The role of vimentin in regulating cell-invasive migration in dense cultures of breast carcinoma cells

Cell migration and mechanics are tightly regulated by the integrated activities of the various cytoskeletal networks. In cancer cells, cytoskeletal modulations have been implicated in the loss of tissue integrity, and acquisition of an invasive phenotype. In epithelial cancers, for example, increased expression of the cytoskeletal filament protein vimentin correlates with metastatic potential. Nonetheless, the exact mechanism whereby vimentin affects cell motility remains poorly understood. In this study, we measured the effects of vimentin expression on the mechano-elastic and migratory properties of the highly invasive breast carcinoma cell line MDA231. We demonstrate here that vimentin stiffens cells and enhances cell migration in dense cultures, but exerts little or no effect on the migration of sparsely plated cells. These results suggest that cell-cell interactions play a key role in regulating cell migration, and coordinating cell movement in dense cultures. Our findings pave the way towards understanding the relationship between cell migration and mechanics, in a biologically relevant context.Comment: 26+21 pages, 6+11 figures, supplementary movies available at http://doi.org/10.6084/m9.figshare.5480149, submitted to Nano Letters journa

Two Zn(II) coordination polymers based on 1,3-di(4’-carboxyl-phenyl)benzene and N-donor coligands: syntheses, crystal structures, and luminescent properties

<div><p>Two coordination polymers, {[Zn(dpb)(3-bpmp)_0.5]·1.5(DMF)}_n (<b>1</b>) and [Zn(dpb)(4-bpmp)]_n (<b>2</b>) (H₂dpb = 1,3-di(4′-carboxyl-phenyl)benzene, 3-bpm<i>p</i> = 1,4-bis(3-pyridylmethy)piperazine, 4-bpm<i>p</i> = 1,4-bis(4-pyridylmethy)piperazine and DMF = N,N-dimethylformamide), were solvothermally synthesized and characterized. Tuning the difference of N-donor ligands, we obtained <b>1</b> and <b>2</b> which display different topological nets. Complex <b>1</b> features a 6-connected topological net and <b>2</b> shows a 4-connected three-fold interpenetrated framework. Luminescent properties of <b>1</b> and <b>2</b> are investigated at room temperature.</p></div

Core–Shell SiO₂‑PS Colloids with Controlled Eccentric Ratio

Precisely controlling microstructure of colloidal particles is crucial for their applications. Core–shell colloids have been extensively synthesized and used in past decades. However, controlling the location of cores in core–shell particles remains a challenge. To address this problem we explored the synthesis of SiO₂-PS core–shell colloids by using a simple system containing only core particles, monomer, initiator, and water/ethanol and found the increase of ethanol/water ratio can induce a structure transition sequence from eccentric to concentric to eccentric to concentric to eccentric. Furthermore, we illustrate that the eccentric ratios of SiO₂-PS core–shell colloids, that is, the location of SiO₂ cores in the whole particles, can be precisely controlled by a two-step polymerization procedure. It is anticipated that our results can widen the application of core–shell colloids, especially after the introduction of functionality for core or shell materials

High-Throughput Transformation of Colloidal Polymer Spheres to Discs Simply via Magnetic Stirring of Their Dispersions

In this article, we have successfully demonstrated the high-throughput production of colloidal discs via magnetic stirring of aqueous dispersions of monodisperse, sulfate-stabilized polystyrene (PS) spheres in the presence of a good organic solvent. The organic solvent could be water-miscible, such as tetrahydrofuran, or water-immiscible, such as chloroform. Water-immiscible organic solvents were mixed into aqueous dispersions of PS spheres in the presence of sodium dodecyl sulfate. The geometry of the resulting discs could be easily adjusted by the magnetic stirring time and speed, the stirring bar weight, and the amount of organic solvent. Our strategy is simple, scalable, and hardly dependent on the nature of the organic solvent and the PS sphere diameter; PS spheres with diameters ranging from 200 nm to 5 μm were deformed into discs with almost 100% yield. When organic solutions of fluorescent dyes and nanoparticles were used instead of pure organic solvents for PS sphere liquefaction, fluorescent discs were obtained, underlining the effective, efficient encapsulation of the fluorescent substance in the discs

Liquid-Phase Pulsed Laser Ablation and Electrophoretic Deposition for Chalcopyrite Thin-Film Solar Cell Application

We report ligand-free synthesis of colloidal metallic nanoparticles using liquid-phase pulsed laser ablation, and electrophoretic deposition of the nanoparticles for fabrication of Cu­(In,Ga)­Se₂ (CIGS) thin film solar cells. First, colloidal metallic nanoparticles of Cu–In and Cu–Ga alloys are produced by pulsed laser ablation in common organic solvents without using stabilizing ligands. The nanoparticles are examined for phase, composition, and electrical surface charging and charge modulation mechanisms. Metallic precursor thin films with high purity and precise composition are produced by electrophoretic deposition of the colloids without transferring to another solvent and without using binders. Finally, we demonstrate fabrication of CIGS solar cells on Mo sheet substrates with an (active area) energy conversion efficiency up to 7.37%

Cytotoxicity and <b>Synergistic Effect</b> of the Constituents from Roots of <i>Aglaia odorata</i> (<b>Meliaceae</b>)

<div><p>Twelve compounds were isolated from the roots of <i>Aglaia odorata.</i> Their structures were established on the basis of NMR and MS data as rocaglaol (<b>1</b>), rocaglamide (<b>2</b>), eichlerialactone (<b>3</b>), sapelins A (<b>4</b>), isofouquierone (<b>5</b>), eichlerianic acid (<b>6</b>), shoreic acid (<b>7</b>), agladupol E (<b>8</b>), 3-epimeliantriol (<b>9</b>), cleomiscosins B (<b>10</b>), 2β,3β-dihydroxy-5α-pregnane-16-one (<b>11</b>) and β-d-glucopyranos-1-yl <i>N</i>-methylpyrrole-2-carboxylate (<b>12</b>). Among them, compounds <b>1</b> and <b>2</b> showed significant cytotoxicity against human cancer cell (HL-60, SMMC-7721, A-549, MCF-7 and SW480) with IC₅₀ values of 0.007–0.095 μM, while compounds <b>3</b>–<b>5</b> and <b>10</b> and <b>11</b> showed moderate to no cytotoxicity (IC₅₀ 0.43 to values >40 μM). Compound <b>6</b> showed only weak cytotoxicity (IC₅₀ 6.87 to >40 μM) and its epmier <b>7</b> was completely inactivite (IC₅₀>40 μM) in the assay. However, potent synergistic effect was observed when the molar ratio of <b>6</b> to <b>7</b> is between 4:1 and 1:1.</p></div

Table1_Development and validation of a nomogram prediction model based on albumin-to-alkaline phosphatase ratio for predicting the prognosis of gallbladder carcinoma.docx

Gallbladder carcinoma (GBC) is a rare biliary tract cancer with a high recurrence rate and a poor prognosis. Albumin-alkaline phosphatase ratio (AAPR) has been demonstrated to be a prognostic predictor for several cancers, but its predictive value for GBC patients remains unknown. The aim of this study was to investigate the predictive role of AAPR in GBC patients and to develop a novel nomogram prediction model for GBC patients. We retrospectively collected data from 80 patients who underwent surgery at the Hospital of 81st Group Army PLA as a training cohort. Data were collected from 70 patients with the same diagnosis who underwent surgery at the First Affiliated Hospital of Hebei North University as an external verification cohort. The optimal cut-off value of AAPR was determined using X-tile software. A nomogram for the overall survival (OS) based on multivariate Cox regression analysis was developed and validated using calibration curves, Harrell’s concordance index, the receiver operating characteristic curves, and decisive curve analyses. The optimal cut-off value of AAPR was .20. Univariate and multivariate Cox regression analyses demonstrated that BMI (p = .043), R0 resection (p = .001), TNM stage (p = .005), and AAPR (p = .017) were independent risk factors for GBC patients. In terms of consistency, discrimination, and net benefit, the nomogram incorporating these four independent risk factors performed admirably. AAPR is an independent predictor of GBC patients undergoing surgery, and a novel nomogram prediction model based on AAPR showed superior predictive ability.</p

Effect of early goal directed therapy in the treatment of severe sepsis and/or septic shock

<p><b>Background:</b> Many investigators have reproduced the mortality reduction shown in the original trial of early goal directed therapy (EGDT) in patients with severe sepsis and/or septic shock. Three large randomized controlled trials (RCTs) found neutral results when compared to usual care and a modified form of EGDT. Some have interpreted these studies as a reason to question the efficacy of EGDT.</p> <p><b>Objectives:</b> The purpose of this study was to comprehensively examine the effect of EGDT in the treatment of severe sepsis and/or septic shock in the literature.</p> <p><b>Methods:</b> A systematic review and meta-analysis of RCTs and prospective studies were performed, which extracted studies from PubMed, Elsevier ScienceDirect, Cochrane, Clinicaltrials.gov, Google Scholar, China Knowledge Resource Integrated Database, and Wanfang Database. The mortality trend in the control group from included studies was analyzed.</p> <p><b>Results:</b> Seven RCTs and twelve prospective studies enrolling 3502 EGDT and 3791 usual care participants were included in the analysis. EGDT was found to reduce overall mortality compared to usual care groups. This reduction in mortality was apparent in prospective and randomized control trials conducted before 2010. Over this time period there was a reduction in mortality in patients receiving usual care.</p> <p><b>Limitations:</b> This conclusion was limited by the small size of some selected studies and complicated by the long range of time during the conduction of these studies. These studies were further biased because of the lack of blinding and the crossover of care between the EGDT and usual care groups.</p> <p><b>Conclusions:</b> EGDT significantly reduced mortality in patients with severe sepsis and/or septic shock over 15 years since its publication. Recent studies examining usual care with EGDT have similar mortality benefit because of the diminished treatment effect. This treatment effect is diminished for multiple reasons. With progress in the management of this disease the benefit of EGDT on overall mortality has become comparable with the usual care for sepsis patients. This is because many of the components of EGDT have been incorporated into usual care protocols. As a result, the conclusion that EGDT is ineffective cannot be made. A more rigorous RCT which adjusts for the factors that narrows the treatment effect between groups is required. Given the current state of sepsis care and equipoise that exist, this would be difficult.</p

Catalytic Conversion of Fructose and 5‑Hydroxymethylfurfural into 2,5-Furandicarboxylic Acid over a Recyclable Fe₃O₄–CoO_<i>x</i> Magnetite Nanocatalyst

A nano-Fe₃O₄–CoO_<i>x</i> catalyst was prepared via a simple wet impregnation method. The nano-Fe₃O₄–CoO_<i>x</i> catalyst showed good catalytic performance for the conversion of 5-hydroxymethylfurfural into 2,5-furandicarboxylic acid (FDCA) with <i>t</i>-BuOOH as the oxidant. Several important reaction parameters were explored, with the highest FDCA yield of 68.6% obtained from HMF after 15 h at a reaction temperature of 80 °C. One-pot conversion of fructose into FDCA was also successful via two steps. Catalytic conversion of fructose over Fe₃O₄@SiO₂–SO₃H yielded 93.1% HMF, which was oxidized in situ into FDCA with a yield of 59.8%. Furthermore, recycling of nano-Fe₃O₄–CoO_<i>x</i> was accomplished with the help of a magnetic field. Nano-Fe₃O₄–CoO_<i>x</i> showed high stability in the reaction process. The use of nonprecious metals and no requirement of a base additive made this method much more economical and environmentally friendly

Type III Interferon Induces Distinct SOCS1 Expression Pattern that Contributes to Delayed but Prolonged Activation of Jak/STAT Signaling Pathway: Implications for Treatment Non-Response in HCV Patients

<div><p>Suppressor of cytokine signaling 1 (SOCS1) has long been thought to block type I interferon signaling. However, IFN-λ, a type III IFN with limited receptor expression in hepatic cells, efficiently inhibits HCV (Hepatitis C virus) replication in vivo with potentially less side effects than IFN-α. Previous studies demonstrated that type I and type III activated Janus kinase/signal transducer and activator of transcription (Jak/STAT) signaling pathway differently, with delayed but prolonged activation by IFN-λ stimulation compared to IFNα/β. However, the molecular mechanisms underlying this observation is not well understood. Here, we found that there are distinct differences in SOCS1 expression patterns in Huh-7.5.1 cells following stimulation with IFN-α and IFN-λ. IFN-λ induced a faster but shorter expression of SOCS1. Furthermore, we confirmed that SOCS1 over-expression abrogates anti-HCV effect of both IFN-α and IFN-λ, leading to increased HCV RNA replication in both HCV replicon cells and JFH1 HCV culture system. In line with this, SOCS1 over-expression inhibited STAT1 phosphorylation, attenuated IFN-stimulated response elements (ISRE) reporter activity, and blocked IFN-stimulated genes (ISGs) expression. Finally, we measured SOCS1 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) with or without IFN-α treatment from 48 chronic hepatitis C patients and we found the baseline SOCS1 expression levels are higher in treatment non-responders than in responders before IFN-α treatment. Taken together, SOCS1 acts as a suppressor for both type I and type III IFNs and is negatively associated with sustained virological response (SVR) to IFN-based therapy in patients with HCV. More importantly, faster but shorter induction of SOCS1 by IFN-λ may contribute to delayed but prolonged activation of IFN signaling and ISG expression kinetics by type III IFN.</p></div