Exosome-derived circTRPS1 promotes malignant phenotype and CD8+ T cell exhaustion in bladder cancer microenvironments.

Circular RNAs (circRNAs) play critical roles in different diseases. Exosomes are important intermediates of intercellular communication. While both have been widely reported in cancers, exosome-derived circRNAs are rarely studied. In this work, we identified the differently expressed circRNAs in bladder cancer (BCa) tissue and exosomes through high-throughput sequencing. RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays were used to investigate the interactions between specific circRNAs, microRNAs (miRNAs), and mRNAs. Wound-healing, Transwell, Cell Counting Kit-8 (CCK8), and colony-formation assays were used to study the biological roles in vitro. Metabolomics were used to explore the mechanism of how specific circRNAs influenced BCa cell behavior. Flow cytometry was used to study how specific circRNAs affected the function of CD8+ T cells in tumor microenvironments. We identified that exosome-derived hsa_circ_0085361 (circTRPS1) was correlated with aggressive phenotypes of BCa cells via sponging miR-141-3p. Metabolomics and RNA sequencing (RNA-seq) identified GLS1-mediated glutamine metabolism was involved in circTRPS1-mediated alterations. Exosomes derived from circTRPS1 knocked down BCa cells, prevented CD8+ T cells from exhaustion, and repressed the malignant phenotype of BCa cells. In conclusion, exosome-derived circTRPS1 from BCa cells can modulate the intracellular reactive oxygen species (ROS) balance and CD8+ T cell exhaustion via the circTRPS1/miR141-3p/GLS1 axis. Our work may provide a potential biomarker and therapeutic target for BCa.

Membrane-Bound EMC10 Is Required for Sperm Motility via Maintaining the Homeostasis of Cytoplasm Sodium in Sperm.

Endoplasmic reticulum membrane protein complex subunit 10 (EMC10) is an evolutionarily conserved and multifunctional factor across species. We previously reported that Emc10 knockout (KO) leads to mouse male infertility. Emc10-null spermatozoa exhibit multiple aspects of dysfunction, including reduced sperm motility. Two subunits of a Na/K-ATPase, ATP1A4 and ATP1B3, are nearly absent in Emc10 KO spermatozoa. Here, two isoforms of EMC10 were characterized in the mouse testis and epididymis: the membrane-bound (mEMC10) and secreted (scEMC10) isoforms. We present evidence that mEMC10, rather than scEMC10, is required for cytoplasm sodium homeostasis by positively regulating ATP1B3 expression in germ cells. Intra-testis mEMC10 overexpression rescued the sperm motility defect caused by Emc10 KO, while exogenous recombinant scEMC10 protein could not improve the motility of spermatozoa from either Emc10 KO mouse or asthenospermic subjects. Clinically, there is a positive association between ATP1B3 and EMC10 protein levels in human spermatozoa, whereas no correlation was proven between seminal plasma scEMC10 levels and sperm motility. These results highlight the important role of the membrane-bound EMC10 isoform in maintaining cytoplasm sodium homeostasis and sperm motility. Based on the present results, the mEMC10-Na, K/ATPase α4ß3 axis is proposed as a novel mechanism underlying the regulation of cytoplasmic sodium and sperm motility, and its components seem to have therapeutic potential for asthenospermia.

Ureteral reconstruction using a tapered non-vascularized bladder graft: an experimental study in a canine animal model.

BACKGROUND: Reconstruction of ureteral defects and strictures remains problematic for urologists. We aimed to investigate the possibility of a tapered non-vascularized bladder graft as a novel substitute for ureteral reconstruction. METHODS: This experimental study was conducted on nine beagles. Under general anesthesia, a full-thickness graft with 5-6 cm in length was disassociated from the anterior upper wall of the bladder, and tapered into 1/3 to 1/2 thickness, remaining the urothelial surface. After removal of 5 cm of right-sided mid-ureter, the tapered bladder graft was tubularized along the long axis and then respectively anastomosed to the upper and lower stumps of the ureter. A retrograde urography through a cystostomy was performed 8 weeks after the ureteral reconstruction. The animals were euthanized, and histopathologic examinations of the neoureters were performed. RESULTS: There were no severe complications during postoperative follow-up. The urography indicated patent urine excretion and no fistula or stenosis. Histopathologic examinations of the neoureters showed open lumen with urothelial lining. Nutrient vessels were observed in healthy submucosa, lamina muscularis and peripheral connective tissue. CONCLUSIONS: Our study implied that ureteral reconstruction by a tapered non-vascularized bladder graft was anatomically possible in our animal model. Further studies are expected to confirm long-term and functional outcomes.

Antitumoral action of icaritin in LNCaP prostate cancer cells by regulating PEA3/HER2/AR signaling.

Human epidermal growth factor receptor type 2 (HER2) and androgen receptor (AR) are critical factors for prostate cancer (PCa) progression. These factors regulate tumor cell survival and proliferation, and remain as crucial drivers of castration-resistant PCa progression. Icaritin (ICT) is a prenyl flavonoid derived from the Epimedium genus, which has many biological and pharmacological effects. Using androgen-sensitive human prostate carcinoma LNCaP cell lines, we found that 35 µg/ml of ICT could inhibit more than 50% of cell proliferation, induce cell apoptosis, and lead to a strong G1 phase arrest by targeting cyclin-related proteins and suppressing the ability of cell invasion. Moreover, ICT exerts its potent anticancer efficacy by inducing polyomavirus enhancer activator 3 (PEA3) to inhibit the aberrantly activated HER2/AR signaling. In addition, after PEA3 expression was silenced by specific small-interference RNA, we found that both the ICT-inhibited effect on LNCaP cell proliferation and the ICT-induced cell apoptosis rate decreased. These results provide alternative mechanisms for the antitumor actions of ICT, indicating that ICT might be a promising therapeutic agent, as well as a preventive agent, for hormone therapy-resistant PCa.

Elevated plasma aldosterone is an independent risk factor for erectile dysfunction in men.

INTRODUCTION: Erectile dysfunction (ED) and cardiovascular disease (CVD) share a great number of common risk factors. There is growing evidence that aldosterone, an independent CVD risk factor, is associated with ED. AIMS: The purpose of this study was to determine the relationship between plasma aldosterone and erectile dysfunction. METHODS: This study recruited 287 participants, ranging from 18 to 84 years old; 217 were suffering from ED, diagnosed by the International Index of Erectile Function 5 (IIEF-5) scores. Based on IIEF-5 scores, patients were divided into one control group and three ED groups (mild ED; moderate ED; severe ED). MAIN OUTCOME MEASURES: The differences in principal characteristics, blood routine, sexual hormone, adrenal hormone, thyroid hormone, renal function, liver function and blood lipid were compared between ED and control groups. RESULTS: Our study demonstrated that the difference of mean plasma aldosterone levels between ED group and the control group was statistically significant (P < 0.05). Stepwise logistic regression analysis of all the possible factors support the role of aldosterone as an independent risk factor for ED (OR 1.011; 95 % CI 1.003-1.018; P = 0.004). Similar statistical methods were applied to the comparison between moderate to severe ED group and control to mild ED group (OR 1.017; 95 % CI 1.009-1.024; P < 0.001). ROC curve and the area under the curve (0.718; 95 % CI 0.643-0.794; P < 0.001) were performed to assess the diagnostic effect and to compare the severity of risk with the known independent risk factors, such as age and cholesterol (0.704; 95 % CI 0.631-0.778; P < 0.001). When using a 374 pg/mL cut-off value from Youden index, the OR of ED group versus controls is 3.106 (95 % CI 1.458-6.617), while the OR of moderate to severe ED versus control and mild ED is 5.480 (95 % CI 3.108-9.662). CONCLUSIONS: We determined that elevated plasma aldosterone concentration is an independent risk factor for ED. Our findings also indicate that the aldosterone, a well-recognized contributor to vascular injury, might be a potential bond between ED and CVD.

The safety and efficacy of bladder cryoablation in a beagle model by using a novel balloon cryoprobe.

The poor quality of initial transurethral resection (TUR) would leave residual tumor and compromise the prognosis. The common therapeutic option is to perform re-TUR, which adds burden to patients. We assumed that cryoablation could be applied as adjuvant therapy combined with TUR, thus lead to maxium tumor control. In our study, we investigated the safety and effects of focal bladder wall cryoablation in beagle model using a novel cryoablation balloon probe. Temperature was recorded throughout the freeze process in different parts of the bladder. The bladder was harvested immediately, 2 weeks or 3 months after surgery for histological evaluation. The results demonstrated cryoablation using our newly designed probe is safe and effective. Two-minute cryoablation could induce necrosis within 2-cm range in diameter to superficial muscle layer. The findings provided us reference before cryoablation could be applied in clinical practice.

Icaritin inhibits the progression of urothelial cancer by suppressing PADI2-mediated neutrophil infiltration and neutrophil extracellular trap formation.

Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer. In the tumor microenvironment, negative regulatory molecules and various immune cell subtypes suppress antitumor immunity. The inflammatory microenvironment, associated with neutrophils and neutrophil extracellular traps (NETs), promotes tumor metastasis. However, no drugs are currently available to specifically inhibit neutrophils and NETs. In this study, we first demonstrated that icaritin (ICT), a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma, reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment. Mechanistically, ICT binds to and inhibits the expression of PADI2 in neutrophils, thereby suppressing PADI2-mediated histone citrullination. Moreover, ICT inhibits ROS generation, suppresses the MAPK signaling pathway, and inhibits NET-induced tumor metastasis. Simultaneously, ICT inhibits tumoral PADI2-mediated histone citrullination, which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6. The downregulation of IL-6 expression, in turn, forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis. Through a retrospective study of clinical samples, we found a correlation between neutrophils, NETs, UCa prognosis, and immune evasion. Combining ICT with immune checkpoint inhibitors may have synergistic effects. In summary, our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment.

Cell-Free DNA, MicroRNAs, Proteins, and Peptides as Liquid Biopsy Biomarkers in Prostate Cancer and Bladder Cancer.

Liquid biopsy, as a novel noninvasive tool for biomarker discovery, has gained a lot of attention and represents a significant innovation in precision medicine. Due to its minimally invasive nature, liquid biopsy has fewer complications and can be scheduled more frequently to provide individualized snapshots of the disease at successive time points. This is particularly valuable in providing simultaneous measurements of tumor burden during treatment and early detection of tumor recurrence or drug resistance. Blood-based liquid biopsy is an attractive, minimally invasive alternative, which has shown promise in diagnosis, risk stratification, disease monitoring, and more. Urine has gained popularity due to its less invasive sampling, the ability to easily repeat samples, and the ability to track tumor evolution in real time, making it a powerful tool for diagnosis and treatment monitoring, especially in urologic cancers. In this review, we provide a detailed discussion on the potential clinical applications of prostate cancer (PCa) and bladder cancer (BCa), with cell-free DNA (cfDNA), microRNAs (miRNAs), proteins, and peptides as liquid biopsy biomarkers.

Blood lipids, lipid-regulatory medications, and risk of bladder cancer: a Mendelian randomization study.

Background: The influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study. Methods: Genetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests. Results: There was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625-0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p > 0.05). Conclusion: This MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. The current study indicated that lipid metabolism may not be as important in the tumorigenesis of bladder cancer as previously believed.

Methionine orchestrates the metabolism vulnerability in cisplatin resistant bladder cancer microenvironment.

Metabolism vulnerability of cisplatin resistance in BCa cells remains to be discovered, which we applied integrated multi-omics analysis to elucidate the metabolism related regulation mechanism in bladder cancer (BCa) microenvironment. Integrated multi-omics analysis of metabolomics and proteomics revealed that MAT2A regulated methionine metabolism contributes to cisplatin resistance in BCa cells. We further validated MAT2A and cancer stem cell markers were up-regulated and circARHGAP10 was down-regulated through the regulation of MAT2A protein stability in cisplatin resistant BCa cells. circARHGAP10 formed a complex with MAT2A and TRIM25 to accelerate the degradation of MAT2A through ubiquitin-proteasome pathway. Knockdown of MAT2A through overexpression of circARHGAP10 and restriction of methionine up-take was sufficient to overcome cisplatin resistance in vivo in immuno-deficiency model but not in immuno-competent model. Tumor-infiltrating CD8+ T cells characterized an exhausted phenotype in tumors with low methionine. High expression of SLC7A6 in BCa negatively correlated with expression of CD8. Synergistic inhibition of MAT2A and SLC7A6 could overcome cisplatin resistance in immuno-competent model in vivo. Cisplatin resistant BCa cells rely on methionine for survival and stem cell renewal. circARHGAP10/TRIM25/MAT2A regulation pathway plays an important role in cisplatin resistant BCa cells while circARHGAP10 and SLC7A6 should be evaluated as one of the therapeutic target of cisplatin resistant BCa.

The potential mechanism of Longsheyangquan Decoction on the treatment of bladder cancer: Systemic network pharmacology and molecular docking.

Our goal was to explore the bioactive constituents of Longsheyangquan (LSYQ) Decoction and elucidate its mechanisms on the treatment of bladder cancer (BCa). A total of 38 compounds were selected based on their pharmacokinetic properties in three large traditional Chinese medicine (TCM) databases. 654 putative targets of LSYQ Decoction were predicted using a structure-based, reverse-docking algorithm online, of which 343 overlapped with BCa-related protein-coding genes. The protein-protein interaction (PPI) network was constructed to perform module analysis for further Gene Ontology (GO) annotations and Kyoto Encyclopedia Genes and Genomes (KEGG) pathway enrichment analysis, which identified CDK2, EGFR, MMP9 and PTGS2 as hub targets. The TCM-compound-target network and compound-target-pathway network together revealed that quercetin, diosmetin, enhydrin and luteolin were the main components of LSYQ Decoction. Finally, molecular docking showed the affinity between the key compounds and the hub target proteins to verify the accuracy of drug target prediction in the first place. The present study deciphered the core components and targets of LSYQ Decoction on the treatment of BCa in a comprehensive systemic pharmacological manner.

High-throughput sequencing identified circular RNA circUBE2K mediating RhoA associated bladder cancer phenotype via regulation of miR-516b-5p/ARHGAP5 axis.

Bladder cancer (BC) is known as a common and lethal urinary malignancy worldwide. Circular RNAs (circRNAs), an emerging non-coding RNA, participate in carcinogenesis process of several cancers including BC. In this study, high-throughput sequencing and RT-qPCR were applied to discover and validate abnormal high expression of circUBE2K in BC tissues. Fluorescence in situ hybridization (FISH) was used to detect hsa_circ_0009154 (circUBE2K) expression and subcellular localization in BC tissues. High circUBE2K predicted unfavorable prognoses in BCs, as well as correlated with clinical features. CCK8, transwell, EdU and wound healing assays demonstrated down-regulating circUBE2K decreased BC cell phenotype as proliferation, invasion, and migration, respectively. Further studies showed that circUBE2K promoted BC progression via sponging miR-516b-5p and enhancing ARHGAP5 expression through regulating RhoA activity. Dual-luciferase reporter, FISH and RNA pulldown assays were employed to verify the relationships among circUBE2K/miR-516b-5p/ARHGAP5/RhoA axis. Down-regulating miR-516b-5p or overexpressing ARHGAP5 restored RhoA activity mediated BC cell properties after silencing circUBE2K. Subcutaneous xenograft and metastasis model identified circUBE2K significantly increased BC cell metastasis and proliferation in-vivo. Taken together, we found that circUBE2K is a tumor-promoting circRNA in BC that functions as a ceRNA to regulate ARHGAP5 expression via sponging miR-516b-5p.

Recent Advances in DNA Repair Pathway and Its Application in Personalized Care of Metastatic Castration-Resistant Prostate Cancer (mCRPC).

Prostate cancer (PCa) is one of the common malignancies in male adults. In the era of precision medicine, many other novel agents targeting advanced prostate cancer, especially metastatic castration-resistant prostate cancer (mCRPC), are currently being evaluated. Among all these candidate therapies, poly-ADP ribose polymerase (PARP) inhibitors targeting DNA damage response (DDR) pathway has proven improving survival outcomes in clinical trials. In this review, we focus on recent advances in biology and clinical implication of DDR pathway and aim to discuss the latest results in advanced prostate cancer, especially mCRPC.

First-time versus recurrent penoscrotal extramammary Paget's disease: Clinicopathological characteristics and risk factors in 164 Chinese male patients.

BACKGROUND: Penoscrotal extramammary Paget's disease is a rare, slow-growing neoplasm with high frequency of local recurrence. AIMS: The aim of this study was to investigate the difference in clinicopathological characteristics between first-time and recurrent penoscrotal Paget's disease, and to discover the potential risk factors of recurrence. METHODS: Between January 2007 and February 2014, a total of 164 Chinese patients with biopsy-proven tramammary Paget's diseaseex in penis and scrotum underwent wide local resection in our institution. Among them, 142 patients with first-time disease and other 22 patients with recurrent disease were enrolled in this retrospective analysis. RESULTS: The median duration of symptoms was much shorter in recurrent disease than in first-timers (3 vs. 24 months, P < 0.001). Patients with recurrent disease tended to have lower lesion exudation rates (27.3% vs. 51.8%, P= 0.032). In addition, patients with distant stage were more likely to obtain recurrent disease compared with first-time disease (P = 0.005). Through immunohistochemical detection of extramammary Paget's specimen, we found that HER2/neu protein expression in the recurrent group was significantly higher than first-timers (P = 0.036). LIMITATIONS: In this study, the information on familial history of most patients was insufficient. Moreover, due to the lack of follow-up data of our included cases, we were unable to evaluate the prognosis after diagnosis of extramammary Paget's disease. CONCLUSION: Patients with penoscrotal Paget's disease, especially those with shorter duration of symptoms, exudation of lesions, distant-stage, Paget cells infiltrating into adnexa, and HER2/neu expression, should be followed up more carefully after surgery, as they were more likely to suffer recurrence.

Aldosterone induces inflammatory cytokines in penile corpus cavernosum by activating the NF-κB pathway.

Emerging evidence indicates that aldosterone and mineralocorticoid receptors (MRs) are associated with the pathogenesis of erectile dysfunction. However, the molecular mechanisms remain largely unknown. In this study, freshly isolated penile corpus cavernosum tissue from rats was treated with aldosterone, with or without MRs inhibitors. Nuclear factor (NF)-kappa B (NF-κB) activity was evaluated by real-time quantitative PCR, luciferase assay, and immunoblot. The results demonstrated that mRNA levels of the NF-κB target genes, including inhibitor of NF-κB alpha (IκB-α), NF-κB1, tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6), were higher after aldosterone treatment. Accordingly, phosphorylation of p65/RelA, IκB-α, and inhibitor of NF-κB kinase-ß was markedly increased by aldosterone. Furthermore, knockdown of MRs prevented activation of the NF-κB canonical pathway by aldosterone. Consistent with this finding, ectopic overexpression of MRs enhanced the transcriptional activation of NF-κB by aldosterone. More importantly, the MRs antagonist, spironolactone blocked aldosterone-mediated activation of the canonical NF-κB pathway. In conclusion, aldosterone has an inflammatory effect in the corpus cavernosum penis, inducing NF-κB activation via an MRs-dependent pathway, which may be prevented by selective MRs antagonists. These data reveal the possible role of aldosterone in erectile dysfunction as well as its potential as a novel pharmacologic target for treatment.

Evaluation of PSA-age volume score in predicting prostate cancer in Chinese population.

This study was performed to evaluate prostate-specific antigen-age volume (PSA-AV) scores in predicting prostate cancer (PCa) in a Chinese biopsy population. A total of 2355 men who underwent initial prostate biopsy from January 2006 to November 2015 in Huashan Hospital were recruited in the current study. The PSA-AV scores were calculated and assessed together with PSA and PSA density (PSAD) retrospectively. Among 2133 patients included in the analysis, 947 (44.4%) were diagnosed with PCa. The mean age, PSA, and positive rates of digital rectal examination result and transrectal ultrasound result were statistically higher in men diagnosed with PCa (all P < 0.05). The values of area under the receiver operating characteristic curves (AUCs) of PSAD and PSA-AV were 0.864 and 0.851, respectively, in predicting PCa in the entire population, both performed better than PSA (AUC = 0.805; P < 0.05). The superiority of PSAD and PSA-AV was more obvious in subgroup with PSA ranging from 2.0 ng ml-1 to 20.0 ng ml-1. A PSA-AV score of 400 had a sensitivity and specificity of 93.7% and 40.0%, respectively. In conclusion, the PSA-AV score performed equally with PSAD and was better than PSA in predicting PCa. This indicated that PSA-AV score could be a useful tool for predicting PCa in Chinese population.

EMC10 governs male fertility via maintaining sperm ion balance.

Infertility is a severe public health problem worldwide that prevails up to 15% in reproductive-age couples, and male infertility accounts for half of total infertility. Studies on genetically modified animal models have identified lots of genes involved in the pathogenesis of male infertility. The underlying causes, however, remain largely unclear. In this study, we provide evidence that EMC10, one subunit of endoplasmic reticulum (ER) membrane protein complex (EMC), is required for male fertility. EMC10 is significantly decreased in spermatozoa from patients with asthenozoospermia and positively associated with human sperm motility. Male mice lacking Emc10 gene are completely sterile. Emc10-null spermatozoa exhibit multiple defects including abnormal morphology, decreased motility, impaired capacitation, and impotency of acrosome reaction, thereby which are incapable of fertilizing intact or ZP-free oocytes. However, intracytoplasmic sperm injection could rescue this defect caused by EMC10 deletion. Mechanistically, EMC10 deficiency leads to inactivation of Na/K-ATPase, in turn giving rise to an increased level of intracellular Na+ in spermatozoa, which contributes to decreased sperm motility and abnormal morphology. Other mechanistic investigations demonstrate that the absence of EMC10 results in a reduction of HCO3- entry and subsequent decreases of both cAMP-dependent protein kinase A substrate phosphorylation and protein tyrosine phosphorylation. These data demonstrate that EMC10 is indispensable to male fertility via maintaining sperm ion balance of Na+ and HCO3-, and also suggest that EMC10 is a promising biomarker for male fertility and a potential pharmaceutical target to treat male infertility.

TDRP deficiency contributes to low sperm motility and is a potential risk factor for male infertility.

TDRP (Testis Development-Related Protein), a nuclear factor, might play an important role in spermatogenesis. However, the molecular mechanisms of TDRP underlying these fundamental processes remain elusive. In this study, a Tdrp-deficient mouse model was generated. Fertility tests and semen analysis were performed. Tdrp-deficient mice were not significantly different from wild-type littermates in development of testes, genitourinary tract, or sperm count. Morphologically, spermatozoa of the Tdrp-deficient mice was not significantly different from the wild type. Several sperm motility indexes, i.e. the average path velocity (VAP), the straight line velocity (VSL) and the curvilinear velocity (VCL) were significantly decreased in Tdrp-deficient mice (p<0.05). The proportion of slow velocity sperm also increased significantly in the mutant mice (p<0.05). However, fertility tests showed that no significant difference inaverage offspring amount (AOA), frequency of copulatory plug (FCP), and frequency of conception (FC). Furthermore, TDRP1 could interact with PRM2, which might be the molecular mechanism of its nuclear function in spermatozoa. In conclusion, these data collectively demonstrated that Tdrp deficiency impaired the sperm motility, but Tdrp deficiency alone was not sufficient to cause male infertility in mice. Additionally, TDRP1 might participate in spermatogenes is through interaction with PRM2.

Unilateral long-segment ureteral reconstruction using a bilateral Boari flap bridge: An experimental model in dogs.

OBJECTIVE: The aim of this experimental study was to evaluate the feasibility of a bilateral Boari flap bridge as a novel method for unilateral long-segment ureteral reconstruction. MATERIALS AND METHODS: The study was conducted on eight dogs. After resection of 10 cm of right-sided distal ureter, bilateral Boari flaps were made from the anterior upper wall of the bladder and then anastomosed head to head, forming a flap bridge. The left base of the flap bridge was transected, and the free end was then anastomosed to the proximal stump of the ureter with a stent inside. A retrograde urography through a cystostomy was performed 8 weeks after the ureteral reconstruction. The animals were killed and the neoureters were examined histologically. RESULTS: There were almost no obvious complications during the postoperative period. The urography suggested patent urine excretion and no obvious fistula or stenosis. Histopathological examinations showed an open lumen with complete urothelial lining and a healthy muscular layer with nutrient vessels. CONCLUSION: This study showed that ureteral reconstruction by a bilateral Boari flap bridge was anatomically possible in an animal model. Further studies are needed to confirm long-term functional efficacy.