Search

By a pilot trial on investigating immunomodulatory activity and target of ginsenosides, the major bioactive components of ginseng, here we report that structural analogues in herbal medicines hit a shared target to achieve cumulative bioactivity. A ginsenoside analogues combination with definite immunomodulatory activity in vivo was designed by integrating pharmacodynamics, serum pharmacochemistry and pharmacokinetics approaches. The cumulative bioactivity of the ginsenoside analogues was validated on LPS/ATP-induced RAW264.7 macrophages. The potentially shared target NLRP3 involved in this immunomodulatory activity was predicted by systems pharmacology. The steady binding affinity between each ginsenoside and NLRP3 was defined by molecular docking and bio-layer interferometry assay. The activation of NLRP3 inflammasomes in LPS/ATP-induced RAW264.7 was significantly suppressed by the combination, but not by any individual, and the overexpression of NLRP3 counteracted the immunomodulatory activity of the combination. All these results demonstrate that the ginsenoside analogues jointly hit NLRP3 to achieve cumulative immunomodulatory activity., Zhang et al. design ginsenoside structural analogues and demonstrate that their combination shows more potent immunomodulatory activities than individual ginsenosides used alone at the same dosages. They predict that these analogues act on the joint target NLRP3 and consequently suggest that structural analogues hit a shared target to achieve cumulative bioactivity.

In this paper, the effects of melt thermal-rate treatment (MTRT) and modification of Y on the microstructure and mechanical properties of Zn-27Al alloy are discussed. The experimental results suggest that the microstructure can be refined and the mechanical properties can be improved with the MTRT technique. The effect of grain refinement achieves the best when the melt temperature is up to 830°C, the tensile strength of alloy is 452 MPa and the hardness is 123 HB, each measure increasing by 13.6% and 7.1% compared with the untreated alloy, respectively. When the alloy is treated with the MTRT + Y technique, the mechanical properties of the alloys cannot improve compared with that of the alloy treated with MTRT. The mechanism of the effects of MTRT and Y are discussed.

This article will discuss the influence of the rare earth Y on the microstructure and mechanical properties of Zn-Al alloys (ZA27, ZA35, and ZA40), and it will provide reference to rare-earth microalloying through the cast ingot metallurgy process. The results also suggest that the microstructure can be refined and mechanical properties can be improved obviously when adding the right amount of Y, and its tensile strength and brinell hardness increased by 9.1% and 11.7% compared with the unmodified ZA27 alloys, respectively. Compared with non-Y addition, the alloys will form dispersed YZn12 phase, which can strongly pin dislocations and subgrain boundary, inhibiting further recrystallization. On this basis, the impacts of Y on the microstructure and mechanical properties of ZA27, ZA35, and ZA40 have been explored. After adding Y, the microstructures of as-cast Zn-Al alloys are refined at different degree. However, with the increase of Al content, the microstructure shows a certain coarsening and the segregation and shrinkage porosity occur. The most effective refining appears in ZA27-0.4%Y.

Monodisperse quantum dots (QDs) were prepared by low-temperature process. The remarkable narrow emission peak of the QDs helps the liquid crystal displays (LCD) and electroluminescence displays (QD light-emitting diode, QLED) to generate wide color gamut performance. The range of the color gamut for QD light-converting device (QLCD) is controlled by both the QDs and color filters (CFs) in LCD, and for QLED, the optimized color gamut is dominated by QD materials. Electronic supplementary material The online version of this article (doi:10.1186/s11671-017-1907-1) contains supplementary material, which is available to authorized users.

Our group was the first one reporting that autophagy could be triggered by airborne fine particulate matter (PM) with a mean diameter of less than 2.5 μm (PM2.5) in human lung epithelial A549 cells, which could potentially lead to cell death. In the present study, we further explored the potential interactions between autophagy and apoptosis because it was well documented that PM2.5 could induce apoptosis in A549 cells. Much to our surprise, we found that PM2.5-exposure caused oxidative stress, resulting in activation of multiple cell death pathways in A549 cells, that is, the tumor necrosis factor-alpha (TNF-α)-induced pathway as evidenced by TNF-α secretion and activation of caspase-8 and -3, the intrinsic apoptosis pathway as evidenced by increased expression of pro-apoptotic protein Bax, decreased expression of anti-apoptotic protein Bcl-2, disruption of mitochondrial membrane potential, and activation of caspase-9 and -3, and autophagy as evidenced by an increased number of double-membrane vesicles, accompanied by increases of conversion and punctuation of microtubule-associated proteins light chain 3 (LC3) and expression of Beclin 1. It appears that reactive oxygen species (ROS) function as signaling molecules for all the three pathways because pretreatment with N-acetylcysteine, a scavenger of ROS, almost completely abolished TNF-α secretion and significantly reduced the number of apoptotic and autophagic cells. In another aspect, inhibiting autophagy with 3-methyladenine, a specific autophagy inhibitor, enhanced PM2.5-induced apoptosis and cytotoxicity. Intriguingly, neutralization of TNF-α with an anti-TNF-α special antibody not only abolished activation of caspase-8, but also drastically reduced LC3-II conversion. Thus, the present study has provided novel insights into the mechanism of cytotoxicity and even pathogenesis of diseases associated with PM2.5 exposure.

Purpose To identify bioactive equivalent combinatorial components (BECCs) in herbal medicines. The exact composition of effective components in herbal medicines is often elusive due to the lack of adequate screening methodology. Herein, we propose a hypothesis that BECCs accounting for the whole efficacy of original herbal medicines could be discovered from a complex mixture of constituents. Methods We developed a bioactive equivalence oriented feedback screening method and applied it to discover the BECCs from an herbal preparation Cardiotonic Pill (CP). The operations include chemical profiling of CP, followed by an iterative loop of determining, collecting and evaluating candidate BECCs. Results A combination of 18 compounds was identified as BECCs from CP, which accounts for 15.0% (w/w) of original CP. We have demonstrated that the BECCs were as effective as CP in cell models and in a rat model of myocardial infarction. Conclusions This work answers the key question of which are real bioactive components for CP that have been used in clinic for many years, and provides a promising approach for discovering BECCs from herbal medicines. More importantly, the BECCs could be extended to improve quality control of herbal products and inspire an herbal medicines based discovery of combinatorial therapeutics. Electronic supplementary material The online version of this article (doi:10.1007/s11095-013-1283-1) contains supplementary material, which is available to authorized users.

In this study, effects of thermalrate treatment (TRT) technique on microstructure and mechanical properties of hypoeutectic Al–Si alloys with addition of Ti were studied. The superheating temperatures of the melt were ascertained based on the DSC result. The results show that when the alloy castings in sand mold were treated with TRT technique at the superheating temperature of 930 °C, α-Al changes into smaller equiaxial crystals from coarse dendrites, and hardness of the alloy increases by 12.7 %, compared to that of the alloy treated with conventional casting technique. In addition, the supercooling increases to 8.5 °C and the characteristic temperatures of eutectic solidification are all the lowest with TRT technique at the superheating temperature of 930 °C. As holding time increases at the pouring temperature of 730 °C in TRT at the superheating temperature of 930 °C, the effects on microstructure and mechanical properties of the alloy casting in sand mold decrease. TRT technique plays a limited role in the alloy casting in permanent mold.

In order to reduce the traffic pressure of urban arterial road with the rational utilization of the branch road, the vehicle meeting behavior on the branch road without divided lane was described, and the cellular automation (CA) model was put forward by introducing meeting behavior to reflect the relation between safe meeting speed and road width. The numerical simulation results depict several relation curves between road section capacity, speed and road width under different directional distributions of traffic flow, as well as the curves between the major and minor direction saturation flow, speed and road width. These relation characteristics indicate that except the one-way road section capacity and speed remaining unchanged, other road section capacities and speeds under different directional distributions increase with the increase of road width. On narrow road, the two-way traffic capacity and speed are less than those of one-way traffic; on wide road, the two-way traffic capacity doubles that of one-way traffic, but their speeds are almost the same. As the directional distribution moves to an even distribution of 50/50, the major direction saturation flows and speeds as well as the minor direction speeds tend to decease, while the minor direction saturation flow tends to increase.

It has been well claimed that herbal medicines (HMs) elicit effects via a multi-compounds and multi-targets synergistic mode. However, it lacks appropriate strategies to uncover the combinatory compounds that take effect together and contribute to a certain pharmacological effect of an herb as a whole, which represents a major bottleneck in providing sound evidence in supporting the clinic benefits of HMs. Here, we proposed a strategy to the identification of combinatory compounds contributing to the anti-inflammatory activity of Cardiotonic Pill (CP). The strategy proposed herein contains four core steps, including the identification of bioequivalent combinatorial compounds, chemical family classification-based combinatorial screen, interactive mode evaluation and activity contribution index assay. Using this strategy, we have successfully identified six compounds in combination responsible for the anti-inflammatory effect of CP, whose anti-inflammatory activities were found comparable to that of the whole CP. Additionally, these six compounds take effect via an additive mode but little synergism. This study, together with our recent work in the identification of bioactive equivalent compounds combination, provides a widely applicable strategy to the identification of combinatory compounds responsible for a certain pharmacological activity of HMs.

In this paper electric load is forecast for the classified power consumers of Shanghai urban area for the scheduled years in short term and in long term respectively. The monthly load in 1999 is forecast on the basis of the data during 1992–1998, and the approximate load in 2010 is forecast on the basis of the data during 1990–1998.

Introduction Recently, we reported that high levels of resistin are present in the peripheral blood of patients with intracerebral hemorrhage and are associated with a poor outcome. However, not much is known regarding the change in plasma resistin and its relation with mortality after traumatic brain injury (TBI). Thus, we sought to investigate change in plasma resistin level after TBI and to evaluate its relation with disease outcome. Methods Fifty healthy controls and 94 patients with acute severe TBI were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5 and 7 after TBI. Its concentration was measured by enzyme-linked immunosorbent assay. Results Twenty-six patients (27.7%) died from TBI within 1 month. After TBI, plasma resistin level in patients increased during the 6-hour period immediately after TBI, peaked within 24 hours, plateaued at day 2, decreased gradually thereafter and was substantially higher than that in healthy controls during the 7-day period. A forward stepwise logistic regression selected plasma resistin level (odds ratio, 1.107; 95% confidence interval, 1.014-1.208; P = 0.023) as an independent predictor for 1-month mortality of patients. A multivariate linear regression showed that plasma resistin level was negatively associated with Glasgow Coma Scale score (t = -6.567, P < 0.001). A receiver operating characteristic curve identified plasma resistin cutoff level (30.8 ng/mL) that predicted 1-month mortality with the optimal sensitivity (84.6%) and specificity (75.0%) values (area under curve, 0.854; 95% confidence interval, 0.766-0.918; P < 0.001). Conclusions Increased plasma resistin level is found and associated with Glasgow Coma Scale score and mortality after TBI.