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Abstract Background Prostate cancer is one of the most common cancers in men with a significant proportion of patients developing biochemical recurrence (BCR) after treatment. Programmed cell death (PCD) mechanisms are known to play critical roles in tumor progression and can potentially serve as prognostic and therapeutic biomarkers in PCa. This study aimed to develop a prognostic signature for BCR in PCa using PCD-related genes. Materials and methods We conducted an analysis of 19 different modes of PCD to develop a comprehensive model. Bulk transcriptomic, single-cell transcriptomic, genomic, and clinical data were collected from multiple cohorts, including TCGA-PRAD, GSE58812, METABRIC, GSE21653, and GSE193337. We analyzed the expression and mutations of the 19 PCD modes and constructed, evaluated, and validated the model. Results Ten PCD modes were found to be associated with BCR in PCa, with specific PCD patterns exhibited by various cell components within the tumor microenvironment. Through Lasso Cox regression analysis, we established a Programmed Cell Death Index (PCDI) utilizing an 11-gene signature. High PCDI values were validated in five independent datasets and were found to be associated with an increased risk of BCR in PCa patients. Notably, older age and advanced T and N staging were associated with higher PCDI values. By combining PCDI with T staging, we constructed a nomogram with enhanced predictive performance. Additionally, high PCDI values were significantly correlated with decreased drug sensitivity, including drugs such as Docetaxel and Methotrexate. Patients with lower PCDI values demonstrated higher immunophenoscores (IPS), suggesting a potentially higher response rate to immune therapy. Furthermore, PCDI was associated with immune checkpoint genes and key components of the tumor microenvironment, including macrophages, T cells, and NK cells. Finally, clinical specimens validated the differential expression of PCDI-related PCDRGs at both the gene and protein levels. Conclusion In conclusion, we developed a novel PCD-based prognostic feature that successfully predicted BCR in PCa patients and provided insights into drug sensitivity and potential response to immune therapy. These findings have significant clinical implications for the treatment of PCa.

Abstract Background Although men with premature ejaculation (PE) always show more negative emotions, including embarrassment, guilt and worry, this may be related to the stigma of PE. To investigated stigma and its associations with self-confidence and sexual relations in 4 PE syndromes, a survey was conducted in our hospital from December 2018 to December 2019 among 350 men with self-reported PE and 252 men without self-reported PE. The stigma, self-confidence and sexual relations were assessed by the Social Impact Scale (SIS) and Self-Esteem and Relationship questionnaire (SEAR), respectively. Ejaculation control, sexual life satisfaction and distress caused by PE were evaluated by the Index of PE. Results Men with self-reported PE had higher internalized shame and social isolation scores and lower SEAR scores than control subjects. The highest score of internalized shame and social isolation and the lowest score of SEAR appeared in men with lifelong PE (LPE). After age adjustment, the positive relationships were stronger between distress about PE and internalized shame. Whereas, the stronger negative associations were found between social isolation and sexual satisfaction. The strongest association was observed between social isolation and sexual relationship. Therefore, the stigma associated with PE adversely affects the self-confidence, self-esteem, and sexual relationships of men with PE. Conclusion Men with PE, especially LPE, have a high level of stigma and disharmonious sexual relations, and often lack self-confidence and self-esteem, which have a certain negative impact on their physical and mental health and life. These will be the key issues to be considered when we formulate a personalized treatment plan for PE.

Abstract Objective Shift work and Shift Work Sleep Disorder (SWSD) are known to affect the secretion of several neurotransmitters and hormones associated with premature ejaculation (PE). However, their specific influence on the regulation of male ejaculation remains unclear. This study explores the relationship between shift work, SWSD, and PE. Methods From April to October 2023, a cross-sectional survey was conducted across five regions of China to explore the work schedules, sleep quality, and sexual function of male workers. Participants' sleep quality was evaluated using a validated SWSD questionnaire, and their erectile function and ejaculatory control were assessed with the International Inventory of Erectile Function (IIEF-5) scores and Premature Ejaculation Diagnostic Tool (PEDT) scores, respectively. Univariate and multivariate linear regression analyses were employed to identify risk factors associated with PE. Confounders were controlled using multiple regression models, and clinical prediction models were developed to predict PE onset and assess the contribution of risk factors. Results The study included 1239 eligible participants, comprising 840 non-shift workers and 399 shift workers (148 with SWSD and 251 without SWSD). Compared to non-shift working males, those involved in shift work (β 1.58, 95% CI 0.75 – 2.42, p

Highlights MXene sediments is innovatively used as photothermal material for seawater desalination. Inspired by the natural wood transpiration process, a 3D MXene sediment-based aerogel with vertically aligned channels is innovatively prepared as solar evaporator. With unique structure and composition, excellent photothermal conversion efficiency, evaporation rate, salt resistance, and resistance to biological/oil/special environments are achieved in practical desalination.

Abstract Background PCD-related long non-coding RNAs (PRLs) are rarely investigated in relation to clear cell renal carcinoma (ccRCC). As part of this study, we evaluated the immunological potential of PRL signatures as a biomarker for ccRCC prognosis and immunological function. Materials and methods Data were downloaded from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases. A Pearson correlation analysis was conducted on the 27 PCD-associated genes to determine whether lncRNAs were significantly associated with PCD. Kaplan–Meier analysis, biological function identification, immune infiltration analysis, estimation of efficacy of immunotherapy and targeted drug screening, and exploration of the landscape of mutation status were conducted by analyzing the risk scores. Results Seven PRLs, LINC02747, AP001636.3, AC022126.1, LINC02657, LINC02609, LINC02154, and ZNNT1, were used to divide patients with ccRCC into groups with high and low risk. High-risk patients had a worse prognosis than low-risk patients, according to the results, and the PRL signature showed promising predictive ability. More immune cells were clustered in the high-risk group, whereas the immune cell function of the low-risk group was significantly suppressed. The high-risk group was less sensitive to immunotherapy, whereas the low-risk group had positive responses to most drugs. Conclusions Collectively, we established and verified a PRL signature that could competently guide the prognostic survival and immunotherapy of ccRCC. In addition, molecular subtypes were determined for ccRCC based on PRL expression, which may help elucidate the underlying molecular mechanism of ccRCC and develop targeted treatments.

Polystyrene nanoplastics (PS-NPs), emerging and increasingly pervasive environmental contaminants, have the potential to cause persistent harm to organisms. Although previous reports have documented local accumulation and adverse effects in a variety of major organs after PS-NPs exposure, the impact of PS-NPs exposure on erectile function remains unexplored. Herein, we established a rat model of oral exposure to 100 nm PS-NPs for 28 days. To determine the best dose range of PS-NPs, we designed both low-dose and high-dose PS-NPs groups, which correspond to the minimum and maximum human intake doses, respectively. The findings indicated that PS-NPs could accumulate within the corpus cavernosum and high dose but not low dose of PS-NPs triggered erectile dysfunction. Moreover, the toxicological effects of PS-NPs on erectile function include fibrosis in the corpus cavernous, endothelial dysfunction, reduction in testosterone levels, elevated oxidative stress and apoptosis. Overall, this study revealed that PS-NPs exposure can cause erectile dysfunction via multiple ways, which provided new insights into the toxicity of PS-NPs.

Abstract Background Few studies were conducted to explore the association between sleep quality and nocturnal erection. Here, we intended to explore the association between sleep quality and nocturnal erection monitor when conducting nocturnal erection monitor. All erectile dysfunction (ED) patients underwent sleep monitors using Fitbit Charge 2™ (Fitbit Inc.) and nocturnal penile tumescence and rigidity (NPTR) monitors using RigiScan® (GOTOP medical, Inc., USA) for two nights. Subsequently, the patients were divided into two groups: Group A included patients who experienced effective erections only on the second night, while Group B included patients who had effective erections on both nights. To explore the associations between NPTR parameters and sleep parameters, a comparative analysis was performed between Group A and Group B for both nights. Results Finally, our study included 103 participants, with 47 patients in Group A and 56 patients in Group B. Notably, the Group A patients showed significant improvements in NPTR parameters on the second night compared to the first night. Conversely, the NPTR parameters on Group B of the second night did not demonstrate a superior outcome when compared to the second night of Group A. Interestingly, it was found that only the disparities in sleep parameters accounted for the variation in NPTR parameters between the two groups on the first night. After correlation and ROC analysis, we identified the rapid eye movement (REM) sleep time and wake after sleep onset (WASO) time monitoring by the Fitbit Charge 2 as the primary parameters for predicting abnormal NPTR results in the first night. Conclusions Therefore, our study strongly suggests a close association between sleep parameters and NPTR parameters. It emphasizes the importance of incorporating sleep monitoring alongside nocturnal erection monitoring to enhance the reliability of the NPTR results.

Abstract The sole situation of semi-crystalline structure induced single performance remarkably limits the green cryogels in the application of soft devices due to uncontrolled freezing field. Here, a facile strategy for achieving multifunctionality of cryogels is proposed using total amorphization of polymer. Through precisely lowering the freezing point of precursor solutions with an antifreezing salt, the suppressed growth of ice is achieved, creating an unusually weak and homogenous aggregation of polymer chains upon freezing, thereby realizing the tunable amorphization of polymer and the coexistence of free and hydrogen bonding hydroxyl groups. Such multi-scale microstructures trigger the integrated properties of tissue-like ultrasoftness (Young’s modulus

Purpose: The aim of the present study was to test the hypothesis that recovery sleep could counteract the detrimental effects of sleep deprivation (SD) on male rats’ fertility. Materials and Methods: Twenty-two rats were housed in groups of six per cage with unrestricted access to food and water in a room. The modified multiple platform method was used to induce SD in rats over a 96-hour period. We examined the effect of SD on semen quality, reproductive hormones, and testicular histology in adult male rats. Then, we investigated the effect of 7 days recovery sleep on impaired reproductive function induced by SD. Results: After the acclimation period, 22 rats were randomly separated into three experimental groups (SD, recovery sleep, and the control groups). Ninety-six hours of SD resulted in a significant decrease in sperm motility (24.33±10.93 vs . 48.20±8.55, p

This study aimed to compare the efficacy and risk of adverse events of sildenafil plus vitamin D3 versus sildenafil alone in improving erectile dysfunction (ED) in ED patients with low serum 25-hydroxy vitamin D3 (25-(OH)D3). The clinical data of ED patients with low serum 25-(OH)D3 treated at our center from December 2015 to December 2020 were retrieved, and the patients (n = 157) were randomly divided into an experimental group (n = 80) or a control group (n = 77). The experimental group was treated with 1 capsule of vitamin D3 (400u) daily for a month and advised to use 100 mg sildenafil (po) within 1 hour before sexual intercourse, while the control group was only given 100 mg sildenafil (po) 1 hour before sexual intercourse. The indexes of international erectile function (IIEF-5), serum 25-(OH)D3 level, testosterone (T) level and adverse events between the two groups were compared before and after treatment. The results showed that the IIEF-5 values of the two groups were significantly higher after treatment than before treatment (p < 0.05). However, the serum levels of 25-(OH)D3 and T in the experimental group were significantly higher than before treatment (p < 0.05), while no significant differences were observed in the same markers in the control group before and after treatment (p > 0.05). The overall effective rate, serum 25-(OH)D3 level and T level in the experimental group were significantly higher than the control group (p < 0.05). During the treatment, no significant difference in adverse events was observed between the two groups (p > 0.05), which mostly comprised mild and tolerable headache, dyspepsia, back pain and muscle soreness, not requiring any medical intervention. Although both methods could effectively treat ED patients with low 25-(OH)D3, the efficacy of sildenafil plus vitamin D3 was significantly superior to sildenafil alone, and the adverse reactions are mild and tolerable, which is worthy of clinical application.

Abstract Background We investigated the association between premature ejaculation (PE) and the quality of residential environment from a new perspective to explore the influencing factors of PE, especially in four PE subtypes. We selected 499 adult males to participate in this study from September 2021 to September 2022. The satisfaction of residential environment was assessed by the Perceived Residential Environment Quality Indicators (PREQIs) scale, the control ability over ejaculation was assessed using the premature ejaculation diagnostic tool (PEDT), and their depression was assessed using the self-rating depression scale (SDS). Results The Architectural and Town-planning Spaces (ATS), Green Spaces (GS), and Commercial Services (CS) of PE patients (N = 346) were compared with those of control group (N = 153), showed a significant difference (p

Abstract Background Plant and animal embryogenesis have conserved and distinct features. Cell fate transitions occur during embryogenesis in both plants and animals. The epigenomic processes regulating plant embryogenesis remain largely elusive. Results Here, we elucidate chromatin and transcriptomic dynamics during embryogenesis of the most cultivated crop, hexaploid wheat. Time-series analysis reveals stage-specific and proximal–distal distinct chromatin accessibility and dynamics concordant with transcriptome changes. Following fertilization, the remodeling kinetics of H3K4me3, H3K27ac, and H3K27me3 differ from that in mammals, highlighting considerable species-specific epigenomic dynamics during zygotic genome activation. Polycomb repressive complex 2 (PRC2)-mediated H3K27me3 deposition is important for embryo establishment. Later H3K27ac, H3K27me3, and chromatin accessibility undergo dramatic remodeling to establish a permissive chromatin environment facilitating the access of transcription factors to cis-elements for fate patterning. Embryonic maturation is characterized by increasing H3K27me3 and decreasing chromatin accessibility, which likely participates in restricting totipotency while preventing extensive organogenesis. Finally, epigenomic signatures are correlated with biased expression among homeolog triads and divergent expression after polyploidization, revealing an epigenomic contributor to subgenome diversification in an allohexaploid genome. Conclusions Collectively, we present an invaluable resource for comparative and mechanistic analysis of the epigenomic regulation of crop embryogenesis.

Objectives To explore the value of dual-energy computed tomography (DE-CT) angiography in diagnosis of arteriogenic erectile dysfunction (ED) patients and feasibility of new scanning area that excludes the testis.Materials and methods Ninety-three patients suspected of suffering arterial ED and 40 health volunteers underwent penile duplex Doppler ultrasound and DE-CT angiography (DE-CTA). The scanning range of DE-CTA covered whole arterial system of pelvis and testis was excluded. Two blinded investigators independently evaluated the arterial system that supplies the penis.Results Finally, 1596 segments were evaluated and 470 segments were judged to be abnormal. The distribution was: 2 (0.4%) in common iliac artery, 7 (1.5%) in internal iliac artery, 82 (17.5%) in internal pudendal artery, 89 (18.9%) in penile artery, 120 (25.5%) in dorsal artery, and 170 (36.2%) in cavernosal artery. The specificity, sensitivity, positive predictive value, and negative predictive value of DE-CTA in diagnostic were 86.02%, 87.50%, 94.12%, and 72.92%. Besides, the new scan area allowed for effective evaluation of the arteries while excluding the testis.Conclusion DE-CTA can provide unbiased, safe evaluation of the vascular status of the penile bed in patients with ED.

Abstract Background: To date, no study has evaluated trends in the burden of alcohol-induced cirrhosis and other chronic liver diseases based on the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2019 study. Herein, we report on the global burden of alcohol-induced cirrhosis and other chronic liver diseases in terms of age, sex, and sociodemographic index (SDI) from 1990 to 2019, based on analysis of GBD 2019 data. Methods: The estimated annual percentage change (EAPC) was calculated to determine the trends in the age-standardized incidence and mortality rates and disability-adjusted life years (DALYs) for alcohol-induced cirrhosis and other chronic liver diseases. Results: From 1990 to 2019, the global age-standardized incidence rate showed an upward trend (EAPC = 0.10), whereas the global age-standardized mortality rate and DALYs showed a downward trend (EAPC = − 0.88 and − 0.89, respectively). Low-(187.08 in 2019) and low-middle (178.11 in 2019)SDI regions had much higher age-standardized DALYs. Eastern Europe saw the largest increases in the age-standardized mortality rate and DALYs. Lithuania had the largest increase in mortalities caused by alcohol-induced cirrhosis and other chronic liver diseases(EAPC = 4.61). The age-standardized mortality rates and DALYs were higher in men than in women. Conclusion: From 1990 to 2019, the age-standardized incidence rate of alcohol-induced cirrhosis and other chronic liver diseases increased globally; however, both the age-standardized mortality rate and DALYs caused by alcohol-induced cirrhosis and other chronic liver diseases showed decreasing trends. Future studies should devise preventive strategies for low and low-middle SDI regions, Eastern Europe, Lithuania, and other high-risk regions.

Abstract Background Shengjing capsule (SJC) is a traditional Chinese medicine (TCM) and has gained widespread clinical application for the treatment of male infertility (MI). However, the pharmacological mechanism of SJC against MI remains vague to date. Method The active ingredients of SJC and their targets were identified from the database, and MI-related genes were retrieved from several databases. Protein–protein interaction (PPI) data were obtained to construct the PPI networks. The candidate targets of SJC against MI were identified through topological analysis of the PPI network. Functional enrichment analysis of candidate targets was performed, and the key target genes were identified from the gene-pathway network. Results We identified 154 active ingredients and 314 human targets of SJC, as well as 564 MI-related genes. Eight pharmacological network diagrams illustrating the interactions among herbs, active ingredients, targets, and pathways, were constructed. The four dominating network maps included a compound-target network of SJC, a compound-anti-MI targets network, a candidate targets PPI network, a pathway-gene network, and a drug-key compounds-hub targets-pathways network. Systematic analysis indicated that the targets of SJC in the treatment of MI mainly involved RPS6, MAPK1, MAPK3, MDM2, and DDX5. Pathway enrichment analysis showed that SJC had the potential to impact multiple biological pathways, such as cancer-related pathways, viral/bacterial infection-related pathways, and signal transduction-related pathways. Conclusion Our results preliminarily revealed the pharmacological basis and molecular mechanism SJC in treating MI, but further experimental research is required to verify these findings.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Non-obstructive azoospermia (NOA) is the most severe type of male infertility, affecting 1% of men worldwide. Most of its etiologies remain idiopathic. Although genetic studies have identified dozens of NOA genes, monogenic mutations can also account for a small proportion of idiopathic NOA cases. Hence, this genetic study was conducted to explore the causes of monogenic variants of NOA in a cohort of Chinese patients. Methods Following the screening using chromosomal karyotyping, Y chromosome microdeletion analyses, and sex hormone assessments, subsequent whole-exome sequencing analysis was performed in 55 unrelated idiopathic NOA patients with male infertility to explore potential deleterious variants associated with spermatogenesis. We also performed Sanger sequencing to demonstrate the variants. Testicular biopsy or microsurgical testicular sperm extraction was also performed to confirm the diagnosis of NOA and identify spermatozoa. Hematoxylin and eosin staining was performed to assess the histopathology of spermatogenesis. Results Abnormal testicular pathological phenotypes included Sertoli cell-only syndrome, maturation arrest, and hypospermatogenesis. Using bioinformatics analysis, we detected novel variants in two recessive genes, FANCA (NM_000135, c.3263C > T, c.1729C > G) and SYCE1 (NM_001143763, c.689_690del); one X-linked gene, TEX11 (NM_031276, c.466A > G, c.559_560del); and two dominant genes, DMRT1 (NM_021951, c.425C > T, c.340G > A) and PLK4 (NM_001190799, c.2785A > G), in eight patients, which corresponded to 14.55% (8/55) of the patients. Conclusion This study presented some novel variants of known pathogenic genes for NOA. Further, it expanded the variant spectrum of NOA patients, which might advance clinical genetic counseling in the future.

Abnormal body mass index (BMI) is associated with an increased risk of erectile dysfunction (ED). However, the relationship between different BMI categories and the levels of ED severity remains unclear. In the current study, 878 men from the andrology clinic in Central China were recruited. Erectile function was assessed by the International Index of Erectile Function (IIEF) scores. Questionnaires included questions about demographic characteristics (age, height, weight, educational status), lifestyle habits (drinking, smoking, sleep time), and medical history. Logistic regression was used to examine the association between ED risk and BMI. The incidence of ED was 53.1%. BMI was significantly higher in men from the ED group than in those from the non-ED group (P = 0.01). Compared with the normal weight group, obese men had a higher risk of ED (OR = 1.97, 95% CI = 1.25-3.14, P = 0.004), even after adjustment for potential confounders (OR = 1.78, 95% CI = 1.10-2.90, P = 0.02). Moreover, the positive correlation between obesity and moderate/severe ED severity was confirmed by logistic regression analysis (moderate/severe ED, OR = 2.71, 95% CI = 1.44-5.04, P = 0.002), even after adjusting for potential confounders (OR = 2.51 95% CI = 1.24-5.09, P = 0.01). Collectively, our findings indicate a positive correlation between obesity and the risk of moderate/severe ED. Clinicians could pay more attention to moderate/severe ED patients to maintain a healthy body weight to improve erectile function.

Abstract The heavy metal cadmium is proposed to be one of the environmental endocrine disruptors of spermatogenesis. Cadmium-induced inhibition of spermatogenesis is associated with a hormone secretion disorder. Letrozole is an aromatase inhibitor that increases peripheral androgen levels and stimulates spermatogenesis. However, the potential protective effects of letrozole on cadmium-induced reproductive toxicity remain to be elucidated. In this study, male mice were administered CdCl2 (4 mg/kg BW) orally by gavage alone or in combination with letrozole (0.25 mg/kg BW) for 30 days. Cd exposure caused a significant decreases in body weight, sperm count, motility, vitality, and plasma testosterone levels. Histopathological changes revealed extensive vacuolization and decreased spermatozoa in the lumen. However, in the Cd + letrozole group, letrozole treatment compensated for deficits in sperm parameters (count, motility, and vitality) induced by Cd. Letrozole treatment significantly increased serum testosterone levels, which were reduced by Cd. Histopathological studies revealed a systematic array of all germ cells, a preserved basement membrane and relatively less vacuolization. For a mechanistic examination, RNA-seq was used to profile alterations in gene expression in response to letrozole. Compared with that in the Cd-treated group, RNA-Seq analysis showed that 214 genes were differentially expressed in the presence of letrozole. Gene ontology (GO) enrichment analysis and KEGG signaling pathway analysis showed that steroid biosynthetic processes were the processes most affected by letrozole treatment. Furthermore, we found that the expression of the testosterone synthesis-related genes LHCGR (luteinizing hormone/choriogonadotropin receptor) and Hsd3b6 (3 beta- and steroid delta-isomerase 6) was significantly downregulated in Cd‐treated testes, but these genes maintained similar expression levels in letrozole-treated testes as those in the control group. However, the transcription levels of inflammatory cytokines, such as IL-1β and IL-6, and oxidative stress-related genes (Nrf2, Nqo1, and Ho-1) showed no changes. The present study suggests that the potential protective effect of letrozole on Cd-induced reproductive toxicity might be mediated by the upregulation of LHCGR and Hsd3b6, which would beneficially increase testosterone synthesis to achieve optimum protection of sperm quality and spermatogenesis.

Highlights The 3D honeycomb-like fabric decorated with MXene is woven as solar evaporator. The honeycomb structure enables light-trapping and recycling of convective and radiative heat. The 3D honeycomb-fabric evaporator possesses high solar efficiency up to 93.5% under 1 sun irradiation and excellent salt harvesting ability. Abstract Solar steam generation technology has emerged as a promising approach for seawater desalination, wastewater purification, etc. However, simultaneously achieving superior light absorption, thermal management, and salt harvesting in an evaporator remains challenging. Here, inspired by nature, a 3D honeycomb-like fabric decorated with hydrophilic Ti3C2Tx (MXene) is innovatively designed and successfully woven as solar evaporator. The honeycomb structure with periodically concave arrays creates the maximum level of light-trapping by multiple scattering and omnidirectional light absorption, synergistically cooperating with light absorbance of MXene. The minimum thermal loss is available by constructing the localized photothermal generation, contributed by a thermal-insulating barrier connected with 1D water path, and the concave structure of efficiently recycling convective and radiative heat loss. The evaporator demonstrates high solar efficiency of up to 93.5% and evaporation rate of 1.62 kg m−2 h−1 under one sun irradiation. Moreover, assisted by a 1D water path in the center, the salt solution transporting in the evaporator generates a radial concentration gradient from the center to the edge so that the salt is crystallized at the edge even in 21% brine, enabling the complete separation of water/solute and efficient salt harvesting. This research provides a large-scale manufacturing route of high-performance solar steam generator.

ABSTRACT: Background: Leptin, which was only discovered in humans in 1994, has recently been shown to have a possible link with premature ejaculation. Aim: To evaluate whether serum leptin levels differed between patients with premature ejaculation and healthy men, and to analyze the changes in leptin levels before and after treatment. Methods: Six studies assessing the relationship between leptin and premature ejaculation published up to October 2021 were identified from multiple databases (PubMed, Web of Science, Cochrane) and the data were analyzed by Stata software. Outcomes: Differences in leptin levels in premature ejaculation patients and healthy people, and changes of leptin levels in premature ejaculation population before and after treatment. Results: Analysis of studies assessing differences in leptin concentrations between patients with PE and healthy men showed that there was a statistically significant difference in leptin levels between PE patients and controls (WMD (95% CI) = 17.89 (8.64, 27.14), P < .001). On the other hand, the analysis of data from 3 studies describing serum leptin levels in PE patients before and after treatment with selective serotonin reuptake inhibitors (SSRIs) showed that there was a significant decrease with leptin levels in PE patients after treatment (WMD (95%CI) = 22.06 (17.21, 26.92), P < .001). Clinical Implications: It is possible that leptin can be used as a new marker for premature ejaculation. Strength & Limitations: The strength of this study is that it is the first meta- analysis to assess the differences of serum leptin levels between patients with premature ejaculation and healthy subjects and the changes of leptin levels before and after treatment in patients with premature ejaculation. A major limitation is that a greater heterogeneity was identified through our analysis, however we did not find a definitive source of heterogeneity. Conclusion: There was a statistically significant relationship between serum leptin levels and patients with PE. In addition, serum leptin levels in patients with PE decreased significantly after 8 weeks of treatment with SSRIs.Liu G, Zhang Y, Zhang W, et al. Novel Marker for Premature Ejaculation: Serum Leptin Level. Sex Med 2022;10:100509.

Résumé Contexte L’éjaculation précoce (EP) est. un problème multifactoriel, avec une étiologie compliquée, qui a des effets néfastes sur la fonction sexuelle des partenaires féminines. Cependant, il existe un manque d’études en Chine portant sur la relation entre les facteurs liés à l’EP et la dysfonction sexuelle féminine (DSF). Nos objectifs étaient d’identifier et d’explorer la relation entre les facteurs associés à l’EP et la DSF. Résultats Finalement, des informations ont été recueillies auprès de 761 couples: 445 couples avec plaintes d’EP et 316 couples sans plaintes d’EP. L’âge moyen des hommes avec et sans plaintes d’EP était respectivement de 36,29 ± 9,87 ans et 31,48 ± 10,77 ans. Les partenaires féminines du groupe avec plaintes d’EP ont obtenu des valeurs abaissées des scores, totaux et par sous-domaines, de l’indice de la fonction sexuelle féminine (IFSF), et environ 65% d’entre elles ont eu un diagnostic de DSF (pour 31,96% dans le groupe témoin). Une durée d’EP de plus de 14 mois, un temps intravaginal auto-estimé de latence d’éjaculation (IELT auto-estimé) de moins de 2 min, une attitude négative envers des problèmes d’EP, une introversion des hommes, et une dépression chez les hommes étaient des facteurs de risque de la DSF dans le groupe avec EP. Conclusions L’EP affecte non seulement le patient lui-même, mais aussi la conjointe. L’analyse complète révèle une relation et une interaction claires entre la fonction sexuelle féminine et l’EP. En outre, dans le traitement de l’EP, nous ne devrions pas ignorer l’apparition de la DSF et son impact, et nous devrions mettre l’accent sur le traitement du couple.

Abstract Background Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a disease with diverse clinical manifestations, such as pelvic pain or perineal pain. Although recent studies found several risk factors related to the pain severity of CP/CPPS patients, results were inconsistent. Here, we aimed to identify novel risk factors that are closely related to the severity of pain in patients with CP/CPPS. Methods We retrospectively collected the clinical records from patients with CP/CPPS from March 2019 to October 2019. The questionnaire was used to obtain related parameters, such as demographics, lifestyle, medical history, etc. To identify potential risk factors related to pain severity, we used the methods of univariate and multivariate logistic regression analyses. Further, to confirm the relationship between these confirmed risk factors and CP/CPPS, we randomly divided CP/CPPS patients into the training and the validation cohorts with a ratio of 7:3. According to the co-efficient result of each risk factor calculated by multivariate logistic regression analysis, a predicting model of pain severity was established. The receiver operating characteristic curve (ROC), discrimination plot, calibration plot, and decision curve analyses (DCA) were used to evaluate the clinical usage of the current model in both the training and validation cohorts. Results A total of 272 eligible patients were enrolled. The univariate and multivariate logistic regression analysis found that age [odds ratio (OR): 2.828, 95% confidence intervals (CI): 1.239–6.648, P = 0.004], holding back urine (OR: 2.413, 95% CI: 1.213–4.915, P = 0.005), anxiety or irritability (OR: 3.511, 95% CI: 2.034–6.186, P

Ejaculation is a complex biphasic process involving a series of neurophysiological activities, such as the contraction of a large number of muscle groups and the ejaculation of semen from the urethra anterior. Due to the complexity of the process, many related factors have not been fully clarified, resulting in ejaculation dysfunction. As a common ejaculation dysfunction, lifelong premature ejaculation (LPE) is a problem for many people. Notably, gene polymorphism might play an important role in the etiology of LPE. However, the quest for identifying the actual genetic loci that contribute to LPE etiology has not been successful. Due to discrepancies in the design and methods of research, the correlation of most reports was not obtained in subjective replication experiments, and the conclusions may be inconsistent. In our study, three groups of ejaculation rats, namely, “rapid, normal, and delayed,” were selected based on the animal model of premature ejaculation (PE) in rats and the theory of ejaculation. Among them, the rats in the “rapid” ejaculation group can be used to stimulate humans with PE. Subsequently, we used the rat brain tissue for whole-transcriptome sequencing to screen the differential genes among the three groups. We tried to identify the actual genetic loci that contribute to PE etiology and provide a theoretical basis for the targeted therapy of PE.

Abstract Introduction We treated a patient with late-stage unilateral bypass thrombosis after bilateral axillary-femoral bypass with lateral axillary-profunda femoris artery (LAx-PF) bypass. Case presentation A 64-year-old male patient was admitted to our hospital for acute left lower limb ischemia. Six years ago, he underwent bilateral axillary-femoral bypass due to Leriche syndrome. On emergency admission, thrombosis of the left bypass vessel was identified. Blood flow could not be restored due to failure to restore patency of the proximal and distal anastomosis of the left bypass vessel during surgery. We performed LAx-PF bypass surgery to successfully rescue the limb, which was on the verge of necrosis. Conclusion If thrombectomy cannot restore blood flow in the previous axillary-femoral bypass, LAx-PF bypass is an easy procedure to rescue the ischemic limb.

Introduction: Premature ejaculation (PE) is widely regarded as one of the most common sexual dysfunctions in men. The neurobiogenesis of PE is complex and involves the serotoninergic (5-HT) system. Aim: In this study, we investigated whether polymorphisms in the tryptophan hydroxylase 2 (TPH2) gene were associated with lifelong PE (LPE). Methods: A total of 121 men diagnosed with LPE were recruited from our outpatient clinics and 94 healthy controls from the health examination center. Intravaginal ejaculation latency time (IELT) was measured using a stopwatch. The PE diagnostic tool (PEDT) data were collected at the same time. All subjects with LPE and healthy controls were genotyped for polymorphisms in the TPH2 gene. Allele and genotype frequencies of single-nucleotide polymorphisms (SNPs) were compared between the patients and controls. Main Outcome Measure: The main outcome measures are IELT and PEDT to diagnose LPE. The association of LPE with TPH2 gene polymorphisms in these areas was investigated. Results: The IELT, PEDT scores, and education levels in the LPE group were significantly different from those in the control group. Statistically significant differences were found in the SNPs of SNV019 and rs4290270. The frequencies of the G allele and G/A genotype of SNV019 were significantly higher in the patients with LPE than in the controls (P = .045 and .037, respectively). The A allele and A/A genotype of rs4290270 were more frequent in the patients with LPE than in the controls (P = .037 and .049, respectively). In the dominant model of inheritance, the SNV019 polymorphism in the patients with LPE was significantly different from that in the controls (odds ratio [95% confidence interval] = 2.936 [1.066–8.084], P = .037). In men with LPE, there was no statistically significant association between genotype and median IELT. Conclusion: The SNPs SNV019 and rs4290270 of the TPH2 gene seemed to be associated with LPE in the Han population. Men with the A allele of SNV019 or the T allele of rs4290270 may be less likely to suffer from LPE.Fu X, Zhang X, Jiang T, et al. Association Between Lifelong Premature Ejaculation and Polymorphism of Tryptophan Hydroxylase 2 Gene in the Han Population. Sex Med 2020;8:223–229.

BackgroundFew studies have explored the optimal examined lymph node count and lymph node density cutoff values that could be used to predict the survival of patients with penile cancer. We further clarify the prognostic value of lymph node density and examined lymph node count in penile cancer.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was explored to recruit penile cancer patients from 2010 to 2015. A retrospective analysis of penile cancer patients’ data from the First Affiliated Hospital of Anhui Medical University was performed for verification (2006–2016). The cutoff values of examined lymph node count and lymph node density were performed according to the ROC curve. Kaplan-Meier survival analysis was used to compare survival differences among different groups. Univariate and multivariate Cox proportional hazard regression analyses were used to determine the significant variables. On the basis of Cox proportional hazards regression model, a nomogram was established and validated by calibration plot diagrams and concordance index (C-index).ResultsA total of 528 patients in the Surveillance, Epidemiology, and End Results cohort and 156 patients in the Chinese cohort were included in this study. Using the ROC curve, we found that the recommended cutoff values of ELN and LND were 13 and 9.3%, respectively (P 9.3% as the cutoff value for evaluating the prognosis of penile cancer patients.

Introduction: The association between folic acid (FA) and erectile dysfunction (ED) was contradictory in the published original articles, and no meta-analysis was conducted to pool these data. Aim: To verify the role of FA in the pathology of ED and explore the treatment efficacy of FA for ED patients. Methods: An extensive search was performed on PubMed, Cochrane Library, and Web of Science to obtain all relevant studies published up to October 31, 2020. Studies comparing the serum FA level between ED patients and healthy controls, or comparing the score of the IIEF-5, or IIEF before and after folic acid therapy alone or combination in ED patient were eligible for our meta-analysis. The Newcastle-Ottawa Scales (NOS) was used to qualify included studies. Main Outcome Measures: The standardized mean differences (SMD) and their corresponding 95% confidence intervals (95% CIs) were calculated to pool our data. Results: Nine studies were eligible for our meta-analysis to verify the association between FA and ED, and to explore the treatment efficacy of FA for ED patients. The pooled SMD of the FA level difference between ED patients and healthy subjects was -0.94 (95% CI: -1.59, -0.30, P = .004). Moreover, the level of folic acid in healthy subjects, Mild ED patients, Moderate ED patients and Severe ED patients was 11.847 (95%CI = 9.671, 14.022), 9.496 (95%CI = 8.425, 10.567), 6.597 (95%CI = 5.187, 8.007) and 5.623 (95%CI = 3.535, 7.711) respectively. The SMD of changes in score of IIEF-5 was 1.89 with 95%CI (1.60, 2.17) after FA administration in ED patients. Our analysis also showed that combination therapy of FA plus tadalafil changed the score of IIEF with 0.90 (95%CI = 0.44, 1.36) comparing to combination of placebo plus tadalafil. Conclusion: This novel meta-analysis demonstrated that FA was an independent risk factor for ED and FA supplement may have potentially positive effects in the treatment of ED patients.Zhang Y, Zhang W, Dai Y, et al. Serum Folic Acid and Erectile Dysfunction: A Systematic Review and Meta-Analysis. Sex Med 2021;9:100356.

Abstract Background Cryptorchidism as a common genitourinary malformation with the serious complication of male infertility draws widespread attention. With several reported miRNAs playing critical roles in spermatogonial stem cells (SSCs), we aimed to explore the fundamental function of the highly conserved miR-34c in cryptorchidism. Methods To explore whether miR-34c participates in spermatogenesis by regulating Nanos2, we examined the effect of overexpression and inhibition for miR-34c on Nanos2 expression in GC-1 cells. Moreover, the expression levels of miR-34c and Nanos2 with cryptorchidism in humans and mice were examined. Furthermore, the homeostasis of SSCs was evaluated through counting the number of promyelocytic leukemia zinc finger (PLZF) positive spermatogonia in murine cryptorchid testes. Results In the present study, we show that miR-34c could inhibit the expression of Nanos2 in GC-1 cells. Meanwhile, miR-34c significantly decreased in both the testicular tissues of patients with cryptorchidism and surgery-induced murine model of cryptorchidism. Western blot revealed that the protein level of Nanos2 was up-regulated and showed to be negatively correlated to the expression of miR-34c in our model. The abnormal expression of miR-34c/Nanos2 disrupted the balance between SSC self-renewal and differentiation, eventually damaging the spermatogenesis of cryptorchid testes. Conclusions The miR-34c/Nanos2 pathway provides new insight into the mechanism of male infertility caused by cryptorchidism. Our results indicate that miR-34c may serve as a biological marker for treatment of infertility caused by cryptorchidism.

Purpose: We developed a nomogram to predict the possibility of lymph node metastasis in patients with squamous cell carcinoma of the penis.Methods: Identifying patients with squamous cell carcinoma of the penis diagnosed between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analyses were carried out by logistic regression to assess significant predictors associated with lymph node metastasis. A nomogram was established and validated by a calibration plot and receptor operating characteristic curve (ROC) analysis.Results: A total of 1,016 patients with penile squamous cell carcinoma (SCCP) were enrolled in this study. One hundred and ninety-five patients (19%) had lymph node involvement (N1-3). Multivariate analysis showed that age, primary tumor site, grade, tumor size, and T stage were identified as being significantly (p < 0.05) associated with lymph node involvement. All the above factors that showed a statistically significant predictive capability were selected for building the nomogram. This model had a calibration slope of 0.9 and a c-index of 0.776, indicating the good discrimination and effectiveness of the nomogram in predicting lymph node status.Conclusion: Although the prediction model has some limitations, the nomogram revealed the relationship between the clinicopathological characteristics of SCCP patients and the risk of lymph node metastasis. This tool will assist patients in counseling and guide treatment decisions for SCCP patients.

Auxin-responsive genes AUX/IAA are important during plant growth and development, but there are few relevant reports in peanut. In this study, 44 AhIAA genes were identified from cultivated peanut, of which 31 genes were expressed in seed at varying degrees. AhIAA-3A, AhIAA-16A and AhIAA-15B were up-regulated, while AhIAA-11A, AhIAA-5B and AhIAA-14B were down-regulated with seed development and maturation. The expression patterns of seven genes, AhIAA-1A, AhIAA-4A, AhIAA-10A, AhIAA-20A, AhIAA-1B, AhIAA-4B and AhIAA-19B, were consistent with the change trend of auxin, and expression in late-maturing variety LM was significantly higher than that in early-maturing EM. Furthermore, allelic polymorphism analysis of AhIAA-1A and AhIAA-1B, which were specifically expressed in seeds, showed that three SNP loci in 3′UTR of AhIAA-1A could effectively distinguish the EM- and LM- type germplasm, providing a basis for breeding markers development. Our results offered a comprehensive understanding of Aux/IAA genes in peanut and provided valuable clues for further investigation of the auxin signal transduction pathway and auxin regulation mechanism in peanut.

Long non-coding RNAs (lncRNAs) can enhance plant stress resistance by regulating the expression of functional genes. Sweet sorghum is a salt-tolerant energy crop. However, little is known about how lncRNAs in sweet sorghum respond to salt stress. In this study, we identified 126 and 133 differentially expressed lncRNAs in the salt-tolerant M-81E and the salt-sensitive Roma strains, respectively. Salt stress induced three new lncRNAs in M-81E and inhibited two new lncRNAs in Roma. These lncRNAs included lncRNA13472, lncRNA11310, lncRNA2846, lncRNA26929, and lncRNA14798, which potentially function as competitive endogenous RNAs (ceRNAs) that influence plant responses to salt stress by regulating the expression of target genes related to ion transport, protein modification, transcriptional regulation, and material synthesis and transport. Additionally, M-81E had a more complex ceRNA network than Roma. This study provides new information regarding lncRNAs and the complex regulatory network underlying salt-stress responses in sweet sorghum.

N6-methyladenosine (m6A) is the most common type of eukaryotic mRNA modification and has been found in many organisms, including mammals, and plants. It has important regulatory effects on RNA splicing, export, stability, and translation. The abundance of m6A on RNA depends on the dynamic regulation between methyltransferase (“writer”) and demethylase (“eraser”), and m6A binding protein (“reader”) exerts more specific regulatory function by binding m6A modification sites on RNA. Progress in research has revealed important functions of m6A modification in plants. In this review, we systematically summarize the latest advances in research on the composition and mechanism of action of the m6A system in plants. We emphasize the function of m6A modification on RNA fate, plant development, and stress resistance. Finally, we discuss the outstanding questions and opportunities exist for future research on m6A modification in plant.

Abstract Background Cryptorchidism is one of the most common causes of non-obstructive azoospermia (NOA) leading to male infertility. Despite various medical approaches been utilised, many patients still suffer from infertility. MicroRNAs (miRNAs) play vital roles in the progress of spermatogenesis; however, little is known about the miRNA expression profile in the testes. Therefore, the miRNA profile was assessed in the testis of post-cryptorchidopexy patients. Methods Three post-cryptorchidopexy testicular tissue samples from patients aged 23, 26 and 28 years old and three testis tissues from patients with obstructive azoospermia (controls) aged 24, 25 and 36 years old were used in this study. Next-generation sequencing (NGS) was used to perform the miRNA expression profiling. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) assays were subsequently used to confirm the results of several randomly-selected and annotated miRNAs. Results A series of miRNAs were found to be altered between post-cryptorchidopexy testicular tissues and control tissues, including 297 downregulated and 152 upregulated miRNAs. In the subsequent qRT-PCR assays, the expression levels of most of the selected miRNAs (9/12, P

Summary: The root stem cell niche, which is composed of four mitotically inactive quiescent center (QC) cells and the surrounding actively divided stem cells in Arabidopsis, is critical for growth and root development. Here, we demonstrate that the Arabidopsis prohibitin protein PHB3 is required for the maintenance of root stem cell niche identity by both inhibiting proliferative processes in the QC and stimulating cell division in the proximal meristem (PM). PHB3 coordinates cell division and differentiation in the root apical meristem by restricting the spatial expression of ethylene response factor (ERF) transcription factors 115, 114, and 109. ERF115, ERF114, and ERF109 mediate ROS signaling, in a PLT-independent manner, to control root stem cell niche maintenance and root growth through phytosulfokine (PSK) peptide hormones in Arabidopsis. : Prohibitins (PHBs) have been identified as negative regulators of the cell cycle. Here, Kong et al. demonstrate that Arabidopsis PHB3 is essential to maintain QC and DSC identity, and it controls root meristem activity by restricting the spatial expression of the ROS-responsive factors ERF115, 114, and 109 in root. Keywords: root, stem cell niche, prohibitin 3, ROS, ERF, PSK

The dominant male-sterile geneMs2 has facilitated the release of hundreds of wheat-breeding lines and cultivars in China. Here Ni et al. describe the cloning of the Ms2 gene, which appears as an orphan gene in the Triticinae, and show that Ms2 can be used to confer male sterility in wheat, barley and Brachypodium.