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Upper-room ultraviolet germicidal irradiation (UVGI) technology can potentially inhibit the transmission of airborne disease pathogens. There is a lack of quantitative evaluation of the performance of the upper-room UVGI for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) airborne transmission under the combined effects of ventilation and UV irradiation. Therefore, this study aimed to explore the performance of the upper-room UVGI system for reducing SARS-CoV-2 virus transmission in a hospital isolation environment. Computational fluid dynamics and virological data on SARS-CoV-2 were integrated to obtain virus aerosol exposure in the hospital isolation environment containing buffer rooms, wards and bathrooms. The UV inactivation model was applied to investigate the effects of ventilation rate, irradiation flux and irradiation height on the upper-room UVGI performance. The results showed that increasing ventilation rate from 8 to 16 air changes per hour (ACH) without UVGI obtained 54.32% and 45.63% virus reduction in the wards and bathrooms, respectively. However, the upper-room UVGI could achieve 90.43% and 99.09% virus disinfection, respectively, with the ventilation rate of 8 ACH and the irradiation flux of 10 µW cm-2. Higher percentage of virus could be inactivated by the upper-room UVGI at a lower ventilation rate; the rate of improvement of UVGI elimination effect slowed down with the increase of irradiation flux. Increase irradiation height at lower ventilation rate was more effective in improving the UVGI performance than the increase in irradiation flux at smaller irradiation height. These results could provide theoretical support for the practical application of UVGI in hospital isolation environments.
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Suspected and confirmed cases of infectious diseases such as COVID-19 are diagnosed and treated in specific hospital isolation wards, posing a challenge to preventing cross-infection between patients and healthcare workers. In this study, the Euler-Lagrange method was used to simulate the evaporation and dispersion of droplets with full-size distribution produced by fluctuating coughing and breathing activities in an isolation ward. The effects of supply air temperature and relative humidity, ventilation rates and patient postures on droplet distribution were investigated. The numerical models were validated by an aerosol experiment with an artificial saliva solution containing E. coli bacteria conducted in a typical isolation ward. The results showed that the small size group of droplets (initial size ≤87.5 µm) exhibited airborne transmission in the isolation ward, while the large size group (initial size ≥112.5 µm) were rapidly deposited by gravitational effects. The ventilation rate had a greater effect on the diffusion of droplet nuclei than the supply air temperature and relative humidity. As the air changes per hour (ACH) increased from 8 to 16, the number fraction of suspended droplet nuclei reduced by 14.2% and 6.4% in the lying and sitting cases, respectively, while the number fraction of escaped droplet nuclei increased by 16.2% and 14.6%. Regardless of whether the patient was lying or sitting, the amount of droplet nuclei deposited on the ceiling was highest at lower ventilation rates. These results may provide some guidance for routine disinfection and ventilation strategies in hospital isolation wards.
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The health of intra-urban population in modern megacities relies largely on the biosafety within the microclimate of subway system, which can be vulnerable to epidemical challenges brought by virus-laden bioaerosols under varying factors. The literature has yet to address the association between the exposure risks to infectious pathogens and the dynamic changes of boundary conditions in this densely populated microclimate. This study aims at characterizing the bioaerosol dispersion, evaluating the exposure risks under various train arrival scenarios and hazard releasing positions in a real-world double-decker subway station. The results provide the evidence for the dominating airflow pattern, bioaerosols dispersion behaviors, exposure risk, and evacuation guidance in a representative microclimate of mega-cities. The tunnel effects of nearby pedestrian passageways are found to be dominating the airflow pattern, leading to the discharging of airborne bioaerosols. At least 60 % increasing of discharging rate of bioaerosol is attributed to the arrival of one or two trains at the subway platform compared with the scenario with no train arriving. Results from risk assessment with improved Wells-Riley model estimate 57.62 % of maximum infectivity probability with no train arriving. Large areas near the source at the platform floor still cannot be considered safe within 20 min. For the other two scenarios where trains arrive at the platform, the maximum probability of infection is below 5 %. Moreover, the majority of train carriages can be regarded as safe zones, as the ventilation across the screen door are mostly directed towards the platform. Additionally, releasing the bioaerosols at the platform floor poses the most severe threats to human health, and the corresponding evacuation strategies are suggested. These findings offer practical guidance for the design of the intra-urban microclimate, reinforcing the need for exposure reduction device or contingency plans, and providing potential evacuation strategy towards improved health outcomes.
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Poluentes Atmosféricos , Ferrovias , Humanos , Poluentes Atmosféricos/análise , Cidades , Microclima , Aerossóis/análise , Microbiologia do ArRESUMO
The frequency characteristics of lung sounds have great significance for noninvasive diagnosis of respiratory diseases. The rales in the lower respiratory tract region that can provide rich information about symptoms of respiratory diseases are not clear. In this paper, a three-dimensional idealized bifurcated lower respiratory tract geometric model, which contains 3rd to 13th generation (G3-G13) bronchi is constructed, where Re â¼ 10 1 - 10 3 , and then the large eddy simulation and volume of fluid are used to study the fluid flow characteristics. Ffowcs Williams and Hawkings model are subsequently used to study the frequency characteristics of rale of different generations of bronchi. The results showed that bronchial blockage and sputum movement will enhance the turbulence intensity and vortex shedding intensity of flow. The dominant frequency and highest value of sound pressure level (SPL) of rhonchi/moist crackles decrease with the increase of bronchial generation. The change rates of dominant frequency of rhonchi / moist crackles in adjacent generations were 5.0 ± 0.1 ~ 9.1 ± 0.2% and 3.1 ± 0.1 ~ 11.9 ± 0.3%, respectively, which is concentrated in 290 ~ 420 Hz and 200 ~ 300 Hz, respectively. The change rates of SPL of rhonchi/moist crackles were 8.8 ± 0.1 ~ 15.7 ± 0.1% and 7.1 ± 0.1 ~ 19.5 ± 0.2%, respectively, which is concentrated in 28 ~ 50 dB and 16 ~ 32 dB, respectively. In the same generation of bronchus (e.g., G8, G9) with the same degree of initial blockage, the dominant frequency and SPL of moist crackles can be 3.7 ± 0.2% and 4.5 ± 0.3% slightly higher than that of rhonchi, respectively. This research is conducive to the establishment of a rapid and accurate noninvasive diagnosis system for respiratory diseases.
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Sons Respiratórios , Doenças Respiratórias , Humanos , Sons Respiratórios/diagnóstico , Brônquios , Simulação por ComputadorRESUMO
Glycoside hydrolases (GHs) are industrially important enzymes that hydrolyze glycosidic bonds in glycoconjugates. In this study, we found a GH3 ß-glucosidase (CcBgl3B) from Cellulosimicrobium cellulans sp. 21 was able to selectively hydrolyze the ß-1,6-glucosidic bond linked glucose of ginsenosides. X-ray crystallographic studies of the ligand complex ginsenoside-specific ß-glucosidase provided a novel finding that support the catalytic mechanism of GH3. The substrate was clearly identified within the catalytic center of wild-type CcBgl3B, revealing that the C1 atom of the glucose was covalently bound to the Oδ1 group of the conserved catalytic nucleophile Asp264 as an enzyme-glycosyl intermediate. The glycosylated Asp264 could be identified by mass spectrometry. Through site-directed mutagenesis studies with Asp264, it was found that the covalent intermediate state formed by Asp264 and the substrate was critical for catalysis. In addition, Glu525 variants (E525A, E525Q and E525D) showed no or marginal activity against pNPßGlc; thus, this residue could supply a proton for the reaction. Overall, our study provides an insight into the catalytic mechanism of the GH3 enzyme CcBgl3B.
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Glicosídeo Hidrolases , beta-Glucosidase , Raios X , Hidrólise , Modelos Moleculares , beta-Glucosidase/química , Glicosídeo Hidrolases/química , Glucose/metabolismo , Catálise , Cristalografia por Raios X , Especificidade por SubstratoRESUMO
Frequent toxic gas leakage accidents in urban environments cannot be timely controlled and often cause great harm due to the many factors affecting gas diffusion. In this study, based on the coupling method of the Weather Research and Forecasting Model (WRF) and the open source OpenFOAM software platform, the chlorine gas diffusion process at different temperatures, wind speeds, and wind directions in a chemical laboratory and nearby urban areas in Beijing was studied numerically. A dose-response model was used to calculate chlorine lethality and assess exposure risk at the pedestrian level. To predict the evacuation path, an improved ant colony algorithm, a greedy heuristic search algorithm based on the dose-response model, was applied. The results demonstrated that the combination of WRF and OpenFOAM could consider the effects of various factors such as temperature, wind speed, and wind direction on the diffusion of toxic gases. The direction of chlorine gas diffusion was affected by wind direction, and the range of chlorine gas diffusion was affected by temperature and wind speed. The area of high exposure risk (fatality rate above 40%) at high temperatures was 21.05% larger than that at low temperatures. When the wind direction was opposite the building, the high exposure risk area was 78.95% smaller than that under the building direction. The present work provides a promising approach for exposure risk assessment and evacuation planning for the emergency response to urban toxic gas leakage.
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Mounting interest in modeling outdoor diffusion and transmission of bioaerosols due to the prevalence of COVID-19 in the urban environment has led to better knowledge of the issues concerning exposure risk and evacuation planning. In this study, the dispersion and deposition dynamics of bioaerosols around a vaccine factory were numerically investigated under various thermal conditions and leakage rates. To assess infection risk at the pedestrian level, the improved Wells-Riley equation was used. To predict the evacuation path, Dijkstra's algorithm, a derived greedy algorithm based on the improved Wells-Riley equation, was applied. The results show that, driven by buoyancy force, the deposition of bioaerosols can reach 80 m on the windward sidewall of high-rise buildings. Compared with stable thermal stratification, the infection risk of unstable thermal stratification in the upstream portion of the study area can increase by 5.53% and 9.92% under a low and high leakage rate, respectively. A greater leakage rate leads to higher infection risk but a similar distribution of high-risk regions. The present work provides a promising approach for infection risk assessment and evacuation planning for the emergency response to urban bioaerosol leakage.
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Considering the significance of multipath transmissions of respiratory pathogens in the post-epidemic era, surprisingly little is acknowledged regarding the susceptibility, short-term aerodynamics, and exposure risk of children in indoor environments. Here, experimental and computational investigations were conducted to evaluate the exposure risks associated with respiratory pathogens. The dominant effect of recirculation structure originating from indoor ventilation, including air supply modes and air change rate, on aerosol dispersion was quantitatively proved. A large proportion of deposited aerosol particles was captured by the human body, and deposited particles may further increase under high air change rate, which required a balanced ventilation strategy. Little discrepancies existed between adults and children in exposure risk by airborne transmission. The infection probability by contact transmission for children, however, may be surprisingly high due to high frequency in interactive activities, deposition on upper and lower limbs of accompanying parents, and the wall within arm span.
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With the recognition of the multiple advantages of sulfonated hydrocarbon-based polymers that possess high chemical and mechanical stability with significant low cost, we employed molecular dynamics simulation to explore the morphological effects of side chain length in sulfonated polystyrene grafted poly(arylene ether sulfone)s (SPAES) proton exchange membranes. The calculated diffusion coefficients of hydronium ions (H3O+) are in range of 0.61-1.15 × 10-7 cm2/s, smaller than that of water molecules, due to the electrical attraction between the oppositely charged sulfonate group and H3O+. The investigation into the radial distribution functions suggests that phase segregation in the SPAES membrane is more probable with longer side chains. As the hydration level of the membranes in this study is relatively low (λ = 3), longer side chains correspond to more water molecules in the amorphous cell, which provides better solvent effects for the distribution of sulfonated side chains. The coordination number of water molecules and hydronium ions around the sulfonate group increases from 1.67 to 2.40 and from 2.45 to 5.66, respectively, with the increase in the side chain length. A significant proportion of the hydronium ions appear to be in bridging configurations coordinated by multiple sulfonate groups. The microscopic conformation of the SPAES membrane is basically unaffected by temperature during the evaluated temperature range. Thus, it can be revealed that the side chain length plays a key role in the configuration of the polymer chain and would contribute to the formation of the microphase separation morphology, which profits proton transport in the hydrophilic domains.
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(1) Background: The glucocorticoid receptor (GR) plays a key role in lipid metabolism, but investigations of GR activation as a potential therapeutic approach have been hampered by a lack of selective agonists. Ginsenoside compound K (CK) is natural small molecule with a steroid-like structure that offers a variety of therapeutic benefits. Our study validates CK as a novel GR agonist for the treatment of obesity. (2) Methods: By using pulldown and RNA interference, we determined that CK binds to GR. The anti-obesity potential effects of CK were investigated in obese mice, including through whole-body energy homeostasis, glucose and insulin tolerance, and biochemical and proteomic analysis. Using chromatin immunoprecipitation, we identified GR binding sites upstream of lipase ATGL. (3) Results: We demonstrated that CK reduced the weight and blood lipids of mice more significantly than the drug Orlistat. Proteomics data showed that CK up-regulated autophagy regulatory proteins, enhanced fatty acid oxidation proteins, and decreased fatty acid synthesis proteins. CK induced lipophagy with the initial formation of the phagophore via AMPK/ULK1 activation. However, a blockade of autophagy did not disturb the increase in CK on lipase expression, suggesting that autophagy and lipase are independent pathways in the function of CK. The pulldown and siRNA experiments showed that GR is the critical target. After binding to GR, CK not only activated lipophagy, but also promoted the binding of GR to the ATGL promoter. (4) Conclusions: Our findings indicate that CK is a natural food candidate for reducing fat content and weight.
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A method using UPLC-HRMS has been developed for a rapid, simultaneous qualitative and quantitative analysis of twenty-five ginsenosides. Chromatographic separation was achieved on a C18 analytical column with an elution gradient comprising 0.1% aqueous formate/acetonitrile as the mobile phase. HRMS detection acquired full mass data for quantification and fullms-ddms2 (i.e., data-dependent scan mode) yielded product ion spectra for identification. Furthermore, quantitative analysis of multiginsenosides by single marker (QAMS) was developed and validated using a relative correction factor. Under optimal conditions, we could simultaneously separate eight groups of isomers of the 25 ginsenosides. Good linearity was observed over the validated concentration range for each analyte (r 2 > 0.9924), showing excellent sensitivity (LODs, 0.003-0.349 ng/mL) and lower limit quantification (LOQs, 0.015-1.163 ng/mL). The LC-MS external standard method (ESM) and QAMS were compared and successfully applied to analyze the ginsenoside content from Panax ginseng roots. Overall, our UPLC-HRMS/QAMS approach provides high precision, stability, and reproducibility and can be used for high-throughput analysis of complex ginsenosides and quantitative analysis of multiple components and quality control of traditional Chinese medicines (TCM).
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BACKGROUND: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. METHODS: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. RESULTS: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca2+/calmodulin-dependent protein kinase II. CONCLUSION: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.