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Long non-coding RNAs (lncRNAs) act as important regulators of tumorigenesis and development in bladder cancer. However, the underlying molecular mechanisms remain elusive. We previously identified a novel lncRNA signature related to immunity and progression in bladder cancer. Here we further explored the function of RP11-89, a lncRNA discovered in the previous signature. Loss- and gain-of function experiments were performed using CCK-8 assay, flow cytometry, Transwell assays, scratch tests and subcutaneous nude mouse models. High-throughput RNA sequencing was conducted to identify dysregulated genes in bladder cancer cells with RP11-89 knockdown or overexpression. Regulation of RP11-89 on miR-129-5p and PROM2 was explored through luciferase reporter assay, RIP assay and RNA pull-down assay. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. We found that RP11-89 “sponges” miR-129-5p and upregulates PROM2. Elevated PROM2 in cells was associated with attenuated ferroptosis through iron export, formation of multivesicular bodies and less mitochondrial abnormalities. We demonstrated that RP11-89 is a novel tumorigenic regulator that inhibits ferroptosis via PROM2-activated iron export. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer.

This study aims to construct a robust prognostic model for adult adrenocortical carcinoma (ACC) by large‐scale multiomics analysis and real‐world data. The RPPA data, gene expression profiles and clinical information of adult ACC patients were obtained from The Cancer Proteome Atlas (TCPA), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Integrated prognosis‐related proteins (IPRPs) model was constructed. Immunohistochemistry was used to validate the prognostic value of the IPRPs model in Fudan University Shanghai Cancer Center (FUSCC) cohort. 76 ACC cases from TCGA and 22 ACC cases from GSE10927 in NCBI’s GEO database with full data for clinical information and gene expression were utilized to validate the effectiveness of the IPRPs model. Higher FASN (P = .039), FIBRONECTIN (P

Introduction The cell-surface ectonucleotidase CD39 is a key molecule of the immunosuppressive adenosine pathway within the tumor microenvironment. However, the relationship between CD39 and clear cell renal cell carcinoma (ccRCC) is rarely reported and still remains unclear. Methods CD39 expression was first analyzed using the Oncomine and the Tumor IMmune Estimation Resource (TIMER) databases, and then examined in ccRCC patients (n=367) who had undergone radical nephrectomy using immunohistochemistry (IHC) and real-time quantitative PCR analysis (qPCR). The prognosis value of CD39 in ccRCC was evaluated by Cox proportional hazards analysis. Functional and gene set enrichment analysis (GSEA) was performed using transcriptomic data of ccRCC from TCGA. Correlation analysis between CD39 and tumor-infiltrating lymphocytes (TILs) was performed using the TISIDB database. The impact of CD39 on immune checkpoint therapy (ICT) was evaluated by two public cohorts. Results CD39 mRNA and protein expression was upregulated in tumor tissues from ccRCC patients and aberrant expression of CD39 was associated with advanced tumor stage and poor prognosis in ccRCC patients. EMT, IL-2/STAT5, inflammatory response, interferon gamma and KRAS hallmark gene sets were identified as CD39-related signaling pathway. The expression level of CD39 was significantly and positively correlated with high abundance of the regulatory TILs including NK cells, macrophages, Th cells and Treg cells. CD39 was correlated with expression of several immune checkpoints and higher CD39 expression was associated with better OS of ccRCC patients who received ICT. Conclusion CD39 is a powerful prognostic marker of ccRCC patients. Increased tumor expression of CD39 mRNA is significantly correlated with infiltrating levels of TILs, and better efficacy of ICT to ccRCC. CD39 could be a novel therapeutic target for ccRCC.

Objective: To systematically evaluate the diagnostic efficacy of confocal laser endomicroscopy (CLE) in detection of bladder cancer. Methods: A systematic literature search on CLE in diagnosing bladder cancer in PubMed, Embase, and the Cochrane Library databases was performed. A bivariate meta-regression model was used for meta-analysis to evaluate the pooled diagnostic value of CLE. Results: A total of 5 eligible studies involving 302 lesions were available for this meta-analysis. In a per-lesion analysis, pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver-operating curve (SROC) area under the curve (AUC) of CLE for malignant lesions were 0.90 (95% confidence interval [CI]: 0.85–0.94), 0.72 (95% CI: 0.59–0.82), 3.20 (95% CI: 2.14–4.79), 0.14 (95% CI: 0.09–0.21), 23.27 (95% CI: 11.71–46.25), and 0.91 (95% CI: 0.89–0.94), respectively. For low-grade urothelial carcinomas, pooled sensitivity, specificity, PLR, NLR, DOR, and AUC for CLE were 0.72 (95% CI: 0.57–0.84), 0.87 (95% CI: 0.77–0.93), 5.48 (95% CI: 3.12–9.62), 0.32 (95% CI: 0.20–0.50), 17.19 (95% CI: 8.01–36.89), and 0.85 (95% CI: 0.82–0.88), respectively. For high-grade urothelial carcinomas, pooled sensitivity, specificity, PLR, NLR, DOR, and AUC for CLE were 0.82 (95% CI: 0.62–0.92), 0.84 (95% CI: 0.73–0.91), 4.96 (95% CI: 2.58–9.54), 0.22 (95% CI: 0.09–0.52), 22.49 (95% CI: 5.33–94.85), and 0.89 (95% CI: 0.86–0.91), respectively. Conclusion: CLE is a promising endoscopy technique for real-time tumor grading of bladder cancer.

ObjectiveThis study aimed to explore the role of ACSL4 in CD8+ T cell tumor infiltration and outcomes of bladder cancer (BLCA) patients after immunotherapy.MethodsThe correlation between ACSL4 expression and tumor infiltration of immune cells was analyzed using the Tumor Immune Estimation Resource database. The prognostic significance of ACSL4 in BLCA was analyzed using Kaplan–Meier curves. Immunohistochemistry was used to detect CD8+ T cell infiltration in tumors with high and low ACSL4 expression obtained from patients at the Fudan University Shanghai Cancer Center. The relationships between immune checkpoint genes and immune response were analyzed using The Cancer Genome Atlas and IMvigor 210 cohorts. The molecular functions, cellular components, and biological processes involving ACSL4 were explored using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment pathway analyses.ResultsThe expression level of ACSL4 was significantly correlated with the infiltration of CD8+ T cells in BLCA tumors (r = 0.192, P = 2.22e-04). Elevated ACSL4 was associated with suppressed tumor progression and better outcomes for BLCA patients. The higher expression level of ACSL4 predicted better immunotherapeutic responses and was associated with higher expression levels of core immune checkpoint genes, including CD274, CTLA4, PDCD1, and LAG3, compared with the low ACSL4 expression group.ConclusionThis study demonstrated for the first time that elevated ACSL4 correlated significantly with CD8+ T cell infiltration and contributed to better immunotherapeutic responses in BLCA patients. Furthermore, ACSL4 serves as a novel biomarker for predicting patient outcomes after immunotherapeutic treatments, which may improve the development of individualized immunotherapy for BLCA.

Background Primary urethral carcinoma (PUC) is a rare genitourinary malignancy with a relatively poor prognosis. The aim of this study was to examine the impact of surgery on survival of patients diagnosed with PUC. Methods A total of 1544 PUC patients diagnosed between 2004 and 2016 were identified based on the SEER database. The Kaplan-Meier estimate and the Fine and Gray competing risks analysis were performed to assess overall survival (OS) and cancer-specific mortality (CSM). The multivariate Cox regression model and competing risks regression model were used to identify independent risk factors of OS and cancer-specific survival (CSS). Results The 5-yr OS was significantly better in patients who received either local therapy (39.8%) or radical surgery (44.7%) compared to patients receiving no surgery of the primary site (21.5%) (p < 0.001). Both local therapy and radical surgery were each independently associated with decreased CSM, with predicted 5-yr cumulative incidence of 45.4 and 43.3%, respectively, compared to 64.7% for patients receiving no surgery of the primary site (p < 0.001). Multivariate analyses demonstrated that primary site surgery was independently associated with better OS (local therapy, p = 0.037; radical surgery, p < 0.001) and decreased CSM (p = 0.003). Similar results were noted regardless of age, sex, T stage, N stage, and AJCC prognostic groups based on subgroup analysis. However, patients with M1 disease who underwent primary site surgery did not exhibit any survival benefit. Conclusion Surgery for the primary tumor conferred a survival advantage in non-metastatic PUC patients.

To construct a robust genomic classifier for high-risk sporadic type 2 papillary renal cell carcinoma (sPRCC2) and identify potential therapeutic targets. A cohort from The Cancer Genome Atlas and two datasets from Gene Expression Omnibus were examined. Common differentially expressed genes were screened, and the ConsensusClusterPlus package was used to identify potential high-risk molecular subtypes of sPRCC2. Targeting protein for Xklp2 (TPX2) expression was used to simulate the classifier according to the logistic model. Ninety-two samples from Fudan University Shanghai Cancer Center (FUSCC) were obtained, and TPX2 immunostaining was performed to validate the predictive ability of the genomic classifier. Retrospective analysis was used to compare drug efficacy between the groups. High-risk sPRCC2 had worse overall (hazard ratio [HR] = 7.804) and disease-free survival (HR = 8.777) than low-risk sPRCC2, and the tumor and lymph node stages were significantly higher in high-risk sPRCC2. Gene set enrichment analysis revealed significant enrichment of genes in the mammalian target of rapamycin (mTOR) complex 1 signaling pathway in the high-risk group. In the FUSCC cohort, high-risk sPRCC2 (high TPX2 expression) was significantly correlated with worse overall and progression-free survival. Retrospective analysis indicated that mTOR inhibitor (everolimus) had greater efficacy in the high-risk group than in the low-risk group (overall response rate: 28.6% vs. 16.7%) and that everolimus had greater efficacy than sunitinib in the high-risk group (overall response rate: 28.6% vs. 20%). This study successfully constructed a genomic classifier for identifying high-risk sPRCC2. mTOR inhibitors may have good efficacy in patients with high-risk sPRCC2.

For a HVDC converter station, the commonly used power loss determination methods are difficult to accurately reflect the changes of power loss of the converter in real time, given that the operating parameters of the converter station are dynamically changing when the converter station is running normally. Therefore, this paper proposes a method for predicting power loss of HVDC converters based on support vector regression. According to this method, firstly, the power loss data of a converter is analyzed. Then the appropriate feature in the power loss data is selected and thus a dataset of power loss samples can be obtained for further work. By applying the support vector regression algorithm to the dataset collected before, it is possible to predict the power loss of a converter for various operating parameters of the HVDC converter station. Finally, the cross-validation method was used to validate the stability of the prediction method. The result of the validation shows that the proposed method is able to accurately and stably predict the power loss of a converter of the HVDC converter station in real time.

BACKGROUND: This study aimed to assess the prognostic value of a various of diagnostic immunohistochemical (IHC) markers and develop an IHC-based classifier to predict the disease-free survival (DFS) of patients with bladder cancer (BC) undergoing radical cystectomy (RC).METHODS: IHC was performed on tumor specimens from 366 patients with transitional cell BC. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to develop a multi-marker classifier for predicting DFS of patients with BC. The Kaplan–Meier estimate was performed to assess DFS, and univariate and multivariate Cox regression models were used to identify independent risk factors to predict DFS of patients with BC.RESULTS: Based on the LASSO Cox regression model, nine prognostic markers were identified in the training cohort. Patients were stratified into low- and high-risk groups using the IHC-based classifier. In the training cohort, the 10-year DFS was significantly better in low-risk patients (70.7%) compared with high-risk patients (17.9%) (p＜0.001); in the validation cohort, the 10-year DFS was 85.7% for the low-risk group and 20.4% for the high-risk group (p＜0.001). Multivariable Cox regression analyses showed that the high-risk group based on the nine-IHC-based classifier was associated with poorer DFS adjusted by clinicopathological characteristics. Finally, a nomogram comprising the nine-IHC classifier and clinicopathological factors was developed for clinical application.CONCLUSION: The nine-IHC-based classifier is a reliable prognostic tool, which can eventually guide clinical decision making regarding treatment strategy and follow-up scheduling of BC.

We propose a convenient method to manipulate the behavior of optical bistability (OB) and optical multistability (OM) in a double Λ-type atomic system with hyperfine structure driven by a π-polarized probe field and a σ-polarized elliptically polarized field (EPF). In the scheme, the frequency detuning of two circularly polarized components of the EPF are determined by an applied magnetic field, and the amplitudes and the phase difference of that can be modulated by rotating a quarter-wave plate, which can be used to optimize quantum interference. Our numerical results show that not only the appearance and disappearance of OB can be transformed reciprocally, but also the switch from OB to OM or vice can be easily realized only by adjusting the magnetic field B or rotating the angle ϕ with the 1/4 wave plate.

Premise of the study Understanding resource allocation to reproduction, a key factor in life history tradeoffs, has long intrigued plant ecologists. Despite the recognized importance of understanding the movement of resources among flowers following variable pollination, the patterns of resource reallocation to plant reproductive organs have not been thoroughly addressed. In this study, we aimed to empirically explore how resources redistribute within inflorescences in response to differential pollination intensities. Methods Using a common herb, Sagittaria trifolia, we conducted supplemental and controlled pollination for single, some, or all flowers in simple and complex inflorescences, and compared their resulting fruiting probabilities, seed production, and average seed masses. Key results Pollen supplementation of a single flower significantly increased its fruiting probability; however, the same manipulation of an inflorescence did not increase its overall reproduction. Single pollen-supplemented flowers had a higher percentage fruit set than inflorescences receiving supplemental pollination. In complex inflorescences, supplemental pollination had no effect on the reproductive success of flowers on the lateral or main branches. Conclusions We provided evidence of resource reallocation from controlled to pollen-supplemented flowers in simple inflorescences; however, resources were unlikely to be reallocated between the main and lateral branches in the complex inflorescences, suggesting that flowering branches represent integrated physiological units in S. trifolia. The results also demonstrated that single-flower supplemental pollination would exaggerate pollen limitation and lead to a biased understanding of a plant's reproductive status.

In this paper, Bacterial oxidation-cyanide leaching experiments were carried out and the carbonaceous substances composition of carbonaceous gold concentrate was been studied. The elemental composition was 9.73 % iron, 9.66 % sulfur, 4.84 % arsenic and 13.23 % carbon which element carbon and organic carbon was 12.11wt.% and 0.06 wt.% respectively. The main carbonaceous substances were elemental carbon which the morphology was dense and similar to graphite. The removal rates of iron, arsenic and sulfur were achieved to 93.78%, 97.02% and 95.54% respectively by bioleaching, and the gold recovery of oxidation residue reached 92.34% by carbon inhibited cyanide leaching process. The sulfide minerals packing problem could be effectively solved by bacterial oxidation process and greatly increased the gold recovery. So the bacteria oxidation and carbon inhibited leaching process is applicable to the carbonaceous gold ore.

How to apply big data technique in the innovation of government administration is one of hot issues of e-government. The paper discusses one method that applying visualization modeling technique, builds business model including organization model, resource model and process model. According to the connection rules in or among models, the paper also advances the methods to check integrity of models and simulate the business process for insuring the correctness, and to resolve the problem of normalization and accuracy. Then by extracting and integrating information resources from the business model, obtain unified business frameworks, and according to the efficiency factors that corresponding organization, resource, behavior, collaborative and product performance, collect big data and provide a quantitative analysis for the optimization of government business to guide the government business optimization strategy.

To investigate the application of diagnosis methods for coronary artery disease (CAD) and the status quo of its syndrome typing. The literature content analysis was used in this study. The frequency statistics was performed by comprehensively collecting CAD (thoracic obstruction) syndrome typing correlated literatures, designing content analysis tables, extracting information such as typing methods, typing elements, and syndrome typing, and so on. Results showed that blood stasis, yin deficiency, qi deficiency, yang deficiency, phlegm turbidity, and other syndrome elements extensively exist in literatures concerning CAD syndrome typing. Modem doctors prefer to use syndrome typing of qi, blood, jinye, and eight principles in syndrome typing of CAD more frequently. The asthenia in origin and asthenia in superficiality has been widely recognized as the basic syndrome of CAD.

To explore the diagnostic figures for TCM syndrome typing in coronary heart disease (CHD) patients.A retrospective investigation was carried out in 319 CHD patients hospitalized from Jan. 2004 to Dec. 2004 in authors' hospital. Through cluster analysis, descriptive statistics and frequency normalization in combination of clinical observation, the diagnostic figures of TCM syndromes were obtained.The figures for qi deficiency syndrome were: primary symptoms: chest pain and stuffiness, secondary symptoms: tiredness, short breath, poor appetite, light colored tongue, deep and thready pulse; for qi deficiency with phlegm and blood stasis syndrome: primary symptoms: chest stuffiness and pain, secondary symptoms: tiredness, insomnia, palpitation, obesity, dark red tongue, string and slippery pulse; for turbid-phlegm blocking collateral syndrome: primary symptoms: chest stuffiness, secondary symptoms: cough, expectoration with much white sputum, tiredness, short breath and poor appetite, light colored tongue with white greasy coating, slippery pulse.Research on diagnostic criteria for TCM syndrome typing could be established upon clinical epidemiologic survey and statistic analysis in combining with specialists' suggestions to primarily set the referrence figures.

Objective Animal models are useful for studying disease, but there is a shortage of suitable models of ulcerative colitis. The aim of the present study was to set up an oxazolone-induced murine colitis model and use it to research the pathogenesis of inflammatory bowel disease. Methods BALB/c mice were presensitized by painting the skin with 0.2 mL 3% oxazolone in 100% ethanol on days 0 and 1 followed by intrarectal administration of 0.15 mL 1% oxazolone in 50% ethanol on day 7. The disease activity index (DAI), histological changes of the colon, myeloperoxidase (MPO) activity and production of cytokines (TNF-alpha, IL-4, IFN-gamma) by the mucosa were evaluated. Results There were obvious changes in the DAI, histology and MPO activity, and the production of interleukin-4 was markedly increased compared with the concentrations of TNF-alpha and IFN-gamma, which remained normal, in the lesions. Conclusion Oxazolone colitis is Th2-mediated and has similar histologic features and distribution of inflammation to ulcerative colitis (UC), which has important implications for the use of this model in the study of the pathogenesis and treatment of UC.

We have analyzed the mechanism by which Sop4, a novel ER membrane protein, regulates quality control and intracellular transport of Pma1-7, a mutant plasma membrane ATPase. At the restrictive temperature, newly synthesized Pma1-7 is targeted for vacuolar degradation instead of being correctly delivered to the cell surface. Loss of Sop4 at least partially corrects vacuolar mislocalization, allowing Pma1-7 routing to the plasma membrane. Ste2-3 is a mutant pheromone receptor which, like Pma1-7, is defective in targeting to the cell surface, resulting in a mating defect. sop4delta suppresses the mating defect of ste2-3 cells as well as the growth defect of pma1-7. Visualization of newly synthesized Pma1-7 in sop4delta cells by indirect immunofluorescence reveals delayed export from the ER. Similarly, ER export of wild-type Pma1 is delayed in the absence of Sop4 although intracellular transport of Gas1 and CPY is unaffected. These observations suggest a model in which a selective increase in ER residence time for Pma1-7 may allow it to achieve a more favorable conformation for subsequent delivery to the plasma membrane. In support of this model, newly synthesized Pma1-7 is also routed to the plasma membrane upon release from a general block of ER-to-Golgi transport in sec13-1 cells.