Endothelial cell infection and dysfunction, immune activation in severe COVID-19.

Rationale: Pulmonary vascular endotheliitis, perivascular inflammation, and immune activation are observed in COVID-19 patients. While the initial SARS-CoV-2 infection mainly infects lung epithelial cells, whether it also infects endothelial cells (ECs) and to what extent SARS-CoV-2-mediated pulmonary vascular endotheliitis is associated with immune activation remain to be determined. Methods: To address these questions, we studied SARS-CoV-2-infected K18-hACE2 (K18) mice, a severe COVID-19 mouse model, as well as lung samples from SARS-CoV-2-infected nonhuman primates (NHP) and patient deceased from COVID-19. We used immunostaining, RNAscope, and electron microscopy to analyze the organs collected from animals and patient. We conducted bulk and single cell (sc) RNA-seq analyses, and cytokine profiling of lungs or serum of the severe COVID-19 mice. Results: We show that SARS-CoV-2-infected K18 mice develop severe COVID-19, including progressive body weight loss and fatality at 7 days, severe lung interstitial inflammation, edema, hemorrhage, perivascular inflammation, systemic lymphocytopenia, and eosinopenia. Body weight loss in K18 mice correlated with the severity of pneumonia, but not with brain infection. We also observed endothelial activation and dysfunction in pulmonary vessels evidenced by the up-regulation of VCAM1 and ICAM1 and the downregulation of VE-cadherin. We detected SARS-CoV-2 in capillary ECs, activation and adhesion of platelets and immune cells to the vascular wall of the alveolar septa, and increased complement deposition in the lungs, in both COVID-19-murine and NHP models. We also revealed that pathways of coagulation, complement, K-ras signaling, and genes of ICAM1 and VCAM1 related to EC dysfunction and injury were upregulated, and were associated with massive immune activation in the lung and circulation. Conclusion: Together, our results indicate that SARS-CoV-2 causes endotheliitis via both infection and infection-mediated immune activation, which may contribute to the pathogenesis of severe COVID-19 disease.

Analysis of flavonoids in Coreopsis tinctoria by integrating 2D-TLC and HPLC-IT-TOF-MS / 中国中药杂志

The qualitative analysis of flavonoids in Coreopsis tinctoria was carried out by a combination of 2 D-TLC and HPLC-IT-TOF-MS. The separation was conducted on 2 D-TLC and a Phenomenex Kinetex Evo C_(18) column(2.1 mm×100 mm, 2.6 μm) with methanol-0.05% aqueous formic acid by gradient elution. Electrospray ionization-(ESI) source was applied and operated in both positive and negative ionization modes. Eighteen flavonoids including three flavonoids, one flavonol, nine flavonones, one flavanonol and four chalcones, were putatively identified from the flavone-enriched fraction of C. tinctoria. 2 D-TLC could separate the flavonoids from C. tinctoria. HPLC-IT-TOF-MS was able to quickly and accurately analyze the flavonoids in C. tinctoria. The results would provide experimental information for the efficacy material basis clarification of C. tinctoria.

Anabolic Androgenic Steroid Use as a Cause of Fulminant Heart Failure.

A 39-year-old male weightlifter presented in fulminant heart failure. An echocardiogram revealed severe global biventricular failure. Left ventricular (LV) systolic function was estimated at 15%. His dilated cardiomyopathy was attributed to his use of both testosterone and boldenone in the 3-month period before his presentation. Although the deleterious effects of androgenic- anabolic steroids on diastolic function are well known, the effects of these drugs on systolic function is an area of ongoing investigation. Our case suggests that androgenic anabolic steroid use should be considered in the differential diagnosis of patients presenting with acute heart failure.

[Impact on electrochemical degradation of phenol with different coated electrodes and inhibitors].

Four lead dioxide electrodes on Ti substrates were prepared by thermal-deposition and electro-deposition. Scanning electron microscopy (SEM) was used to study the characterization of surface of electrodes. High performance liquid chromatograph was applied to detect the concentration of the aromatic hydroxylation 2,5-DHBA to determine the amount of .OH with 2-HBA as the capture matter. This study investigated effect of different coated electrodes and inhibitors on degradation of phenol by hydroxyl radicals generated by electrolysis in terms of the measurement of hydroxyl radicals and degradation of phenol. The experimental results show that the highest concentration of hydroxyl radicals generated by thermal-deposition, electro-deposition mingled with nothing, electro-deposition mingled with Bi or La were 0.781 micromol/L, 1.048 micromol/L, 1.838 micromol/L, 2.044 micromol/L, respectively. When phenol was electrolyzed by electrodes prepared by the four electrodes, the removal efficiencies of phenol at 1.5 h were 87.30%, 93.55%, 97.95% and 98.70%, and TOC removal efficiencies at 5 h were 86.76%, 94.26%, 98.53% and 99.60%, respectively. The highest concentration of hydroxyl radicals when CO3(2), PO4(3) or CH3COO-existed was no detected, 0.170 micromol/L, 0.270 micromol/L, and the removal efficiencies of phenol were 99.06%, 99.98% and 99.79%, respectively. The degradation of phenol with electrodes prepared by electro-deposition is better than the electrodes prepared by thermal-deposition, and the electrode mingled with La is better than the electrode mingled nothing and with Bi. The electrode mingled with La is the best. The degradation of phenol is inhibited when CO3(2-), PO4(3-) or CH3COO- exists, and the inhibiting effect of CO3(2-) is the strongest. The catalytic characteristics of electrodes and degradation of phenol by them are different when the electrodes are prepared by different methods or with different additives; the higher the concentration of hydroxyl is, the better the degradation of phenol is. Inhibitors capture hydroxyl radicals, and isn't in favor of degradation of phenol.