Newly Detected Specific Hydrogenation of the Conjugated Double Bond of Unsaturated Alkaloid Lactones by Aspergillus sp.

A new isolate of Aspergillus sp. hydrogenated the γ,δ-double bond of securinine (143 mg l⁻¹) to give 14,15-dihydrosecurinine at over 98% (w/w) yield after 8 h. It also hydrogenated the C11(13) double bond of 3-hydroxy-1(10),3,11(13)-guaiatriene-12,6-olide-2-one (HGT) (200 mg l⁻¹) to give 3-hydroxy-1(10),3-guaiadiene-12,6-olide-2-one with over 98% (w/w) conversion after 24 h.     

Structure of a classical MHC class I molecule that binds "non-classical" ligands

Chicken YF1 genes share a close sequence relationship with classical MHC class I loci but map outside of the core MHC region. To obtain insights into their function, we determined the structure of the YF1*7.1/β₂-microgloblin complex by X-ray crystallography at 1.3 Å resolution. It exhibits the architecture typical of classical MHC class I molecules but possesses a hydrophobic binding groove that contains a non-peptidic ligand. This finding prompted us to reconstitute YF1*7.1 also with various self-lipids. Seven additional YF1*7.1 structures were solved, but only polyethyleneglycol molecules could be modeled into the electron density within the binding groove. However, an assessment of YF1*7.1 by native isoelectric focusing indicated that the molecules were also able to bind nonself-lipids. The ability of YF1*7.1 to interact with hydrophobic ligands is unprecedented among classical MHC class I proteins and might aid the chicken immune system to recognize a diverse ligand repertoire with a minimal number of MHC class I molecules.     

Construction of glycerol synthesis pathway in <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> for bioconversion of glucose into 1,3-propanediol

1,3-Propanediol (1,3-PDO) is an important three-carbon compound widely used in new polyester polymer materials. Natural organisms that can produce 1,3-PDO from glycerol were well studied. However, no natural microorganisms found could directly convert glucose to 1,3-PDO due to its insufficient glycerol synthesis pathway. In this study, two essential glycerol synthesis genes, CgGPD gene (encoding glycerol-3-phosphate dehydrogenase from Candida glycerinogenes) and ScGPP2 gene (encoding glycerol-3-phosphatase from Saccharomyces cerevisiae), were expressed in wild-type Klebsiella pneumoniae, a natural 1,3-PDO producers with reduction pathway for 1,3-PDO synthesis from glycerol. The results of fermentation, key enzyme activities, and metabolites analysis confirmed that recombinant K. pneumoniae now possessed a metabolic pathway capable of converting glucose to 1,3-PDO. The strain could produce 1,3-PDO from glucose with a final titer of 17.27 g/L with 40 g/L glucose in the medium, showing a 1.26-fold increase compared with 30 g/L glucose. Also, adding certain concentrations of glycerol could quickly initiate the 1,3-PDO synthetic pathway and promote the accumulation of 1,3-PDO, which could shorten the fermentation cycle. These results have important implications for further studies involving the use of one strain for bioconversion of glucose to 1,3-PDO.     

Stretchable Lithium‐Ion Batteries Enabled by Device‐Scaled Wavy Structure and Elastic‐Sticky Separator

Fast developments and substantial achievements have been shaping the field of wearable electronic devices, resulting in the persistent requirement for stretchable lithium‐ion batteries (LIBs). Despite recent progress in stretchable electrodes, stretching full batteries, including electrodes, separator, and sealing material, remains a great challenge. Here, a simple design concept for stretchable LIBs via a wavy structure at the full battery device scale is reported. All components including the package are capable of being reversibly stretched by folding the entire pouch cell into a wavy shape with polydimethylsiloxane filled in each valley region. In addition, the stretchable, sticky, and porous polyurethane/poly(vinylidene fluoride) membrane is adopted as a separator for the first time, which can maintain intimate contact between electrodes and separator to continuously secure ion pathway under dynamic state. Commercial cathode, anode, and package can be utilized in this rationally designed wavy battery to enable stretchability. The results indicate good electrochemical performances and long‐term stability at repeatable release–stretch cycles. A high areal capacity of 3.6 mA h cm^?2 and energy density of up to 172 W h L^?1 can be achieved for the wavy battery. The promising results of the cost‐effective wavy battery with high stretchability shed light on the development of stretchable energy storages.     

Synthesis and antiviral activity of novel pyrazole derivatives containing oxime esters group

Fourteen title compounds, 1-substituted-5-substitutedphenylthio-4-pyrazolaldoxime ester derivatives 4a-4n, were synthesized from the starting material 1-substitutedphenyl-3-methyl-5-substitutedphenylthio-4-pyrazolaldoximes 3 by treatment with acyl chloride. The synthesized compounds were characterized by physical constants, and the structures of the title compounds were further confirmed by IR, 1H NMR, 13C NMR and elemental analysis. The bioassay results showed that title compounds possessed weak to good anti-TMV bioactivity with 4l showing significant enhancement of disease resistance in tobacco leaves with high affinity for TMV CP.     

The hyperthermophilic α-amylase from <Emphasis Type="Italic">Thermococcus</Emphasis> sp. HJ21 does not require exogenous calcium for thermostability because of high-binding affinity to calcium

The hyperthermophilic α-amylase from Thermococcus sp. HJ21 does not require exogenous calcium ions for thermostability, and is a promising alternative to commercially available α-amylases to increase the efficiency of industrial processes like the liquefaction of starch. We analyzed the amino acid sequence of this α-amylase by sequence alignments and structural modeling, and found that this α-amylase closely resembles the α-amylase from Pyrococcus woesei. The gene of this α-amylase was cloned in Escherichia coli and the recombinant α-amylase was overexpressed and purified with a combined renaturation-purification procedure. We confirmed thermostability and exogenous calcium ion independency of the recombinant α-amylase and further investigated the mechanism of the independency using biochemical approaches. The results suggested that the α-amylase has a high calcium ion binding affinity that traps a calcium ion that would not dissociate at high temperatures, providing a direct explanation as to why the addition of calcium ions is not required for thermostability. Understanding of the mechanism offers a strong base on which to further engineer properties of this α-amylase for better potential applications in industrial processes.     

Regulation of cyp26a1 on Th17 cells in mouse peri‐implantation

Cytochrome P450 26A1 (cyp26a1) is expressed in the mouse uterus during peri‐implantation. The repression of this protein is closely associated with a reduction in implantation sites, suggesting a specific role for cyp26a1 in pregnancy and prompting questions concerning how a metabolic enzyme can generate this distinct outcome. To explore the effective downstream targets of cyp26a1 and confirm if its role in peri‐implantation depends on its metabolic substrate RA (retinoic acid), we characterized the changes in the peripheral blood, spleen and uterine implantation sites using the cyp26a1 gene vaccine constructed before. Flow cytometry results showed a significant increase in CD4⁺RORγt⁺ Th17 cells in both the peripheral blood and spleen in the experimental group. The expression of RORγt and IL‐17 presented the Th17 cells reduction in uterus followed by the suppression of cyp26a1 expression. For greater certainty, cyp26a1 antibody blocking model and RNA interference model were constructed to determine the precise target immune cell group. High performance liquid chromatography results showed a significant increase in uterine at‐RA followed by the immunization of cyp26a1 gene vaccine. Both the ascertain by measuring RARα protein levels in peri‐implantation uterus after gene vaccine immunization and researches using the specific agonist and antagonist against RARα suggested that RARα may be the main RA receptor for signal transduction. These results provided more evidence for the signal messenger role of RA in cyp26a1 regulation from the other side. Here, we showed that the cyp26a1‐regulated Th17 cells are dependent on at‐RA signalling, which is delivered through RARα in mouse peri‐implantation.     

The design and synthesis of indazole and pyrazolopyridine based glucokinase activators for the treatment of Type 2 diabetes mellitus

Glucokinase activators represent a promising potential treatment for patients with Type 2 diabetes. Herein, we report the identification and optimization of a series of novel indazole and pyrazolopyridine based activators leading to the identification of 4-(6-(azetidine-1-carbonyl)-5-fluoropyridin-3-yloxy)-2-ethyl-N-(5-methylpyrazin-2-yl)-2H-indazole-6-carboxamide (42) as a potent activator with favorable preclinical pharmacokinetic properties and in vivo efficacy.