Expression of genes involved in mouse lung cell differentiation/regulation after acute exposure to photons and protons with or without low-dose preirradiation

The goal of this study was to compare the effects of acute 2 Gy irradiation with photons (0.8 Gy/min) or protons (0.9 Gy/min), both with and without pre-exposure to low-dose/low-dose-rate γ rays (0.01 Gy at 0.03 cGy/h), on 84 genes involved in stem cell differentiation or regulation in mouse lungs on days 21 and 56. Genes with a ≥1.5-fold difference in expression and P < 0.05 compared to 0 Gy controls are emphasized. Two proteins specific for lung stem cells/progenitors responsible for local tissue repair were also compared. Overall, striking differences were present between protons and photons in modulating the genes. More genes were affected by protons than by photons (22 compared to 2 and 6 compared to 2 on day 21 and day 56, respectively) compared to 0 Gy. Preirradiation with low-dose-rate γ rays enhanced the acute photon-induced gene modulation on day 21 (11 compared to 2), and all 11 genes were significantly downregulated on day 56. On day 21, seven genes (aldh2, bmp2, cdc2a, col1a1, dll1, foxa2 and notch1) were upregulated in response to most of the radiation regimens. Immunoreactivity of Clara cell secretory protein was enhanced by all radiation regimens. The number of alveolar type 2 cells positive for prosurfactant protein C in irradiated groups was higher on day 56 (12.4-14.6 cells/100) than on day 21 (8.5-11.2 cells/100) (P < 0.05). Taken together, these results showed that acute photons and protons induced different gene expression profiles in the lungs and that pre-exposure to low-dose-rate γ rays sometimes had modulatory effects. In addition, proteins associated with lung-specific stem cells/progenitors were highly sensitive to radiation.     

Synthesis, biological evaluation, and molecular docking studies of resveratrol derivatives possessing chalcone moiety as potential antitubulin agents

Twenty-three resveratrol derivatives possessing chalcone moiety were synthesized and characterized, and their biological activities were also evaluated as potential antiproliferation and tubulin polymerization inhibitors. Compound C19 exhibited the most potent activity in vitro, which inhibited the growth of HepG2, B16-F10, and A549 cell lines with IC(50) values of 0.2, 0.1, and 1.4 μg/mL, respectively. Compound C19 also exhibited significant tubulin polymerization inhibitory activity (IC(50)=2.6 μg/mL). Docking simulation was performed to position compound C19 into the tubulin-colchicine binding site to determine the probable binding mode.     

Design, synthesis and biological evaluation of pyridine acyl sulfonamide derivatives as novel COX-2 inhibitors

A series of pyridine acyl sulfonamide derivatives (1-24) have been designed and synthesized and their biological activities were also evaluated as potential cyclooxygenase-2 (COX-2) inhibitors. Among all the compounds, compound 23 displayed the most potent COX-2 inhibitory activity with an IC(50) of 0.8 μM. Antitumor and anti-inflammatory assays indicated that compound 23 owned high antiproliferative activity against B16-F10, HepG2 and MCF-7 cancer cell lines as well as COX-2-derived prostaglandin E(2) (PGE(2)) inhibitory activity of murine macrophage RAW 264.7 cell line with IC(50) values of 2.8, 1.2, 1.8 and 0.15 μM, respectively. Docking simulation was performed to position compound 23 into the COX-2 active site to determine the probable binding model.     

白腐真菌Pleurotus sajor-caju预处理对红麻秸秆发酵乙醇的影响

为研究微生物法预处理对红麻秸秆中木质素的降解及后续的红麻纤维素酶促糖化和发酵效率的影响,将白腐真菌Pleurotus sajor-caju接种在红麻秸秆培养基上固态培养,对红麻秸秆进行预处理。经P. sajor-caju培养25~35 d后,有效转化红麻秸秆中的木质素,转化率最高可达50.20％,并提高红麻纤维素的酶促水解效率,糖化率达69.33％~78.64％,与对照组相比提高了3.5~4.1倍。以微生物法预处理后的红麻秸秆样品为底物的同步糖化发酵实验表明,发酵72 h,发酵液中乙醇浓度达到18.35~     

含乙型肝炎病毒S-PreS1 基因的DNA疫苗与蛋白颗粒疫苗联合免疫可增强免疫应答

为研制新型有效的HBV治疗性疫苗,构建了含PreS1与S融合基因的HBV DNA疫苗,即pVRC-HBSS1 (PreS1 21–47 aa融合在S抗原1–223的羧基端),并制备了CHO表达相同结构的蛋白颗粒亚单位疫苗HBSS1。在Balb/C小鼠中采用不同的DNA免疫方式 (即肌肉注射、皮内注射加电转) 初免3次,蛋白颗粒亚单位疫苗 (不同佐剂) 肌肉注射加强免疫1次,然后我们分析比较了各组疫苗所引起的免疫应答特点。抗体检测结果表明：皮内注射结合电转初免组产生的PreS1与 S特异性抗体水平皆高于肌肉直接注射组。进一步还发现DNA疫苗与蛋白颗粒亚单位疫苗两种疫苗联合应用后S抗原特异的细胞免疫应答 (IFN-γ ELISpot分析) 明显高于DNA疫苗或蛋白颗粒亚单位单独应用,其中皮内注射+电转结合蛋白颗粒亚单位疫苗联合免疫组可产生最强的细胞免疫应答。这些研究为新型HBV 治疗性疫苗的优化设计与合理应用提供了依据。     

基于λ-Red重组酶系统的Ⅳa2基因缺失及重组腺病毒的包装

本研究用λ-Red重组酶介导的PCR打靶方法缺失腺病毒基因组上Ⅳa2基因的大部分编码序列(1104 bp),并获得一种Ⅳa2基因缺失的重组腺病毒。首先构建PCR打靶的含有卡那霉素抗性表达盒的模板质粒pAK,再以pAK为模板扩增出两端含39 bp同源臂的线性DNA片段;将pFG140质粒及线性DNA片段依次转化到宿主菌BW25113/pIJ790中,通过λ-Red重组酶介导的同源重组获得了缺失Ⅳa2基因的腺病毒基因组质粒pFG140-ΔⅣa2(1104)。酶切及DNA测序结果显示,用λ-Red重组酶介导的PCR打靶方法在pFG140上精确地缺失了预计的Ⅳa2基因3’端的1104bp片段。用PCR方法扩增获得Ⅳa2基因全长ORF,插入表达载体pAAV2neo中,构建成Ⅳa2基因表达质粒pAAV2neo-Ⅳa2。将pFG140-ΔⅣa2(1104)与pAAV2neo-Ⅳa2共转染HEK293细胞,成功地获得了重组腺病毒Ad5ΔⅣa2(1104)。Western Blot的结果表明,Ad5ΔⅣa2(1104)病毒感染的HEK293细胞检测不到Ⅳa2蛋白的表达。本研究建立了一种对腺病毒基因组直接进行缺失操作的λ-Red重组酶介导的PCR打靶方法,并获得了一种IVa2基因大部分缺失的重组腺病毒。     

Modeling antibiotic resistance in hospitals: the impact of minimizing treatment duration

Infections caused by antibiotic-resistant pathogens are a global public health problem. Numerous individual- and population-level factors contribute to the emergence and spread of these pathogens. An individual-based model (IBM), formulated as a system of stochastically determined events, was developed to describe the complexities of the transmission dynamics of antibiotic-resistant bacteria. To simplify the interpretation and application of the model's conclusions, a corresponding deterministic model was created, which describes the average behavior of the IBM over a large number of simulations. The integration of these two model systems provides a quantitative analysis of the emergence and spread of antibiotic-resistant bacteria, and demonstrates that early initiation of treatment and minimization of its duration mitigates antibiotic resistance epidemics in hospitals.     

Sequence analysis and characterizations of two novel plasmids isolated from Thermus sp. 4C

Two novel plasmids, named pS4C and pL4C, were isolated from the thermophilic bacterium Thermus sp. 4C. The pS4C with a length of 5015bp and 58.25% of G+C content, contains 9 putative open reading frames (ORFs). The larger plasmid, pL4C, consisting of 21,248bp, has a G+C content of 68.60% and 34 putative ORFs. Both plasmids encode their own replication protein. The ORF 22 of pL4C and the ORF 4 of pS4C encode proteins with high sequence similarities to integrase (97%) and transposase (97%), respectively, which are both involved in DNA rearrangement and exchange. Furthermore, sequence analysis of pL4C also showed that several plasmid-encoded genes may be involved in DNA modification and repair, such as DNA G:T-mismatch repair endonuclease and micrococcal nuclease-like protein. These proteins may be involved in raising the repair efficiency and other minor editing needs. Interestingly, the elimination of plasmids significantly lowered the growth temperature of Thermus sp. 4C. Few reports dealing with the DNA repair enzymes on the plasmid from Thermus strains were published so far.     

Ytterbium and trace element distribution in brain and organic tissues of offspring rats after prenatal and postnatal exposure to ytterbium

Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering the environment and eventually accumulating in the human body. Previous studies indicate that the impact of lanthanides on brain function cannot be neglected. Although neurological studies of trace elements are of paramount importance, up to now, little data are provided regarding the status of micronutritional elements in rats after prenatal and long-term exposure to lanthanide. The aim of this study is to determine the ytterbium (Yb) and trace elements distribution in brain and organic tissues of offspring rats after prenatal and long-term exposure to Yb. Wistar rats were exposed to Yb through oral administration at 0,0.1, 2, and 40 mg Yb/kg concentrations from gestation day 0 through 5 mo of age. Concentrations of Yb and other elements (Mg, Ca, Fe, Cu, Mn, and Zn) in the serum, liver, femur, and brain regions (cerebral cortex, hippocampus, cerebellum, and the rest) of offspring rats at the age of 0 d, 25 d, and 5 mo were analyzed by inductively coupled plasma-mass spectrometry. The accumulation of Yb in the brain, liver, and femur is observed; moreover, the levels of Fe, Cu, Mn, Zn, Ca, and Mg in the brain and organic tissues of offspring rats are also altered after Yb exposure. This disturbance of the homeostasis of trace elements might induce adverse effects on normal physiological functions of the brain and other organs.     

Study on the toxic effect of lead(II) ion on <Emphasis Type="Italic">Escherichia coli</Emphasis>

The toxic effects of lead(II) have been studied in Escherichia coli cells. Using microcalorimetric analysis, it was shown that E. coli growth was inhibited in the presence of Pb²⁺ resulting from damage to the cell membrane and that Pb²⁺ takes part in the metabolism of cells. Treatment with lysozyme confirms damage to the cell’s outer membrane. Similarities between the ionic radii and charge/radius ratio cause Pb(II) to replace Ca(II) at the binding sites of lipopolysacharides, leading to rupture of protecting areas on the cell’s surface. Consequently, the protection and functionality of outer membrane is lost, thus becoming the basis for the biological effect of Pb²⁺ on E. coli.