Abstract
Clinical trials showed pangenotypic direct-acting antivirals’ (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, ...glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.
Since 2017, higenamine has been added to the World Anti-Doping Agency (WADA) prohibited list as a β
-agonist prohibited at all times for sportspersons. According to WADA's report, positive cases of ...higenamine misuse have been increasing yearly. However, higenamine occurs naturally in the Chinese herb lotus plumule-the green embryo of lotus (
Gaertn) seeds-commercially available as concentrated powder on the Asian market. This study evaluated the major phytochemical components of lotus plumule products using an appropriate extraction method, followed by a human study in which the products were orally administered in multiple doses to investigate the risk of doping violations. Comparing various extraction methods revealed that optimized microwave-assisted extraction exhibited the highest extraction efficiency (extraction time, 26 min; power, 1046 W; and temperature, 120 °C). Subsequently, the alkaloids in lotus plumule products were quantitatively confirmed and compared. Human study participants (
= 6) consumed 0.8 g of lotus plumule (equivalent to 679.6 μg of higenamine) three times daily for three consecutive days. All participants' urinary higenamine concentrations exceeded the WADA reporting cut-off of 10.0 ng/mL. Accordingly, lotus plumule consumption may engender adverse analytical findings regarding higenamine. Athletes should avoid consuming lotus plumule-containing products during in- and out-of-competition periods.
We report an electrocatalyst, Co bases (metallic Co and Co(OH)
) with fluoride-incorporated CoO coating on the surface of (CoO-F/Co), was synthesized by the electro-deposition method. The porous ...network architecture of CoO-F/Co on the glassy carbon electrode exhibited an ultra-low overpotential of 15 mV, achieving the geometric current density of 10 mA cm
in 1.0 M KOH, which were comparable with the HER performance of numerous reported noble metal electrocatalysts. It is demonstrated that fluoride incorporation improved the electrodeposition particle size, electronic density, conductivity and hydrophilicity of CoO-F/Co the HER performance.
With Pd as an example, a set of quantitative analyses is designed to shed light on the bromide‐mediated reduction kinetics and oxidative etching in determining the twin structure and facet of Pd ...nanocrystals. The success of this work relies on the kinetic measurements of Pd(II) precursor reduction and the close examinations of resultant Pd seeds and nanocrystals at different stages of synthesis. We observe there is a clear trend where low, moderate, and high initial Pd(II) reduction rates regulated by Br− ions correspond to the formation of Pd seeds with singly‐twinned, multiply‐twinned, and single‐crystal structures in the nucleation stage, respectively. Our quantitative analyses also suggest the oxidative etching induced by oxygen/Br− pair can selectively remove the multiply‐twinned Pd seeds from the products in the growth stage while leaving behind singly‐twinned or single‐crystal Pd seeds for the evolution into Pd nanocrystals with well‐defined facets in high purity. The mechanistic insights obtained in this work can be extended to the synthesis of Pd@Pd−Pt core−shell nanocubes with high‐index facets, which can be used as excellent electrocatalysts and photocatalysts for hydrogen generation.
This work demonstrates a set of quantitative analyses to shed light on the bromide‐mediated reduction kinetics and oxidative etching in determining the twin structure and facet of Pd nanocrystals. The mechanistic insights obtained herein can be extended to the synthesis of Pd@Pd−Pt core−shell nanocubes with high‐index facets, which can be used as excellent electrocatalysts and photocatalysts for hydrogen generation.
The ubiquitous function of nitric oxide (NO) guided the biological discovery of the natural dinitrosyliron unit (DNIU) Fe(NO)2 as an intermediate/end product after Fe nitrosylation of nonheme ...cofactors. Because of the natural utilization of this cofactor for the biological storage and delivery of NO, a bioinorganic study of synthetic dinitrosyliron complexes (DNICs) has been extensively explored in the last 2 decades. The bioinorganic study of DNICs involved the development of synthetic methodology, spectroscopic discrimination, biological application of NO-delivery reactivity, and translational application to the (catalytic) transformation of small molecules. In this Forum Article, we aim to provide a systematic review of spectroscopic and computational insights into the bonding nature within the DNIU Fe(NO)2 and the electronic structure of different types of DNICs, which highlights the synchronized advance in synthetic methodology and spectroscopic tools. With regard to the noninnocent nature of a NO ligand, spectroscopic and computational tools were utilized to provide qualitative/quantitative assignment of oxidation states of Fe and NO in DNICs with different redox levels and ligation modes as well as to probe the Fe–NO bonding interaction modulated by supporting ligands. Besides the strong antiferromagnetic coupling between high-spin Fe and paramagnetic NO ligands within the covalent DNIU Fe(NO)2, in polynuclear DNICs, the effects of the Fe···Fe distance, nature of the bridging ligands, and type of bridging modes on the regulation of the magnetic coupling among paramagnetic DNIU Fe(NO)2 are further reviewed. In the last part of this Forum Article, the sequential reaction of {Fe(NO)2}10 DNIC (NO)2Fe(AMP) (1-red) with NO(g), HBF4, and KC8 establishes a synthetic cycle, {Fe(NO)2}9-{Fe(NO)2}9 DNIC (NO)2Fe(μ-dAMP)2Fe(NO)2 (1) → {Fe(NO)2}9 DNIC (NO2)Fe(AMP)BF4 (1-H) → {Fe(NO)2}10 DNIC 1-red → DNIC 1, for the transformation of NO into HNO/N2O. Of importance, the NO-induced transformation of {Fe(NO)2}10 DNIC 1-red and (NO)2Fe(DTA) (2-red; DTA = diethylenetriamine) unravels a synthetic strategy for preparation of the {Fe(NO)2}9-{Fe(NO)2}9 DNICs (NO)2Fe(μ-NHR)2Fe(NO)2 containing amido-bridging ligands, which hold the potential to feature distinctive physical properties, chemical reactivities, and biological applications.
Organic field-effect transistors (OFETs) memory devices based on hybrid nanocomposite electret were fabricated by cooperative supramolecular polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) with ...two different block compositions (asymmetric L1 and symmetric L2) that contain hydroxyl-functionalized ferrocene small molecules (FMs). Because of the selective hydrogen interaction between the hydroxyl groups of FM and pyridine groups in P4VP block, the small FMs can preferentially disperse in the P4VP nanodomain, which can be used as nanostructured charge-trapping nanocomposite electret (L1-FMX and L2-FMX) under solvent-annealing process. The charge-storage functionalities can be easily tailored by morphologies of the hybrid nanocomposite thin film and spatial distribution of the FM molecules in which the relative molecular mass of block copolymers and the FM loading ratio can further control both of them. These block copolymer nanocomposite thin film electrets with charge-controlling guest FM for OFETs memory devices exhibit significant features including the ternary bits storage, high-density trapping sites, charge-carrier trapping of both polarities (ambipolar trapping), and solution processing that can make important progress for future advanced storage and memory technology.
► Waste sludges as replacements for cement raw materials. ► We designed the cement moduli and sintering conditions for eco-cement clinker. ► We found all the major components of Portland cement in ...eco-cement. ► Experimental results revealed the engineering practicability of eco-cement pastes.
In this study, marble sludge, sewage sludge, drinking water treatment plant sludge, and basic oxygen furnace sludge were used as replacements for limestone, sand, clay, and iron slag, respectively, as the raw materials for the production of cement in order to produce eco-cement. It was found that it is feasible to use marble sludge to replace up to 50% of the limestone and also that other materials can serve as total replacements for the raw materials typically used in the production of cement. The major components of Portland cement were all found in eco-cement clinkers. The eco-cement was confirmed to produce calcium hydroxide and calcium silicate hydrates during the hydration process, increasing densification with the curing age. The compressive strength (
S
c
) and microstructural evaluations conducted at 28
d revealed the usefulness of eco-cement. It was observed that the
S
c
data correlated linearly with the pore volume (
P) data at 28
d. The proposed model equation could be represented as
S
c
=
178–461P (correlation coefficient,
R
2
=
0.96). Two parameters, the large capillary pore volume and the medium capillary pore volume, were evaluated using multiple regression analysis.
The crystal phase with a specific stacking sequence of atoms largely affects the catalytic performance of metal nanocrystals. Since the control of the phase at the same composition is extremely ...difficult, the phase-dependent performance of metal nanocrystals is studied rarely. Here, we show the synthesis of Ru nanocrystals with different percentages of face-centered cubic (FCC) and hexagonal close-packed (HCP) phases via kinetic control, further revealing a quantitative correlation between the phase percentage of Ru nanocrystals and the initial reduction rate of Ru(III) precursors. Specifically, we manipulate the single parameter-initial reduction rate by controlling the Ru(III) injection rate into the dropwise synthesis at a fixed reaction temperature and correlate the kinetic data with the Ru phase percentage analyzed by atomic-resolution electron microscopy and synchrotron X-ray scattering. Based on the quantitative analysis, the ranges of initial reduction rates of Ru precursors can be determined for synthesizing Ru nanocrystals with the percentages of unusual FCC phase from 9.0 to 55.1%. We demonstrate that a low initial reduction rate corresponds to the crystallization of the Ru HCP phase, while a high initial reduction rate favors the crystallization of the FCC lattice. Furthermore, we also systematically examine the catalytic performance of Ru nanocrystals with different phases.
Utilizing scaffold-hopping drug-design strategy, we sought to identify a backup drug candidate for BPR0L075 (1), an indole-based anticancer agent. For this purpose, 5,6-fused bicyclic heteroaromatic ...scaffolds were designed and synthesized through shuffling of the nitrogen from the N-1 position or by insertion of one or two nitrogen atoms into the indole core of 1. Among these, 7-azaindole core 12 showed potent in vitro anticancer activity and improved oral bioavailability (F = 35%) compared with 1 (F < 10%).
S4 index is the rapid modification of signals when propagating through small-scale structures in the ionosphere, called ionospheric irregularities. The rapid modification of the signal causes the ...scintillation of the power. The purpose of this letter is to confirm the superposition property of the S4 index by using the ray-tracing method to simulate the signal propagation path through the ionospheric irregularities and then calculate the amplitude and S4 index of the received signal. The relation between the ionospheric scintillation S4 index and the signal propagation path can be understood. Then, the assimilation method for the S4 index can be developed to monitor the ionospheric irregularity in the future.
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