Nanoparticles Encapsulated in Porous Carbon Matrix Coated on Carbon Fibers: An Ultrastable Cathode for Li‐Ion Batteries

Nanostructured V₂O₅ is emerging as a new cathode material for lithium ion batteries for its distinctly high theoretic capacity over the current commercial cathodes. The main challenges associated with nanostructured V₂O₅ cathodes are structural degradation, instability of the solid‐electrolyte interface layer, and poor electron conductance, which lead to low capacity and rapid decay of cyclic stability. Here, a novel composite structure of V₂O₅ nanoparticles encapsulated in 3D networked porous carbon matrix coated on carbon fibers (V₂O₅/3DC‐CFs) is reported that effectively addresses the mentioned problems. Remarkably, the V₂O₅/3DC‐CF electrode exhibits excellent overall lithium‐storage performance, including high Coulombic efficiency, excellent specific capacity, outstanding cycling stability and rate property. A reversible capacity of ≈183 mA h g^?1 is obtained at a high current density of 10 C, and the battery retains 185 mA h g^?1 after 5000 cycles, which shows the best cycling stability reported to date among all reported cathodes of lithium ion batteries as per the knowledge. The outstanding overall properties of the V₂O₅/3DC‐CF composite make it a promising cathode material of lithium ion batteries for the power‐intensive energy storage applications.     

A combined computational-experimental analyses of selected metabolic enzymes in Pseudomonas species

Comparative genomic analysis has revolutionized our ability to predict the metabolic subsystems that occur in newly sequenced genomes, and to explore the functional roles of the set of genes within each subsystem. These computational predictions can considerably reduce the volume of experimental studies required to assess basic metabolic properties of multiple bacterial species. However, experimental validations are still required to resolve the apparent inconsistencies in the predictions by multiple resources. Here, we present combined computational-experimental analyses on eight completely sequenced Pseudomonas species. Comparative pathway analyses reveal that several pathways within the Pseudomonas species show high plasticity and versatility. Potential bypasses in 11 metabolic pathways were identified. We further confirmed the presence of the enzyme O-acetyl homoserine (thiol) lyase (EC: 2.5.1.49) in P. syringae pv. tomato that revealed inconsistent annotations in KEGG and in the recently published SYSTOMONAS database. These analyses connect and integrate systematic data generation, computational data interpretation, and experimental validation and represent a synergistic and powerful means for conducting biological research.     

Inhibition of thioredoxin reductase by mansonone F analogues: Implications for anticancer activity

Mammalian thioredoxin reductase (TrxR), a ubiquitous selenocysteine containing oxidoreductase, catalyzes the NADPH-dependent reduction of oxidized thioredoxin (Trx). TrxR has been suggested as a potential target for anticancer drugs development for its overexpression in human tumors and its diverse functions in intracellular redox control, cell growth and apoptosis. Mansonone F (MF) compounds have been shown to exhibit antiproliferative effects, but their complex mechanisms are unknown. In the present study, we have investigated the effects of some synthesized MF analogues on TrxR and HeLa cells. The studies of the mode of inhibition and the interactions of IG3, one of the most potent MF analogues, with TrxR showed MF compounds could be partly reduced by the C-terminal selenolthiol active site, and possibly by the N-terminal dithiol motif and/or FAD domain of TrxR simultaneously, accompanied by redox cycling with the generation of superoxide anion radicals. In addition, MF analogues exhibited the potential to inhibit the growth of HeLa cells and reduce TrxR activity in cell lysates. The cell cycle was arrested in G2/M phase and apoptosis was induced in a dose-dependent manner. Furthermore, our results showed that IG3-treated HeLa cells induced the change of intracellular ROS. Taken together, the reported results here suggest that inhibition of TrxR by MF analogues provides a possible complex mechanism for explaining the anticancer activity of MF compounds.     

Design and total synthesis of a fluorescent phorboxazole A analog for cellular studies

To enable studies to elucidate the intracellular processing and targeting of the potent cytostatic/apoptotic anticancer natural products phorboxazoles A and B, a fluorescent derivative has been developed. This involved the total syntheses of the terminal alkyne 33-O-Me-45,46-dehydrobromophorboxazole A (MDHBPA) and a terminal vinyl iodide derivative of the blue fluorescent dye N,N,-dimethyl-7-aminocoumarin (DMC). Sonogashira coupling of these partners provided enyne DMC-MDHBPA in high yield.     

The induction of preterm labor in rhesus macaques is determined by the strength of immune response to intrauterine infection

Intrauterine infection/inflammation (IUI) is a major contributor to preterm labor (PTL). However, IUI does not invariably cause PTL. We hypothesized that quantitative and qualitative differences in immune response exist in subjects with or without PTL. To define the triggers for PTL, we developed rhesus macaque models of IUI driven by lipopolysaccharide (LPS) or live Escherichia coli. PTL did not occur in LPS challenged rhesus macaques, while E. coli–infected animals frequently delivered preterm. Although LPS and live E. coli both caused immune cell infiltration, E. coli–infected animals showed higher levels of inflammatory mediators, particularly interleukin 6 (IL-6) and prostaglandins, in the chorioamnion-decidua and amniotic fluid (AF). Neutrophil infiltration in the chorio-decidua was a common feature to both LPS and E. coli. However, neutrophilic infiltration and IL6 and PTGS2 expression in the amnion was specifically induced by live E. coli. RNA sequencing (RNA-seq) analysis of fetal membranes revealed that specific pathways involved in augmentation of inflammation including type I interferon (IFN) response, chemotaxis, sumoylation, and iron homeostasis were up-regulated in the E. coli group compared to the LPS group. Our data suggest that the intensity of the host immune response to IUI may determine susceptibility to PTL.     

Plasma-based approach to measure target engagement for liver-targeting stearoyl-CoA desaturase 1 inhibitors

A positive correlation between stearoyl-CoA desaturase (SCD)1 expression and metabolic diseases has been reported in rodents and humans. These findings indicate that SCD1 is a promising therapeutic target for the chronic treatment of diabetes and dyslipidemia. The SCD1 enzyme is expressed at high levels in several human tissues and is required for the biosynthesis of monounsaturated fatty acids, which are involved in many biological processes. Liver-targeted SCD inhibitors were designed to pharmacologically manipulate SCD1 activity in the liver to avoid adverse events due to systemic inhibition. This article describes the development of a plasma-based SCD assay to assess the level of SCD inhibition, which is defined in this article as target engagement. Essentially, animals are dosed with an exogenous deuterated tracer (d7-stearic acid) as substrate, and the converted d7-oleic acid product is measured to monitor SCD1 inhibition. This study reveals that this plasma-based assay correlates with liver SCD1 inhibition and can thus have clinical utility.     

A local pancreatic renin-angiotensin system: endocrine and exocrine roles

The renin-angiotensin system (RAS) is classically characterized as a circulating hormonal system primarily through the production of the physiologically active product angiotensin II (Ang II) that plays a crucial role in the regulation of blood pressure, fluid and electrolyte homeostasis. In addition to this circulating RAS, numerous tissues and organs have been recently demonstrated to exhibit their own RAS products and activities. Such an intrinsic RAS can modulate the specific local functions of their respective tissues and organs, frequently in a paracrine and autocrine manner. Recent findings from our laboratories and others have made a significant contribution on the expression, localization, regulation, and potential role of a local RAS in the pancreas. Although, it is quite intriguing that components of the local pancreatic RAS are responsive to various physiological and pathophysiological conditions, the crucial role of this system in regulating the exocrine and endocrine functions and ultimately the clinical relevance to pancreatic disease is still largely equivocal. Of particular interest in this context are the actions of pancreatic RAS on the growth, anti-proliferation and free radical generation in the pancreas. The aims of the current article focus on the emerging data on the local pancreatic RAS; its involvement in exocrine acinar and endocrine islet aspects, and the clinical significance in the pancreas are particularly addressed. The target for the local pancreatic RAS may provide a new insight into future management of various clinical conditions including islet transplants, diabetes mellitus, pancreatic cancer, pancreatitis and cystic fibrosis.     

Multiple-binding-site mechanism explains concentration-dependent unbinding rates of DNA-binding proteins

Recent work has demonstrated concentration-dependent unbinding rates of proteins from DNA, using fluorescence visualization of the bacterial nucleoid protein Fis [Graham et al. (2011) (Concentration-dependent exchange accelerates turnover of proteins bound to double-stranded DNA. Nucleic Acids Res., 39:2249)]. The physical origin of this concentration-dependence is unexplained. We use a combination of coarse-grained simulation and theory to demonstrate that this behavior can be explained by taking into account the dimeric nature of the protein, which permits partial dissociation and exchange with other proteins in solution. Concentration-dependent unbinding is generated by this simple model, quantitatively explaining experimental data. This effect is likely to play a major role in determining binding lifetimes of proteins in vivo where there are very high concentrations of solvated molecules.