitial spaces. In this study, we recruited atomic force microscopy to apply mechanical stress to mouse or human breast cancer cells with varying degrees of malignancy and examined their Cl- efflux by N-ethoxycarbonylmethyl-6-methoxyquinolinium bromide (MQAE), which is quenched via collision with Cl- ions. We found that intracellular MQAE fluorescence intensity increased immediately after cell compression, demonstrating induction of Cl- efflux by mechanical force. Furthermore, Cl- efflux ability showed correlation with the cancer metastatic potential. These results suggested that mechanical stress induced Cl- efflux may serve as a potential reporter for estimating the invasion ability of cancer cells.The extracellular matrix of hard connective tissues is composed primarily of mineralized collagen fibrils. Acidic noncollagenous proteins play important roles in mediating mineralization of collagen. Polyaspartate, a homopolymer substitute for such proteins, has been used extensively in in vitro models to produce biomimetic mineralized collagen. Polyglutamate behaves differently in mineralization models, despite its chemical similarity. We show that polyaspartate is a 350 times more effective inhibitor of solution precipitation of hydroxyapatite than polyglutamate. Supersaturated CaP solutions stabilized with polyaspartic acid produce collagen with aligned intrafibrillar mineral, while solutions containing polyglutamate lead to the formation of unaligned mineral clusters on the fibril surface. Molecular analysis showed that the commercial polyaspartic acid contains substantial isomerization, unlike polyglutamic acid. Hence, the secondary structure of polyaspartic acid is more disordered than that of polyglutamic acid. The increased flexibility of the polyaspartic acid chain may explain its potency as an inhibitor of solution crystallization and a mediator of intrafibrillar collagen mineralization.While natural protein-protein interactions have evolved to be induced by complex stimuli, rational design of interactions that can be switched-on-demand still remain challenging in the protein design world. Here, we demonstrate that a computationally redesigned natural interface for improved binding affinity could further be mutated to adopt a pH switchable interaction. The redesigned interface of Protein G/human IgG Fc domain (referred to as PrG/hIgG), when incorporated with histidine and glutamic acid on PrG (PrG-EHHE), showed a switch in binding affinity by 50-fold when the pH was altered from mild acidic to mild basic. The wild-type (WT) interface showed a negligible switch. The overall binding affinity under mild acidic pH for PrG-EHHE outperformed the wild-type PrG (PrG-WT) interaction. The new reagent PrG-EHHE can be revolutionary in IgG purification, since the standard method of using an extreme acidic pH for elution can be circumvented.Dion-Jacobson (DJ) quasi-2D perovskite solar cells (PSCs) have received increasing attention due to their greater potentials in realizing efficient and stable quasi-2D PSCs relative to their Ruddlesden-Popper counterpart. The substitution of methylammonium (MA+) with formamidinium is expected to be able to further increase the stability and power conversion efficiency (PCE) of DJ quasi-2D PSCs. Herein, we report a multifunctional additive strategy for preparing high-quality MA-free DJ quasi-2D perovskite films, where 1,1'-carbonyldi(1,2,4-triazole) (CDTA) molecules are incorporated into the perovskite precursor solution. CDTA modification can control phase distribution, enlarge grain size, modulate crystallinity and crystal orientation, and passivate defects. After CDTA modification, more favorable gradient phase distribution and accordingly gradient band alignment are formed, which is conducive to carrier transport and extraction. The improved crystal orientation can facilitate carrier transport and collection. The enlarged grain size and effective defect passivation contribute to reduced defect density. As a result, the CDTA-modified device delivers a PCE of 16.07%, which is one of the highest PCEs ever reported for MA-free DJ quasi-2D PSCs. The unencapsulated device with CDTA maintains 92% of its initial PCE after aging under one sun illumination for 360 h and 86% after aging at 60 °C for 360 h.Baicalein is an active ingredient extracted from the dried roots of the Scutellaria baicalensis Georgi. It has been demonstrated to improve memory impairment in multiple animal models; however, the underlying mechanisms remain ambiguous. The accumulation of senescent astrocytes and senescence-associated secretory phenotype (SASP) secreted by senescent astrocytes has been deemed as potential contributors to neurodegenerative diseases. Therefore, this study explored the protective effects of baicalein against astrocyte senescence and investigated the molecular mechanisms and metabolic mechanisms of baicalein against astrocyte senescence. Our results demonstrated that treatment with baicalein protects T98G cells from H2O2-induced damage, delays cell senescence, inhibits the secretion of SASP (IL-6, IL-8, TNF-α, CXCL1, and MMP-1), and inhibits SASP-related pathways NF-κB and JAK2/STAT1. 1H NMR metabolomics analysis and correlation analysis revealed that leucine was significantly correlated with SASP factors. Further study demonstrated that supplement with leucine could restrain SASP secretion, and baicalein could significantly increase leucine level through down-regulation of BCAT1 and up-regulation of SLC7A5 expression.