Evidence of cell surface iron speciation of acidophilic iron-oxidizing microorganisms in indirect bioleaching process

While indirect model has been widely accepted in bioleaching, but the evidence of cell surface iron speciation has not been reported. In the present work the iron speciation on the cell surfaces of four typically acidophilic iron-oxidizing microorganism (mesophilic Acidithiobacillus ferrooxidans ATCC 23270, moderately thermophilic Leptospirillum ferriphilum YSK and Sulfobacillus thermosulfidooxidans St, and extremely thermophilic Acidianus manzaensis YN25) grown on different energy substrates (chalcopyrite, pyrite, ferrous sulfate and elemental sulfur (S⁰)) were studied in situ firstly by using synchrotron-based micro- X-ray fluorescence analysis and X-ray absorption near-edge structure spectroscopy. Results showed that the cells grown on iron-containing substrates had apparently higher surface iron content than the cells grown on S⁰. Both ferrous iron and ferric iron were detected on the cell surface of all tested AIOMs, and the Fe(II)/Fe(III) ratios of the same microorganism were affected by different energy substrates. The iron distribution and bonding state of single cell of A. manzaensis were then studied in situ by scanning transmission soft X-ray microscopy based on dual-energy contrast analysis and stack analysis. Results showed that the iron species distributed evenly on the cell surface and bonded with amino, carboxyl and hydroxyl groups.     

Effects of dietary glucose and sodium chloride on intestinal glucose absorption of common carp (Cyprinus carpio L.)

The co-transport of sodium and glucose is the first step for intestinal glucose absorption. Dietary glucose and sodium chloride (NaCl) may facilitate this physiological process in common carp (Cyprinus carpio L.). To test this hypothesis, we first investigated the feeding rhythm of intestinal glucose absorption. Carps were fed to satiety once a day (09:00 a.m.) for 1 month. Intestinal samples were collected at 01:00, 05:00, 09:00, 13:00, 17:00 and 21:00. Result showed that food intake greatly enhanced sodium/glucose cotransporter 1 (SGLT1) and glucose transporter type 2 (GLUT2) expressions, and improved glucose absorption, with highest levels at 09:00 a.m.. Then we designed iso-nitrogenous and iso-energetic diets with graded levels of glucose (10%, 20%, 30%, 40% and 50%) and NaCl (0%, 1%, 3% and 5%), and submitted to feeding trial for 10 weeks. The expressions of SGLT1 and GLUT2, brush border membrane vesicles (BBMVs) glucose transport and intestinal villus height were determined after the feeding trial. Increasing levels of dietary glucose and NaCl up-regulated mRNA and protein levels of SGLT1 and GLUT2, enhanced BBMVs glucose transport in the proximal, mid and distal intestine. As for histological adaptive response, however, high-glucose diet prolonged while high-NaCl diet shrank intestinal villus height. Furthermore, we also found that higher mRNA levels of SGLT1 and GLUT2, higher glucose transport capacity of BBMVs, and higher intestinal villus were detected in the proximal and mid intestine, compared to the distal part. Taken together, our study indicated that intestinal glucose absorption in carp was primarily occurred in the proximal and mid intestine, and increasing levels of dietary glucose and NaCl enhanced intestinal glucose absorption in carp.     

Relationship between shift work schedule and self-reported sleep quality in Chinese employees

Few studies have reported on the effects of fixed and rotating shift systems on the prevalence of sleep disturbance. Thus, in this study, the relationships between different work schedules and sleep disturbance in Chinese workers were investigated. A total of 2180 workers aged 19–65 years responded to the self-report questionnaire on shift work schedule (fixed day-shift, fixed night-shift, two-shift or three-shift system), working hours a day, and working days a week, physical effort, subjective sleep quality and subjective mental state. It was found that the rotating shift workers, namely, two- and three-shift workers, exhibited higher risks of sleep disturbance than with the fixed day-shift workers did (OR 1.37; 95% CI 1.07to 1.74; and OR 2.19; 95% CI 1.52 to 3.15, respectively). The risk was particularly high among two- or three-shift workers who worked more than 8 hours a day or more than 5 days a week and among three-shift workers who reported both light and heavy physical effort at work. Moreover, the two- and three-shift workers (rotating shift workers) suffered from poorer sleep quality than the fixed night shift workers did (OR 1.84; 95% CI 1.01 to 3.32; and OR 2.94; 95% CI 1.53 to 5.64, respectively). Consequently, rotating shift work (two- and three-shift work) is a risk factor for sleep disturbance, and the fixed work rhythm may contribute to the quality of sleep.     

Regulatory crosstalk between KLF5, miR-29a and Fbw7/CDC4 cooperatively promotes atherosclerotic development

Atherogenesis is a chronic inflammatory process that involves complex interactions between endothelial dysfunction, lipid deposition and vascular smooth-muscle cell (VSMC) proliferation. However, the molecular mechanism is still unclear. We found that a pro-atherosclerotic factor (oxLDL) induced the expression of Krüppel-like factor 5 (KLF5), which in turn increased miR-29a expression levels. The increased miR-29a was retained within HASMCs and down-regulated Fbw7/CDC4 expression by targeting the 3´UTR of Fbw7/CDC4, subsequently increasing KLF5 stability by reducing the Fbw7/CDC4-dependent ubiquitination of KLF5, forming a positive feedback loop to enhance VSMC proliferation and promote atherogenesis. These results indicate a potentially important role for the oxLDL-activated feedback mechanism in VSMC proliferation and atherogenesis. Suppression of miR-29a may be an effective way to attenuate atherosclerosis. In conclusion, our data are the first to reveal that the regulatory crosstalk between KLF5, miR-29a, and Fbw7/CDC4 cooperatively promotes atherosclerotic development.     

Investigation of the interactions between aptamer and misfolded proteins: From monomer and oligomer to fibril by single‐molecule force spectroscopy

Increasing knowledge on the understanding interactions of aptamer with misfolded proteins (including monomer, oligomer, and amyloid fibril) is crucial for development of aggregation inhibitors and diagnosis of amyloid diseases. Herein, the interactions of lysozyme monomer–, oligomer‐, and amyloid fibril–aptamer were investigated using single‐molecule force spectroscopy. The results revealed that the aptamer screened against lysozyme monomer could also bind to oligomer and amyloid fibril, in spite of the recognition at a lower binding probability. It may be attributed to the inherent structural differences of misfolded proteins and the flexible conformation of aptamer. In addition, dynamic force spectra showed that there were similar dissociation paths in the dissociation process of lysozyme monomer–, oligomer‐, and amyloid fibril–aptamer complexes. It showed that the dissociation only passed 1 energy barrier from the binding state to the detachment. However, the dynamic parameters suggested that the oligomer‐ and amyloid fibril–aptamer were more stable than lysozyme monomer–aptamer. The phenomena may result from the exposure of aptamer‐recognized sequences on the surface and the electrostatic interactions. This work demonstrated that single‐molecule force spectroscopy could be a powerful tool to study the binding behavior of the aptamer with misfolded proteins at single‐molecule level, providing abundant information for researches and comprehensive applications of aptamer probes in diagnosis of amyloid diseases.     

Novel 6-aryl substituted 4-pyrrolidineaminoquinazoline derivatives as potent phosphoinositide 3-kinase delta (PI3Kδ) inhibitors

In this study, a novel series of 6-aryl substituted 4-pyrrolidineaminoquinazoline derivatives were designed and evaluated as potent PI3Kδ inhibitors. The preliminary SAR was established, and compounds 12d, 20a and 20c displayed leading potent PI3Kδ inhibition, with IC₅₀ values of 4.5, 2.7 and 3.1?nM, respectively, that were comparable to idelalisib (IC₅₀?=?2.7?nM). Moreover, these three compounds showed favorable PI3Kδ isoform selectivity over PI3Kα, PI3Kβ, and PI3Kγ, and showed distinct anti-proliferation profiles against four human B cell lines of Ramos, Raji, RPMI-8226 and SU-DHL-6. In addition, molecular docking simulation showed that several key hydrogen bonding interactions were formed for compounds 12d, 20a and 20c in the PI3Kδ pocket, which might explain their potent PI3Kδ inhibition. These results indicate the 6-aryl substituted 4-pyrrolidineaminoquinazolines were potent PI3Kδ inhibitors.     

线粒体质量控制失调与恶性肿瘤发生和发展相关性的研究进展

线粒体活性氧增多、线粒体DNA突变和拷贝数改变、Ca~(2+)超载、凋亡异常等功能障碍与肿瘤发生、生长、侵袭、转移密切相关.随着研究的逐渐深入,人们认识到线粒体是个动态的细胞器,在生理、病理因素刺激下,经线粒体融合/分裂、线粒体自噬、线粒体生物合成以及线粒体分子伴侣和线粒体未折叠蛋白反应的协同调控,在细胞器和分子水平达到对线粒体及其蛋白质的质量控制,限制和延缓功能受损线粒体的积累和过度增多,维持线粒体数量、形态、功能和蛋白质量的动态平衡,保证细胞正常生命活动的进行,使其更好地适应环境.若线粒体及其蛋白的稳态调节能力下降或失衡,会导致受损线粒体的积累并引发细胞内环境的紊乱,影响线粒体功能的正常发挥,从而诱导正常细胞的恶性转化.     

Effects of GeO<Subscript>2</Subscript> on chlorophyll fluorescence and antioxidant enzymes in apple leaves under strong light

In this study, we chose apple leaf as plant material and studied effects of GeO₂ on operation of photosynthetic apparatus and antioxidant enzyme activities under strong light. When exogenous GeO₂ concentration was below 5.0 mg L^–1, maximum photochemical quantum yield of PSII and actual quantum yield of PSII photochemistry increased significantly compared with the control under irradiances of 800 and 1,600 μmol(photon) m^–2 s^–1. Photosynthetic electron transport chain capacity between Q_A–Q_B, Q_A–PSI acceptor, and Q_B–PSI acceptor showed a trend of rising up with 1.0, 2.0, and 5.0 mg(GeO₂) L^–1 and declining with 10.0 mg(GeO₂) L^–1. On the other hand, dissipated energy via both ΔpH and xanthophyll cycle decreased remarkably compared with the control when GeO₂ concentration was below 5.0 mg L^–1. Our results suggested that low concentrations of GeO₂ could alleviate photoinhibition and 5.0 mg(GeO₂) L^–1 was the most effective. In addition, we found, owing to exogenous GeO₂ treatment, that the main form of this element in apple leaves was organic germanium, which means chemical conversion of germanium happened. The organic germanium might be helpful to allay photoinhibition due to its function of scavenging free radicals and lowering accumulation of reactive oxygen species, which was proven by higher antioxidant enzyme activities.