Strategies and challenges with the microbial conversion of methanol to high-value chemicals

As alternatives to traditional fermentation substrates, methanol (CH3OH), carbon dioxide (CO2) and methane (CH4) represent promising one-carbon (C1) sources that are readily available at low-cost and share similar metabolic pathway. Of these C1 compounds, methanol is used as a carbon and energy source by native methylotrophs, and can be obtained from CO2 and CH4 by chemical catalysis. Therefore, constructing and rewiring methanol utilization pathways may enable the use of one-carbon sources for microbial fermentations. Recent bioengineering efforts have shown that both native and nonnative methylotrophic organisms can be engineered to convert methanol, together with other carbon sources, into biofuels and other commodity chemicals. However, many challenges remain and must be overcome before industrial-scale bioprocessing can be established using these engineered cell refineries. Here, we provide a comprehensive summary and comparison of methanol metabolic pathways from different methylotrophs, followed by a review of recent progress in engineering methanol metabolic pathways in vitro and in vivo to produce chemicals. We discuss the major challenges associated with establishing efficient methanol metabolic pathways in microbial cells, and propose improved designs for future engineering

The mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is a cytosolic pattern recognition receptor (PRR) that recognizes multiple pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Once activated, NLRP3 initiates the inflammasome assembly together with the adaptor ASC and the effector caspase-1, leading to caspase-1 activation and subsequent cleavage of IL-1β and IL-18. Aberrant NLRP3 inflammasome activation is linked with the pathogenesis of multiple inflammatory diseases, such as cryopyrin­associated periodic syndromes, type 2 diabetes, non-alcoholic steatohepatitis, gout, and neurodegenerative diseases. Thus, NLRP3 is an important therapeutic target, and researchers are putting a lot of effort into developing its inhibitors. The review summarizes the latest advances in the mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors

Effects of tMa-Xin-Di-Tan decoction on ovalbumin-induced allergic asthma in mice

Purpose: To investigate the effect of the Ma-Xin-Di-Tan (MXDT) decoction on  ovalbumin-induced allergic asthma (AA) in mice.Methods: Asthma was induced in mice by ovalbumin (OVA) injection, and different doses of MXDT (150, 300, and 600 mg/kg/day) were administered orally for 28 days. Pathological changes in lung tissues were examined, while levels of cytokines, including interleukin (IL)-4, IL-6, IL-17, interferon (IFN)-γ, and transforming growth factor (TGF)-β, were determined using enzyme-linked immunosorbent assays (ELISAs) of the bronchoalveolar lavage fluid. Toll-like receptor (TLR)-4,  GATA-binding protein (GATA)-3, Ox40 ligand (OX40L), indoleamine  2,3-dioxygenase (IDO), forkhead box P3 (Foxp3), and T box expressed in T cells (T-bet) levels were determined in lung tissues by western blot analysis.Results: MXDT inhibited the inflammatory reaction of lung tissues in  OVA-challenged mice. After treatment with MXDT, levels of IL-4, IL-6, IL-17, and TGF-β were downregulated, whereas IFN-γ levels were upregulated. In addition,  MXDT decreased TLR-4, GATA-3, and OX40L levels in lung tissues but increased the expression of Foxp3, T-bet, and IDO.Conclusion: MXDT has antiallergic effects on OVA-induced AA in mice; the possible molecular mechanisms might involve the inhibition of inflammatory reactions and modulation of Th1/Th2 cytokine balance.Keywords: Ma-Xin-Di-Tan decoction, Allergic asthma, Inflammatory reactions, Th1/Th

A Fast Diagnosis Method for Both IGBT Faults and Current Sensor Faults in Grid-Tied Three-Phase Inverters With Two Current Sensors

© 1986-2012 IEEE. This article considers fault detection in the case of a three-phase three-wire (3P3W) inverter, when only two current sensors are used to save cost or due to a faulty current sensor. With two current sensors, there is no current method addressing the diagnosis of both IGBT open-circuit (OC) faults and current sensor faults. In order to solve this problem, this article proposes a method which innovatively combines two kinds of diagnosis variables, line voltage deviations and phase voltage deviations. The unique faulty characteristics of diagnosis variables for each fault are extracted and utilized to distinguish the fault. Using an average model, the method only needs the signals already available in the controller. Both IGBT OC faults and current sensor faults can be detected quickly in inverter mode and rectifier mode, so that the converter can be protected in a timely way to avoid further damages. In addition, error-adaptive thresholds are adopted to make the method robust. Effects such as system unbalance are analyzed to ensure that the method is robust and feasible. Simulation and experimental results are used to verify and validate the effectiveness of the method

Enhanced surface acceleration of fast electrons by using sub-wavelength grating targets

Surface acceleration of fast electrons in intense laser-plasma interaction is improved by using sub-wavelength grating targets. The fast electron beam emitted along the target surface was enhanced by more than three times relative to that by using planar target. The total number of the fast electrons ejected from the front side of target was also increased by about one time. The method to enhance the surface acceleration of fast electron is effective for various targets with sub-wavelength structured surface, and can be applied widely in the cone-guided fast ignition, energetic ion acceleration, plasma device, and other high energy density physics experiments.Comment: 14 pages, 4figure

Polyketides from the Halotolerant Fungus Myrothecium sp. GS-17

Two new polyketides, myrothecol (1) and 5-hydroxy-3-methyl-4-(1- hydroxylethyl)-furan-2(5H)-one (2), were isolated from the fermentation broth of the halotolerant fungus Myrothecium sp. GS-17 along with three known compounds, 5-hydroxyl-3-[(1S)-1-hydroxyethyl]-4-methylfuran-2(5H)-one (3), 3,5-dimethyl-4- hydroxylmethyl-5-methoxyfuran-2(5H)-one (4), and 3,5-dimethyl-4-hydroxymethyl-5- hydroxyfuran-2(5H)-one (5). Compound 1 is the first natural occurring polyketide with a unique furylisobenzofuran skeleton. The structures of these compounds were established via extensive spectroscopic analyses including 1D-, 2D-NMR, HRESI-MS, and crystal X-ray diffraction analysis