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Mucins are heavily glycosylated proteins secreted by various cell types, to protect the epithelial surface of the gastrointestinal tract from damage. Currently, increasing studies provided evidence to suggest that mucins play an essential role in regulating tumor progression. However, the role of mucins and the underpinning mechanism of how mucins drive melanoma progression remains elusive. In this study, we first demonstrated that mucin 21 (MUC21) expression was significantly upregulated in metastatic melanoma tissues, and a higher MUC21 expression resulted in poor overall survival in melanoma patients by The Cancer Genome Atlas database analysis. In vitro, MUC21 overexpression markedly promoted proliferative properties and aggressive behavior of melanoma cell A375 and A875, as assessed by Cell Counting Kit-8 and transwell assay. In mechanism, we proved that MUC21 suppressed expression of SLITRK5, an integral membrane protein, leading to activation of prosurvival hedgehog pathway and sustained melanoma development. More importantly, we found that combination of hedgehog pathway inhibitor cyclopamine and chemotherapy revealed an improved anticancer effect in MUC21 overexpression xenograft model. Altogether, our study described a novel role of MUC21 in regulating tumor progression, which offers a promising target for melanoma diagnosis and therapy.

Background A growing body of evidence shows that E2F transcription factors play a significant role in the tumorigenesis of prostate cancer. However, their functional and prognostic value has not been fully illustrated. Therefore, we used bioinformatics methods to further analyze the possible roles of E2F transcription factors in the development and progression of prostate cancer. Methods We explored the expression levels of E2F transcription factors using data from The Cancer Genome Atlas (TCGA) and Oncomine database in paired and unpaired samples. The clinical correlation and prognostic value of E2F transcription factors were assessed. Using the R package “pROC”, we judged the diagnostic value of E2F transcription factors. The online website tool cBioPortal was also employed to find possible gene alterations of E2F transcription factors in samples from TCGA. The R package “clusterprofiler” was used to conduct functional analysis. Moreover, we also used the Tumor Immune Estimation Resource to search for the associations between E2F transcription factors and the infiltration levels of 6 kinds of immune cells. Finally, quantitative real-time polymerase chain reaction (PCR) was conducted to validate the expression levels of E2F transcription factors in human paired prostate tissues. Results E2F1/2/3/5 messenger RNA (mRNA) expression levels were higher in prostate cancer tissues than in normal tissues, while E2F4 and E2F6 mRNA expression levels were lower (P

Renal cancer is one of the most common urogenital tumors worldwide. Although numerous traditional and relatively new therapeutic strategies have been adopted for clear cell renal cell carcinoma (ccRCC) patients, their effects are not satisfactory enough for the improvement of patients. The pathogenesis and progression of ccRCC requires further investigations.Using a series of bioinformatic analyses, the expression levels, clinical relevance, and prognostic potential of FUT11 as well as its correlations with immune cells in ccRCC were investigated. The mRNA and protein expression levels of FUT11 in renal cancer cell lines and human tissues were determined using quantitative real-time-polymerase chain reaction (RT-PCR) and Western blot analyses. MTT, colony formation, Edu, and wound healing assays were performed to explore the function of FUT11 in renal cancer cell lines. The immunohistochemical staining of human and mouse tissues was performed to reveal the correlations between the expression levels of FUT11 and the infiltration level of immune cell subtypes. Using mouse xenograft models, the role of FUT11 was further investigated in-vivo.The data mining and corresponding analyses indicated that the expression levels of FUT11 were elevated in renal cancer and independently correlated with the prognosis of ccRCC patients. The cibersort and ssGSEA algorithms revealed differential infiltration levels of immune cells between the patients with distinct expression levels of FUT11; these results were verified by the consequent human renal cancer tissues and animal models. The MTT, colony formation, EdU, and wound healing assays showed that the decreased expression level of FUT11 could promote the proliferation and migration of renal cancer cell lines. The animal models-based analysis showed similar results.In conclusion, this study identified a novel important molecule correlated with the prognosis of ccRCC patients and revealed its immune-related role and its function in the proliferation and migration of renal cancer cells. This study might provide a novel basis for the treatment of renal cancer.

Bladder cancer is one of the most prevalent kinds of cancer worldwide, and resistance to gemcitabine is a major problem for patients. The pathogenesis of bladder cancer and mechanism of resistance to chemotherapy remain to be explored. Through bioinformatics analysis, we first found that NXPH4 was independently related to the prognosis of patients with bladder cancer. Through wound healing assays, transwell invasion assays, and plate clone formation assays, we found that NXPH4 promoted the proliferation, migration, and invasion of bladder cancer cells. The induced gemcitabine resistance cell line also showed a higher expression of NXPH4. A glycolytic activity assay demonstrated that the expression of NXPH4 was positively related to glycolysis. A higher level of reactive oxygen species caused by enhanced levels of NXPH4 was found in gemcitabine-resistant cell lines. NDUFA4L2, glycolysis, and reactive oxygen species were shown to be essential for NXPH4-regulated functions through rescue assays in cell lines. The roles of NXPH4-regulated glycolysis, gemcitabine resistance, and NDUFA4L2 were validated in vivo as well. Our results imply that NXPH4 contributes to the proliferation, migration, and invasion of bladder cancer by maintaining the stability of NDUFA4L2 and consequently activating reactive oxygen species and glycolysis.

This paper studies the joint effect of borrowing and short-sale constraints under heterogeneous beliefs and risk aversions. Although the constraints never simultaneously bind in equilibrium, interesting economics emerge in the anticipatory effects of potentially future binding constraints. In particular, the risk-free rate and Sharpe ratio experience endogenous jumps at a critical state, where two equilibria coexist. Moreover, a short-sale ban can lead to a lower stock price and higher volatility depending on the relative tightness between the constraints, and tightening the borrowing constraint during a short-sale ban can also make returns more volatile. (JEL G11, G12)

Prostate cancer (PCa) is one of the most common malignant diseases in male worldwide, yet, the molecular mechanisms involved in PCa progression are still poorly understood. This study aimed to investigate the roles of the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) pathway in PCa progression. It was demonstrated by immunohistochemical analysis that both BDNF and TrkB were overexpressed in PCa tissues and elevated TrkB expression was tightly related with lymph node metastasis and advanced stage of PCa. In vitro studies showed that stimulation with rhBDNF or overexpression of TrkB in PCa cells promoted cell migration, invasion, and anoikis resistance. Overexpression of TrkB also resulted in epithelial-mesenchymal transition (EMT)-like transformation in cell morphology, whereas RNA interference-mediated TrkB depletion caused reversion of EMT. Further investigation demonstrated that protein kinase B (AKT) was responsible for BDNF/TrkB signaling-induced pro-migratory and pro-invasive effects, EMT, and anoikis resistance. Finally, in vivo studies confirmed that enhanced TrkB expression facilitated tumor growth, whereas downregulation of TrkB suppressed tumor growth. Our findings illustrate that BDNF/TrkB pathway is crucial for PCa progression, which may provide a novel therapeutic strategy for the treatment of advanced PCa.

The contents of both water and rock particles are important factors affecting the mechanical strength of a soil–rock mixture (SRM) filled subgrade in the western mountainous area of China. Therefore, the purpose of this paper is to study the mechanisms of reconstituted landslide deposit samples with different water and rock particle contents by analysing the characteristics of shear strength, volumetric strain and ‘jumping’ phenomenon via large-scale direct shear tests. The results show that the influence of water content on shear strength is greater than the influence of rock particle content under a lower normal stress, and the results are reversed in the case of a higher normal stress. The effect of water content on the equivalent cohesion is bigger, especially for the sample with a high rock particle content. The friction angle of the specimen with same water content increases with the increasing rock particle content, but when the number of rock particles increases to a certain extent, there is a little effect on the friction angle. However, the friction angle decreases with increasing water content at the same rock particle content. Specimens with the same rock particle content change from dilation to compression with increasing water content. Finally, the continuous stage of the ‘intense jumping’ at different water content has been analysed. The ‘jumping’ phenomenon of samples with low water and rock particle content will first strengthen and then weaken the samples with increasing normal stress.

Simple Summary Based on machine learning methods, we constructed a prognostic signature to calculate the survival probability of BLCA and to further investigate the underlying mechanism of the ferroptosis-related signature. We found that the signature was not only correlated with the prognostic value but was also associated with the tumor microenvironment (TME), tumor mutation burden (TMB) and the curative outcomes of both immunotherapy and chemotherapy. Furthermore, we proved the reliability of the signature in some external datasets and built a risk score evaluation nomogram for clinical use. Abstract Ferroptosis has been reported to regulate tumorigenesis, metastasis, drug resistance and the immune response. However, the potential roles of ferroptosis regulators in the advancement of bladder cancer remain to be explored. We systematically evaluated the multidimensional alteration landscape of ferroptosis regulators in bladder cancer and checked if their expression correlated with the ferroptosis index. We used least absolute shrinkage and selection operator regression to form a signature consisting of seven ferroptosis regulator. We confirmed the signature’s prognostic and predictive accuracy with five independent datasets. A nomogram was built to predict the overall survival and risk of death of patients. The relative expression of the genes involved in the signature was also clarified by real-time quantitative PCR. We found the risk score was related to tumor progression and antitumor immunity-related pathways. Moreover, there existed negative association between the relative antitumor immune cell infiltration level and the risk score, and higher tumor mutation burden was found in the group of lower risk score. We used The Tumor Immune Dysfunction and Exclusion database and IMvigor210 cohort having immunotherapy efficacy results to confirm the prediction function of the risk score. Furthermore, the ferroptosis regulator signature could also reflect the chemotherapy sensitivity of bladder cancer.

IntroductionIt’s widely reported the “writer” enzymes mediated RNA adenosine modifications which is known as a crucial mechanism of epigenetic regulation in development of tumor and the immunologic response in many kinds of cancers. However, the potential roles of these writer genes in the progression of bladder cancer (BLCA) remain unclear.Materials and MethodsWe comprehensively described the alterations of 26 RNA modification writer genes in BLCA from the genetic and transcriptional fields and identified writer-related genes from four independent datasets. Utilizing least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression, we constructed a ten writer-related gene signature. After that, we confirmed the predictive and prognostic value of this signature on another six independent datasets and established a nomogram to forecast the overall survival (OS) and mortality odds of BLCA patients clinically.ResultsThe writer-related genes signature showed good performance in predicting the OS for BLCA patients. Moreover, the writer-related gene signature was related to EMT-related pathways and immune characteristics. Furthermore, the immune cell infiltration levels of CD8 T cells, cytotoxic cells, M1/2 macrophage cells and tumor mutation burden might be able to predict which patients will benefit from immunotherapy. This could also be reflected by the writer-related gene signature.ConclusionsThis signature might play an important role in precision individualized immunotherapy. The present work highlights the crucial clinical implications of RNA modifications and may help developing individualized therapeutic strategies for patients with BLCA.

In the memory forensics, the Pool Tag Scanning based on the memory pool tag requires a detailed search of the physical memory when scanning the kernel driver object, which is very inefficient. The object scanning of Windows kernel driver by using the pool tag quick scanning is proposed. The method uses the quick pool tag scanning to reduce the memory range of the scan, and then scan the driver object according to the characteristics of the kernel driver object quickly, to help investigator to determine whether the driver is normal. Experimental results shows that the scanning efficiency for object scanning of kernel driver is improved greatly by using the quick pool tag scanning technology and the time spent in the scanning step is reduced while ensuring the false alarm rate is same.

Mechanical ventilation is extensively adopted in general anesthesia and respiratory failure management, but it can also induce ventilator-induced lung injury (VILI). Therefore, it is of great urgency to explore the mechanisms involved in the VILI pathogenesis, which might contribute to its future prevention and treatment. Four microarray datasets from the GEO database were selected in our investigation, and were subjected to the Weighted Gene Co-Expression Network Analysis (WGCNA) to identify the VILI-correlated gene modules. The limma package in R software was used to identify the differentially expressed genes (DEGs) between the VILI and control groups. WGCNA was constructed by merging the GSE9314, GSE9368, GSE11434 and GSE11662 datasets. A total of 49 co-expression network modules were determined as associated with VILI. The intersected genes between hub genes screened from DEGs for VILI and those identified using WGCNA were as follows: Tlr2, Hmox1, Serpine1, Mmp9, Il6, Il1b, Ptgs2, Fos and Atf3, which were determined to be key genes for VILI. Those key genes were validated by GSE86229 and quantitative PCR (qPCR) experiment to have significantly statistical difference in their expression between the VILI and control groups. In a nutshell, nine key genes with expression differences in VILI were screened by WGCNA by integrating multiple datasets.

Shadow financing through off-balance sheet wealth management products (WMPs) has become increasingly important besides deposits in China. We quantify the economic magnitude of the effect of WMPs on banking stability in an equilibrium model calibrated to Chinese banking sector data. Alternative equilibria emerge, which deviate substantially from the observed banking system and lead to severe financial distress and large welfare losses. Rollover costs from the WMP market and negative shocks to the asset market underlying WMPs can exacerbate banking instability. Moreover, we show that smaller and medium sized banks are comparably relevant for financial stability as the systemically important big 4 banks in China.

Background Prostate cancer (PCa) is a form of malignancy that harms the health status of elderly men worldwide. It is unclear which of radical prostatectomy (RP) or brachytherapy (BT) is the more effective treatment for PCa. This study presents the first highly comprehensive and up-to-date comparative analysis of the overall outcomes of RP versus BT. Methods We conducted a systematic literature search for studies published on PubMed, EMBASE, and the Cochrane Library on the outcomes of RP versus BT in clinically localized PCa. The cumulative analysis was performed using Review Manager Version 5.3 software, and the Chi-square test was employed to test the statistical heterogeneity. The summary odds ratio (OR) and standard mean difference (SMD) was estimated using random effects models at 95% confidence intervals (CIs). Results In total, 2 randomized, 2 prospective, and 21 retrospective comparative studies were included. No significant differences in biochemical recurrence rate (BCR) (OR: 1.24; 95% CI: 0.91, 1.68) and prostate cancer-specific mortality (PCSM) (OR: 1.62; 95% CI: 0.86, 3.04) between RP and BT were noted. With erectile dysfunction and urinary incontinence, BT was more protective than RP in both short-term post-operative reports (OR: 2.06; 95% CI: 1.15, 3.70 and OR: 4.62; 95% CI: 2.33, 9.16) and long-term patient outcome reports (SMD: -5.62; 95% CI: -13.81, 2.57 and SMD: -11.52; 95% CI: -18.32, -4.72). Conclusions BT and RP for PCa therapy pose comparable risks of PCSM and BCR, while BT is associated with a lower incidence of erectile dysfunction and urinary incontinence. This study tentatively confirms that BT is an alternative to RP for patients seeking a curative treatment with minimal risks of urinary incontinence and sexual dysfunction.

Background The dreadful prognosis of nonmuscle invasive bladder cancer mainly results from the delay in recognition of individuals with a high risk of progression. Thus, the emphasis of this work lies in developing valuable biomarkers that is conducive to accurately predicting the progression of NMIBC. Methods Microarray data from GSE32894 including 209 NMIBC samples were performed by weighted gene coexpression network analysis (WGCNA), which could find modules of highly correlated genes and relate modules to external sample traits. Besides, we constructed a protein–protein interaction to facilitate screening the hub gene. At last, we used RNA‐seq and microarray data and clinical information from ArrayExpress (E‐MTAB‐4321) and GSE13507 to select and validate the candidate gene. Results In current paper, blue module of 13 gene coexpression clusters we identified was selected as the key modules. Seven genes namely: CDCA8, CENPF, MCM6, MELK, PRC1, STIL, and TPX2 have been identified as candidate genes. Notably, among them, only elevated CENPF in NIMBC tissue was closely associated with low progression‐free survival (PFS) and overall survival (OS) rate in three datasets and had a large area under receiver operating characteristic (ROC) curve. Finally, CENPF was identified as an effective biomarker in NMIBC. Conclusion Therefore, our findings submit a new progressive and prognostic molecular marker and therapeutic target for NMIBC. Moreover, these genes that deserve to be further researched may improve the comprehension about the occurrence and development of superficial bladder cancer.

Objective: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) in bladder cancer. Methods: We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) values were calculated for both the FISH and urine cytology tests. Results: A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population. A total of 4807 patients with hematuria were prospectively, randomly enrolled for the simultaneous analysis of urine cytology, FISH testing, and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen. Overall, the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%, while that of cytology was 33.4% (p

We study how competition for shadow money impacts banking stability. In our model, banks compete for insured depositors and uninsured shadow money investors and default endogenously. We estimate and calibrate our model to the Chinese banking sector and we find that shadow money investors are run-prone while depositors are not. Multiple equilibria emerge and may lead to severe financial distress with large welfare losses. Negative shocks to assets underlying shadow money amplify financial fragility. Furthermore, rollover costs can cause runs on shadow money. Imposing capital requirements on shadow money improves banking stability, but the effectiveness is limited.

Trust companies generate leverage cycle dynamics by intermediating less regulated credit to the financial markets in China. We find that the leverage factor constructed from trust companies can explain the time-series and cross-sectional asset returns. The leverage factor derived from securities companies does not possess the same explanatory power, despite these companies being legitimate financing sources of leveraged investment. Our results provide new evidence that the financial innovations created by shadow banks significantly amplify leverage in less sophisticated financial markets. This not only affects financial fragility, but also determines asset prices.

The mechanical strength of the landslide deposits directly affects the safety and operation of the roads in the western mountainous area of China. Therefore, the research is aimed at studying the mechanisms of a landslide deposit sample with different rock particle contents by analyzing its characteristics of the stress-strain behavior, the “jumping” phenomenon, the volumetric strain, and the shear strength parameters via a large-scale direct shear test. Stress-strain results show that stress-strain curves can be divided into 3 different stages: liner elastic stage, yielding stage, and strain-hardening stage. The shear strength of SRM behaves more like “soil” at a lower rock particle content and behaves more like “rock joints” at a higher rock particle content. Characteristics of the “jumping” phenomenon results show that the “intense jumping” stage becomes obvious with the increasing rock particle content and the normal stress. However, the lower the rock particle content is, the more obvious the “jumping” phenomenon under the same normal stress is. Volumetric strain results show that the sample with a lower rock particle content showed a dilatancy behavior under the low normal stress and shrinkage behavior under the high normal stress. The dilatancy value becomes smaller with the increasing normal stress. The maximum shear stress value of the rock particle content corresponds to the maximum value of dilatancy or shrinkage. We also conclude that the intercept of the Mohr failure envelope of the soil-rock mixture should be called the “equivalent cohesion,” not simply called the “cohesion.” The higher the normal stress and rock particle content are, the bigger the equivalent cohesion and the internal friction angle is.

In order to explore the viscoelastic properties of waste engine oil (WEO) on mixed asphalt, mixed asphalt was prepared by fusing base asphalt and aged asphalt. The effect of waste engine oil content on the physical and viscoelastic properties of asphalt mixtures was studied through experiments. The test results show that the viscosity and softening point of asphalt mixture is reduced by adding waste engine oil. The complex modulus (G*) of asphalt binder decreases with the addition of waste oil at different test frequencies. With the increase of waste oil content, the phase angle (ä) of asphalt mixtures increases at specific frequencies. When the content of waste oil exceeds 6%, G* and δ will not change significantly. The stiffness increase caused by ageing asphalt in mixed asphalt will be offset by adding 2-4% waste oil. This indicates that waste oil can be used as regenerant to provide elasticity and flexibility for asphalt binder.

Renal cell carcinoma (RCC) is the most common solid neoplasm of adult kidney, and the major treatment for metastatic RCC (mRCC) is molecular targeted therapy. Sorafenib, as a multi-targeted tyrosine kinase inhibitor (TKI), has significantly improved clinical outcomes of mRCC patients. However, complete or long-term remissions are rarely achieved due to intolerance to dose-related adverse effects. It is therefore, necessary to explore novel target molecules for treatment or to enhance the therapeutic efficiency of present TKI for mRCC treatment. Anoikis is a specific type of apoptosis that plays a vital physiological role in regulating tissue homoeostasis. Anoikis-resistance is of critical importance for metastasis of various human cancers including mRCC. However, the precise mechanisms on anoikis-resistance in mRCC are still unclear. Tyrosine receptor kinase B (TrkB) belongs to the Trk family of neurotrophin receptors. Previous investigations have implied that activation or overexpression of TrkB promoted proliferation, survival, angiogenesis, anoikis-resistance and metastasis in human cancers. Yet, the correlation between TrkB and anoikis-resistance in mRCC has rarely been reported. The aim of the present study was to explore the impact of TrkB on anoikis-resistance and targeted therapy in mRCC. Our data revealed that anoikis-resistant ACHN cells presented with tolerance to detachment-induced apoptosis, excessive proliferation and aggressive invasion, accompanied by upregulation of TrkB expression in contrast to parental cells. Furthermore, TrkB silencing caused apoptosis, inhibited proliferation, retarded invasion as well as improved anticancer efficiency of sorafenib in anoikis-resistant ACHN cells through inactivation of PI3K/Akt and MEK/ERK pathways. Our data may offer a novel potential therapeutic strategy for mRCC.

Oleanolic acid (OA) is a naturally occurring pentacyclic triterpenoid and possesses diverse pharmacological activities, including anti-cancer effects that have been confirmed in multiple types of human cancers. However, the potential effect of natural OA on human prostate cancer is still unclear. The present study aimed to explore whether and how OA exerted anti-cancer effects in prostate cancer. Our data showed that OA inhibited cell viability and proliferation, and promoted cell apoptosis and G0/G1 phase cell cycle arrest in prostate cancer PC-3, DU145, and LNCaP cells, in a dose-dependent manner. In addition, OA was found to regulate the expression levels of apoptosis-related and cell cycle-related proteins, as well as the activity of PI3K/Akt pathway, in a dose-dependent manner. Mechanistically, our data revealed that OA exerted anti-cancer effects in vitro in PC-3 and DU145 cells by repressing the PI3K/Akt pathway. In agreement, OA also suppressed the tumor growth of PC-3 cells in vivo via inhibition of the PI3K/Akt pathway. In conclusion, our findings demonstrate the anti-cancer properties of OA in prostate cancer cells, both in vitro and in vivo, and provide the experimental evidence for the use of OA as an adjuvant agent for prostate cancer patients.

Trust companies generate leverage cycle dynamics by intermediating less regulated credit to the financial markets in China. We find that the leverage factor constructed from trust companies can explain the time-series and cross-sectional asset returns. The leverage factor derived from securities companies does not possess the same explanatory power, despite these companies being legitimate financing sources of leveraged investment. Our results provide new evidence that the financial innovations created by shadow banks significantly amplify leverage in less sophisticated financial markets. This not only affects financial fragility, but also determines asset prices.

This paper studies the joint effect of borrowing and short-sale constraints under heterogeneous beliefs and risk aversions. Although the constraints never bind simultaneously in equilibrium, there is interesting economics in the anticipatory effects of potentially future binding constraints. In particular, the risk-free rate and Sharpe ratio experience endogenous jumps at a critical state, where two equilibria co-exist. Moreover, a short-sale ban can lead to a lower stock price and higher volatility depending the relative tightness between the constraints, and tightening the borrowing constraint during a short-sale ban can also make returns more volatile.

Lysine-specific demethylase 1 (LSD1) is the first defined histone demethylase, and was found to be closely correlated with the development and progression of various types of cancers, including prostate cancer (PCa). Previous research suggests that LSD1 is closely related with cell proliferation, angiogenesis, migration and invasion in PCa. However, it remains to be elucidated whether LSD1 is correlated with androgen-independent (AI) transition of PCa under androgen-ablated conditions. The present study aimed to investigate the correlation of LSD1 expression with AI transition of human androgen-dependent PCa LNCaP cells. Our data showed that LSD1 was overexpressed in human PCa specimens and in AI PCa LNCaP-AI cells, which were established through a three-month continuous culture of LNCaP cells in androgen-deprived medium. Under androgen-deprived conditions, LNCaP-AI cells grew perfectly with less apoptosis and G0/G1 cell cycle arrest. Overexpression of LSD1 protected the LNCaP cells from androgen deprivation-induced apoptosis and G0/G1 arrest, while knockdown of LSD1 drove LNCaP-AI cells into a higher rate of apoptosis and G0/G1 arrest. Furthermore, LSD1 was found to regulate the androgen receptor (AR) and p53 signaling pathways via demethylation, subsequently influencing apoptosis and cell cycle progression. These findings revealed that overexpression of LSD1 promoted AI transition of PCa LNCaP cells under androgen-ablated conditions via activation of the AR signaling pathway and suppression of the p53 signaling pathway.

The purpose of the present study is to investigate urodynamic characteristics of rats with detrusor instability (DI) induced by different causes. Forty-eight adult female Sprague-Dawly rats were randomly divided into 4 groups: cyclophosphamide group, bladder outlet obstruction group, lipopolysaccharide group and control group. The BL-410 model bio-function experimental system was applied to monitor bladder pressure and a number of urodynamic parameters were recorded and calculated, including the frequency of detrusor instability, maximum voiding pressure (MVP), maximum cystometric capacity (MCC), intercontraction interval (ICI), voiding time (VT), postvoid residual (PVR) and bladder compliance (BC). The positive rates of DI in cyclophosphamide group, bladder outlet obstruction group and lipopolysaccharide group were 83.33%, 75.00% and 58.33%, respectively. And correspondingly the frequency of DI was 10.00?2.00, 4.87?1.24 and 3.50?1.00tmin-1, which was significantly higher than those of the control group (P

© 2016 Informa UK Limited, trading as Taylor & Francis Group. For a firm financed by a mixture of collateralized (short-term) debt and uncollateralized (long-term) debt, we show that fluctuations in margin requirements, reflecting funding liquidity shocks, lead to increasing the firm’s default risk and credit spreads. The severity with which a firm is hit by increasing margin requirements highly depends on both its financing structure and debt maturity structure. Our results imply that an additional premium should be added when evaluating debt in order to account for rollover risks, especially for short-matured bonds. In terms of policy implications, our results strongly indicate that regulators should intervene fast to curtail margins in crisis periods and maintain a reasonably low margin level in order to effectively prevent creditors’ run on debt.

Autophagy is an evolutionarily conserved catabolic process in eukaryotic cells, which allows cells to overcome a wide array of of stresses and has recently been shown to result in drug resistance. This study examined the effect of autophagy on oleanolic acid (OA)-induced cytotoxicity against bladder cancer cells. Our study demonstrated that OA inhibited cell viability, proliferation, and induced apoptosis in bladder cancer lines T24 and EJ. Furthermore, OA induced autophagy in both cell lines by activating AMP-activated protein kinase (AMPK), inhibiting mechanistic target of rapamycin (mTOR) and promoting unc-51 like autophagy activating kinase 1 (ULK1). Moreover, inhibiting autophagy by siRNA to autophagy related 7 (ATG7) or with autophagy inhibitor bafilomycin A1 and 3-methyladenine (3-MA) or AMPK inhibitor dorsomorphin (compound C) promoted OA-induced deaths of bladder cancer cells. In contrast, either autophagy activator rapamycin or AMPK activator acadesine (AICAR) compromised OA-induced anti-cancer effect. Our findings suggested that OA induced protective autophagy through AMPK-mTOR-ULK1 signaling pathway in bladder cancer cells and OA in combination with autophagy inhibitor might be a novel alternative for the treatment of bladder cancer.

Objective: To assess the impact of Doxazosin Oral Intake Therapy on urinary symptoms and pain in patients with indwelling ureteral stents Patients and Methods: A total of 239 patients with ureteral stone-related hydronephrosis who underwent a double-J stent insertion after ureteroscopic lithotripsy were enrolled. Patients were randomized to receive doxazosin cotrolled release 4 mg once daily for 4 weeks or matching placebo. Patients completed the brief-form Chinese version Ureteric Stent Symptom Questionnaire (USSQ) and quality of life (QoL) score 2 weeks and 4 weeks after stent placement and 4 weeks after stent withdrawal. The analgesic use was also recorded during the stenting period. Results: Patients in Doxazosin Oral Intake Therapy group, in the first 2 weeks and second 2 weeks with the stent in situ, expressed significant lower daytime frequency (p=0.028 and p=0.038), nocturia (p=0.021 and p=0.008) and urgency (p=0.012 and p=0.014), respectively. Similarly, flank pain score, QoL score and analgesic use were also significant less in the stenting period. There was no significant difference in scores of urinary symptoms, pain and QoL during the post-stent period between two cohorts. Conclusions: Doxazosin Oral Intake Therapy reduced stent-related urinary symptoms, pain and the negative impact on QoL.

Prostate cancer is one of the most common malignancies in adult males and metastasis is the leading cause of death cases without satisfactory treatment options. Anoikis-resistance and migration are crucial aspects for the metastasis of various human cancer cells including prostate cancer and L -thyroxin (T 4 ) has been proved to play vital roles in tumor metastasis. The present study demonstrated that T 4 promoted migration and depressed detachment-induced apoptosis in anoikis-resistant prostate cancer cells while tetraiodothyroacetic acid (tetrac), a competitive antagonist of T 4 at integrin αvβ3, reversed T 4 induced effects through diminishing expressions of XIAP, MMP-2, VEGF together with inhibited activity of MAPK/ERK pathway. In addition, we illustrated that over-expression of transthyretin (TTR) was positively correlated to the progression and metastatic potential in prostate cancer. Similar to tetrac, TTR silencing also inverted T 4 mediated bioeffects on anoikis-resistant PC-3 cells. The current study sheds light on novel therapeutic strategies for metastatic prostate cancer. Implications This study identified novel compound and target for preventing metastasis in anoikis-resistant prostate cancer cells, which might offer potential therapeutic alternatives for advanced prostate cancer.

We study how margin requirements in the collateralized borrowing affect banks’ risk exposure. In a model where a firm’s asset value and margin requirement follow correlated geometric Brownian motions, we derive analytic expressions for firm’s default probability and debt value. Our results show that variations in margin requirements, reflecting funding liquidity shocks in the short-term collateralized lending market, can lead to a significant increase in firms’ default risks, in particular for those firms heavily relying on short-term collateralized borrowing. Moreover, our results imply that reducing margin in liquidity crises can be very effective to restore market lending confidence.