Introduction: The COVID-19 global epidemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a great public health emergency. Discovering antiviral drug candidates is urgent for the prevention and treatment of COVID-19. Objectives: This work aims to discover natural SARS-CoV-2 inhibitors from the traditional Chinese herbal medicine licorice. Methods: We screened 125 small molecules from Glycyrrhiza uralensis Fisch. (licorice, Gan-Cao) by virtual ligand screening targeting the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. Potential hit compounds were further evaluated by ELISA, SPR, luciferase assay, antiviral assay and pharmacokinetic study. Results: The triterpenoids licorice-saponin A3 (A3) and glycyrrhetinic acid (GA) could potently inhibit SARS-CoV-2 infection, with EC50 of 75 nM and 3.17 µM, respectively. Moreover, we reveal that A3 mainly targets the nsp7 protein, and GA binds to the spike protein RBD of SARS-CoV-2. Conclusion: In this work, we found GA and A3 from licorice potently inhibit SARS-CoV-2 infection by affecting entry and replication of the virus. Our findings indicate that these triterpenoids may contribute to the clinical efficacy of licorice for COVID-19 and could be promising candidates for antiviral drug development. Keywords: COVID-19; Glycyrrhetinic acid; Licorice; Licorice-saponin A3; SARS-CoV-2.
The common pool resource (CPR) theory has made invaluable contributions to the governance of natural resources in the past decades, but few literatures have specifically paid attention to the different property right arrangements of resource system and resource units, and their relationship. In this paper, we take two types of grassland property right system on the Qinghai-Tibetan Plateau (QTP) in China, one is grassland contract system under that the previous grassland common use was given up and the other is grazing quota system under that the common use is still kept in the community level, as cases to present the different consequences on the ecological conditions, herders’ livelihoods and livestock husbandry. Furthermore, from the perspective of property rights of resource system-units, we explore why the two systems resulted in the different consequences. We find that the grazing quota system indicated by the number of livestock each household allowed to raise has more advantages in improving the herders’ livelihoods and reducing the livestock production costs, and both systems could alleviate the grazing pressure though the long-term effects of the contract system might be negative on ecological conditions. The main reason why the grazing quota system works better is that this type of individual use rights were clarified based on the resource units so the grassland could be kept common use as an integrated resource system, while the contract system was claimed by physically dividing the resource system by fencing, thus the resource system was fragmented which led to mismatch with the large scope movement needs of livestock grazing. We argue that, theoretically, the grazing quota system is a private property rights embedded in the grassland common property right system, which forms a nested property right regime. Our findings have important implications for both of the CPR theory and practical rangeland management worldwide.
A growing number of governments and companies are pledging net-zero emissions by 2050. For the US as a whole to achieve this requires eliminating or offsetting today's emission of ~6 billion tCO2e/year. There is a dearth of analysis for understanding requirements, costs, and impacts of this transition. The goal of this study is to help fill this gap by providing insights at visceral, human scales of how the nation will look following a pathway to net-zero and the localized benefits, costs, and impacts for different industries, professions, and communities. The analysis aims to inform debates on public and corporate policies needed to achieve net-zero, but specific policy recommendations are not offered.Energy service demands projected to 2050 by the EIA for 14 regions across the continental US provide the starting point for modeling. Five different pathways are constructed for meeting these demands by varying exogenously applied constraints to create the different pathways.End-use technologies to meet service demands are exogenously specified in 5-year time steps to determine final energy demands that must be delivered by the energy supply system. Pathways to net-zero emissions by 2050 are constructed by finding the energy supply mix that minimizes the 30-year NPV of total energy-system costs, subject to exogenous constraints. The model has perfect foresight and seamless integration between all sectors. These modeling results are “downscaled” to state or sub-state geographies to quantify local plant and infrastructure investments, construction activities, land-use, jobs, and health impacts, 2020 - 2050.
Microbial densities, functional genes, and their responses to environment factors have been studied for years, but still a lot remains unknown about their interactions with each other. In this study, the abundances of 7 nitrogen cycling genes in the sediments from Hangzhou Bay were analyzed along with bacterial and archaeal 16S rRNA abundances as the biomarkers of their densities. The amount of organic matter (OM) and total nitrogen (TN) strongly positively correlated with each other and microbial densities, while total phosphate (TP) and ammonia-nitrogen (NH3–N) did not. Most studied genes were density suppressed, while nirS was density stable, and nosZ and hzo were density irrelevant. This suggests eutrophication could limit inorganic nitrogen cycle pathways and the removal of nitrogen in the sediment and emit more greenhouse gases. This study provides a new insight of microbial community structures, functions and their interactions in the sediments of eutrophic bays.
Recent Chinese air pollution actions have significantly lowered the levels of fine particulate matter (PM2.5) in North China via controlling emissions of sulfur dioxide (SO2) and nitrogen oxides (NO x ) together with primary aerosols, while the emissions of another precursor, ammonia (NH3), have not yet been regulated. This raises a question that how effective the NH3 emission controls can be on the mitigation of PM2.5 pollution along with the reduction of SO2 and NO x emissions. Here we use a regional air quality model to investigate this issue focusing on the PM2.5 pollution in North China for January and July 2015. We find that the efficiency of the PM2.5 reduction is highly sensitive to the NH3 emission and its reduction intensity. Reductions in the population-weighted PM2.5 concentration (PWC) in the Beijing–Tianjin–Hebei region are only 1.4–3.8 μg m−3 (1.1%–2.9% of PM2.5) with 20%–40% NH3 emission reductions, but could reach 8.1–26.7 μg m−3 (6.2%–21%) with 60%–100% NH3 emission reductions in January 2015. Besides, the 2015–2017 emission changes (mainly reduction in SO2 emissions) could lower the PM2.5 control efficiency driven by the NH3 reduction by up to 30% for high NH3 emission conditions, while lead to no change or increase in the efficiency when NH3 emissions become low. NO x emission reductions may enhance the wintertime PM2.5 pollution due to the weakened titration effect and can be offset by simultaneously controlling NH3 emissions. Our results emphasize the need to jointly consider NH3 with SO2 and NO x emission controls when designing PM2.5 pollution mitigation strategies.
Existing critical point theories including metric and topological critical point theories are difficult to be applied directly to some concrete problems in particular polyhedral settings, because the notions of critical sets could be either very vague or too large. To overcome these difficulties, we develop critical point theory for nonsmooth but Lipschitzian functions defined on convex polyhedrons. This yields natural extensions of classical results in critical point theory, such as the Liusternik-Schnirelmann multiplicity theorem. More importantly, eigenvectors for some eigenvalue problems involving graph 1-Laplacian coincide with critical points of the corresponding functions on polytopes, which indicates that the critical point theory proposed in the present paper can be applied to study the nonlinear spectral graph theory.
Coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV) may result in severe liver disease and frequent progression to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that HBV replication is suppressed by replicating HCV and often rebounds after treatment with drugs against HCV. Thus, a highly efficient cell culture system permissive for HBV/HCV would facilitate investigation on the interaction and pathogenesis after coinfection. Here we reported a robust HBV/HCV coinfection cell culture model by overexpressing human sodium-taurocholate cotransporting polypeptide (NTCP), CD81 and Mir122 into HepG2 cells and investigated interactions between HBV and HCV. In this system, HepG2-NTCP/CD81/Mir122 cells not only supported robust infection and replication of HBV and HCV, but also allowed HBV/HCV coinfection in the single cell level. Our result showed cells with replicating HBV still supported HCV infection. However, HBV replication was suppressed by HCV through the inhibition of HBV core promoter and S promoter II activity, and this inhibition was attenuated by the interferon alpha (IFNα) treatment, suggesting HCV influence on HBV at transcriptional level. Coinfection of HBV/HCV in this system did not block IFN stimulated genes expression. Inhibition of HCV by direct-acting antiviral drugs restored HBV replication and expression of viral genes. Conclusions: HepG2-NTCP/CD81/Mir122 fully supports HBV/HCV coinfection, replication and interaction. This novel cell model offers a platform to advance our understanding of the molecular details of the interaction, pathogenesis and outcomes of HBV/HCV coinfection.
In this study, we designed an integrated electrochemical filtration system for catalytic activation of peroxymonosulfate (PMS) and degradation of aqueous microcontaminants. Composites of carbon nanotube (CNT) and nanoscale zero valence copper (nZVC) were developed to serve as high-performance catalysts, electrode and filtration media simultaneously. We observed both radical and nonradical reaction pathways, which collectively contributed to the degradation of model pollutants. Congo red was completely removed via a single-pass through the nZVCCNT filter (τ <2 s) at neutral pH. The rapid kinetics of Congo red degradation were maintained across a wide pH range (from 3.0–7.0), in complicated matrixes (e.g., tap water and lake water), and for the degradation of a wide array of persistent organic contaminants. The superior activity of nZVCCNT stems from the boosted redox cycles of Cu2+/Cu+ in the presence of an external electric field. The flow-through design remarkably outperformed the conventional batch system due to the convection-enhanced mass transport. Mechanism studies suggested that the carbonyl group and electrophilic oxygen of CNT served as electron donor and electron acceptor, respectively, to activate PMS to generate •OH and 1O2 via one-electron transport. The electron-deficient Cu atoms are prone to react with PMS via surface hydroxyl group to produce reactive intermediates (Cu2+-O-O-SO3−), and then 1O2 will be generated by breaking the coordination bond of the metastable intermediate. The study will provide a green strategy for the remediation of organic pollution by a highly efficient and integrated system based on catalytic oxidation, electrochemistry, and nano-filtration techniques.