山奈酚与水的氢键作用对其抗氧化活性影响的理论研究

本文用密度泛函理论在(RO)B3LYP/6-31G(2d,2p)水平上对山奈酚及其与水分子之间形成的氢键复合物进行结构优化,通过热力学计算研究了不同位置的酚羟基发生抽氢反应的键离解能(BDE)、质子解离反应过程的质子解离能(DPE)受分子间氢键的影响。结果表明:与H2O形成的分子间氢键会影响化合物结构,改变化合物B环与AC环的二面角,A5位酚羟基更容易发生抽氢反应和质子解离反应,此位点的BDE和DPE均明显降低,同时也降低C3位质子解离的DPE。分子间氢键的形成促使酚羟基的抽氢和质子解离反应,提高化合物抗氧化活性。     

Do U.S. county data disprove linear no‐threshold predictions of lung cancer risk for residential radon?‐A preliminary assessment of biological plausibility

Lung‐cancer mortality (LCM) is elevated in underground miners who chronically inhaled the mutagenic, cytotoxic α‐decay products of radon gas. Epidemiologie studies of LCM rates vs. residential‐radon concentration levels are generally considered inconclusive. However, Cohen (Health Physics 68, 157–174, 1995) has hypothesized that data on LCM vs. residential radon concentrations at the U.S. county level are clearly inconsistent with a linear no‐threshold (LN) dose‐response model, and rather are consistent with threshold or hormesis model. Cohen's hypothesis has been criticized as “ecological fallacy,”; particularly because LN (but not threshold or hormesis) models are generally considered biologically plausible for agents like α radiation that damage DNA in linear proportion to dose. To assess the biological plausibility of Cohen's hypothesis, a preliminary study was made of whether a biologically realistic, cytodynamic 2‐stage (CD2) cancer model can provide a good, joint fit to Cohen's set of U.S. county data as well as to underground‐miner data. The CD2 model used adapts a widely applied, mechanistic, 2‐stage stochastic model of carcinogenesis to realistically account for interrelated cell killing and mutation (both assumed to have a LN dose‐response), cell turnover, and incomplete exposure of stem cells. A CD2 fit was obtained to combined summary data on LCM vs. radon‐exposure in white males in 1, 601 U.S. counties (from Cohen) and in white male Colorado Plateau (CP) uranium miners (from the National Research Council's “BEIRIV”; report). The CD2 fit is shown to: (i) be consistent with the combined data; (ii) have parameter values all consistent with biological data; and (iii) predict inverse dose‐rate‐effects data for CP and other radon‐exposed miners, despite the fact that optimization had not involved any of these dose‐rate data. The latter data were not predicted by a simplified CD2 model in which all stem cells were presumed to be exposed. It is concluded that this study provides preliminary evidence that Cohen's hypothesis is biologically plausible.     

Long‐term dynamics of mycorrhizal root tips in a loblolly pine forest grown with free‐air CO2 enrichment and soil N fertilization for 6 years

Large‐scale, long‐term FACE (Free‐Air CO₂ enrichment) experiments indicate that increases in atmospheric CO₂ concentrations will influence forest C cycling in unpredictable ways. It has been recently suggested that responses of mycorrhizal fungi could determine whether forest net primary productivity (NPP) is increased by elevated CO₂ over long time periods and if forests soils will function as sources or sinks of C in the future. We studied the dynamic responses of ectomycorrhizae to N fertilization and atmospheric CO₂ enrichment at the Duke FACE experiment using minirhizotrons over a 6 year period (2005–2010). Stimulation of mycorrhizal production by elevated CO₂ was observed during only 1 (2007) of 6 years. This increased the standing crop of mycorrhizal tips during 2007 and 2008; during 2008, significantly higher mortality returned standing crop to ambient levels for the remainder of the experiment. It is therefore unlikely that increased production of mycorrhizal tips can explain the lack of progressive nitrogen limitations and associated increases in N uptake observed in CO₂‐enriched plots at this site. Fertilization generally decreased tree reliance on mycorrhizae as tip production declined with the addition of nitrogen as has been shown in many other studies. Annual NPP of mycorrhizal tips was greatest during years with warm January temperatures and during years with cool spring temperatures. A 2 °C increase in average late spring temperatures (May and June) decreased annual production of mycorrhizal root tip length by 50%. This has important implications for ecosystem function in a warmer world in addition to potential for forest soils to sequester atmospheric C.     

外来植物南美蟛蜞菊、裂叶牵牛和五爪金龙的光合特性

对南美蟛蜞菊、裂叶牵牛和五爪金龙的光合生理特性进行研究 ,结果表明 :(1) 3种植物都具有较强的 CO2 固定能力 ,南美蟛蜞菊的净光合速率峰值达 2 2 .1μm ol/ (m2 · s) ,高于裂叶牵牛 (17.2 μmol/ (m2 · s) )和五爪金龙 (18.6 μmol/ (m2 · s) ) ;(2 ) 3种植物光合速率、蒸腾速率的日进程曲线呈“双峰”型 ,气孔导度变化规律与蒸腾速率相似 ,在中午前后均出现一定程度的下降 ;(3)暗呼吸速率曲线呈单峰型 ,在中午时出现高峰 ,暗呼吸速率大小次序为 :五爪金龙 >裂叶牵牛 >南美蟛蜞菊。(4 )南美蟛蜞菊的光饱和点为 15 31μm ol/ (m2· s) ,光补偿点为 2 0 .0 μmol/ (m2· s) ,而裂叶牵牛的光饱和点 114 6 μmol/ (m2· s) ,光补偿点39.3μmol/ (m2· s) ;五爪金龙的光饱和点 12 6 1μmol/ (m2· s) ,光补偿点 4 4 .1μm ol/ (m2· s) ,3种植物都表现为喜阳植物的特性 ,且对弱光条件的适应力也较强 ,其中尤以南美蟛蜞菊的有效光合辐射范围最广 ,光量子利用效率较高 ,具有很强忍耐强光及适应阴生环境的能力。该项研究有助于解释南美蟛蜞菊生长迅速、生产力高、竞争性强的生物学特点     

Structure-based tailoring of compound libraries for high-throughput screening: discovery of novel EphB4 kinase inhibitors

High-throughput docking is a computational tool frequently used to discover small-molecule inhibitors of enzymes or receptors of known three-dimensional structure. Because of the large number of molecules in chemical libraries, automatic procedures to prune multimillion compound collections are useful for high-throughput docking and necessary for in vitro screening. Here, we propose an anchor-based library tailoring approach (termed ALTA) to focus a chemical library by docking and prioritizing molecular fragments according to their binding energy which includes continuum electrostatics solvation. In principle, ALTA does not require prior knowledge of known inhibitors, but receptor-based pharmacophore information (hydrogen bonds with the hinge region) is additionally used here to identify molecules with optimal anchor fragments for the ATP-binding site of the EphB4 receptor tyrosine kinase. The 21,418 molecules of the focused library (from an initial collection of about 730,000) are docked into EphB4 and ranked by force-field-based energy including electrostatic solvation. Among the 43 compounds tested in vitro, eight molecules originating from two different anchors show low-micromolar activity in a fluorescence-based enzymatic assay. Four of them are active in a cell-based assay and are potential anti-angiogenic compounds.     

Critical role of Toll‐like receptor 2 in Bacteroides fragilis‐mediated immune responses in murine peritoneal mesothelial cells

In this study, the role of Toll‐like receptor 2 (TLR2) in immune responses of murine peritoneal mesothelial cells against Bacteroides fragilis was investigated. Enzyme linked immunosorbent assay was used to measure cytokines and chemokines. Activation of nuclear factor κB (NF‐κB‐α) and mitogen‐activated protein kinases (MAP kinases) was investigated by western blot analysis. B. fragilis induced production of interleukin‐6, chemokine (C‐X‐C motif) ligand 1 (CXCL1) and chemokine (C‐C motif) ligand 2 (CCL2) in wild type peritoneal mesothelial cells; this was impaired in TLR2‐deficient cells. In addition, in response to B. fragilis, phosphorylation of inhibitory NF‐κB‐α and c‐Jun N‐terminal kinase mitogen‐activated protein kinase (MAPK) was induced in wild type mesothelial cells, but not in TLR2‐deficient cells,. Inhibitor assay revealed that NF‐κB and MAPKs are essential for B. fragilis‐induced production of CXCL1 and CCL2 in mesothelial cells. These findings suggest that TLR2 mediates immune responses in peritoneal mesothelial cells in response to B. fragilis.     

Tissue culture on a chip: Developmental biology applications of self‐organized capillary networks in microfluidic devices

Organ culture systems are used to elucidate the mechanisms of pattern formation in developmental biology. Various organ culture techniques have been used, but the lack of microcirculation in such cultures impedes the long‐term maintenance of larger tissues. Recent advances in microfluidic devices now enable us to utilize self‐organized perfusable capillary networks in organ cultures. In this review, we will overview past approaches to organ culture and current technical advances in microfluidic devices, and discuss possible applications of microfluidics towards the study of developmental biology.     

Exceptionally Enhanced Electrode Activity of (Pr,Ce)O2−δ‐Based Cathodes for Thin‐Film Solid Oxide Fuel Cells

It is shown that an electrochemically‐driven oxide overcoating substantially improves the performance of metal electrodes in high‐temperature electrochemical applications. As a case study, Pt thin films are overcoated with (Pr,Ce)O_2?δ (PCO) by means of a cathodic electrochemical deposition process that produces nanostructured oxide layers with a high specific surface area and uniform metal coverage and then the coated films are examined as an O₂‐electrode for thin‐film‐based solid oxide fuel cells. The combination of excellent conductivity, reactivity, and durability of PCO dramatically improves the oxygen reduction reaction rate while maintaining the nanoscale architecture of PCO layers and thus the performance of the PCO‐coated Pt thin‐film electrodes at high temperatures. As a result, with an oxide coating step lasting only 5 min, the electrode resistance is successfully reduced by more than 1000 times at 500 °C in air. These observations provide a new direction for the design of high‐performance electrodes for high‐temperature electrochemical cells.