Reconstruction of cytosolic fumaric acid biosynthetic pathways in Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Fumaric acid is a commercially important component of foodstuffs, pharmaceuticals and industrial materials, yet the current methods of production are unsustainable and ecologically destructive.</p> <p>Results</p> <p>In this study, the fumarate biosynthetic pathway involving reductive reactions of the tricarboxylic acid cycle was exogenously introduced in <it>S. cerevisiae </it>by a series of simple genetic modifications. First, the <it>Rhizopus oryzae </it>genes for malate dehydrogenase (<it>RoMDH</it>) and fumarase (<it>RoFUM1</it>) were heterologously expressed. Then, expression of the endogenous pyruvate carboxylase (<it>PYC2</it>) was up-regulated. The resultant yeast strain, FMME-001 ↑<it>PYC2 </it>+ ↑<it>RoMDH</it>, was capable of producing significantly higher yields of fumarate in the glucose medium (3.18 ± 0.15 g liter^-1) than the control strain FMME-001 empty vector.</p> <p>Conclusions</p> <p>The results presented here provide a novel strategy for fumarate biosynthesis, which represents an important advancement in producing high yields of fumarate in a sustainable and ecologically-friendly manner.</p

Understanding and Tuning Nanostructured Materials for Chemical Energy Conversion

The conversion of energy that employs chemical reaction is termed chemical energy conversion. In my dissertation, I have focused on chemical energy conversion systems involving energetic materials and lithium ion batteries, where performance is strongly dependent on the properties of materials and their architecture. The objective of this study is to enhance our understanding and tuning of nanostructured materials that might find application toward energetic materials and electrode materials in lithium ion batteries. Rapid heating diagnostics tools, i.e. temperature-jump techniques, have been used to study the ignition of aluminum nanoparticles, nanothermite reaction mechanism and metal oxides nanoparticles decomposition under rapid heating conditions (~105-106 K/s). Time-resolved mass spectra results support the hypothesis that Al containing species diffuse outwards through the oxide shell. Low effective activation energies were found for metal oxides nanoparticles decomposition at high heating rates, implying the mass transfer control at high heating rates. The role of oxygen release from oxidizer in nanothermite reactions have been examined for several different systems, including some using microsized oxidizer (i.e., nano-Al/micro-I2O5). In particular, for periodate based nanothermites, direct evidence from high heating rate SEM and mass spectrometry results support that direct gas phase oxygen release from oxidizer decomposition is critical in its ignition and combustion. Efforts have also been made to synthesize nanostructured materials for nanoenergetic materials and lithium ion batteries applications. Hollow CuO spheres were synthesized by aerosol spray pyrolysis, employing a gas blowing mechanism for the formation of hollow structure during aerosol synthesis. The materials synthesized as oxidizers in nanothermite demonstrated superior performance, and of particular note, periodate salts based nanothermite demonstrated the best gas generating performance for nanothermite materials. Energetic composite nanofibrous mats (NC/Al-CuO, NC/Al-Fe2O3, and NC/Al-Bi2O3) were also prepared by an electrospinning method and evaluated for their combustion performance. Aerosol spray pyrolysis was employed to produce carbon coated CuO hollow spheres, Mn3O4 hollow spheres, and Fe2O3 mesoporous spheres. These hollow/mesoporous spheres demonstrated superior electrochemical performance when used as anode materials in lithium ion batteries. The effects of the amorphous and crystal structures on the electrochemical performance and the structure evolution during electrochemical tests were also investigated

CASE STUDY ON THE LARGE DIAMETER PIPE JACKING FOR UTILITY TUNNEL

Pipe jacking have been widely used in utility tunnel constructions as an environment-friendly method in China. This study is focus on the critical technologies used in the pipe jacking for the utility tunnel in Huanggang Mingzhu road. The inner and outer diameter of this utility tunnel are 4m and 4.8m respectively, which is the largest circular pipe jacking project in China at present. This utility tunnel is designed under the urban main road with a heavy traffic, so the control accuracy of pipe jacking construction is required to be high. According to the characteristics of the project and actual construction technical measures, the key construction technologies including pipe jacking equipment, launching of small spacing, slurry circulating, the drag reduction technology, and the control of surface settlement are discussed in this paper. Meanwhile, the jacking force and ground settlement during pipe jacking construction are monitored. The results show that the selected pipe jacking machine has good adaptability to the geological conditions of the project. The actual jacking force is much smaller than the theoretical value, and the two intermediate jacking stations are not activated. In addition, the road surface deformation is -8–5mm during the whole process of pipe jacking construction, which has no impact on surface traffic

An Improved Modeling for Low-grade Organic Rankine Cycle Coupled with Optimization Design of Radial-inflow Turbine

This document is the Accepted Manuscript of the following article: Lijing Zhai, Guoqiang Xu, Jie Wen, Yongkai Quan, Jian Fu, Hongwei Wu, and Tingting Li, ‘An improved modeling for low-grade organic Rankine cycle coupled with optimization design of radial-inflow turbine’, Energy Conversion and Management, Vol. 153: 60-70, December 2017. Under embargo. Embargo end date: 10 October 2018. The final, published version is available online at DOI: https://doi.org/10.1016/j.enconman.2017.09.063. Published by Elsevier Ltd.Organic Rankine cycle (ORC) has been proven to be an effective and promising technology to convert low-grade heat energy into power, attracting rapidly growing interest in recent years. As the key component of the ORC system, turbine significantly influences the overall cycle performance and its efficiency also varies with different working fluids as well as in different operating conditions. However, turbine efficiency is generally assumed to be constant in the conventional cycle design. Aiming at this issue, this paper couples the ORC system design with the radial-inflow turbine design to investigate the thermodynamic performance of the ORC system and the aerodynamic characteristics of radial-inflow turbine simultaneously. The constrained genetic algorithm (GA) is used to optimize the radial-inflow turbine with attention to six design parameters, including degree of reaction, velocity ratio, loading coefficient, flow coefficient, ratio of wheel diameter, and rotational speed. The influence of heat source outlet temperature on the performance of the radial-inflow turbine and the ORC system with constant mass flow rate of the heat source and constant heat source inlet temperature is investigated for four kinds of working fluids. The net electrical powers achieved are from few tens kWs to one hundred kWs. The results show that the turbine efficiency decreases with increasing heat source outlet temperature and that the decreasing rate of turbine efficiency becomes faster in the high temperature region. The optimized turbine efficiency varies from 88.06% (using pentane at the outlet temperature of 105 ºC) to 91.01% (using R245fa at the outlet temperature of 80 ºC), which appears much higher compared to common values reported in the literature. Furthermore, the cycle efficiency increases monotonously with the growth of the heat source outlet temperature, whereas the net power output has the opposite trend. R123 achieves the maximum cycle efficiency of 12.21% at the heat source outlet temperature of 110 ºC. Based on the optimized results, the recommended ranges of the key design parameters for ORC radial-inflow turbine are presented as well.Peer reviewe

Anti-IL-17 Antibody Improves Hepatic Steatosis by Suppressing Interleukin-17-Related Fatty Acid Synthesis and Metabolism

To investigate the relationship between interleukin-17 and proteins involved in fatty acid metabolism with respect to alcoholic liver disease, male ICR mice were randomized into five groups: control, alcoholic liver disease (ALD) at 4 weeks, 8 weeks, and 12 weeks, and anti-IL-17 antibody treated ALD. A proteomic approach was adopted to investigate changes in liver proteins between control and ALD groups. The proteomic analysis was performed by two-dimensional difference gel electrophoresis. Spots of interest were subsequently subjected to nanospray ionization tandem mass spectrometry (MS/MS) for protein identification. Additionally, expression levels of selected proteins were confirmed by western blot. Transcriptional levels of some selected proteins were determined by RT-PCR. Expression levels of 95 protein spots changed significantly (ratio >1.5, P<0.05) during the development of ALD. Sterol regulatory element-binding protein-lc (SREBP-1c), carbohydrate response element binding protein (ChREBP), enoyl-coenzyme A hydratase (ECHS1), and peroxisome proliferator-activated receptor alpha (PPAR-α) were identified by MS/MS among the proteins shown to vary the most; increased IL-17 elevated the transcription of SREBP-1c and ChREBP but suppressed ECHS1 and PPAR-α. The interleukin-17 signaling pathway is involved in ALD development; anti-IL-17 antibody improved hepatic steatosis by suppressing interleukin-17-related fatty acid metabolism

Structural basis for energy transfer in a huge diatom PSI-FCPI supercomplex

Diatom is an important group of marine algae and contributes to around 20% of the global photosynthetic carbon fixation. Photosystem I (PSI) of diatoms is associated with a large number of fucoxanthin-chlorophyll a/c proteins (FCPIs). We report the structure of PSI-FCPI from a diatom Chaetoceros gracilis at 2.38 Å resolution by single-particle cryo-electron microscopy. PSI-FCPI is a monomeric supercomplex consisting of 12 core and 24 antenna subunits (FCPIs), and 326 chlorophylls a, 34 chlorophylls c, 102 fucoxanthins, 35 diadinoxanthins, 18 β-carotenes and some electron transfer cofactors. Two subunits designated PsaR and PsaS were found in the core, whereas several subunits were lost. The large number of pigments constitute a unique and huge network ensuring efficient energy harvesting, transfer and dissipation. These results provide a firm structural basis for unraveling the mechanisms of light-energy harvesting, transfer and quenching in the diatom PSI-FCPI, and also important clues to evolutionary changes of PSI-LHCI

Anoikis resistance regulates immune infiltration and drug sensitivity in clear-cell renal cell carcinoma: insights from multi omics, single cell analysis and in vitro experiment

BackgroundAnoikis is a form of programmed cell death essential for preventing cancer metastasis. In some solid cancer, anoikis resistance can facilitate tumor progression. However, this phenomenon is underexplored in clear-cell renal cell carcinoma (ccRCC).MethodsUsing SVM machine learning, we identified core anoikis-related genes (ARGs) from ccRCC patient transcriptomic data. A LASSO Cox regression model stratified patients into risk groups, informing a prognostic model. GSVA and ssGSEA assessed immune infiltration, and single-cell analysis examined ARG expression across immune cells. Quantitative PCR and immunohistochemistry validated ARG expression differences between immune therapy responders and non-responders in ccRCC.ResultsARGs such as CCND1, CDKN3, PLK1, and BID were key in predicting ccRCC outcomes, linking higher risk with increased Treg infiltration and reduced M1 macrophage presence, indicating an immunosuppressive environment facilitated by anoikis resistance. Single-cell insights showed ARG enrichment in Tregs and dendritic cells, affecting immune checkpoints. Immunohistochemical analysis reveals that ARGs protein expression is markedly elevated in ccRCC tissues responsive to immunotherapy.ConclusionThis study establishes a novel anoikis resistance gene signature that predicts survival and immunotherapy response in ccRCC, suggesting that manipulating the immune environment through these ARGs could improve therapeutic strategies and prognostication in ccRCC