Down-Regulation of Neogenin Accelerated Glioma Progression through Promoter Methylation and Its Overexpression in SHG-44 Induced Apoptosis

Dependence receptors have been proved to act as tumor suppressors in tumorigenesis. Neogenin, a DCC homologue, well known for its fundamental role in axon guidance and cellular differentiation, is also a dependence receptor functioning to control apoptosis. However, loss of neogenin has been reported in several kinds of cancers, but its role in glioma remains to be further investigated.Western blot analysis showed that neogenin level was lower in glioma tissues than in their matching surrounding non-neoplastic tissues (n = 13, p<0.01). By immunohistochemical analysis of 69 primary and 16 paired initial and recurrent glioma sections, we found that the loss of neogenin did not only correlate negatively with glioma malignancy (n = 69, p<0.01), but also glioma recurrence (n = 16, p<0.05). Kaplan-Meier plot and Cox proportional hazards modelling showed that over-expressive neogenin could prolong the tumor latency (n = 69, p<0.001, 1187.6 ± 162.6 days versus 687.4 ± 254.2 days) and restrain high-grade glioma development (n = 69, p<0.01, HR: 0.264, 95% CI: 0.102 to 0.687). By Methylation specific polymerase chain reaction (MSP), we reported that neogenin promoter was methylated in 31.0% (9/29) gliomas, but absent in 3 kinds of glioma cell lines. Interestingly, the prevalence of methylation in high-grade gliomas was higher than low-grade gliomas and non-neoplastic brain tissues (n = 33, p<0.05) and overall methylation rate increased as glioma malignancy advanced. Furthermore, when cells were over-expressed by neogenin, the apoptotic rate in SHG-44 was increased to 39.7% compared with 8.1% in the blank control (p<0.01) and 9.3% in the negative control (p<0.01).These observations recapitulated the proposed role of neogenin as a tumor suppressor in gliomas and we suggest its down-regulation owing to promoter methylation is a selective advantage for glioma genesis, progression and recurrence. Furthermore, the induction of apoptosis in SHG-44 cells after overexpression of neogenin, indicated that neogenin could be a novel target for glioma therapy

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

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Effect of GS-Rd on NSCLC cells (NCI-H460 and 95-D )</p

Investigating the Impact of Spatial Distribution of Sustainable Drainage System (SuDS) Components on Their Flood Mitigation Performance in Communities with High Groundwater Levels

This paper investigated the impact of the spatial distribution of SuDS components on their flood reduction performance and the underlying mechanisms in a community with high groundwater levels. The effects of SuDS components&rsquo; connectivity, decentralized level, and installation position along the flow direction on the reduction of total discharge volume (TDV), average discharge flow rate (ADFR), maximum discharge flow rate (MDFR), inundated area (IA), average inundated depth (AID), and maximum inundated depth (MID) were studied by coupling of the storm water management model (SWMM) and high-performance integrated hydrodynamic modelling system (HiPIMS). The results demonstrate that the connectivity has a positive linear correlation with the reduction of TDV (R2 &gt; 0.991), ADFR (R2 &gt; 0.992), and MDFR (R2 &gt; 0.958), while the decentralized level of rain gardens and green roofs present positive one-phase exponential correlation with the reduction of TDV (R2 &gt; 0.935), ADFR (R2 &gt; 0.934) and MDFR (R2 &gt; 0.967). A better-integrated mitigation of TDV and ADFR could be achieved by installing SuDS upstream along the flow direction. The connectivity from green roofs to rain gardens has a positive effect on the reduction of AID and MID but leads to the increase of IA. The findings of this study may contribute to the development of general spatial distribution guidelines and strategies to optimize the overall performance of SuDS components, especially at a community scale

Investigating the Impact of Spatial Distribution of Sustainable Drainage System (SuDS) Components on Their Flood Mitigation Performance in Communities with High Groundwater Levels

This paper investigated the impact of the spatial distribution of SuDS components on their flood reduction performance and the underlying mechanisms in a community with high groundwater levels. The effects of SuDS components’ connectivity, decentralized level, and installation position along the flow direction on the reduction of total discharge volume (TDV), average discharge flow rate (ADFR), maximum discharge flow rate (MDFR), inundated area (IA), average inundated depth (AID), and maximum inundated depth (MID) were studied by coupling of the storm water management model (SWMM) and high-performance integrated hydrodynamic modelling system (HiPIMS). The results demonstrate that the connectivity has a positive linear correlation with the reduction of TDV (R2 > 0.991), ADFR (R2 > 0.992), and MDFR (R2 > 0.958), while the decentralized level of rain gardens and green roofs present positive one-phase exponential correlation with the reduction of TDV (R2 > 0.935), ADFR (R2 > 0.934) and MDFR (R2 > 0.967). A better-integrated mitigation of TDV and ADFR could be achieved by installing SuDS upstream along the flow direction. The connectivity from green roofs to rain gardens has a positive effect on the reduction of AID and MID but leads to the increase of IA. The findings of this study may contribute to the development of general spatial distribution guidelines and strategies to optimize the overall performance of SuDS components, especially at a community scale

Digitally tailoring arbitrary structured light of generalized ray-wave duality

Structured lights, particularly those with tunable and controllable geometries, are highly topical due to a myriad of their applications from imaging to communications. Ray-wave duality (RWD) is an exotic physical effect in structured light that the behavior of light can be described by both the geometric ray-like trajectory and a coherent wave-packet, thus providing versatile degrees of freedom (DoFs) to tailor more general structures. However, the generation of RWD geometric modes requires a solid-state laser cavity with strict mechanical control to fulfill the ray oscillation condition, which limits the flexiblility of applications. Here we overcome this confinement to generate on-demand RWD geometric modes by digital holographic method in free space without a cavity. We put forward a theory of generalized ray-wave duality, describing all previous geometric modes as well as new classes of RWD geometric modes that cannot be generated from laser cavities, which are verified by our free-of-cavity creation method. Our work not only breaks the conventional cavity limit on RWD but also enriches the family of geometric modes. More importantly, it offers a new way of digitally tailoring RWD geometric modes on-demand, replacing the prior mechanical control, and opening up new possibilities for applications of ray-wave structured light.</p

Polysaccharides of Floccularia luteovirens Alleviate Oxidative Damage and Inflammatory Parameters of Diabetic Nephropathy in db/db Mice

Background: Floccularia luteovirens (Alb. & Schwein.) Pouzar, is an extremely rare edible and medicinal mushroom in China. The crude polysaccharides of F. luteovirens (FLPs) has significant antioxidant and anti-inflammation activities and exerts excellent protective functions in diabetic nephropathy (DN) complications, but the material basis of the pharmacological effects of FLPs and the molecular mechanism of its pharmacological action are still unclear. Methods: First, we performed systemic composition analysis on extracted and isolated FLPs. Next, the spontaneous db/db mouse DN model was used to investigate the mitigation and protection functions of FLPs in DN and the underlying mechanism through the mammalian target of the rapamycin (mTOR)/GSK-3β/NRF-2 pathway. Results: FLPs contained 65.0% total sugars, 7.2% reducing sugars, 7.93% proteins, 0.36% total flavonoids, 17 amino acids, 13 fatty acids, and 8 minerals. After intragastric administration of FLPs with concentrations of 100, 200 and 400 mg/kg for 8 weeks, FLPs inhibited excessive weight gain, relieved the symptoms of obesity, and significantly improved glucose metabolism and lipid metabolism in the db/db mice. In addition, FLPs were also involved in regulating the indicators of various oxidases and inflammatory factors in the serum and kidney of db/db mice. Conclusions: FLPs effectively improved and relieved kidney tissue injury caused by high glucose, targeted and regulated phospho-GSK-3β, and suppressed inflammatory factor accumulation. Furthermore, FLPs activated the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (NRF2/HO-1) pathway and enhanced the activity of catalase (CAT) to further play a role in relieving and treating T2DM and nephropathy complications

Synthesis, Antifungal Activity and QSAR of Some Novel Carboxylic Acid Amides

A series of novel aromatic carboxylic acid amides were synthesized and tested for their activities against six phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to good activity. Among them N-(2-(1H-indazol-1-yl)phenyl)-2-(trifluoromethyl)benzamide (3c) exhibited the highest antifungal activity against Pythium aphanidermatum (EC50 = 16.75 µg/mL) and Rhizoctonia solani (EC50 = 19.19 µg/mL), compared to the reference compound boscalid with EC50 values of 10.68 and 14.47 µg/mL, respectively. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were employed to develop a three-dimensional quantitative structure-activity relationship model for the activity of the compounds. In the molecular docking, a fluorine atom and the carbonyl oxygen atom of 3c formed hydrogen bonds toward the hydroxyl hydrogens of TYR58 and TRP173

Down-regulation of miR-21 with antagomir-21 inhibits angiogenesis through targeting HIF-1α/VEGF/VEGFR2 signaling pathway.

<p>(A)Expression levels of miR-21 in tumors treated with miR-21 mimic, antagomir-21 or scramble. Data are expressed as mean ± SEM. **<i>P</i><0.01 <i>vs</i> control group. (B–E) Protein levels of PTEN, HIF-1α, VEGF and VEGFR2 were analyzed by Western blotting assay. Data are expressed as mean ± SEM. n = 3 in each group. *<i>P</i><0.05 <i>vs</i> control group, **<i>P</i><0.01 <i>vs</i> control group.</p

The effect of miR-21 antagomir on the cell proliferation and apoptosis.

<p>MTT assay of 4T1 cells (A) and HUVECs (B). Data are expressed as mean ± SEM, n = 3, **<i>P</i><0.01 <i>vs</i> control. Quantification of apoptotic 4T1 cells (C) and HUVECs (D) were determined and shown in the diagram. The number of apoptotic cells was significantly increased in cells transfected with antagomir-21 than in control group. Data are expressed as mean ± SEM, n = 10, **<i>P</i><0.01 <i>vs</i> control. (F). Apoptotic 4T1 cells (E) and HUVECs (F) were determined by TUNEL staining and visualized at 200× magnification. Green color is TUNEL staining representing apoptotic cell; blue color is the cell nucleus stained by DAPI.</p