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INTRODUCTION: Hyperactivity of the sympathetic nervous system can play an important role in lifelong premature ejaculation (PE). Our previous study found that amyloid precursor protein (APP) levels in seminal plasma of patients with PE were clearly increased. Amyloid-ß (Aß) is derived from APP. Excessive Aß, especially Aß42, can cause neuronal dysfunction. AIM: To determine whether APP and Aß42 are associated with an abnormal penile sympathetic skin response (PSSR). METHODS: From November 2015 to April 2016, 24 patients with lifelong PE (mean age = 29.2 ± 5.3) with self-estimated intravaginal ejaculatory latency time no longer than 2 minutes and 10 control subjects (mean age = 28.0 ± 5.5) were enrolled consecutively from andrology clinics. PSSR was measured in patients with lifelong PE. APP and Aß42 levels in seminal plasma were determined. MAIN OUTCOME MEASURES: PSSR in patients with lifelong PE and APP and Aß42 levels in all subjects. RESULTS: Patients with PE presented 1.5-fold higher levels of APP (P = .004) than control subjects. Seminal plasma protein concentration (C) in the PE group was lower than that in the control group (P = .007). APP divided by C (APP/C) was 2.0-fold higher (P < .001) in the PE group. Aß42 level was not different between the PE and control groups, but Aß42 divided by C (Aß42/C) was significantly higher in the PE group (P < .001). No differences in APP and APP/C were found between patients with PE in the abnormal and normal PSSR groups. The abnormal PSSR group presented significantly higher Aß42 (P = .007) and Aß42/C (P < .001) levels. The latency of PSSR was negatively correlated with Aß42/C (r = -0.436; P = .033). CONCLUSION: These results showed that patients with lifelong PE had higher APP and Aß42 levels in seminal plasma. Abnormal PSSR was related to a higher Aß42 level. Drugs that decrease Aß could be treatment of PE.
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Ejaculação Precoce/fisiopatologia , Pele/metabolismo , Sistema Nervoso Simpático/metabolismo , Adulto , Andrologia , Estudos de Casos e Controles , Ejaculação/fisiologia , Humanos , Masculino , Pênis/fisiopatologia , Sêmen , Adulto JovemRESUMO
Potassium carbonate-promoted coupling reactions between 3-diazoindolin-2-imines and nucleophiles were tested. By respectively applying 2-naphthalenols and 2-arylacetates as nucleophiles, 3-azoindoles and 3-hydrazonoindolin-2-imines were obtained in excellent yields. Moreover, 3-azoindol-2-amines could be used as NNO pincer ligands for boron and resulted in the formation of hexacycleborofluorides with their absorption around 580 nm in dichloromethane.
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3-Amino-2-carbamimidoylacrylamides were efficiently prepared via a copper(I)-catalyzed three-component reaction of sulfonylazides, propriolamides, and amidines. The synthesized compounds provided three kinds of crystalline structures based on the position of halogen. Two of them presented channel-type inclusion complexes with ethyl acetate through intermolecular hydrogen bonding, intermolecular C-H···π and π-π interactions, and van der Waals forces.
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Introduction: Guilingji, a famous traditional Chinese medicine (TCM) formula, has been used to combat aging and male sexual dysfunction in China for centuries. To date, there has been little evidence-based clinical research on the use of Guilingji to treat idiopathic oligo-asthenoteratozoospermia (OAT), and the therapeutic mechanism from a metabolic perspective needs to be investigated further. Methods: This was a multicenter, double-blind, randomized controlled clinical study of 240 patients with idiopathic OAT recruited from four hospitals between January 2020 and January 2022. Patients were randomly assigned in a 1ê1 ratio to receive oral Guilingji capsules or placebo for 12 weeks. The total progressive motile sperm count (TPMSC) was considered the primary outcome, and the other sperm parameters, seminal plasma parameters and serum hormones were considered the secondary outcome. A nontargeted metabolomics analysis of serum from OAT patients before and after Guilingji administration was performed by HPLC-MS to identify key metabolites. Furthermore, we used a rat model to show spermatogenesis phenotypes to validate the effect of the key metabolites screened from the patients. Results: At weeks 4, 8 and 12, TPMSC and other sperm parameters were significantly improved in the Guilingji group compared with the placebo group (P < 0.05 for all comparisons). At week 4, superoxide dismutase (SOD) and acrosomal enzyme activity of seminal plasma were significantly elevated in the Guilingji group compared with the placebo group, while reactive oxygen species (ROS) levels were significantly reduced (P < 0.05). Lactate dehydrogenase-X (LDHX) levels appeared to be significantly increased after 12 weeks continuous medication compared with Placebo group (P = 0.032). The metabolomics analysis of serum from OAT patients before and after Guilingji administration showed that the glucose-6-phosphate (G6P) concentration in patients' serum was significantly elevated after Guilingji treatment. Compared to the control, when Kidney-Yang deficiency model rats were treated with Guilingji or its key intermediate metabolite G6P, their sperm concentration and spermatozoic activity were improved similarly, and their structural damage of rat's testicular and epididymal tissues were recovered. Conclusion: This study provided valuable clinical evidence for the utility of Guilingji as a treatment for OAT. These findings thus demonstrate that G6P is involved in the therapeutic mechanism of Guilingji in OAT treatment based on clinical and rat intervention studies.
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The rational design of ultrathin and few-layered structures for three-dimensional MoS2 nanospheres is crucial for achieving attractive lithium-ion batteries (LIBs). Herein, hollow nanospheres constructed by ultrafine and few-layered MoS2 homogeneously incorporated in N-doped amorphous carbon (HUF-MoS2/NC) have been successfully synthesized as high-performance anode for LIBs. Using Mo-glycerol spheres as templates and dopamine hydrochloride as coordination ligands, hollow Mo-glycerol-polydopamine precursors are formed with Mo-containing groups which are surrounded by organic carbon species. Consequently, the MoS2 is confined to the nanoscale and grows partially amorphous fragments while being uniformly embedded in NC. This unique architecture can not only hinder the substantial restacking between MoS2 interlayers, offering more active sites, but also vastly enhance the electrical conductivity and relieve the mechanical stress ascribed to volume changes. As a result, the HUF-MoS2/NC composite anode exhibits excellent cyclic stability (980mAhg-1 after 300 cycles at 0.2Ag-1) and superior rate performance (498mAhg-1 at 5.0Ag-1) for LIBs.
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2-Amino-3-arylindoles were conveniently prepared from 3-diazoindolin-2-imines and arylboronic acids through palladium carbene intermediates in moderate to excellent yields. The synthesized 2-amino-3-arylindoles could be fluorinated with NFSI to afford 3-aryl-3-fluoroindolin-2-imines.
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A rhodium-catalyzed reaction between 3-diazoindolin-2-imines and 2H-azirines, followed by treatment with a base, furnishes 5H-pyrazino[2,3-b]indoles in excellent yields. A number of functional groups tolerate the reaction conditions, and the resulting 5H-pyrazino[2,3-b]indoles present strong photoluminecence in solutions, powders, and films.
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3-Diazoindolin-2-imines were constructed from indoles and sulfonylazides via an electronically matched 1,3-dipolar cycloaddition and a subsequent dehydroaromatization/ring-opening cascade. The reaction between 3-substituted indoles and sulfonyl azides provided 2-aminoindoles, while 2-substituted indoles furnished 3-aminoindoles. Moreover, 2,3-diaminoindoles could be prepared from the resulting 3-diazoindolin-2-imines and secondary amines via a rhodium-catalyzed amination. Further extension of 2,3-diaminoindoles led to the formation of imidazo[4,5-b]indoles.