Prostate cancer (PCa) is one of the most common malignancies in men; recently, PCa-related mortality has increased worldwide. Although androgen deprivation therapy (ADT) is the standard treatment for PCa, patients often develop aggressive castration-resistant PCa (CRPC), indicating the presence of an alternative source of androgen. Clostridium scindens is a member of the gut microbiota and can convert cortisol to 11β-hydroxyandrostenedione (11β-OHA), which is a potent androgen precursor. However, the effect of C. scindens on PCa progression has not been determined. In this study, androgen-dependent PCa cells (LNCaP) were employed to investigate whether C. scindens-derived metabolites activate androgen receptor (AR), which is a pivotal step in the development of PCa. Results showed that cortisol metabolites derived from C. scindens-conditioned medium promoted proliferation and enhanced migration of PCa cells. Furthermore, cells treated with these metabolites presented activated AR and stimulated AR-regulated genes. These findings reveal that C. scindens has the potential to promote PCa progression via the activation of AR signaling. Further studies on the gut-prostate axis may help unravel an alternative source of androgen that triggers CRPC exacerbation.

Prostate cancer (PCa) is a major diagnosed cancer among men globally, and about 20% of patients develop metastatic prostate cancer (mPCa) in the initial diagnosis. PCa is a typical androgen-dependent disease; thus, hormonal therapy is commonly used as a standard care for mPCa by inhibiting androgen receptor (AR) activities, or androgen metabolism. Inevitably, almost all PCa will acquire resistance and become castration-resistant PCa (CRPC) that is associated with AR gene mutations or amplification, the presence of AR variants, loss of AR expression toward neuroendocrine phenotype, or other hormonal receptors. Treating CRPC poses a great challenge to clinicians. Research efforts in the last decade have come up with several new anti-androgen agents to prolong overall survival of CRPC patients. In addition, many potential targeting agents have been at the stage of being able to translate many preclinical discoveries into clinical practices. At this juncture, it is important to highlight the emerging strategies including small-molecule inhibitors to AR variants, DNA repair enzymes, cell survival pathway, neuroendocrine differentiation pathway, radiotherapy, CRPC-specific theranostics and immune therapy that are underway or have recently been completed.

以文化人是高校促进少数民族人才培养质量提升的重要实践方向.时代变革背景下,少数民族大学生面临诸多发展的新问题和新挑战.对此,应当以思想道德塑造为内核,以知识文化传授为基础,以审美文化涵育为追求,以制度文化建设为保障,不断提升以文化人在少数民族大学生人才培养中的针对性和实效性.

作为与人生相伴而行的教育,美育与思想政治教育在价值导向、育人目标、教育内容上相辅相成.在以媒介融合为鲜明特征的网络时代,将美育引入高校网络思想政治工作,可以丰富高校网络思想政治教育的方式和内容,提升高校思想政治教育工作的针对性和实效性,促进大学生全面发展.

The film stiffness of dry gas seal must be sufficient to keep gas film stable at high and low speed. A generalized geometric model based on triangles is proposed to characterize spiral grooves. A mathematical model is established and solved using the finite-difference method to obtain steady performance. The optimum spiral grooves for maximum opening force and film stiffness are obtained at low speed, and their steady performance is compared with conventional spiral grooves numerically and experimentally. The pressure and flow field of optimum spiral grooves and conventional spiral grooves are simulated to reveal the mechanism of the performance difference. Results show that through-combined spiral grooves outperform the other derived spiral grooves. Their film stiffness is up to 15% larger than that of conventional spiral grooves at low speed.

The receptor for advanced glycation end products (RAGE) interacts with various molecules in the cell membrane to induce an inflammatory response. The cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Amongst, CdtA and CdtC interact with membrane lipid rafts, by which CdtB enters the nucleus to induce pathogenesis. In this study, we first explored the relationships between RAGE, lipid rafts, and inflammation in gastrointestinal epithelial cells exposed to CDT. Our results showed that CDT activated the expression of RAGE and high mobility group box 1 (HMGB1), followed by the recruitment of RAGE into lipid rafts. In contrast, RAGE antagonist inhibited CDT-induced inflammation via the RAGE-HMGB1 axis. Disruption of lipid rafts decreased CDT-induced downstream signaling, which in turn attenuated the inflammatory response. Furthermore, in vivo studies revealed severe inflammation and upregulation of RAGE and IL-1β in the intestinal tissues of CDT-treated mice. These results demonstrate that mobilization of RAGE to lipid rafts plays a crucial role in CDT-induced inflammation.

A subpopulation of cancer stem cells (CSCs) plays a critical role of cancer progression, recurrence, and therapeutic resistance. Many studies have indicated that castration-resistant prostate cancer (CRPC) is associated with stem cell phenotypes, which could further promote neuroendocrine transdifferentiation. Although only a small subset of genetically pre-programmed cells in each organ has stem cell capability, CSCs appear to be inducible among a heterogeneous cancer cell population. However, the inductive mechanism(s) leading to the emergence of these CSCs are not fully understood in CRPC. Tumor cells actively produce, release, and utilize exosomes to promote cancer development and metastasis, cancer immune evasion as well as chemotherapeutic resistance; the impact of tumor-derived exosomes (TDE) and its cargo on prostate cancer (PCa) development is still unclear. In this study, we demonstrate that the presence of Cav-1 in TDE acts as a potent driver to induce CSC phenotypes and epithelial–mesenchymal transition in PCa undergoing neuroendocrine differentiation through NFκB signaling pathway. Furthermore, Cav-1 in mCRPC-derived exosomes is capable of inducing radio- and chemo-resistance in recipient cells. Collectively, these data support Cav-1 as a critical driver for mCRPC progression.

为探求现阶段高职院校辅导员职业认同的现状特点,编订高职院校辅导员职业认同问卷,对10所高职院校的382名辅导员进行调研,发现现今高职院校辅导员的职业认同水平不高;高职院校辅导员职业认同在学历、学校类型、编制类型、职称、工龄上具有显著差异;高职院校辅导员职业认同在性别上无显著差异.

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in the western world, and the mortality rate from PCa in Asia has been increasing recently. Statins are potent inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and are commonly used for treating hyperlipidemia, with beneficial effects for cardiovascular disease and they also exhibit anti-cancer activity. However, the protective effects of statins against PCa are controversial. In this study, we investigated the effect of two types of statins (simvastatin and lovastatin) and the mortality rate of PCa patients by using the Taiwan National Health Insurance Research Database (NHIRD). A total of 15,264 PCa patients with hyperlipidemia records and medical claims from the Registry of Catastrophic Illness were enrolled. The patients were divided into two cohorts based on their statin use before the diagnosis of PCa: statin users (n = 1,827) and non-statin users (n = 1,826). The results showed that patients who used statins exhibited a significantly reduced risk of mortality from PCa [adjusted hazard ratio (HR) = 0.84, 95% CI = 0.73-0.97]. Analysis of the cumulative defined daily dose (DDD) indicated that patients who were prescribed simvastatin ≥ 180 DDD had a dramatically decreased risk of death from PCa (adjusted HR = 0.63; 95% CI = 0.51-0.77). This population-based cohort study demonstrated that statin use significantly decreased the mortality of PCa patients, and that this risk was inversely associated with the cumulative DDD of simvastatin therapy. The results of this study revealed that statins may be used for drug repositioning and in the development of a feasible approach to prevent death from PCa.

Because of great axial vibration of the rotor system, dry gas seal has a big film thickness disturbance, which may cause contact rubbing of seal faces or excessive leakage. Focusing on this problem, experimental studies on transient-state film thickness and leakage rate of a spiral groove dry gas seal at high-speeds are carried out under different spring pressures and different spiral groove depths. And the experimental results of film thickness disturbance and average leakage rate are predicted by perturbation method and gas lubrication theory. Results show that the theoretical results of variation trends of film thickness disturbance amplitudes coincide well with the experimental data, and it also represents that the perturbation method is an effective forecasting method in dynamic analysis.

Cholesterol-α-glucosyltransferase (CGT) encoded by the type 1 capsular polysaccharide biosynthesis protein J (capJ) gene of Helicobacter pylori converts cellular cholesterol into cholesteryl glucosides. H. pylori infection induces autophagy that may increase bacterial survival in epithelial cells. However, the role of H. pylori CGT that exploits lipid rafts in interfering with autophagy for bacterial survival in macrophages has not been investigated. Here, we show that wild-type H. pylori carrying CGT modulates cholesterol to trigger autophagy and restrain autophagosome fusion with lysosomes, permitting a significantly higher bacterial burden in macrophages than that in a capJ-knockout (∆CapJ) mutant. Knockdown of autophagy-related protein 12 impairs autophagosome maturation and decreases the survival of internalised H. pylori in macrophages. These results demonstrate that CGT plays a crucial role in the manipulation of the autophagy process to impair macrophage clearance of H. pylori.

Radiotherapy is one of the most common treatment options for local or regional advanced prostate cancer (PCa). Importantly, PCa is prone to radioresistance and often develops into malignancies after long-term radiotherapy. Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, possesses pharmacological efficacy against various cancer types; however, its therapeutic potential requires comprehensive exploration, particularly in radioresistant PCa cells. In this study, we emphasized the effects of antrocin on radioresistant PCa cells and addressed the molecular mechanism underlying the radiosensitization induced by antrocin. Our results showed that a combination treatment with antrocin and ionizing radiation (IR) synergistically inhibited cell proliferation and induced apoptosis in radioresistant PCa cells. We further demonstrated that antrocin downregulated PI3K/AKT and MAPK signaling pathways as well as suppressed type 1 insulin-like growth factor 1 receptor (IGF-1R)-mediated induction of β-catenin to regulate cell cycle and apoptosis. Using xenograft mouse models, we showed that antrocin effectively enhanced radiotherapy in PCa. Our study demonstrates that antrocin sensitizes PCa to radiation through constitutive suppression of IGF-1R downstream signaling, revealing that it can be developed as a potent therapeutic agent to overcome radioresistant PCa.

Cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB) and, consequently, cell cycle arrest at the G2/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa). However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR). In this study, we further demonstrated that CDT suppresses the IR-induced autophagy pathway in PCa cells by attenuating c-Myc expression and therefore sensitizes PCa cells to radiation. We further showed that CDT prevents the formation of autophagosomes via decreased high-mobility group box 1 (HMGB1) expression and the inhibition of acidic vesicular organelle (AVO) formation, which are associated with enhanced radiosensitivity in PCa cells. The results of this study reveal the detailed mechanism of CDT for the treatment of radioresistant PCa.

高校文化活动建设要把校园文化从抽象的意识形态方向向具象的品牌建设方向发展.高校势必重视校园文化活动的创新发展,通过科学的组织领导机制、有效的物质保障机制、合理的考核评价机制、有效的导向激励机制、推动运行的动力机制和统一协调的运行机制创造本校特色的新成果.

校园文化品牌建设要求有科学的运行机制及有效策略.本文以当代校园文化品牌建设面临的问题为背景,以中国药科大学"远志"综合素质提升计划项目为例,探讨校园文化品牌建设的运行机制、建设原则、建设路径及高校校园文化建设品牌的载体培育.

This paper puts forward dry gas seals with novel face grooves that are called as hyperelliptic curve grooves. At high PV value, gas film dynamic characteristic coefficients isoline distributions are obtained under the different polar angle and hyperelliptic coefficient. Disturbance behaviors of gas film thickness and pressure are studied whether there is angular excitation or not. Saltation peak and period peak are defined, and their isoline distributions are presented which reveal the influence mechanism of gas film dynamic characteristics coefficients on dynamic tracking property. A dynamic wedge-shaped gap with a fixed angle between seal faces will form under the influence of angular excitation, and it has a significant impact on transient behaviors of the dry gas seals.

The dry gas seal(DGS) has been widely used in high parameters centrifugal compressor, but the intense vibrations of shafting, especially in high-speed condition, usually result in DGS’s failure. So the DGS’s ability of resisting outside interference has become a determining factor of the further development of centrifugal compressor. However, the systematic researches of which about gas film disturbance characteristics of high parameters DGS are very little. In order to study gas film disturbance characteristics of high-speed and high-pressure spiral groove dry gas seal(S-DGS) with a flexibly mounted stator, rotor axial runout and misalignment are taken into consideration, and the finite difference method and analytical method are used to analyze the influence of gas film thickness disturbance on sealing performance parameters, what’s more, the effects of many key factors on gas film thickness disturbance are systematically investigated. The results show that, when sealed pressure is 10.1MPa and seal face average linear velocity is 107.3 m/s, gas film thickness disturbance has a significant effect on leakage rate, but has relatively litter effect on open force; Excessively large excitation amplitude or excessively high excitation frequency can lead to severe gas film thickness disturbance; And it is beneficial to assure a smaller gas film thickness disturbance when the stator material density is between 3.1 g/cm 3 to 8.4 g/cm 3 ; Ensuring sealing performance while minimizing support axial stiffness and support axial damping can help to improve dynamic tracking property of dry gas seal. The proposed research provides the instruction to optimize dynamic tracking property of the DGS.

Cytolethal distending toxin (CDT), a genotoxin produced by Campylobacter jejuni, is composed of three subunits: CdtA, CdtB, and CdtC. CdtB is a DNase that causes DNA double-strand breaks (DSB) in the nucleus resulting in cell cycle arrest at the G2/M stage and apoptosis. CdtA and CdtC bind to cholesterol-rich microdomains on the cytoplasmic membrane, a process required for the delivery of CdtB to cells. Although a unique motif associated with cholesterol-binding activity has been identified in other pathogens, the mechanism underlying the interaction between the CdtA and CdtC subunits and membrane cholesterol remains unclear. Also, the processes of cell uptake and delivery of CdtB in host cells and the translocation of CdtB into the nucleus are only partially understood. In this review, we focus on the underlying relationship among CDT, membrane cholesterol, and the intracellular trafficking pathway as a unique mechanism for C. jejuni-induced pathogenesis. Moreover, we discuss the clinical aspects of a possible therapeutic application of CDT in cancer therapy. Understanding the molecular mechanism of CDT-host interactions may provide insights into novel strategies to control C. jejuni infection and the development of potential clinical applications of CDT.

Gastric cancer is the second leading cause of cancer-related death worldwide. The correlation of Helicobacter pylori and the etiology of gastric cancer was substantially certain. Cholesterol-rich microdomains (also called lipid rafts), which provide platforms for signaling, are associated with H. pylori-induced pathogenesis leading to gastric cancer. Patients who have been prescribed statins, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, have exhibited a reduced risk of several types of cancer. However, no studies have addressed the effect of statins on H. pylori-associated gastric cancer from the antineoplastic perspective. In this study, we showed that treatment of gastric epithelial cells with simvastatin reduced the level of cellular cholesterol and led to attenuation of translocation and phosphorylation of H. pylori cytotoxin-associated gene A (CagA), which is recognized as a major determinant of gastric cancer development. Additionally, a nationwide case-control study based on data from the Taiwanese National Health Insurance Research Database (NHIRD) was conducted. A population-based case-control study revealed that patients who used simvastatin exhibited a significantly reduced risk of gastric cancer (adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.70-0.83). In patients exhibiting H. pylori infection who were prescribed simvastatin, the adjusted OR for gastric cancer was 0.25 (95% CI = 0.12-0.50). Our results combined an in vitro study with a nationwide population analysis reveal that statin use might be a feasible approach to prevent H. pylori-associated gastric cancer.