A Multifunctional Secondary Based on Heterogeneous Co-MnO@NC for Depth-Induced Deposition and Conversion of Polysulfides in Li─S Batteries.

The conductive carbon-based interlayer, as the secondary current collector in the self-dissolving battery system, can effectively capture escaping cathode active materials, inducing deep release of remaining capacity. In the multi-step reactions of Li─S batteries, the environmental tolerance of the conductive carbon-based interlayer to polysulfides determines the inhibition of shuttle effects. Here, a modified metal-organic framework (Mn-ZIF67) is utilized to obtain nitrogen-doped carbon-coated heterogeneous Co-MnO (Co-MnO@NC) with dual catalytic center for the functional interlayer materials. The synergistic coupling mechanism of NC and Co-MnO achieves rapid deposition and conversion of free polysulfide and fragmented active sulfur on the secondary current collector, reducing capacity loss in the cathode. The Li─S battery with Co-MnO@NC/PP separator maintains an initial capacity of 1050 mAh g-1 (3C) and excellent cycle stability (0.056% capacity decay rate). Under extreme testing conditions (S load = 5.82 mg cm-2, E/S = 9.1 µL mg-1), a reversible capacity of 501.36 mAh g-1 is observed after 200 cycles at 0.2 C, showing good further practical reliability. This work demonstrates the advancement application of Co-MnO@NC bimetallic heterojunctions catalysts in the secondary current collector for high-performance Li─S batteries, thereby providing guidance for the development of interlayer in various dissolution systems.

[Therapeutic effect of Lingze Tablets on benign prostatic hyperplasia in rats: An exploration based on the VEGFA/TNF/IL-6 signaling pathway].

OBJECTIVE: To explore the mechanism of Lingze Tablets (LZT) acting on BPH in rats based on the VEGFA/TNF/IL-6 signaling pathway. METHODS: We equally randomized 30 SPF SD male rats into five groups, normal control, BPH model control, low-dose LZT, medium-dose LZT and high-dose LZT, and established a BPH model in the latter four groups by induction with non-castrate testosterone propionate. After the modeling, we treated the rats in the normal and model groups by intragastrical administration of physiological saline, and those in the latter three groups with low-, medium-, and high-dose LZT respectively, all for 28 successive days. Then we collected the prostate tissue from the animals for observation of the changes in the prostatic indexes and histomorphology, detected the expressions of the proteins related to the VEGFA/TNF/IL-6 signaling pathway, and compared the data obtained among different groups. RESULTS: Compared with the normal controls, the rats in the model control group showed significant prostatic hyperplasia, markedly increased prostatic index (ï¼»0.84 ± 0.01ï¼½ g, P<0.05), thickness of the prostatic epithelia and infiltration of the luminal area, and dramatically up-regulated protein expressions of VEGFA (0.60 ± 0.02, P< 0.05), TNF (0.76 ± 0.02, P< 0.05) and IL-6 (0.64 ± 0.02, P< 0.05). In comparison with the model controls, the rats in the low-, medium- and high-dose LZT groups exhibited significantly decreased prostatic indexes (ï¼»0.76 ± 0.02ï¼½ g, ï¼»0.58 ± 0.02ï¼½ g and ï¼»0.52 0.01ï¼½ g, all P< 0.05), improved prostatic histomorphology, and down-regulated expressions of VEGFA (0.45 ± 0.01, 0.35 ± 0.01 and 0.31 ± 0.02, all P< 0.05), TNF (0.45 ± 0.01, 0.33 ± 0.01 and 0.27 ± 0.01, all P< 0.01) and IL-6 (0.44 ± 0.01, 0.36 ± 0.01 and 0.30 ± 0.01, all P< 0.01) in a dose-dependent manner. CONCLUSION: LZT produces therapeutic effect on BPH by negatively regulating the VEGFA/TNF/IL-6 signaling pathway, reducing the expression levels of VEGFA, TNF and IL-6 proteins, and regulating cell proliferation, apoptosis and inflammatory response.

Zuogui Wan improves spermatogenesis of GC1-spg cells through modulating AR-related pathways.

Zuogui Wan (ZGW) is a common prescription medication used in traditional Chinese medicine (TCM) to significantly improve the sperm quality and treat male infertility. This study evaluated the repair effect of ZGW and Levocarnitine (LEV) on GC1-spg cell injury induced by Glucosides of Tripterygium WilforDII Hook (GTW). The results showed that the ultrastructure and apoptosis rate of GC1- spg cells in LEV and ZGW group were considerably better than GTW. The transcriptional and translational level of CYP1A1, CYP17A1, androgen receptor (AR), SRD5A2 and proliferating cell nuclear antigen (PCNA) in GC-1spg cells of the LEV group were considerably elevated than GTW group (p < 0.05 or 0.01). Furthermore, the transcriptional and translational levels of CYP19A1, CYP17A1, AR, SRD5A2 and PCNA in GC-1spg cells in ZGW group were found to be considerably elevated than the LEV group (p < 0.05 or 0.01). The findings indicate that ZGW and LEV could increase the expression of PCNA, CYP17A1, CYP19A1, SRD5A2 and AR at transcriptional and translational levels, inhibit GC-1spg cell apoptosis and promoting cell proliferation, and the effect of ZGW was found to be significantly better than that of LEV.

The mechanism analysis using PI3K/AKT pathway for the effects of levocarnitine in the treatment of spermatogenic dysfunction.

LEV improves the percentage of forward-motion spermatozoon and total sperm motility in patients with oligozoospermia or asthenospermia in clinical settings. However, the mechanism of action of levocarnitine (LEV) in the treatment of spermatogenic dysfunction was unclear. Based on in vitro and in vivo experiments, we used Glucosides of Tripterygium wilfordii Hook F (GTW) to construct a cell model (using spermatogenic GC-1 spg cells) and an animal model (using rats) of spermatogenic dysfunction. LEV and LY294002 (a PI3K pathway inhibitor) were then administered. By assessing apoptosis and sperm quality and motility, the underlying mechanism was explored. We found that GTW induced spermatogenic dysfunction, and LEV ameliorated the GTW-induced spermatogenic dysfunction. LEV inhibited GC-1 spg cell apoptosis and improved the sperm count and percentages of PR (forward motion) + NP (non-forward motion) (p < .01). Besides, the morphology of testicular tissue in the GTW + LEV and LY + LEV groups was superior to that in the GTW group. We can to the conclusion that LEV may operate via the PI3K/AKT signalling pathway, with increases in PI3K, p-AKT, and BCL-2 protein and mRNA expression, so that the percentages of GC-1 spg cells apoptosis decrease, and the sperm count and motility improve.

Effect of liver cirrhosis on erectile function in rats: A study combining bioinformatics analysis and experimental research.

To explore the mechanism through which liver cirrhosis (LC) causes erectile dysfunction (ED). Bioinformatic analysis was used to predict the potential signalling pathways in LC-induced ED, and N-nitrosodiethylamine was used to establish a rat model of LC. H&E staining, Western blotting and RT-qPCR were used to detect pathological tissue damage and changes in mRNA and protein expression levels. In addition, the expression levels of sex hormones such as estradiol (E2), prolactin (PRL) and testosterone (T) were measured. The hypoxia-inducible factor (HIF) pathway was an important pathway in our bioinformatics prediction. Pathological damages were detected in the liver and penile tissues of the model rats. Compared with the normal group's serum hormone levels, E2 and PRL were increased in LC rats, while T was decreased (p < 0.01). The mRNA and protein expression results from penis tissues showed that endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) were both downregulated, and HIF-1α was upregulated in the model group compared to the normal group (p < 0.01). These data suggest that LC hinders erectile function and causes histopathological changes in the penis by affecting the expression of HIF-1α, eNOS, iNOS, E2, PRL and T.

Explore the effects of pulmonary fibrosis on sperm quality and the role of the PI3K/Akt pathway based on rat model.

Researches were reported that respiratory diseases can lead to male infertility; however, it is unclear whether there is a relationship between pulmonary fibrosis (PF) and male infertility. This study examined the influence of PF on sperm quality and its mechanisms. The key signalling pathway of male infertility caused by PF was predicted based on bioinformatics research. After modelling, we evaluated semen quality. Real-time quantitative polymerase chain reaction and Western blotting were used to measure the protein and mRNA expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylation-protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl2) in rat testicular cells. Compared with group A (48.77 ± 4.67; 59.77 ± 4.79), the sperm concentration and total sperm viability of group B (8.44 ± 1.71; 15.39 ± 3.48) showed a downward trend (p < 0.05). Western blotting showed that the protein expressions of PI3K, p-Akt and Bcl2 in the testes of group B (0.30 ± 0.06; 0.27 ± 0.05; 0.15 ± 0.03) was significantly lower than those of group A (0.71 ± 0.07; 0.72 ± 0.06; 0.50 ± 0.06) (p < 0.05). The hypoxic environment induced by PF can inhibit the expression of PI3K, p-Akt and Bcl2 protein and eventually cause dysfunctional spermatogenesis.

A rat study model of depression-driven chronic prostatitis by modulating the PI3K/Akt/mTOR network.

Depression and chronic prostatitis (CP) are two common diseases that affect the human population worldwide. Clinically, it has been demonstrated that andrological patients often simultaneously suffer from depression and CP. Prior investigations have established that depression acts as an independent risk factor for CP. Herein, we explored the correlation between depression and CP using bioinformatics tools and through animal experiments. The potential targets and signalling pathways involved in depression and CP were predicted using bioinformatics tool, while depression in the rat model was established through chronic restraint stress. The expression of the related proteins and mRNA was assessed by Western blotting and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Relative to those in the control rats, the protein contents of PI3K, p-Akt, and p-mTOR were lower in the model rats (p < 0.05). Similarly, the transcript levels of PI3K, Akt, and mTOR was also relatively lower in the model rats (p < 0.05). And PI3K/Akt agonists reduced inflammation in rat prostate tissue, accompanied by significant increases in the transcript and protein expression levels of PI3K, Akt, and mTOR. Thus, we proposed that depression model rats may induce CP as a result of mediation by the negative regulation of the PI3K/Akt/mTOR signalling network.

Effects of Diabetes Mellitus on Sperm Quality in the Db/Db Mouse Model and the Role of the FoxO1 Pathway.

BACKGROUND Studies have shown that diabetes mellitus (DM) has a negative impact on male reproductive function, which may lead to changes in the testis and epididymis and a decline in semen quality. MATERIAL AND METHODS We performed animal experiments with 6 diabetic db/db mice as the model group (group B) and 6 C57BL/6J mice as the control group (group A). After adaptive feeding for 7 days, the sperm quality of each group was measured. Concurrently, the morphology of the mouse testis was observed by hematoxylin-eosin (H&E) staining. The expression of the PI3K, Akt, FoxO1, FasL, IL-6, and Stat3 proteins and mRNAs in the testicular tissue was detected by western blotting and RT-qPCR. RESULTS The number of spermatozoa and sperm motility of group A was significantly higher than that of group B (P<0.05). H&E staining of the testicular tissue showed the seminiferous tubules in group B mice were damaged to varying degrees and the seminiferous tubules were sparsely arranged. Compared with those of group A, the expression levels of PI3K, Akt, and Stat3 proteins and mRNAs in group B were significantly lower (P<0.05), while the expression levels of FoxO1, FasL, and IL-6 proteins and mRNAs in group B mice were significantly higher (P<0.05). CONCLUSIONS This study demonstrated that DM inhibited the expression of PI3K, Akt, and Stat3 proteins and mRNAs in the FoxO1 pathway and promoted the expression of FoxO1, FasL, and IL-6 proteins and mRNAs, leading to abnormal apoptosis of testicular tissue cells and functional damage, and eventually spermatogenic dysfunction.

Xuefu Zhuyu decoction improves asthma-induced asthenozoospermia based on network pharmacology and in vivo experiment.

This study aimed to verify that Xuefu Zhuyu decoction (XFZYD) can improve asthenozoospermia caused by asthma, and explore its potential mechanism. Ovalbumin solution is used to induce asthma rat models. Sperm concentration and motility are used to evaluate semen quality. Immunohistochemistry (IHC), Western blotting and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) are used to detect proteins and mRNA related to rat testis tissue. Haematoxylin and eosin (H&E) staining was used to observe changes in testicular tissues. Through network pharmacology, eriodictyol, 18-ß-glycyrrhetinic acid, naringenin, chrysin and Hispidulin were prominent active ingredients of XFZYD. We found that XFZYD regulates the expression levels of albumin (ALB), vascular endothelial growth factor A (VEGFA), interleukin 6 (IL-6) protein and mRNA, thereby improving the histopathological morphology of the testis, increasing the concentration and motility of spermatozoa. We suggest that future research can increase the detection of hormones and oxidative stress and other related indicators, so as to conduct more in-depth exploration.

Exploration of the effect of pulmonary fibrosis on erectile function in rats: A study based on bioinformatics and experimental research.

First, the bioinformatics database was used to predict the potential targets and signaling pathways of pulmonary fibrosis (PF) leading to erectile dysfunction (ED), and bleomycin sulfate was used to create a PF rat model. Then, enzyme-linked immunosorbent assay (ELISA), Western blotting, Real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression of sex hormones and related proteins and mRNA, and Hematoxylin and eosin (H&E) staining was used to compare the pathological changes of penile tissue. The results showed that, compared with group A, cyclic guanosine phosphate (cGMP) content in group B decreased, protein kinase CGMP-dependent 1(PKG1) and nitric oxide synthase 3 (eNOS) protein and mRNA expression were down-regulated, and phosphodiesterase 5A (PDE5A) protein and mRNA expression was up-regulated (p < .05); the penile tissue of rats in group B had pathological damage. And there was no change in sex hormone-related indicators in the two groups (p > .05). Therefore, PF inhibits erectile function by inhibiting the cGMP-PKG pathway and reducing the expression of eNOS and PKG1 protein and mRNA. And by up-regulating the expression of PDE5A to impair erectile function.

In vitro and in vivo investigation of the therapeutic mechanism of Lycium Chinense and Cuscutae Semen on oligoasthenozoospermia.

Through network pharmacology research, we found that CYP19, CYP17, AR and SRD5A2 were potential targets for lycium chinense-cuscutae semen (LC-CS) treatment of oligoasthenozoospermia. Using in vitro and in vivo experiments, tripterygium glycosides were used to induce spermatogenic dysfunction models in GC-1spg cells and SD male rats, respectively, and LC-CS was used to intervene in a spermatogenic dysfunction model. In vitro, LC-CS could repair the ultrastructure of GC-1spg cells damaged by tripterygium glycosides (TG). Compared with TG group, LC-CS could upregulate protein and mRNA expression of CYP19, CYP17, AR and SRD5A2. In vivo, compared with TG, the body mass, testicular mass and epididymal weights of rats in TG + LC-CS increased. Progressive motility + nonprogressive motility spermatozoon (PR + NP) of TG + LC-CS were upregulate than TG. The levels of FSH, LH and testosterone in TG + LC-CS were upregulate than TG. LC-CS can repair the ultrastructure of spermatogonia damaged by TG (the above results are statistically significant, p <.05). Results of H&E staining and TEM showed that the morphology and ultrastructure of testicular tissue in TG + LC-CS were better than that in TG. Compared with TG, LC-CS could upregulate the expression of CYP19, CYP17, AR and SRD5A2 proteins and mRNA.

Effect of leech-centipede medicine on improving erectile function in diabetes-induced erectile dysfunction rats via PDE5 signalling pathway-related molecules.

CONTEXT: The leech and centipede granules have good curative effects on many diabetic vascular diseases, including diabetes-induced erectile dysfunction (DIED). OBJECTIVE: To explore the effect of leech and centipede on erectile function in rats with diabetes-induced erectile dysfunction and its possible mechanism. MATERIALS AND METHODS: Thirty male Sprague-Dawley DIED rats were randomly divided into the model group (Group M), low-dose group (Group DD), high-dose group (Group DG) and tadalafil group (Group T) (n = 6); diabetic rats were induced by streptozotocin. Apomorphine was used to induce diabetic erectile dysfunction. The 'leech-centipede' granules (0.15 and 0.6 g/kg) were intragastrically administered in the DD and DG groups for 8 weeks. Blood glucose, serum insulin, testosterone, cGMP levels and protein expression changes were measured in each group. RESULTS: After 8 weeks, the erectile function of rats in the DG group significantly improved (1.26 ± 0.73). Penis tissue cGMP levels were higher in the DG group (1.48 ± 0.11) than in the M group (0.58 ± 0.15). Protein and mRNA expression levels of NOS were significantly higher (0.77 ± 0.05; 0.61 ± 0.02) but those of PDE5 (0.43 ± 0.05; 0.61 ± 0.03) were lower in the DG group than in the M group (0.37 ± 0.06; 0.51 ± 0.01; 0.78 ± 0.06; 0.81 ± 0.04). CONCLUSION: The leech-centipede can improve erectile dysfunction in DIED rats by regulating the expression of cGMP, NOS, and PDE5-related molecules in the PDE5 pathway. This study provides a potential mechanism for the treatment of DIED with leech-centipede.

Potential mechanism of Achyranthis bidentatae radix plus semen vaccariae granules in the treatment of diabetes mellitus-induced erectile dysfunction in rats utilizing combined experimental model and network pharmacology.

CONTEXT: Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects. OBJECTIVE: Explore mechanistic details of ABR + SV treatment against DMED. MATERIALS AND METHODS: Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 µg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix-semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA. RESULTS: The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03). CONCLUSION: ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.

[Asthma affects erectile function in rats: An experimental study].

Objective: To investigate the impact of asthma on erectile function in rats and the expressions of related proteins. METHODS: Male rats were injected intraperitoneally with ovalbumin solution to induce asthma followed by subcutaneous injection of apomorphine at 100 µg/kg into the neck, and then observed for reduced frequency or loss of penile erection. Based on the results of observation, a model of asthma-induced ED (AED) was made in 6 of the animals, and another 6 normal male rats were taken as controls. The histomorphology of the corpus cavernosum was observed by HE staining, and the mRNA and protein expressions of phosphodiesterase 5 (PDE5) and nitric oxide synthase 3 (eNOS) in the testis tissue were determined by RT-qPCR and Western blot. RESULTS: Compared with the normal controls, the rats in the AED model group showed disorderly distribution of sinusoids and decreased density of endothelial and smooth muscle cells in the corpus cavernosum. The mRNA and protein expressions of PDE5 were significantly higher (P < 0.05), while those of eNOS remarkably lower in the AED model than in the control group (P < 0.05). CONCLUSIONS: Asthma can induce ED and change the histomorphology of the corpus cavernosum in rats by affecting the expressions of PDE5 and eNOS proteins.

Effect of Asthma on Erectile Dysfunction in Rats as Determined by Biological Network Analysis.

BACKGROUND We explored the effect of asthma on erectile dysfunction (ED) and the effects of the expression of related proteins. MATERIAL AND METHODS We used a bioinformatics database to predict the targets and pathways associated with asthma and ED. The rat model of asthma was caused by an ovalbumin solution. The number of erections in 30 min was observed by injecting apomorphine into the neck at a dose of 100 µg/kg. Rats with no erection were regarded as the model group (group B), and the previous random 6 normal rats were regarded as the control group (group A). We used hematoxylin and eosin (HE) to compare the tissue structure of the cavernous body of the penis. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to determine the expression levels of insulin (INS), interleukin 6 (IL6), albumin (ALB), tumor necrosis factor (TNF), and vascular endothelial growth factor A (VEGFA) at both the protein and messenger ribonucleic acid (mRNA) levels. RESULTS HE staining results show that compared with group A, the blood sinus distribution of the cavernous body in group B was disordered, and the density of endothelial cells and smooth muscle cells decreased significantly. Western blotting and RT-qPCR showed that the levels of IL6, TNF, and VEGFA protein and mRNA in group B were significantly higher (P<0.05) than those in group A. The levels of INS and ALB were not significantly different between the 2 groups. CONCLUSIONS On the basis of the results, we found that asthma caused pathological changes in the penises of rats and led to reduced erectile function via changes in the expression of IL6, TNF, and VEGFA proteins.

Biological Network Model of Effect of Chronic Intermittent Hypoxia on Spermatogenesis in Rats.

BACKGROUND The aim of this study was to explore the effect of obstructive sleep apnea hypopnea syndrome (OSAHS) on spermatogenesis and the effects of the expression of related proteins. MATERIAL AND METHODS Rats in Group A were normoxic (exposed to a normal level of oxygen). Rats in Group B were exposed to intermittent hypoxia. After 6 weeks, the rats were killed and their epididymides were removed. The epididymis of one testis was used to test indices of semen quality. The epididymis of the other testis was stained with hematoxylin & eosin to observe pathologic changes in the testis. We used real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting to measure expression of the protein and mRNA of leptin, Janus kinase (JAK), and signal transducer and activator of transcription (STAT) in rat testicular cells. Cytoscape v3.7.1 was employed to construct the OSAHS-male infertility network and protein-protein interactions network. Information on common targets of OSAHS and male infertility was imported into the Database for Annotation, Visualization and Integrated Discovery (DAVID). Then, analyses of pathway enrichment were undertaken using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. RESULTS Data were obtained 6 weeks after completion of OSAHS modeling. Compared with Group A, the total sperm count and sperm motility in Group B showed a downward trend (P<0.05). Staining showed no obvious abnormality in Group A. However, numerous structurally abnormal spermatogenic tubules were observed in Group B samples, and the lumen was atrophied and thinned, arranged unevenly, and the gap between the tubules was markedly increased. Western blotting and RT-qPCR showed that, compared with Group A, expression of the protein and mRNA of leptin, JAK, and STAT in the testes of rats in Group B was significantly increased (P<0.05 for all). CONCLUSIONS These data suggest that: (1) Chronic intermittent hypoxia can cause pathologic damage to rat testes; (2) Oligozoospermia was highly correlated and regulated by the JAK2/STAT6 signaling pathway; and (3) Chronic intermittent hypoxia can lead to decreased spermatogenesis in rats.

Association of serum uric acid with male sexual hormones and erectile dysfunction: a bidirectional 2-sample Mendelian randomization analysis.

Background: Observational studies indicated that serum uric acid (SUA) was associated with male sexual hormones and erectile dysfunction (ED). However, their relationship was still heterogeneous. Aim: This study conducted 2-sample univariate mendelian randomization (UVMR) and multivariate mendelian randomization (MVMR) to explore the causal relationship between SUA and sexual hormones as well as ED. Methods: Genetic variants associated with SUA were derived from the UK Biobank database (N = 437 354). Outcomes from the IEU Open GWAS and summary data sets were sexual hormones (sex hormone-binding globulin [SHBG], testosterone, estradiol [E2], follicle-stimulating hormone, luteinizing hormone) and ED, with 3301 to 625 650 participants. UVMR analysis primarily utilized the inverse variance weighted method, complemented by MVMR analysis. Thorough sensitivity analyses were carried out to ensure the reliability of results. Moreover, mediation analysis was conducted to estimate the mediated effect between SUA and outcomes. Outcomes: The primary outcomes included results of UVMR and MVMR analysis and mediation analysis, along with sensitivity analyses involving the Cochran Q test, the MR Egger intercept test, leave-1-out analysis, and the MR-PRESSO method (mendelian randomization pleiotropy residual sum and outlier). Results: UVMR analysis revealed that an elevated SUA level could decrease levels of SHBG (ß = -0.10, P = 1.70 × 10-7) and testosterone (ß = -0.10, P = 5.94 × 10-3) and had a positive causal effect on ED (odds ratio, 1.10; P = .018). According to reverse mendelian randomization results, increased levels of SHBG (ß = -0.06, P = 4.82 × 10-4) and E2 (ß = -0.04, P = .037) could also reduce SUA levels. As shown by MVMR analysis, SUA had a negative effect on SHBG and testosterone levels (P < .05), while the significant causal relationship between SUA and ED disappeared. Furthermore, SHBG mediated 98.1% of the effect of SUA on testosterone levels. Results of other mendelian randomization analyses were not statistically significant. No pleiotropy was found by sensitivity analysis in this study. Clinical Implications: Given the causal relationship between SUA and sexual hormones, we must focus on SUA and E2 levels in men, especially patients with hypogonadism and ED. Strengths and Limitations: This study evaluated the causal effect of SUA on male sexual hormones and ED genetically for the first time, clarifying the common biases in observational studies and confirming the negative relationship between SUA and testosterone level. Limitations include a population based on European ancestry, some crossover of the samples, and unobserved confounding factors. Conclusion: Genetic studies provide evidence for the causal relationship between SUA and male sexual hormones (SHBG, testosterone, E2), while the relationship between SUA and ED should be further evaluated.

Genetically predicted hypertension, antihypertensive drugs, and risk of erectile dysfunction: a Mendelian randomization study.

Background: The causal relationship between hypertension, antihypertensive drugs and the risk of erectile dysfunction is still uncertain. We performed a univariable and multivariable Mendelian randomization study to investigate whether they are causally related to erectile dysfunction. Methods: Genetic variants associated with blood pressure were derived from the genome-wide association study meta-analysis of the UK Biobank and International Consortium of Blood Pressure (N = 757,601). Summary association data for hypertension were obtained from the UK Biobank (N = 463,010) and the FinnGen study (N = 356,077). The summary statistics of erectile dysfunction were obtained from the European ancestry with 223,805 subjects. The SNP instruments used to assess the effect of the protein targets of antihypertensive drugs on erectile dysfunction were obtained from previous studys. Causal effects were estimated using the univariate Mendelian randomization method (inverse variance weighted, MR-Egger, weighted median, MR-PRESSO and Wald ratios) and the multivariate Mendelian randomization method. Sensitivity analyses were implemented with the Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Results: Univariate MR found that elevated diastolic blood pressure may increase the occurrence of erectile dysfunction (odds ratio [OR] = 1.012; 95% confidence interval [CI]: 1.000-1.024; P = 0.047). Genetically predicted hypertension is also associated with ED (For the FinnGen, OR = 1.106; 95% CI: 1.027-1.191; P = 0.008. For the UK Biobank, OR = 3.832; 95% CI: 1.410-10.414; P = 0.008). However, after adjusting for systolic blood pressure, diastolic blood pressure and hypertension using multivariate Mendelian randomization, only hypertension was causally associated with ED occurrence (For the FinnGen, OR = 1.103; 95% CI: 1.018-1.195; P = 0.017. For the UK Biobank, OR = 5.037; 95% CI: 1.601-15.846; P = 0.006). We found no evidence that the use of angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and thiazide diuretic increased the risk of erectile dysfunction. Conclusions: Genetically predicted hypertension increases the risk of erectile dysfunction, but we found no causal relationship between elevated systolic/diastolic blood pressure and erectile dysfunction. We speculate that the relationship between elevated blood pressure and erectile dysfunction risk may be nonlinear. We found little evidence that antihypertensive drugs increase the risk of erectile dysfunction.

Context-Fused Guidance for Image Captioning Using Sequence-Level Training.

Recent image captioning models based on the encoder-decoder framework have achieved remarkable success in humanlike sentence generation. However, an explicit separation between encoder and decoder brings out a disconnection between the image and sentence. It usually leads to a rough image description: the generated caption only contains main instances but neglects additional objects and scenes unexpectedly, which reduces the caption consistency of the image. To address this issue, we proposed an image captioning system within context-fused guidance in this paper. It incorporates regional and global image representation as the compositional visual features to learn the objects and attributes in images. To integrate image-level semantic information, the visual concept is employed. To avoid misleading decoding, a context fusion gate is introduced to calculate the textual context by selectively aggregating the information of visual concept and word embedding. Subsequently, the context-fused image guidance is formulated based on the compositional visual features and textual context. It provides the decoder with informative semantic knowledge. Finally, a captioner with a two-layer LSTM architecture is constructed to generate captions. Moreover, to overcome the exposure bias, we train the proposed model through sequence decision-making. The experiments conducted on the MS COCO dataset show the outstanding performance of our work. The linguistic analysis demonstrates that our model improves the caption consistency of the image.

Global research trends in penile cancer: Bibliometric and visualized analysis.

Background: Penile cancer is a malignant tumor of the genitourinary system that mostly occurs in middle-aged and elderly men aged 50-70 years, which can seriously affect physical, psychological, and sexual health. Hundreds of original articles and reviews on penile cancer are published each year. However, a bibliometric analysis of these publications has not been performed. Objective: This study aimed to systematically analyze and visualize penile cancer-related publications through bibliometrics and reveal identified topics, hotspots, and knowledge gaps in related fields. Methods: Based on the Web of Science core collection database, we first analyzed the quantity and quality of publications in the field of penile cancer. Second, we profiled the publishing groups in terms of country, institution, author's publication, and cooperation network. Then, we systematized and summarized the hot topics of research. Results: This bibliometric analysis was conducted from 2001 to 2022. The analysis identified 1,687 articles and reviews, which were published in 432 journals. The number of publications and citations on penile cancer-related research has steadily increased over the last two decades. Furthermore, academic institutions in Europe and the United States play a leading role in penile cancer research. The country, institution, journal, and author with the most publications were the United States (507), H Lee Moffitt Cancer Research Center (96), Journal of Urology (83), and Spiess P (87), respectively. The most frequently used keywords were penile cancer (743), squamous-cell carcinoma (717), cancer (380), carcinoma (232), lymphadenectomy (229). 16 keyword clustering information was obtained, including #0 male circumcision, #1 lichen sclerosus, #2 chemotherapy, #3 penile neoplasms, #4 targeted therapy, #5 resection margin, #6 cervical cancer, #7 lymph node dissection, #8 prognostic factor, #9 prostate cancer, #10 inguinal lymph node dissection, #11 human papillomavirus DNA, #12 gene, #13 penile intraepithelial neoplasia, #14 male sexual function, and #15 penile cancer. Conclusion: More and more scholars are devoted to the research on penile cancer. This bibliometric analysis revealed that the main research topics and hotspots in penile cancer included risk factors and surgical treatment plans.