Two new supramolecular polyoxmetalates were synthesized from 1, 4-bis4-nitrile-pyridine)-N-methylenephenyldibromide (L1) and 1, 2-bis4-nitrile-pyridine)-N-methylenephenyldibromide (L2) and ...(NH4)6Mo7–O24·4H2O under hydrothermal conditions. They are named p-C20H18N2O4Mo8O26 0.5·H2O (1) and o-C20H18N2O4Mo8O26 ċ 0.5·H2O (2) respectively. The structures have been confirmed through single-crystal X-ray diffraction analyses and further characterized by elemental analyses, IR spectra. The adsorption test of compound 1 and compound 2 in organic dyes were carried out. It was found that compound 1 had a good adsorption effect on methylene blue (MB) and rhodamine B (RhB). The adsorption effect of compound 2 on MB is stronger than that of compound 1.
: Growing evidence has proved that MRE11, a protein underpinned to be involved in DNA double-strand break (DSB) repair process, is correlated with cancer outcomes. However, its role in prostate ...cancer (PCa) remains unclear. This study aimed to investigate the expression of MRE11 in tumor tissue and defining its value in predicting prognosis of PCa patients.
: A total of 578 patients from two cohorts were enrolled in this study. Distribution of categorical clinical-pathological data together with levels of MRE11 expression was compared with χ
-test in a contingency table. Immunohistochemical (IHC) staining and evaluation was detected from 78 paired PCa and adjacent normal tissues. Partial likelihood test from univariate and multivariate Cox regression analysis was developed to address the influence of independent factors on disease-free survival (DFS) and overall survival (OS) in two cohorts. The Kaplan-Meier method and log-rank test were performed to assess the survival benefits between discrete levels. Set Enrichment Analysis (GSEA) was performed to select related genes and pathways from The Cancer Genome Atlas (TCGA) database.
: In the current study, we demonstrated that MRE11 was highly expressed in PCa compared with normal tissues (
0.011). In addition, in the TCGA cohort, the median DFS in patients with IHC positive and negative MRE11 expression levels was 24.5 and 30.6 months, and median OS was 28.7 and 33.0 months, respectively. In FUSCC cohort, median DFS in patients with IHC positive and negative MRE11 expression was 28.0 and 35.6 months. Furthermore, survival curves suggested that PCa patients with elevated MRE11 expression levels showed poorer OS (
=0.019) in TCGA cohort and poor DFS (
=0.047) in FUSCC cohort.
: In conclusion, our study reveals that elevated MRE11 expression is significantly correlated with cancer progression and poor survival in PCa patients. These data suggest that MRE11 may act as an oncoprotein and a promising prognostic marker for PCa patients.
It is often proposed that the wear performance of high-chromium white cast irons could be improved by adding Nb to form NbC. However, NbC can form with a needle-like “Chinese-script” morphology ...and/or as nodular particles, and clear evidence is not available as to which morphology is more beneficial against slurry erosion, a common application for these alloys. The lack of evidence is due to the difficulty of differentiating between the effect of NbC and that of a second type of carbide, M7C3, on slurry erosion resistance. Therefore, we created a martensitic stainless steel resembling the ferrous matrix of a typical high-chromium white cast iron, but without the M7C3 phase, that was reinforced with Chinese-script NbC. A second specimen was prepared by substituting a small amount of Nb for Ti to inoculate the NbC, thus forming nodular particles. An AISI 440C stainless steel was used as a commercial benchmark since it has a similar hardness and microstructure. All three samples were subjected to slurry erosion tests against garnet and sand, with the Chinese-script NbC sample being the worst performer in both cases. Analysis of the worn surfaces revealed that the Chinese-script morphology promoted fracturing, resulting in a higher erosion rate.
•NbC has been known to improve the wear performance in ferrous alloys.•NbC can form Chinese-script structures, dissolving Ti promotes a nodular structure.•NbC and (Nb,Ti)C-reinforced stainless steels were tested for slurry erosion.•Chinese-script NbC was particularly detrimental to slurry erosion.•This has implications for Nb-containing high-chromium white cast iron design.
Somatic depression (SD) is different from non-somatic depression (NSD), and insular subregions have been associated with somatic symptoms. However, the pattern of damage in the insular subregions in ...SD remains unclear. The aim of this study was to use functional connectivity (FC) analyses to explore the bilateral ventral anterior insula (vAI), bilateral dorsal anterior insula (dAI), and bilateral posterior insula (PI) brain circuits in SD patients.
The study included 28 SD patients, 30 NSD patients, and 30 matched healthy control (HC) subjects. All participants underwent 3.0 T resting state functional magnetic resonance imaging. FC analyses were used to explore synchronization between insular subregions and the whole brain in the context of depression with somatic symptoms. Pearson correlation analyses were performed to assess relationships between FC values in brain regions showing significant differences and the total and factor scores on the 17-item Hamilton Rating Scale for Depression (HAMD
).
Compared with the NSD group, the SD group showed significantly decreased FC between the left vAI and the right rectus gyrus, right fusiform gyrus, and right angular gyrus; between the right vAI and the right middle cingulate cortex, right precuneus, and right superior frontal gyrus; between the left dAI and the left fusiform gyrus; and between the right dAI and the left postcentral gyrus. Relative to the NSD group, the SD group exhibited increased FC between the left dAI and the left fusiform gyrus. There were no differences in FC between bilateral PI and any brain regions among the SD, NSD, and HC groups. Within the SD group, FC values between the left vAI and right rectus gyrus were positively correlated with cognitive impairment scores on the HAMD
; FC values between the right vAI and right superior frontal gyrus were positively related to the total scores and cognitive impairment scores on the HAMD
(p < 0.05, uncorrected).
Aberrant FC between the anterior insula and the frontal and limbic cortices may be one possible mechanism underlying SD.
C5a and its receptor, C5a receptor (C5aR), play critical roles in tumor progression. However, mechanisms of C5a–C5aR axis in hepatocellular carcinoma (HCC) cell invasiveness are not fully elucidated. ...In this study, we found that C5aR expression was highly expressed in HCC cell lines and tumor tissues, and associated with capsular invasion, tumor stage and some epithelial–mesenchymal transition (EMT)-related markers. Activation of C5aR by C5a promoted HCC cell invasion and migration, whereas depletion of C5aR expression significantly impaired C5a-stimulated invasion and migration. Furthermore, we found that C5aR induced EMT in HCC cells, through downregulation of E-cadherin and Claudin-1 expression, and upregulation of Snail expression. Finally, we demonstrated that C5aR stimulated activation of ERK1/2, and ERK1/2 pathway was involved in C5aR-mediated EMT, cell invasion and migration of HCC cells. Thus, our data suggest that C5aR stimulates cell invasion and migration via ERK1/2-mediated EMT in HCC cells, and implicate that blocking C5aR expression has therapeutic promise to inhibit HCC invasiveness.
We describe the synthesis and self-assembly behaviour of a series of ten optically active triphenylenedicarboxyimide (TDI) derivatives with a stereogenic center attached to the imide nitrogen ...carrying an end aromatic ring. All TDIs show an enantiotropic hexagonal columnar mesophase with high clearing temperatures up to 260 °C, which means that branching of the introduced stereocenter does not disrupt the columnar π−stacking of the TDI cores. Although all chiral TDIs in THF solution showed CD signal indicative of optical activity, chiral supramolecular structures were only observed in the columnar mesophase of three pairs of chiral TDIs (2, 4 and 5) having one end phenyl or naphthyl ring linked directly or close to the chiral center. DFT calculations suggests that the axially connected aromatic ring at the stereocenter provides steric repulsion upon stacking, thereby leading to the formation of chiral supramolecular structures. Besides, a small amount exclusively single-handed helical ribbons along with bundles of straight ribbons were simultaneously observed in SEM image of self-assembled R- or S-5 in mixed solution of ethyl acetate and ethanol, suggesting that the configuration of the stereogenic center is not the only factor responsible for inducing helical structures in solution.
Display omitted
•Optically active mesogenic triphenylenedicarboxyimides were synthesized and characterized.•Having excellent thermally stability.•Having high clearing temperatures over 200 °C and exhibiting wide mesophase ranges.•Five of the mesogens are room temperature liquid crystalline materials.•Three pairs of enantiomers form chiral supramolecular structures in the mesophase.
Human ribonuclease 1 (hRNase 1) is critical to extracellular RNA clearance and innate immunity to achieve homeostasis and host defense; however, whether it plays a role in cancer remains elusive. ...Here, we demonstrate that hRNase 1, independently of its ribonucleolytic activity, enriches the stem-like cell population and enhances the tumor-initiating ability of breast cancer cells. Specifically, secretory hRNase 1 binds to and activates the tyrosine kinase receptor ephrin A4 (EphA4) signaling to promote breast tumor initiation in an autocrine/paracrine manner, which is distinct from the classical EphA4-ephrin juxtacrine signaling through contact-dependent cell-cell communication. In addition, analysis of human breast tumor tissue microarrays reveals a positive correlation between hRNase 1, EphA4 activation, and stem cell marker CD133. Notably, high hRNase 1 level in plasma samples is positively associated with EphA4 activation in tumor tissues from breast cancer patients, highlighting the pathological relevance of the hRNase 1-EphA4 axis in breast cancer. The discovery of hRNase 1 as a secretory ligand of EphA4 that enhances breast cancer stemness suggests a potential treatment strategy by inactivating the hRNase 1-EphA4 axis.
Abstract Background Endothelial progenitor cells (EPCs) play a pivotal role in endothelial repair following artery injury, however, the molecular mechanism of late outgrowth EPCs (LEPCs) in ...endothelial repair remained to be studied. Bone morphogenetic protein 4 (BMP4) is involved in vascular injury-mediated mobilization and homing of LEPCs. Here, we investigated the influence of BMP4-modified signaling pathway in LEPC-related endothelial repair of human and underlying molecular mechanism. Methods and results In vitro , after a 28 day culture, human LEPCs were pretreated with different concentrations of recombinant BMP4 (0, 10, 50, or 100 ng/mL), which markedly augmented the migration and adhesion in vitro and demonstrated a significantly accelerated in vivo endothelial repair capacity of human LEPCs after transplantation into nude mice with carotid artery denudation injury. Moreover, the main Id gene (Id2), a well-characterized down-streaming target of BMP4, upregulated in LEPCs incubated with recombinant BMP4. The BMP4-induced enhancement in in vitro functional activities and in vivo endothelial repair capacity of human LEPCs were abolished by pretreatment with BMP antagonist Noggin or shRNA-mediated knockdown of BMP4 expression. Furthermore, BMP4 gene transfer remarkably activated BMP4-mediated signaling pathway and facilitated therapeutic endothelial repair capacity of LEPCs, and the improved functional activities of human LEPCs could be inhibited by Noggin. Conclusion Thus, the present study demonstrates for the first time that BMP4-related signaling pathway is essential with endothelial repair capacity of LEPCs in human. The upregulation of BMP4-modified signaling pathway in human LEPCs may be a novel therapeutic strategy for endothelial repair after injury.
Licorice (Glycyrrhiza) species have been widely used as a traditional medicine and a natural sweetener in foods. The 18β-glycyrrhetinic acid (18β-GA) is a bioactive compound in licorice that exhibits ...potential anti-cancer, anti-inflammatory, and anti-microbial activities. Many synthesized derivatives of 18β-GA have been reported to be cytotoxic and suggested for the treatment of malignant diseases. In this study, we explored the possible pharmacological roles of an 18β-GA derivative in skin biology using primary human dermal fibroblasts and HaCaT keratinocytes as cell models. We found that this 18β-GA derivative did not cause cell death, but significantly enhanced the proliferation of dermal fibroblasts and HaCaT keratinocytes. A scratch wound healing assay revealed that the 18β-GA derivative promoted the migration of fibroblasts. Due to the important role of aquaporin-3 in cell migration and proliferation, we also investigated the expression of aquaporin-3 and found this compound up-regulated the expression of aquaporin-3 in dermal fibroblasts and HaCaT keratinocytes. In dermal fibroblasts, the 18β-GA derivative induced the phosphorylation of Akt, ERK, and p38. The inhibitor of Akt predominantly suppressed the 18β-GA derivative-induced expression of aquaporin-3. Collectively, this compound had a positive effect on the proliferation, migration, and aquaporin-3 expression of skin cells, implying its potential role in the treatment of skin diseases characterized by impaired wound healing or dermal defects.
Purpose: Breast immobilization with personalized breast holder (PERSBRA) is a promising approach for normal organ protection during whole breast radiotherapy. The aim of this study is to evaluate the ...skin surface dose for breast radiotherapy with PERSBRA using different radiotherapy techniques. Materials and methods: We designed PERSBRA with three different mesh sizes (large, fine and solid) and applied them on an anthropomorphic(Rando) phantom. Treatment planning was generated using hybrid, intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques to deliver a prescribed dose of 5000 cGy in 25 fractions accordingly. Dose measurement with EBT3 film and TLD were taken on Rando phantom without PERSBRA, large mesh, fine mesh and solid PERSBRA for (a) tumor doses, (b) surface doses for medial field and lateral field irradiation undergoing hybrid, IMRT, VMAT techniques. Results: The tumor dose deviation was less than five percent between the measured doses of the EBT3 film and the TLD among the different techniques. The application of a PERSBRA was associated with a higher dose of the skin surface. A large mesh size of PERSBRA was associated with a lower surface dose. The findings were consistent among hybrid, IMRT, or VMAT techniques. Conclusions: Breast immobilization with PERSBRA can reduce heart toxicity but leads to a build-up of skin surface doses, which can be improved with a larger mesh design for common radiotherapy techniques.
PDF
