Lithium, an anti-psychotic drug, greatly enhances the generation of induced pluripotent stem cells

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by defined factors. The low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limited the potential application of iPSCs. Here we report that Lithium (Li), a drug used to treat mood disorders, greatly enhances iPSC generation from both mouse embryonic fibroblast and human umbilical vein endothelial cells. Li facilitates iPSC generation with one (Oct4) or two factors (OS or OK). The effect of Li on promoting reprogramming only partially depends on its major target GSK3β. Unlike other GSK3β inhibitors, Li not only increases the expression of Nanog, but also enhances the transcriptional activity of Nanog. We also found that Li exerts its effect by promoting epigenetic modifications via downregulation of LSD1, a H3K4-specific histone demethylase. Knocking down LSD1 partially mimics Li's effect in enhancing reprogramming. Our results not only provide a straightforward method to improve the iPSC generation efficiency, but also identified a histone demethylase as a critical modulator for somatic cell reprogramming

TANGLE: Two-Level Support Vector Regression Approach for Protein Backbone Torsion Angle Prediction from Primary Sequences

Protein backbone torsion angles (Phi) and (Psi) involve two rotation angles rotating around the Cα-N bond (Phi) and the Cα-C bond (Psi). Due to the planarity of the linked rigid peptide bonds, these two angles can essentially determine the backbone geometry of proteins. Accordingly, the accurate prediction of protein backbone torsion angle from sequence information can assist the prediction of protein structures. In this study, we develop a new approach called TANGLE (Torsion ANGLE predictor) to predict the protein backbone torsion angles from amino acid sequences. TANGLE uses a two-level support vector regression approach to perform real-value torsion angle prediction using a variety of features derived from amino acid sequences, including the evolutionary profiles in the form of position-specific scoring matrices, predicted secondary structure, solvent accessibility and natively disordered region as well as other global sequence features. When evaluated based on a large benchmark dataset of 1,526 non-homologous proteins, the mean absolute errors (MAEs) of the Phi and Psi angle prediction are 27.8° and 44.6°, respectively, which are 1% and 3% respectively lower than that using one of the state-of-the-art prediction tools ANGLOR. Moreover, the prediction of TANGLE is significantly better than a random predictor that was built on the amino acid-specific basis, with the p-value<1.46e-147 and 7.97e-150, respectively by the Wilcoxon signed rank test. As a complementary approach to the current torsion angle prediction algorithms, TANGLE should prove useful in predicting protein structural properties and assisting protein fold recognition by applying the predicted torsion angles as useful restraints. TANGLE is freely accessible at http://sunflower.kuicr.kyoto-u.ac.jp/~sjn/TANGLE/

A combined biomarker panel shows improved sensitivity for the early detection of ovarian cancer allowing the identification of the most aggressive Type II tumours.

Background: There is an urgent need for biomarkers for the early detection of ovarian cancer (OC). The purpose of this study was to assess whether changes in serum levels of lecithin-cholesterol acyltransferase (LCAT), sex hormone-binding globulin (SHBG), glucoseregulated protein, 78 kDa (GRP78), calprotectin and insulin-like growth factor-binding protein 2 (IGFBP2) are observed before clinical presentation and to assess the performance of these markers alone and in combination with CA125 for early detection. Methods: This nested case–control study used samples from the United Kingdom Collaborative Trial of Ovarian Cancer Screening trial. The sample set consisted of 482 serum samples from 49 OC subjects and 31 controls, with serial samples spanning up to 7 years pre-diagnosis. The set was divided into the following: (I) a discovery set, which included all women with only two samples from each woman, the first ato14 months and the second at 432 months to diagnosis; and (ii) a corroboration set, which included all the serial samples from the same women spanning the 7-year period. Lecithin-cholesterol acyltransferase, SHBG, GRP78, calprotectin and IGFBP2 were measured using ELISA. The performance of the markers to detect cancers pre-diagnosis was assessed. Results: A combined threshold model IGFBP2 478.5 ng ml 1 : LCAT o8.831 mg ml 1 : CA125 435 Uml 1 outperformed CA125 alone for the earlier detection of OC. The threshold model was able to identify the most aggressive Type II cancers. In addition, it increased the lead time by 5–6 months and identified 26% of Type I subjects and 13% of Type II subjects that were not identified by CA125 alone. Conclusions: Combined biomarker panels (IGFBP2, LCAT and CA125) outperformed CA125 up to 3 years pre-diagnosis, identifying cancers missed by CA125, providing increased diagnostic lead times for Type I and Type II OC. The model identified more aggressive Type II cancers, with women crossing the threshold dying earlier, indicating that these markers can improve on the sensitivity of CA125 alone for the early detection of OC

Pullout behavior of GFRP anti-floating anchor based on the FBG sensor technology

Building anti-floating anchors have been increasingly used in recent years, but conventional steel anchors under service conditions are easily subjected to chemical erosion. Glass fiber reinforcement polymer (GFRP) is a promising solution to this problem. In this study, field pullout tests were conducted on three full instrumented GFRP anti-floating anchors in weathered granite. Specifically, the GFRP anchors during pultrusion were innovatively embedded with bare fiber Bragg grating (FBG) sensors to monitor the axial force distribution along depth. It was found that the embedded FBG could reliably monitor the axial force distribution of GFRP anchors. The ultimate pullout force of a GFRP anchor with diameter of 28 mm and anchorage length of 5 m was up to 400 kN. The GFRP anchor yielded at 0.8 m underground. Force distribution and field photos at failure indicated shear failure occurred at the anchor/bolt interface at the end of the tests. The feasibility of the GFRP anti-floating anchor was also verified in civil engineering. Finally, an elastic mechanical model and Mindlin's displacement solution are used to get distribution functions of axial force and shear stress along the depth, and the results accord with the test results.Department of Civil and Environmental Engineering201903 bcrcpublished_fina

Ethanol ablation of hepatocellular carcinoma Up to 5.0 cm by using a multipronged injection needle with high-dose strategy

PURPOSE: To investigate whether ethanol ablation by using a multipronged needle delivery system (multipronged ethanol ablation) could eradicate hepatocellular carcinoma (HCC) up to 5.0 cm in diameter with a single-session high-dose strategy. MATERIALS AND METHODS: The hospital ethics committee approved the prospective study, and each patient provided written informed consent. One hundred forty-one patients (125 men, 16 women; mean age, 53 years; range, 27-76 years) with 164 primary or recurrent HCC ranging from 1.3 to 5.0 cm in diameter (mean, 2.9 cm +/- 0.9) were treated with high-dose multipronged ethanol ablation. Patients were unsuitable for surgery, declined surgery and radiofrequency ablation, or had tumors located at unfavorable sites. Primary technique effectiveness (PTE) (complete ablation within two sessions), local tumor progression (LTP), and complications after the treatment were observed. Twenty risk factors of local effectiveness and complications were analyzed by means of univariate and multivariate analysis. RESULTS: Mean number of treatment sessions was 1.1. The mean volume of ethanol per tumor was 31 mL (range, 8-68 mL). PTE was achieved in 134 (95%) of 141 patients and was significantly associated with tumor pattern (capsulated vs noncapsulated, P = .018). After a mean follow-up period of 25 months, LTP was observed in 16 (12%) of 134 patients, and in nine (56%) patients, LTP occurred in tumors 3.1-5.0 cm in diameter. Alanine aminotransferase level (P = .023) was the independent risk factor for LTP. Three (2%) of 141 patients had major complications. CONCLUSION: Multipronged ethanol ablation with a high-dose strategy can be used to treat HCC up to 5.0 cm in diameter effectively and safely, often in a single sessio

Biomarker and competing endogenous RNA potential of tumor-specific long noncoding RNA in chromophobe renal cell carcinoma

Hai-Tao He,1,2,* Mu Xu,1,* Ye Kuang,1 Xiao-Yun Han,1 Ming-Qi Wang,1 Qing Yang1 1Department of Pathogenobiology, 2Department of Cell Biology, College of Basic Medical Sciences, Jilin University, Changchun, People&rsquo;s Republic of China *These authors contributed equally to this work Background: Accumulating evidence suggests long noncoding RNAs (lncRNAs) play important roles in the initiation and progression of cancers. However, their functions in chromophobe renal cell carcinoma (chRCC) are not fully understood.Methods: We analyzed the expression profiles of lncRNA, microRNA, and protein-coding RNA, along with the clinical information of 59 primary chRCC patients collected from The Cancer Genome Atlas database to identify lncRNA biomarkers for prognosis. We also constructed an lncRNA&ndash;microRNA&ndash;mRNA coexpression network (competitive endogenous RNAs network) by bioinformational approach.Results: One hundred and forty-two lncRNAs were found to be differentially expressed between the cancer and normal tissues (fold change &ge;1.5, P&lt;0.001). Among them, 12 lncRNAs were also differentially expressed with the corresponding clinical characteristics (fold change &ge;1.5, P&lt;0.01). Besides, 7 lncRNAs (COL18A1-AS, BRE-AS1, SNHG7, TMEM51-AS1, C21orf62-AS1, LINC00336, and LINC00882) were identified to be significantly correlated with overall survival (log-rank P&lt;0.05). A competitive endogenous RNA network in chRCC containing 16 lncRNAs, 18 miRNAs, and 168 protein-coding RNAs was constructed.Conclusion: Our results identified specific lncRNAs associated with chRCC progression and prognosis, and presented competing endogenous RNA potential of lncRNAs in the tumor. Keywords: long noncoding RNA, chromophobe renal cell carcinoma, biomarker, competing endogenous RNA network&nbsp

Controllable fabrication of SnO2-coated nanotubes by chemical vapor multiwalled carbon deposition

A simple and efficient approach for coating multiwalled carbon nanotubes (MWCNTs) with size-controllable SnO2 nanoparticles by chemical vapor deposition has been developed using tin hydride (SnH4) gas as the source of SnO2 at 550 degrees C. The size and coverage of SnO2 nanoparticles can be adjusted by simply controlling the deposition time and the flow rate of the SnH4/N-2 mixture gas during the CVD procedure. In addition, by using the MWCNTs as a sacrificial template, a kind of one-dimensional chain-like SnO2 nanostructure has been synthesized by increasing the deposition temperature to 730 degrees C. This technique may provide a good way to produce tunable SnO2-MWCNT composites. (c) 2005 Elsevier Ltd. All rights reserved