Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral ...entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.
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•Statin treatment among 13,981 patients with COVID-19 was retrospectively studied•Statin use in this cohort was associated with a lower risk of all-cause mortality•Adding an ACE inhibitor or an ARB did not affect statin-associated outcome in the cohort•The benefit of statins among this cohort may be due to immunomodulatory benefits
Statins have anti-inflammatory benefits and were suggested as an adjunct therapy for COVID-19. But statins may increase the expression of ACE2, the receptor for SARS-CoV-2. Here, Zhang et al. retrospectively analyzed 13,981 COVID-19 cases and found that in-hospital statin use is associated with a lower risk of all-cause mortality.
Abstract
Higher-order correlated excitonic states arise from the mutual interactions of excitons, which generally requires a significant exciton density and therefore high excitation levels. Here, we ...report the emergence of two biexcitons species, one neutral and one charged, in monolayer tungsten diselenide under moderate continuous-wave excitation. The efficient formation of biexcitons is facilitated by the long lifetime of the dark exciton state associated with a spin-forbidden transition, as well as improved sample quality from encapsulation between hexagonal boron nitride layers. From studies of the polarization and magnetic field dependence of the neutral biexciton, we conclude that this species is composed of a bright and a dark excitons residing in opposite valleys in momentum space. Our observations demonstrate that the distinctive features associated with biexciton states can be accessed at low light intensities and excitation densities.
Developing red thermally activated delayed fluorescence (TADF) emitters for high‐performance OLEDs is still facing great challenge. Herein, three red TADF emitters, pDBBPZ‐DPXZ, pDTBPZ‐DPXZ, and ...oDTBPZ‐DPXZ, are designed and synthesized with same donor–acceptor (D‐A) backbone with different peripheral groups attaching on the A moieties. Their lowest triplet states change from locally excited to charge transfer character leading to significantly enhance reverse intersystem crossing process. In particular, oDTBPZ‐DPXZ exhibits efficient TADF feature and exciton utilization. It not only achieves an external quantum efficiency (EQE) of 20.1 % in red vacuum‐processed OLED, but also realize a high EQE of 18.5 % in a solution‐processed OLED, which is among the best results in solution‐processed red TADF OLEDs. This work provides an effective strategy for designing red TADF molecules by managing energy level alignments to facilitate the up‐conversion process and thus enhance exciton harvesting.
By introducing phenyl or o‐tolyl groups into different positions of the same acceptor backbone, the lowest triplet energy levels of red thermally activated delayed fluorescence emitters can be tuned from locally excited triplet (3LEA) to charge transfer triplet (3CT) states, resulting in enhancement of the rates of reverse intersystem crossing (RISC), and boosting efficiencies in both vacuum‐ and solution‐processed OLEDs.
Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. Individuals with NAFLD have a high frequency of developing progressive liver disease and ...metabolism‐related comorbidities, which result from of a lack of awareness and poor surveillance of the disease and a paucity of approved and effective therapies. Managing the complications of NAFLD has already begun to place a tremendous burden on health‐care systems. Although efforts to identify effective therapies are underway, the lack of validated preclinical NAFLD models that represent the biology and outcomes of human disease remains a major barrier. This review summarizes the characteristics and prevalence of the disease and the status of our understanding of its mechanisms and potential therapeutic targets.
Genomic insertions, duplications and insertion/deletions (indels), which account for ~14% of human pathogenic mutations, cannot be accurately or efficiently corrected by current gene-editing methods, ...especially those that involve larger alterations (>100 base pairs (bp)). Here, we optimize prime editing (PE) tools for creating precise genomic deletions and direct the replacement of a genomic fragment ranging from ~1 kilobases (kb) to ~10 kb with a desired sequence (up to 60 bp) in the absence of an exogenous DNA template. By conjugating Cas9 nuclease to reverse transcriptase (PE-Cas9) and combining it with two PE guide RNAs (pegRNAs) targeting complementary DNA strands, we achieve precise and specific deletion and repair of target sequences via using this PE-Cas9-based deletion and repair (PEDAR) method. PEDAR outperformed other genome-editing methods in a reporter system and at endogenous loci, efficiently creating large and precise genomic alterations. In a mouse model of tyrosinemia, PEDAR removed a 1.38-kb pathogenic insertion within the Fah gene and precisely repaired the deletion junction to restore FAH expression in liver.
Speaker recognition is a task of identifying persons from their voices. Recently, deep learning has dramatically revolutionized speaker recognition. However, there is lack of comprehensive reviews on ...the exciting progress. In this paper, we review several major subtasks of speaker recognition, including speaker verification, identification, diarization, and robust speaker recognition, with a focus on deep-learning-based methods. Because the major advantage of deep learning over conventional methods is its representation ability, which is able to produce highly abstract embedding features from utterances, we first pay close attention to deep-learning-based speaker feature extraction, including the inputs, network structures, temporal pooling strategies, and objective functions respectively, which are the fundamental components of many speaker recognition subtasks. Then, we make an overview of speaker diarization, with an emphasis of recent supervised, end-to-end, and online diarization. Finally, we survey robust speaker recognition from the perspectives of domain adaptation and speech enhancement, which are two major approaches of dealing with domain mismatch and noise problems. Popular and recently released corpora are listed at the end of the paper.
•The study examines how language, visual-spatial, and executive function skills together contribute to number competence among very young children.•It uses a sample of 109 Chinese three-year-olds ...tested individually on their number competence, oral and written language, spatial perception, and behavioral executive skills.•Receptive vocabulary, print knowledge, spatial perception, and executive skills all make a unique contribution to early number competence.•Findings the highlight importance of considering fundamental domain-general factors that may be crucial for early number learning.
Early number competence is highly predictive of later mathematics achievement. The present study aims to examine how fundamental domain-general skills, including language, visual-spatial, and executive functions, together relate to early acquisition of numbers among very young children. A total of 109 Chinese children, aged approximately three years, in Hong Kong were tested individually on their number competence, receptive vocabulary, knowledge of written letters, rapid automatized naming, spatial perception, and behavioral executive skills. The results showed that vocabulary, letter knowledge, spatial perception, and executive skills all made a unique contribution to number competence. The findings add to the literature by documenting the critical importance of spatial perception and written language for early number learning. They also suggest that language, visual-spatial, and executive skills provide the building blocks for children’s number acquisition at a very young age.
Current enzyme‐responsive, fluorogenic probes fail to provide in situ information because the released fluorophores tend to diffuse away from the reaction sites. The problem of diffusive signal ...dilution can be addressed by designing a probe that upon enzyme conversion releases a fluorophore that precipitates. An excited‐state intramolecular proton transfer (ESIPT)‐based solid‐state fluorophore HTPQ was developed that is strictly insoluble in water and emits intense fluorescence in the solid state, with λex/em=410/550 nm, thus making it far better suited to use with a commercial confocal microscope. HTPQ was further utilized in the design of an enzyme‐responsive, fluorogenic probe (HTPQA), targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion‐resistant in situ detection of endogenous ALP in live cells. It was also employed in the visualizing of different levels of ALP in osteosarcoma cells and tissue, thus demonstrating its interest for the diagnosis of this type of cancer.
A solid‐state fluorophore (HTPQ) that is well‐suited to confocal microscopy was developed. HTPQ was used to design an enzyme‐responsive, fluorogenic probe (HTPQA) targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion‐resistant detection of endogenous ALP in live cells and visualization of ALP levels in Saos‐2 and U‐2OS osteosarcoma cells and tissue.
Skin effect, where macroscopically many bulk states are aggregated toward the system boundary, is one of the most important and distinguishing phenomena in non-Hermitian quantum systems. We discuss a ...new aspect of this effect whereby, despite its topological origin, applying a magnetic field can largely suppress it. Skin states are pushed back into the bulk, and the skin topological area, which we define, is sharply reduced. As seen from exact solutions of representative models, this is fundamentally rooted in the fact that the applied magnetic field restores the validity of the low-energy description that is rendered inapplicable in the presence of non-Bloch skin states. We further study this phenomenon using rational gauge fluxes, which reveals a unique irrelevance of the generalized Brillouin zone in the standard non-Bloch band theory of non-Hermitian systems.
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A high‐performance hybrid white organic light‐emitting device (WOLED) is demonstrated based on an efficient novel thermally activated delayed fluorescence (TADF) blue exciplex system. This device ...shows a low turn‐on voltage of 2.5 V and maximum forward‐viewing external quantum efficiency of 25.5%, which opens a new avenue for achieving high‐performance hybrid WOLEDs with simple structures.
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