The re-emergence of Zika virus (ZIKV) in the Western Hemisphere has resulted in global public health crisis since 2015. ZIKV preferentially infects and targets human neural progenitor cells (hNPCs) ...and causes fetal microcephaly upon maternal infection. hNPCs not only play critical roles during fetal brain development, but also persist in adult brain throughout life. Yet the mechanism of innate antiviral immunity in hNPCs remains largely unknown. Here, we show that ZIKV infection triggers the abundant production of virus-derived small interfering RNAs in hNPCs, but not in the more differentiated progenies or somatic cells. Ablation of key RNAi machinery components significantly enhances ZIKV replication in hNPCs. Furthermore, enoxacin, a broad-spectrum antibiotic that is known as an RNAi enhancer, exerts potent anti-ZIKV activity in hNPCs and other RNAi-competent cells. Strikingly, enoxacin treatment completely prevents ZIKV infection and circumvents ZIKV-induced microcephalic phenotypes in brain organoid models that recapitulate human fetal brain development. Our findings highlight the physiological importance of RNAi-mediated antiviral immunity during the early stage of human brain development, uncovering a novel strategy to combat human congenital viral infections through enhancing RNAi.
Zika virus (ZIKV) has evolved into a global health threat because of its unexpected causal link to microcephaly. Phylogenetic analysis reveals that contemporary epidemic strains have accumulated ...multiple substitutions from their Asian ancestor. Here we show that a single serine-to-asparagine substitution Ser139→Asn139 (S139N) in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates in neonatal mice. Evolutionary analysis indicates that the S139N substitution arose before the 2013 outbreak in French Polynesia and has been stably maintained during subsequent spread to the Americas. This functional adaption makes ZIKV more virulent to human NPCs, thus contributing to the increased incidence of microcephaly in recent ZIKV epidemics.
A highly stable electrochemical acetylcholinesterase (AChE) biosensor for detection of organophosphorus pesticides (OPs) was developed simply by adsorption of AChE on chitosan (CS), TiO2 sol-gel, and ...reduced graphene oxide (rGO) based multi-layered immobilization matrix (denoted as CS@TiO2-CS/rGO). The biosensor fabrication conditions were optimized, and the fabrication process was probed and confirmed by scanning electron microscopy and electrochemical techniques. The matrix has a mesoporous nanostructure. Incorporation of CS and electrodeposition of a CS layer into/on the TiO2 sol-gel makes the gel become mechanically strong. The catalytic activity of the AChE immobilized CS@TiO2-CS/rGO/glassy carbon electrode to acetylthiocholine is significantly higher than those missing any one of the component in the matrix. The detection linear range of the biosensor to dichlorvos, a model OP compound, is from 0.036μM (7.9 ppb) to 22.6μM, with a limit of detection of 29nM (6.4 ppb) and a total detection time of about 25min. The biosensor is very reproducibly and stable both in detection and in storage, and can accurately detect the dichlorvos levels in cabbage juice samples, providing an efficient platform for immobilization of AChE, and a promisingly applicable OPs biosensor with high reliability, simplicity, and rapidness.
•Chitosan (CS) was electrodeposited on and also incorporated in TiO2 sol-gel.•The TiO2 sol-gel was layered on rGO film modified GC electrode.•AChE was efficiently immobilized into the matrix.•The CS@TiO2-CS/rGO matrix is mechanically strong.•The biosensor is stable, sensitive, reproducible and accurate in detection OP.
There is increasing interest in capturing H2 generated from renewables with CO2 to produce methanol. However, renewable hydrogen production is expensive and in limited quantity compared to CO2. ...Excess CO2 and limited H2 in the feedstock gas is not favorable for CO2 hydrogenation to methanol, causing low activity and poor methanol selectivity. Now, a class of Rh‐In catalysts with optimal adsorption properties to the intermediates of methanol production is presented. The Rh‐In catalyst can effectively catalyze methanol synthesis but inhibit the reverse water‐gas shift reaction under H2‐deficient gas flow and shows the best competitive methanol productivity under industrially applicable conditions in comparison with reported values. This work demonstrates a strong potential of Rh‐In bimetallic composition, from which a convenient methanol synthesis based on flexible feedstock compositions (such as H2/CO2 from biomass derivatives) with lower energy cost can be established.
The bimetallic Rh‐In catalyst offers selective sites for capturing hydrogen and CO2 to approach methanol formation under H2‐deficient feedstock compositions with high methanol yield but minimizing the reverse water‐gas shift reaction. Using this catalyst, a convenient methanol synthesis based on renewable biomass‐derived feedstocks with lower energy costs can be established.
This study aims at identifying the dimensions of experiential quality and investigating the interrelationships among experiential quality, experiential value, experiential satisfaction, theme park ...image, and revisit intention perceived by theme park visitors. Analysis of data from 424 visitors in Janfusan Fancyworld of Taiwan indicates that the proposed model fits the data well. The results reveal that there are 4 primary dimensions and 11 subdimensions of experiential quality perceived by theme park visitors. In addition, the results indicate that physical environment quality is identified as the most primary dimension of experiential quality perceived by theme park visitors.
AbstractObjectiveTo evaluate the efficacy and safety of standard term (12 months) or long term (>12 months) dual antiplatelet therapy (DAPT) versus short term (<6 months) DAPT after percutaneous ...coronary intervention (PCI) with drug-eluting stent (DES).DesignSystematic review and network meta-analysis.Data sourcesRelevant studies published between June 1983 and April 2018 from Medline, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, ClinicalTrials.gov, and Clinicaltrialsregister.eu.Review methodsRandomised controlled trials comparing two of the three durations of DAPT (short term, standard term, and long term) after PCI with DES were included. The primary study outcomes were cardiac or non-cardiac death, all cause mortality, myocardial infarction, stent thrombosis, and all bleeding events.Results17 studies (n=46 864) were included. Compared with short term DAPT, network meta-analysis showed that long term DAPT resulted in higher rates of major bleeding (odds ratio 1.78, 95% confidence interval 1.27 to 2.49) and non-cardiac death (1.63, 1.03 to 2.59); standard term DAPT was associated with higher rates of any bleeding (1.39, 1.01 to 1.92). No noticeable difference was observed in other primary endpoints. The sensitivity analysis revealed that the risks of non-cardiac death and bleeding were further increased for ≥18 months of DAPT compared with short term or standard term DAPT. In the subgroup analysis, long term DAPT led to higher all cause mortality than short term DAPT in patients implanted with newer-generation DES (1.99, 1.04 to 3.81); short term DAPT presented similar efficacy and safety to standard term DAPT with acute coronary syndrome (ACS) presentation and newer-generation DES placement. The heterogeneity of pooled trials was low, providing more confidence in the interpretation of results.ConclusionsIn patients with all clinical presentations, compared with short term DAPT (clopidogrel), long term DAPT led to higher rates of major bleeding and non-cardiac death, and standard term DAPT was associated with an increased risk of any bleeding. For patients with ACS, short term DAPT presented similar efficacy and safety with standard term DAPT. For patients implanted with newer-generation DES, long term DAPT resulted in more all cause mortality than short term DAPT. Although the optimal duration of DAPT should take personal ischaemic and bleeding risks into account, this study suggested short term DAPT could be considered for most patients after PCI with DES, combining evidence from both direct and indirect comparisons.Systematic review registrationPROSPERO CRD42018099519.
Objective
To evaluate the effectiveness of using WeChat platform to manage the patients with H. pylori infection.
Methods
566 patients were randomly divided into two groups: The control group was ...treated with traditional management method, and the experimental group established WeChat group and implemented the informatization management. The two groups were given a unified plan to eradicate H. pylori. After the treatment, the C14 breath test was reexamined. The follow‐up rate and H. pylori eradication rate of the two groups were counted.
Results
In the experimental group, 289 patients were enrolled and 271 patients were followed up. The follow‐up rate was 93.8%. The number of H. pylori‐negative patients was 244, and the eradication rate was 90.0%. In the control group, 277 patients were enrolled in the study, and 215 patients were followed up. The follow‐up rate was 77.6%. 169 cases of H. pylori‐negative conversion were found, and the eradication rate was 78.6%.
Conclusion
Through WeChat management, the medication adherence, regular follow‐up, and H.pylori infection eradication rate of the patients with H.pylori infection in the experimental group were better than that in control group, during the treatment of eradicating H.pylori, and the difference was statistically significant.
Infrared nonlinear optical (IR-NLO) crystals possessing excellent comprehensive performance are highly desirable, yet their preparation remains extremely challenging. Particularly, inorganic ...chalcogenides with diamond-like (DL) structures provide a tunable material platform for their structural design and functional control. In this work, a strategy involving the construction of chalcogenides with DL structures using the strong polarizability of metal cations has been put forward; thus, a quaternary Hg-containing metal sulfide HgCuPS4 has been successfully discovered by the high-temperature solid-state technology. A remarkable structural characteristic of HgCuPS4 is the three-dimensional (3D) defect DL framework constructed by vertex-sharing alignments of asymmetric building motifs (ABMs). The combination of the unique defect DL structure and the strong polarizability of the Hg2+ cations enables such compound to achieve phase matchability in the IR range with a high laser-induced damage threshold (4.2 × AgGaS2) and a strong second harmonic generation response (dij = 6.5 × AgGaS2), the best among the quaternary DL chalcogenides reported so far. Moreover, the detailed local dipole moment calculations and the theoretical results based on the length-gauge formalism elucidate that the very high dij value of HgCuPS4 originates from the combined effects of distorted HgS4, CuS4, and PS4 ABMs, that is, the 3D defect DL structure. This discovery can effectively help understand and design other promising defect DL metal chalcogenides toward future high-performing IR-NLO applications.
We define the anisotropic structure building unit that encompasses diverse chemical bonds (ABUCB). The ABUCB is highly likely to cause anisotropy in both crystallographic structure and spatial ...electron distribution, ultimately resulting in enhanced macroscopic optical anisotropy. Accordingly, the (PO
3
F)
2−
or (SO
3
F)
−
tetrahedron involving the unique P-F or S-F bond serves as such an ABUCB. The distinct chemical bond effectively alters the microscopic nature of the structure building unit, such as polarizability anisotropy, hyperpolarizability, and geometry distortion; this consequently changes the macroscopic second-order nonlinear optical (2nd-NLO) properties of the materials. In this review, we summarize both typical and newly emerged compounds containing ABUCBs. These compounds encompass approximately 90 examples representing six distinct categories, including phosphates, borates, sulfates, silicates, chalcogenides and oxyhalides. Furthermore, we demonstrate that the presence of ABUCBs in DUV/UV NLO compounds contributes to an increase in birefringence and retention of a large band gap, facilitating phase matching in high-energy short-wavelength spectral ranges. On the other hand, the inclusion of ABUCBs in IR NLO compounds offers a feasible method for increasing the band gap and consequently enhancing the larger laser-induced damage threshold. This review consolidates various trial-and-error explorations and presents a novel strategy for designing 2nd-NLO compounds, potentially offering an opportunity for the development of high-performance 2nd-NLO materials.
We report the concept of anisotropic structure building units encompassing diverse chemical bonds (ABUCB), which play a crucial role in optimizing the overall second-order nonlinear optical performance of both DUV/UV and IR NLO materials.
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