Antiviral activity of luteolin against porcine epidemic diarrhea virus in silico and in vitro.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) mainly causes acute and severe porcine epidemic diarrhea (PED), and is highly fatal in neonatal piglets. No reliable therapeutics against the infection exist, which poses a major global health issue for piglets. Luteolin is a flavonoid with anti-viral activity toward several viruses. RESULTS: We evaluated anti-viral effects of luteolin in PEDV-infected Vero and IPEC-J2 cells, and identified IC50 values of 23.87 µM and 68.5 µM, respectively. And found PEDV internalization, replication and release were significantly reduced upon luteolin treatment. As luteolin could bind to human ACE2 and SARS-CoV-2 main protease (Mpro) to contribute viral entry, we first identified that luteolin shares the same core binding site on pACE2 with PEDV-S by molecular docking and exhibited positive pACE2 binding with an affinity constant of 71.6 µM at dose-dependent increases by surface plasmon resonance (SPR) assay. However, pACE2 was incapable of binding to PEDV-S1. Therefore, luteolin inhibited PEDV internalization independent of PEDV-S binding to pACE2. Moreover, luteolin was firmly embedded in the groove of active pocket of Mpro in a three-dimensional docking model, and fluorescence resonance energy transfer (FRET) assays confirmed that luteolin inhibited PEDV Mpro activity. In addition, we also observed PEDV-induced pro-inflammatory cytokine inhibition and Nrf2-induced HO-1 expression. Finally, a drug resistant mutant was isolated after 10 cell culture passages concomitant with increasing luteolin concentrations, with reduced PEDV susceptibility to luteolin identified at passage 10. CONCLUSIONS: Our results push forward that anti-PEDV mechanisms and resistant-PEDV properties for luteolin, which may be used to combat PED.

High-Performance Detection of Mycobacterium bovis in Milk Using Recombinase-Aided Amplification-Clustered Regularly Interspaced Short Palindromic Repeat-Cas13a-Lateral Flow Detection.

Mycobacterium bovis (M. bovis), the microorganism responsible for bovine tuberculosis (bTB), is transferred to people by the ingestion of unpasteurized milk and unprocessed fermented milk products obtained from animals with the infection. The identification of M. bovis in milk samples is of the utmost importance to successfully prevent zoonotic diseases and maintain food safety. This study presents a comprehensive description of a highly efficient molecular test utilizing recombinase-aided amplification (RPA)-clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein (Cas) 13a-lateral flow detection (LFD) for M. bovis detection. In contrast to ELISA, RPA-CRISPR-Cas13a-LFD exhibited greater accuracy and sensitivity in the detection of M. bovis in milk, presenting a detection limit of 2 × 100 copies/µL within a 2 h time frame. The two tests exhibited a moderate level of agreement, as shown by a kappa value of 0.452 (95%CI: 0.287-0.617, p < 0.001). RPA-CRISPR-Cas13a-LFD holds significant potential as a robust platform for pathogen detection in complex samples, thereby enabling the more dependable regulation of food safety examination, epidemiology research, and medical diagnosis.

Surface Wind Speed Changes and Their Potential Impact on Wind Energy Resources Across China During 1961-2021.

Enabling the rational use of energy and the realization of the "dual carbon goals" across China will require systematic analysis of temporal and spatial changes in surface wind speed (SWS), determination of key factors influencing SWS, and quantification of wind energy resources. We investigated changes of SWS and their potential impact on wind energy resources using daily SWS data from meteorological observations and based on wind power density (WPD) across China during 1961-2021. The SWS changes were related to atmospheric circulation, surface friction (urbanization and vegetation changes), aerosol emissions and the replacement of observation instruments. The increase of SWS after 2015 was closely related to changes of atmospheric circulation that were reflected by changes of Asian Meridional Circulation Index, North Atlantic Oscillation, and Arctic Oscillation. Compared with the mean SWS, the extreme SWS exhibited a more obvious downward trend and earlier abrupt change. The annual mean SWS decreased by 16.80% in the last six decades, resulting in a decrease of 47.78% in wind energy potential. Regions with annual WPD more than 100 W · m-2 were mainly in western China, northeastern China, northwestern China and some coastal areas. The WPD decreased mainly in northeastern China, northern China, and some coastal areas during the last six decades; it increased mainly in western China. Regions with annual WPD more than 100 W · m-2 and robust coefficient of variation less than 0.5 are high-quality wind energy resource areas and were found mainly in western China, northern China, northeast China, and coastal areas.

Sediment reduction in the middle Yellow River basin over the past six decades: Attribution, sustainability, and implications.

Understanding the underlying driving forces causing changes in sediment yield is crucial for decision-making and major strategy development for the management of the middle Yellow River basin (MYRB). In this work, we quantified the causes of sediment yield reduction in the MYRB and investigated the sustainability of sediment reduction strategies. The sediment yield in the middle Yellow River during 1957-2017 exhibits a significant downward trend. The average sediment yield in 1970-2017 decreased by 798.84 × 106 t compared with that during the 1950s to 1960s, with 27.40 % ascribed to decreased precipitation and 72.60 % attributed to human activities. The sediment yield modulus of all sub-basins within the MYRB has been reduced to <5000 t/km2, demonstrating the dominant influence of water and soil conservation measures. Check dams have limited on-site effectiveness in reducing sediment yield but exhibit a dominant effect in trapping the already yielded sediment and preventing it from being delivered into the lower Yellow River. The strong dependence on the storage capacity of check dams makes the system unsustainable in the long run, since it necessitates ongoing investment in check dam construction to maintain the sediment trapping effect. Promoting biological measures such as planting trees and grass to increase vegetation coverage is a more sustainable way to fix the sediment on-site and keep it from being eroded. These efforts should be intensified, with appropriate consideration for local conditions.

High-quality reconstruction of China's natural streamflow.

Reconstruction of natural streamflow is fundamental to the sustainable management of water resources. In China, previous reconstructions from sparse and poor-quality gauge measurements have led to large biases in simulation of the interannual and seasonal variability of natural flows. Here we use a well-trained and tested land surface model coupled to a routing model with flow direction correction to reconstruct the first high-quality gauge-based natural streamflow dataset for China, covering all its 330 catchments during the period from 1961 to 2018. A stronger positive linear relationship holds between upstream routing cells and drainage areas, after flow direction correction to 330 catchments. We also introduce a parameter-uncertainty analysis framework including sensitivity analysis, optimization, and regionalization, which further minimizes biases between modeled and inferred natural streamflow from natural or near-natural gauges. The resulting behavior of the natural hydrological system is represented properly by the model which achieves high skill metric values of the monthly streamflow, with about 83% of the 330 catchments having Nash-Sutcliffe efficiency coefficient (NSE) > 0.7, and about 56% of the 330 catchments having Kling-Gupta efficiency coefficient (KGE) > 0.7. The proposed construction scheme has important implications for similar simulation studies in other regions, and the developed low bias long-term national datasets by statistical postprocessing should be useful in supporting river management activities in China.

The effects of terrain factors on the drainage area threshold: comparison of principal component analysis and correlation analysis.

How and to which extent terrain factors affecting the drainage area threshold (DAT) are disputable. This paper uses principal component analysis (PCA) and correlation analysis to study the influence degree of terrain factors on DAT. Firstly, 22 watersheds, locating in the severe soil erosion region (SSER) of Loess Plateau of China, are picked out as the example areas. The purpose of the mean change point method (MCP) to detect the relationship between DAT and gully density (GD) is to get a reasonable DAT. Secondly, nine terrain factors are calculated, and their statistical values are compared and put in the matrix to clear the different effects on DAT. Finally, the effects of statistical eigenvalues of terrain factors on DAT are compared with PCA and the correlation analysis. According to the PCA, the nine terrain factors are summarized into three principal components, which are slope, height variation, and relief factor. By calculating the score weighted by each factor coefficient matrix and eigenvalue, the result states that slope (S), terrain curvatures (K), and surface roughness (SR) are the factors that have great influence on DAT. Meanwhile, the results of correlation analysis indicate that S, SR, and K have exerted a great influence on the DAT, and the significance level was above 0.05. Both the results of PCA and correlation analysis make clear that the slope is the most direct and influential factor affecting DAT, while other factors are more or less related to slope directly and indirectly. The result implies that the vertical variation of terrain has a strong correlation with the slope, and also has a great influence on DAT. This research not only would be of great significance to recognize the mechanism of gully development, but also able to provide a scientific reference for soil and water conservation in the Loess Plateau.

Long-term trends in Songhua River Basin streamflow and its multivariate relationships with meteorological factors.

Long-term streamflow trends are closely related to meteorological factors; understanding the relationships between them helps to improve water resources management in advance. In this study, we examined long-term annual and seasonal streamflow trends over 1961-2010 in 28 stations in the Songhua River Basin (SRB), China, using four kinds of trend detection methods and then determined the optimal meteorological predictors for SRB streamflow based on the multiple wavelet coherence. We found significant downward trends in annual streamflow in a large part of the study stations (varies from 10 to 18 for different methods), and fewer decreasing stations were detected when we consider the full autocorrelation and the long-term persistence in streamflow. In contrast to annual streamflow, fewer stations showed significant downward trends in summer and winter streamflow. Streamflow generally followed the pattern of precipitation (PRE); the largest streamflow changes occurred in summer and August monthly streamflow variation contributed the most to the annual streamflow variation. We found PRE and potential evapotranspiration (PET) combined was the optimal predictor for streamflow above Jiangqiao and on the Jiangqiao-Dalai section of the Songhua River; as for the Dalai-Harbin section and the Harbin-Jiamusi section, the optimal predictor combinations are PRE and number of rainy days (WET), and PRE and average monthly temperature (TMP) respectively.

Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor.

Central neuromedin U 2 receptor (NMU2R) plays important roles in the regulation of food intake and body weight. Identification of NMU2R agonists may lead to the development of pharmaceutical agents to treat obesity. Based on the structure of rutin, a typical flavonoid and one of the NMU2R agonists we previously identified from an in-house made natural product library, 30 flavonoid derivatives have been synthesized and screened on a cell-based reporter gene assay. A number of compounds were found to be selective and highly potent to NMU2R. For example, the EC50 value of compound NRA 4 is very close to that of NMU, the endogenous peptide ligand of NMU2R. Structure-activity relationship analysis revealed that a 3-hydroxyl group in ring C and a 2'-fluoride group in ring B were essential for this class of compounds to be active against NMU2R.