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Cyperus rotundus L. is widely used in Traditional Chinese Medicine and studies have reported its anticancer effect, but its chemical composition and therapy mechanism remains unknown. This research aims to analyze the chemical components of the ethanol extract of Cyperus rotundus L. (EECR), detect its treatment effects on human Triple-negative breast cancer (TNBC) cells, and elucidate possible therapy mechanisms. The chemical components of EECR were detected by the Waters UPLC combined with Bruker Q-TOF mass spectrometer (UPLC-Q-TOF-MS). The phytochemical compounds were identified by comparing the mass fragmentations of each metabolite with databases such as METLIN, HMDB, and NCBI. A total of 21 compounds were identified in EECR. MDA-MB-231 and MDA-MB-468 cells were treated with various concentrations of EECR. Cell proliferation was examined using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell apoptosis and cell cycle were detected by flow cytometry. Apoptosis- and autophagy-related protein expression was detected by Western blot. EECR inhibits the proliferation of TNBC cells (MDA-MB-231 and MDA-MB-468) in a dose-dependent manner, which may be related to the arrest of cell cycle in G0/G1 phase. It induces apoptosis by promoting the expression of BAX and inhibiting the expression of BCL-2. In addition, autophagy inhibitor 3-Methyladenine (3-MA) inhibited TNBC cells pro-survival autophagy and increased the sensitivity of EECR. The present results demonstrated that EECR has potential effects on inhibits the proliferation and induction apoptosis in TNBC.

ObjectivesThe NCCN guidelines recommend that the addition of bevacizumab should be considered in metastatic breast cancers in some circumstances, but there are no recommendations for the similar antiangiogenic drug apatinib. The aim of this study was to evaluate the safety and efficacy of apatinib in metastatic breast cancer patients pretreated with multiline treatment in a real-world setting.Materials and MethodsMetastatic breast cancer patients pretreated with multiline treatment who had apatinib treatment initiated from September 2015 to August 2019 at Shandong Cancer Hospital and Institute were included. The primary endpoints included PFS and OS, and the secondary endpoint was treatment-related toxicity.ResultsA total of 66 patients with metastatic breast cancer received apatinib treatment after failure of multiline chemotherapy in this study. The median PFS and OS of all 66 patients were 6.0 months and 10.0 months, respectively. The clinical beneficial rate was 40.9%. All patients tolerated treatment well, and no patients died of toxicity. The common toxicities of apatinib were hand and foot syndrome, secondary hypertension and fatigue events. The number of prior chemotherapy regimens was significantly associated with DFS and OS. Capecitabine may be a better choice for combination with a longer median OS of 19 months, while apatinib combined with other drugs was 9 months, and the apatinib monotherapy was 10 months.ConclusionApatinib produced moderate efficacy in metastatic breast cancer patients pretreated with multiline treatment with no significant treatment-related adverse events. Apatinib might be a choice for women as a maintenance salvage therapy following multiline chemotherapy failure.

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Variable geometry turbines are widely employed to improve the off-design performance of gas turbine engines; however, there is a performance penalty associated with the vane-end partial gap required for the movement of variable vanes. This paper is a continuation of the previous work and aims to understand the leakage flow and loss mechanisms under the influence of the pivoting axis. Experimental investigations with a variable geometry turbine linear cascade have been conducted for tip gap heights of 1.1% and 2.2% blade spans as well as setting angles of À6 , 0 , and 6 , so as to reveal the three-dimensional clearance flow characteristics associated with partial gaps. Besides, numerical predictions are also carried out to better understand the experimental results. Pressure measurements were performed on the tip endwall as well as on the vane surface, and three-dimensional clearance flow fields downstream of the variable cascade were measured with a five-hole probe. The results show that as the vane setting angle is changed from design to closed, the vane loading increases and tends to be more aft-loaded, thus increasing the tip leakage loss, and vice versa. There are strong interactions between the flow around the pivoting axis and the leakage flow in the vane tip rear part, which leads to a low-pressure region on the tip endwall. The leakage vortex core is made up of the leakage flow in the vane tip rear part at both two tip gap heights, and the leakage vortex core formation process is different from the one in the rotor blade. The present results can provide useful references for the vane-end clearance design of variable geometry turbines.

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Background: Triple-negative breast cancer (TNBC) is a kind of malignant tumor with higher recurrence and metastasis rate. According to historical records, the dry rhizomes Cyperus rotundus L. could be ground into powder and mixed with ginger juice and wine for external application for breast cancer. We studied the effect of the ethanol extract of Cyperus rotundus L. (EECR) on TNBC cells and found its' apoptosis-inducing effect with a doserelationship. But the function mechanism of EECR on TNBC is still mysterious. Hence, the present research aimed to detect its function mechanism at the small molecule level through ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) metabolomics. Methods: The CCK-8 assay and the Annexin V-FITC/PI assay were applied to test the effect of EECR on MDA-MB-231 cells and MDA-MB 468 cells at various concentrations of 0, 200, 400, and 600 μg/ml. UPLC-Q-TOF-MS/MS based metabolomics was used between the control group and the EECR treatment groups. Multivariate statistical analysis was used to visualize the apoptosis-inducing action of EECR and filtrate significantly changed metabolites. Results: The apoptosis-inducing action was confirmed and forty-nine significantly changed metabolites (VIP > 1, p < 0.05, and FC > 1.2 or FC < 0.8) were identified after the interference of EECR. The level of significant differential metabolites between control group, middle dose group, and high dose group were compared and found that which supported the apoptosis-inducing action with dose-dependence. Conclusion: By means of metabolism, we have detected the mechanism of EECR inducing apoptosis of TNBC cells at the level of small molecule metabolites and found that EECR impacted the energy metabolism of TNBC cells. In addition, we concluded that EECR induced apoptosis by breaking the balance between ATP-production and ATP-consumption: arresting the pathways of Carbohydrate metabolism such as Central carbon metabolism in cancer, aerobic glycolysis, and Amino sugar and nucleotide sugar metabolism, whereas accelerating the pathways of ATP-consumption including Amino Acids metabolism, Fatty acid metabolism, Riboflavin metabolism and Purine metabolism. Although further study is still needed, EECR has great potential in the clinical treatment of TNBC with fewer toxic and side effects.

Variable geometry turbines are widely used to improve the part-load performance of gas turbine engines. However, there is a performance penalty associated with the vane-end clearance required for the movement of variable vanes. Especially for variable geometry turbines with high casing-endwall angles, greater vane-end clearances are necessary due to annulus slope, and then high endwall leakages would occur, which further deteriorates turbine efficiency. The variable geometry design of the first stage stator vane in a four-stage power turbine featuring very high endwall angles has been carried out by proposed stepped spherical endwall concept. The vane endwalls are spherically shaped so as to maintain constant endwall clearance at all turning angles. And, downstream of the spherical endwall an endwall step is introduced, in order to match the original S-shaped endwall contour and to reduce the leakage loss. Meantime, the rotating shaft is inclined upstream to further match the original endwall contour, and cavity tip design has been used to further reduce the leakage loss. An efficient numerical method has been employed to validate the variable geometry design as mentioned, and the effect of a rotating shaft has been included in the calculations. Then, the four-stage variable geometry power turbine characteristics are evaluated. Results show that the proposed stepped spherical endwall concept can be applied to the variable geometry design of the power turbine featuring very high endwall angles, and compared to the fixed geometry turbine, the efficiency of the new-designed variable geometry power turbine keeps nearly unchanged. Detailed results from this investigation are well presented and discussed in this paper.