Graphene and its derivatives have got numerous exciting applications due to the monolayer of tightly packed carbon atoms that possess many interesting properties. In this work, as-prepared graphene ...oxide (GO) was modified by hyperbranched polyethylenimine (HPEI) and then blended into polyethersulfone (PES) casting solution to prepare PES ultrafiltration membrane via phase inversion method. GO and its modified products were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and transmission electron microscopy (TEM). The morphology and performance of the hybrid membranes were characterized by scanning electron microscopy (SEM), TEM, water contact angle, permeation measurement, mechanical measurement, antifouling and antibacterial tests. Mechanical tests revealed that the hybrid membranes exhibited a higher tensile strength and Young's modulus. The hybrid membranes exhibited a slightly lower pure water flux compared with pure membranes; however, the antifouling tests revealed that the hybrid membranes blended with HPEI-GO nanosheets displayed a preferable antifouling performance. The antibacterial tests confirmed that the as-formed hybrid membranes showed an effective antibacterial performance against Escherichia coli (E. coli).
Display omitted
•HPEI-GO/PES hybrid ultrafiltration membrane was firstly fabricated.•The membranes blending with HPEI-GO/PES had a good antifouling performance.•The membranes showed good antibacterial and mechanical performance.
Abstract
Aims
Alcohol intake has been shown to increase the risk of breast cancer. However, the dose-response analysis of different alcoholic beverages (spirits, wine and beer) is not clear. Our ...meta-analysis aims to provide a dose-response estimation between different alcohols and breast cancer risk.
Methods
Search of PubMed and Web of Science and manual searches were conducted up to 1 December 2018, and summary relative risks (RRs) and attributable risk percentage (ARP) for alcohol intake on the development of breast cancer were calculated. Dose-response meta-analysis modeled relationships between drinking type and breast cancer risk. Sources of heterogeneity were explored, and sensitivity analyses were conducted to test the robustness of findings.
Results
In total, 22 cohort studies and 45,350 breast cancer cases were included. Current drinkers for ER+ had an increased risk compared with never drinkers. In dose-response analysis, there was a statistically significant linear trend with breast cancer risk increasing gradually by total alcohol and wine dose: when adding 10 g per day, the risk increased by 10.5% (RR = 1.10, 95%CI = 1.08–1.13) in total alcohol and 8.9% (RR = 1.08, 95%CI = 1.04–1.14) in wine. For postmenopausal women, the risk increases by 11.1% (RR = 1.11, 95%CI = 1.09–1.13) with every 10 g of total alcohol increase. Furthermore, the breast cancer alcohol-attributed percentage is higher in Europe than in North America and Asia.
Conclusions
The effect of drinking on the incidence of breast cancer is mainly manifested in ER+ breast cancer. Quantitative analysis showed total drinking had a significant risk for breast cancer, especially for postmenopausal women. However, for different alcohols, just wine intake has the similar results.
Acute myeloid leukemia (AML) is one of the most common hematological malignancies with high heterogeneity, characterized by a differentiating block at the early progenitor stage. The selective BCL-2 ...inhibitor, Venetoclax (Ven), has shown exciting clinical results in a certain group of AML patients. However, Ven alone is insufficient to reach an enduringly complete response, which leads to the concern of Ven resistance. Alternative combined therapies with Ven are demanded in AML. Here, we reported the synergistic effect and molecular mechanism of the enhancer of zeste homolog 2 (EZH2) inhibitor DZNeP with Ven in AML cells. Results showed that the combination of DZNeP with Ven significantly induces cell proliferation arrest compared to single-drug control in AML cells and primary samples, and CalcuSyn analysis showed their significant synergy. The combination also significantly promotes apoptosis and increases the expression of pro-apoptotic proteins. The whole transcriptome analysis showed that phosphoinositide-3-kinase-interacting protein1 (PIK3IP1), the PI3K/AKT/mTOR signaling suppressor, is upregulated upon DZNeP treatment. Moreover, EZH2 is upregulated but PIK3IP1 is downregulated in 88 newly diagnosed AML cohorts compared to 70 healthy controls, and a higher expression of EZH2 is associated with poor outcomes in AML patients. Particularly, the combination of DZNeP with Ven dramatically eliminated CD117 (c-KIT) (+) AML blasts, suggesting the effect of the combination on tumor stem cells. In summary, our data indicated that DZNeP increases the sensitivity of Ven in AML by affecting PI3K and c-KIT signaling in AML. Our results also suggested that the therapeutic targeting of both EZH2 and BCL-2 provides a novel potential combined strategy against AML.
Fragrant woodfern (
) is a medicinal plant rich in terpenoids. Ultraviolet-B (UV-B) light could increase concentration of terpenoids. The aim of this study was to analyze how UV-B regulates the ...terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern. In this study, compared with the control group, the content of the terpenes was significantly higher in fragrant woodfern leaves under UV-B treatment for 4 days (d). In order to identify how UV-B regulates the terpenoid metabolic mechanism in fragrant woodfern, we examined the mRNAs and small RNAs in fragrant woodfern leaves under UV-B treatment. mRNA and miRNA-seq identified 4533 DEGs and 17 DEMs in the control group compared with fragrant woodfern leaves under UV-B treatment for 4 d. mRNA-miRNA analysis identified miRNA target gene pairs consisting of 8 DEMs and 115 miRNAs. The target genes were subjected to GO and KEGG analyses. The results showed that the target genes were mainly enriched in diterpene biosynthesis, terpenoid backbone biosynthesis, plant hormone signal transduction, MEP pathway and MVA pathway, in which miR156 and miR160 regulate these pathways by targeting
and
, respectively. The mRNA and miRNA datasets identified a subset of candidate genes. It provides the theoretical basis that UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern.
Acute myeloid leukemia (AML) is a high-mortality malignancy with poor outcomes. Azacitidine induces cell death and demonstrates treatment effectiveness against AML. Selinexor (KPT-330) exhibited ...significant benefits in combination with typical induction treatment for AML patients. Here, we explore the antitumor effect of KPT-330 combined with AZA in AML through CCK-8, flow cytometry, RT-qPCR, western blot, and RNA-seq. Our results showed that KPT-330 combined with AZA synergistically reduced cell proliferation and induced apoptosis in AML primary cells and cell lines. Compared to the control, the KPT-330 plus AZA down-regulates the expression of XPO1, eIF4E, and c-MYC in AML. Moreover, the knockdown of c-MYC could sensitize the synergy of the combination on suppression of cell proliferation and promotion of apoptosis in AML. Moreover, the expression of
and
was elevated in AML patient cohorts, respectively.
and
overexpression was associated with poor prognosis. In summary, KPT-330 with AZA exerted synergistic effects by suppressing XPO1/eIF4E/c-MYC signaling, which provided preclinical evidence for further clinical application of the novel combination in AML.
The present study aimed to select anti‐tumor‐associated antigen (TAA) autoantibodies as biomarkers in the immunodiagnosis of gastric adenocarcinoma (GAC) by the recursive partitioning approach (RPA) ...and further construct and evaluate a predictive model. A case‐control study was designed including 407 GAC patients as the case group and 407 normal controls. In addition, 67 serial serum samples from 25 GAC patients were collected at different time points before and after gastrectomy treatment. Autoantibodies against 14 TAA were measured in sera from all subjects by enzyme immunoassay. Finally, RPA resulted in the selection of nine‐panel TAA (c‐Myc, p16, HSPD1, PTEN, p53, NPM1, ENO1, p62, HCC1.4) from all detected TAA in the case‐control study; the classification tree based on this nine‐TAA panel had area under curve (AUC) of 0.857, sensitivity of 71.5% and specificity of 71.3%; The optimal panel also can identify GAC patients at an early stage from normal individuals, with AUC of 0.737, sensitivity of 64.9% and specificity of 70.5%. However, frequencies of the nine autoantibodies showed no correlation with GAC stage, tumor size, lymphatic metastasis or differentiation. GAC patients positive for more than two autoantibodies in the nine‐TAA panel had a worse prognosis than that of the GAC patients positive for no or one antibody. Titers of 10 autoantibodies in serial serum samples were significantly higher in GAC patients after surgical resection than before. In conclusion, this study showed that the panel of nine multiple TAAs could enhance the detection of anti‐TAA antibodies in GAC, and may be potential prognostic biomarkers in GAC.
Recursive partitioning approach (RPA) is a powerful method for selecting markers in cancer and a panel selected by RPA showed high diagnostic values for gastric adenocarcinoma. Antibody levels showed no correlation with tumor stage, size, or differentiation. Certain anti‐TAA antibodies increased after gastrectomy in gastric adenocarcinoma sera.
Cadmium is a persistent heavy metal commonly found in aquatic ecosystems and has a strong toxic effect on organisms. The sensitivity of phytoplankton to environmental changes and its role as an ...indicator of aquatic ecosystem health have been well-established. However, the mechanisms by which phytoplankton respond to cadmium remain incompletely understood. In this study, we chose the typical planktonic diatom Cyclotella meneghiniana Kützing, by integrating physiological-biochemical data and transcriptome analysis, to reveal the molecular mechanisms of C. meneghiniana responing to cadmium. Under cadmium stress, the cell density and chlorophyll-a content of C. meneghiniana significantly decreased, while MDA content and SOD activity gradually increased. At 72 h of cadmium stress, we found that at this time point, cell abundance and physiological variation were very significant, therefore we selected 72 h for subsequent analysis. To better understand the cadmium stress response mechanisms of C. meneghiniana, a de novo transcriptome method was used to analyse C. meneghiniana under cadmium stress for 72 h, and 1704 (M vs. CK) and 4788 (H vs. CK) differentially expressed genes were found. Our results showed that the changes in gene expression were closely correlated to the physiological-biochemical changes. Although cadmium stress could promote the nitrogen metabolism pathway, ROS scavenging system, and photosynthesis. While, C. meneghiniana under medium and high concentrations of cadmium can also limit various intracellular metabolic pathways, such as the MAPK pathway and phosphatidylinositol metabolic pathway, and the degree of inhibition increases with the increase of stress concentration. In present study, the complete molecular mechanism of the planktonic diatom response to cadmium has been established, which provided important information for further studies on heavy metal pollutants and the multiple functional genes responsible for cadmium sensitivity and tolerance in planktonic diatoms.
•Cadmium responsive DEGs in C. meneghiniana was firstly characterized with RNA-seq.•A total of 5646 DEGs were identified under cadmium stress in C. meneghiniana.•Expression profiles of cadmium responsive DEGs were validated by qRT-PCR analysis.•Proposed a schematic model of C. meneghiniana responsive cadmium’s regulatory network
Highlights • Trs920778 in lncRNA HOTAIR was associated with higher risk of breast cancer. • GT + TT rs1899663 and AG + GG rs4759314 were associated with lower breast cancer risk. • rs920778 has ...interaction with age at menopause, No. of abortion and family history. • We extend available data on the association of HOTAIR SNP and BC susceptibility. • Further studies with larger sample size and in different populations are warranted.
PDF
