Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, ...and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.
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•CH25H and its enzymatic product, 25HC, inhibit ZIKV entry in vitro•25HC attenuates ZIKV-associated viremia and disease in mice and non-human primates•25HC prevents ZIKV infection in human cortical organoids•25HC protects fetal mice from microcephaly caused by ZIKV infection
Zika virus (ZIKV) presents a major challenge to the global health system. Li et al. find that 25-hydroxycholesterol (25HC) inhibits ZIKV infection in monkeys and human cortical organoids and protects mice from microcephaly. 25HC has potential as a first-line antiviral agent to combat a broad array of pathogenic species, including ZIKV.
Natron-based glass was a vital part of material culture in the Mediterranean and Europe for nearly two millennia, but natron glass found elsewhere on the Eurasian Continent has not received adequate ...discussion, despite its influence on ancient Asian glass. Here we present a new interpretation of natron glass finds from both the West and the East. After establishing the compositional types and technological sequence of Mediterranean natron glass (eighth-second century BCE) using trace elements, we report the analysis of a mid-1st millennium BCE glass bead from Xinjiang, China, which was likely made with Levantine raw glass, and identify common types of stratified eye beads in Eurasia based on a compositional and typological comparison. Combining these findings, we propose that a considerable number of Mediterranean natron glass products had arrived in East Asia at least by the fifth century BCE, which may have been a contributing factor in the development of native Chinese glass-making. The swift diffusion of natron glass across Eurasia in the 1st millennium BCE was likely facilitated by a three-stage process involving maritime and overland networks and multiple forms of trade and exchange, indicating a highly adaptable and increasingly efficient transcontinental connection along the 'Proto-Silk Road'.
The cosmopolitan red algal genus Pyropia sensu lato is the most speciose of the bladed Bangiales genera. In a major revision of the Bangiales, Pyropia was resurrected from Porphyra, although there ...was evidence at the time that species of Pyropia could be separated into several genera. Subsequent global phylogenetic analyses continued to resolve species assigned to Pyropia into several major clades with strong support, and the latest biogeographic analyses indicated that species distribution was also a pointer to the underlying phylogeny of Pyropia sensu lato. Therefore, in the present study, we have redefined the genus Pyropia, resurrected Porphyrella, and proposed four new genera: Calidia, Neoporphyra, Neopyropia, and Uedaea. Based on a molecular phylogenetic study of the bladed Bangiales of China, a species which did not match any known taxa was resolved in the new genus Calidia. The species, Calidia pseudolobata sp. nov., is described based on both morphological and molecular data. Molecular sequence data for rbcL, 18S, and COI‐5P were amplified for 15 samples in the present study. All the obtained rbcL sequences were identical to each other except for one (LYCN117) with one base pair difference. Two haplotypes of 18S (V9 region) were observed with one base pair difference (C/T30). All the obtained COI‐5P sequences were identical. Morphological comparisons were conducted not only with species in Calidia, but also with generically uncertain species currently assigned to Porphyra.
Recently, it was reported that anesthetizing infant rats for 6 h with a combination of anesthetic drugs (midazolam, nitrous oxide, isoflurane) caused widespread apoptotic neurodegeneration in the ...developing brain, followed by lifelong cognitive deficits. It has also been reported that ketamine triggers neuroapoptosis in the infant rat brain if administered repeatedly over a period of 9 h. The question arises whether less extreme exposure to anesthetic drugs can also trigger neuroapoptosis in the developing brain.
To address this question we administered ketamine, midazolam or ketamine plus midazolam subcutaneously at various doses to infant mice and evaluated the rate of neuroapoptosis in various brain regions following either saline or these various drug treatments. Each drug was administered as a single one‐time injection in a dose range that would be considered subanesthetic, and the brains were evaluated by unbiased stereology methods 5 h following drug treatment.
Neuroapoptosis was detected by immunohistochemical staining for activated caspase‐3. It was found that either ketamine or midazolam caused a dose‐dependent, statistically significant increase in the rate of neuroapoptosis, and the two drugs combined caused a greater increase than either drug alone. The apoptotic nature of the neurodegenerative reaction was confirmed by electron microscopy.
We conclude that relatively mild exposure to ketamine, midazolam or a combination of these drugs can trigger apoptotic neurodegeneration in the developing mouse brain.
British Journal of Pharmacology (2005) 146, 189–197. doi:10.1038/sj.bjp.0706301
Conventional impervious pavements have dark surface and large thermal inertia. During summertime they tend to absorb and store solar radiation but negate the evaporative cooling, contributing to the ...development of urban heat island (UHI). The idea of using cool pavements to mitigate the UHI has gained momentum recently. This review synthesizes the existing definition, physical mechanism, and typical cooling techniques of cool pavements, presenting the influence of cool pavements on the urban thermal environment. Benefits, penalties, costs and policies for the applications of cool pavements are presented with special emphasis on reflective pavements and evaporative pavements. The review suggests that the definition of cool pavements remain incomplete; that the influence of cool pavements on the air temperature in the urban canopy layer is unknown; and that the impact of cool pavements on the thermal conditions of adjacent buildings and pedestrians remains unknown. Many speculations of using cool pavements to battle the UHI effect need refinements and validations. Heat-harvesting pavements seem interesting because they not only stay cool but harness renewable energy. However, the results from the heat-harvesting pavement prototype require scrutiny on the power output, durability, and lifetime of the pavement system. Future studies are expected to understanding the impacts of cool pavements on pedestrian thermal stress, on adjacent building’s energy loads, and on the air temperature in the urban canopy layer.
Massive emissions of CO2 have caused environmental problems all over the world. The fixation of CO2 into cyclic carbonates is regarded as an effective way of capturing and utilizing CO2. Ionic liquid ...catalysts (ILCs) have received great attention and been employed for catalyzing the above reaction in recent years due to their unique properties. However, there are still a few problems requiring solutions in order to finally find the “ideal catalyst”. Herein, we reviewed a number of recent related literature. The progresses of both homogeneous and heterogeneous ILCs were discussed to find out where we are and which directions to work on. The effects of cations and anions of ionic liquids (ILs), functional groups, reaction phase states, structures of supports, preparation methods of supported ionic liquids (SILs), and interactions between the ILs and supports were investigated systematically. Accordingly, basic principles of designing ILCs for the title reaction are summarized and directions of future investigations are highlighted.
Designing ILs: Homogeneous and heterogeneous ionic liquid catalysts for the cycloaddition reaction of CO2 and epoxides to synthesize cyclic carbonates were reviewed. The effects of cations and anions of ionic liquids, functional groups, reaction phase states, structures of supports, preparation methods of supported ionic liquids, and interactions between the ILs and supports were investigated. Accordingly, basic principles of designing ionic liquid catalysts for the reaction were summarized.
The main objective of this study is to get the asymmetric effects of environmental policy stringency on CO2 emissions in top emitter's economies named China, USA, India, Russia, and Japan by using ...non-linear panel ARDL approach. The non-linear model infers that an increase in environmental policy stringency improves the environmental quality by reducing CO2 emissions in the long run. While a negative change in environmental policy stringency is also reducing the CO2 emissions in the long run. Indeed the asymmetric effects between positive and negative change in the environmental policy stringency are also confirmed in magnitude only in the long-run, thus the policymakers should consider positive as well as negative changes while devising the rules and regulations related to the environment. The study suggests that the high polluted economies need to revisit green environmental regulations policies.
Summary
Epidemiologic evidence has shown inconsistent findings regarding the relationships between abdominal fatness, as measured by waist circumferences (WC) or waist‐to‐hip ratio (WHR), and risks ...of pre‐ and postmenopausal breast cancer (BC). A dose–response meta‐analysis of prospective studies was conducted to address these issues. Potentially eligible studies were identified by searching PubMed and EMBASE databases, and by carefully reviewing the bibliographies of retrieved publications and related reviews. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random‐effects model. When the most fully adjusted RRs were combined, both WC (14 studies, RR per 10‐cm increase = 1.06, 95% CI: 1.04–1.09, I2 = 29.9%) and WHR (15 studies, RR per 0.1‐unit increase = 1.07, 95% CI: 1.01–1.14, I2 = 52.9%) were significantly positively associated with postmenopausal BC, but neither WC (eight studies, RR per 10‐cm increase = 1.05, 95% CI: 0.99–1.10, I2 = 0%) nor WHR (11 studies, RR per 0.1‐unit increase = 1.07, 95% CI: 0.95–1.21, I2 = 59.7%) were associated with premenopausal BC. The WHR‐postmenopausal BC association lost statistical significance after correcting publication bias (RR per 0.1‐unit increase = 1.06, 95% CI: 0.99–1.13). When considering BMI‐adjusted RRs, WC was associated with both pre‐ (five studies, RR per 10‐cm increase = 1.09, 95% CI: 1.02–1.16, I2 = 0%) and postmenopausal BC (seven studies, RR per 10‐cm increase = 1.05, 95% CI: 1.02–1.08, I2 = 6.3%), whereas WHR was not associated with either pre‐ (seven studies, RR per 0.1‐unit increase = 1.12, 95% CI: 0.94–1.34, I2 = 70.9%) or postmenopausal BC (eight studies, RR per 0.1‐unit increase = 1.05, 95% CI: 0.98–1.13, I2 = 57.3%). Among non‐current (former or never) users of hormone replacement therapy, the summary RR per 10‐cm increase of postmenopausal BC associated with WC was 1.08 (95% CI: 1.03–1.05, I2 = 69.2%, seven studies; BMI‐adjusted RR = 1.05, 95% CI: 1.02–1.09, I2 = 22.8%, four studies). This meta‐analysis indicates that central obesity measured by WC, but not by WHR, is associated with modestly increased risks of both pre‐ and postmenopausal BC independent of general obesity.
The localized faults of rolling bearings can be diagnosed by the extraction of the impulsive feature. However, the approximately periodic impulses may be submerged in strong interferences generated ...by other components and the background noise. To address this issue, this paper explores a new impulsive feature extraction method based on the sparse representation. According to the vibration model of an impulse generated by the bearing fault, a novel impulsive wavelet is constructed, which satisfies the admissibility condition. As a result, this family of model-based impulsive wavelets can form a Parseval frame. With the model-based impulsive wavelet basis and Fourier basis, a convex optimization problem is formulated to extract the repetitive impulses. Based on the splitting idea, an iterative thresholding shrinkage algorithm is proposed to solve this problem, and it has a fast convergence rate. Via the simulated signal and real vibration signals with bearing fault information, the performance of the proposed approach for repetitive impulsive feature extraction is validated and compared with the noted spectral kurtosis method, the optimized spectral kurtosis method based on simulated annealing, and the resonance-based signal decomposition method. The results demonstrate its advantage and superiority in weak repetitive transient feature extraction.
Abstract
Peroxisome, a special cytoplasmic organelle, possesses one or more kinds of oxidases for hydrogen peroxide (H
2
O
2
) production and catalase for H
2
O
2
degradation, which serves as an ...intracellular H
2
O
2
regulator to degrade toxic peroxides to water. Inspired by this biochemical pathway, we demonstrate the reactive oxygen species (ROS) induced tumor therapy by integrating lactate oxidase (LOx) and catalase (CAT) into Fe
3
O
4
nanoparticle/indocyanine green (ICG) co-loaded hybrid nanogels (designated as FIGs-LC). Based on the O
2
redistribution and H
2
O
2
activation by cascading LOx and CAT catalytic metabolic regulation, hydroxyl radical (·OH) and singlet oxygen (
1
O
2
) production can be modulated for glutathione (GSH)-activated chemodynamic therapy (CDT) and NIR-triggered photodynamic therapy (PDT), by manipulating the ratio of LOx and CAT to catalyze endogenous lactate to produce H
2
O
2
and further cascade decomposing H
2
O
2
into O
2
. The regulation reactions of FIGs-LC significantly elevate the intracellular ROS level and cause fatal damage to cancer cells inducing the effective inhibition of tumor growth. Such enzyme complex loaded hybrid nanogel present potential for biomedical ROS regulation, especially for the tumors with different redox state, size, and subcutaneous depth.
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