The risk factors, pathological mechanisms and therapeutic strategies of sexual dysfunction.
Display omitted
Sexual dysfunction (SD) is a disorder of sexual behavior and sexual sensation that appears ...as an abnormality or absence of sexual psychology and physiological reaction. It is a general term for many different symptoms includes several aspects, erectile dysfunction (ED), failure of sexual intercourse and loss of libido/desire. According to statistics, 52% of 40˜70 year old men suffer from varying degrees of SD. And these diseases caused by a variety of biological and psychological factors. In world about 15% of couples are affected by sexual disharmony among these 40 to 50% are because of male factors. Considering the sensitivity of male reproduction system, it is being easily affected by multiple risk factors, such as chronic diseases, environmental contaminants, drug toxicity and unhealthy lifestyle and so on. In the last few years, significant progress have been made toward understanding the various forms of male SD and the possible potential pathological mechanisms. However, for the time being, the exact cause of SD is not fully understood from the literature. What is also significant about there are quite limited treatments in reproductive medicine being directed against these lesions. The purpose of this review is to summarize the current findings of pathogenic factors of SD in clinical or animal studies, to elaborate the underlying mechanisms of these diseases from studies in vivo and in vitro, to analyses the risk factors, and to describe the management strategies traditionally recommended of male sexual dysfunction. The review findings elucidate a systematic strategies for effectively preventing these diseases.
Purpose
A population-level description and analysis of sepsis-related mortality in China is key to the planning and assessment of interventional strategies.
Methods
Retrospective analysis of multiple ...cause of death (MCOD) recorded in the population-based national mortality surveillance system (NMSS) of China. All sepsis-related deaths occurring in 605 disease surveillance points (DSPs) covering 323.8 million population across China were included in our study. Age-standardized mortality and national estimate of sepsis-related deaths were estimated using the census population in 2010 and 2015, respectively.
Results
In 2015, a total of 1,937,299 deaths occurring in any of the 605 DSPs and standardized sepsis-related mortality rate was 66.7 (95% confidence interval CI 66.4–67.0) deaths per 100,000 population. This produced a national estimate of 1,025,997 sepsis-related deaths. Sepsis-related mortality rates exhibited significant geographic variation. In multilevel analysis, male sex (rate ratio RR 1.582, 95% CI 1.570–1.595), increasing age (RR 1.914 for 5-year group, 95% CI 1.910–1.917), and presence of comorbidity (RR 2.316, 95% CI 2.298–2.335) were independently associated with increased sepsis-related mortality. Higher disposable income (RR 0.717 for the fourth interquartile range vs. the first interquartile range, 95% CI 0.515–0.978) and mean years of education (RR 0.808 for the fourth interquartile range vs. the first interquartile range, 95% CI 0.684–0.955) were negatively associated with sepsis-related mortality. However, population-based hospital doctors were not significantly associated with sepsis-related mortality.
Conclusions
The standardized sepsis-related mortality rate in China was high and varied according to socioeconomic indices, even though some uncertainty remained.
New carbon-carbon bond formation reactions expand our horizon of retrosynthetic analysis for the synthesis of complex organic molecules. Although many methods are now available for the formation of ...C(sp(2))-C(sp(3)) and C(sp(3))-C(sp(3)) bonds via transition metal-catalyzed cross-coupling of alkyl organometallic reagents, direct use of readily available olefins in a formal fashion of hydrocarbonation to make C(sp(2))-C(sp(3)) and C(sp(3))-C(sp(3)) bonds remains to be developed. Here we report the discovery of a general process for the intermolecular reductive coupling of unactivated olefins with alkyl or aryl electrophiles under the promotion of a simple nickel catalyst system. This new reaction presents a conceptually unique and practical strategy for the construction of C(sp(2))-C(sp(3)) and C(sp(3))-C(sp(3)) bonds without using any organometallic reagent. The reductive olefin hydrocarbonation also exhibits excellent compatibility with varieties of synthetically important functional groups and therefore, provides a straightforward approach for modification of complex organic molecules containing olefin groups.
Energy is unarguably the key factor for today's economic and social development within nations. Electricity as one of many energy forms is a critical input to developing countries in the struggle to ...the national self-satisfaction in all domains. Rural electricity supply involved institutions have recently recommended the pump as turbine (PAT)-based micro hydropower plant (MHP) schemes for remote off-grid electrification, mostly from their economic advantages. However, from different published research findings, PAT-based MHP is not only simple and economically feasible, but has presented bottlenecks in the move to its full understanding. Moreover, compared to other clean energy technologies, PAT technology has not found much literature in academic published researches, thus contributing to its limited understanding within the community. Therefore, the PAT literature availability is one way to level up its understanding, which can be helpful to academic and professional communities. In the present study, a state-of-the-art review on the two most challenging PAT aspects, namely PAT performance prediction and PAT flow stability aspects are presented. In the presented literature, the selected energy sources history leading to the actual MHP global adoption was first briefly explained, followed by an intensive literature on PAT operations, where details about PAT selection and performance prediction were provided. Finally, the PAT flow stability aspects where pump-turbine S-shape and Saddle-type characteristics constitute the main focus, were discussed. It is worth an attention to mention that the words “pump-turbine”, “Pump as turbine”, and “reversible pump turbine”; are equally used throughout the whole literature. It is within the authors wish that this paper can scale up the reader's PAT technology understanding, thus serving awareness in the same.
Small hydropower is the most preferred clean energy technology, especially in remote areas away from national electrical grid reach. Within these plants, Pump as Turbines (PATs) suffer from a very ...small range of optimum operating conditions, leading to a chronic vulnerability to off-design conditions and associated flow instability, as well as the resultant pressure pulsations. PAT impeller design presents a great opportunity to alter the flow dynamics within PAT flow zone, probably leading to PAT performance improvement. In this respect, the present study seeks to investigate the effect of blade trailing edge hub position on pressure field characteristics within a centrifugal PAT. Using the k-ɛ turbulence model, unsteady numerical simulations were carried on a three centrifugal PAT with different blade trailing edge hub positions, namely 15 mm, 20 mm, and 25 mm. The results showed that for PAT pressure pulsations distribution, the Rotor-stator Interaction (RSI) constitutes the main influencing factor, where the Blade Passing Frequency and its harmonics were the dominant frequencies, for the three models. Moreover; different PAT models exhibited different pressure pulsation characteristics. The Rh20 model exhibited the highest level of pressure pulsation amplitudes, while the lowest level of pressure pulsation was recorded with Rh15 model.
•Numerical simulations were conducted to investigate the effect of runner blade design on PAT pressure field characteristics.•Fast Fourier Transform-based pressure pulsations were extracted from different flow zones.•Analysis of pressure pulsation characteristics vis-à-vis the changing runner blade design was carried out.
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor for hypertension (HTN). The oral microbiota plays a pathophysiological role in cardiovascular diseases; however, there ...are few reports directly investigating and identifying the organisms involved in OSAHS-related HTN. Therefore, this study aimed to identify those organisms. We obtained 139 oral samples and determined the microbiome composition using pyrosequencing and bioinformatic analyses of the 16S rRNA. We examined the fasting levels of cytokines and homocysteine in all participants and analyzed the correlations between the oral microbiota and homocysteine levels. We determined the molecular mechanism underlying HTN by investigating the genetic composition of the strains in the blood. We detected higher relative abundances of Porphyromonas and Aggregatibacter and elevated proinflammatory cytokines in patients with OSAHS of varying severity compared with individuals without OSAHS; however, the two organisms were not measured in the blood samples from all participants. High levels of specific Porphyromonas bacteria were detected in patients with OSAHS with and without HTN, whereas the relative abundance of Aggregatibacter was negatively correlated with the homocysteine level. The receiver operating characteristic curve analysis of controls and patients with OSAHS resulted in area under the curve values of 0.759 and 0.641 for patients with OSAHS with or without HTN, respectively. We found that the predictive function of oral microbiota was different in patients with OSAHS with and without HTN. However, there was no direct invasion by the two organisms causing endothelial cell injury, leading to speculation regarding the other mechanisms that may lead to HTN. Elucidating the differences in the oral microbiome will help us understand the pathogenesis of OSAHS-related HTN.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low-density lipoprotein cholesterol (LDL-C). PCSK9 inhibitors are developed ...to primarily reduce the cardiovascular risk by lowering LDL-C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its effects on central nervous system (CNS) diseases have been increasingly identified. Emerging clinical evidence have revealed that PCSK9 may play a significant role in neurocognition, depression, Alzheimer's disease, and stroke. The focus of this review is to elucidate the functions of PCSK9 and highlight the effects of PCSK9 in CNS diseases, with the aim of identifying the potential risks that may arise from low PCSK9 level (variant or inhibitor) in the clinical practice.
The mechanical seal performance in reactor coolant pump (RCP) is of great importance for the efficient and safe operation of primary loop in nuclear power plant. The sealing medium filling inside the ...seal encounters strong thermal gradient. In this paper, thermo-viscous effect on sealing characteristics with two typical mechanical seal faces, namely the tapered-end-face and wave-tilt-dam, is numerically studied, by introducing the temperature-viscosity equation according to the real physical properties of the sealing medium. Performance of mechanical seal with two different temperature-viscosity equations are compared. In addition, the influence of thermo-viscous effect on cavitation is also analyzed. It is revealed that the temperature-viscosity variation significantly influences the internal flow field, temperature field, two-phase distribution, and the opening force as well. With low base film thickness, the temperature difference will reduce 58% as considering the thermal effect on viscosity, and the difference in leakage may be as high as 43%. Also, the prediction of cavitation under small film thickness indicates that the thermo-viscous effect decreases the cavitating area. This work contributes to the mechanical seal design and performance prediction by assessing the thermal influences on viscosity of seal medium, and meanwhile revealing the effect on the possible cavitation event.
Display omitted
Despite the exact biological role of HNF1 homolog A (HNF1A) in the regulatory mechanism of glioblastoma (GBM), the molecular mechanism, especially the downstream regulation as a ...transcription factor, remains to be further elucidated. Immunohistochemistry was used to detect the expression and clinical relevance of HNF1A in GBM patients. CCK8, TUNEL, and subcutaneous tumor formation in nude mice were used to evaluate the effect of HNF1A on GBM in vitro and in vivo. The correction between HNF1A and epidermal growth factor receptor pathway substrate 8 (EPS8) was illustrated by bioinformatics analysis and luciferase assay. Further mechanism was explored that the transcription factor HNF1A regulated the expression of EPS8 and downstream signaling pathways by directly binding to the promoter region of EPS8. Our comprehensive analysis of clinical samples in this study showed that upregulated expression of HNF1A was associated with poor survival in GBM patients. Further, we found that knockdown of HNF1A markedly suppressed the malignant phenotype of GBM cells in vivo and in vitro as well as promoted apoptosis of tumor cells, which was reversed by upregulation of HNF1A. Mechanistically, HNF1A could significantly activate PI3K/AKT signaling pathway by specifically binding to the promoter regions of EPS8. Moreover, overexpression of EPS8 was able to reverse the apoptosis of tumor cells caused by HNF1A knockdown, thereby exacerbating the GBM progression. Correctively, our study has clarified the explicit mechanism by which HNF1A promotes GBM malignancy and provides a new therapeutic target for further clinical application.
Display omitted
Investigating the role of ubiquitin-specific peptidase 10 (USP10) in triple-negative breast cancer (TNBC). Analyzed USP10 expression levels in tumors using public databases. Detected ...USP10 mRNA and protein levels in cell lines. Examined USP10 expression in tumor tissues from breast cancer patients. Conducted USP10 knockdown experiments and analyzed changes in cell proliferation and metastasis. Confirmed protein–protein interactions with USP10 through mass spectrometry, Co-IP, and fluorescence experiments. Assessed impact of USP10 on transcription factor 4 (TCF4) ubiquitination and validated TCF4′s influence on TNBC cells. We initially identified a pronounced overexpression of USP10 across multiple tumor types, including TNBC. Subsequently, we observed a conspicuous upregulation of USP10 expression levels in breast cancer cell lines compared to normal breast epithelial cells. However, upon subsequent depletion of USP10 within cellular contexts, we noted a substantial attenuation of malignant proliferation and metastatic potential in TNBC cells. In subsequent experimental analyses, we elucidated the physical interaction between USP10 and the transcription factor TCF4, whereby USP10 facilitated the deubiquitination modification of TCF4, consequently promoting its protein stability and contributing to the initiation and progression of TNBC. Collectively, this study demonstrates that USP10 facilitated the deubiquitination modification of TCF4, consequently promoting its protein stability and contributing to the initiation and progression of TNBC.
PDF
