Transcriptomic analysis of micropapillary high grade T1 urothelial bladder cancer

No consensus currently exist on the optimal treatment of patients with high-risk nonmuscle invasive (HGT1) micropapillary variant of bladder cancer (MPBC). Transcripsome analysis may allow stratification of MPBC-HGT1 enabling prediction of recurrence and guide therapeutic management for individual patients. Whole transcriptome RNA-Sequencing of tumors from 23 patients with MPBC-HGT1 and 64 conventional urothelial carcinomas (cUC) (reference set) was performed. Differentially expressed genes between MPBC-HGT1 and cUC-HGT1 were explored. Cox proportional hazard models and Kapplan-Meier methods were used to assess the relation between time to progression (TTP) and individual gene expression adjusting for clinical covariates. Over 3000 genes were differentially expressed in MPBC-HGT1 as compared with cUC-HGT1 and a 26-gene signature is characteristic of MPBC within HGT1. A set of three genes; CD36, FAPB3 and RAETE1 ; were significantly associated with TTP. High expression of FABP3 and CD36 were associated with shorter TTP (p = 0.045 and p = 0.08) as was low expression of RAET1E (p = 0.01). Our study suggest that a 26-gene signature can define MPBC-HGT1 within conventional urothelial carcinomas. A prognostic risk index of three genes (FABP3, CD36 and RAET1E) was found to be associated with shorter TTP and may help classify a group of patients with MPBC-HGT1 with high-risk of early progression. These observations might have implications in terms of radical cystectomy recommendation in MPBC patients

Association of tumour microRNA profiling with outcomes in patients with advanced urothelial carcinoma receiving first-line platinum-based chemotherapy

Background: Tumour expression of selected microRNAs (miRs) correlates with cisplatin efficacy in multiple cancers. We investigated the role of selected miRs in patients receiving cisplatin-based therapy for advanced urothelial carcinoma (UC). Methods: RNA was extracted from formalin-fixed paraffin-embedded tumour from 83 advanced UC patients who received cisplatin. A miR panel based on relevance for platinum sensitivity and UC was studied by quantitative reverse transcription quantitative PCR (RT–qPCR). Association of progression-free survival (PFS) with miR expression was analysed using cox regression. Selected TFs were chosen by association with the panel of miRs using the Transcription Regulation algorithm (GeneGo MetaCore+MetaDrug version 6.23 build 67496). Bladder cancer (BC) cell lines were used to investigate the previously described role of miR-21 mediating cisplatin sensitivity. Results: The 83 patients had a median PFS of 8 months. In multivariate analysis, higher levels of E2F1 (P=0.01, HR: 1.95 (1.14, 3.33)), miR-21 (P=0.01, HR: 2.01 (1.17, 3.45)) and miR-372 (P=0.05, HR: 1.70 (1.00, 2.89)) were associated with a shorter PFS. In the 8 BC cell lines, miR-21 was not shown to be necessary nor sufficient for modulating cisplatin sensitivity. Conclusions: In metastatic UC patients treated with cisplatin-based therapy, high primary tumour levels of E2F1, miR-21 and miR-372 are associated with poor PFS independent of clinical prognostic factors. The in vitro study could not confirm miR-21 levels role in modulating platinum sensitivity

Treatment of Ammonia Nitrogen Wastewater in Low Concentration by Two-Stage Ozonization

Ammonia nitrogen wastewater (about 100 mg/L) was treated by two-stage ozone oxidation method. The effects of ozone flow rate and initial pH on ammonia removal were studied, and the mechanism of ammonia nitrogen removal by ozone oxidation was discussed. After the primary stage of ozone oxidation, the ammonia removal efficiency reached 59.32% and pH decreased to 6.63 under conditions of 1 L/min ozone flow rate and initial pH 11. Then, the removal efficiency could be over 85% (the left ammonia concentration was lower than 15 mg/L) after the second stage, which means the wastewater could have met the national discharge standards of China. Besides, the mechanism of ammonia removal by ozone oxidation was proposed by detecting the products of the oxidation: ozone oxidation directly and ·OH oxidation; ammonia was mainly transformed into NO3−-N, less into NO2−-N, not into N2

Non-LTE ionization potential depression model for warm and hot dense plasma

For warm and hot dense plasma (WHDP), the ionization potential depression (IPD) is a key physical parameter in determining its ionization balance, therefore a reliable and universal IPD model is highly required to understand its microscopic material properties and resolve those existing discrepancies between the theoretical and experimental results. However, the weak temperature dependence of the nowadays IPD models prohibits their application through much of the WHDP regime, especially for the non-LTE dense plasma produced by short-pulse laser. In this work, we propose a universal non-LTE IPD model with the contribution of the inelastic atomic processes, and found that three-body recombination and collision ionization processes become important in determining the electron distribution and further affect the IPD in warm and dense plasma. The proposed IPD model is applied to treat the IPD experiments available in warm and hot dense plasmas and excellent agreements are obtained in comparison with those latest experiments of the IPD for Al plasmas with wide-range conditions of 70-700 eV temperature and 0.2-3 times of solid density, as well as a typical non-LTE system of hollow Al ions. We demonstrate that the present IPD model has a significant temperature dependence due to the consideration of the inelastic atomic processes. With the low computational cost and wide range applicability of WHDP, the proposed model is expected to provide a promising tool to study the ionization balance and the atomic processes as well as the related radiation and particle transports properties of a wide range of WHDP

Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation

Enantioselectivity in the aquatic toxicity of chiral pesticides has been widely investigated, while the molecular mechanisms remain unclear. Thus far, few studies has focused on genomic expression related to selective toxicity in chiral pesticide, nor on epigenetic changes, such as DNA methylation. Here, we used fipronil, a broad-spectrum insecticide, as a model chemical to probe its enantioselective toxicity in embryo development. Our results showed that S-(+)-fipronil caused severer developmental toxicity in embryos. The MeDIP-Seq analysis demonstrated that S-(+)-fipronil dysregulated a higher level of genomic DNA methylation than R-(−)-fipronil. Gene Ontology analysis revealed that S-(+)-fipronil caused more differentially methylated genes that are involved in developmental processes. Compared with R-(−)-fipronil, S-(+)-fipronil significantly disrupted 7 signaling pathways (i.e., mitogen-activated protein kinases, tight junctions, focal adhesion, transforming growth factor-β, vascular smooth muscle contraction, and the hedgehog and Wnt signaling pathways) by hyper-methylation of developmentally related genes, which further induced the downregulation of those genes. Together, these data suggest that differences in DNA methylation may partly explain the enantioselectivity of fipronil to zebrafish embryos. The application of epigenetics to investigate the enantioselective toxicity mechanism of chiral chemicals would provide a further understanding of their stereoselectivity biological effects

FOLDNA, a Web Server for Self-Assembled DNA Nanostructure Autoscaffolds and Autostaples

DNA self-assembly is a nanotechnology that folds DNA into desired shapes. Self-assembled DNA nanostructures, also known as origami, are increasingly valuable in nanomaterial and biosensing applications. Two ways to use DNA nanostructures in medicine are to form nanoarrays, and to work as vehicles in drug delivery. The DNA nanostructures perform well as a biomaterial in these areas because they have spatially addressable and size controllable properties. However, manually designing complementary DNA sequences for self-assembly is a technically demanding and time consuming task, which makes it advantageous for computers to do this job instead. We have developed a web server, FOLDNA, which can automatically design 2D self-assembled DNA nanostructures according to custom pictures and scaffold sequences provided by the users. It is the first web server to provide an entirely automatic design of self-assembled DNA nanostructure, and it takes merely a second to generate comprehensive information for molecular experiments including: scaffold DNA pathways, staple DNA directions, and staple DNA sequences. This program could save as much as several hours in the designing step for each DNA nanostructure. We randomly selected some shapes and corresponding outputs from our server and validated its performance in molecular experiments

Lanthanum Lead Oxide Hydroxide Nitrates with a Nonlinear Optical Effect

Two new lanthanum lead oxide hydroxide nitrates with acentric structure, [LaPb₈O­(OH)₁₀(H₂O)]­(NO₃)₇ (<b>1</b>) and [LaPb₈O­(OH)₁₀(H₂O)]­(NO₃)₇·2H₂O (<b>2</b>), have been prepared under subcritical hydrothermal conditions and crystallize in the space groups of <i>Cc</i> and <i>P</i>2₁2₁2₁, respectively. The crystal structure of compound <b>1</b> consists of the novel [LaPb₈O­(OH)₁₀(H₂O)]⁷⁺ clusters regularly arranged along the <i>ab</i> plane with nitrate ions as the counterions around the clusters by Pb–O bonds, developing into a three-dimensional net framework, while the structure of compound <b>2</b> is composed of [LaPb₈O­(OH)₁₀(H₂O)]⁷⁺ clusters and [NO₃]⁻ groups as the bridging groups, forming a three-dimensional net framework with crystallized water molecules filling in the gaps. The experiments confirmed that compound <b>1</b> is the residue of compound <b>2</b> after efflorenscence. Besides, the [LaPb₈O­(OH)₁₀(H₂O)]⁷⁺ clusters present mirror symmetry in structures of the two compounds. The second-harmonic-generation (SHG) measurements for the two nitrates indicate that the SHG responses for compounds <b>1</b> and <b>2</b> are 1.3 and 1.1 times that of KH₂PO₄, respectively. Theoretical calculations confirmed that the SHG efficiency of compounds <b>1</b> and <b>2</b> mainly arises from the NO₃^– groups in the structure