•Rural residents in central China were exposed to high levels of PM1.•PM1 exposure was related to increased TC and LDL-C, and decreased TG and HDL-C.•High levels of PM1 was associated with higher ...risk of dyslipidemias.•Males, older and overweight participants were vulnerable to adverse effects of PM1.
Air pollution has been shown to be associated with blood lipid levels. However, studies on long-term ambient particulate matter with aerodynamic diameter ≤1 μm (PM1) exposure in high-exposure areas are still limited. This study aimed to explore the associations among long-term PM1 exposure, blood lipids and dyslipidemias.
Baseline data of The Henan Rural Cohort study was used in present study, including a total of 39,259 participants aged from 18 to 79 years. Daily levels of PM1 were estimated by a spatiotemporal model using ground-level measurements of PM1, satellite remote sensing data and other predictors, according to participants' home addresses. Individual exposure to PM1 was the 3-year average before baseline investigation. Linear regression and logistic regression models were applied to examine the associations among PM1, blood lipids ((total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)), and prevalence of dyslipidemias.
The 3-year concentration of PM1 was 55.7 ± 2.1 μg/m3. Each 1 μg/m3 increment of PM1 was associated with an increase of 0.21% (95% confidence interval (CI): 0.11%–0.31%) in TC and 0.75% (95% CI: 0.61%–0.90%) in LDL-C, while decrease of 2.68% (95% CI: 2.43%–2.93%) in TG and 0.47% (95% CI: 0.35%–0.59%) in HDL-C. Each 1 μg/m3 increase in PM1 was associated with 6% (95% CI: 4%–8%), 3% (95% CI: 2%–5%) and 5% (95% CI: 3%–7%) higher risks of hypercholesterolemia, hyperbetalipoproteinemia and hypoalphalipoproteinemia. Sex, age and BMI statistically modified the associations between PM1 with blood lipid levels and dyslipidemias.
Higher PM1 exposure was associated with adverse changes of blood lipid levels and dyslipidemias. Males, older and overweight participants were susceptive to the adverse effects of PM1.
RAG1-deficient mice are a frequently used immunodeficient mouse strain lacking mature lymphocytes. Apart from an elevated risk for infections, no predispositions for diseases of this strain have been ...described so far. We here report a high incidence of spontaneous pro B cell leukemia resulting in hind limb paralysis in our colony of RAG1-deficient mice. At an age of 7–13 months, animals developed hind limb paralysis and rapid decrease of the overall health condition leading to the need of euthanasia. Histological and flow cytometric analyses as well as micro-computed tomography (micro-CT) scans revealed CD45
+
CD19
+
IgM
−
cell infiltrates in the spleen, the bone marrow, and the spinal canal. Monthly blood sampling and screening for CD19
+
blast frequency in the peripheral blood was successfully established for monitoring of leukemia development before symptom onset. We conclude that facilities that breed RAG1-deficient mice should be aware of the risk of leukemia development in this strain and recommend to implement regular blood sampling for aged RAG1-deficient animals.
Abstract
Background
Coronavirus disease 2019 (COVID-19) is primarily an acute respiratory tract infection. Distinctively, a substantial proportion of COVID-19 patients develop olfactory dysfunction. ...Especially in young patients, loss of smell can be the first or only symptom. The roles of inflammatory obstruction of the olfactory clefts, inflammatory cytokines affecting olfactory neuronal function, destruction of olfactory neurons or their supporting cells, and direct invasion of olfactory bulbs in causing olfactory dysfunction are uncertain.
Methods
We investigated the location for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the olfactory epithelium (OE) to the olfactory bulb in golden Syrian hamsters.
Results
After intranasal inoculation with SARS-CoV-2, inflammatory cell infiltration and proinflammatory cytokine/chemokine responses were detected in the nasal turbinate tissues. The responses peaked between 2 and 4 days postinfection, with the highest viral load detected at day 2 postinfection. In addition to the pseudo-columnar ciliated respiratory epithelial cells, SARS-CoV-2 viral antigens were also detected in the mature olfactory sensory neurons labeled by olfactory marker protein, in the less mature olfactory neurons labeled by neuron-specific class III β-tubulin at the more basal position, and in the sustentacular cells, resulting in apoptosis and severe destruction of the OE. During the entire course of infection, SARS-CoV-2 viral antigens were not detected in the olfactory bulb.
Conclusions
In addition to acute inflammation at the OE, infection of mature and immature olfactory neurons and the supporting sustentacular cells by SARS-CoV-2 may contribute to the unique olfactory dysfunction related to COVID-19, which is not reported with SARS-CoV-2.
In addition to acute inflammation at the olfactory epithelium, infection of mature and immature olfactory neurons and of the supporting sustentacular cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may contribute to the unique olfactory dysfunction of coronavirus disease 2019, which is not reported with SARS-CoV.
TIMM13 (translocase of inner mitochondrial membrane 13) located at the mitochondrial intermembrane space is vital for the integrity and function of mitochondria. We found that the mitochondrial ...protein TIMM13 is upregulated in human OS tissues and cells. In patient-derived primary OS cells and established cell lines, TIMM13 shRNA or knockout provoked mitochondrial dysfunction, causing mitochondrial depolarization, reactive oxygen species production, and oxidative injury, as well as lipid peroxidation, DNA damage, and ATP depletion. Moreover, TIMM13 depletion provoked OS cell apoptosis and inhibited cell proliferation and migration. Conversely, ectopic TIMM13 overexpression increased ATP contents, enhancing OS cell proliferation and migration. Moreover, we discovered that Akt-mTOR activation was inhibited with TIMM13 depletion in primary OS cells. Further studies revealed that HOXC13 (Homeobox C13)-dependent TIMM13 transcription was significantly increased in OS tissues and cells. Whereas TIMM13 transcription and expression were decreased following HOXC13 silencing in primary OS cells. In vivo, TIMM13 KO potently inhibited OS xenograft growth in the proximal tibia of nude mice. TIMM13 KO also induced Akt-mTOR inactivation, ATP depletion, oxidative injury, and apoptosis in the in situ OS tumors. Together, upregulation of the mitochondrial protein TIMM13 is important for OS cell growth, representing a novel and promising therapeutic target.
Illumina's MiSeq has become the dominant platform for gene amplicon sequencing in microbial ecology studies; however, various technical concerns, such as reproducibility, still exist. To assess ...reproducibility, 16S rRNA gene amplicons from 18 soil samples of a reciprocal transplantation experiment were sequenced on an Illumina MiSeq. The V4 region of 16S rRNA gene from each sample was sequenced in triplicate with each replicate having a unique barcode. The average OTU overlap, without considering sequence abundance, at a rarefaction level of 10,323 sequences was 33.4±2.1% and 20.2±1.7% between two and among three technical replicates, respectively. When OTU sequence abundance was considered, the average sequence abundance weighted OTU overlap was 85.6±1.6% and 81.2±2.1% for two and three replicates, respectively. Removing singletons significantly increased the overlap for both (~1-3%, p<0.001). Increasing the sequencing depth to 160,000 reads by deep sequencing increased OTU overlap both when sequence abundance was considered (95%) and when not (44%). However, if singletons were not removed the overlap between two technical replicates (not considering sequence abundance) plateaus at 39% with 30,000 sequences. Diversity measures were not affected by the low overlap as α-diversities were similar among technical replicates while β-diversities (Bray-Curtis) were much smaller among technical replicates than among treatment replicates (e.g., 0.269 vs. 0.374). Higher diversity coverage, but lower OTU overlap, was observed when replicates were sequenced in separate runs. Detrended correspondence analysis indicated that while there was considerable variation among technical replicates, the reproducibility was sufficient for detecting treatment effects for the samples examined. These results suggest that although there is variation among technical replicates, amplicon sequencing on MiSeq is useful for analyzing microbial community structure if used appropriately and with caution. For example, including technical replicates, removing spurious sequences and unrepresentative OTUs, using a clustering method with a high stringency for OTU generation, estimating treatment effects at higher taxonomic levels, and adapting the unique molecular identifier (UMI) and other newly developed methods to lower PCR and sequencing error and to identify true low abundance rare species all can increase reproducibility.
Several epidemiological studies have evaluated the fractional exhaled nitric oxide (FeNO) of ambient air pollution but the results were controversial. We therefore conducted a systematic review and ...meta-analysis to investigate the associations between short-term exposure to air pollutants and FeNO level. We searched PubMed and Web of Science and included a total of 27 articles which focused on associations between ambient air pollutants (PM10, PM2.5, black carbon (BC), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3)) exposure and the change of FeNO. Random effect model was used to calculate the percent change of FeNO in association with a 10 or 1 μg/m3 increase in air pollutants exposure concentrations. A 10 μg/m3 increase in short-term PM10, PM2.5, NO2, and SO2 exposure was associated with a 3.20% (95% confidence interval (95%CI): 1.11%, 5.29%), 2.25% (95%CI: 1.51%, 2.99%),4.90% (95%CI: 1.98%, 7.81%), and 8.28% (95%CI: 3.61%, 12.59%) change in FeNO, respectively. A 1 μg/m3 increase in short-term exposure to BC was associated with 3.42% (95%CI: 1.34%, 5.50%) change in FeNO. The association between short-term exposure to O3 and FeNO level was insignificant (P＞0.05). Future studies are warranted to investigate the effect of multiple pollutants, different sources and composition of air pollutants on airway inflammation.
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•This meta-analysis investigated the association between air pollutants and FeNO.•High level of short-term exposure to PM and BC was associated with increased FeNO.•Short-term exposure to NO2 and SO2 was significant positively associated with FeNO.•The association between short-term exposure to O3 and FeNO was insignificant.
Abstract
Background
Clinical outcomes of the interaction between the co-circulating pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seasonal influenza viruses are unknown.
...Methods
We established a golden Syrian hamster model coinfected by SARS-CoV-2 and mouse-adapted A(H1N1)pdm09 simultaneously or sequentially. The weight loss, clinical scores, histopathological changes, viral load and titer, and serum neutralizing antibody titer were compared with hamsters challenged by either virus.
Results
Coinfected hamsters had more weight loss, more severe lung inflammatory damage, and tissue cytokine/chemokine expression. Lung viral load, infectious virus titers, and virus antigen expression suggested that hamsters were generally more susceptible to SARS-CoV-2 than to A(H1N1)pdm09. Sequential coinfection with A(H1N1)pdm09 one day prior to SARS-CoV-2 exposure resulted in a lower lung SARS-CoV-2 titer and viral load than with SARS-CoV-2 monoinfection, but a higher lung A(H1N1)pdm09 viral load. Coinfection also increased intestinal inflammation with more SARS-CoV-2 nucleoprotein expression in enterocytes. Simultaneous coinfection was associated with delay in resolution of lung damage, lower serum SARS-CoV-2 neutralizing antibody, and longer SARS-CoV-2 shedding in oral swabs compared to that of SARS-CoV-2 monoinfection.
Conclusions
Simultaneous or sequential coinfection by SARS-CoV-2 and A(H1N1)pdm09 caused more severe disease than monoinfection by either virus in hamsters. Prior A(H1N1)pdm09 infection lowered SARS-CoV-2 pulmonary viral loads but enhanced lung damage. Whole-population influenza vaccination for prevention of coinfection, and multiplex molecular diagnostics for both viruses to achieve early initiation of antiviral treatment for improvement of clinical outcome should be considered.
Coinfection of hamsters by 2020 pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 2009 pandemic influenza A(H1N1) virus given simultaneously or sequentially within 24 hours was associated with increased disease severity, delayed resolution of lung pathology, and suppressed neutralizing antibody response against SARS-CoV-2.
Pulse transit time (PTT) and blood pressure (BP) are widely used to quantify arterial characteristics. Arm position influences arterial BP and peripheral PTT. This study aims to quantify the ...relationship between PTT changes with internal vascular pressure variations induced by the arm moving. With left arm at horizontal position as reference and the right arm moving from 90 to 45, 0, -45, and -90° respectively, PTT difference was calculated by the difference of the pulse foot between right arm and left arm within the same heartbeat. The change in the BP was calculated from the gravitational effect with the measured arm length. Our results showed that the change in PTT with arm elevating is more obvious than that with arm lowering, indicating the different relationship between PTT changes due to the internal BP changes. This can help in understanding the inherent physiological/pathological mechanism of cardiovascular system.
To investigate whether driving pressure-guided ventilation could contribute to a more homogeneous distribution in the lung for gynecological laparoscopy. Chinese patients were randomized, after ...pneumoperitoneum, to receive either positive end expiratory pressure (PEEP) of 5 cm H
O (control group), or individualized PEEP producing the lowest driving pressure (titration group). Ventilation homogeneity is quantified as the global inhomogeneity (GI) index based on electrical impedance tomography, with a lower index implying more homogeneous ventilation. The perioperative arterial oxygenation index and respiratory system mechanics were also recorded. Blood samples were collected for lung injury biomarkers including interleukin-10, neutrophil elastase, and Clara Cell protein-16. A total of 48 patients were included for analysis. We observed a significant increase in the GI index immediately after tracheal extubation compared to preinduction in the control group (p = 0.040) but not in the titration group (p = 0.279). Furthermore, the GI index was obviously lower in the titration group than in the control group 0.390 (0.066) vs 0.460 (0.074), p = 0.0012. The oxygenation index and respiratory compliance were significantly higher in the titration group than in the control group. No significant differences in biomarkers or hemodynamics were detected between the two groups. Driving pressure-guided PEEP led to more homogeneous ventilation, as well as improved gas exchange and respiratory compliance for patients undergoing gynecological laparoscopy.Trial Registration: ClinicalTrials.gov NCT04374162; first registration on 05/05/2020.
Despite the widespread popularity of the Bhatnagar–Gross–Krook lattice Boltzmann (BGK-LB) model due to its simplicity and efficiency, its application in heat transfer involving non-Newtonian fluids ...(NNFs) has been limited by inherent constraints. This paper proposes a numerically stable BGK-LB model for the thermal flow of NNFs. The modified model incorporates the local shear rate into the equilibrium distribution function of the velocity field and addresses the numerical instability problems encountered in the traditional BGK-LB model under low viscosity conditions by introducing an additional parameter. In addition, a temperature evolution equation that can accurately recover the convective diffusion equation is adopted. The accuracy of the current method is validated by performing simulations of Rayleigh–Bénard convection (RBC) in a square cavity filled with Newtonian fluids and NNFs. Subsequently, simulations are conducted to investigate the behavior of RBC in power-law fluids. The analysis focuses on examining the impact of the Rayleigh number (Ra = 5 × 103 − 105) and the power-law index (n = 0.8–1.3) on the convective structure and heat transfer characteristics while maintaining a fixed Prandtl number (Pr = 7) and aspect ratio (L/H = 2). It is discovered that, for a given n value, the convection intensity and heat transfer rate increase with increasing Ra, which is supported by the increasing trend of the mean Nusselt number (Nū) with Ra. Furthermore, compared to NFs, pseudo-plastic fluids display a higher Nū value due to an augmented heat transfer rate, while dilatant fluids exhibit a lower Nū value owing to a diminished heat transfer rate.
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