Background:Randomized trial evidence suggests that some antiviral drugs are effective in patients with COVID-19. However, the comparative effectiveness of antiviral drugs in nonsevere COVID-19 is unclear.Methods:We searched the Epistemonikos COVID-19 L·OVE (Living Overview of Evidence) database for randomized trials comparing antiviral treatments, standard care or placebo in adult patients with nonsevere COVID-19 up to Apr. 25, 2022. Reviewers extracted data and assessed risk of bias. We performed a frequentist network meta-analysis and assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.Results:We identified 41 trials, which included 18 568 patients. Compared with standard care or placebo, molnupiravir and nirmatrelvir–ritonavir each reduced risk of death with moderate certainty (10.9 fewer deaths per 1000, 95% confidence interval [CI] 12.6 to 4.5 fewer for molnupiravir; 11.7 fewer deaths per 1000, 95% CI 13.1 fewer to 2.6 more). Compared with molnupiravir, nirmatrelvir–ritonavir probably reduced risk of hospital admission (27.8 fewer admissions per 1000, 95% CI 32.8 to 18.3 fewer; moderate certainty). Remdesivir probably has no effect on risk of death, but may reduce hospital admissions (39.1 fewer admissions per 1000, 95% CI 48.7 to 13.7 fewer; low certainty).Interpretation:Molnupiravir and nirmatrelvir–ritonavir probably reduce risk of hospital admissions and death among patients with nonsevere COVID-19. Nirmatrelvir–ritonavir is probably more effective than molnupiravir for reducing risk of hospital admissions. Most trials were conducted with unvaccinated patients, before the emergence of the Omicron variant; the effectiveness of these drugs must thus be tested among vaccinated patients and against newer variants.Most trials addressing the treatment of patients with COVID-19 have targeted patients admitted to hospital with severe or critical disease.1 However, more recently, several treatments, including antiviral drugs, antidepressants, monoclonal antibodies and inhaled corticosteroids, have been studied for patients with nonsevere COVID-19.2 Preliminary evidence from ongoing or recently completed trials suggests that 2 novel antiviral drugs — molnupiravir and nirmatrelvir–ritonavir (Paxlovid) — may be effective at reducing risk of hospital admission.3–5 To date, evidence on antiviral drugs for nonsevere COVID-19 has not been systematically synthesized or appraised. Furthermore, although efficacy data from trials of molnupiravir, nirmatrelvir–ritonavir and remdesivir are promising, no head-to-head trials have compared these drugs.A network meta-analysis allows for comparison of treatments that have not been compared in randomized controlled trials (RCTs), using pooled estimates from direct and indirect evidence. They can provide guidance to clinicians and evidence users in determining which treatments are superior. This is particularly important as health care systems attempt to prioritize access to effective COVID-19 treatments in the early stages of the disease.We sought to compare the effectiveness of antiviral drugs for patients with nonsevere COVID-19. 相似文献
A non-canonical nuclear genetic code, in which TAG and TAA have been reassigned from stop codons to glutamine, has evolved
independently in several eukaryotic lineages, including the ulvophycean green algal orders Dasycladales and Cladophorales.
To study the phylogenetic distribution of the standard and non-canonical genetic codes, we generated sequence data of a representative
set of ulvophycean green algae and used a robust green algal phylogeny to evaluate different evolutionary scenarios that may
account for the origin of the non-canonical code. 相似文献
Functional traits are often used to examine ecological patterns and processes. Ontogeny—changes that occur over time as the result of development—generates variation in traits within individual organisms. We aimed to quantify the role of ontogeny in structuring functional trait variation across a range of co-existing herbaceous perennial species and hypothesized that ontogenetic variation in traits would be greater in younger vs. older plants. We grew eight herbaceous perennial forb species common in tallgrass prairies from seed in a greenhouse in Madison, Wisconsin, USA to determine how and when time-related variation in functional traits is large relative to other sources of variation, such as differences between leaves and species. We destructively measured common functional traits on four individuals of each species every two weeks for 19 weeks, including leaf mass fraction, root mass fraction, stem mass fraction, specific leaf area, leaf dry matter content, and leaf area. We found that most functional traits indeed change through time, that the direction of many changes are consistent between species but the magnitude of change is species specific, and most time-related variation occurred earlier in development. These results emphasize the importance of considering sampling timing and differences between young and old plants when measuring functional traits. Our results suggest that ontogenetic intraspecific variation can be substantial, especially early in life. It may be problematic to use traits measured from mature plants to interpret the importance of processes that occur at earlier life stages or vice versa; using seedling traits to understand adult plant responses may also be inappropriate.
Summary A pot experiment with peas var. Pauli is described in which it was observed that plants fertilized with NH4NO3 were much less attacked by powdery mildew than those which did not receive any nitrogen. 相似文献
RalA is a membrane-associated small GTPase that regulates vesicle trafficking. Here we identify a specific interaction between RalA and ERp57, an oxidoreductase and signalling protein. ERp57 bound specifically to the GDP-bound form of RalA, but not the GTP-bound form, and inhibited the dissociation of GDP from RalA in vitro. These activities were inhibited by reducing agents, but no disulphide bonds were detected between RalA and ERp57. Mutation of all four of ERp57’s active site cysteine residues blocked sensitivity to reducing agents, suggesting that redox-dependent conformational changes in ERp57 affect binding to RalA. Mutations in the switch II region of the GTPase domain of RalA specifically reduced or abolished binding to ERp57, but did not block GTP-specific binding to known RalA effectors, the exocyst and RalBP1. Oxidative treatment of A431 cells with H2O2 inhibited cellular RalA activity, and the effect was exacerbated by expression of recombinant ERp57. The oxidative treatment significantly increased the amount of RalA localised to the cytosol. These findings suggest that ERp57 regulates RalA signalling by acting as a redox-sensitive guanine-nucleotide dissociation inhibitor (RalGDI). 相似文献
Estimates of average rates of stalk formation over several generations of growth in Caulobacter crescentus showed that long-stalked Sk1 mutant and phosphate-starved wild-type cultures produce stalk material at about twice the rate of wild-type C. crescentus grown with adequate nutrients. Thus, the long stalks of Sk1 or phosphate-starved caulobacters are not merely a function of their longer doubling times. Inhibition of cell division of Sk1 418 with mitomycin C (MC) caused production of cellular filaments and resulted in inhibition of stalk formation. There was no appreciable decrease in total cell mass or in rates of ribonucleic acid and protein synthesis in the MC-treated cultures as compared with controls, but stalk formation, which is normally dependent on these processes, was severely retarded. Average stalk lengths in MC-treated Sk1 cultures were 30% of those found in control cultures. MC-produced cellular filaments were also subjected to deoxyribonucleic acid analysis and ultrastructural examination. The deoxyribonucleic acid content of MC-treated bacteria was about 50 to 60% that of untreated bacteria. Hydroxyurea also was found to produce some cellular filaments and shorter stalks, but with accompanying decreases in growth rate and yield. 相似文献
The symbiotic gut microbial community is generally known to have a strong impact on the fitness of its host. Nevertheless, it is less clear how the impact of symbiotic interactions on the hosts'' fitness varies according to environmental circumstances such as changes in the diet. This study aims to get a better understanding of host–microbiota interactions under different levels of food availability. We conducted experiments with the invertebrate, experimental model organism Daphnia magna and compared growth, survival and reproduction of conventionalized symbiotic Daphnia with germ-free individuals given varying quantities of food. Our experiments revealed that the relative importance of the microbiota for the hosts'' fitness varied according to dietary conditions. The presence of the microbiota had strong positive effects on Daphnia when food was sufficient or abundant, but had weaker effects under food limitation. Our results indicate that the microbiota can be a potentially important factor in determining host responses to changes in dietary conditions. Characterization of the host-associated microbiota further showed that Aeromonas sp. was the most prevalent taxon in the digestive tract of Daphnia. 相似文献
IL-28A, IL-28B and IL-29 (also designated type III interferons) constitute a new subfamily within the IL-10–interferon family. They are produced by virtually any nucleated cell type, particularly dendritic cells, following viral infection or activation with bacterial components, and mediate their effects via the IL-28R1/IL-10R2 receptor complex. Although IL-28/IL-29 are closer to the IL-10-related cytokines in terms of gene structure, protein structure, and receptor usage, they display type I interferon-like anti-viral and cytostatic activities. Unlike type I interferons, the target cell populations of IL-28/IL-29 are restricted and mainly include epithelial cells and hepatocytes. These properties suggest that IL-28/IL-29 are potential therapeutic alternatives to type I interferons in terms of viral infections and tumors. This review describes the current knowledge about these cytokines. 相似文献