Single-cell transcriptome profiling implicates the psychological stress-induced disruption of spermatogenesis.

Male infertility has emerged as a global issue, partly attributed to psychological stress. However, the cellular and molecular mechanisms underlying the adverse effects of psychological stress on male reproductive function remain elusive. We created a psychologically stressed model using terrified-sound and profiled the testes from stressed and control rats using single-cell RNA sequencing. Comparative and comprehensive transcriptome analyses of 11,744 testicular cells depicted the cellular landscape of spermatogenesis and revealed significant molecular alterations of spermatogenesis suffering from psychological stress. At the cellular level, stressed rats exhibited delayed spermatogenesis at the spermatogonia and pachytene phases, resulting in reduced sperm production. Additionally, psychological stress rewired cellular interactions among germ cells, negatively impacting reproductive development. Molecularly, we observed the down-regulation of anti-oxidation-related genes and up-regulation of genes promoting reactive oxygen species (ROS) generation in the stress group. These alterations led to elevated ROS levels in testes, affecting the expression of key regulators such as ATF2 and STAR, which caused reproductive damage through apoptosis or inhibition of testosterone synthesis. Overall, our study aimed to uncover the cellular and molecular mechanisms by which psychological stress disrupts spermatogenesis, offering insights into the mechanisms of psychological stress-induced male infertility in other species and promises in potential therapeutic targets.

Cell apoptosis in the testis of male rats is elevated by intervention with ß-endorphin and the mu opioid receptor.

ß-endorphin (ß-EP) is involved in the regulation of male germ cells; however, little is known about the effect of ß-EP on primary germ cells via opioid receptors. In this study, we first revealed significant cell apoptosis in the testis of male rats after ß-EP intervention. Subsequently, the expression of the mu opioid receptor (MOR) was detected in both Leydig cells (LCs) and spermatogonia (SGs) by fluorescence colocalization; overlapping signals were also detected in apoptotic cells. In addition, LCs and SGs were separated from the testis of male rats and primary cells were treated with ß-EP; this increased the mRNA levels of MOR and was accompanied by acute cell apoptosis. Our findings provide a foundation for the further study of apoptosis in reproductive cells regulated by ß-EP and the MOR receptor.

Dry Friction Properties of Diamond-Coated Silicon Carbide.

Dry friction between seal faces, caused by unstable or extreme operating conditions, significantly affects the running stability and service life of mechanical seals. Therefore, in this work, nanocrystalline diamond (NCD) coatings were prepared on the surface of silicon carbide (SiC) seal rings by hot filament chemical vapor deposition (HFCVD). The friction test results under dry environment reveals that the coefficient of friction (COF) of SiC-NCD seal pairs is about 0.07-0.09, which were reduced by 83-86% compared to SiC-SiC seal pairs. The wear rate of SiC-NCD seal pairs is relatively low, ranging from 1.13 × 10-7 mm3/N·m to 3.26 × 10-7 mm3/N·m under different test conditions, which is due to the fact that the NCD coatings prevent adhesive and abrasive wear between the SiC seal rings. The analysis and observation of the wear tracks illustrate that the excellent tribological performance of the SiC-NCD seal pairs is due to a self-lubricating amorphous layer formed on the worn surface. In conclusion, this work highlights a pathway to enable mechanical seals to satisfy the high application requirements under highly parametric working conditions.

Tropisetron Ameliorated Cyclophosphamide-Induced Hemorrhagic Cystitis via Restraining TLR-4/NF-κB and JAK1/STAT3 Signaling Pathways.

OBJECTIVE: The main pathological changes of hemorrhagic cystitis (HC) are bladder inflammation, bladder epithelial damage and mast cell infiltration. Tropisetron has been corroborate to conduct a protective role in HC, but its specific etiology remains unclear. The objective of this research was to estimate the mechanism of action of Tropisetron in haemorrhagic cystitis tissue. METHODS: Cyclophosphamide (CTX) was utilized to induce the construction of HC rat model, and rats were handled with different doses of Tropisetron. The impact of Tropisetron on the expression of inflammatory factors and oxidative stress factors in the rats with cystitis were measured by western blot, as well as the related proteins of toll-like receptor 4/nuclear transcription factor-κB (TLR-4/NF-κB) and januskinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways. RESULTS: CTX-induced cystitis in rats was accompanied by notable pathological tissue damage and increased bladder wet weight ratio, elevated mast cell numbers and collagen fibrosis compared to controls. Tropisetron ameliorated CTX-induced injury in a concentration-dependent manner. Futhermore, CTX induced oxidative stress and inflammatory damage, while Tropisetron can alleviate these injuries. Besides, Tropisetron ameliorated CTX-induced cystitis by restraining TLR-4/NF-κB and JAK1/STAT3 signalling pathways. CONCLUSIONS: Taken together, Tropisetron ameliorates cyclophosphamide-induced haemorrhagic cystitis via modulating TLR-4/NF-κB and JAK1/STAT3 signalling pathways. These findings carry important implication for the study of the molecular mechanisms of pharmacological treatment of hemorrhagic cystitis.

Tropisetron Ameliorated Cyclophosphamide-Induced Hemorrhagic Cystitis via Restraining TLR-4/NF-kB and JAK1/STAT3 Signaling Pathways

Objective: The main pathological changes of hemorrhagic cystitis (HC) are bladder inflammation, bladder epithelial damage and mast cell infiltration. Tropisetron has been corroborate to conduct a protective role in HC, but its specific etiology remains unclear. The objective of this research was to estimate the mechanism of action of Tropisetron in haemorrhagic cystitis tissue. Methods: Cyclophosphamide (CTX) was utilized to induce the construction of HC rat model, and rats were handled with different doses of Tropisetron. The impact of Tropisetron on the expression of inflammatory factors and oxidative stress factors in the rats with cystitis were measured by western blot, as well as the related proteins of toll-like receptor 4/nuclear transcription factor-κB (TLR-4/NF-κB) and januskinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways. Results: CTX-induced cystitis in rats was accompanied by notable pathological tissue damage and increased bladder wet weight ratio, elevated mast cell numbers and collagen fibrosis compared to controls. Tropisetron ameliorated CTX-induced injury in a concentration-dependent manner. Futhermore, CTX induced oxidative stress and inflammatory damage, while Tropisetron can alleviate these injuries. Besides, Tropisetron ameliorated CTX-induced cystitis by restraining TLR-4/NF-κB and JAK1/STAT3 signalling pathways. Conclusions: Taken together, Tropisetron ameliorates cyclophosphamide-induced haemorrhagic cystitis via modulating TLR-4/NF-κB and JAK1/STAT3 signalling pathways. These findings carry important implication for the study of the molecular mechanisms of pharmacological treatment of hemorrhagic cystitis (AU)

Analysis of Dust Emission Characteristics of Peanut Whole-Feed Harvesting Based on Total Amount Collection Method.

In view of the lack of a total amount collection method of dust emitted from a peanut whole-feed harvester and the unknown characteristic parameters of dust emission, a total amount dust collection method based on the combined action of centrifugation and filtration was proposed. The structural parameters of a total amount dust collection device were designed through theoretical analysis. On this basis, the production of a total amount dust collection device and a total amount dust collection test of the peanut whole-feed harvester were completed. The test showed that the total amount dust collection device could meet the needs of dust emission characteristics research. After analyzing the collected dust, it was found that the emitted particles were a mixture of soil particles and fiber particles. When the engine speed of the harvester was increased from 1600 rpm to 2400 rpm, the total emission rate increased from 3.36% to 4.28%, and the particulate emission rate increased from 1.44% to 2.63%; it also caused 4.29~4.98% of seedling blowing loss. The emission proportion of soil particles was reduced from 58.93% to 44.25%, and the emission proportion of fiber particles was increased from 41.07% to 55.75%. Among the emitted particles, the particle size peak of soil particles was concentrated at 22.9~30.2 µm; the particle size peak of fiber particles was concentrated at 478.6~631.0 µm. The research method and results can provide a reference for the optimization of dust reduction and emission reduction of peanut whole-feed harvesters and similar crop harvesters.

[Corrigendum] MicroRNA­218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2.

Subsequently to the publication of the above article, the authors have realized that the cell migration and tube formation assay data portrayed in Figs. 2 and 4 in their paper were published with some inadvertent errors. Specifically, the photograph selected for the ACHN-SFM group was accidentally misused for the 769P/LV-miR-218 group in Fig. 2F. Secondly, the photograph for the 786O/LV­NC group in Fig. 2F was accidentally misused as the image for the 786O/shNC group in Fig. 4E; and thirdly, the photograph selected for the ACHN/shNC group in Fig. 4C was inadvertently misused for the ACHN/shNC group in Fig. 4D. These errors arose inadvertently as a consequence of the authors' mishandling their data; however, the authors were able to retrieve their original data, and have been able to reassemble these figures to show the data as was originally intended. The revised versions of Figs. 2 and 4, featuring the corrected data panels for the 769P/LV­miR­218 group in Fig. 2F, the ACHN/shNC group in Fig. 4D and the 786O/shNC group in Fig. 4E, are shown on the next two pages. The revised data shown for these Figures do not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 44: 1961­1970, 2020; DOI: 10.3892/or.2020.7759].

Correction: Tumor-suppressive microRNA-218 inhibits tumor angiogenesis via targeting the mTOR component RICTOR in prostate cancer.

[This corrects the article DOI: 10.18632/oncotarget.14131.].

Unprecedented enhancement of wear resistance for epoxy-resin graphene composites.

Epoxy resins (ERs) have extraordinary mechanical, electrical and chemical properties, and are widely used in the aerospace, electronics and marine industries. Nonetheless, solidified ERs have intrinsic brittleness and low wear resistance. Until now, the promotion of the wear resistance of ER is limited to 30 times, through blending from one to four reinforcing materials. Therefore, it has been a challenge to enhance the wear resistance of ER to over 30 times. Additionally, mechanisms to improve the tribological properties of polymer composites are elusive. In this study, novel ER/graphene composites (ECs) were developed, and the wear resistance of EC with 5 wt% graphene (EC5) was shown to be 628 times that of pure ER at 10 N. To the best of our knowledge, the unprecedented enhancement of wear resistance for ER is the highest reported. The enhancement mechanisms of graphene reinforcement to ER were determined by molecular dynamics simulations. When the content of graphene reaches 5 wt%, exfoliated graphene flakes adhere the most on the surface of a stainless-steel ball during sliding tests, reducing the wear most effectively. However, when the content of graphene is over 5 wt%, graphene flakes accumulate inside the composites, and less exfoliated graphene flakes adhere to the surface of the ball during sliding, increasing the wear. The developed binary ECs are light-weight and cost-effective and have minimal impact on the environment. This composite has many potential applications for high-performance components used in the aerospace, electronics and marine industries.

FOXM1-Dependent Transcriptional Regulation of EZH2 Induces Proliferation and Progression in Prostate Cancer.

BACKGROUND: Prostate cancer is one of the most commonly diagnosed cancers and one of the most common causes of cancer-related deaths among men worldwide. Patients who are diagnosed with localized prostate cancer and treated with radical prostatectomy often respond well to therapy. The current standard therapy for prostate cancer involves maximal surgical resection, followed by radiotherapy and chemotherapy. Clarifying the molecular mechanism of tumor proliferation and recurrence becomes more and more important for clinical therapies of prostate cancer. METHODS: Quantitative Real-Time PCR and Western-blot were used in the detection of mRNA and protein expression. Lentivirus infection was used to overexpress or knockdown the target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between the two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett's posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis. RESULTS: In this study, we identified that FOXM1 expression was significantly enriched in prostate cancer compared with normal tissue. Additionally, FOXM1 was functionally required for tumor proliferation and its expression was associated with poor prognosis in prostate cancer patients. Mechanically, FOXM1-dependent regulation of EZH2 is essential for proliferation and progression in prostate cancer. CONCLUSION: Taken together, our data suggest that oncogenic transcription factor FoxM1 is up-regulated in prostate cancer, suggesting that the growth of cancer cells may depend on FOXM1 activity. FOXM1 may serve as a clinical prognostic factor and a therapeutic target for prostate cancer.

Chloride channel 7 protects from redox status impairment-induced renal tubular epithelial cell apoptosis by activating autophagy.

AIM: Chloride channel 7 (CLC-7), broadly expressed in kidney tissues, affects the lysosome degradation pathway. And redox status impairment contributes to cell apoptosis and activates autophagy flux. This study mainly investigates the role and molecular mechanism of CLC-7 in redox status impairment-induced autophagic flux and apoptosis. MAIN METHODS: When NRK52E cells, rat renal tubular epithelial cells, were exposed to H2O2 treatment, apoptosis, autophagy flux, and CLC-7 expression were detected. Further investigation was done to observe the change of apoptosis and autophagy flux in renal cells under overexpression or knocking down of CLC-7. The lysosomes acidity, lysosome enzyme Cathepsin D activity and phosphorylation of Ampk/mTOR were also examined when CLC-7 was overexpressed or knocked down. KEY FINDINGS: Redox status impairment induced apoptosis and autophagy flux in NRK52E cells and upregulated CLC-7. Overexpression of CLC-7 increased lysosome acidity and Cathepsin D activity. In cells with CLC-7 overexpression, we observed a significant increase of autophagy flux and decline of apoptosis, as well as an apparent increase of p-Ampk and decrease of p-mTOR. On the contrary, cells with knocking down CLC-7 led to opposite results. SIGNIFICANCES: CLC-7 is essential to maintain and enhance acidity and enzyme activity in lysosome. Through activating autophagy flux, it exerts survival against renal tubular epithelial cell apoptosis induced by redox status impairment. Its function to modulate Ampk/mTOR pathway is the possible reason why CLC-7 can trigger autophagy flux.

MicroRNA­218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2.

Renal cell carcinoma (RCC) is one of the most common malignant cancers in the adult urinary system worldwide. Tumor angiogenesis is a critical process during cancer progression, as it modulates carcinogenesis and metastasis. In recent years, microRNA­218 (miR­218) has been confirmed to play a crucial role in tumor suppression. However, the role of miR­218 in RCC angiogenesis remains unclear. In the present study, it was found that the expression of miR­218 was decreased in RCC tumor tissues and cell lines as detected by real­time PCR analysis. Tube formation assays and migration assays also confirmed that miR­218 inhibited the interaction between RCC cells and vascular endothelial cells by suppressing proangiogenic factor vascular endothelial growth factor A (VEGFA) in RCC cells. miR­218 also repressed the subcutaneous tumorigenesis of RCC cells in nude mice, and the corneal angiogenesis in rabbit eyes. The underlying molecular mechanism was elucidated; miR­218 targets GRB2­associated binding protein 2 (GAB2), thereby inhibiting the PI3K/AKT/mTOR/VEGFA pathway. These results provide new insights into the mechanism of RCC carcinogenesis and progression, suggesting that miRNA­218 may be a therapeutic target for the treatment of RCC.

GRB2-associated binding protein 2 regulates multiple pathways associated with the development of prostate cancer.

The development of prostate cancer is complicated and involves a number of tumor-associated gene expression level abnormalities. Gene chip technology is a high-throughput method that can detect gene expression levels in different tissues and cells on a large scale. In the present study, gene chip technology was used to screen differentially expressed genes in PC-3 human prostate cancer cells following GRB-associated binding protein 2 (GAB2) gene knockdown, and the corresponding biological information was analyzed to investigate the role of GAB2 in prostate cancer. The PC-3 human prostate cancer cell GAB2 gene was knocked out and gene chip hybridization and bioinformatics methods were used to analyze the classical pathway and predict upstream regulatory molecules, disease and function associations and genetic interaction networks. According to the screening conditions |fold change|>1 and P<0.05, 1,242 differential genes were screened; 665 genes were upregulated, and 577 genes were downregulated. Ingenuity Pathway Analysis software demonstrated that GAB2 regulates pathways, such as the superpathway of cholesterol biosynthesis and p53 signaling in cells, and serves a role in diseases and functions such as 'non-melanoma solid tumors', 'viral infections' and 'morbidity or mortality'. In the occurrence and development of prostate cancer, factors such as the activation of genes involved in the proliferative cycle, abnormalities in metabolism-associated enzyme gene activities and viral infection play key roles. The present study provides novel research directions and therapeutic targets for prostate cancer.

The Value of Prostate-Specific Antigen-Related Indexes and Imaging Screening in the Diagnosis of Prostate Cancer.

OBJECTIVE: The aim of this study was to explore the value of the prostate-specific antigen (PSA) levels, the ratio of free PSA to total PSA (fPSA/TPSA), the PSA density (PSAD), digital rectal examination (DRE), transrectal prostate ultrasound (TRUS), and multiparameter MRI (MP-MRI) in the differential diagnosis of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). METHODS: From February 2016 to September 2019, data from 620 patients who underwent systematic transrectal ultrasound-guided prostate biopsy (STURS-PB) in our hospital were retrospectively collected, including the PSA levels, the fPSA/TPSA ratio, the PSAD, DRE, TRUS, MP-MRI, prostate volume, and other clinical data. RESULTS: Among the 620 patients, 249 patients were in the PCa group, and 371 patients in the BPH group. The positive puncture rate was 40.16%. The positive predictive values of DRE, TRUS, mpMRI, and TPSA levels for PCa were 39.91%, 39.38%, 64.14%, and 41.57%, respectively; the sensitivity of these parameters was 37.35%, 51.41%, 74.69%, and 57.43%, respectively; and the specificity of these parameters was 62.26%, 46.90%, 71.97%, and 45.82%, respectively. When the TPSA concentration was in the range of 4-20 ng/mL, the positive puncture rate of STURS-PB was 23.18%, with a high rate of misdiagnosis. When the TPSA concentration was in the range of 4-20 ng/mL, the fPSA/TPSA ratio was 0.15, the PSAD was 0.16, the comprehensive evaluation of PCa was optimal (the sensitivity of these parameters was 88.85% and 84.09%, respectively; the specificity was 80.17% and 67.29%, respectively; the positive predictive value was 57.41% and 51.39%, respectively). When the TPSA concentration >4 ng/mL, the fPSA/TPSA ratio ≤0.15 and the PSAD ≥0.16, the sensitivity, specificity, and correctness index of the PCa and BPH diagnosis were 80.54%, 82.75%, and 67.07%, respectively. CONCLUSION: When using DRE, TRUS, and MP-MRI to screen for PCa, MP-MRI has a relatively high sensitivity and specificity. Using these three thresholds (TPSA >4 ng/mL combined with an fPSA/TPSA ratio ≤0.15 and a PSAD ≥0.16) is significantly better than using TPSA levels alone for the differential diagnosis of PCa and BPH.

The miR-218/GAB2 axis regulates proliferation, invasion and EMT via the PI3K/AKT/GSK-3ß pathway in prostate cancer.

Altered expression of microRNA (miRNA) is associated with the occurrence and metastasis of various tumors. We previously found that miR-218 inhibits tumor angiogenesis through the RICTOR/VEGFA axis in prostate cancer (PCa). In this study, we determined that miR-218 also had a negative effect on cell growth, migration, and invasion ability in PCa. Our data showed that miR-218 bound to the Grb2-associated binding protein 2 (GAB2) 3'-UTR region and inhibited GAB2 expression. As a novel downstream target of miR-218, GAB2 has been reported to be involved in the occurrence and development of various human tumors, but its role in the progression and metastasis of PCa has not been addressed. We demonstrated for the first time that the expression of GAB2 in the PCa cell lines was increased, while knocking down GAB2 significantly inhibited cell growth, metastatic ability and EMT process in PCa. In addition, the recovery of GAB2 could reverse the changes in the biological function of PCa cells caused by the ectopic expression of miR-218. Mechanistically, miR-218-mediated GAB2 transcriptional suppression significantly inhibited the activity of the PI3K/AKT/GSK-3ß pathway, whose abnormal activation was found to be related to the malignant progression of PCa. Taken together, our findings suggest that the miR-218/GAB2 axis may become a novel prognostic indicator and potential therapeutic target in PCa.

Comparative Study of the Effectiveness and Safety of Transurethral Bipolar Plasmakinetic Enucleation of the Prostate and Transurethral Bipolar Plasmakinetic Resection of the Prostate for Massive Benign Prostate Hyperplasia (>80 ml).

BACKGROUND The aim of this study was to compare the clinical safety and effectiveness of transurethral bipolar plasmakinetic enucleation of the prostate (PKEP) vs. transurethral bipolar plasmakinetic resection of the prostate (PKRP) in the treatment of benign prostate hyperplasia (BPH) more than 80 ml. MATERIAL AND METHODS From June 2015 to February 2019, 179 BPH patients with prostate volume greater than 80 ml were enrolled and separated into a PKEP (n=81) group and a PKRP group (n=98). The patients in the 2 groups were followed up for 6 months. We collected and analyzed data from the international Prostate Symptom Score (IPSS), residual urine volume (RUV), quality of life (QOL), maximum urine flow rate (Qmax), and international erectile function index (ILEF-5). The clinical data collected during and after the operation and surgical complications were compared between the 2 groups. RESULTS The PKEP group had significantly shorter operation time, bladder flushing time, indwelling catheter time, and hospitalization time, and has less intraoperative blood loss, intraoperative blood transfusion, postoperative secondary hemorrhage, bladder neck contracture, capsule perforation, and retrograde ejaculation (P<0.05). Compared with the PKRP group, the postoperative IPSS and QOL scores were significantly lower in the PKEP group (P<0.05), while the excision glandular tissue weight and Qmax were significantly improved (P<0.05). There were no significant differences in ILEF-5 scores, RUV, urethral stricture, urinary incontinence, or erectile dysfunction between the 2 groups (p>0.05). CONCLUSIONS PKEP treatment of BPH with a large volume (>80 ml) has the advantages of complete gland resection, good surgical effect, improved surgical safety, and reduced intraoperative and postoperative complications.

Macroscale Superlubricity Enabled by Graphene-Coated Surfaces.

Friction and wear remain the primary modes for energy dissipation in moving mechanical components. Superlubricity is highly desirable for energy saving and environmental benefits. Macroscale superlubricity was previously performed under special environments or on curved nanoscale surfaces. Nevertheless, macroscale superlubricity has not yet been demonstrated under ambient conditions on macroscale surfaces, except in humid air produced by purging water vapor into a tribometer chamber. In this study, a tribological system is fabricated using a graphene-coated plate (GCP), graphene-coated microsphere (GCS), and graphene-coated ball (GCB). The friction coefficient of 0.006 is achieved in air under 35 mN at a sliding speed of 0.2 mm s-1 for 1200 s in the developed GCB/GCS/GCP system. To the best of the knowledge, for the first time, macroscale superlubricity on macroscale surfaces under ambient conditions is reported. The mechanism of macroscale superlubricity is due to the combination of exfoliated graphene flakes and the swinging and sliding of the GCS, which is demonstrated by the experimental measurements, ab initio, and molecular dynamics simulations. These findings help to bridge macroscale superlubricity to real world applications, potentially dramatically contributing to energy savings and reducing the emission of carbon dioxide to the environment.

BUB1B Promotes Proliferation of Prostate Cancer via Transcriptional Regulation of MELK.

BACKGROUND: Prostate cancer remains one of the most common and deadliest forms of cancer, generally respond well to radical prostatectomy and associated interventions, up to 30% of individuals will suffer disease relapse. Although BUB1B was found to be essential for cell growth and proliferation, even in several kinds of tumor cells, the specific importance and mechanistic role of BUB1B in prostate cancer remain unclear. METHODS: Quantitative Real-Time PCR and Western-blot were used in the detection of mRNA and protein expression. Lentivirus infection was used to overexpression or knock down the target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between the two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett's posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis. RESULTS: In the present report, we found BUB1B expression to be highly increased in prostate cancer tissues relative to normal controls. We further found BUB1B to be essential for efficient tumor cell proliferation, and to correlate with poorer prostate cancer patient outcomes. From a mechanistic perspective, the ability of BUB1B to regulate MELK was found to be essential for its ability to promote prostate cancer cell proliferation. CONCLUSION: Altogether, our data suggest that BUB1B is up-regulated in prostate cancer, suggesting that the growth of cancer cells may depend on BUB1B-dependent regulation of MELK transcription. BUB1B may serve as a clinical prognostic factor and a druggable target for prostate cancer.

Efficacy and Safety of "On-Demand" Dapoxetine in Treatment of Patients with Premature Ejaculation: A Meta-Analysis.

BACKGROUND The aim of this study was to assess the efficacy and safety of "on-demand" dapoxetine in the treatment of premature ejaculation (PE). MATERIAL AND METHODS We performed a meta-analysis of intravaginal ejaculatory latency time (IELT), patient-reported global impression of change (PGIC), perceived control over ejaculation (PCOE), and drug-related adverse effects (AEs). We searched Medline, PubMed, Embase, CNKI, Wanfang, and VIP databases up to May 30, 2018 with the following search terms: "dapoxetine" or "SSRIs" and "premature ejaculation" or "sexual dysfunction". RESULTS Our analysis included 11 RCTs (8521 cases and 4338 controls). We found that IELT, PGIC, and PCOE in PE patients with "on-demand" dapoxetine were significantly higher than in the control group, and we observed higher proportions in 60 mg vs. 30 mg dapoxetine. The AEs were mild and tolerable. CONCLUSIONS "On-demand" dapoxetine is effective and safe for patients with PE, and a dose of 60 mg may be more effective than 30 mg.

MicroRNA-218 inhibits the migration, epithelial-mesenchymal transition and cancer stem cell properties of prostate cancer cells.

MicroRNA (miRNA) is a class of non-coding single-stranded RNA, able to regulate tumor-associated genes via binding the 3'-UTR of the target gene mRNA. Previous publications have demonstrated that miRNA-218 (miR-218) acts as a tumor-suppressive miRNA in various types of human cancer, including prostate cancer (PCa). However, the role of miR-218 in regulating PCa cell stemness and epithelial-mesenchymal transition remains unknown and requires further research. In the present study, it is demonstrated that miR-218 was downregulated in 2 PCa cell lines and could suppress cell migration, EMT and the exhibition of cancer stem cell-like properties. The expression of GLI family zinc finger 1 (Gli1) was inhibited by miR-218 overexpression, suggesting miR-218-suppression of Gli1 as a potential mechanism for the tumor-suppressive effect of miR-218. Overall, the results indicate that miR-218 served a critical role in the inhibition of PCa development. This may provide new insight for elucidating the mechanisms of PCa oncogenesis and suggests that miR-218 may be a novel therapeutic target for PCa.