Dielectric performance and conductive mechanism of KNN-based ceramics prepared via sol–gel core–shell process

Journal of Materials Science: Materials in Electronics - 0.95(Li0.02Na0.50K0.48)(Nb0.95Sb0.05)O3–0.05AgTaO3@BaZrO3 (LNKNbSAT@BZ) lead-free ceramics were prepared via a sol–gel...     

Phenolic profiling reveals the metabolite basis of flesh colour and fresh-cut browning in apple fruit

Flesh colour, which is affected by cultivars and browning, can largely impact consumer acceptance in fresh-cut apples. The study profiled phenolic metabolites from apple flesh of twenty-three cultivars by widely targeted metabolomics. Comparison among white- and yellow-fleshed cultivars showed fifteen phenolics, mainly quercetin 3-O-glucoside, hyperoside, hesperetin 5-O-glucoside and cymaroside, in white-fleshed apples were significantly higher than those in yellow-fleshed apples. It may indicate a metabolite basis of yellow and white flesh colour, and better potential nutrition in white-fleshed apples. In addition, ten phenolic metabolites including five cyanidin glycosides showed significant differences between the highest and the lowest browning groups, indicating them may be crucial in browning of fresh-cut apple. This work elucidates the differences of phenolic profiles among apple cultivars with different flesh colour and provides useful data to evaluate the suitability of apple for fresh-cut processing.     

Cloning,sequencing and structural analysis of membrane-bound polyphenol oxidase from Granny Smith apples (Malus × domestica Borkh)

The gene sequence coding for the membrane-bound polyphenol oxidase (mPPO) with a length of 1761 bp was cloned by PCR method and shown to contain one highly conserved sequence encoding a di-copper-binding region. The predicted three-dimensional structure of mPPO indicated that the active site was located near two copper ions and composed of a typical bundle of four α-helices. Each of the two catalytic copper ions was coordinated with three histidine residues in the hydrophobic pocket, yielding His 180, His 201, His 210, His 332, His 336 and His 366. Docking studies showed that 4-methylcatechol and chlorogenic acid have different binding models due to different ligand sizes and binding sites in the active centre, and it was found that the smaller compound exhibited a higher affinity for mPPO. Molecular dynamic simulation results indicated that Phe 353 is important in controlling enzymatic activity through influencing substrate coordination in the active site.     

E7766, a Macrocycle-Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan-Genotypic Activity

A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766 , exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.     

4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene,a Major Active Metabolite of Bisphenol A,Triggers Pancreatic β-Cell Death via a JNK/AMPKα Activation-Regulated Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway

4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway.     

A Highly Sensitive,Reversible, and Bidirectional Humidity Actuator by Calcium Carbonate Ionic Oligomers Incorporated Poly(Vinylidene Fluoride)

Sensitivity and multi-directional motivation are major two factors for developing optimized humidity-response materials, which are promising for sensing, energy production, etc. Organic functional groups are commonly used as the water sensitive units through hydrogen bond interactions with water molecules in actuators. The multi-coordination ability of inorganic ions implies that the inorganic ionic compounds are potentially superior water sensitive units. However, the particle forms of inorganic ionic compounds produced by classical nucleation limit the number of exposed ions to interact with water. Recent progress on the inorganic ionic oligomers has broken through the limitation of classical nucleation, and realized the molecular-scaled incorporation of inorganic ionic compounds into an organic matrix. Here, the incorporation of hydrophilic calcium carbonate ionic oligomers into hydrophobic poly(vinylidene fluoride) (PVDF) is demonstrated. The ultra-small calcium carbonate oligomers within a PVDF film endow it with an ultra-sensitive, reversible, and bidirectional response. The motivation ability is superior to other bidirectional humidity-actuators at present, which realizes self-motivation on an ice surface, converting the chemical potential energy of the humidity gradient from ice to kinetic energy.