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Galectin-3 Has Anti-Necroptotic and Anti-Apoptotic Consequences throughout Cisplatin-Induced Acute Tubular Necrosis.
Porcine epidemic diarrhea virus (PEDV), being highly virulent and contagious in piglets, has caused significant damage to the pork industries of many countries worldwide. There are no commercial drugs targeting coronaviruses (CoVs), and few studies on anti-PEDV inhibitors. The coronavirus 3C-like protease (3CLpro) has a conserved structure and catalytic mechanism and plays a key role during viral polyprotein processing, thus serving as an appealing antiviral drug target. Here, we report the anti-PEDV effect of the broad-spectrum inhibitor GC376 (targeting 3Cpro or 3CLpro of viruses in the picornavirus-like supercluster). GC376 was highly effective against the PEDV 3CLpro and exerted similar inhibitory effects on two PEDV strains. Furthermore, the structure of the PEDV 3CLpro in complex with GC376 was determined at 1.65 Å. We elucidated structural details and analyzed the differences between GC376 binding with the PEDV 3CLpro and GC376 binding with the transmissible gastroenteritis virus (TGEV) 3CLpro. Finally, we explored the substrate specificity of PEDV 3CLpro at the P2 site and analyzed the effects of Leu group modification in GC376 on inhibiting PEDV infection. This study helps us to understand better the PEDV 3CLpro substrate specificity, providing information on the optimization of GC376 for development as an antiviral therapeutic against coronaviruses.BACKGROUND Liver diseases drive the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB4) index is a non-invasive scoring method for detecting liver fibrosis, but the prognostic impact of using it for AF patients is still unknown. Herein, we evaluated using the FIB4 index as a risk assessment tool for cardiovascular events and mortality in patients with AF. METHODS We performed a post-hoc analysis of a prospective, observational multicenter study. A total of 3067 patients enrolled in a multicenter Japanese registry were grouped as first tertile (FIB4 index less then 1.75, n = 1022), second tertile (1.75 ≤ FIB4 index less then 2.51, n = 1022), and third tertile (FIB4 index ≥ 2.51, n = 1023). RESULTS The third tertile had statistically significant results older age, lower body mass index, increased heart failure prevalence, and lower clearances of hemoglobin and creatinine (all p less then 0.05). During the follow-up period, incidences of major bleeding, cardiovascular events, and all-cause mortality were significantly higher for the third tertile (all p less then 0.05). After multivariate adjustment, the third tertile associated independently with cardiovascular events (HR 1.72; 95% CI 1.31-2.25) and all-cause mortality (HR 1.43; 95% CI 1.06-1.95). learn more Adding the FIB4 index to a baseline model with CHA2DS2-VASc score improved the prediction of cardiovascular events and all-cause mortality, as shown by the significant increase in the C-statistic (all p less then 0.05), net reclassification improvement (all p less then 0.001), and integrated discrimination improvement (all p less then 0.001). A FIB4 index ≥ 2.51 most strongly associated with cardiovascular events and all-cause mortality in AF patients with high CHADS2 scores (all p less then 0.001). CONCLUSIONS The FIB4 index is independently associated with risks of cardiovascular events and all-cause mortality in AF patients.Many remote sensing scene classification algorithms improve their classification accuracyby additional modules, which increases the parameters and computing overhead of the model atthe inference stage. In this paper, we explore how to improve the classification accuracy of themodel without adding modules at the inference stage. First, we propose a network trainingstrategy of training with multi-size images. Then, we introduce more supervision information bytriplet loss and design a branch for the triplet loss. In addition, dropout is introduced between thefeature extractor and the classifier to avoid over-fitting. These modules only work at the trainingstage and will not bring about the increase in model parameters at the inference stage. We useResnet18 as the baseline and add the three modules to the baseline. We perform experiments onthree datasets AID, NWPU-RESISC45, and OPTIMAL. Experimental results show that our modelcombined with the three modules is more competitive than many existing classification algorithms.In addition, ablation experiments on OPTIMAL show that dropout, triplet loss, and training withmulti-size images improve the overall accuracy of the model on the test set by 0.53%, 0.38%, and0.7%, respectively. The combination of the three modules improves the overall accuracy of themodel by 1.61%. It can be seen that the three modules can improve the classification accuracy of themodel without increasing model parameters at the inference stage, and training with multi-sizeimages brings a greater gain in accuracy than the other two modules, but the combination of thethree modules will be better.In this work, we reveal in detail the effects of high-temperature treatment in air at 600 °C on the microstructure as well as the physico-chemical and electrochemical properties of boron-doped diamond (BDD) electrodes. The thermal treatment of freshly grown BDD electrodes was applied, resulting in permanent structural modifications of surface depending on the exposure time. High temperature affects material corrosion, inducing crystal defects. The oxidized BDD surfaces were studied by means of cyclic voltammetry (CV) and scanning electrochemical microscopy (SECM), revealing a significant decrease in the electrode activity and local heterogeneity of areas owing to various standard rate constants. This effect was correlated with a resultant increase of surface resistance heterogeneity by scanning spreading resistance microscopy (SSRM). The X-ray photoelectron spectroscopy (XPS) confirmed the rate and heterogeneity of the oxidation process, revealing hydroxyl species to be dominant on the electrode surface. Morphological tests using scanning electron microscopy (SEM) and atomic force microscopy (AFM) revealed that prolonged durations of high-temperature treatment lead not only to surface oxidation but also to irreversible structural defects in the form of etch pits. Our results show that even subsequent electrode rehydrogenation in plasma is not sufficient to reverse this surface oxidation in terms of electrochemical and physico-chemical properties, and the nature of high-temperature corrosion of BDD electrodes should be considered irreversible.This paper analyzes the co-movement and causal linkages between environmental pollution and healthcare expenditure, taking economic growth as a control variable by using wavelet analysis for Taiwan over the period 1995 Q1-2016 Q4. The results show that there exists co-movement and causality between environmental pollution and healthcare expenditure at different frequencies and times. The changes in the relationships of the two variables are observed in certain events such as the period of the expansion stage, the policy of environmental pollution, and the issue of the National Health Insurance Integrated Circuit card (NHI-IC) in Taiwan. In the short-term, positive causality runs from healthcare expenditure to environmental pollution before 2004, while negative causality runs from healthcare expenditure to environmental pollution before 2007 in the long-term. After adding economic growth as a control variable, positive causality runs from healthcare expenditure to environmental pollution in the period 2009-2011 in the short-term, while negative causality running from healthcare expenditure to environmental pollution is shown in 2008 in the long-term. The results indicate that "higher government health expenditure leading to higher demand for environment quality" exists in different sub-periods and the argument may concern the factor of economics in the long-term. The positive healthcare lead in the short-term may be based on economics in the expansion stage. Also, the issue of NHI-IC possibly affects the dynamic relationship between healthcare expenditure and environmental pollution without considering economics. Based on empirical analysis, certain policy and managerial implications are addressed for decision-makers at macroeconomic and microeconomic levels.This paper puts forward a novel methodology of employing inverse filtering technique to extract bridge features from acceleration signals recorded on passing vehicles using smartphones. Since the vibration of a vehicle moving on a bridge will be affected by various features related to the vehicle, such as suspension and speed, this study focuses on filtering out these effects to extract bridge frequencies. Hence, an inverse filter is designed by employing the spectrum of vibration data of the vehicle when moving off the bridge to form a filter that will remove the car-related frequency content. Later, when the same car is moving on the bridge, this filter is applied to the spectrum of recorded data to suppress the car-related frequencies and amplify the bridge-related frequencies. The effectiveness of the proposed methodology is evaluated with experiments using a custom-built robot car as the vehicle moving over a lab-scale simply supported bridge. Nine combinations of speed and suspension stiffness of the car have been considered to investigate the robustness of the proposed methodology against car features. The results demonstrate that the inverse filtering method offers significant promise for identifying the fundamental frequency of the bridge. Since this approach considers each data source separately and designs a unique filter for each data collection device within each car, it is robust against device and car features.Transition from cangrelor to oral P2Y12 inhibitors after PCI carries the risk of platelet function recovery and acute stent thrombosis. Whether the recommended transition regimen is appropriate for hypothermic cardiac arrest survivors is unknown. We assessed the rate of high platelet reactivity (HPR) after transition from cangrelor to ticagrelor in hypothermic cardiac arrest survivors. Adult survivors of out-of-hospital cardiac arrest with ST-segment elevation myocardial infarction (STEMI), who were treated for hypothermia (33 °C ± 1) and received intravenous cangrelor during PCI and subsequent oral loading with 180mg ticagrelor were enrolled in this prospective observational cohort study. Platelet function was assessed using whole blood aggregometry. HPR was defined as AUC > 46U. The primary endpoint was the rate of HPR (%) at predefined time points during the first 24 h after cangrelor cessation. Poisson regression was used to estimate the relationship between the overlap time of cangrelor and ticagrelor co-administration and the number of subsequent HPR episodes, expressed as incidence rate ratio (IRR) with 95% confidence interval (95%CI). Between December 2017 and October 2019 16 patients (81% male, 58 years) were enrolled. On average, ticagrelor was administered 39 min (IQR 5-50) before the end of cangrelor infusion. The rate of HPR was highest 90 min after cangrelor cessation and was present in 44% (7/16) of patients. The number of HPR episodes increased significantly with decreasing overlap time of cangrelor and ticagrelor co-administration (IRR 1.03, 95%CI 1.01-1.05; p = 0.005). In this selected cohort of hypothermic cardiac arrest survivors who received cangrelor during PCI, ticagrelor loading within the recommended time frame before cangrelor cessation resulted in a substantial amount of patients with HPR.
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