The worm Caenorhabditis elegans is a model system for studying many aspects of biology, including host responses to bacterial pathogens, but it is not known to support replication of any virus. ...Plants and insects encode multiple Dicer enzymes that recognize distinct precursors of small RNAs and may act cooperatively. However, it is not known whether the single Dicer of worms and mammals is able to initiate the small RNA-guided RNA interference (RNAi) antiviral immunity as occurs in plants and insects. Here we show complete replication of the Flock house virus (FHV) bipartite, plus-strand RNA genome in C. elegans. We show that FHV replication in C. elegans triggers potent antiviral silencing that requires RDE-1, an Argonaute protein essential for RNAi mediated by small interfering RNAs (siRNAs) but not by microRNAs. This immunity system is capable of rapid virus clearance in the absence of FHV B2 protein, which acts as a broad-spectrum RNAi inhibitor upstream of rde-1 by targeting the siRNA precursor. This work establishes a C. elegans model for genetic studies of animal virus-host interactions and indicates that mammals might use a siRNA pathway as an antiviral response.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
At present, the severity of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been a focal point.
Methods
To assess the factors associated with ...severity and prognosis of patients infected with SARS‐CoV‐2, we retrospectively investigated the clinical, imaging and laboratory characteristics of confirmed 280 cases of novel coronavirus disease (COVID‐19) from 20 January to 20 February 2020.
Results
The median age of patients in the mild group was 37.55 years, whilst that in the severe group was 63.04 years. The proportion of patients aged over 65 years in the severe group was significantly higher than that of the mild group (59.04% vs. 10.15%, P < 0.05). 85.54% of severe patients had diabetes or cardiovascular diseases, which was significantly higher than that of the mild group (51.81% vs. 7.11%, P = 0.025; 33.73% vs. 3.05%, P = 0.042). Patients in the mild group experienced earlier initiation of antiviral treatment (1.19 ± 0.45 vs. 2.65 ± 1.06 days in the severe group, P < 0.001). Our study showed that comorbidity, time from illness onset to antiviral treatment and age >=65 were three major risk factors for COVID‐19 progression, whilst comorbidity and time from illness onset to antiviral treatment were two major risk factors for COVID‐19 recovery.
Conclusions
The elderly and patients with underlying diseases are more likely to experience a severe progression of COVID‐19. It is recommended that timely antiviral treatment should be initiated to slow the disease progression and improve the prognosis.
Discovery of the Earth's Van Allen radiation belts by instruments flown on Explorer 1 in 1958 was the first major discovery of the Space Age. The observation of distinct inner and outer zones of ...trapped megaelectron volt (MeV) particles, primarily protons at low altitude and electrons at high altitude, led to early models for source and loss mechanisms including Cosmic Ray Albedo Neutron Decay for inner zone protons, radial diffusion for outer zone electrons and loss to the atmosphere due to pitch angle scattering. This scattering lowers the mirror altitude for particles in their bounce motion parallel to the Earth's magnetic field until they suffer collisional loss. A view of the belts as quasi‐static inner and outer zones of energetic particles with different sources was modified by observations made during the Solar Cycle 22 maximum in solar activity over 1989–1991. The dynamic variability of outer zone electrons was measured by the Combined Radiation Release and Effects Satellite launched in July 1990. This variability is caused by distinct types of heliospheric structure that vary with the solar cycle. The launch of the twin Van Allen Probes in August 2012 has provided much longer and more comprehensive measurements during the declining phase of Solar Cycle 24. Roughly half of moderate geomagnetic storms, determined by intensity of the ring current carried mostly by protons at hundreds of kiloelectron volts, produce an increase in trapped relativistic electron flux in the outer zone. Mechanisms for accelerating electrons of hundreds of electron volts stored in the tail region of the magnetosphere to MeVenergies in the trapping region are described in this review: prompt and diffusive radial transport and local acceleration driven by magnetospheric waves. Such waves also produce pitch angle scattering loss, as does outward radial transport, enhanced when the magnetosphere is compressed. While quasilinear simulations have been used to successfully reproduce many essential features of the radiation belt particle dynamics, nonlinear wave‐particle interactions are found to be potentially important for causing more rapid particle acceleration or precipitation. The findings on the fundamental physics of the Van Allen radiation belts potentially provide insights into understanding energetic particle dynamics at other magnetized planets in the solar system, exoplanets throughout the universe, and in astrophysical and laboratory plasmas. Computational radiation belt models have improved dramatically, particularly in the Van Allen Probes era, and assimilative forecasting of the state of the radiation belts has become more feasible. Moreover, machine learning techniques have been developed to specify and predict the state of the Van Allen radiation belts. Given the potential Space Weather impact of radiation belt variability on technological systems, these new radiation belt models are expected to play a critical role in our technological society in the future as much as meteorological models do today.
Plain Language Summary
Discovery of the Earth's Van Allen radiation belts by instruments flown on Explorer 1 in 1958 was the first major discovery of the Space Age. The dynamic properties of trapped outer zone electrons and the outer boundary of the inner zone proton population, along with source populations, have recently been studied in great detail by instruments on National Aeronautics and Space Administration's Van Allen Probes spacecraft, as well as other data sources like operational spacecraft designed for navigation and terrestrial weather forecasting. The vulnerability of the myriad of spacecraft that is strongly affected by space weather disruptions, as compared to 1958, has motivated the radiation belt community to develop essential improved models for forecasting the space environment we will inhabit in the 21st century and evaluate its impacts on our technological society. In this paper, we provide a review on historical background and recent advances in understanding and modeling acceleration, transport, and loss processes of energetic particles in the Earth's Van Allen radiation belts, followed by outstanding challenges for developing future radiation belt models. The findings on the fundamental physics of the Van Allen radiation belts potentially provide insights into understanding energetic particle dynamics at other magnetized planets in the solar system, exoplanets throughout the universe, as well as in astrophysical and laboratory plasmas. Given the potential Space Weather impact of radiation belt variability on technological systems, these new radiation belt models are expected to play a critical role in our technological society in the future much as meteorological models do today.
Key Points
A brief historical background on the discovery of the Van Allen radiation belts and their response to solar activity is introduced
Recent advances in understanding mechanisms responsible for radiation belt electron acceleration, transport, and loss are reviewed
Outstanding challenges for developing future radiation belt models are summarized
With the rapid economic development, a better living condition leads to longer life expectancy, which increased the total population, in particular the elderly group. It may result in increase in the ...demand of pharmaceuticals for people in domestic use or in hospital. Although most sewage treatment plants or waste water treatment plantsmet the regulatory requirement, there are still many pharmaceuticals removed incompletely and thus discharged to the environment. Therefore, the pharmaceuticals residue draws the public concern because they might cause adverse effects on the organism even human beings. Recently, many studies have published on the source and occurrence as well as the fate of pharmaceuticals all over the world. This paper summarized and reviewed the recent studies on the sources, occurrence, fate and the effects of the most common pharmaceuticals. Finally, it gave the suggestion and risk management for controlling the pharmaceuticals.
•The sources of pharmaceutical residuals are studied.•Occurrence and fate of pharmaceutical in environment are studied.•Risk management and recommendation are provided on pharmaceutical pollution.
Concentration of pharmaceuticals in the natural environment is lower than in effluent of sewage treatment plants in which carbamazepine is found frequently in soil and water body.
As an inorganic cousin of graphene, MoS2 monolayer has attracted considerable attention. However, a full understanding of its structure and stability is still lacking due to its dependence on ...experimental synthesis conditions. Using first-principle calculations combined with Boltzmann transport equation, we have extensively studied the geometry, energetics, electronic structure, optical absorption, and carrier mobility of various phases of MoS2. We have not only identified the stable phases of a MoS2 monolayer, but also clarified the specific conditions under which different phases are formed. The possible pathways for transitions among different phases are also discussed.
The interleukin-1 family of cytokines are potent inducers of inflammation and pain. Proteolytic activation of this family of cytokines is under the control of several innate immune receptors that ...coordinate to form large multiprotein signalling platforms, termed inflammasomes. Recent evidence suggests that a wide range of inflammatory diseases, cancers, and metabolic and autoimmune disorders, in which pain is a common complaint, may be coordinated by inflammasomes. Activation of inflammasomes results in cleavage of caspase-1, which subsequently induces downstream initiation of several potent pro-inflammatory cascades. Therefore, it has been proposed that targeting inflammasome activity may be a novel and effective therapeutic strategy for these pain-related diseases. The purpose of this narrative review article is to provide the reader with an overview of the activation and regulation of inflammasomes and to investigate the potential therapeutic role of inflammasome inhibition in the treatment of diseases characterized by pain, including the following: complex regional pain syndrome, gout, rheumatoid arthritis, inflammatory pain, neuropathic pain, chronic prostatitis, chronic pelvic pain syndrome, and fibromyalgia. We conclude that the role of the inflammasome in pain-associated diseases is likely to be inflammasome subtype and disease specific. The currently available evidence suggests that disease-specific targeting of the assembly and activity of the inflammasome complex may be a novel therapeutic opportunity for the treatment of refractory pain in many settings.
Nearly 400,000 people worldwide are known to have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) beginning in December 2019. The virus has now spread to over 168 ...countries including the United States, where the first cluster of cases was observed in the Seattle metropolitan area in Washington. Given the rapid increase in the number of cases in many localities, the availability of accurate, high-throughput SARS-CoV-2 testing is vital to efforts to manage the current public health crisis. In the course of optimizing SARS-CoV-2 testing performed by the University of Washington Clinical Virology Lab (UW Virology Lab), we evaluated assays using seven different primer-probe sets and one assay kit. We found that the most sensitive assays were those that used the E-gene primer-probe set described by Corman et al. (V. M. Corman, O. Landt, M. Kaiser, R. Molenkamp, et al., Euro Surveill 25:2000045, 2020, https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000045) and the N2 set developed by the CDC (Division of Viral Diseases, Centers for Disease Control and Prevention, 2020, https://www.cdc.gov/coronavirus/2019-ncov/downloads/rt-pcr-panel-primer-probes.pdf). All assays tested were found to be highly specific for SARS-CoV-2, with no cross-reactivity with other respiratory viruses observed in our analyses regardless of the primer-probe set or kit used. These results will provide valuable information to other clinical laboratories who are actively developing SARS-CoV-2 testing protocols at a time when increased testing capacity is urgently needed worldwide.
Modified Cu electrodes were prepared by annealing Cu foil in air and electrochemically reducing the resulting Cu2O layers. The CO2 reduction activities of these electrodes exhibited a strong ...dependence on the initial thickness of the Cu2O layer. Thin Cu2O layers formed by annealing at 130 °C resulted in electrodes whose activities were indistinguishable from those of polycrystalline Cu. In contrast, Cu2O layers formed at 500 °C that were ≥ ∼3 μm thick resulted in electrodes that exhibited large roughness factors and required 0.5 V less overpotential than polycrystalline Cu to reduce CO2 at a higher rate than H2O. The combination of these features resulted in CO2 reduction geometric current densities >1 mA/cm2 at overpotentials <0.4 V, a higher level of activity than all previously reported metal electrodes evaluated under comparable conditions. Moreover, the activity of the modified electrodes was stable over the course of several hours, whereas a polycrystalline Cu electrode exhibited deactivation within 1 h under identical conditions. The electrodes described here may be particularly useful for elucidating the structural properties of Cu that determine the distribution between CO2 and H2O reduction and provide a promising lead for the development of practical catalysts for electrolytic fuel synthesis.
Autopsy examination of lungs from seven patients who died from Covid-19 showed intussusceptive angiogenesis in greater profusion than was found in lungs from patients who died from influenza or in ...uninfected lungs that were rejected for transplantation.
Preoperative evaluation of the number of lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC). However, the routinely used preoperative ...determination method is not accurate enough.
We enrolled 730 LAGC patients from five centers in China and one center in Italy, and divided them into one primary cohort, three external validation cohorts, and one international validation cohort. A deep learning radiomic nomogram (DLRN) was built based on the images from multiphase computed tomography (CT) for preoperatively determining the number of LNM in LAGC. We comprehensively tested the DLRN and compared it with three state-of-the-art methods. Moreover, we investigated the value of the DLRN in survival analysis.
The DLRN showed good discrimination of the number of LNM on all cohorts overall C-indexes (95% confidence interval): 0.821 (0.785–0.858) in the primary cohort, 0.797 (0.771–0.823) in the external validation cohorts, and 0.822 (0.756–0.887) in the international validation cohort. The nomogram performed significantly better than the routinely used clinical N stages, tumor size, and clinical model (P < 0.05). Besides, DLRN was significantly associated with the overall survival of LAGC patients (n = 271).
A deep learning-based radiomic nomogram had good predictive value for LNM in LAGC. In staging-oriented treatment of gastric cancer, this preoperative nomogram could provide baseline information for individual treatment of LAGC.
•Evaluation of the lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC).•Deep leaning radiomic nomogram (DLRN) based on CT images can preoperatively determine the number of LNM in LAGC.•DLRN is significantly superior to the routinely used clinical N stages, tumor size, and clinical model.•DLRN is significantly associated with the overall survival of LAGC.
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