Identification of BST2 Contributing to the Development of Glioblastoma Based on Bioinformatics Analysis

Rigorous molecular analysis of the immune cell environment and immune response of human tumors has led to immune checkpoint inhibitors as one of the most promising strategies for the treatment of human cancer. However, in human glioblastoma multiforme (GBM) which develops in part by attracting immune cell types intrinsic to the human brain (microglia), standard immunotherapy has yielded inconsistent results in experimental models and patients. Here, we analyzed publicly available expression datasets to identify molecules possibly associated with immune response originating from or influencing the tumor microenvironment in primary tumor samples. Using three glioma datasets (GSE16011, Rembrandt-glioma and TCGA-glioma), we first analyzed the data to distinguish between GBMs of high and low tumor cell purity, a reflection of the cellular composition of the tumor microenvironment, and second, to identify differentially expressed genes (DEGs) between these two groups using GSEA and other analyses. Tumor purity was negatively correlated with patient prognosis. The interferon gamma-related gene BST2 emerged as a DEG that was highly expressed in GBM and negatively correlated with tumor purity. BST2high tumors also tended to harbor PTEN mutations (31 vs. 9%, BST2high versus BST2low) while BST2low tumors more often had sustained TP53 mutations (8 versus 36%, BST2high versus BST2low). Prognosis of patients with BST2high tumors was also poor relative to patients with BST2low tumors. Further molecular in silico analysis demonstrated that high expression of BST2 was negatively correlated with CD8+ T cells but positively correlated with macrophages with an M2 phenotype. Further functional analysis demonstrated that BST2 was associated with multiple immune checkpoints and cytokines, and may promote tumorigenesis and progression through interferon gamma, IL6/JAK/STAT3 signaling, IL2/STAT5 signaling and the TNF-α signaling via NF-kB pathway. Finally, a series of experiments confirmed that the expression of BST2 can be significantly increased by IFN induction, and knockdown of BST2 can significantly inhibit the growth and invasion of GBM cells, and may affect the phenotype of tumor-associated macrophages. In conclusion, BST2 may promote the progression of GBM and may be a target for treatment.publishedVersio

Quality-of-life outcomes and unmet needs between ileal conduit and orthotopic ileal neobladder after radical cystectomy in a Chinese population: a 2-to-1 matched-pair analysis

Peri-operative outcomes. (DOCX 15 kb

A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population.

Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer.This work was conducted on behalf of the CHIPGECS and The PRACTICAL consortia (see Supplementary Consortia). We acknowledge the contribution of doctors, nurses and postgraduate research students at the CHIPGENCS sample collecting centers. We thank Orchid and Rosetrees for funding support. This work was also supported by National Natural Science foundation of China for funding support to H Zhang (Grant No: 30671793 and 81072377), N Feng (Grant No: 81272831), X Zhang (Grant No: 30572139, 30872924 and 81072095), S Zhao (Grant No: 81072092 and 81328017), Y Yu (Grant No: 81172448) and Program for New Century Excellent Talents in University from Department of Education of China (NCET-08-0223) and the National High Technology Research and Development Program of China (863 Program 2012AA021101) to X Zhang.This is the final version of the article. It first appeared from Impact Journals via http://dx.doi.org/10.18632/oncotarget.725

Relationship between urodynamic patterns and lower urinary tract symptoms in Chinese women with a non-neurogenic bladder

Objective: To investigate the urodynamic study (UDS) patterns, obstruction status, continence status, and their correlations among neurologically intact women with lower urinary tract symptoms (LUTS) through an epidemiological and logistic regression analyses. Methods: We retrospectively analyzed the UDS data of 3265 neurologically intact women with LUTS (2002–2014). Five UDS patterns were identified: normo-active detrusor/sphincter (NA, or DSI, detrusor/sphincter intact), idiopathic detrusor overactivity (IDO), idiopathic sphincter overactivity (ISO), IDO + ISO, and detrusor underactivity (DUA). Analyses of UDS pattern distribution and stratification were performed (based on a modification of the European Urological Association-Madersbacher classification system), and their correlations with bladder outlet obstruction (BOO) and stress urinary incontinence (SUI) status were evaluated via logistic regression analysis. Results: NA, IDO, IDO + ISO, ISO, and DUA were noted in 927 (28.4%), 678 (20.8%), 320 (9.8%), 689 (21.1%), and 651 (19.9%) cases, respectively. Moreover, storage, storage + voiding, and voiding symptoms were noted in 62.4%, 21.1%, and 16.5% cases, respectively, whereas BOO and SUI were observed in 12.1% and 29.0% cases, respectively. The risk factors for BOO included NA, IDO, ISO, and IDO + ISO, whereas the protective factors against BOO included storage symptoms, SUI, storage + voiding symptoms, and complaint duration within 1–12 months. NA was the only risk factor for SUI, whereas BOO, storage + voiding symptoms, IDO, and storage symptoms were protective factors for SUI. Conclusion: Five UDS patterns were identified among neurologically intact women with LUTS. Functional abnormalities of the detrusor and/or sphincter were the main causes of LUTS, and were correlated with the BOO or SUI status. Thus, the UDS pattern can provide additional information regarding the risk factors for BOO or SUI status, as compared to symptomatic typing

Quick Decision-Making for Close-Boiling Distillation Schemes

Separating close-boiling components using distillation is very common in industry. Considering the higher capital and energy intensity of the task, schematic selection of optimal distillation strategies becomes a significant decision of both industrial and methodological importance. In this sense, this paper introduces a reliable shortcut method of simplicity and robustness for optimizing the target of total annualized cost (TAC). In detail, selective analyses are carried out among four schematic candidates for three close-boiling systems. The schemes are conventional distillation column, mechanical vapor recompression (MVR), double-effect distillation, and distillation with a recycle process. The mixtures to be separated are methyltrichlorosilane/dimethylchlorosilane, methylcyclopentane/cyclohexane, and isobutanol/<i>n</i>-butanol. After the first round evaluation, hydraulic calculations through rigorous simulations are worked out to size the equipment, which is necessary for TAC analyses. In the second round comparison, MVR stands out to be a more attractive option for close-boiling separations than other configurations

Integration of intratumoral RASSF10 expression and tumor-associated macrophages into the established clinical indicators better predicts the prognosis of clear cell renal cell carcinoma patients

A helpful evaluation system is crucial for the postoperative prognosis prediction of clear cell renal cell carcinoma (ccRCC) patients. This study determined the prognostic value of combining intratumoral RASSF10 expression and tumor-associated macrophages (TAMs) with the established clinicopathological indicators in ccRCC patients. RASSF10 expression was analyzed in ccRCC patient data from online databases and ccRCC cell lines. Two independent ccRCC patient cohorts were employed to examine the prognostic value of RASSF10 and other markers by immunohistochemistry (IHC) and statistical analyses. We found that RASSF10 expression was downregulated in ccRCC specimens from the TCGA datasets and three independent institutions. RASSF10 expression was negatively correlated with disease progression and TAM infiltration in ccRCC. In addition, low RASSF10 expression and high TAM infiltration predicted a high TNM stage, SSIGN score, WHO/ISUP grading, and a poor prognosis in two independent ccRCC patient cohorts. Moreover, RASSF10, CD68 or CD163, TNM stage, and SSIGN score were identified as independent risk factors in predicting ccRCC patients’ prognosis. Time-dependent c-index analyses revealed that the combination of RASSF10 and TAMs resulted in a higher index than that resulting from each alone in the postoperative prognosis of ccRCC patients, and the integration of RASSF10 and TAMs with the TNM stage or SSIGN score achieved the best accuracy in assessing the prognosis of ccRCC patients. These findings were validated in the randomized training, validation, and combined cohorts. Taken together, the combination of the RASSF10-TAM classifier and current clinical parameters yields superior accuracy in predicting the ccRCC patients’ postoperative outcome

Graphene Oxide/Single-Walled Carbon Nanotube Membranes for CO2 and N2 Separation from Blast Furnace Gas

A novel molecular sieve membrane was synthesized using graphene oxide/single-walled carbon nanotubes (GO/SWCNTs). The composite was characterized by transmission electron microscopy, field emission scanning electron microscopy, X-ray diffraction, thermogravimetric analysis, Fourier transform infrared spectroscopy, and Brunauer–Emmett–Teller-specific surface area analyzers. The results revealed that laminar GO was interwoven with tubular SWCNTs and the carbon nanotubes were attached onto the surface of GO or interspersed among GO to form a three-dimensional structure. Moreover, the interlayer spacing of GO/SWCNTs increased to 0.826 nm. On condition that the inlet pressure of N2 was 0.10 MPa and the temperature was 323 K, the N2 permeability of GO/SWCNTs was 1595 Barrer. With increasing temperature, the N2 permeability decreased while it increased with the inlet pressure. When the inlet pressure of CO was 0.10 MPa and the temperature was 323 K, the CO permeability was 109 Barrer. At the temperature of 323 K, the selectivities of N2/CO and CO2/CO were 32.8 and 37, respectively. These results indicated that GO/SWCNTs may be a promising molecular sieve for gas separation