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

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

Soil amendments reduce CH4 and CO2 but increase N2O and NH3 emissions in saline-alkali paddy fields.

Limited research has been conducted on ammonia (NH3) volatilization and greenhouse gases (GHGs) emissions in saline-alkali paddy fields, along with complex interaction involving various genes (16sRNA, amoA, narG, nirK, nosZ, and nifH). This study employed mesocosm-scale experiment to investigate NH3 volatilization and GHGs emissions, focusing on bacterial communities and genic abundance, in saline-alkali paddy fields with desulfurized gypsum (DG) and organic fertilizer (OF) amendments. Compared to the control (CK) treatment, DG and OF treatments reduced methane (CH4) and carbon dioxide (CO2) emissions by 78.05 % and 26.18 %, and 65.84 % and 11.62 %, respectively. However, these treatments increased NH3 volatilization by 26.26 % and 45.23 %, and nitrous oxide (N2O) emission by 41.00 % and 12.31 %. Notably, NH3 volatilization primarily stemmed from ammonia nitrogen (NH4+-N), rather than total nitrogen (TN) in soil and water. N2O was mainly produced from nitrate nitrogen (NO3--N) in soil and water, as well as NH4+-N in water. The increase in NH3 volatilization and N2O emission in DG and OF treatments, was attributed to the reduced competition among bacterial communities, rather than the increased bacterial activity and genic copies. These findings offer valuable insights for managing nutrient loss and gaseous emissions in saline-alkali paddy fields.

Soil aggregate-driven changes in nutrient redistribution and microbial communities after 10-year organic fertilization.

Research studies on nutrient content and microbial communities after the application of organic manure have been reported, while available information about multi-interaction mechanisms of nutrient stoichiometry and microbial succession in soil aggregates remains limited. This work conducted a 10-year field experiment amended with cow manure (1.5 t/ha), during which the application of organic manure stimulated the fragmentation of soil macro-aggregates (>5 mm) and the agglomeration of soil micro-aggregates (<0.25 mm). Hence, the proportion of medium-size aggregates (0.25-5 mm) was increased in bulk soil, and there was an insignificant difference in the stability of soil aggregates. Meanwhile, the application of organic manure increased soil organic carbon (SOC), total nitrogen (TN) and phosphorus (TP) in all soil aggregate fractions. SOC, TN and TP were higher in micro-aggregates (<0.25 mm) after the application of organic manure, thus the dominating phylum of bacteria and fungi was more abundance in micro-aggregates due to the increase in nutrient level. During the organic fertilization process, fungal communities significantly changed because the variation of carbon-to-nitrogen ratio (C:N) in soil aggregates. Cultivated farmland in Northeast China showed a considerable capacity to sequestrate SOC during the organic fertilization process, but nitrogen may be a primary macro-element limiting soil productivity. Theoretically, organic manure amended with nitrogen fertilizer could be an effective measure to maintain microbial diversity and crop productivity in agro-ecosystems in Northeast China.

FeCa-based layered double hydroxide, a high-performance phosphorus adsorbent in constructed wetlands and ecological dams - A pilot scale study.

Research studies have modified traditional substances to seek fast-acting removal of phosphorus in constructed wetlands (CWs) and ecological dams, rather than develop a brand-new nano-adsorbent. This work synthesized FeCa-based layered double hydroxide (FeCa-LDH) with a chemical co-precipitation method, and the performance, mechanism and factors of phosphorus removal were investigated. FeCa-LDH showed a marked ability to adsorb phosphorus from waste water, with a removal efficiency of 94.4% and 98.2% in CWs and ecological dams, respectively. Both FTIR and XPS spectrum evidenced that FeCa-LDH removed phosphorus via electrostatic and hydrogen-bonding adsorption, as well as a coordination reaction and interlayer anion exchange. FeCa-LDH showed a higher capacity to remove phosphorus in alkaline and neutral waste water than in acid conditions. Co-occurrence anions, which influenced the efficiency of the phosphorus removal capacity are considered in the sequence below: CO32- ≈ HCO3- > SO42- > NO3-. Innovatively, FeCa-LDH was not affected by the low-temperature limitation for CWs, and phosphorus removal efficiency at 5 °C was almost equal to that at 25 °C. These results cast a new idea on the construction, application and phosphorus removal performance of CWs and ecological dams.

Comparative study on the gene expression of corticosterone metabolic enzymes in embryonic tissues between Tibetan and broiler chickens.

Glucocorticoids (GCs) are an essential mediator hormone that can regulate animal growth, behavior, the phenotype of offspring, and so on, while GCs in poultry are predominantly corticosterones. The biological activity of GCs is mainly regulated by the intracellular metabolic enzymes, including 11ß-hydroxysteroid dehydrogenases 1 (11ß-HSD1), 11ß-hydroxysteroid dehydrogenases 2 (11ß-HSD2), and 20-hydroxysteroid dehydrogenase (20-HSD). To investigate the embryonic mechanisms of phenotypic differences between breeds, we compared the expression of corticosterone metabolic enzyme genes in the yolk-sac membrane and chorioallantoic membrane (CAM). We described the tissue distribution and ontogenic patterns of corticosterone metabolic enzymes during embryonic incubation between Tibetan and broiler chickens. Forty fertilized eggs from Tibetan and broiler chickens were incubated under hypoxic and normoxic conditions, respectively. Real-time fluorescence quantitative PCR was used to examine the expression of 11ß-HSD1/2, and 20-HSD mRNA in embryonic tissues. The results showed that the expression levels of yolk-sac membrane mRNA of 11ß-HSD2 and 20-HSD in Tibetan chickens on E14 (embryonic day of 14) were significantly lower than those of broiler chickens (P < 0.05), and these genes expression of CAM in Tibetan chickens were higher than those of broiler chickens (P < 0.05). In addition, the three genes in the yolk-sac membrane and CAM were followed by a down-regulation on E18 (embryonic day of 18). The 11ß-HSD1 and 11ß-HSD2 genes followed a similar tissue-specific pattern: the expression level was more abundantly in the liver, kidney, and intestine, with relatively lower abundance in the hypothalamus and muscle, and the expression level of 20-HSD genes in all tissues tested was higher. In the liver, 20-HSD of both Tibetan and broiler chickens showed different ontogeny development patterns, and hepatic mRNA expression of 20-HSD in broiler chickens was significantly higher than that of Tibetan chickens of the same age from E14 to E18 (P < 0.05). This study preliminarily revealed the expression levels of cortisol metabolic genes in different tissues during the development process of Tibetan and broiler chicken embryos. It provided essential information for in-depth research of the internal mechanism of maternal GCs programming on offspring.

Single-pixel neural network object classification of sub-Nyquist ghost imaging.

A single-pixel neural network object classification scenario in the sub-Nyquist ghost imaging system is proposed. Based on the neural network, objects are classified directly by bucket measurements without reconstructing images. Classification accuracy can still be maintained at 94.23% even with only 16 measurements (less than the Nyquist limit of 1.56%). A parallel computing scheme is applied in data processing to reduce the object acquisition time significantly. Random patterns are used as illumination patterns to illuminate objects. The proposed method performs much better than existing methods for both binary and grayscale images in the sub-Nyquist condition, which is also robust to environment noise turbulence. Benefiting from advantages of ghost imaging, it may find applications for target recognition in the fields of remote sensing, military defense, and so on.

Isolation, identification, characterization, synthesis and quality control strategy of new process-related impurities in ambrisentan.

Ambrisentan is a highly selective endothelin-A receptor antagonist for the treatment of pulmonary arterial hypertension (PAH). The analysis of the process-related impurities will help not only to optimize the process parameters but also to develop reasonable analytical methods and set the quality standard for a quality control strategy in pharmaceutical manufacturing. During the manufacture of ambrisentan, five unknown impurities were detected in pilot batches ranging from 0.05% to 0.15% by HPLC. All of these impurities were isolated and synthesized successfully and were identified and characterized by LC-MS, HRMS, ESI-MS/MS(Q-Tof), 1D-NMR (1H, 13C, DEPT) and 2D-NMR (COSY, HSQC, HMBC) techniques. The formation mechanisms that yield these impurities are discussed for the first time. Quality control strategies to deal with these impurities are developed to obtain bulk drug of ICH-grade quality.

Deregulation of MicroRNA-375 Inhibits Proliferation and Migration in Gastric Cancer in Association With Autophagy-Mediated AKT/mTOR Signaling Pathways.

Gastric cancer is a deadly disease. Some microRNAs are involved in tumor invasion and metastasis. Underexpression of miR-375 has been correlated with tumorigenesis, treatment resistance, and poor prognosis. In this study, we first analyzed the profiles and prognostic values of miR-375 expression in gastric cancer tissues from a public database, and the expression level of miR-375 in gastric cancer samples and gastric cancer cell lines was then analyzed by quantitative real- time polymerase chain reaction. Significant underexpression of miR-375 was seen in all the gastric cancer samples compared to paired paracarcinoma tissues, and the expression level of miR-375 in the gastric cancer cell lines was negatively associated with the cell migration ability. A Cell proliferation (CCK-8) assay was performed to examine cell viability. Overexpression of miR-375 suppressed the proliferation of gastric cancer cells. A Western blot analysis was carried out to test protein expression. Overexpression of miR-375 inhibited autophagy through the AKT/ mammalian target of rapamycin signaling pathway. MiR-375 regulated invasion and migration via AKT/ mammalian target of rapamycin pathway-mediated epithelial-to-mesenchymal transition. Wound healing and migration assays were used to determine the motility of gastric cancer cells. A gastric cancer xenograft nude mouse model was used for an in vivo efficacy evaluation. Overexpression of miR-375 significantly suppressed cell proliferation in the established gastric cancer xenograft nude mouse model. Our results demonstrate that increasing the expression level of miR-375 suppresses proliferation in vitro and in vivo, and they provide a mechanistic and applicable rationale for the future clinical evaluation of miR-375 in gastric cancer treatment. Our findings provide not only new information about the molecular mechanism of microRNAs in regulating invasion and migration in gastric cancer but also a theoretical principle for a potential targeted therapy for gastric cancer.

Risk factors of recurrence of atrial fibrillation in aged patients with chronic diseases after cryoballoon ablation / 上海交通大学学报（医学版）

Objective • To evaluate the recurrence rate of atrial fibrillation (Af) and its related risk factors in aged patients with chronic diseases after cryoballoon ablation. Methods • With the method of convenient sampling, a total of 159 patients with Af after cryoballoon ablation were enrolled in the Department of Cardiology, Ruijin Hospital from Oct. 2016 to Jan. 2018. Self-rating depression scale (SDS) and CHA2DS2-VASc scores [congestive heart failure, hypertension, age ≥ 75 y (doubled), diabetes mellitus, stroke(doubled)-vascular disease, age 65-74 and sex category(female)] were used to assess the patients. Follow-up checks consisted of chief complaint, postoperative electrocardiogram (ECG), and 24 h Holter monitoring. Logistic regression models were performed to explore the independent risk factors of Af recurrence after cryoballoon ablation. Results • 152 patients (95.6%) completed the follow-up checks, with an average age of (61.9±8.9) years. The average time of follow-up period was (8.35±2.41) months. A total of 41 patients (27.0%) developed Af after cryoballoon ablation. Logistic regression analysis showed the number of chronic disease ≥ 2 (OR=2.466, 95% CI: 1.375-4.452), CHA2DS2-VASc scores ≥ 2 (OR=2.088, 95% CI: 1.142-5.557), irregular use of anti-arrhythmic drugs (OR=1.581, 95% CI: 1.351-2.125), hypertension (OR=1.317, 95% CI: 1.076-2.809), and body mass index (BMI) (OR=1.147, 95% CI: 1.009-1.174) were the independent risk factors of Af recurrence. Conclusion • There is still a certain percentage of recurrence in aged patients with chronic diseases after cryoballoon ablation. 2 and more chronic diseases, irregular use of anti-arrhythmic drugs, hypertension, CHA2DS2-VASc scores ≥ 2, and overweight may be potential risk factors of Af recurrence after cryoballoon ablation.