Structures of the ADGRG2-Gs complex in apo and ligand-bound forms.

Adhesion G protein-coupled receptors are elusive in terms of their structural information and ligands. Here, we solved the cryogenic-electron microscopy (cryo-EM) structure of apo-ADGRG2, an essential membrane receptor for maintaining male fertility, in complex with a Gs trimer. Whereas the formations of two kinks were determinants of the active state, identification of a potential ligand-binding pocket in ADGRG2 facilitated the screening and identification of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate and deoxycorticosterone as potential ligands of ADGRG2. The cryo-EM structures of DHEA-ADGRG2-Gs provided interaction details for DHEA within the seven transmembrane domains of ADGRG2. Collectively, our data provide a structural basis for the activation and signaling of ADGRG2, as well as characterization of steroid hormones as ADGRG2 ligands, which might be used as useful tools for further functional studies of the orphan ADGRG2.

Activation of PTH1R alleviates epididymitis and orchitis through Gq and ß-arrestin-1 pathways.

Inflammation in the epididymis and testis contributes significantly to male infertility. Alternative therapeutic avenues treating epididymitis and orchitis are expected since current therapies using antibiotics have limitations associated to side effects and are commonly ineffective for inflammation due to nonbacterial causes. Here, we demonstrated that type 1 parathyroid hormone receptor (PTH1R) and its endogenous agonists, parathyroid hormone (PTH) and PTH-related protein (PTHrP), were mainly expressed in the Leydig cells of testis as well as epididymal epithelial cells. Screening the secretin family G protein-coupled receptor identified that PTH1R in the epididymis and testis was down-regulated in mumps virus (MuV)- or lipopolysaccharide (LPS)-induced inflammation. Remarkably, activation of PTH1R by abaloparatide (ABL), a Food and Drug Administration-approved treatment for postmenopausal osteoporosis, alleviated MuV- or LPS-induced inflammatory responses in both testis and epididymis and significantly improved sperm functions in both mouse model and human samples. The anti-inflammatory effects of ABL were shown to be regulated mainly through the Gq and ß-arrestin-1 pathway downstream of PTH1R as supported by the application of ABL in Gnaq± and Arrb1-/- mouse models. Taken together, our results identified an important immunoregulatory role for PTH1R signaling in the epididymis and testis. Targeting to PTH1R might have a therapeutic effect for the treatment of epididymitis and orchitis or other inflammatory disease in the male reproductive system.

Highly Luminescent Earth-Benign Organometallic Manganese Halide Crystals with Ultrahigh Thermal Stability of Emission from 4 to 623 K.

The phosphor-converted light-emitting diode (PC-LED) has become an indispensable solid-state lighting and display technologies in the modern society. Nevertheless, the use of scarce rare-earth elements and the thermal quenching (TQ) behavior are still two most crucial issues yet to be solved. Here, this work successfully demonstrates a highly efficient and thermally stable green emissive MnI2 (XanPO) crystals showing a notable photoluminescence quantum yield (PLQY) of 94% and a super TQ resistance from 4 to 623 K. This unprecedented superior thermal stability is attributed to the low electron-phonon coupling and the unique rigid crystal structure of MnI2 (XanPO) over the whole temperature range based on the temperature-dependent photoluminescence (PL) and single crystal X-ray diffraction (SCXRD) analyses. Considering these appealing properties, green PC-LEDs with a power efficacy of 102.5 lm W-1 , an external quantum efficiency (EQE) of 22.7% and a peak luminance up to 7750 000 cd m-2 are fabricated by integrating MnI2 (XanPO) with commercial blue LEDs. Moreover, the applicability of MnI2 (XanPO) in both micro-LEDs and organic light-emitting diodes (OLEDs) is also demonstrated. In a nutshell, this study uncovers a candidate of highly luminescent and TQ resistant manganese halide suitable for a variety of emission applications.

Highly Efficient MAPbI3 -Based Quantum Dots Exhibiting Unusual Nonblinking Single Photon Emission at Room Temperature.

Highly emissive semiconductor nanocrystals, or so-called quantum dots (QDs) possess a variety of applications from displays and biology labeling, to quantum communication and modern security. Though ensembles of QDs have already shown very high photoluminescent quantum yields (PLQYs) and have been widely utilized in current optoelectronic products, QDs that exhibit high absorption cross-section, high emission intensity, and, most important, nonblinking behavior at single-dot level have long been desired and not yet realized at room temperature. In this work, infrared-emissive MAPbI3 -based halide perovskite QDs is demonstrated. These QDs not only show a ≈100% PLQY at the ensemble level but also, surprisingly, at the single-dot level, display an extra-large absorption cross-section up to 1.80 × 10-12 cm2 and non-blinking single photon emission with a high single photon purity of 95.3%, a unique property that is extremely rare among all types of quantum emitters operated at room temperature. An in-depth analysis indicates that neither trion formation nor band-edge carrier trapping is observed in MAPbI3 QDs, resulting in the suppression of intensity blinking and lifetime blinking. Fluence-dependent transient absorption measurements reveal that the coexistence of non-blinking behavior and high single photon purity in these perovskite QDs results from a significant repulsive exciton-exciton interaction, which suppresses the formation of biexciton, and thus greatly reduces photocharging. The robustness of these QDs is confirmed by their excellent stability under continuous 1 h electron irradiation in high-resolution transmission electron microscope inspection. It is believed that these results mark an important milestone in realizing nonblinking single photon emission in semiconductor QDs.

Micro-TESE strategy in patients with NOA caused by AZFc deletion: synchronous or asynchronous?

In the treatment of infertile patients with non-obstructive azoospermia (NOA) caused by the deletion of the azoospermia factor c region (AZFc) on the Y chromosome, synchronous and asynchronous surgical strategies are discussed. Clinical data from NOA patients with the AZFc deletion who underwent micro-TESE were analyzed retrospectively. The sperm retrieval rate (SRR) and sperm utilization rate of synchronous and asynchronous operation groups were followed up and compared. The fertilization rate, high-quality embryo rate, clinical pregnancy rate, abortion rate, and cumulative live birth rate of ICSI in patients with successful sperm retrieval were compared between the two groups. The two groups had sperm utilization rates of 98.9% (93/94) and 50.0% (14/28), respectively. The asynchronous group's sperm consumption rates were much lower than those of the synchronous operation group. Fertilization rate, high-quality embryo rate, clinical pregnancy rate of fresh transfer cycle, abortion rate, and cumulative live birth rate of patients in the synchronous operation group with fresh sperm, and the asynchronous operation group with thawed sperm, respectively, were 30.6% vs 33.8%, 33.8% vs 40.7%, 40.0% vs 12.5%, 30.4% vs 7.1%. Between the two groups, there was no significant difference. This suggests that individuals with NOA caused by the AZFc deletion have a high possibility of successfully acquiring sperm using micro-TESE and ICSI to conceive their own offspring. Synchronous micro-TESE is recommended to improve sperm utilization rate and the cumulative live birth rate.

Silencing a Chitinase Gene, PstChia1, Reduces Virulence of Puccinia striiformis f. sp. tritici.

Chitin is the main component of fungal cell walls, which can be recognized by pattern recognition receptors (PRRs) as pathogen-associated molecular patterns (PAMP). Chitinase in filamentous fungi has been reported to degrade immunogenic chitin oligomers, thereby preventing chitin-induced immune activation. In this study, we identified the chitinase families in 10 fungal genomes. A total of 131 chitinase genes were identified. Among the chitinase families, 16 chitinase genes from Puccinia striiformis f. sp. tritici (Pst) were identified, and the expression of PstChia1 was the highest during Pst infection. Further studies indicated that PstChia1 is highly induced during the early stages of the interaction of wheat and Pst and has chitinase enzyme activity. The silencing of PstChia1 revealed that PstChia1 limited the growth and reduced the virulence of Pst. The expression level of TaPR1 and TaPR2 was induced in PstChia1 knockdown plants, suggesting that PstChia1 is involved in regulating wheat resistance to Pst. Our data suggest that PstChia1 contributes to pathogenicity by interfering with plant immunity and regulating the growth of Pst.

Sexual life and medication taking behaviours in young men: An online survey of 92 620 respondents in China.

OBJECTIVES: To assess sexual life and medication taking behaviours in young Chinese men. METHODS: An online survey was conducted across China between January 2017 and April 2017. Among the participants, men aged 19-40 years were included in the analysis. The respondents filled in the online questionnaire assessing sexual life and medication taking behaviours by themselves, including general information, cognition of erectile dysfunction (ED) and treatment-related questions. Erection hardness score (EHS) was used to measure the erection hardness status. RESULTS: Among the young respondents, 20.54% had grade I-II EHS, 58.14% searched the internet for online ED-related information, 26.49% took an ED medication and 50.89% took an ED medication without the advice of a physician or pharmacist. The respondents who took medication had less sexual intercourse per week (P < .001) and worse EHS (P < .001), and were more willing to seek information from physicians, pharmacists, friends and relatives instead of online sources (P < .001), compared with those not taking medication. The most common comorbidities in patients with grade I-II EHS were hyperlipidaemia, cardiovascular disease (CVD), prostate diseases and diabetes mellitus. CONCLUSION: About 20% of young Chinese men needed further assessment for ED. The majority of respondents obtained ED-related information by online search and took an ED medication without professional advice. These data could help clinicians understand the current status of sexual life and medication taking behaviours of young Chinese men.

Low androgen status inhibits erectile function by up-regulating the expression of P2X receptors in rat corpus cavernosum.

The aim of our study was to investigate whether low androgen level inhibits the erectile function of rats by regulating the expression of P2X receptors. Thirty-six 8-week-old male SD rats were randomly divided into six groups: sham-operated groups (4w-sham, 8w-sham), castration groups (4w-cast, 8w-cast) and androgen replacement after castration groups (4w-cast + T, 8w-cast + T). The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), the levels of serum testosterone (T) and nitric oxide (NO), and the expression of P2X1, P2X2, P2X3, eNOS, p-eNOS, ROCK1 and ROCK2 in the cavernous tissue of rats were determined. The serum T, ICPmax/MAP and NO levels in penile corpus cavernosum in the castration groups were significantly lower than those in other groups (p < .01). The protein expression of P2X1, P2X2, P2X3, ROCK1 and ROCK2 in the castration groups was significantly higher than those in other groups (p < .01). P-eNOS/eNOS of the castration groups were significantly lower than those of other groups (p < .01). The serum T level was negatively correlated with the expression of P2X1, P2X2 and P2X3 in the corpus cavernosum. Low androgen level inhibits erectile function by up-regulating the expression of P2X1, P2X2, P2X3 and RhoA/Rho-kinase resulting in reducing the ratio of p-eNOS/eNOS and the level of NO in corpus cavernosum of rats.

Ran-binding protein 3 is associated with human spermatogenesis and male infertility.

Ran-binding protein 3 (RanBP3) is a Ran-interacting protein, which participates in the Ran GTPase system in cancer cell biology. However, the expression pattern and physiological role of RanBP3 remain largely unknown. In this study, we found that RanBP3 was expressed in human testes and localised to spermatogonium and spermatocyte of germ cells. In subcellular structure, its localisation is in the nucleus and cytoplasm. Interestingly, compared with normal groups, RanBP3 expression was lower in groups of patients with Maturation Arrest (MA) and Sertoli cell-only syndrome (SCO) when considered by the Johnson Score. RanBP3 expression in the MA group and SCO groups was dramatically lower than that in the normal control group. Studies have shown that RanBP3, which is one of the helper factors of Ran, is mainly participate in the nucleocytoplasmic transport of cells. RanBP3 helps Ran to achieve some functions such as nucleocytoplasmic transport, spindle assembly during mitosis and nuclear assembly after mitosis. Consequent changes in the expression of RanBP3 may associate with human spermatogenesis disorders and male infertility. The identification and characterisation of RanBP3 enhances our understanding of the molecular mechanisms underpinning its function in human spermatogenesis and male infertility.

The Immunoscore system predicts prognosis after liver metastasectomy in colorectal cancer liver metastases.

BACKGROUND: The Immunoscore was initially established to evaluate the prognosis of stage I/II/III colorectal cancer patients. However, the feasibility of the Immunoscore for the prognosis of colorectal cancer liver metastases (CRCLM) has not been reported. METHODS: Liver metastases in 249 CRCLM patients were retrospectively analyzed. The Immunoscore was assessed according to the counts and densities of CD3+ and CD8+ T cells in the central- and peritumoral areas by immunohistochemistry. The prognostic role of the Immunoscore for relapse-free survival (RFS) and overall survival (OS) was analyzed with Kaplan-Meier curves and Cox multivariate models, and confirmed via an internal validation. Receiver operating characteristic (ROC) curves were plotted to compare the prognostic values of the Immunoscore and the clinical risk score (CRS) system. RESULTS: CRCLM patients with high Immunoscores (> 2) had significantly longer RFS [median RFS (95% confidence interval; 95% CI) 21.4 (7.8-35.1) vs. 8.7 (6.8-10.5) months, P < 0.001] and OS [median OS (95% CI): not reached vs. 28.7 (23.2-34.2) months, P < 0.001] than those with low Immunoscores (≤ 2). After stratification by CRS, the Immunoscore retained a statistically significant prognostic value for OS. The areas under the ROC curves (AUROCs) of the Immunoscore and the CRS system for RFS were 0.711 [95% CI 0.642-0.781] and 0.675[95% CI 0.601-0.749] (P = 0.492), whereas the AUROC of the Immunoscore system for OS was larger than that of the CRS system [0.759 (95% CI 0.699-0.818) vs. 0.660 (95% CI 0.592-0.727); P = 0.029]. CONCLUSIONS: The Immunoscore of liver metastases can be applied to predict the prognosis of CRCLM patients following liver resection.

Effect of Penile Traction and Vacuum Erectile Device for Peyronie's Disease in an Animal Model.

BACKGROUND: Penile traction therapy with the use of a traction device (TD) or vacuum erectile device (VED) has been studied as local modalities for Peyronie's disease (PD). AIM: To identify changes of penile curvature, erectile function, and possible cellular and molecular mechanisms between the TD and VED in a rat model of PD. METHODS: Peyronie's plaque was induced in 30 adult male rats. Then, rats were randomly divided into control (PD without treatment), VED, and TD groups. In the VED group, vacuum pressure was applied to the cylinder to induce penile engorgement inside the cylinder for 1 minute. The penis was allowed to deflate completely for another 1 minute. This was repeated for five cycles (inflate and deflate). In the TD group, the rat penis was straightened by a suspended tension gauge at the same tension by clamping the prepuce. This was performed three times per day at 20 minutes per session, with 5-minute intervals between sessions. The entire treatment duration was 4 weeks. OUTCOMES: Penile curvature, intracavernosal pressure, and mean arterial pressure were measured. Immunohistochemistry for α-smooth muscle actin, transforming growth factor-ß1 and mothers against decapentaplegic homolog 2/3 were performed. RESULTS: The TD and VED groups had less penile curvature compared with the control group (15.3 ± 5.3° for TD, 28.4 ± 6.8° for VED, 38.6 ± 10.5° for control; P < .001 for TD vs control, P < .05 for VED vs control). The TD group also had less penile curvature compared with the VED group (P < .05). The VED group had a higher ratio of intracavernosal pressure to mean arterial pressure compared with the two other groups (0.56 ± 0.10 for VED, 0.38 ± 0.06 for TD, 0.32 ± 0.07 for control; P < .001). The immunohistochemistry results showed the VED group had more preserved α-smooth muscle actin with less transforming growth factor-ß1 and mothers against decapentaplegic homolog 2/3 than the TD and control groups in the corpus cavernosa. CLINICAL TRANSLATION: Various benefits can be observed with the TD and VED for the treatment of PD. STRENGTHS AND LIMITATIONS: This study explored the mechanism and benefits of TD and VED therapies for the treatment of PD. The rat model might not represent the human condition. CONCLUSION: Penile traction therapy with the TD or VED is beneficial to decrease penile curvature in animal models of PD. The underlying mechanism could be related to antiapoptosis, antifibrosis, and smooth muscle preservation. Lin H, Liu C, Wang R. Effect of Penile Traction and Vacuum Erectile Device for Peyronie's Disease in an Animal Model. J Sex Med 2017;14:1270-1276.

Sodium-Hydrogen-Exchanger expression in human sperm and its relationship with semen parameters.

PURPOSE: Sperm-specific sodium-hydrogen exchanger (sNHE) is essential to maintain sperm normal function in mice; however, its role in human sperm has not been clarified to date. The aim of this study is to investigate the expression pattern of sNHE in human spermatozoa and its relationship with sperm functional parameters. METHOD: Semen samples from 68 asthenozoospermic and 61 normozoospermic men were analyzed for sperm concentration, motility, and acrosome reaction, and high motile spermatozoa were collected by swim-up method. The expression of sNHE in spermatozoa was detected by Western blot and immunofluorescence staining. The relationship between sNHE expression and sperm parameters was assessed. RESULTS: We identified sNHE is mainly localized to the principal piece of the human sperm tail. The expression of sNHE was positively correlated with sperm concentration, total number, and progressive motility. Moreover, sNHE expression was upregulated in swim-up sperm and associated with most of sperm motility parameters including straight line velocity and curvilinear velocity. Our results also showed that sNHE expression is decreased in sperm from patients with asthenozoospermia compared with that from normal controls. However, no correlation was found between sNHE expression and acrosome reaction in spermatozoa. CONCLUSIONS: The expression pattern of sNHE suggested that this protein may be involved in the regulation of sperm motility, and aberration of its expression in sperm may contribute to the pathogenesis of asthenozoospermia.

Serum Metabolomic Profiling Identifies Characterization of Non-Obstructive Azoospermic Men.

Male infertility is considered a common health problem, and non-obstructive azoospermia with unclear pathogenesis is one of the most challenging tasks for clinicians. The objective of this study was to investigate the differential serum metabolic pattern in non-obstructive azoospermic men and to determine potential biomarkers related to spermatogenic dysfunction. Serum samples from patients with non-obstructive azoospermia (n = 22) and healthy controls (n = 31) were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Serum metabolomic profiling could differentiate non-obstructive azoospermic patients from healthy control subjects. A total of 24 metabolites were screened and identified as potential markers, many of which are involved in energy production, oxidative stress and cell apoptosis in spermatogenesis. Moreover, the results showed that various metabolic pathways, including d-glutamine and d-glutamate metabolism, taurine and hypotaurine metabolism, pyruvate metabolism, the citrate cycle and alanine, aspartate and glutamate metabolism, were disrupted in patients with non-obstructive azoospermia. Our results indicated that the serum metabolic disorders may contribute to the etiology of non-obstructive azoospermia. This study suggested that serum metabolomics could identify unique metabolic patterns of non-obstructive azoospermia and provide novel insights into the pathogenesis underlying male infertility.

[Collagenase clostridium histolyticum for Peyronie's disease: A new minimally invasive and effective treatment].

The treatment of Peyronie's disease has been a challenge to urologists, as most of the current oral medications are considered hardly valid and the rest of the therapies require strict control of indications, some of which remain controversial, while the final surgical option may be associated with complications such as penile shortening or erectile dysfunction. Collagenase clostridium histolyticum has been proved to be effective in dissolving the penile cavernosal plaque and approved by the Food and Drug Administration of the USA as the first drug to be used for the treatment of Peyronie's disease. This article presents an introduction to the characteristics, safety, efficacy, and procedures of this new treatment, which may benefit urologists and the patients with Peyronie's disease.

[Microdissection testicular sperm extraction for patients with nonmosaic Klinefelter syndrome: A report of 143 cases].

OBJECTIVE: To investigate the clinical application and outcomes of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS). METHODS: A total of 143 nonmosaic KS patients underwent micro-TESE in the Center of Reproductive Medicine of Peking University Third Hospital between July 2012 and August 2016. We analyzed their clinical and follow-up data and evaluated the outcomes. RESULTS: Spermatozoa were successfully retrieved from the testicular tissue in 44.76% (64/143) of the patients, 84.4% (54/64) by unilateral and 15.6% (10/64) by bilateral micro-TESE. Seventy-five of the KS patients were followed up in the years of 2014 and 2015. Of the 34 patients with successful sperm retrieval, 73.52% (25/34) achieved clinical pregnancy and 8 boys and 8 girls were already born in 14 of the 25 cases. CONCLUSIONS: The micro-TESE is a useful method for sperm retrieval in nonmosaic KS patients, with high rates of sperm retrieval, clinical pregnancy, and birth of biological offspring.

Nanoparticle Improved Stem Cell Therapy for Erectile Dysfunction in a Rat Model of Cavernous Nerve Injury.

PURPOSE: Recently intracavernous injection of stem cells has garnered great interest as a potential treatment of erectile dysfunction. However, most stem cells are washed out immediately after intracavernous injection. The goal of this study was to investigate using NanoShuttle™ magnetic nanoparticles to maintain stem cells in the corpus cavernosum after intracavernous injection, thereby improving stem cell therapy of erectile dysfunction in an animal model. MATERIALS AND METHODS: Adipose derived stem cells were magnetized with NanoShuttle magnetic nanoparticles to create Nano-adipose derived stem cells. A total of 24 rats underwent bilateral cavernous nerve crush and were randomly assigned to 3 groups, including adipose derived stem cells, Nano-adipose derived stem cells and Nano-adipose derived stem cells plus magnet. Cells were tracked at days 1, 3, 5 and 9 after intracavernous injection. Another 40 rats with bilateral cavernous nerve crush were randomly assigned to 4 groups, including bilateral cavernous nerve crush, bilateral cavernous nerve crush plus adipose derived stem cell intracavernous injection, bilateral cavernous nerve crush plus Nano-adipose derived stem cell intracavernous injection and bilateral cavernous nerve crush plus Nano-adipose derived stem cell intracavernous injection plus magnet. Functional testing and histological analysis were performed 4 weeks after intracavernous injection. RESULTS: In the in vitro study 1) NanoShuttle magnetic nanoparticles were successfully bound to adipose derived stem cells and 2) Nano-adipose derived stem cells migrated toward the magnet. In the in vivo study 1) cell tracking showed that Nano-adipose derived stem cells were successfully retained in the corpus cavernosum using the magnet for up to 3 days while most adipose derived stem cells were washed out in other groups by day 1 after intracavernous injection, and 2) intracavernous pressure/mean arterial pressure, and αSMA (α-smooth muscle actin) and PECAM-1 (platelet endothelial cell adhesion molecule 1) expression in the Nano-adipose derived stem cell group was significantly higher than in the other groups. CONCLUSIONS: Magnetization of adipose derived stem cells with NanoShuttle magnetic nanoparticles kept adipose derived stem cells in the corpus cavernosum and improved adipose derived stem cell therapy of erectile dysfunction in an animal model.

Hyperuricemia Is an Independent Risk Factor for Erectile Dysfunction.

INTRODUCTION: Hyperuricemia may be related to the development of endothelial dysfunction and cardiovascular diseases. However, the association between hyperuricemia and erectile dysfunction (ED) is not currently clear. AIM: The goal of this study is to investigate the effect of hyperuricemia on erectile function and possible mechanisms. METHODS: Twenty-four 8-week-old male SD rats were randomly divided into 4 groups. Group A (control): Rats received normal saline and served as controls. Group B (hyperuricemia): rats were given oxonic acid 250 mg/kg bw/day through gastric gavage for 4 weeks. Group C (febuxostat): normal rats were treated with 5 mg/kg febuxostat through gastric gavage for 4 weeks. Group D (hyperuricemia + Febuxostat): normal rats were treated with 250 mg/kg bw/day oxonic acid and 5 mg/kg bw/day febuxostat with 1 hour interval for 4 weeks. MEASUREMENTS: The level of serum uric acid, the maximum intracavernosal pressure (ICPmax), mean arterial pressure (MAP), and the expression of endothelial nitric oxide synthase (eNOS), phospho-eNOS, neuronal NOS, Rho-associated protein kinaise (ROCK)1 and ROCK2 and the level of nitric oxide (NO) and reactive oxygen species (ROS) in cavernous tissue were determined. RESULTS: The level of serum uric acid and ROS in hyperuricemic rats was significantly higher than that in the other 3 groups (P < .05). After electrostimulation with 3 and 5 voltage, the ratio of ICPmax/MAP in hyperuricemic rats was significantly less than that in other 3 groups (P < .05), respectively. eNOS, p-eNOS, and nNOS expression in hyperuricemic rats were significantly decreased compared to the other 3 groups (P < .05), respectively. CONCLUSION: Erectile function is impaired by hyperuricemia. The decrease of eNOS, p-eNOS, and nNOS protein expression and increase of ROS in cavernous tissue may be one of the key mechanisms of ED caused by hyperuricemia.

[Application of the vacuum erectile device in penile rehabilitation for erectile dysfunction after radical prostatectomy].

OBJECTIVE: The vacuum erectile device (VED) uses negative pressure to increase blood inflow into the corpora cavernosum, with a ring at the base of the penis to maintain erection for intercourse or without a ring for penile rehabilitation. Owing to the limitation of phosphodiesterase 5 inhibitors (PDE5I) shown in the treatment of refractory erectile dysfunction (ED), the use of VED has resurged and is becoming the first line therapy in the treatment of ED following radical prostatectomy (RP). Currently, the combination therapy of VED with PDE5I and that of VED with intracavernous injection are advocated for post-RP ED. Hereby, we review the role of VED in penile rehabilitation, its underlying mechanisms, and the combination therapies for it.

Identification and validation of new fatty acid metabolism-related mechanisms and biomarkers for erectile dysfunction.

Background: Erectile dysfunction (ED) is a common condition affecting middle-aged and elderly men. Aim: The study sought to investigate differentially expressed fatty acid metabolism-related genes and the molecular mechanisms of ED. Methods: The expression profiles of GSE2457 and GSE31247 were downloaded from the Gene Expression Omnibus database and merged. Differentially expressed genes (DEGs) between ED and normal samples were obtained using the R package limma. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of DEGs were conducted using the R package clusterProfiler. Fatty acid metabolism-related DEGs (FAMDEGs) were further identified and analyzed. Machine learning algorithms, including Lasso (least absolute shrinkage and selection operator), support vector machine, and random forest algorithms, were utilized to identify hub FAMDEGs with the ability to predict ED occurrence. Coexpression analysis and gene set enrichment analysis of hub FAMDEGs were performed. Outcome: Fatty acid metabolism-related functions (such as fatty acid metabolism and degradation) may play a vital role in ED. Results: In total, 5 hub FAMDEGs (Aldh2, Eci2, Acat1, Acadl, and Hadha) were identified and found to be differentially expressed between ED and normal samples. Gene set enrichment analysis identified key pathways associated with these genes. The area under the curve values of the 5 hub FAMDEGs for predicting ED occurrence were all >0.8. Clinical Translation: Our results suggest that these 5 key FAMDEGs may serve as biomarkers for the diagnosis and treatment of ED. Strengths and Limitations: The strengths of our study include the use of multiple datasets and machine learning algorithms to identify key FAMDEGs. However, limitations include the lack of validation in animal models and human tissues, as well as research on the mechanisms of these FAMDEGs. Conclusion: Five hub FAMDEGs were identified as potential biomarkers for ED progression. Our work may prove that fatty acid metabolism-related genes are worth further investigation in ED.

An Ion Concentration Polarization Microplatform for Efficient Enrichment and Analysis of ctDNA.

Strategies for rapid, effective nucleic acid processing hold tremendous significance to the clinical analysis of circulating tumor DNA (ctDNA), a family of important markers indicating tumorigenesis and metastasis. However, traditional techniques remain challenging to achieve efficient DNA enrichment, further bringing about complicated operation and limited detection sensitivity. Here, we developed an ion concentration polarization microplatform that enabled highly rapid, efficient enrichment and purification of ctDNA from a variety of clinical samples, including serum, urine, and feces. The platform demonstrated efficiently separating and enriching ctDNA within 30 s, with a 100-fold improvement over traditional methods. Integrating an on-chip isothermal amplification module, the platform further achieved 100-fold enhanced sensitivity in ctDNA detection, which significantly eliminated false-negative results in the serum or urine samples due to the low abundance of ctDNA. Such a simple-designed platform offers a user-friendly yet powerful diagnosis technique with a wide applicability, ranging from early tumor diagnosis to infection screening.