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Pulmonary embolism (PE) is a disease caused by blood clots, tumor embolism, and other emboli within the pulmonary arteries. Various scoring scales are used for PE. One such same is the PESI, but it has 12 variables, making it inconvenient for clinical application.The aim of this study was to develop a new simple nomogram model to assess 30-day survival in PE patients. The new nomogram makes it easier and faster for clinicians to assess the prognosis of patients with PE.We collected data about the patients with PE from the Medical Information Mart for Intensive Care-III (MIMIC-III) database and used the receiver operating characteristic (ROC) curve, area under the ROC curve (AUROC), calibration plot, integrated discrimination improvement (IDI), and decision curve analysis (DCA) to evaluate the predictive power of the new model, and compared these with the PESI.According to the multivariable Cox regression model results, alongside the actual clinical conditions, we included the following seven variables: race, bicarbonate, age, tumor, systolic blood pressure (SBP), body temperature, and oxygen saturation (Spo2). The AUROC of the new model was greater than 0.70. Its IDI exceeded 0, but with P-value0.05.The predictive performance of the new model was not worse than the PESI, but the new model only has seven variables, and is therefore more convenient for clinicians to use.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

To improve the work efficiency of each rescue team in case of emergency and increase the responsiveness of emergency rescue work, a multi-objective optimization model of site selection of rescue stations was established. Timeliness and economy of each rescue group, as well as its workload and due responsibility was considered during in the process of modeling. A heuristic method for solving the multi-objective optimization model was presented. In addition, the key parameters of the algorithm to improve the efficiency of model solving were analyzed. The accuracy and advantages of the proposed model were verified through the calculation results of an example and sensitivity analysis.

Farnesoid X receptor (FXR) agonists play important regulatory roles in bile acid, lipid and glucose metabolism in vitro and in vivo. Thus, FXR agonists exhibit potential therapeutic effects on metabolism-related diseases that are associated with extrahepatic manifestations induced by hepatitis C virus (HCV) infection. This study investigated the effect and mechanism of FXR agonist GW4064 against HCV in vitro to explore the potential application of FXR agonists. Results showed that GW4064 and other FXR agonists have potent antiviral activity against HCV in Huh7.5 cells. GW4064 down-regulated the expression of scavenger receptor class B type I protein via FXR and thereby indirectly inhibited HCV entry into cells, leading to interruption of HCV life cycle. GW4064 also exhibited synergistic anti-HCV effect with known direct-acting antiviral agents (DAAs) used in the clinic and remained sensitive to DAA-resistant HCV mutations. Therefore, FXR agonists are also a kind of antiviral agent, and might be helpful in treatment of HCV-induced hepatic and extrahepatic manifestations.

Bicyclol, a synthetic hepatoprotective and anti-inflammatory agent approved in China, was widely used to treat various hepatitis accompanied by elevated serum aminotransferases. However, the pharmacological effects and mechanisms of bicyclol on advanced liver diseases, such as fibrosis/cirrhosis and hepatocellular carcinoma (HCC), remain to be explored. Here, we revealed that bicyclol prevents from formatting severe fibrosis, slows the progression of moderate liver fibrosis, accelerates the regression of moderate liver fibrosis, decreases the malignancy of HCC in rat models induced by diethylnitrosamine (DEN), and also blocks steatohepatitis to HCC in mice induced by western diet plus carbon tetrachloride and DEN. The detailed pharmacological mechanism showed that bicyclol alleviates chronic progressive liver diseases by inhibiting the levels of IL-6 and subsequent phosphorylated STAT3. Conclusion: Bicyclol plays significant protective roles in multiply stages of fibrosis/cirrhosis-HCC and nonalcoholic fatty liver disease-related HCC via inhibiting IL-6/STAT3 signaling pathway. Therefore, bicyclol might be a promising therapeutic strategy for treating advanced liver diseases.

A series of novel biaryl amide derivatives were synthesized and evaluated for anti-HCV virus activity. Some significant SARs were uncovered. The intensive structural modifications led to fifteen novel compounds with more potent inhibitory activity compared to the hit compounds IMB 26 and IMB1f. Among them, compound 80 was the most active, with EC50 values almost equivalent to the clinical drug telaprevir (EC50 = 15 nM). Furthermore, it also had a good safety and in vitro and oral pharmacokinetic (oral bioavailability in rats: 34%) profile, suggesting a highly drug-like nature. Compound 80represents a more promising scaffold for anti-HCV virus activity for further study., Graphical abstract Image 1

In this work, the microwave was used to investigate the changes in activities and the possible passivation mechanism of PPO during the maceration stage of winemaking at different microwave conditions. Under the condition of microwave power 500 W, temperature 50 °C, and time 8 min, the activity of PPO decreased 0.853 U/(g·min) in grape maceration solution, having a decrease of 39.58% compared to the untreated PPO. The carbon-centred free radicals were induced in PPO solution at different microwave conditions. Besides, the changes of PPO conformational properties confirmed that microwave did affect the activity of PPO by influencing the PPO's composition, microenvironment, groups, chemical bonds, structure, and hydrolysis degree. The study will contribute to understanding the mechanism of higher extraction rate of phenols compounds in the maceration stage of winemaking by microwave irradiation.

In emergency system design, evacuating people from dangerous buildings has always been a significant yet challenging undertaking. This paper combines evacuation demand analysis with a toxic gas dispersion process to create an underground space risk assessment model for toxic gas leaks. The emergency evacuation capacity of a subway transfer station in Guangzhou has been evaluated and optimized based on computational fluid dynamics (CFD) and agent-based simulation. A strategy is proposed in which the subway ventilation system in the underground space is utilized to mitigate evacuation risks during gas leaks. The influence of the ventilation system on the gas diffusion process under different working conditions during simulations of toxic gas diffusion is also analyzed. A comparative analysis is conducted to discuss whether to adopt the ventilation system. Then, the effectiveness of the risk methods when the ventilation system is utilized in different working conditions is also verified. An empirical model of the impacts of the number of evacuees and individual risk perception levels on the evacuation risk has been obtained. Results indicate that the new risk assessment and risk mitigation methods are effective and can help guide the emergency evacuation and ventilation system design for underground buildings.

Catalytic decomposition of formic acid is regarded as one of the most promising hydrogen source conversion technologies. Nitrogen doped carbon supported metal catalyst emerges in recent years and delivers excellent performance in formic acid hydrogenation. However, there is not a well-recognized explanation about the real role of the nitrogen dopant in carbon support. In this work, density functional theory-based calculations were used to individually study the ligand effect and catalytic effect from the nitrogen dopant. Ligand effect mainly tunes the electronic properties of metal active center by shifting d-band center far away from Fermi level. The result unravels that C H scission path is more favorable compared with O H scission path. Catalytic effect is originated from the lower electrostatic potential of nitrogen active site compared with platinum, making N site an efficient capturer for hydrogen atom. Though activation energy for cleaving O H bond is higher than C H bond, nitrogen site can efficiently cleave the O H bond. Microkinetic simulations are performed to obtain the best nitrogen doping concentration in the carbon support. It implies that the optimal nitrogen concentration is a function of temperature, according to the optimized curve. This work will improve the understanding of mechanism of formic acid decomposition and provide new method in modifying metal/carbon support catalysts.

To investigate the effects of inhibition of NF-κB activation on left ventricular (LV) remodelling in a rat model of myocardial infarction (MI).The acute MI model was established by ligation of left anterior descending coronary artery. Pyrrolidine dithiocarbamate (PDTC) (20mg/kg, Qd) was administered intraperitoneally to inhibit NF-κB activation. Eight weeks later, the cardiac structure and LV ejection fraction were assessed with echocardiography. The rat body, heart, and LV weights were measured to calculate LV mass indices. Activation of NF-κB in non-infarcted myocardium was detected by a TransAM NF-κB p65 Transcription Factor Assay Kit. Cardiac collagen volume fraction was evaluated by Masson staining.Eight weeks after the MI model was established, the LV posterior wall thickness in PDTC and MI group was 1.75±0.07mm and 1.85±0.07mm respectively (p0.05). The LV mass index in the PDTC group (2.53±0.09) was lower than in the MI group (2.65±0.08, p0.05). The LVEF in the PDTC group (63.89%±4.21%) was higher than in the MI group (42.73%±8.94%, p0.05). The interstitial collagen deposition in the non-infarcted myocardium in the PDTC group was less than in the MI group (7.25%±1.88% vs. 10.09%±2.19%, p0.05).Inhibition of activation of NF-κB may result in improvement of myocardial remodelling after myocardial infarction, which is possibly attributable to reduced collagen deposition in non-infarcted areas.

With the development of the city, the number of establishments that are proposed or under construction is increasing year by year, and if they are industries that handle flammable, explosive, toxic, harmful, and dangerous substances, the public safety will face great threats, which will bring great challenges to emergency rescue work. Therefore, providing reasonable solutions to the problem of location selection of emergency supplies repositories are necessary for improving the emergency response efficiency in chemical industrial parks. A mathematical model for location selection of emergency supplies repositories in emergency logistics management are presented considering more actual factors. The optimization objectives of the model are to minimize total transport length and cost. And then a Variable Weighted Algorithm is designed to solve the model, where an auxiliary function was constructed with different methods of building weighting factors based on the theory and method of solving multi-objective optimization problems in operational research. Simulation results show the effectiveness and feasibility of the models and algorithms presented in this paper.