Previous studies have reported that recombinant tumor necrosis factor (TNF)-α has powerful antiviral activity but severe systematic side effects. Jasminin is a common bioactive component found in ...Chinese herbal medicine beverage "Jasmine Tea". Here, we report that jasminin-induced endogenous TNF-α showed antiviral activity in vitro. The underlying TNF-α-inducing action of jasminin was also investigated in RAW264.7 cells. The level of endogenous TNF-α stimulated by jasminin was first analyzed by an enzyme-linked immunosorbent assay (ELISA) from the cell culture supernatant of RAW264.7 cells. The supernatants were then collected to investigate the potential antiviral effect against herpes simplex virus 1 (HSV-1). The antiviral effects of jasminin alone or its supernatants were evaluated by a plaque reduction assay. The potential activation of the PI3K-Akt pathway, three main mitogen-activated protein kinases (MAPKs), and nuclear factor (NF)-κB signaling pathways that induce TNF-α production were also investigated. Jasminin induces TNF-α protein expression in RAW264.7 cells without additional stimuli 10-fold more than the control. No significant up-expression of type I, II, and III interferons; interleukins 2 and 10; nor TNF-β were observed by the jasminin stimuli. The supernatants, containing jasminin-induced-TNF-α, showed antiviral activity against HSV-1. The jasminin-stimulated cells caused the simultaneous activation of the Akt, MAPKs, and NF-κB signal pathways. Furthermore, the pretreatment of the cells with the Akt, MAPKs, and NF-κB inhibitors effectively suppressed jasminin-induced TNF-α production. Our research provides evidence that endogenous TNF-α can be used as a strategy to encounter viral infections. Additionally, the Akt, MAPKs, and NF-κB signaling pathways are involved in the TNF-α synthesis that induced by jasminin.
The friction coefficient between a railway wheel and rail surface is a crucial factor in maintaining high acceleration and braking performance of railway vehicles; therefore, monitoring this friction ...coefficient is important. Due to the difficulty in directly measuring the friction coefficient, the creep force or creepage, indirect methods using state observers are used more frequently. This paper presents an approach using an unscented kalman filter to estimate the creep force and creepage and the friction coefficient from traction motor behaviours. A scaled roller rig is designed and a series of experiments is carried out to evaluate the estimator performance.
In recent decades, infections caused by the opportunistic fungus
Candida albicans
have increased, especially in patients with immunodeficiency. In this study, we investigated the mechanism of action ...of sanguinarine (SAN) against
C. albicans
both
in vitro
and
in vivo
. SAN exhibited antifungal activity against
C. albicans
clinical isolates, with MICs in the range of 112.8–150.5 μM. Furthermore, scanning electron and transmission electron microscopy showed that SAN induced morphological changes as well as structure disruption in
C. albicans
cells, including masses of cellular debris, ruptured cell walls, and membrane deformation. Flow cytometry revealed that SAN could lead to cell membrane damage, and ergosterol content analysis indicated that SAN could cause ergosterol content reduction exceeding 90%. Further, we validated the efficacy of SAN against candidiasis caused by
C. albicans
in a murine model, and SAN significantly improved survival and reduced weight loss compared to vehicle. The treatment of 1.5 and 2.5 mg/kg/d SAN obviously reduced the fungal burden in the kidney. In addition, histopathological examination indicated that no fungal cells were observed in lung and kidney tissues after SAN treatment. Hence, this study suggests that SAN is a promising plant-derived compound for the development of an effective anticandidal agent.
In this study, the coding sequence of the lipase from Proteus sp. SW1 was optimized via codon optimization and subjected to expression in Pichia pastoris GS115. The maximum enzyme yield was 387 mg/L ...in the supernatants of the shake-flask culture. The purified recombinant lipase exhibited a specific activity of 130 U/mg toward p-nitrophenyl Laurate. Its optimum pH and temperature were 8.0 and 40°C, respectively. It was highly stable and even activated in water-miscible solvents, showing over 102% residual activity after 24 h incubation in ethanol, acetone, isopropanol and acetonitrile. In addition, the enzyme showed promoted activity with the increasing concentrations of methanol/ethanol and exhibited the maximum activity at 80%. In a solvent-free system for biodiesel synthesis with a one-step addition of methanol, the recombinant lipase displayed a 87% conversion rate toward palm oil at the high water content of 80%. The highly improved expression level and activity of the recombinant lipase may contribute to enable its commercial-scale production, and the unique properties would make it a particularly promising biocatalyst for biodiesel production in the future.
•The lipase gene was systematically codon-optimized and highly expressed in Pichia pastoris.•The expression and specific activity of 257- and 18-fold increased, respectively, compared to those in E. coli.•RLipase displayed a long-term tolerance to high concentrations of methanol or ethanol.•Instead of being deactivated, RLipase was activated by 70–98% of methanol or ethanol.•RLipase showed a high conversion rate toward palm oil at the high water content of 80%.
Dynamics of a long beam on the elastic foundation subjected to moving loads is studied in the present paper. The sliding window technique is used to dynamically truncate the long beam and a reduced ...time-varying beam system is obtained. The Hamilton’s principle is employed to establish the equations of motion of the reduced system. The variable separation method is adopted to solve dynamical responses of the reduced system. Examples of a long simply supported Timoshenko beam on the nonlinear foundation subjected to a single moving load and multiple loads are included. Numerical results of the reduced model compared with the ones obtained from the moving element model adapted in literature are carried out to show the validity and the good efficiency of the method proposed in the present paper.
This paper reports on fundamental research to investigate the influence of wheelset flexibility on the development of wheel polygonization of a locomotive. After preparing a flexible wheelset model ...by importing a FE (Finite Element) model into the MBS (Multi-Body System) environment, the investigation work proceeded in 3 steps. Firstly, FRF (Frequency Response Function) of the contact responses against the track irregularity is analysed for a free wheelset and an on-track wheelset, with consideration of rotation effect. Secondly, the influence of the wheelset flexibility on the contact responses excited by white noise is investigated for straight and curved tracks. The final step is to check the influence of the wheelset flexibility on the development of wheel polygonization based on a developed prediction program for railway wheel polygonization. 6 scenarios are investigated with comparison between rigid and flexible wheelsets. Results show that, the wheelset flexibility cannot dominate the railway wheel polygonization in a general sense, unless some prerequisites are fulfilled to provide a suitable environment for the wheelset flexibility to be effectively and continually excited to fluctuate the contact responses, and thereby initiate wheel polygonization. The torsional mode of the wheelset can be effectively excited by stick-slip vibration due to saturated contact adhesion that can occur on track with small curve radii or by large traction torque. In this case, the developed wheel polygonization order will be exactly determined by the wheelset torsional modal frequency and the vehicle speed.
•The influence of wheelset flexibility on wheel polygonal wear is identified based on a prediction program.•All the investigated wheelset flexible modes can be excited to influence the contact responses, but in very different way.•The wheelset flexibility cannot dominate the wheel polygonization unless some prerequisites are fulfilled.•The torsional mode of wheelset can be excited by stick-slip vibration to initiate the wheel polygonization.
Chelerythrine (CHE) inhibits HSV-1 infection by suppressing virus binding to the cells.CHE inhibits HSV-1 ICP0 expression in the immediate early stage of infection.CHE might interact with gB and/or ...gD, resulting in conformational changes to interfere virus-cell fusion.
Herpes simplex virus type 1 (HSV-1) is a worldwide pathogen and mainly puts immunocompromised patients at higher risk of various complications. This research aims to demonstrate the antiviral activity of chelerythrine (CHE), an alkaloid compound derived from the traditional Chinese medicine Mcleaya cordata, towards the HSV-1 F strain.
Bioassay-guided fractionation was carried out in order to isolate the antiviral compound CHE. The plaque reduction assay was used to evaluate the antiviral activity of CHE. The combination of quantitative PCR (qPCR) and western blot was used to elucidate whether CHE interferes with viral DNA synthesis, followed by time-of-addition assay to examine which steps of HSV-1 infection CHE affected. The immunofluorescent assay and transmission electron microscopy assay were performed to further analyze the intracellular localization and the ultrastructural features of HSV-1 virions with the treatment of CHE. The binding affinity in CHE to targeted viral glycoprotein was investigated by surface plasmon resonance (SPR) assay and docking simulation.
CHE displayed a significant antiviral effect against HSV-1 at 0.312 to 2.5 µM with a viral titer reduction of 29.38% to 61.02%. CHE had an EC50 value of 1.78 µM against HSV-1, and the selectivity index (SI) for CHE was 4.07. Additionally, CHE inhibits ICP0 expression in the immediate early stage of infection, which further affected the early stage of infection, and subsequent viral replication. Results of the SPR assay showed that CHE had strong-binding affinity to gB with a KD value of 7.80 × 107 M, while gD with a value of 1.18 × 106 M. TEM revealed that CHE can clearly inhibit the virion release. In silico experiments further confirmed that CHE had low binding free energy in the activity sites of gB and gD.
This study revealed that CHE directly targeted viral gB or gD as a potent glycoprotein inhibitor, which suggested that CHE could be a virus entry inhibitor for HSV-1 treatment.
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•A method was to classify train stopping at red aspects using industrial data.•A hybrid of physical model and statistical model was used and validated.•The industry can understand and mitigate SPAD ...risks better based on this research project.
The paper describes a novel technique to reliably classify whether or not a train approaching a signal at red actually came to a stand before the signal cleared (red aspect approaches) using the data from conventional signalling systems. This data is limited to the times at which the signal aspect changes and the times at which the train enters and leaves the signalling section (‘berth’) in advance of the signal. Knowing the percentage of red aspect approaches is potentially important for understanding the likelihood of a signal being passed at danger (SPAD) at individual signals and also for normalisation of SPAD data, both locally and nationally, for trending and benchmarking. The industry currently uses the number of red aspect approaches based on driver surveys as estimates, which are considered to have significant shortcomings. The development of the classification model is described together with the validation procedures. The techniques presented in this paper allow red approach rates to be reliably determined without the need for complex integration of signalling system and on-train data recorder data. The initial study of 94 million train approaches shows that 5% of them stopped at red aspects. It is also highlighted that there is a large variation in the red aspect approach rates between signalling areas and between individual signals. SPAD risk assessment at individual signals could be significantly enhanced by the ability to estimate red aspect approach rates using the techniques described.
The friction coefficient at the wheel-rail interface is crucial for the traction, braking and guidance of the railway vehicle. Real-time knowledge of the friction coefficient could reduce wheel-rail ...damages as well as improve the vehicle running performance. The friction coefficient is very difficult to be directly measured; hence an indirect measurement method using an unscented Kalman filter was proposed in this paper. A re-adhesion controller was also developed. The method was assessed in a Simpack-Simulink co-simulation environment. The friction coefficient estimation method was found to be accurate, and the re-adhesion controller improved the vehicle braking performance as well as reduced the wheel-rail damage.
Monitoring the condition of suspension systems is significant to ensure the safe operation of modern railway vehicles. For this purpose, an online modal identification scheme, denoted as Correlation ...Subset based Stochastic Subspace Identification (CoS-SSI) is proposed in this paper to monitor the suspension conditions. Because of the widespread of the dynamic contact status between wheel and track, especially under faulty suspension cases, the vibration responses measured online exhibit high nonstationarity and nonlinearity. To take into account these characteristics of signals, the input correlation signals for SSI are clustered into several successive subsets according to their magnitudes, on which SSI is implemented one by one. In this way it yields a magnitude adaptive SSI for more reliable and accurate identification. Experimental studies were conducted on a 1/5th scaled roller rig system to verify the effectiveness of the proposed method for suspension monitoring. The experimental results show that the CoS-SSI outperform the conventional SSI in that it produces more reliable and realistic identification for the nonlinear system. Furthermore, the effectiveness of the CoS-SSI was verified experimentally with two faulty suspension faults induced into the system.
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