Identification and Validation of a Novel Glycolysis-Related Gene Signature for Predicting the Prognosis and Therapeutic Response in Triple-Negative Breast Cancer.

INTRODUCTION: A high malignancy rate and poor prognosis are common problems with triple-negative breast cancer (TNBC). There is increasing evidence that glycolysis plays vital roles in tumorigenesis, tumor invasion, immune evasion, chemoresistance, and metastasis. However, a comprehensive analysis of the diagnostic and prognostic significance of glycolysis in TNBC is lacking. METHODS: Transcriptomic and clinical data of TNBC patients were obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, respectively. Glycolysis-related genes (GRGs) were collected from the Molecular Signatures Database (MSigDB). Differential comparative analysis was performed to obtain the differentially expressed (DE)-GRGs associated with TNBC. Based on the DE-GRGs, a glycolysis-related risk signature was established using Least Absolute Shrinkage and Selector Operation (LASSO) and multivariable Cox regression analyses. The prognostic value, tumor microenvironment, mutation status, and chemotherapy response of different risk groups were analyzed. An independent cohort from the METABRIC database was used for external validation. Furthermore, the expression patterns of five genes derived from the prognostic model were validated by quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS: The glycolysis-related prognostic signature included five genes (IFNG, ACSS2, IRS2, GFUS, and GAL3ST1) and predicted the prognosis of TNBC patients independent of clinical factors (p < 0.05). Patients were divided into high- and low-risk groups based on the median risk score. Compared to low-risk TNBC patients, high-risk patients had significantly decreased overall survival (HR = 2.718, p < 0.001). Receiver operating characteristic and calibration curves demonstrated that the model had high performance in terms of predicting survival and risk stratification. The results remained consistent after external verification. Additionally, the tumor immune microenvironment significantly differed between the risk groups. Low-risk TNBC patients had a better immunotherapy response than high-risk patients. High-risk TNBC patients with a poor prognosis may benefit from targeted therapy. CONCLUSIONS: This study developed a novel glycolysis and prognosis-related (GRP) signature based on GRGs to predict the prognosis of TNBC patients, and may aid clinical decision-making for these patients.

Discovery and synthesis of novel indole derivatives-containing 3-methylenedihydrofuran-2(3H)-one as irreversible LSD1 inhibitors.

Lysine-specific demethylase 1 (LSD1), demethylase against mono- and di - methylated histone3 lysine 4, has emerged as a promising target in oncology. More specifically, it has been demonstrated as a key promoter in acute myeloid leukemia (AML), and several LSD1 inhibitors have already entered into clinical trials for the treatment of AML. In this paper, a series of new indole derivatives were designed and synthesized based on a lead compound obtained by a high-throughput screening with our in-house compound library. Among the synthetic compounds, 9e was characterized as a potent LSD1 inhibitor with an IC50 of 1.230 µM and can inhibit the proliferation of THP-1 cells effectively. And most importantly, this is the first irreversible LSD1 inhibitor that is not derived from monoamine oxidase inhibitors. Hence, the discovery of 9e may serve as a proof of concept work for AML treatment.

Efficient three-component one-pot synthesis of steroidal polysubstituted anilines.

An efficient and practical base-promoted cascade reaction has been developed to access steroidal polysubstituted anilines from simple precursors. The protocol reported herein achieved the formation of a benzene ring as well as three continuous C-C bonds in a single operation. The reaction mechanism was proposed on the basis of the key intermediate obtained. Besides, this method could be potentially employed for the synthesis of biphenyl compounds. The adjacent amine and nitrile groups existed in the final products have the potential for late stage functionalization, which would provide efficient access to steroidal compound collections with structural diversity and complexity.

[Analysis of predictors of axillary node metastases in 787 breast cancer patients].

OBJECTIVE: To explore the predictors of axillary nodal metastass in patients with breast cancer. METHODS: A retrospective study was performed using the clinicopathological data of breast cancer cases diagnosed and treated in our Hospital between Dec 2006 and Nov 2008. Logistic regression analysis was used to determine the predictors of axillary node positivity. RESULTS: The total number of patients was 1133. 69.5% of them (787) had complete clinical and pathological data. The median age was 49 years old (range 20-85). The average number of lymph nodes removed was 14.6 per person. The average number of involved nodes was 3.5 per person. Increasing tumor size was associated with increased risk of lymph node metastases. Assessed by multivariate analysis, the tumor size, age, ER status, and pathological type were significantly associated with node metastasis. CONCLUSIONS: Axillary nodal metastases are significantly affected by the tumor size, ER status, age, and pathological type in breast cancer patients.

[Effect of nucleation modes on the induced crystallization process for copper contained wastewater treatment].

The effect of nucleation modes on the induced crystallization process for copper contained wastewater treatment was studied. Tests were undertaken to observe the difference of copper removal efficiency and the crystal growth with homogeneous and heterogeneous nucleation. When the influent copper concentration was 50 mg x L(-1), copper removal efficiency could achieve 98.0% with the heterogeneous and 26.3% with homogeneous nucleation. And the SEM-EDS showed that the growth of crystals with heterogeneous nucleation was better and the purity of the crystals was higher than that with homogeneous nucleation. It is obvious that the homogeneous nucleation was an unfavorable condition on the induced crystallization process. Then the research devoted to discuss the process of induced crystallization with the two different nucleation mode and analysis the influencing mechanism of the homogeneous nucleation on the induced crystallization.

[Research on improving spectrum resolution of optimized Wollaston prism array].

In order to not affect the image quality of interference fringes on the basis of the structure by increasing the structure angle of Wollaston prism to improve spectrum resolution, the authors optimized the structure of Wollaston prism. Calculating the function of the splitting angle and the structure angle, analysis indicated that taking the isosceles triangle prism with the same nature of the second wedge-shaped prism after the Wollaston prism, which makes the o and e light parallel to the optical axis, and alpha=0 degrees, the imaging interference fringes are no longer affected by changes in the splitting angle. Several optimized Wollaston prisms were made as an array to improve the spectral resolution. Experiments used traditional and optimized Wollaston prism array to detect the spectrum of the 980 nm laser. Experimental data showed that using optimized Wollaston prism array gets a clearer contrast of interference fringes, and the spectral data with Fourier transform are more accurate with DSP.

[Removing nitrate-nitrogen from wastewater using rotten wood as carbon source].

In this research, COD release of rotten wood was studied and rotten wood was investigated as the sole carbon source as well as biofilm carrier to remove nitrate from wastewater in up-flow laboratory reactor. The experimental results indicated that rotten wood could release carbon source continuously. COD released of rotten wood inoculated with humus was 2. 3 times higher than that of sterilized rotten wood, and VFA was 5 times. The research of denitrification was carried out at 25 degrees +/- 1 degrees C, 30 mg/L of initial NO3(-) -N concentration and 12 h of hydraulic retention time. Nitrate removal efficiency was above 80%. A time-dependent decrease in nitrate removal efficiency was observed after 46 days of operation. The results showed that rotten wood could be used as an effective carbon source for denitrification.