Mechanism of N-0385 blocking SARS-CoV-2 to treat COVID-19 based on molecular docking and molecular dynamics.

Purpose: 2019 Coronavirus disease (COVID-19) has caused millions of confirmed cases and deaths worldwide. TMPRSS2-mediated hydrolysis and maturation of spike protein is essential for SARS-CoV-2 infection in vivo. The latest research found that a TMPRSS2 inhibitor called N-0385 could effectively prevent the infection of the SARS-CoV-2 and its variants. However, it is not clear about the mechanism of N-0385 treatment COVID-19. Therefore, this study used computer simulations to investigate the mechanism of N-0385 treatment COVID-19 by impeding SARS-CoV-2 infection. Methods: The GeneCards database was used to search disease gene targets, core targets were analyzed by PPI, GO and KEGG. Molecular docking and molecular dynamics were used to validate and analyze the binding stability of small molecule N-0385 to target proteins. The supercomputer platform was used to simulate and analyze the number of hydrogen bonds, binding free energy, stability of protein targets at the residue level, radius of gyration and solvent accessible surface area. Results: There were 4,600 COVID-19 gene targets from GeneCards database. PPI, GO and KEGG analysis indicated that signaling pathways of immune response and inflammation played crucial roles in COVID-19. Molecular docking showed that N-0385 could block SARS-CoV-2 infection and treat COVID-19 by acting on ACE2, TMPRSS2 and NLRP3. Molecular dynamics was used to demonstrate that the small molecule N-0385 could form very stable bindings with TMPRSS2 and TLR7. Conclusion: The mechanism of N-0385 treatment COVID-19 was investigated by molecular docking and molecular dynamics simulation. We speculated that N-0385 may not only inhibit SARS-CoV-2 invasion directly by acting on TMPRSS2, ACE2 and DPP4, but also inhibit the immune recognition process and inflammatory response by regulating TLR7, NLRP3 and IL-10 to prevent SARS-CoV-2 invasion. Therefore, these results suggested that N-0385 may act through multiple targets to reduce SARS-CoV-2 infection and damage caused by inflammatory responses.

Mining Geological Environment Monitoring and Real-Time Transmission Based on Internet of Things Technology.

A landslide monitoring technology based on BeiDouand, a wireless sensor network, is proposed in order to solve the problem that landslide has brought severe threat to people's life and safety of property. The landslide monitoring system based on the BeiDouand wireless sensor network is analyzed and designed from the point of view of hardware and software. BeiDou message and GPRS double redundancy transmission mode are adopted to improve the reliability of transmission. It also adopts the factor compression method to improve the effectiveness of BeiDoutransmission and adopts queue management and packet scheduling mechanism to improve the real-time and reliability of wireless sensor network transmission. The result is that, as the number of visible satellites increases, the efficiency of the algorithm decreases. However, the overall efficiency of the algorithm has been significantly improved. When there are 28 visible satellites, the number of algorithm times decreases from 20,475 to 1,140, and the efficiency of the algorithm increases by 16.9 times. The GDOP simulated by the fast star selection algorithm proposed in this paper is less than 3.9, reaching an excellent grade.

Association between peripheral blood WBCs C3aR mRNA level and plasma C3a, C3aR, IL-1ß concentrations and acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: The relationship between C3a-C3aR, IL-1ß, and the acute exacerbation of chronic obstructive pulmonary disease is still unclear. This study aims to explore the expression levels of C3aR in peripheral blood WBCs and the concentrations of C3a, C3aR, and IL-1ß in plasma in healthy controls and patients with chronic obstructive pulmonary disease (COPD). METHODS: WBCs C3aR level in the peripheral blood, the concentrations of C3a, C3aR, and IL-1ß in plasma were measured in 60 patients with acute exacerbation of COPD (AECOPD), 30 patients with stable COPD (SCOPD), and 30 healthy controls. The baseline characteristics and clinical data collected from enrolled patients, including age, gender, laboratory indicators, and lung function. We analyzed the correlation between C3a, C3aR, IL-1ß, and lung function indicators (forced expiratory volume in the first second as a percentage of predicted value, FEV1%pred) in the AECOPD group. RESULTS: The white blood cell count (WBC), neutrophil/lymphocyte ratio (NLR), and C-reactive protein (CRP) of patients in COPD were higher than in healthy controls (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1ß in AECOPD were higher than in SCOPD and healthy controls (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3aR, and IL-1ß in AECOPD combined with respiratory failure were higher than in the non-respiratory failure group (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1ß in AECOPD with high-risk were higher than in the low-risk group (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1ß in AECOPD were negatively correlated with FEV1pred%. The peripheral blood WBCs C3aR mRNA, the plasma C3a and C3aR in AECOPD were positively correlated with IL-1ß. CONCLUSION: The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1ß in COPD patients were significantly related to the risk of disease deterioration. The C3a-C3aR axis may be involved in airway inflammation in patients with COPD.

Environmental behaviors of PAHs in Ordovician limestone water of Fengfeng coal mining area in China.

In this study, we collected a total of 15 Ordovician limestone (OL) water, 4 shallow groundwater, 3 mine water, 2 surface water, and 2 coal bedrock water samples, aiming to analyze the characteristics of distributions and sources of polycyclic aromatic hydrocarbons (PAHs) in OL water in a typical exploited coal mine named as Fengfeng mining area. Firstly, the PAHs behaviors and characteristics in different types of water of the mining area were investigated and summarized. And then, the hydrogen and oxygen isotopes were combined with isomer ratio method to determine the characteristics, sources, and behaviors of PAHs in OL water, respectively. Results showed that the concentration of PAHs ranged from 0.06 to 0.56 ng/L in OL water of Fengfeng Mine. Among them, the dominant 2-4 cyclic PAHs, including Nap, Phe, Flt, and Flu, were detected at a low concentration level with high detection rate. Characteristic compound ratios Ant/(Ant + Phe) and Flt/(Flt + Pyr) showed that the PAHs were derived from the combustion of the coal and biomass. The results of δD/δ18O and δD/Phe testing showed that the PAHs in most OL water came from rainfall infiltration recharge with coal and biomass combustion products in exposed bedrock area at high altitude. The PAHs of some polluted areas were derived from leakage recharge of shallow groundwater, mine water, and coal bedrock water.