Parasite Recognition and Signaling Mechanisms in Innate Immune Responses to Malaria

Malaria caused by the Plasmodium family of parasites, especially P.falciparum and P. vivax, is a major health problem in many countries in the tropical and subtropical regions of the world. The disease presents a wide array of systemic clinical conditions and several life-threatening organ pathologies, including the dreaded cerebral malaria. Like many other infectious diseases, malaria is an inflammatory response-driven disease, and positive outcomes to infection depend on finely tuned regulation of immune responses that efficiently clear parasites and allow protective immunity to develop. Immune responses initiated by the innate immune system in response to parasites play key roles both in protective immunity development and pathogenesis. Initial pro-inflammatory responses are essential for clearing infection by promoting appropriate cell-mediated and humoral immunity. However, elevated and prolonged pro-inflammatory responses owing to inappropriate cellular programming contribute to disease conditions. A comprehensive knowledge of the molecular and cellular mechanisms that initiate immune responses and how these responses contribute to protective immunity development or pathogenesis is important for developing effective therapeutics and/or a vaccine. Historically, in efforts to develop a vaccine, immunity to malaria was extensively studied in the context of identifying protective humoral responses, targeting proteins involved in parasite invasion or clearance. The innate immune response was thought to be non-specific. However, during the past two decades, there has been a significant progress in understanding the molecular and cellular mechanisms of host-parasite interactions and the associated signaling in immune responses to malaria. Malaria infection occurs at two stages, initially in the liver through the bite of a mosquito, carrying sporozoites, and subsequently, in the blood through the invasion of red blood cells by merozoites released from the infected hepatocytes. Soon after infection, both the liver and blood stage parasites are sensed by various receptors of the host innate immune system resulting in the activation of signaling pathways and production of cytokines and chemokines. These immune responses play crucial roles in clearing parasites and regulating adaptive immunity. Here, we summarize the knowledge on molecular mechanisms that underlie the innate immune responses to malaria infection

The Nucleosome (Histone-DNA Complex) Is the TLR9-Specific Immunostimulatory Component of Plasmodium falciparum That Activates DCs

The systemic clinical symptoms of Plasmodium falciparum infection such as fever and chills correspond to the proinflammatory cytokines produced in response to the parasite components released during the synchronized rupture of schizonts. We recently demonstrated that, among the schizont-released products, merozoites are the predominant components that activate dendritic cells (DCs) by TLR9-specific recognition to induce the maturation of cells and to produce proinflammatory cytokines. We also demonstrated that DNA is the active constituent and that formation of a DNA-protein complex is essential for the entry of parasite DNA into cells for recognition by TLR9. However, the nature of endogenous protein-DNA complex in the parasite is not known. In this study, we show that parasite nucleosome constitute the major protein-DNA complex involved in the activation of DCs by parasite nuclear material. The parasite components were fractionated into the nuclear and non-nuclear materials. The nuclear material was further fractionated into chromatin and the proteins loosely bound to chromatin. Polynucleosomes and oligonucleosomes were prepared from the chromatin. These were tested for their ability to activate DCs obtained by the FLT3 ligand differentiation of bone marrow cells from the wild type, and TLR2−/−, TLR9−/− and MyD88−/− mice. DCs stimulated with the nuclear material and polynucleosomes as well as mono- and oligonucleosomes efficiently induced the production of proinflammatory cytokines in a TLR9-dependent manner, demonstrating that nucleosomes (histone-DNA complex) represent the major TLR9-specific DC-immunostimulatory component of the malaria parasite nuclear material. Thus, our data provide a significant insight into the activation of DCs by malaria parasites and have important implications for malaria vaccine development

The Effect of Building Electricity Consumption on Residents’ Subjective Well-Being: Evidence from China

Residential electricity consumption has an important impact on China’s construction of a low-carbon society. However, at present, little of the literature analyzes the influencing factors of residents’ overall well-being from the perspective of micro investigation. Based on the micro mixed cross section data of the Chinese General Social Survey (CGSS), this paper empirically studies the impact of residential electricity consumption on residents’ subjective well-being. In addition, in the heterogeneity analysis, we found that an increase in residential electricity consumption will improve the overall well-being of females and people with low levels of education, but it has no significant effect on males and people with high levels of education. Moreover, the increase in residential electricity consumption has improved the life satisfaction of young people and middle-aged people. Meanwhile, the increase in residential electricity consumption has a significant, positive impact on both low-income and high-income households. Further analysis shows that no nonlinear relationship exists between the increase in residents’ power consumption and the improvement in life satisfaction. This paper enriches the research on residential energy and provides policy implications for the current Chinese government to save energy, reduce emissions, and improve residents’ quality of life

Integration and scale application of shale gas exploration and development engineering technologies in Sichuan and Chongqing areas

Based on 8 years' exploration and production since the spud in of the first shale gas well in the Changning–Weiyuan national demonstration zone in the Sichuan Basin in 2009, great progress and all-sided development have been achieved in shale gas exploration and development engineering technologies in China. In order to promote scale shale gas development efficiently with high benefits in Sichuan and Chongqing areas, it is of great significance to summarize in time the optimized and integrated support technologies of shale gas exploration and development engineering. And the following research results were obtained. First, 10 principal technology series at the domestic leading level in shale gas well drilling and completion engineering are formed and completed, providing a technical support for a drastic increase of shale gas production. Second, volumetric fracturing support technologies from design to laboratory experiment evaluation and to real time monitoring of fracturing networks based on borehole seismic data are developed, ensuring the implementation effects of shale gas stimulation schemes. Third, simultaneous operation modes are innovatively established, such as drilling–fracturing, drilling–production & transportation and fracturing–production & transportation, and pad arrangement is optimized so that batch, modularized, programmed and integrated operation is realized and the commissioning schedule of shale gas wells is sped up greatly. Fourth, six series of environmental protection and energy saving technologies for shale gas development are developed, and consequently clean and energy saving production of shale gas is realized. Fifth, a technological system with a high-precision 3D seismic prospecting technology as the base is established to provide a basis for the realization of “transparent” gas reservoirs. Sixth, ground gathering technologies are optimized and intellectual and digital management of gas reservoir production and transportation is realized. It is concluded that these support technologies for shale gas exploration and development engineering provide an effective support for the increase of shale gas production of the Changning–Weiyuan shale gas national demonstration zone and they play a guiding and demonstrating role in technological progress and managerial innovation. Keywords: Sichuan Basin, Changning–Weiyuan shale gas national demonstration zone, Engineering series, Drilling-fracturing, Drilling–production & transportation, Fracturing–production & transportation, Large-scale benefi

Tribological Properties of Porous PEEK Composites Containing Ionic Liquid under Dry Friction Condition

NaCl particles were added into Polyetheretherketone (PEEK) and its composites to produce porous PEEK-based materials by washing NaCl away after the high-temperature compression molding process. After that, an ionic liquid was added into the porous materials under vacuum condition. Carbon fibers (CF), as reinforcement, and PTFE, as an internal solid lubricant, were employed to prepare PEEK composites. Tribological properties under dry friction condition were studied on a ring-on-disc tribo-meter. The influence of CF and PTFE on tribological properties was carefully investigated. The results indicated that, in comparison with traditional PEEK composites (CF/PTFE/PEEK), the porous PEEK composites containing ionic liquid showed much better tribological properties. It is found that CF can help PEEK form effective pores to suck in the ionic liquid resulting in a better tribological performance. CF reinforced porous PEEK containing ionic liquid (p-CF/PEEK + IL) demonstrated the lowest friction coefficient (27% of CF/PTFE/PEEK) and the lowest wear loss (only 0.9% of CF/PTFE/PEEK). Long time tribological test revealed that the wear mass loss comes from the running-in period, while its wear is negligible after this period. It is also found that the addition of PTFE has a negative influence on the tribological behaviors, especially under high sliding velocity and applied load

Drilling and completion technologies for deep carbonate rocks in the Sichuan Basin: Practices and prospects

The exploration and development of oil and gas resources in the Sichuan Basin is shifting to the deeper strata. The deep and ultra-deep wells in deep carbonate gas reservoirs are faced with many difficulties, such as multiple pressure systems, poor drillability, ultra-high pressure, ultra-high temperature and high sulfur content, which bring great challenges to drilling and completion engineering. In order to ensure the smooth exploration and development of deep carbonate oil and gas resources in the Sichuan Basin, the overall concept of combining field practice and technological research is followed. During the 13th Five-Year Plan, a batch of ultra-deep wells (well depth about 8000 m) have been drilled fast and safely (such as Well SYX133 in the Shuangyushi structure), and great progresses have been achieved in the experimental research of the support technologies in drilling and completion of deep and ultra-deep wells. And the achievements are as follows. First, the optimization of non-standard well structure, combined with the application of precisely managed pressure drilling technology and under-pressure plugging technology, lays a foundation for the optimized fast drilling and the safe reaching of geological targets. Second, a high-efficiency customized PDC drill bit is comprehensively optimized, popularized and applied, which effectively improves the average rate of penetration (ROP) in difficult-to-drill formations. Third, the development and application of drilling fluids (e.g. being resistant to high temperature of 200 °C and anti-composite brine) and active under-pressure plugging technology effectively reduces downhole complexities while drilling the complex formations, such as high temperature and high pressure brine and circulation loss. Fourth, when precisely managed pressure drilling and precisely managed pressure cementing methods are applied in the strata with a narrow density window, multiple pressure systems and pressure sensitivity, the average drilling and completion fluid loss is reduced by more than 90%, and the complexity treatment time is cut down by more than 85%, and the cementing quality pass rate is increased by more than 20%. Fifth, the integrated application of ROP improvement technologies and tools (e.g. air drilling) results in a great reduction of drilling cycle and cost. It is concluded that the experimental research achievements provide basic support for the fast development of natural gas resources in the Anyue Gas Field, Sichuan Basin, and the great discovery of the Permian and Devonian natural gas resources in the northwestern Sichuan Basin. What's more, in order to adapt to the development of the deep natural gas (over 9000 m) in the Sichuan Basin during the 14th Five-Year Plan, it is necessary to speed up researches on drilling and completion technologies in nine aspects, e.g. high-temperature downhole tools and working fluid