Melatonin Induced Schwann Cell Proliferation and Dedifferentiation Through NF-ĸB,FAK-Dependent but Src-Independent Pathways

Background:Peripheral nerve injury (PNI) is a common condition that compromises motor and sensory functions. Peripheral nerves are known to have regenerative capability and the pineal hormone, melatonin, is known to aid nerve regeneration. However, the role of Schwann cells and the pathways involved remain unclear. Thus, the aim of this study is to identify the effects of melatonin on Schwann cell proliferation, dedifferentiation, and the involvement of nuclear factor kappa light chain enhancer of activated B cells (NF-ĸB), focal adhesion kinase (FAK) and proto-oncogene tyrosine-protein kinase, Src pathways in this process.Methods:Schwann cells was treated with melatonin and its proliferation and dedifferentiation were identified using MTT assay and immunofluorescence staining for SRY (sex determining region Y)-box 2 (SOX2). Next, the protein expressions of NF-ĸB, FAK and Src pathways were identified by Western blot.Results:MTT results confirmed increased proliferation of Schwann cells with melatonin treatment, and it was highest at 10 μM melatonin. Immunofluorescent staining revealed an increase in the green fluorescence staining for SOX2 in melatonin-treated cells, showing enhanced dedifferentiation. Western blot assay revealed melatonin increased phospho-NF-ĸB (PNF-ĸB), IKK-α, FAK (D2R2E), phospho-FAK (Tyr 576/577 and Tyr 397) protein expressions as compared with control. However, Src (32G6), Lyn (C13F9), Fyn, Csk (C74C1) protein expressions were not increased as compared with control.Conclusion:Melatonin promotes Schwann cell proliferation and dedifferentiation via NF-ĸB, FAK-dependent but Src-independent pathways.Key Words: Dedifferentiation, Melatonin, Peripheral nerve injury, Proliferation, Schwann cells     

Geogrid‐Inspired Nanostructure to Reinforce a CuxZnySnzS Nanowall Electrode for High‐Stability Electrochemical Energy Conversion Devices

Inspired by geogrids commonly applied in construction engineering to reinforce side slopes and retaining walls, the use of a “nano‐geogrid” to reinforce a Cu_x Zn_y Sn_z S (CZTS) nanowall electrode for application in electrochemical reactions is demonstrated. The CZTS nanowall electrode reinforced by the nano‐geogrid (denoted as NWD) shows not only remarkable mechanical and electrochemical stability but also considerable electrochemical performances. The NWD demonstrated as a counter electrode in a dye‐sensitized solar cell shows a power conversion efficiency of 7.44 ± 0.04%, comparable with the device using Pt as electrode, and also significantly improves device stability as compared with that afforded by an electrode comprising a CZTS nanowall without the nano‐geogrid (denoted as NOD). In addition, applying the NWD electrode as a cathode in photo‐electrochemical hydrogen evolution reactions (HERs) yields a photocurrent density of ?10 mA cm^?2 at ?0.162 V (vs RHE) under AM 1.5 illumination. Moreover, when HERs are conducted under extreme conditions, the NWD electrode remains intact, whereas the NOD electrode is completely peeled off after 10 min of reaction. Therefore, the concept of using a mimetic rational nanostructure could pave the way for the possibility of improving the performance and stability of various devices.     

基于资源环境承载力的国家级新区空间开发管控研究

随着我国城市工业化和城镇化的快速推进,由于不合理的空间开发导致生态空间被挤占、城市资源环境超载现象日益突出。以资源环境承载力为基础的空间开发管控制度是体现生态优先、绿色发展理念,从源头实现城市经济社会发展和环境协调发展的重要路径。选取国家级新区江北新区为案例地区,通过构建涵盖生态保护重要性、土地承载力、环境容量、环境压力4个要素层、10项具体指标的评价体系,基于GIS空间分析工具评估区域资源环境承载力。研究表明江北新区资源环境承载力呈现由沿江向内陆、平原地区向丘陵地区逐级递减趋势,根据要素层在空间分布差异性,将区域分为资源环境承载力饱和区域、资源承载力尚好但环境压力较大区域、资源承载力较好且环境压力较小区域、生态环境安全保障区域四个类型,并制定差异化的空间准入和管控措施。研究不仅为资源环境要素全面融入国家新一轮空间规划体系制定和实施全过程提供技术支撑,也可为长江经济带制造业发达地区探索可持续发展空间开发路径提供案例借鉴。     

Factors associated with inflammation markers, a cross-sectional analysis

Epidemiological studies have reported associations between circulating inflammation markers and risk of chronic diseases. It is of interest to examine whether risk factors for these diseases are associated with inflammation. We conducted a cross-sectional analysis to evaluate whether reproductive and lifestyle factors and circulating vitamin D were associated with inflammation markers, including C-reactive protein, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα), and cytokine modulators (IL-1RA, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1/R2), among 616 healthy women. We confirmed associations of several inflammation markers with age and BMI. We also observed significantly higher levels of certain inflammation markers in postmenopausal vs. premenopausal women (TNFα, sIL-1RII, sIL-2Ra), with increasing parity (IL-12p40), and with higher circulating 25(OH) vitamin D (IL-13) and lower levels among current users of non-steroidal anti-inflammatory drugs (NSAIDs) (IL-1β, IL-2, IL-10, IL-12p70, and IL-12p40), current smokers (IL-4, IL-13, IL-12p40), and women with a family history of breast or ovarian cancer (IL-4, IL-10, IL-13). Our findings suggest that risk factors for chronic diseases (age, BMI, menopausal status, parity, NSAID use, family history of breast and ovarian cancer, and smoking) are associated with inflammation markers in healthy women.     

Sustained release of proteins from electrospun biodegradable fibers

Electrospinning is a simple and versatile technique of producing polymeric fibers ranging from submicron to micron in diameter. Incorporation of bioactive agents into the fibers could make a biofunctional tissue engineering scaffold. In this study, we investigated the feasibility of encapsulating human beta-nerve growth factor (NGF), which was stabilized in a carrier protein, bovine serum albumin (BSA) in a copolymer of epsilon-caprolactone and ethyl ethylene phosphate (PCLEEP) by electrospinning. Partially aligned protein encapsulated fibers were obtained and the protein was found to be randomly dispersed throughout the electrospun fibrous mesh in aggregate form. A sustained release of NGF via diffusion process was obtained for at least 3 months. PC12 neurite outgrowth assay confirmed that the bioactivity of electrospun NGF was retained, at least partially, throughout the period of sustained release, thus clearly demonstrating the feasibility of encapsulating proteins via electrospinning to produce biofunctional tissue scaffolds.     

Reproducibility of serum cytokines and growth factors

Background: In most studies, circulating biomarkers are usually assessed from a single sample, assuming that this single measurement represents the long-term biomarker status of the individual. Such an assumption is rarely tested although it may not be valid for all biomarkers. The objective of this study was to investigate the temporal reproducibility of a panel of cytokines and growth factors. Methods: Thirty-five postmenopausal women with two annual visits and 30 premenopausal women with three annual visits were randomly selected from the participants in an existing prospective cohort. A total of 23 serum cytokines, nine growth factors and C-reactive protein (CRP) were measured using the Luminex xMap? technology. In addition, for eight biomarkers, regular and high sensitivity (hs) assays were compared. Results: The biomarkers with adequate (>60%) detection rates and acceptable (?0.55) intra-class correlation coefficients (ICCs) were: hsIL-1β, IL-1RA, hsIL-2, hsIL-4, hsIL-5, hsIL-6, hsIL-10, IL-12p40, hsIL-12p70, hsTNF-α, TNF-R1, TNF-R2, CRP, HGF, NGF, and EGFR. The remaining biomarkers either had low temporal reproducibility or were undetectable in more than 40% of samples. Conclusions: The results suggest that 16 of the 41 biomarkers measured with Luminex technology showed sufficient sensitivity and temporal reproducibility in sera.     

AlgX is a periplasmic protein required for alginate biosynthesis in Pseudomonas aeruginosa

Alginate, an exopolysaccharide produced by Pseudomonas aeruginosa, provides the bacterium with a selective advantage that makes it difficult to eradicate from the lungs of cystic fibrosis (CF) patients. Previous studies identified a gene, algX, within the alginate biosynthetic gene cluster on the P. aeruginosa chromosome. By probing cell fractions with anti-AlgX antibodies in a Western blot, AlgX was localized within the periplasm. Consistent with these results is the presence of a 26-amino-acid signal sequence. To examine the requirement for AlgX in alginate biosynthesis, part of algX in P. aeruginosa strain FRD1::pJLS3 was replaced with a nonpolar gentamicin resistance cassette. The resulting algXDelta::Gm mutant was verified by PCR and Western blot analysis and was phenotypically nonmucoid (non-alginate producing). The algXDelta::Gm mutant was restored to the mucoid phenotype with wild-type P. aeruginosa algX provided on a plasmid. The algXDelta::Gm mutant was found to secrete dialyzable oligouronic acids of various lengths. Mass spectroscopy and Dionex chromatography indicated that the dialyzable uronic acids are mainly mannuronic acid dimers resulting from alginate lyase (AlgL) degradation of polymannuronic acid. These studies suggest that AlgX is part of a protein scaffold that surrounds and protects newly formed polymers from AlgL degradation as they are transported within the periplasm for further modification and eventual transport out of the cell.     

Identification of small molecule inhibitors of anthrax lethal factor

The virulent spore-forming bacterium Bacillus anthracis secretes anthrax toxin composed of protective antigen (PA), lethal factor (LF) and edema factor (EF). LF is a Zn-dependent metalloprotease that inactivates key signaling molecules, such as mitogen-activated protein kinase kinases (MAPKK), to ultimately cause cell death. We report here the identification of small molecule (nonpeptidic) inhibitors of LF. Using a two-stage screening assay, we determined the LF inhibitory properties of 19 compounds. Here, we describe six inhibitors on the basis of a pharmacophoric relationship determined using X-ray crystallographic data, molecular docking studies and three-dimensional (3D) database mining from the US National Cancer Institute (NCI) chemical repository. Three of these compounds have K(i) values in the 0.5-5 microM range and show competitive inhibition. These molecular scaffolds may be used to develop therapeutically viable inhibitors of LF.     

经气管灌注血管紧张素Ⅱ导致凋亡性急性肺损伤(英文)

为研究外源性血管紧张素Ⅱ（angiotensinⅡ,ANG）在急性肺损伤和肺泡上皮细胞凋亡中的作用,经气管分别给雄性Wistar大鼠（175-200g）灌注ANG、ANG加caspase抑制剂ZVAD—fmk、ANG加ANG受体1阻断剂losartan和仅灌注磷酸盐缓冲溶液（PBS）。6或20h后在体灌洗动物肺脏,测定灌洗液中血红蛋白（hemoglobin,Hb）和荧光物质（BODIPY）标定的白蛋白含量（在灌洗前15min静脉注入BODIPY-白蛋白）。TUNEL测定显示,灌注ANG6h后,支气管和肺泡上皮细胞内标定的DNA片断显著增2H（P〈0．05）;ANG所致的DNA片断增加可被同时灌注ZVAD—fmk或losartan阻断。灌注ANG后免疫标定caspase3阳性细胞数量显著增多（P〈0．01）,ZVAD—fmk或losartan同样显著减少caspase3阳性细胞的数量。灌注ANG显著增加肺泡灌洗液中荧光标定的白蛋白（P〈0．01）和Hb的含量（P〈0．05）;ZVAD—fmk或losartan亦显著抑制荧光白蛋白和Hb含量的变化。结果表明,肺泡上皮细胞在体暴露于外源性ANG足以引起ANG受体1介导的上皮细胞凋亡和肺泡屏障损伤。     

A cDNA Microarray for Crassostrea virginica and C. gigas

The eastern oyster, Crassostrea virginica, and the Pacific oyster, C. gigas, are species of global economic significance as well as important components of estuarine ecosystems and models for genetic and environmental studies. To enhance the molecular tools available for oyster research, an international group of collaborators has constructed a 27,496-feature cDNA microarray containing 4460 sequences derived from C. virginica, 2320 from C. gigas, and 16 non-oyster DNAs serving as positive and negative controls. The performance of the array was assessed by gene expression profiling using gill and digestive gland RNA derived from both C. gigas and C. virginica, and digestive gland RNA from C. ariakensis. The utility of the microarray for detection of homologous genes by cross-hybridization between species was also assessed and the correlation between hybridization intensity and sequence homology for selected genes determined. The oyster cDNA microarray is publicly available to the research community on a cost-recovery basis.