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Because of the high heterogeneity of breast cancer outcome, identification of novel prognostic biomarkers is critical to improve patient stratification and guide precise treatment. We examined the prognostic value of gamma-interferon-inducible lysosomal thiol reductase (GILT) expression in a training set of 416 breast cancer patients and a validation set of 210 patients, and performed functional studies to investigate the functions and underlying mechanisms of GILT on breast cancer prognosis. Our results indicated that high GILT expression in breast cancer cells was associated with improved disease-free survival (DFS; hazard ratio [HR] = 0.189, 95% confidence interval [CI]: 0.099-0.361) and breast cancer-specific survival (BCSS; HR = 0.187, 95% CI: 0.080-0.437) of breast cancer patients both in the training set and the external validation set (HR = 0.453, 95% CI: 0.235-0.873 for DFS, HR = 0.488, 95% CI: 0.245-0.970 for BCSS). In vitro and in vivo studies showed that GILT overexpression inhibited breast cancer cells proliferation, invasion, migration and tumor formation in nude mice and increased sensitivity of breast cancer cells to standard treatment. Proteomics analysis indicated that GILT inhibited reactive oxygen species (ROS) and autophagy activation in breast cancer cells, and GILT overexpression-mediated tumor growth was further enhanced in the presence of autophagy or ROS inhibitors. Our results demonstrate that GILT expression can be effectively used to predict the prognosis and guide treatment strategies of breast cancer patients.

Background X‐ray repair cross‐complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene‐environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. Methods The study included 1039 patients with breast cancer and 1040 controls. Four single‐nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene‐environment interactions were analyzed using logistic regression with multiplicative interaction models. Results XRCC5 rs16855458 was associated with increased breast cancer risk in the co‐dominant (p trend = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07–1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor‐negative/progesterone receptor‐negative (ER−/PR−) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12–2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (p interaction = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (p interaction = 0.0497). However, these interactions became insignificant after Bonferroni correction. Conclusion XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER−/PR− breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation., XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER−/PR− breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.

Objective Obesity is closely associated with metastasis in breast cancer patients. Secreted frizzled-related protein 5 (SFRP5), one of the novel adipokines with anti-inflammatory properties, is associated with obesity. This study aims to study the role of SFRP5 in the crosstalk between obesity and breast cancer metastasis and identify the underlying mechanism. Methods 3T3-L1 pre-adipocytes were differentiated to mature adipocytes and a hypertrophic adipocyte model was induced with palmitic acid (PA). Cell motility was measured in MDA-MB-231 and MCF-7 breast cancer cells co-cultured with adipocytes conditioned medium (CM) with or without SFRP5 protein. Wnt and epithelial-mesenchymal transition (EMT) signal pathways were investigated by western blot. Circulating SFRP5 level in 218 breast cancer patients and the association with clinicopathologic characteristics of breast cancer were further determined. Online databases ENCORI and PREDICT Plus were used to exam the link between SFRP5 and prognosis. Results Reduced SFRP5 level was detected in the hypertrophic adipocyte model. Recombinant SFRP5 protein inhibited MDA-MB-231 and MCF-7 cells invasion and migration induced by PA-treated adipocyte CM, and SFRP5 inhibition by specific antibody reversed the effect of SFRP5. Furthermore, SFRP5 significantly inhibited Wnt and downstream EMT in breast cancer cells. Low circulating SFRP5 level correlated with body mass index (BMI), lymph node (LN) metastasis, TNM stage and high Ki67 expression in breast cancer patients. Increased SFRP5 level was associated with favorable predicted survival. Kaplan-Meier curves showed high SFRP5 level in tumor tissue was associated with better outcome of breast cancer patients. Conclusions Our findings demonstrated SFRP5 is a vital adipokine that mediates the crosslink between obesity and the metastatic potential of breast cancer. Promotion of SFRP5 expression in the adipose microenvironment may represent a novel approach for preventing breast cancer metastasis.

The electroreduction of CO

Developing active and selective electrocatalysts is of prime importance in shifting society toward utilizing renewable energy sources. Such developments often require catalysts with particular morphologies because many chemical reactions are sensitive to the catalyst structure. However, it can be challenging to synthesize and stabilize shape-controlled catalysts. It would therefore be desirable to tailor the morphology of an existing electrocatalyst to exhibit favorable catalytic properties. In this work, such morphological alteration is explored using cathodic corrosion: an electrochemical etching process that can generate geometrical shapes on metallic surfaces. Specifically, cathodic corrosion is utilized to tailor a well-defined Pt(111) electrode for oxygen reduction and glycerol oxidation catalysis. Both the oxygen reduction activity and the glycerol oxidation selectivity can be tailored by controlling the cathodic corrosion conditions. These results demonstrate the specific potential of cathodic corrosion for tailoring catalyst activity and selectivity.

Background Postoperative pain is one of the most common symptoms after surgery, which brings physical discomfort to patients. In addition, it may cause a series of complications, and even affect the long-term quality of life. The purpose of this prospective, randomized, double-blinded, controlled trial is to investigate the efficacy and safety of dexmedetomidine combined with sufentanil to attenuate postoperative pain in patients after laparoscopic nephrectomy. Methods Ninety patients undergoing laparoscopic nephrectomy were randomized into three groups: the control (sufentanil 0.02 μg/kg/h, Group C), sufentanil plus low dose of dexmedetomidine (0.02 μg/kg/h each, Group D1), and sufentanil plus high dose of dexmedetomidine (0.04 μg/kg/h, Group D2). The patient-controlled analgesia was programmed to deliver a bolus dose of 0.5 ml, followed by an infusion of 2 ml/h and a lockout time of 10 min. The primary goal was to calculate the cumulative amount of self-administered sufentanil; the secondary goals were to estimate pain intensity using the numerical rating scale (NRS), level of sedation, the first bowel movement, concerning adverse effects as well as duration of postoperative hospital stay. Results The total consumption of sufentanil in group D1 and D2 were significantly lower than in group C during the first 8 h after surgery (P 0.05) between group D1 and D2. Compared with group C, the NRS scores at rest during first 8 h after surgery were significantly lower in group D1 (P 0.05). The time to first flatus was shorter in group D1 compared with the control group (P

Background Breast cancer (BC) risk, development, and prognosis were closely related to obesity, diabetes mellitus, and metabolic syndrome. Protein tyrosine phosphatase, non-receptor type 1 (PTPN1) located on chromosome 20q13, could negatively regulate insulin and leptin signaling. In this study, we determined the association of PTPN1 polymorphisms with BC risk. Methods We analyzed the distribution of 11 selected PTPN1 single nucleotide polymorphisms in Chinese female patients with BC (n = 953) and healthy controls (n = 963) based on a multicenter case-control study. The association of PTPN1 genotypes and haplotypes frequencies with BC risk were determined by logistic regression analysis. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), diabetes mellitus history, and fasting plasma glucose level. The eQTL (expression Quantitative Trait Loci) analysis for PTPN1 was conducted by GTEx database. Results There were significant differences between BC cases and control groups in menopausal status, number of births, and BMI. Four single nucleotide polymorphisms (SNPs; rs3215684, rs3787345, rs718049, and rs718050) decreased overall BC risk, and other seven SNPs showed no significant association with BC risk. In multivariate analysis, BMI and rs3215684 DT + DD genotype were identified as independent risk factors for BC, and mutated genotypes of rs3215684 were correlated with increased PTPN1 expression. There are no haplotypes showed different frequencies between cases and controls. In the stratified analysis, rs2206656 showed a significant association with decreased BC risk in the subgroup of BMI ≤ 24 kg/m 2 , while rs3215684 and rs718049 showed lower BC risk in the subgroup of WHR > 0.85. Seven SNPs showed lower BC risk in the subgroup with diabetes mellitus history and/or fasting plasma glucose level ≥ 7 mM, while rs754118 decreased BC risk in the subgroup of fasting plasma glucose level Conclusion Our findings suggest that PTPN1 SNPs associated with BC susceptibility in Chinese females, which also suggested a novel mechanism between obesity, diabetes mellitus, and BC risk.

Nanomaterials with unique edge sites have received increasing attention due to their superior performance in various applications. Herein, we employed an effective ethylenediaminetetraacetic acid (EDTA)-assisted method to synthesize a series of exotic Bi2Se3 nanostructures with distinct edge sites. It was found that the products changed from smooth nanoplates to half-plate-containing and crown-like nanoplates upon increasing the molar ratio of EDTA to Bi3+. Mechanistic studies indicated that, when a dislocation source and relatively high supersaturation exist, the step edges in the initially formed seeds can serve as supporting sites for the growth of epilayers, leading to the formation of half-plate-containing nanoplates. In contrast, when the dislocation source and a suitably low supersaturation are simultaneously present in the system, the dislocation-driven growth mode dominates the process, in which the step edges form at the later stage of the growth responsible for the formation of crown-like nanoplates.

Shape control has proven to be a powerful and versatile means of tailoring the properties of Bi2Se3 nanostructures for a wide variety of applications. Here, three different Bi2Se3 nanostructures, i.e., spiral-type nanoplates, smooth nanoplates, and dendritic nanostructures, were prepared by manipulating the supersaturation level in the synthetic system. This mechanism study indicated that, at low supersaturation, defects in the crystal growth could cause a step edge upon which Bi2Se3 particles were added continuously, leading to the formation of spiral-type nanoplates. At intermediate supersaturation, the aggregation of amorphous Bi2Se3 particles and subsequent recrystallization resulted in the formation of smooth nanoplates. Furthermore, at high supersaturation, polycrystalline Bi2Se3 cores formed initially, on which anisotropic growth of Bi2Se3 occurred. This work not only advances our understanding of the growth mechanism but also offers a new approach to control the morphology of Bi2Se3 nanostructures.

Objective: The aim of this study was to reveal the exact changes during the occurrence of breast cancer to explore significant new and promising genes or factors related to this disease. Methods: We compared the gene expression profiles of breast cancer tissues with its uninvolved normal breast tissues as controls using the cDNA microarray analysis in seven breast cancer patients. Further, one representative gene, named IFI30, was quantitatively analyzed by real-time PCR to confirm the result of the cDNA microarray analysis. Results: A total of 427 genes were identified with significantly differential expression, 221 genes were up-regulated and 206 genes were down-regulated. And the result of cDNA microarray analysis was validated by detection of IFI30 mRNA level changes by real-time PCR. Genes for cell proliferation, cell cycle, cell division, mitosis, apoptosis, and immune response were enriched in the up-regulated genes, while genes for cell adhesion, proteolysis, and transport were significantly enriched in the down-regulated genes in breast cancer tissues compared with normal breast tissues by a gene ontology analysis. Conclusion: Our present study revealed a range of differentially expressed genes between breast cancer tissues and normal breast tissues, and provide candidate genes for further study focusing on the pathogenesis and new biomarkers for breast cancer. Keywords: Breast neoplasms, Candidate genes, Microarray

The expression of insulin-like growth factor-1 receptor (IGF-1R), which is involved in the genesis and progression of breast cancer, is thought to be associated with the overall survival (OS) of patients. However, the predictive and prognostic significance of the IGF-1R expression in breast cancer remains controversial. The present study aimed to identify the factors associated with the levels of phosphorylated (p)-IGF-1R in breast cancer, their impact on the outcomes of breast cancer patients, and the prognostic value of alterations of p-IGF-1R during neoadjuvant chemotherapy (NAC). The present study included 348 female breast cancer patients whose paraffin-embedded tumor tissue sections had been collected by biopsy and/or resection, among which the pre-NAC and post-NAC sections were available from 40 patients. Human epidermal growth factor receptor 2 (HER2) positivity and molecular subtype were significantly associated with the presence of p-IGF-1R in the tumor tissue (P

Improving power of goodness-of-fit tests is an important research topic in statistics. The goal of the goodness-of-fit test is to check whether the underlying probability distribution, from which a sample is drawn, differs from a hypothesized distribution. Numerous research papers have been published in this area. It has been shown that the power of the existing goodness-of-fit tests in the literature is unsatisfactory when the alternative distributions are of V-shape or when the sample sizes are small. This motivates the development of more powerful test statistics. In this research, a new test statistic is proposed. The result can be used to test whether the underlying probability distribution differs from a uniform distribution. By applying the probability integral transformation, the proposed test statistic can be used to check whether the underlying distribution differs from any hypothesized distribution. The performance of the method proposed in this research is compared with the Kolmogorov–Smirnov test, which is a widely adopted statistical test in the literature. It has been shown that the test proposed in this proposal is more powerful than the Kolmogorov–Smirnov test in some cases.

Enhanced H2 evolution efficiency is achieved via manipulating the spatial location of oxygen vacancies in niobates. The ultrathin K4 Nb6O17 nanosheets which are rich in surface oxygen vacancies show enhanced optical absorption and band gap narrowing. Meanwhile, the fast charge separation effectively reduces the probability of hole-electron recombination, enabling 20 times hydrogen evolution rate compared with the defect-free bulk counterpart.

*† The unsteady flow and heat transfer in a microchannel with periodically mounted in-line array of vortex-generated bars (VG bars) are investigated numerically using a threedimensional model at various Reynolds numbers and arrays of VG bars. Conjugate heat transfer calculations were used to study the conduction in the solid bars and convection in the fluid. The governing equations in continuum regime were solved by a control volume based finite difference method. Numerical data are presented and discussed to evaluate the performance of the bar arrays periodically mounted in a microchannel. It was found that the array of VG bars affected the strength of oscillating flow in the microchannel, and the heat transfer was significantly enhanced due to the presence of the VG bars. Nomenclature Ac = cross-section area of microchannel Cp = specific heat, dh = hydraulic diameter f = friction factor h = heat transfer coefficient H = microchannel height, μm k = thermal conductivity L = microchannel length L r = the periodic length vector

Saltcake, previously dissolved salts, such as sodium nitrate and sodium nitrite that crystallize out of solution, is a kind of porous media and an important component in many nuclear waste tanks. In this paper both one-dimensional single-phase and multi-phase flow model was employed to simulate unsaturated drainage of saltcake in a column caused by gravity or external forces under given initial and boundary conditions. Porous media properties used in the modeling was determined from our previous experimental data by inverse modeling method. Good agreement was found between the drainage result from available experiments and that from the numerical simulation using multiphase flow model. The impact on drainage by external pressure applying at the top of column and the influence of the height of column were also be investigated and presented in this study.Copyright © 2006 by ASME

In this paper, 2D heat transfer and solidification process of a binary mixture of ammonium chloride and water in a horizontal pipeline were investigated numerically. A standard k-e turbulent model and an enthalpy-porosity technique were used to model the turbulent flow and solidification process in a straight pipeline. The model was validated with existing experimental results for solidification process in enclosures and channels. The governing equations of the model were solved by a control volume method. The effect of pipeline wall temperature variations on the solidification process and transport characteristics were carried out. Pressure drop in the pipeline, flow area reduction due to solidification, and quantity of formed solid, were evaluated. Information about the solidification process characteristics, such as temperature distribution, liquid fraction contours, and detailed description of transient evolution of liquid-solid interface during under variant initial wall temperature were presented and discussed.