Identification of Potential Lead Compounds Targeting Novel Druggable Cavity of SARS-CoV-2 Spike Trimer by Molecular Dynamics Simulations.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an urgent public health problem. Spike (S) protein mediates the fusion between the virus and the host cell membranes, consequently emerging as an important target of drug design. The lack of comparisons of in situ full-length S homotrimer structures in different states hinders understanding the structures and revealing the function, thereby limiting the discovery and development of therapeutic agents. Here, the steady-state structures of the in situ full-length S trimer in closed and open states (Sclosed and Sopen) were modeled with the constraints of density maps, associated with the analysis of the dynamic structural differences. Subsequently, we identified various regions with structure and property differences as potential binding pockets for ligands that promote the formation of inactive trimeric protein complexes. By using virtual screening strategy and a newly defined druggable cavity, five ligands were screened with potential bioactivities. Then molecular dynamic (MD) simulations were performed on apo protein structures and ligand bound complexes to reveal the conformational changes upon ligand binding. Our simulation results revealed that sulforaphane (SFN), which has the best binding affinity, could inhibit the conformational changes of S homotrimer that would occur during the viral membrane fusion. Our results could aid in the understanding of the regulation mechanism of S trimer aggregation and the structure-activity relationship, facilitating the development of potential antiviral agents.

Family Sphingomonadaceae as the key executor of triclosan degradation in both nitrification and denitrification systems

The usage of triclosan (TCS) has increased with the COVID-19 virus outbreak, causing more TCS were released into wastewater treatment systems. However, the difference in TCS removal pathway and TCS degrading bacteria between nitrification and denitrification systems was still unknown. In this study, batch tests of TCS biodegradation mechanism and DNA stable isotope probing (DNA-SIP) technique were applied to decrypt the different TCS removal pathway and the corresponding degrading taxon between two nitrification and two denitrification systems. The main TCS degradation pathway in both nitrification and denitrification systems were the metabolism of heterotrophic bacteria, only a little TCS was degraded by the co-metabolism of heterotrophic or nitrifying bacteria, and higher NH4+-N or NO3--N concentration contributed to more TCS degradation. Moreover, denitrification system had stronger TCS removal capacity (0.11 and 0.65 mg TCS/g SS) than nitrification system (0.83 and 1.12 mg TCS/g SS). DNA-SIP assay further revealed that active TCS degrading bacteria in both systems belonged to Sphingomonadaceae family. Furthermore, the oligotype TATGCC, TAATCA and GCCCCG of Sphingomonadaceae played important roles in degrading TCS in both systems. Moreover, reactor performance and mixed liquor suspended solids might play important roles in shaping the ecotypes of Sphingomonadaceae, which caused the difference in degrading TCS between nitrification and denitrification systems. This lab-scale research might provide meaningful opportunities for evaluating the scale-up applications, and the TCS degrading bacteria identified in present study might be recommended to be used as bioaugmentation strains in practical engineering.

The Different Impacts of Emissions and Meteorology on PM2.5 Changes in Various Regions in China: A Case Study

Emissions and meteorology are significant factors affecting aerosol pollution, but it is not sufficient to understand their relative contributions to aerosol pollution changes. In this study, the observational data and the chemical model (GRAPES_CUACE) are combined to estimate the drivers of PM2.5 changes in various regions (the Beijing–Tianjin–Hebei (BTH), the Central China (CC), the Yangtze River Delta (YRD), and the Pearl River Delta (PRD)) between the first month after COVID-19 (FMC_2020) (i.e., from 23 January to 23 February 2020) and the corresponding period in 2019 (FMC_2019). The results show that PM2.5 mass concentration increased by 26% (from 61 to 77 µg m−3) in the BTH, while it decreased by 26% (from 94 to 70 µg m−3) in the CC, 29% (from 52 to 37 µg m−3) in the YRD, and 32% (from 34 to 23 µg m−3) in the PRD in FMC_2020 comparing with FMC_2019, respectively. In the BTH, although emissions reductions partly improved PM2.5 pollution (−5%, i.e., PM2.5 mass concentration decreased by 5% due to emissions) in FMC_2020 compared with that of FMC_2019, the total increase in PM2.5 mass concentration was dominated by more unfavorable meteorological conditions (+31%, i.e., PM2.5 mass concentration increased by 31% due to meteorology). In the CC and the YRD, emissions reductions (−33 and −36%) played a dominating role in the total decrease in PM2.5 in FMC_2020, while the changed meteorological conditions partly worsened PM2.5 pollution (+7 and +7%). In the PRD, emissions reductions (−23%) and more favorable meteorological conditions (−9%) led to a total decrease in PM2.5 mass concentration. This study reminds us that the uncertainties of relative contributions of meteorological conditions and emissions on PM2.5 changes in various regions are large, which is conducive to policymaking scientifically in China.

Triclocarban shifted the microbial communities and promoted the spread of antibiotic resistance genes in nitrifying granular sludge system.

Triclocarban (TCC) is in great market demand especially after the outbreak of COVID-19 pandemic, becoming an emerging pollutant. However, the impacts of TCC on the performance of nitrifying granular sludge system and the occurrence of antibiotic resistance genes (ARGs) were still unknown. This work explored the impacts of different concentrations of TCC on nitrifying granular sludge. Results showed that TCC suppressed the activities of ammonia-oxidizing microorganisms and decreased the abundance of Nitrospira. Adsorption was the main way for the removal of TCC and the biodegradation efficiency of TCC increased to 28.00% under 19.70 mg/L TCC addition. TCC enriched the ARGs and promoted the risks of their transferring in microorganisms. Pseudomonas might not only have strong resistance to TCC, but also propagate ARGs. The removal process of TCC and bacterial communities were important factors to promote the spread of ARGs. Thus, the existence of TCC presented a great environmental risk.

Perceived Stress, Resilience, and Anxiety Among Pregnant Chinese Women During the COVID-19 Pandemic: Latent Profile Analysis and Mediation Analysis.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has posed a major threat to pregnant women's mental health. This study aimed to characterize the patterns of perceived stress in pregnant Chinese women during the COVID-19 pandemic, to examine the profile differences on anxiety and resilience, and to investigate whether the differences in these profiles on anxiety were mediated by resilience. Methods: From February 28, 2020 to April 26, 2020, a sample of 2,116 pregnant Chinese women who participated in online crisis interventions completed an online self-reporting questionnaire assessing their demographic characteristics, perceived stress, resilience, and anxiety. Results: Latent profile analysis (LPA) on two stress dimensions [perceived helplessness (HEL) and perceived self-efficacy (SEL)] indicated four perceived stress profiles: adaptive (33.7% of the sample), resistant (44.6%), insensitive (19.1%), and sensitive (2.6%). The women with both adaptive and insensitive profiles had the lowest levels of anxiety, whereas those with the resistant profile had the lowest levels of resilience. Multicategorical mediation analysis showed that resilience partially mediated the differences in the pregnant women's anxiety between the adaptive/insensitive and resistant profile. Conclusion: This study showed the heterogeneity in the perceived stress patterns of pregnant women during the COVID-19 pandemic, revealing the internal mechanisms of pregnant women's anxiety using a person-centered approach, and provided initial evidence guiding the development of differentiated stress interventions to alleviate pregnant women's anxiety during the pandemic.