亚热带不同树种凋落叶分解对氮添加的响应

为探究不同质量凋落物对氮(N)沉降的响应, 该研究采用尼龙网袋分解法, 在亚热带福建三明格氏栲(Castanopsis kawakamii)自然保护区的米槠(Castanopsis carlesii)天然林, 选取4种本区常见的具有不同初始化学性质的树种凋落叶进行模拟N沉降(N添加)分解实验(施N水平为对照0和50 kg·hm ^-2·a ^-1)。研究结果表明: 在2年的分解期内, 对照处理的各树种凋落叶的分解速率依次为观光木(Michelia odora, 0.557 a ^-1)、米槠(0.440 a ^-1)、台湾相思(Acacia confusa, 0.357 a ^-1)、杉木(Cunninghamia lanceolata, 0.354 a ^-1); N添加处理凋落叶分解速率依次为观光木(0.447 a ^-1)、米槠(0.354 a ^-1)、杉木(0.291 a ^-1)、台湾相思(0.230 a ^-1), 除杉木凋落叶外, N添加显著降低了其他3种凋落叶分解速率。N添加不仅使4种树木凋落叶分解过程中的N释放减慢, 同时还抑制凋落叶化学组成中木质素和纤维素的降解; N添加在凋落叶分解过程中总体上提高β-葡萄糖苷酶(βG)和酸性磷酸酶活性, 对纤维素水解酶的活性影响不一致, 而降低β-N-乙酰氨基葡萄糖苷酶活性和酚氧化酶活性。凋落叶分解速率与凋落叶中的碳获取酶(βG)活性以及其化学组分中的可萃取物含量极显著正相关, 与初始碳浓度、纤维素和木质素含量极显著负相关, 与初始N含量没有显著相关性。凋落物类型和N添加的交互作用虽未影响干质量损失速率, 但对木质素和纤维素的降解具有显著效应。综上所述, 化学组分比初始N含量能更好地预测凋落叶分解速率, 而N添加主要通过抑制分解木质素的氧化酶(如PHO)来降低凋落叶分解速率。     

Roles of N-methyl-d-aspartate receptors and d-amino acids in cancer cell viability

Molecular Biology Reports - N-methyl-d-aspartate (NMDA) receptors, which are widely present in the central nervous system, have also been found to be up-regulated in a variety of cancer cells and...     

Downscaling screening cultures in a multifunctional bioreactor array-on-a-chip for speeding up optimization of yeast-based lactic acid bioproduction

A key challenge for bioprocess engineering is the identification of the optimum process conditions for the production of biochemical and biopharmaceutical compounds using prokaryotic as well as eukaryotic cell factories. Shake flasks and bench-scale bioreactor systems are still the golden standard in the early stage of bioprocess development, though they are known to be expensive, time-consuming, and labor-intensive as well as lacking the throughput for efficient production optimizations. To bridge the technological gap between bioprocess optimization and upscaling, we have developed a microfluidic bioreactor array to reduce time and costs, and to increase throughput compared with traditional lab-scale culture strategies. We present a multifunctional microfluidic device containing 12 individual bioreactors (V_t = 15 µl) in a 26 mm × 76 mm area with in-line biosensing of dissolved oxygen and biomass concentration. Following initial device characterization, the bioreactor lab-on-a-chip was used in a proof-of-principle study to identify the most productive cell line for lactic acid production out of two engineered yeast strains, evaluating whether it could reduce the time needed for collecting meaningful data compared with shake flasks cultures. Results of the study showed significant difference in the strains' productivity within 3 hr of operation exhibiting a 4- to 6-fold higher lactic acid production, thus pointing at the potential of microfluidic technology as effective screening tool for fast and parallelizable industrial bioprocess development.     

Electrically tunable organic bioelectronics for spatial and temporal manipulation of neuron-like pheochromocytoma (PC-12) cells

Background

Organic bioelectronic devices consisting of alternating poly(3,4-ethylenedioxythiophene) (PEDOT) and reduced graphite oxide (rGO) striped microelectrode arrays were fabricated by lithography technology. It has been demonstrated that the organic bioelectronic devices can be used to spatially and temporally manipulate the location and proliferation of the neuron-like pheochromocytoma cells (PC-12 cells).

Methods

By coating an electrically labile contact repulsion layer of poly(l-lysine-graft-ethylene glycol) (PLL-g-PEG) on the PEDOT electrode, the location and polarity of the PC-12 cells were confined to the rGO electrodes.

Results

The outgrowth of spatially confined bipolar neurites was found to align along the direction of the 20 μm wide electrode. The location of the PC-12 cells can also be manipulated temporally by applying electrical stimulation during the neurite differentiation of PC-12 cells, allowing the PC-12 cells to cross over the boundary between the PEDOT and the rGO regions and construct neurite networks in an unconfined manner where the contact repulsive coating of PLL-g-PEG was removed.

Conclusions

This adsorption and desorption of the PLL-g-PEG without and with electrical stimulation can be attributed to the tunable surface properties of the PEDOT microelectrodes, whose surface charge can switch from being negative to positive under electrical stimulation.

General significance

The electrically tunable organic bioelectronics reported here could potentially be applied to tissue engineering related to the development and regeneration of mammalian nervous systems. The spatial and temporal control in this device would also be used to study the synapse junctions of neuron–neuron contacts in both time and space domains. This article is part of a Special Issue entitled Organic Bioelectronics — Novel Applications in Biomedicine.     

Discovery of 3-phenyl-1H-5-pyrazolylamine derivatives containing a urea pharmacophore as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)

Preclinical investigations and early clinical trials suggest that FLT3 inhibitors are a viable therapy for acute myeloid leukemia. However, early clinical data have been underwhelming due to incomplete inhibition of FLT3. We have developed 3-phenyl-1H-5-pyrazolylamine as an efficient template for kinase inhibitors. Structure–activity relationships led to the discovery of sulfonamide, carbamate and urea series of FLT3 inhibitors. Previous studies showed that the sulfonamide 4 and carbamate 5 series were potent and selective FLT3 inhibitors with good in vivo efficacy. Herein, we describe the urea series, which we found to be potent inhibitors of FLT3 and VEGFR2. Some inhibited growth of FLT3-mutated MOLM-13 cells more strongly than the FLT3 inhibitors sorafenib (2) and ABT-869 (3). In preliminary in vivo toxicity studies of the four most active compounds, 10f was found to be the least toxic. A further in vivo efficacy study demonstrated that 10f achieved complete tumor regression in a higher proportion of MOLM-13 xenograft mice than 4 and 5 (70% vs 10% and 40%). These results show that compound 10f possesses improved pharmacologic and selectivity profiles and could be more effective than previously disclosed FLT3 inhibitors in the treatment of acute myeloid leukemia.     

油棕（Elaeis guineensis）中果皮发育过程中miRNA的表达动态分析

以CTAB法提取油棕（Elaeis guineensis）中果皮5个不同发育时期（G1～G5）的小RNA。从前期研究获得的油棕小RNA测序数据库中筛选12个候选miRNA,实时荧光定量PCR法（qRT-PCR）检测其在果实发育过程中的表达量变化,并进一步对显著差异表达的miRNA进行靶基因预测。结果表明：中果皮5个不同发育时期小RNA的OD260/OD280比值在1.7～2.0之间;浓度分别是289、364、476、213、390 ng/μL;qRT-PCR检测结果显示,12个候选miRNA在5个发育时期均显著性差异表达,特别是在中果皮发育第4个时期（G4）和第5个时期（G5）表达量极显著增高,其中miR395和miR156在第4个时期表达量最高;miR395和miR528在发育第5时期表达量最高;靶基因预测结果显示差异表达的部分miRNA,其靶基因可能参与了脂肪酸代谢通路,如磷脂酸磷酸脂酶和磷脂酶D。本研究筛选的与脂肪酸代谢相关的miRNA为今后油棕脂肪酸代谢调控通路研究提供了可能的线索。     

Development and validation of a liquid chromatography-tandem mass spectrometry for the determination of BPR0L075, a novel antimicrotuble agent, in rat plasma: application to a pharmacokinetic study

A rapid and sensitive liquid chromatography-tandem mass spectrometric method (LC-MS/MS) had been developed and validated to determine the concentrations of BPR0L075 in rat plasma. After a simple protein precipitation of plasma samples by acetonitrile, BPR0L075 was analyzed on a C(8) column at a flow rate of 0.5 mL/min. The mobile phase consisted of a mixture of 10 mM ammonium acetate containing 0.1% formic acid and acetonitrile (20:80, v/v). Both BPR0L075 (analyte) and the internal standard (BPR0L092) were determined using electro-spray ionization and the MS data acquisition was via multiple reactions monitoring (MRM) in positive scanning model. The MS/MS ion transitions monitored are m/z 342.2/195.2 and 312.5/165.2 for BPR0L075 and BPR0L092, respectively. The low limit of quantitation was 0.5 ng/mL. Each plasma sample was chromatographed within 5 min. The method was validated with respect to linearity, accuracy, precision, recovery, and stability. A good linear relationship was observed over the concentration range of 0.5-1000 ng/mL (r>0.9994). Absolute recoveries ranged from 63.45 to 68.34% in plasma at the concentrations of 2, 40, 400, and 800 ng/mL. The intra- and inter-day accuracy ranged from 92.04 to 111.80%. Intra- and inter-day relative standard deviations were 1.08-3.29% and 1.96-5.46%, respectively. This developed and validated assay method had been successfully applied to a pharmacokinetic study after intravenous injection of BPR0L075 in rats at a dose of 5mg/kg.     

Reduction of atherosclerosis by the peroxisome proliferator-activated receptor alpha agonist fenofibrate in mice

Several clinical and angiographic intervention trials have shown that fibrate treatment leads to a reduction of the coronary events associated to atherosclerosis. Fibrates are ligands for peroxisome proliferator-activated receptor alpha (PPARalpha) that modulate risk factors related to atherosclerosis by acting at both systemic and vascular levels. Here, we investigated the effect of treatment with the PPARalpha agonist fenofibrate (FF) on the development of atherosclerotic lesions in apolipoprotein (apo) E-deficient mice and human apoA-I transgenic apoE-deficient (hapoA-I Tg x apoE-deficient) mice fed a Western diet. In apoE-deficient mice, plasma lipid levels were increased by FF treatment with no alteration in the cholesterol distribution profile. FF treatment did not reduce atherosclerotic lesion surface area in the aortic sinus of 5-month-old apoE-deficient mice. By contrast, FF treatment decreased total cholesterol and esterified cholesterol contents in descending aortas of these mice, an effect that was more pronounced in older mice exhibiting more advanced lesions. Furthermore, FF treatment reduced MCP-1 mRNA levels in the descending aortas of apoE-deficient mice, whereas ABCA-1 expression levels were maintained despite a significant reduction of aortic cholesterol content. In apoE-deficient mice expressing a human apoA-I transgene, FF increased human apoA-I plasma and hepatic mRNA levels without affecting plasma lipid levels. This increase in human apoA-I expression was accompanied by a significant reduction in the lesion surface area in the aortic sinus. These data indicate that the PPARalpha agonist fenofibrate reduces atherosclerosis in these animal models of atherosclerosis.