Blood-circulating microRNAs (miRNAs) have been reported to be used as potential biomarkers in various cancers. MiR-101 has been found to act as a tumor suppressor in many tumor types, but little is ...known for osteosarcoma. The purpose of this study was to investigate miR-101 expression in osteosarcoma patients and assess its correlation with clinical features and prognosis. Serum samples from 152 osteosarcoma patients and 70 healthy controls were detected using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The data showed that miR-101 expression levels were remarkably underexpressed in serum samples from osteosarcoma patients compared to controls, and the post-treatment serum miR-101 expression was significantly higher than that in the pre-treatment expression. Low serum miR-101 expression was positively associated with advanced clinical stage and distant metastasis. Receiver operating characteristic (ROC) curve analysis showed that serum miR-101 could serve as a useful marker for osteosarcoma diagnosis, with a high sensitivity and specificity. Moreover, patients with high miR-101 expression had longer overall survival and recurrence free survival than those with low miR-101 expression. In addition, both univariate and multivariate analyses showed that serum miR-101 downregulation was associated with shorter overall survival and recurrence free survival. Our present results implicated serum miR-101 might be a useful biomarker for the clinical diagnosis and prognosis of osteosarcoma.
We report the observation of new properties of primary cosmic rays He, C, and O measured in the rigidity (momentum/charge) range 2 GV to 3 TV with 90×10^{6} helium, 8.4×10^{6} carbon, and 7.0×10^{6} ...oxygen nuclei collected by the Alpha Magnetic Spectrometer (AMS) during the first five years of operation. Above 60 GV, these three spectra have identical rigidity dependence. They all deviate from a single power law above 200 GV and harden in an identical way.
Summary
Background
A previous study provided evidence for a genetic association between PPP2CA on 5q31.1 and systemic lupus erythematosus (SLE) across multi‐ancestral cohorts, but failed to find ...significant evidence for an association in the Han Chinese population.
Objectives
To explore the association between this locus and SLE using data from our previously published genome‐wide association study (GWAS).
Methods
Single‐nucleotide polymorphisms (SNPs) rs7726414 and rs244689 (near TCF7 and PPP2CA in 5q31.1) were selected as candidate independent associations from a large‐scale study in a Han Chinese population consisting of 1047 cases and 1205 controls. Subsequently, 3509 cases and 8246 controls were genotyped in two further replication studies. We then investigated the SNPs' associations with SLE subphenotypes and gene expression in peripheral blood mononuclear cells.
Results
Highly significant associations with SLE in the Han Chinese population were detected for SNPs rs7726414 and rs244689 by combining the genotype data from our previous GWAS and two independent replication cohorts. Further conditional analyses indicated that these two SNPs contribute to disease susceptibility independently. A significant association with SLE, age at diagnosis < 20 years, was found for rs7726414 (P = 0·001). The expression levels of TCF7 and PPP2CA messenger RNA in patients with SLE were significantly decreased compared with those in healthy controls.
Conclusions
This study found evidence for multiple associations with SLE in 5q31.1 at genome‐wide levels of significance for the first time in a Han Chinese population, in a combined genotype dataset. These findings suggest that variants in the 5q31.1 locus not only provide novel insights into the genetic architecture of SLE, but also contribute to the complex subphenotypes of SLE.
What's already known about this topic?
Systemic lupus erythematosus (SLE) is a prototype multisystem autoimmune inflammatory disease involving genetic and environmental predisposing factors.
Genome‐wide association studies have been performed to identify and confirm over 70 risk genes associated with SLE.
What does this study add?
This study confirmed two independent SLE association signals in 5q31.1, with genome‐wide levels of significance for the first time in a Han Chinese population.
Significant and suggestive associations were revealed between clinical manifestations and genetic variants.
Both TCF7 and PPP2CA are within the association interval and are very likely to be involved in the development of SLE.
What is the translational message?
The genetic variant in 5q31.1 contributes to the complex subphenotypes of SLE, which suggests that this variant can be a novel marker for SLE phenotypes.
The expression levels of TCF7 and PPP2CA messenger RNA in patients with SLE were significantly decreased, which suggests that TCF7 and PPP2CA can be used as an auxiliary method for the diagnosis of SLE.
Linked Comment: Sarin. Br J Dermatol 2017; 177:620–621
We report on the observation of new properties of secondary cosmic rays Li, Be, and B measured in the rigidity (momentum per unit charge) range 1.9 GV to 3.3 TV with a total of 5.4×10^{6} nuclei ...collected by AMS during the first five years of operation aboard the International Space Station. The Li and B fluxes have an identical rigidity dependence above 7 GV and all three fluxes have an identical rigidity dependence above 30 GV with the Li/Be flux ratio of 2.0±0.1. The three fluxes deviate from a single power law above 200 GV in an identical way. This behavior of secondary cosmic rays has also been observed in the AMS measurement of primary cosmic rays He, C, and O but the rigidity dependences of primary cosmic rays and of secondary cosmic rays are distinctly different. In particular, above 200 GV, the secondary cosmic rays harden more than the primary cosmic rays.
Physical activity has been shown to suppress tumor initiation and progression. The neurotransmitter dopamine (DA) is closely related to movement and exhibits antitumor properties. However, whether ...the suppressive effects of physical activity on tumors was mediated by the nervous system via increased DA level remains unknowns. Here we show that regular moderate swimming (8 min/day, 9 weeks) raised DA levels in the prefrontal cortex, serum and tumor tissue, suppressed growth, reduced lung metastasis of transplanted liver cancer, and prolonged survival in a C57BL/6 mouse model, while overload swimming (16 and 32 min/day, 9 weeks) had the opposite effect. In nude mice that were orthotopically implanted with human liver cancer cell lines, DA treatment significantly suppressed growth and lung metastasis by acting on the D2 receptor (DR2). Furthermore, DR2 blockade attenuated the suppressive effect of moderate swimming on liver cancer. Both moderate swimming and DA treatment suppressed the transforming growth factor-beta (TGF-β1)-induced epithelial-mesenchymal transition of transplanted liver cancer cells. At the molecular level, DR2 signaling inhibited extracellular signal-regulated kinase phosphorylation and expression of TGF-β1 in vitro. Together, these findings demonstrated a novel mechanism by which the moderate exercise suppressed liver cancer through boosting DR2 activity, while overload exercise had the opposite effect, highlighting the possible importance of the dopaminergic system in tumor growth and metastasis of liver cancer.
The introduction of the Simian virus 40 (SV40) early region, the telomerase catalytic subunit (hTERT) and an oncogenic allele of H-Ras directly transforms primary human cells. SV40 small T antigen ...(ST), which forms a complex with protein phosphatase 2A (PP2A) and inhibits PP2A activity, is believed to have a critical role in the malignant transformation of human cells. Recent evidence has shown that aberrant microRNA (miRNA) expression patterns are correlated with cancer development. Here, we identified miR-27a as a differentially expressed miRNA in SV40 ST-expressing cells. miR-27a is upregulated in SV40 ST-transformed human bronchial epithelial cells (HBERST). Suppression of miR-27a expression in HBERST cells or lung cancer cell lines (NCI-H226 and SK-MES-1) that exhibited high levels of miR-27a expression lead to cell growth arrested in the G(0)-G(1) phase. In addition, suppression of miR-27a in HBERST cells attenuated the capacity of such cells to grow in an anchorage-independent manner. We also found that suppression of the PP2A B56γ expression resulted in upregulation of miR-27a similar to that achieved by the introduction of ST, indicating that dysregulation of miR-27a expression in ST-expressing cells was mediated by the ST-PP2A interaction. Moreover, we discovered that Fbxw7 gene encoding F-box/WD repeat-containing protein 7 was a potential miR-27a target validated by dual-luciferase reporter system analysis. The inverse correlation between miR-27a expression levels and Fbxw7 protein expression was further confirmed in both cell models and human tumor samples. Fbxw7 regulates cell-cycle progression through the ubiquitin-dependent proteolysis of a set of substrates, including c-Myc, c-Jun, cyclin E1 and Notch 1. Thus, promotion of cell growth arising from the suppression of Fbxw7 by miR-27a overexpression might be responsible for the viral oncoprotein ST-induced malignant transformation. These observations demonstrate that miR-27a functions as an oncogene in human tumorigenesis.
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Neovascularization plays a key role in bone repair and regeneration. In the present study, four types of porous calcium phosphate (CaP) ceramics, namely hydroxyapatite (HA), biphasic ...calcium phosphates (BCP-1 and BCP-2) and β-tricalcium phosphate (β-TCP), with HA to β-TCP ratios of 100/0, 70/30, 30/70 and 2/98, respectively, were investigated in terms of their angiogenic induction. The in vitro cell culture revealed that the ceramics could promote proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs). This result could be achieved by stimulating CCD-18Co human fibroblasts to secrete angiogenic factors (vascular endothelial growth factor, basic fibroblast growth factor and transforming growth factor-β) as a paracrine effect, as well as by up-regulating HUVECs to express these angiogenic factors and their receptors (KDR, FGFR1 and ACVRL1) and the downstream eNOS as an autocrine effect. These effects were more significant in β-TCP and BCP-2, which had a higher content of β-TCP phase. In the in vivo implantation into the thigh muscles of mice, the process of neovascularization of the ceramics was initiated at 2weeks and the mature vascular networks were formed at 4weeks as visualized by hematoxylin and eosin staining and scanning electron microscopy. Microvessel density count confirmed that β-TCP and BCP-2 induced more microvessels to form than HA or BCP-1. This phenomenon was further confirmed by the significantly up-regulated expressions of angiogenesis-related genes in the ingrowth of cells into the inner pores of the two ceramics. All the results confirmed the angiogenic induction of porous CaP ceramics, and a higher content of β-TCP phase had an enhanced effect on the neovascularization of the ceramics.
Creating oxide interfaces with precise chemical specificity at the atomic layer level is desired for the engineering of quantum phases and electronic applications, but highly challenging, owing ...partially to the lack of in situ tools to monitor the chemical composition and completeness of the surface layer during growth. Here we report the in situ observation of atomic layer-by-layer inner potential variations by analysing the Kikuchi lines during epitaxial growth of strontium titanate, providing a powerful real-time technique to monitor and control the chemical composition during growth. A model combining the effects of mean inner potential and step edge density (roughness) reveals the underlying mechanism of the complex and previously not well-understood reflection high-energy electron diffraction oscillations observed in the shuttered growth of oxide films. General rules are proposed to guide the synthesis of atomically and chemically sharp oxide interfaces, opening up vast opportunities for the exploration of intriguing quantum phenomena at oxide interfaces.
Annealing of metallic glasses (MGs) at temperature near glass transition temperature (Tg) triggers relaxation and often hampers their performances in service. Rejuvenation treatment of MGs by thermal ...cycling is recently intensively investigated. However, the mechanism responsible for the structural rejuvenation still remains elusive. In this work, we present a systematic study on the rejuvenation effect of a Zr46Cu38Al8Ag8 MG annealed at 0.9Tg for various durations, subjected to thermo-cycling treatment. It is found that well relaxed samples after long-term annealing are almost unaffected, while short-term annealed samples exhibit large rejuvenation effect by thermo-cycling treatment. Using synchrotron X-ray diffraction, we find that thermal cycling results in a disordering at the short-range scale, where the rejuvenation effect is large in a heterogeneous sample. More interestingly, the thermo-cycling treatment on intermediate structure with 20 h-annealed sample relatively exhibits a high degree rejuvenation effect, as compared to shorter- and longer-term annealed samples. This finding indicates that the activation barrier for rejuvenation strongly depends on the original structural states, e.g., free volume, inherent stress and structural heterogeneity.
•Thermo-cycling indeed causes rejuvenation and disordering in metallic glass.•Well-relaxed sample with homogeneous structure is unaffected by thermo-cycling.•Intermediate structure state maximizes the rejuvenation effect.•Competition between relaxation effect and homogeneity effect controls rejuvenation.
Hydrogels are promising materials in the applications of wound adhesives, wearable electronics, tissue engineering, implantable electronics, etc. The properties of a hydrogel rely strongly on its ...composition. However, the optimization of hydrogel properties has been a big challenge as increasing numbers of components are added to enhance and synergize its mechanical, biomedical, electrical, and self‐healable properties. Here in this work, it is shown that high‐throughput screening can efficiently and systematically explore the effects of multiple components (at least eight) on the properties of polysulfobetaine hydrogels, as well as provide a useful database for diverse applications. The optimized polysulfobetaine hydrogels that exhibit outstanding self‐healing and mechanical properties, have been obtained by high‐throughput screening. By compositing with poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), intrinsically self‐healable and stretchable conductors are achieved. It is further demonstrated that a polysulfobetaine hydrogel‐based electronic skin, which exhibits exceptionally fast self‐healing capability of the whole device at ambient conditions. This work successfully extends high‐throughput synthetic methodology to the field of hydrogel electronics, as well as demonstrates new directions of healable flexible electronic devices in terms of material development and device design.
A high‐throughput screening method, known as material genome engineering, has been employed to efficiently screen eight ingredients for the optimization of intrinsically stretchable and self‐healable polysulfobetaine hydrogels. The optimized hydrogels are successfully applied as electrodes and dielectric layer in an electronic skin, which displays impressively fast self‐healing and pressure sensing properties.
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