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BackgroundDeep venous thrombosis (DVT) highly occurs in patients with severe COVID-19 and probably accounted for their high mortality. DVT formation is a time-dependent inflammatory process in which NETosis plays an important role. However, whether ginsenoside Rg5 from species of Panax genus could alleviate DVT and its underlying mechanism has not been elucidated.MethodsThe interaction between Rg5 and P2RY12 was studied by molecular docking, molecular dynamics, surface plasmon resonance (SPR), and molecular biology assays. The preventive effect of Rg5 on DVT was evaluated in inferior vena cava stasis–induced mice, and immunocytochemistry, Western blot, and calcium flux assay were performed in neutrophils from bone marrow to explore the mechanism of Rg5 in NETosis via P2RY12.ResultsRg5 allosterically interacted with P2RY12, formed stable complex, and antagonized its activity via residue E188 and R265. Rg5 ameliorated the formation of thrombus in DVT mice; accompanied by decreased release of Interleukin (IL)-6, IL-1β, and tumor necrosis factor-α in plasma; and suppressed neutrophil infiltration and neutrophil extracellular trap (NET) release. In lipopolysaccharide- and platelet-activating factor–induced neutrophils, Rg5 reduced inflammatory responses via inhibiting the activation of ERK/NF-κB signaling pathway while decreasing cellular Ca2+ concentration, thus reducing the activity and expression of peptidyl arginine deiminase 4 to prevent NETosis. The inhibitory effect on neutrophil activity was dependent on P2RY12.ConclusionsRg5 could attenuate experimental DVT by counteracting NETosis and inflammatory response in neutrophils via P2RY12, which may pave the road for its clinical application in the prevention of DVT-related disorders.

Using dual-frequency satellite-borne GPS observations from May 24 to May 30, 2015, the linear combination of Melbourne-Wübbena and ionosphere-free linear combination, based on the basis of precise point positioning technology, the batch least squares estimation method is used to precisely determine the Swarm undifferenced kinematic orbits with different orbital attitudes. The orbit accuracy is assessed using three methods, which include satellite-borne GPS phase observation residuals analysis, comparison with ESA reduced-dynamic orbits and external evaluation with SLR measurements. The results indicate: ①Swarm satellite-borne GPS phase observation residual RMS is in the range of 6~7 mm level. ②Comparisons with reduced-dynamic orbits computed by European Space Agency (ESA), radial, along-track and cross-track orbit difference RMS are in the range of 2~4 cm level. ③Comparisons with kinematic orbits computed by ESA, Radial, along-track and cross-track orbit difference RMS are in the range of 1~2 cm level. ④The external validation with satellite laser ranging (SLR) measurement shows RMS errors are in the range of 3~4 cm level. Therefore, it is feasible to use the undifferenced kinematic orbit determination method and the orbit determination strategy provided in this paper to carry out the precise orbit determination of swarm series satellites. The orbit determination accuracy is centimeter level.

Additional file 1: Table S1. Primers, probes and siRNA/shRNA used in this study. Table S2. Antibodies for western blot and IHC and in vivo used in this study. Table S3. Differentially expressed lncRNAs in HCC.

Additional file 2: Fig. S1. Genomic and transcriptome alterations of lncRNAs in cancer. Fig. S2. Expression of LINC01132 in HCC cell lines. Fig. S3. LINC01132 increases cancer cell growth, proliferation, invasion and metastasis in vitro. Fig. S4. PDX models shLINC01132. Fig. S5. Expression and clinical association of NRF1 and KDM5B. Fig. S6. Integrative Genomics Viewer of KDM5B binding around the TSS of DPP4 in HCC cell lines. Fig. S7. Interactions of DPP4 in protein-protein interaction networks.

Terrestrial water storage (TWS) is a key variable in global and regional hydrological cycles. In this study, the TWS changes in the Yangtze River Basin (YRB) were derived using the Lagrange multiplier method (LMM) from Gravity Recovery and Climate Experiment (GRACE) data. To assess TWS changes from LMM, different GRACE solutions, different hydrological models, and in situ data were used for validation. Results show that TWS changes from LMM in YRB has the best performance with the correlation coefficients of 0.80 and root mean square error of 1.48 cm in comparison with in situ data. The trend of TWS changes over the YRB increased by 10.39 ± 1.27 Gt yr-1 during the 2003−2015 period. Moreover, TWS change is disintegrated into the individual contributions of hydrological components (i.e., glaciers, surface water, soil moisture, and groundwater) from satellite data, hydrologic models, and in situ data. The estimated changes in individual TWS components in the YRB show that (1) the contribution of glaciers, surface water, soil moisture, and groundwater to total TWS changes is 15%, 12%, 25% and 48%, respectively; (2) Geladandong glacier melt from CryoSat-2/ICESat data has a critical effect on TWS changes with a correlation coefficients of −0.51; (3) the Three Gorges Reservoir Impoundment has a minimal effect on surface water changes (mainly lake water storage), but it has a substantial effect on groundwater storage (GWS), (4) the Poyang and Doting Lake water storage changes are mainly caused by climate change, (5) soil moisture storage change is mainly influenced by surface water, (6) human-induced GWS changes accounted for approximately half of the total GWS. The results of this study can provide valuable information for decision-making in water resources management.