Directly Deposited Antimony on a Copper Silicide Nanowire Array as a High-Performance Potassium-Ion Battery Anode with a Long Cycle Life

Antimony (Sb) is a promising anode material for potassium-ion batteries (PIBs) due to its high capacity and moderate working potential. Achieving stable electrochemical performance for Sb is hindered by the enormous volume variation that occurs during cycling, causing a significant loss of the active material and disconnection from conventional current collectors (CCs). Herein, the direct growth of a highly dense copper silicide (Cu₁₅Si₄) nanowire (NW) array from a Cu mesh substrate to form a 3D CC is reported that facilitates the direct deposition of Sb in a core-shell arrangement (Sb@Cu₁₅Si₄ NWs). The 3D Cu₁₅Si₄ NW array provides a strong anchoring effect for Sb, while the spaces between the NWs act as a buffer zone for Sb expansion/contraction during K–cycling. The binder-free Sb@Cu₁₅Si₄ anode displays a stable capacity of 250.2 mAh g⁻¹ at 200 mA g⁻¹ for over 1250 cycles with a capacity drop of ≈0.028% per cycle. Ex situ electron microscopy revealed that the stable performance is due to the complete restructuring of the Sb shell into a porous interconnected network of mechanically robust ligaments. Notably, the 3D Cu₁₅Si₄ NW CC is expected to be widely applicable for the development of alloying-type anodes for next-generation energy storage devices.     

A phase 3b,multicenter, open-label,single-arm study of roxadustat (ASPEN): Operational learnings within United States dialysis organizations

Introduction

Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved in several regions for the treatment of anemia of chronic kidney disease (CKD). ASPEN evaluated the efficacy, safety, and feasibility of roxadustat in patients with anemia of CKD in US dialysis organizations.

Methods

This open-label, single-arm study (NCT04484857) comprised a 6-week screening period, followed by 24 weeks of treatment (with optional extension ≤1 year) and a 4-week follow-up. Patients aged ≥18 years, receiving chronic dialysis, with hemoglobin (Hb) 9.0–12.0 g/dL if converting from erythropoiesis-stimulating agents (ESAs), or <10.0 g/dL if receiving ESAs for <6 weeks, received oral roxadustat three times weekly in-center. Primary efficacy endpoints included proportion of patients with mean Hb ≥10 g/dL, averaged over weeks 16–24, and mean Hb change from baseline to the average over weeks 16–24. Safety was also assessed.

Findings

Overall, 283 patients were enrolled and treated, 282 (99.6%) were included in the full analysis set, and 216 (76.3%) continued into the extension period. Most patients enrolled were from DaVita sites (71%), with the rest from US Renal Care sites (29%). Mean (standard deviation [SD]) baseline Hb was 10.6 (0.7) g/dL. Nearly all patients were prior ESA users (n = 274; 97.2%). The proportion of patients with mean Hb ≥10 g/dL during weeks 16–24 was 83.7% (95% confidence interval 78.9–88.6). Mean (SD) Hb increase from baseline to the average over weeks 16–24 was 0.2 (1.0) g/dL. During the treatment period, 82 (29.0%) patients reported treatment-emergent serious adverse events (TESAEs). The most common TESAEs were COVID-19 pneumonia (n = 10; 3.5%), acute respiratory failure (n = 9; 3.2%), COVID-19 (n = 7; 2.5%), acute myocardial infarction (n = 7; 2.5%), and fluid overload (n = 6, 2.1%).

Discussion

Roxadustat was effective in maintaining Hb in patients with anemia of CKD on dialysis in large, community-based dialysis organizations.     

Understanding the Visible Absorption of Electron Accepting and Donating CNDs

Carbon nanodots (CNDs) synthesized from citric acid and formyl derivatives, that is, formamide, urea, or N-methylformamide, stand out through their broad-range visible-light absorbance and extraordinary photostability. Despite their potential, their use has thus far been limited to imaging research. This work has now investigated the link between CNDs’ photochemical properties and their chemical structure. Electron-rich, yellow carbon nanodots (yCNDs) are obtained with in situ addition of NaOH during the synthesis, whereas otherwise electron-poor, red carbon nanodots (rCNDs) are obtained. These properties originate from the reduced and oxidized dimer of citrazinic acid within the matrix of yCNDs and rCNDs, respectively. Remarkably, yCNDs deposited on TiO₂ give a 30% higher photocurrent density of 0.7 mA cm⁻² at +0.3 V versus Ag/AgCl under Xe-lamp irradiation (450 nm long-pass filter, 100 mW cm⁻²) than rCNDs. The difference in overall photoelectric performance is due to fundamentally different charge-transfer mechanisms. These depend on either the electron-accepting or the electron-donating nature of the CNDs, as is evident from photoelectrochemical tests with TiO₂ and NiO and time-resolved spectroscopic measurements.     

Distribution and behavior of trace metals in the sediment and porewater of a tropical coastal wetland

Vertical profiles (0-30 cm below surface) of four trace metals-Cadmium (Cd), Chromium (Cr), Lead (Pb) and Zinc (Zn)-in the sediment and sediment porewater of an ecologically important intertidal mudflat in the Mai Po and Inner Deep Bay Ramsar Site were thoroughly studied over a period of 10 months (from March 1999 to January 2000). Two surveys, one in summer and another in winter, involving a total of eight sampling stations were conducted to study the seasonal variation of the remobilization characteristics of these trace metals in the mudflat sediment. The range of depth averaged concentration of these trace metals in the mudflat sediment was: 0.3-0.8 microg/g (Cd); 9.8-91.0 microg/g (Cr); 7.3-69.1 microg/g (Pb); and 39.5-192.0 microg/g (Zn), while that in the sediment porewater was: 0.3-121.1 microg/l (Cd); 3.0-2704.1 microg/l (Cr); 2.6-105.6 microg/l (Pb); and 32.6-4238.3 microg/l (Zn). In general, levels of dissolved trace metals in the sediment porewater were much higher in the summer than in the winter while their concentrations in the sediment were more or less the same throughout the year. Enrichment of Cd, Pb and Zn in the sediment porewater of the upper oxic layer and that of Cr in the oxic-sub-oxic boundary was generally observed. Regions in the vicinity of the Mai Po mangroves and the river mouths of Shenzhen River and Shan Pui River were found to be hotspots of trace metal pollution. Benthic diffusive fluxes of trace metals from the mudflat sediment were also estimated. Of the four trace metals, cadmium showed the greatest tendency toward remobilization from the sediment phase to the more bio-available porewater phase.     

Analytical‐Based Methodologies for Examining the In Vitro Absorption,Distribution, Metabolism,and Elimination (ADME) of Silver Nanoparticles

The clinical applications of silver nanoparticles (AgNPs) remain limited due to the lack of well‐established methodologies for studying their nanokinetics. Hereby, the primary goal is to adapt a suite of analytical‐based methodologies for examining the in vitro absorption, distribution, metabolism, and elimination of AgNPs. Vero 76 and HEK 293 cells are exposed to ≈10‐nm spherical AgNPs⁺ and AgNPs^? at relevant concentrations (0–300 µg mL^?1) and times (4–48 h). Absorption: Inductively coupled plasma optical emission spectroscopy (ICP‐OES) demonstrates that the two AgNP formulations are not bioequivalent. For example, different bioavailabilities (C _maximum < 20.7 ± 4% and 6.82 ± 0.4%), absorption times (T _maximum > 48 and ≈24 h), and absorption rate laws (first‐ and zeroth‐order at 300 µg mL^?1) are determined in Vero 76 for AgNPs⁺ and AgNPs^?, respectively. Distribution: Raman and CytoViva hyperspectral imaging show different cellular localizations for AgNPs⁺ and AgNPs^?. Metabolism: Cloud point extraction (CPE)‐tangential flow filtration (TFF) reveal that ≤ 11% ± 4% of the administered, sublethal AgNPs release Ag⁺ and contribute to the observed cytotoxicity. Elimination: ICP‐OES‐CPE suggests that AgNPs are cleared via exocytosis.     

Human DDX17 Unwinds Rift Valley Fever Virus Non-Coding RNAs

Rift Valley fever virus (RVFV) is a mosquito-transmitted virus from the Bunyaviridae family that causes high rates of mortality and morbidity in humans and ruminant animals. Previous studies indicated that DEAD-box helicase 17 (DDX17) restricts RVFV replication by recognizing two primary non-coding RNAs in the S-segment of the genome: the intergenic region (IGR) and 5′ non-coding region (NCR). However, we lack molecular insights into the direct binding of DDX17 with RVFV non-coding RNAs and information on the unwinding of both non-coding RNAs by DDX17. Therefore, we performed an extensive biophysical analysis of the DDX17 helicase domain (DDX17_135–555) and RVFV non-coding RNAs, IGR and 5’ NCR. The homogeneity studies using analytical ultracentrifugation indicated that DDX17_135–555, IGR, and 5’ NCR are pure. Next, we performed small-angle X-ray scattering (SAXS) experiments, which suggested that DDX17 and both RNAs are homogenous as well. SAXS analysis also demonstrated that DDX17 is globular to an extent, whereas the RNAs adopt an extended conformation in solution. Subsequently, microscale thermophoresis (MST) experiments were performed to investigate the direct binding of DDX17 to the non-coding RNAs. The MST experiments demonstrated that DDX17 binds with the IGR and 5’ NCR with a dissociation constant of 5.77 ± 0.15 µM and 9.85 ± 0.11 µM, respectively. As DDX17_135–555 is an RNA helicase, we next determined if it could unwind IGR and NCR. We developed a helicase assay using MST and fluorescently-labeled oligos, which suggested DDX17_135–555 can unwind both RNAs. Overall, our study provides direct evidence of DDX17_135–555 interacting with and unwinding RVFV non-coding regions.     

Reversible Control of Gelatin Hydrogel Stiffness by Using DNA Crosslinkers**

Biomaterials with dynamically tunable properties are critical for a range of applications in regenerative medicine and basic biology. In this work, we show the reversible control of gelatin methacrylate (GelMA) hydrogel stiffness through the use of DNA crosslinkers. We replaced some of the inter-GelMA crosslinks with double-stranded DNA, allowing for their removal through toehold-mediated strand displacement. The crosslinks could be restored by adding fresh dsDNA with complementary handles to those on the hydrogel. The elastic modulus (G’) of the hydrogels could be tuned between 500 and 1000 Pa, reversibly, over two cycles without degradation of performance. By functionalizing the gels with a second DNA strand, it was possible to control the crosslink density and a model ligand in an orthogonal fashion with two different displacement strands. Our results demonstrate the potential for DNA to reversibly control both stiffness and ligand presentation in a protein-based hydrogel, and will be useful for teasing apart the spatiotemporal behavior of encapsulated cells.     

The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.     

α-Methylene-β-Lactone Scaffold for Developing Chemical Probes at the Two Ends of the Selectivity Spectrum

The utilities of an α-methylene-β-lactone (MeLac) moiety as a warhead composed of multiple electrophilic sites are reported. We demonstrate that a MeLac-alkyne not only reacts with diverse proteins as a broadly reactive measurement probe, but also recruits reduced endogenous glutathione (GSH) to assemble a selective chemical probe of GSH-β-lactone (GSH-Lac)-alkyne in live cells. Tandem mass spectrometry reveals that MeLac reacts with nucleophilic cysteine, serine, lysine, threonine, and tyrosine residues, through either Michael or acyl addition. A peptide-centric proteomics platform demonstrates that the proteomic selectivity profiles of orlistat and parthenolide, which have distinct reactivities, are measurable by MeLac-alkyne as a high-coverage probe. The GSH-Lac-alkyne selectively probes the glutathione S-transferase P responsible for multidrug resistance. The assembly of the GSH-Lac probe exemplifies a modular and scalable route to develop selective probes with different recognizing moieties.