Suzuki-Miyaura Cross-Coupling Reaction Catalyzed by Al12M (M = Be, Al, C, and P) Superatoms with Different Numbers of Valence Electrons.

The exploration of low-cost, efficient, environmentally safe, and selective catalysts for the activation of carbon-halogen bonds has become an important and challenging topic in modern chemistry. With the help of density functional theory (DFT), it is found that phenyl bromide (PhBr) can be efficiently chemisorbed by the Al12M (M = Be, Al, C, and P) superatoms via forming highly polarized Al-Br covalent bonds, where the C-Br bonds of PhBr can be effectively activated through the electron transfer from Al12M. The different electronic structures of these four Al12M superatoms pose a substantial effect on their performances on the activation of PhBr and the catalytic mechanisms of the Suzuki-Miyaura (SM) reaction. Among them, the alkali-metal-like superatom Al12P exhibits the best performance for the activation of PhBr. In particular, Al13 and Al12P with open-shell electronic structures exhibit catalytic performances comparable to those of previously reported catalysts for this coupling reaction. Hence, it is highly expected that Al13 and Al12P could be used as novel superatom catalysts for C-C coupling reactions and, therefore, open up new possibilities to use nonprecious superatoms in catalyzing the activation and transformation of carbon-halogen bonds.

Bioinformatic Analysis of the Significance of the KIR2DL4 Gene in Recurrent Implantation Failure.

Related studies have pointed out that Killer immunoglobulin-like receptor 2DL4 (KIR2DL4) was associated with vascular remodeling in early pregnancy, and it might play an important role in immunity. In this study, recurrent implantation failure (RIF)-related GSE58144 dataset was extracted from the Gene Expression Omnibus (GEO) database. Firstly, the immune micro-environment analyses were conducted to analyze the pathogenesis of KIR2DL4 in RIF. Then, the gene set enrichment analysis (GSEA) was performed to investigate the function of KIR2DL4. Moreover, the TF-mRNA-miRNA and the co-expression networks were constructed to reveal the potential regulation of KIR2DL4. Furthermore, the genes that were associated with KIR2DL4 and differentially expressed in RIF were obtained and defined as key genes, and the functions of these genes were further explored. KIR2DL4 could be used for clinical diagnosis of RIF, and it was correlated with the changes in the immune micro-environment in RIF. From the perspective of function, KIR2DL4 was associated with complement and coagulation cascades, natural killer cell-mediated cytotoxicity, etc. Moreover, the TF-mRNA-miRNA regulatory network was constructed with KIR2DL4, 9 TFs, and 29 miRNAs. Furthermore, KIR2DL4, ACSM1, IL2RB, and PTPN11 were screened as key genes, which were associated with immune-related functions. This study deeply analyzed the function of KIR2DL4 and its role in RIF, and we found that STAT1 might up-regulate KIR2DL4 by INF-γ/JAK2/STAT1 signaling pathway. Besides, over-expressed KIR2DL4 in the mid-luteal endometrium might influence embryo implantation by affecting the embryo implantation microenvironment, which might help deepen the understanding of the molecular mechanism of RIF.

Theoretical prediction of superatom WSi12-based catalysts for CO oxidation by N2O.

Catalytic conversion of N2O and CO into nonharmful gases is of great significance to reduce their adverse impact on the environment. The potential of the WSi12 superatom to serve as a new cluster catalyst for CO oxidation by N2O is examined for the first time. It is found that WSi12 prefers to adsorb the N2O molecule rather than the CO molecule, and the charge transfer from WSi12 to N2O results in the full activation of N2O into a physically absorbed N2 molecule and an activated oxygen atom that is attached to an edge of the hexagonal prism structure of WSi12. After the release of N2, the remaining oxygen atom can oxidize one CO molecule via overcoming a rate-limiting barrier of 28.19 kcal mol-1. By replacing the central W atom with Cr and Mo, the resulting MSi12 (M = Cr and Mo) superatoms exhibit catalytic performance for CO oxidation comparable to the parent WSi12. In particular, the catalytic ability of WSi12 for CO oxidation is well maintained when it is extended into tube-like WnSi6(n+1) (n = 2, 4, and 6) clusters with energy barriers of 25.63-29.50 kcal mol-1. Moreover, all these studied MSi12 (M = Cr, Mo, and W) and WnSi6(n+1) (n = 2, 4, and 6) species have high structural stability and can absorb sunlight to drive the catalytic process. This study not only opens a new door for the atomically precise design of new silicon-based nanoscale catalysts for various chemical reactions but also provides useful atomic-scale insights into the size effect of such catalysts in heterogeneous catalysis.

[Research progress of combination therapy in the treatment of erectile dysfunction and premature ejaculation comorbidity].

There is a close relationship between male erectile dysfunction (ED) and premature ejaculation (PE) on the pathogenesis, leading a high comorbidity rate and a need of simultaneous treatment in clinical practice. Phosphodiesterase 5 inhibitors (PDE5i) and selective serotonin reuptake inhibitor (SSRI) Dapoxetine are first-line oral drugs for ED and PE, respectively. In recent years, multi-country clinical guidelines have provided suggestions and guidance for the combination of these two drugs, with the safety and effectiveness being further explored and verified. This review summarized the status of ED and PE comorbidity, treatment principles, and research progress on the safety and effectiveness of Dapoxetine combined with PDE5i, in order to provide reference for the combination therapy of ED and PE comorbidity.

[Application value of color Doppler ultrasonography in the diagnosis of ruptured tunica albuginea of the corpus cavernosum penis].

OBJECTIVE: To assess the accuracy and value of ultrasonography in the diagnosis of ruptured tunica albuginea (RTA) of the corpus cavernosum penis. Factors affecting prognosis were analyzed. METHODS: This retrospective study included 57 cases of RTA of the corpus cavernosum penis ultrasonographically diagnosed and surgically treated in Peking University First Hospital from 2013 to 2021. We analyzed the location, size and number of ruptures and the presence or absence of urethral injury, and compared the intraoperative with the ultrasonographic findings. RESULTS: Of the 57 cases of RTA of the corpus cavernosum penis diagnosed by ultrasonography, 54 (94.7%) were confirmed by surgery. Preoperative ultrasonography indicated 2 cases of bilateral RTA and 6 cases of urethral injury, while surgery revealed 7 cases of bilateral RTA and 13 cases of combined urethral injury. Those with urethral injury developed no urethral stricture or urinary fistula after one-stage urethral repair. And no severe or moderate ED was found in any of the patients during the 12-month follow-up. CONCLUSION: Ultrasonography has a high accuracy in the diagnosis of ruptured tunica albuginea of the corpus cavernosum penis, and contributes to the determination of the site of surgical incision.

[Influence of epididymitis history on the results of vasoepididyostomy in patients with epididymal obstruction].

OBJECTIVE: To evaluate the influence of epididymitis history on the results of microsurgical vasoepididymostomy and spontaneous pregnancy in patients with epididymal obstruction. METHODS: Totally 205 patients with epididymal obstruction underwent microsurgical two-suture longitudinal intussusception vasoepididymostomy from January 2014 to December 2016. After surgery, we evaluated the semen quality of the patients every 3 months till conception and compared the rates of patency and spontaneous pregnancy between the patients with and those without an epididymitis history. RESULTS: The patients ranged in age from 22 to 46 (mean 31) years, 37 (22.2%) with and 126 (77.8%) without an epididymitis history among the 163 patients for whom a 25.4-month follow-up (from 7 to 42 months) was completed. No statistically significant differences were observed postoperatively between the patients with and those without an epididymitis history in the patency rate (73.0% vs 81.7%, P = 0.243), sperm concentration (18 ï¼»1.3－33.6ï¼½ vs 15.2 ï¼»0.8－33.4ï¼½ ×106/ml, P = 0.710), percentage of progressively motile sperm (27.5 ï¼»0－46.1ï¼½% vs 19.3 ï¼»0－41ï¼½% (P = 0.592) or rate of spontaneous pregnancy (24.3% vs 38.9%, P = 0.104). CONCLUSION: Microsurgical vasoepididymostomy is an effective method for the treatment of epididymal obstruction, and epididymitis history does not affect the results of the strategy.

[Testosterone supplementation therapy for improvement of lower urinary tract symptoms: Progress in studies].

The theory that prostate growth depends on androgens has caused the worry clinically that the testosterone supplementation therapy (TST) may increase the prostate volume and worsen lower urinary tract symptoms (LUTS). However, more and more findings show that TST does not increase the prostate volume in patients with late-onset hypogonadism (LOH) or affect the IPSS, which may be attributed to the saturation of the androgen receptor. Testosterone deficiency and metabolic syndrome are risk factors for LUTS, the former affecting the autonomic nerve function, relaxation and blood supply of the bladder and urethral smooth muscle, and Rho enzyme activity, while the latter enhancing sympathetic activity and causing the body's inflammatory state and arteriosclerosis. Findings have proved that TST can improve LUTS in patients with LOH, with even better effect in those with a higher baseline IPSS or metabolic syndrome. More researches are needed to confirm the role of TST in improving LUTS.

[Point electro-cauterization versus holmium laser cauterization in the treatment of post-ejaculation hematuria].

OBJECTIVE: To investigate the advantages and disadvantages of point electro-cauterization (PEC) and holmium laser cauterization (HLC) in the treatment of post-ejaculation hematuria. METHODS: From January 2015 to December 2018, 73 patients with post-ejaculation hematuria, aged 24－63 (36.8 ± 4.2) years, underwent PEC (n = 35) or HLC (n = 38) after failure to respond to 3 months of conservative treatment. We compared the hospital days, total hospitalization expenses, maximum urinary flow rate (Qmax), average urinary flow rate (Qavg), Hamilton Anxiety Rating Scale (HAMA) score, postoperative duration of hematuria, and recurrence rate at 3 and 6 months after surgery. RESULTS: All the patients experienced first ejaculation but no post-ejaculation hematuria at 1 month after operation. The recurrence rates were lower in the PEC than in the HLC group at 3 months (5.71% vs 2.63%, P > 0.05) and 6 months postoperatively (8.57% vs 5.26%, P > 0.05). Compared with the baseline, the Qmax was decreased from (18.56 ± 2.53) ml/s to (13.68 ± 3.31) ml/s (P < 0.05) and the Qavg from (14.35 ± 2.26) ml/s to (9.69±1.84) ml/s in the PEC group at 1 month after surgery (P < 0.01), but neither showed any statistically significant difference in the HLC group. Mild to moderate anxiety was prevalent in the patients preoperatively, particularly in those without job or regular income and those with a long disease course or frequent onset, the severity of which was not correlated with age, education or marital status. The HAMA score was decreased from18.65 ± 4.33 before to 12.35 ± 3.63 after surgery in the PEC group (P < 0.01), and from 16.88 ± 2.11 to 6.87 ± 4.36 in the HLC group (P < 0.01). The mean hospital stay was significantly longer in the former than in the latter group (ï¼»5.2 + 1.3ï¼½ vs ï¼»3.4 ± 0.5ï¼½ d, P < 0.01), while the total cost markedly lower (ï¼»6.35 ± 1.20ï¼½ vs ï¼»12.72 ± 2.15ï¼½ thousand RMB ¥, P < 0.05). CONCLUSIONS: Both PEC and HLC are safe and effective for the treatment of post-ejaculation hematuria, with no significant difference in the recurrence rate at 3 and 6 months after operation, but their long-term effect needs further follow-up studies. PEC may increase the risk of negative outcomes of the postoperative urinary flow rate, while HLC has the advantages of better relieving the patient's anxiety, sooner discharge from hospital and earlier recovery from postoperative hematuria, though with a higher total cost than the former.

Can the pathway of stepwise nucleation be predicted and controlled?

Predicting the critical nucleus size and the nucleation barrier is of central importance in controlling the dynamics of nucleation. However, as the nucleation of a crystal involves intermediate states, the prediction becomes inaccessible with currently available models. Here, we show that based on single-particle level observations, the properties of crystal nuclei in a microscopic stepwise nucleation (MSN) can be well-quantified by incorporating the size and structure order parameter into the formula of free energy without prior knowledge of interfacial tension. The quantified free energy reveals that the intermediate structures arise from thermodynamics rather than kinetics. Precritical and postcritical nuclei are distinct not only in structure but also in the mechanism of crystalline ordering. The relative stability of intermediate structures and the pathway of nucleation can be well-controlled by supercooling. Our studies offer a successful approach to quantify MSN and shed new light on resolving the long-standing discrepancies between simulations and experiments.

Pair aligning improved motility of Quincke rollers.

Density-dependent speed is studied in a two-dimensional active colloid in which the colloidal particles are propelled by an external electric field via a Quincke rotation. Above the critcal electric field, dense dynamic clusters form spotaneously, in which the particles are highly aligned in velocity and move much faster than isolated units. Detailed observations on pair collision reveal that the alignment of velocity is induced by the long-ranged hydrodynamic interactions and the improvement of speed in the clusters arises from pair aligning in which two particles are closely paired and rotate synchronically. In the aligning state, the short-range in-plane dipole-dipole attraction enhances the rotation torque and gives rises to a larger rolling speed. The pair aligning becomes difficult and unstable at high electric field where the normal dipole-dipole repulsion becomes dominant. As a consequence, the dependence of speed on density becomes weak increasingly upon the increase of the electric field. This result offers an interpretation for the discrepancy between our and previous observations on Quincke rollers.

[Qilin Pills for idiopathic oligoasthenospermia: A multi-centered randomized double-blind controlled clinical trial].

OBJECTIVE: To evaluate the clinical efficacy and safety of Qilin Pills in the treatment of oligoasthenospermia in infertile men. METHODS: This multi-centered randomized double-blind controlled clinical trial included 216 infertile males with oligoasthenospermia, 108 in the trial group and the other 108 in the control, the former treated with Qilin Pills at the dose of 6 g tid while the latter with Wuziyanzong Pills at 6 g bid, both for 12 weeks. We examined the total sperm count, sperm motility and the count of progressively motile sperm of the patients before and at 4, 8 and 12 weeks after medication and evaluated the safety of the drug based on the adverse events and the laboratory results of blood and urine routine examinations and liver and kidney function tests. RESULTS: Compared with the baseline, the patients in the trial group showed a significant time-dependent improvement after 4, 8 and 12 weeks of medication in sperm motility (21.75% vs 27.54%, 29.04% and 32.95%, P <0.05), total sperm count (156.27 ×106 vs 177.33, 188.18 and 205.44 ×106, P <0.05), and the count of progressively motile sperm (32.08 ×106/ml vs 46.33, 50.98 and 61.10 ×106/ml, P <0.05). The three parameters above were also improved in the controls, but more significantly in the trial group (P <0.05). CONCLUSIONS: Qilin Pills can evidently improve the semen quality of oligoasthenospermia patients with no obvious adverse events.

Amelioration of free fatty acid-induced fatty liver by quercetin-3-O-ß-D-glucuronide through modulation of peroxisome proliferator-activated receptor-alpha/sterol regulatory element-binding protein-1c signaling.

AIM: To investigate the therapeutic effect and potential mechanisms of the natural flavonoid quercetin-3-O-ß-D-glucuronide (Q3GA) against lipid metabolism disorder in free fatty acid (FFA)-induced fatty liver in vivo and in vitro. METHODS: Fat accumulation was documented by oil red O staining, and intracellular triglyceride levels were detected by triglyceride(TG) enzymatic assay. Flow cytometry and enzyme-linked immunoassay assay were performed to observe the effect of Q3GA on lipotoxicity and inflammation response of primary rat hepatocytes with FFA treatment. Administration with Q3GA at doses of 25 and 50 mg/kg from the fifth week during high fat diet (HFD) induced non-alcoholic fatty liver disease (NAFLD) model for 8 weeks. Expression of the genes involved in the lipogenesis and fatty acid ß-oxidation were assayed by reverse transcription polymerase chain reaction. RESULTS: Q3GA reduced bodyweight gain, liver weight, liver index, dyslipidemia and hepatic TG level in a dose-dependant manner. In the FFA-overloaded primary rat hepatocytes, Q3GA decreased the fat overload and TG content, inhibited hepatocyte apoptosis and reduced inflammation cytokine expression. Importantly, the histopathological examination of liver showed that Q3GA could decrease hepatic lipid accumulation and liver injury. Besides, Q3GA decreased the expression of sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase and increased the expression of peroxisome proliferator-activated receptor-α (PPAR-α), carnitine palmitoyl-transferase 1 and medium-chain acyl-coenzyme A dehydrogenase in vivo and in vitro. CONCLUSION: The therapeutic effect of Q3GA on lipid metabolism disorder in FFA-induced fatty liver rats is partly due to downregulating SREBP-1c and upregulating PPAR-α-mediated metabolic pathways.

Enantioselective N-H insertion reaction of α-aryl α-diazoketones: an efficient route to chiral α-aminoketones.

A highly enantioselective NH insertion reaction of α-diazoketones was developed by using cooperative catalysis by dirhodium(II) carboxylates and chiral spiro phosphoric acids. The insertion reaction provides a new access route to diverse chiral α-aminoketones, which are versatile building blocks in organic synthesis, with fast reaction rates, good yields and high enantioselectivity under mild and neutral conditions.

Long-term tadalafil once daily in Chinese men with erectile dysfunction: a 2-year final analysis of a post-marketing, multicenter, randomized, open-label trial.

The long-term safety and effectiveness of once-daily tadalafil is crucial, but limited data are available in Chinese patients with erectile dysfunction (ED). In this post-marketing, multicenter, randomized, open-label trial with 2-year follow-up, 635 ED cases were randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months, of whom 580 continued once-daily tadalafil 5 mg for 21 months. Treatment-emergent adverse events in the 12-month and 24-month period were similar, with the most common being viral upper respiratory tract infection, upper respiratory tract infection, and headache. Significant improvement from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) score was detected at month 12 (least squares mean [LSM] change: 7.9, 95% confidence interval [CI]: 7.5-8.4, P < 0.001) and was maintained to month 24 (LSM change: 8.6, 95% CI: 8.1-9.0, P < 0.001). The proportions of patients regaining normal erectile function (IIEF-EF score ≥26) were 43.7% and 48.0% at months 12 and 24, respectively. Global Assessment Questionnaire results showed improved erection function in 97.5% of patients and improved ability to engage in sexual activity in 95.9% of patients at month 12; these values were 96.1% and 95.0% at month 24, respectively. The quality of sexual life score based on the Sexual Life Quality Questionnaire (SLQQ) was increased by 52.2% at month 12 and by 55.3% at month 24 (both P < 0.001). The treatment satisfaction score determined by SLQQ (mean ± standard deviation) was 62.4 ± 21.0 at month 12 versus 65.9 ± 20.2 at month 24. Two-year daily application of tadalafil 5 mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

METTL14 downregulation drives S100A4+ monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression.

Without intervention, a considerable proportion of patients with metabolism-associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism-associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1+Ccr2+ monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1+Ccr2+ Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1+Ccr2+ Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.

Characterization of the Expression Profile and Genetic Polymorphism of the Cellular Retinol-Binding Protein (CRBP IV) Gene in Erlang Mountainous Chickens.

In this study, we cloned the coding sequence of chicken CRBP IV, quantified the mRNA expression in Erlang Mountainous Chickens, and investigated a polymorphism in this gene and its association with egg production traits among 349 individuals. The cloned fragment contained a 384 bp open reading frame, which encoded a predicted protein of 127 amino acids and was highly conserved among species. Expression of CRBP IV mRNA was detected in all eight tissues (small intestine, heart, liver, kidney, oviduct, ovary, pituitary, and hypothalamus) at different ages (12, 24, 32 and 45 w). High expression was found in small intestine, pituitary, kidney and liver, whereas it was low in the heart (p < 0.05). The CRBP IV mRNA levels changed with age in the various tissues, and were highly expressed in all tissues at 32 w, except for the heart. We identified one nucleotide substitution (c. 826T>C) in the second exon, which caused an amino acid change (p. S49L). Genotypes (TT, TC and CC) had significant effects on the age at first egg (AFE), total eggs for 300 days (TE300) and highest continuous laying days (HCLD). The CC genotype would be genetically advantageous to improve egg production traits due to earlier AFE, more TE300, and longer HCLD.

[Efficacy of microsurgical vasectomy reversal on patients after vasectomy].

OBJECTIVE: To evaluate the efficacy of microsurgical vasectomy reversal on patients after vasectomy. METHODS: In the study, 41 patients after vasectomy were admitted for microsurgical vasectomy reversal. The mean (range) age was 45 (29 to 66) years for the men. The mean duration of obstruction was 12 years. All the patients were seen by the surgeon for a complete history and physical examination. Semen analyses proved azoopermia, and their serum levels of sexual hormone were normal. They were all offered scrotal exploration. Microvasovasostomy was performed if the sperm was found in the material coming from the proximal vas lumen. The decision for microvasoepididymostomy was made during surgery, if the fluid was creamy, containing only debris or there was no fluid whatsoever when the vas was milked toward the cut end. Microvasovasostomy was performed in 40 patients, of whom 6 were with lateral microvasoepididymostomy and 1 with bilateral microvasoepididymostomy. The initial semen analysis was then done after usually 3 months postoperatively. Patency was arbitrarily defined as>10 000 sperm/mL in ejaculate in at least one semen analysis after surgery. Postoperative patency rate and postoperative impregnation rate were followed. RESULTS: The 41 patients were followed up for 3 to 72 months, and 5 cases were lost. In the 28 patients who had obstructions for less than 15 years, 3 were lost. Sperm was found by semen analysis in 21 patients. Their sperm density was 2×10(6) to 46×10(6) sperms/mL and motility was 0% to 60%. The semen analysis revealed azoospermia in 2 patients after 12 months, who were advised to undergo intracytoplasmic sperm injection. Natural conception occurred in 6 patients followed for more than 12 months. The overall patency rate was 84% (21/25). Among the patients with a follow-up of >6 months, the natural paternity rate was 29% (6/21). In the 13 patients who had obstructions for more than 15 years, 2 were lost. The patency and pregnancy rates were 64% (7/11) and 14% (1/7) respectively. Their sperm density was 0.02×10(6) to 30× 10(6) sperms/mL and motility was 0% to 43%. CONCLUSION: Microsurgical vasectomy reversal is an effective method to treat vasal obstruction due to vasectomy. The patency and pregnancy rates are related to the time of vasectomy. The patency and pregnancy rates are higher in patients with obstruction for less than 15 years than those for more than 15 years.

[UPOINT system: a new diagnostic/therapeutic algorithm for chronic prostatitis/chronic pelvic pain syndrome].

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition in urological outpatients, and is often improperly treated for its multifactorial etiology and non-specific clinical phenotype. Doctor Shoskes proposed a clinical phenotype system for CP/CPPS--the UPOINT system, which is a new diagnostic/therapeutic algorithm addressing 6 CP/CPPS phenotypic domains, including the urinary, psychosocial, organ specific, infection, neurological/systemic and muscle tenderness domains. Under the guidance of UPOINT, doctors can give a multimodal therapy for patients with CP/CPPS according to its clinical phenotype, and several clinical studies have demonstrated obvious clinical benefit from the UPOINT-based therapy.

[Daily low-dose tadalafil for erectile dysfunction induced by pelvic fracture urethral disruption].

OBJECTIVE: To evaluate the effect of daily low-dose tadalafil on erectile dysfunction (ED) induced by pelvic fracture urethral disruption (PFUD). METHODS: This study included 46 cases of PFUD-induced ED treated from Jan 2008 to Dec 2011. The patients were aged 33.9 +/- 7.2 years (range 25 -51 yr), and the interval between injury and treatment was 19.6 +/- 12.7 months (range 3 - 72 mo), all with normal erectile function before PFUD. Based on the nocturnal penile tumescence and rigidity (NPTR) recorded by erectometry without medication of phosphodiesterase type 5 inhibitor (PDE-5I), the patients were divided into an abnormal nocturnal erection group and a non-nocturnal erection group, and treated with tadalafil 10 mg once daily for 3 months. The therapeutic effect was evaluated by IIEF-5 scores and the rate of yes responses to questions 2 and 3 of the Sexual Encounter Profile (SEP). RESULTS: Totally 38 (82.6%) of the patients accomplished the treatment and follow-up, 26 (68.4%) in the abnormal nocturnal erection group and 12 (31.6%) in the non-nocturnal erection group. After 3 months of daily tadalafil treatment at 10 mg, the IIEF-5 scores were significantly improved in the abnormal nocturnal erection group than in the non-nocturnal erection group (P < 0.05), and the rate of yes responses to SEP2 and SEP3 was remarkably higher in the former than in the latter (76.9% vs 41.7% and 65.4% vs 25.0%, P < 0.05). CONCLUSIONS: Daily low-dose tadalafil can effectively improve the erectile function of PFUD-induced ED patients, particularly in those with nocturnal erection.

Influence of N Terminus Amino Acid on Peptide Cleavage in Solution through Diketopiperazine Formation.

Diketopiperazine (DKP) formation is an important degradation pathway for peptides and proteins. It can occur during synthesis and storage in either solution or the solid state. The kinetics of peptide cleavage through DKP formation have been analyzed for the model peptides Xaa1-Pro2-Gly4-Lys7 [Xaa = Gln, Glu, Lys, Ser, Phe, Trp, Tyr, Cha (ß-cyclohexylalanine), Aib (α-aminoisobutyric acid), Gly, and Val] at multiple elevated temperatures in ethanol with ion mobility spectrometry-mass spectrometry (IMS-MS). When Xaa is an amino acid with a charged or polar side chain, degradation is relatively fast. When Xaa is an amino acid with a nonpolar alkyl side chain, the peptide is relatively stable. For these peptides, a bulky group on the α carbon speeds up dissociation, but the kinetic effects vary in a complicated manner for bulky groups on the ß or γ carbon. Peptides where Xaa has a nonpolar aromatic side chain show moderate dissociation rates. The stability of these peptides is a result of multiple factors. The reaction rate is enhanced by (1) the stabilization of the late transition state through the interaction of an aromatic ring with the nascent DKP ring or lowering the activation energy of nucleophilic attack intermediate state through polar or charged residues and (2) the preference of the cis proline bond favored by the aromatic N-terminus. The number of unseen intermediates and transition state thermodynamic values are derived for each peptide by modeling the kinetics data. Most of the transition states are entropically favored (ΔS⧧ ∼ -5 to +31 J·mol-1·K-1), and all are enthalpically disfavored (ΔH⧧ ∼ 93 to 109 kJ·mol-1). The Gibbs free energy of activation is similar for all of the peptides studied here (ΔG⧧ ∼ 90-99 kJ·mol-1).