Air pollution constitutes a significant stimulus of asthma exacerbations; however, the impacts of exposure to major air pollutants on asthma-related hospital admissions and emergency room visits ...(ERVs) have not been fully determined.
We sought to quantify the associations between short-term exposure to air pollutants ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and particulate matter ≤10 μm (PM10) and PM2.5 and the asthma-related emergency room visits (ERV) and hospitalizations.
Systematic computerized searches without language limitation were performed. Pooled relative risks (RRs) and 95% confidence intervals (95%CIs) were estimated using the random-effect models. Sensitivity analyses and subgroup analyses were also performed.
After screening of 246 studies, 87 were included in our analyses. Air pollutants were associated with significantly increased risks of asthma ERVs and hospitalizations O3: RR(95%CI), 1.009 (1.006, 1.011); I2 = 87.8%, population-attributable fraction (PAF) (95%CI): 0.8 (0.6, 1.1); CO: RR(95%CI), 1.045 (1.029, 1.061); I2 = 85.7%, PAF (95%CI): 4.3 (2.8, 5.7); NO2: RR(95%CI), 1.018 (1.014, 1.022); I2 = 87.6%, PAF (95%CI): 1.8 (1.4, 2.2); SO2: RR(95%CI), 1.011 (1.007, 1.015); I2 = 77.1%, PAF (95%CI): 1.1 (0.7, 1.5); PM10: RR(95%CI), 1.010 (1.008, 1.013); I2 = 69.1%, PAF (95%CI): 1.1 (0.8, 1.3); PM2.5: RR(95%CI), 1.023 (1.015, 1.031); I2 = 82.8%, PAF (95%CI): 2.3 (1.5, 3.1). Sensitivity analyses yielded compatible findings as compared with the overall analyses without publication bias. Stronger associations were found in hospitalized males, children and elderly patients in warm seasons with lag of 2 days or greater.
Short-term exposures to air pollutants account for increased risks of asthma-related ERVs and hospitalizations that constitute a considerable healthcare utilization and socioeconomic burden.
The conversion of skeletal muscle fiber from fast twitch to slow‐twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. ...Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber‐type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss‐of‐function models generated by phospholipase Cβ antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius‐specific knockdown, we found that the effects of succinate on skeletal muscle fiber‐type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate‐based compounds in both athletic and sedentary populations.
Synopsis
Aerobic exercise leads to skeletal muscle remodelling. This study reveals that dietary succinate is sufficient to elicit muscle remodelling and increased endurance in sedentary mice.
Dietary succinate increases endurance exercise ability in mice.
Dietary succinate induces skeletal muscle fiber transition from fast‐twitch to slow‐twitch.
SUNCR1 signaling pathway is required for the succinate induced skeletal muscle remodeling.
Aerobic exercise leads to skeletal muscle remodelling. This study reveals that dietary succinate is sufficient to elicit muscle remodelling and increased endurance in sedentary mice.
Pre-metastatic niche formation is critical for the colonization of disseminated cancer cells in distant organs. Here we find that lung mesenchymal stromal cells (LMSCs) at pre-metastatic stage ...possess potent metastasis-promoting activity. RNA-seq reveals an upregulation of complement 3 (C3) in those LMSCs. C3 is found to promote neutrophil recruitment and the formation of neutrophil extracellular traps (NETs), which facilitate cancer cell metastasis to the lungs. C3 expression in LMSCs is induced and sustained by Th2 cytokines in a STAT6-dependent manner. LMSCs-driven lung metastasis is abolished in Th1-skewing Stat6-deficient mice. Blockade of IL-4 by antibody also attenuates LMSCs-driven cancer metastasis to the lungs. Consistently, metastasis is greatly enhanced in Th2-skewing T-bet-deficient mice or in nude mice adoptively transferred with T-bet-deficient T cells. Increased C3 levels are also detected in breast cancer patients. Our results suggest that targeting the Th2-STAT6-C3-NETs cascade may reduce breast cancer metastasis to the lungs.
Pathogenic bacterial membrane proteins (MPs) are a class of vaccine and antibiotic development targets with widespread clinical application. However, the inherent hydrophobicity of MPs poses a ...challenge to fold correctly in living cells. Herein, we present a comprehensive method to improve the soluble form of MP antigen by rationally designing multi‐epitope chimeric antigen (ChA) and screening two classes of protein‐assisting folding element. The study uses a homologous protein antigen as a functional scaffold to generate a ChA possessing four epitopes from transferrin‐binding protein A of Glaesserella parasuis. Our engineered strain, which co‐expresses P17 tagged‐ChA and endogenous chaperones groEL‐ES, yields a 0.346 g/L highly soluble ChA with the property of HPS‐positive serum reaction. Moreover, the protein titer of ChA reaches 4.27 g/L with >90% soluble proportion in 5‐L bioreactor, which is the highest titer reported so far. The results highlight a timely approach to design and improve the soluble expression of MP antigen in industrially viable applications.
Chen et al. present a novel strategy to improve soluble form of multi‐epitope chimeric antigen via computer‐assisted strategy and folding elements is developed in this study, which provides potential applications to achieve high soluble expression and productivity of membrane protein antigen against Glaesserella parasuis. By using this strategy, an industrial E. coli recombinant strain capable of efficiently expressing subunit vaccine candidate was obtained.
Long-duration (>2 s) γ-ray bursts that are believed to originate from the death of massive stars are expected to be accompanied by supernovae. GRB 060614, that lasted 102 s, lacks a supernova-like ...emission down to very stringent limits and its physical origin is still debated. Here we report the discovery of near-infrared bump that is significantly above the regular decaying afterglow. This red bump is inconsistent with even the weakest known supernova. However, it can arise from a Li-Paczyński macronova--the radioactive decay of debris following a compact binary merger. If this interpretation is correct, GRB 060614 arose from a compact binary merger rather than from the death of a massive star and it was a site of a significant production of heavy r-process elements. The significant ejected mass favours a black hole-neutron star merger but a double neutron star merger cannot be ruled out.
An additive genetic model is usually employed in case-control-based genome-wide association studies. The model usually encodes "AA", "Aa" and "aa" ("a" represents the minor allele) as three different ...numbers, implying the contribution of genotype "Aa" to the phenotype is different from "AA" and "aa". From the perspective of biological phenomena, the coding is reasonable since the phenotypes of lives are not "black and white". A case-control based study, however, has only two phenotypes, case and control, which means that the phenotypes are "black and white". It suggests that a recessive/dominant model may be an alternative to the additive model. In order to investigate whether the alternative is feasible, we conducted comparative experiments on several models used in those studies through chi-square test and logistic regression. Our simulation experiments demonstrate that a recessive model is better than the additive model. The area under the curve of the former has increased by 5% compared with the latter, the discrimination of identifying risk single nucleotide polymorphisms has been improved by 61%, and the precision has also reached 1.10 times that of the latter. Furthermore, the real data experiments show that the precision and area under the curve of the former are 16% and 20% higher than the latter respectively, and the area under the curve of dominant model of the former is 13% higher than the latter. The results indicate a recessive/dominant model may be an alternative to the additive model and suggest a new route for case-control-based studies.
Abstract
The physical composition of the ejecta of gamma-ray bursts (GRBs) remains an open question. The radiation mechanism of the prompt gamma rays is also in debate. This problem can be solved for ...the bursts hosting distinct thermal radiation. However, the events with dominant thermal spectral components are still rare. In this work, we focus on GRB 220426A, a recent event detected by the Fermi Gamma-ray Burst Monitor. The time-resolved and time-integrated data analyses yield very hard low-energy spectral indices and rather soft high-energy spectral indices. This means that the spectra of GRB 220426A are narrowly distributed. And the Bayesian inference results are in favor of the multicolor blackbody model. The physical properties of the relativistic outflow are calculated. Assuming a redshift
z
= 1.4, the bulk Lorentz factors Γ of the shells are found to be between
274
−
18
+
24
and
827
−
71
+
100
, and the corresponding photosphere radii
R
ph
are in the range of
1.83
−
0.50
+
0.52
×
10
11
and
2.97
−
0.15
+
0.14
×
10
12
cm. Similar to GRB 090902B, the time-resolved properties of GRB 220426A satisfy the observed Γ–
L
and
E
p
–
L
correlations, where
L
is the luminosity of the prompt emission and
E
p
is the spectral peak energy.
The quorum sensing (QS) system controls bacterial biofilm formation, which is highly related to the virulence and resistance of pathogens. In the present study, the effect of two traditional Chinese ...medicine (TCM) monomers, berberine and matrine, on biofilm formation and QS-related gene expression of antimicrobial-resistant (AMR)
Escherichia coli
strains was investigated by laser scanning confocal microscopy (LSCM) observation and real-time PCR. The results indicated a roughly positive relationship between biofilm formation ability and antimicrobial resistance. LSCM observation showed that berberine and matrine inhibited biofilm formation of AMR
E. coli
strains at 1/2 minimal inhibitory concentration (MIC) (1/2 MIC berberine at OD
630
: 0.1020; 1/2 MIC matrine: OD
630
: 0.1045); furthermore, abnormal cell morphology such as rounded and elongated cells was also observed. This finding was consistent with the downregulation of QS-related genes:
luxS
,
pfS
,
sdiA
,
hflX
,
motA
, and
fliA
. At 1/2 MIC and 1/4 MIC concentrations of berberine, a significant downregulation of
luxS
,
pfS
,
hflX
,
ftsQ
, and
ftsE
was observed. The results indicate that berberine and matrine can inhibit biofilm formation by inhibiting the QS system and that berberine is more effective than matrine.
During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in ...other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences.
Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined.
At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7
44.9 years), had more cases with comorbidity (32.9%
19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7
4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0%
11.1%, death rate 7.3%
0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4
4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)).
There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.
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