ABSTRACT
Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Induction of ACE2 expression may represent an effective tactic employed by SARS-CoV-2 to facilitate its own propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. By employing an array of 45 different luciferase reporters, we identify that the transcription factor Sp1 positively and HNF4 negatively regulate the expression of ACE2 at the transcriptional levels in HPAEpiC cells, a human lung epithelial cell line. SARS-CoV-2 infection promotes and inhibits the transcription activity of Sp1 and HNF4, respectively. The PI3K/AKT signaling pathway, which is activated by SARS-CoV-2 infection, is a crucial node for induction of ACE2 expression by increasing Sp1 phosphorylation, an indicator of its activity, and reducing HNF4 nuclear location. Furthermore, we show that colchicine could inhibit the PI3K/AKT signaling pathway, thereby suppressing ACE2 expression. Inhibition of Sp1 by either its inhibitor mithramycin A or colchicine reduces viral replication and tissue injury in Syrian hamsters infected with SARS-CoV-2. In summary, our study uncovers a novel function of Sp1 in regulating ACE2 expression and suggests that Sp1 is a potential target to reduce SARS-CoV-2 infection.
Subject(s)
Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
OBJECTIVE: To investigate the diagnosis and clinical characteristics of 10 cases of clustered Chlamydia pneumoniae pneumonia during the prevention and control of the COVID-19 pandemic. METHODS: The clinical data of 10 patients with clustered Chlamydia pneumoniae infection in a college diagnosed and treated by the Third Medical Center of the PLA General Hospital from Mar. 10, 2021 to Mar. 17, 2021 were retrospectively analyzed, the clinical characteristics of Chlamydia pneumoniae infection were summarized, and the diagnosis and treatment plan was selected quickly and accurately. RESULTS: All 10 cases with Chlamydia pneumoniae pneumonia infection had no history of contact with live or dead birds, 80% of them had cough symptom, 50% of them had fever symptom. Laboratory test results showed that 80% of patients had white blood cell count in normal range, 60% of patients had increased c-reactive protein level to varying degrees, 70% of patients had creatine kinase above normal, creatinine and procalcitonin were all normal, and some coagulation function indexes were abnormal. Lung CT scan showed increased density of unilateral lung floccus, nodules or spots, with air bronchial signs and even consolidation. The results of respiratory tract five-link card showed that all 10 patients were positive for Chlamydia pneumoniae immunoglobulin M(IgM) antibody. The nucleic acid sequence of Chlamydia pneumoniae was detected by metagenomics next-generation sequencing(mNGS)in 2 patients after hospitalization. 10 patients were treated with moxifloxacin hydrochloride and sodium chloride injection and moxifloxacin hydrochloride tables in sequences, all of which were cured. After 1 month, the outpatient reexamination of lung CT showed that the inflammation was basically absorbed. CONCLUSION: Chlamydia pneumoniae infection can cause outbreak through respiratory transmission, which tend to occur in the spring. The combination of respiratory pathogen antibody detection and mNGS technology can improve the efficiency of clinical diagnosis and treatment.
ABSTRACT
Scutellaria baicalensis Georgi is a medicinal plant commonly used in China and other parts of East Asia. A high flavonoid content endows it with multiple beneficial biological activities that have anti-inflammatory, antibacterial, antiviral, and anti-COVID19 properties. Light-emitting diodes (LEDs) have been recognized as effective artificial lights to enhance plant growth and the accumulation of secondary metabolites for commercial plant production. However, little is known regarding the effects of LEDs on S. baicalensis. Here, we explored the effects of monochromatic blue light (B, 460 nm), monochromatic red light (R, 660 nm), white light (CK), and different combinations of R and B (R9B1, R7B3, R5B5, R3B7, and R1B9) on the growth of, and flavonoid accumulation in S. baicalensis. The results revealed that under R:B ratios of 9:1 or 7:3, the whole plant and roots of S. baicalensis seedlings had a higher biomass and flavonoid content. Targeted metabolomics analysis showed that 48 differentially expressed metabolites (DEMs) were verified between different groups, and the number of upregulated DEMs, particularly flavonoids, were higher in the R9B1 and R7B3 groups compared with the CK. Transcriptome data identified 1412 and 1508 differentially expressed genes (DEGs) in the R9B1 and R7B3 groups, respectively, in contrast to the CK. KEGG pathway analysis indicated that DEGs in both the R9B1 and R7B3 groups were primarily enriched in the phenylpropane biosynthesis, plant hormone signal transduction, flavonoid biosynthesis, starch and sucrose metabolism, galactose metabolism, cartenoid biosynthesis, zeatin biosynthesis, and nitrogen metabolism pathways. The qRT-PCR results showed that SbPAL, SbCLL-7, SbCHI, SbFNS, and SbOMT encoding enzymes for the flavonoid biosynthesis pathway were significantly upregulated in S. baicalensis, which was consistent with the transcriptome data. Finally, based on correlation analysis between the main flavonoids in S. baicalensis and the genes encoding transcription factors and enzymes for the flavonoid metabolism pathway, a co-expression network map was developed, which provided a basis for the mining of light responsive genes related to flavonoids biosynthesis in S. baicalensis. This is the first report to articulate how the combination of red light and blue light influences the growth and secondary metabolism of S. baicalensis.
ABSTRACT
This study investigates the transport of air pollutants around the Yangtze River Delta with an aim to identify if there would be a relationship towards health effects during the COVID-19 lockdown period. It is well-known that due to lockdown, the number of socio-economical activities are reduced and hence there is an observable reduction in air pollution. We would like to investigate if this consequential reduction of air pollution would lead to improvement in health amongst its population. A number of integrated methodologies are utilized, including collection and correlation of statistical data and numerical modeling to correlate the mortality rates difference with and without COVID-19 lockdown. In particular air quality changes during the COVID-19 lockdown period are compared with similar periods of the previous years using Brute Force Method. It is found that in general there is significant reduction in air-pollution related mortality, like stroke, ischemic cardio diseases, obstructive pulmonary disease, lung cancer and acute lower respiratory infection are all reduced as a result of relative improvement in PM2.5 level during the lockdown period. Further investigation of the trajectories suggests that these PM2.5 originate from afar with multiple sources, and do not suggest COVID-19 are transported to the region via long-range transport. Our results demonstrate the need for more stringent policy measure to tackle air pollution as it has strong evidence that it increases mortality rate.