An improved numerical model for epidemic transmission and infection risks assessment in indoor environment

Social distance will remain the key measure to contain COVID-19 before the global widespread vaccination coverage expected in 2024. Containing the virus outbreak in the office is prioritised to relieve socio-economic burdens caused by COVID-19 and potential pandemics in the future. However, “what is the transmissible distance of SARS-CoV-2” and “what are the appropriate ventilation rates in the office” have been under debate. Without quantitative evaluation of the infection risk, some studies challenged the current social distance policies of 1–2 m adopted by most countries and suggested that longer social distance rule is required as the maximum transmission distance of cough ejected droplets could reach 3–10 m. With the emergence of virus variants such as the Delta variant, the applicability of previous social distance rules are also in doubt. To address the above problem, this study conducted transient Computational Fluid Dynamics (CFD) simulations to evaluate the infection risks under calm and wind scenarios. The calculated Social Distance Index (SDI) indicates that lower humidity leads to a higher infection risk due to weaker evaporation. The infection risk in office was found more sensitive to social distance than ventilation rate. In standard ventilation conditions, social distance of 1.7 m–1.8 m is sufficient distances to reach low probability of infection (PI) target in a calm scenario when coughing is the dominant transmission route. However in the wind scenario (0.25 m/s indoor wind), distance of 2.8 m is required to contain the wild virus type and 3 m is insufficient to contain the spread of the Delta variant. The numerical methods developed in this study provide a framework to evaluate the COVID-19 infection risk in indoor environment. The predicted PI will be beneficial for governments and regulators to make appropriate social-distance and ventilation rules in the office

Rapamycin attenuated the inflammatory cell infiltration after LAD ligation.

<p>The representative images and statistical result of immunohistochemical assay of the infarct border zone of different time points after LAD ligation to test the infiltration of CD45⁺ leukocytes, including CD68⁺ macrophages (n = 5, *<i>P</i><0.05 <i>vs</i> Sham; #<i>P</i><0.05 <i>vs</i> CTL). Sham, mice without LAD ligation; CTL, LAD ligation with saline; Rapa, LAD ligation with Rapamycin treatment; 3MA, LAD ligation with 3MA treatment.</p

Impaired Autophagy Contributes to Adverse Cardiac Remodeling in Acute Myocardial Infarction

<div><p>Objective</p><p>Autophagy is activated in ischemic heart diseases, but its dynamics and functional roles remain unclear and controversial. In this study, we investigated the dynamics and role of autophagy and the mechanism(s), if any, during postinfarction cardiac remodeling.</p><p>Methods and results</p><p>Acute myocardial infarction (AMI) was induced by ligating left anterior descending (LAD) coronary artery. Autophagy was found to be induced sharply 12–24 hours after surgery by testing LC3 modification and Electron microscopy. P62 degradation in the infarct border zone was increased from day 0.5 to day 3, and however, decreased from day 5 until day 21 after LAD ligation. These results indicated that autophagy was induced in the acute phase of AMI, and however, impaired in the latter phase of AMI. To investigate the significance of the impaired autophagy in the latter phase of AMI, we treated the mice with Rapamycin (an autophagy enhancer, 2.0 mg/kg/day) or 3-methyladenine (3MA, an autophagy inhibitor, 15 mg/kg/day) one day after LAD ligation until the end of experiment. The results showed that Rapamycin attenuated, while 3MA exacerbated, postinfarction cardiac remodeling and dysfunction respectively. In addition, Rapamycin protected the H9C2 cells against oxygen glucose deprivation <i>in vitro</i>. Specifically, we found that Rapamycin attenuated NFκB activation after LAD ligation. And the inflammatory response in the acute stage of AMI was significantly restrained with Rapamycin treatment. <i>In vitro</i>, inhibition of NFκB restored autophagy in a negative reflex.</p><p>Conclusion</p><p>Sustained myocardial ischemia impairs cardiomyocyte autophagy, which is an essential mechanism that protects against adverse cardiac remodeling. Augmenting autophagy could be a therapeutic strategy for acute myocardial infarction.</p></div

The effect of autophagy against oxygen glucose deprivation in the H9C2 cells <i>in vitro</i>.

<p><b>A</b>, Rapamycin induced LC3 modification in the H9C2 cells after OGD tested by Western blotting (n = 4). MTT assay (<b>B</b>) and trypan blue staining (<b>C</b>) to test the effect of different concentrations of Rapamycin on the cell survival after OGD for 24 hours (n = 8, *<i>P</i><0.05 <i>vs</i> OGD without Rapamycin). <b>D</b>, MTT assay to test the effect of Rapamycin and 3MA on the cell survival after OGD for different time (n = 8, *<i>P</i><0.05 <i>vs</i> OGD). <b>E</b>, The protein expression of ATG5 and LC3 after transfection of si<i>ATG5</i> in the H9C2 cells tested by Western blotting (n = 5, *<i>P</i><0.05 <i>vs</i> NC). <b>F</b>, The effect of si<i>ATG5</i> on the cell survival after OGD for different time in the H9C2 cells tested by MTT assay (n = 8, *<i>P</i><0.05 <i>vs</i> NC). <b>G</b>, The representative images and the analysis result of TUNEL staining in the H9C2 cells to test the effect of Rapamycin on cell apoptosis after OGD (n = 6, *<i>P</i><0.05 <i>vs</i> CTL, #<i>P</i><0.05 <i>vs</i> OGD). CTL, normal control; OGD, oxygen glucose deprivation; C+Rapa, normal control with Rapamycin treatment; O+Rapa, OGD with Rapamycin treatment. C+3MA, normal control with 3MA treatment; O+3MA, OGD with 3MA treatment. NC, negative control.</p

The effect of autophagy in the cardiac function and remodeling after AMI.

<p><b>A</b>, Rapamycin induced LC3 modification in the heart tissue (n = 4, *<i>P</i><0.05 <i>vs</i> CTL). <b>B</b>, the representative images and analysis results of echocardiographic assessment of hearts subjected to LAD ligation. (n = 8, *<i>P</i><0.05 <i>vs</i> Sham; #<i>P</i><0.05 <i>vs</i> CTL). <b>C</b>, the representative images and analysis results of TTC staining assessment of the hearts subjected AMI (n = 5, *<i>P</i><0.05 <i>vs</i> Sham; #<i>P</i><0.05 <i>vs</i> CTL). <b>D</b>, the representative images of Masson’s trichrome staining assessment of the infarct border zone at different time points after LAD ligation. Sham, mice without LAD ligation; CTL, LAD ligation with saline; Rapa, LAD ligation with Rapamycin treatment; 3MA, LAD ligation with 3MA treatment.</p

Rapamycin inhibited NFκB activation after myocardial ischemia and inhibition of NFκB activated autophagy in return.

<p><b>A</b>, Rapamycin inhibited NFκB phosphorylation in the border zone of ischemic hearts tested by Western blotting (n = 5, *<i>P</i><0.05 <i>vs</i> Sham; #<i>P</i><0.05 <i>vs</i> CTL). <b>B</b>, The effect of Rapamycin on nuclear p65 and cytoplasm IκBα of the H9C2 cells after OGD tested by Western blotting (n = 5, *<i>P</i><0.05 <i>vs</i> CTL; #<i>P</i><0.05 <i>vs</i> OGD). <b>C</b>, The effect of Rapamycin on p65 translocation to the nuclei in the H9C2 cells after OGD tested by immunostaining assay. <b>D</b>, The effect of Rapamycin on the transcriptional activity of NFκB in the H9C2 cells after OGD (n = 6, *<i>P</i><0.05 <i>vs</i> CTL; #<i>P</i><0.05 <i>vs</i> OGD). <b>E and F</b>, inhibition of NFκB upregulated LC3 protein modification in the H9C2 cells 4 hours after oxygen glucose deprivation for by Western blot (E) and Immunostaining assay (F) (*<i>P</i><0.05 <i>vs</i> OGD, n = 6) OGD, oxygen glucose deprivation; CTL, normal control with serum and oxygen; C+Rapa, normal control with Rapamycin treatment; O+Rapa, OGD with Rapamycin treatment.</p