Aerobic Exercise in Male Mice Prevents Ventilator-Induced Lung Injury by Inhibiting Mitochondrial Damage from sirt1 Dysregulation.

BACKGROUND: Ventilator-induced lung injury (VILI) is a common complication of mechanical ventilation under general anesthesia. Regular aerobic exercise before surgery improves postoperative recovery and reduces postoperative pulmonary complications, but the mechanism driving this protective effect is unclear. METHODS: To determine how aerobic exercise prevents VILI, we investigated the effects of exercise and mechanical ventilation on the lungs of male mice and the effects of AMPK stimulation (simulating exercise) and cyclic stretching on human lung microvascular endothelial cells (HLMVEC). Sirtuin 1 (Sirt1) knockdown male mice were generated to explore the regulating mechanisms of sirt1 on mitochondrial function in male mice after mechanical ventilation was explored. Western blot, flow cytometry, live cell imaging, and mitochondrial function evaluations were used to determine the protective effects of aerobic exercise in preventing mitochondrial damage in VILI. RESULTS: Mitochondrial function and cell junctions were destroyed by mechanical ventilation in male mice or cyclic stretching in HLMVEC, a model of VILI. However, mitochondrial function and cell junction dysfunction were improved by exercise before mechanical ventilation (male mice) or treatment with AMPK before cyclic stretching (HLMVEC). p66shc, a marker of oxidative stress, was increased, and PINK1, a marker of mitochondrial autophagy, was decreased by mechanical ventilation or cyclic stretching. Sirt1 knockdown increased p66shc and decreased PINK1. Increased sirt1 expression was observed in the exercise and exercise + ventilation groups, suggesting that sirt1 inhibits mitochondrial damage in VILI. CONCLUSIONS: Mechanical ventilation induces mitochondrial damage in lung cells and leads to VILI. Regular aerobic exercise before ventilation may prevent VILI by improving mitochondrial function.

Malignancy is a risk factor for higher COVID-19 severity:A meta-analysis.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has been an almost global pandemic with significant public health impacts. The increasing prevalence of malignancy has become a leading cause of human mortality. However, conflicting findings have been published on the association between malignancy and COVID-19 severity. This study aims to assess the pooled proportion of malignancy amongst 2019-nCov patients and to investigate the association between malignancy and COVID-19 severity. METHODS: Correlative studies were identi?ed by systematically searching electronic databases (PubMed, Web of Sciences and Embase) up to September 2, 2020. All data analyses were carried out using Stata 15.0. RESULTS: Twenty-nine studies consisting of 9475 confirmed COVID-19 patients (median age 54.4 years [IQR 49-62], 54.0% men) were included. The overall proportion of malignancy was 2.5% (95% CI 1.6%-3.4%). The proportion of malignancy was higher in patients with severe/critical 2019-nCoV than those in non-severe/non-critical group (3.9% [95% CI 2.0-6.3] vs 1.4% [95% CI 0.8-2.2]). Furthermore, pre-existing malignancy was associated with more than twofold higher risk of severe/critical patients with COVID-19 (OR 2.25, 95% CI 1.65-3.06 I2 = 0.0%). CONCLUSION: Malignancy was associated with up to 2.3-fold higher risk of severe/critical COVID-19 and may serve as a clinical predictor for adverse outcomes.

[Cost-effective analysis of seasonal influenza vaccine in elderly Chinese population].

Objective: To evaluate the cost-effectiveness of seasonal influenza vaccination, compared to no vaccination, for the elderly aged ≥60 years old in China. Methods: A static life-time Markov model is conducted to simulate the Chinese elderly population aged ≥60 years old. Taking the health care system perspective, one-year analytic cycle length is used for each influenza season. The model was assumed to be repeated until the individual reaches 100 years old. Three interventions were evaluated, including no vaccination, annual trivalent influenza vaccination, and annual quadrivalent influenza vaccination. Using the threshold of 3 times GDP per capita per Quality-adjusted life year (QALY) (193 932/QALY), the incremental cost-effectiveness ratio (ICER) was calculated to compare the cost-effectiveness of every two interventions.Model inputs like data for costs and utilities were from studies on Chinese population if they were available. QALY was used to measure health utility. One-way sensitivity analysis and probabilistic sensitivity analysis were adopted to quantify the level of confidence of the model output. Results: The total influenza associated costs of no vaccination would be 603 CNY per person, while the total costs of annual trivalent vaccination would be 1 027 CNY. Using trivalent vaccine would result in 0.007 QALY gained per person compared to no vaccination, with an increased cost of 424 CNY per person. The ICER of trivalent vaccination over no vaccination for all the elderly population in China would be 64 026 CNY per QALY gained, which was less than the threshold of 3 times GDP per capita. The total costs of annual quadrivalent vaccination would be 1 988 CNY. Using quadrivalent vaccine would result in 0.008 additional QALY gained per person compared to no vaccination, with an increased cost of 1 385 CNY per person. The ICER of quadrivalent vaccination over no vaccination would be 174 081 CNY per QALY gained, which was less than the threshold of 3 times GDP per capita. Conclusion: Vaccinating elderly population would improve health utilities at higher health care costs for the elderly. Using the threshold of 3 times GDP per capita per QALY (193 932/QALY), both trivalent and quadrivalent vaccination would be cost-effective compared to no vaccination in elderly Chinese population.

A high-resolution whole-genome map of the distinctive epigenomic landscape induced by butyrate in bovine cells.

This report presents a study utilizing next-generation sequencing technology, combined with chromatin immunoprecipitation (ChIP-seq) technology to analyze histone modification induced by butyrate and to construct a high-definition map of the epigenomic landscape with normal histone H3 and H4 and their variants in bovine cells at the whole-genome scale. A total of 10 variants of histone H3 and H4 modifications were mapped at the whole-genome scale (acetyl-H3K18-ChIP-seq, trimethy-H3K9, histone H4 ChIP-seq, acetyl-H4K5 ChIP-seq, acetyl-H4K12 ChIP-seq, acetyl-H4K16 ChIP-seq, histone H3 ChIP-seq, acetyl H3H9 ChIP-seq, acetyl H3K27 ChIP-seq and tetra-acetyl H4 ChIP-seq). Integrated experiential data and an analysis of histone and histone modification at a single base resolution across the entire genome are presented. We analyzed the enriched binding regions in the proximal promoter (within 5 kb upstream or at the 5'-untranslated region from the transcriptional start site (TSS)), and the exon, intron and intergenic regions (defined by regions 25 kb upstream and 10 kb downstream from the TSS). A de novo search for the binding motif of the 10 ChIP-seq datasets discovered numerous motifs from each of the ChIP-seq datasets. These consensus sequences indicated that histone modification at different locations changes the histone H3 and H4 binding preferences. Nevertheless, a high degree of conservation in histone binding also was presented in these motifs. This first extensive epigenomic landscape mapping in bovine cells offers a new framework and a great resource for testing the role of epigenomes in cell function and transcriptomic regulation.

Detection of germline and somatic copy number variations in cattle.

As a complement to the Bovine HapMap Consortium project, we initiated a systematic study of the copy numbervariation (CNV) within the same cattle population using array comparative genomic hybridization (array CGH). Oligonucleotide CGH arrays were designed and fabricated to cover all chromosomes with an average interval of 6 kb using the latest bovine genome assembly. In the initial screening, three Holstein bulls were selected to represent major paternal lineages of the Holstein breed with some maternal linkages between these lines. Dual-label hybridizations were performed using either Hereford L1 Dominette 01449 or L1 Domino 99375 as reference. The CNVs were represented by gains and losses of normalized fluorescence intensities relative to the reference. The data presented here, for the first time, demonstrated that significant amounts of germline and fewer somatic CNVs exist in cattle, that many CNVs are common both across diverse cattle breeds and among individuals within a breed, and that array CGH is an effective tool to systematically detect bovine CNV. Selected CNVs have been confirmed by independent methods using real-time (RT) PCR. The strategy used in this study, based on genome higher-orderarchitecture variation, is a powerful approach to generating resources for the identification of novel genomic variation and candidate genes for economically important traits.

Characterization of a novel microdeletion polymorphism on BTA5 in cattle.

We present a detailed breakpoint mapping and population frequency analysis of a 214-kb microdeletion that removes multiple olfactory receptor genes. Using progressive rounds of PCR assays, we mapped the upstream and downstream breakpoints of this microdeletion event to approximately 1 and 12 kb genomic regions, respectively. We developed PCR-based genotyping assays, characterized a dairy cattle panel of 96 samples and found that the frequency of the deletion allele was over 51%. Our results indicated that this microdeletion is an ancient event occurring in one of the earlier founders, and that it has been stably inherited across generations in the North American dairy cattle population.

Neutralization and buffering capacity of leaves of sugar maple, largetooth aspen, paper birch and balsam fir.

We compared the acidity, the external acid neutralizing capacity and the buffering capacity of leaves of four commercially important tree species, largetooth aspen (Populus grandidentata Michx.), sugar maple (Acer saccharum Marsh.), paper birch (Betula papyrifera Marsh.) and balsam fir (Abies balsamea (L.) Mill), at two sites of contrasting soil fertility in southern Quebec. External acid neutralizing capacity (ENC) of leaves was determined by measuring the change in pH induced by soaking fresh leaves in an acidic solution (pH 4.0) for two hours. The ENC was highest for largetooth aspen (14.3 micro equiv H(+) g(-1)), and lowest for sugar maple and balsam fir (< 5 micro equiv H(+) g(-1)). The buffering capacity index (BCI) was determined by measuring the amount of acid necessary to produce a change of 5 micro equiv H(+) in the leaf homogenate. The BCI ranged from 883 micro equiv H(+) g(-1) for largetooth aspen to less than 105 micro equiv H(+) g(-1) for sugar maple and balsam fir. Leaves of sugar maple and balsam fir had a lower internal pH and a higher percentage of ENC over BCI than paper birch and largetooth aspen. Overall, ENC was correlated with the concentration of all leaf nutrients except Ca, and BCI was correlated with Mg, N and Ca. The site effect was relatively unimportant for all variables.