Exploring potential genes and mechanisms linking erectile dysfunction and depression

BackgroundThe clinical correlation between erectile dysfunction (ED) and depression has been revealed in cumulative studies. However, the evidence of shared mechanisms between them was insufficient. This study aimed to explore common transcriptomic alterations associated with ED and depression.Materials and methodsThe gene sets associated with ED and depression were collected from the Gene Expression Omnibus (GEO) database. Comparative analysis was conducted to obtain common genes. Using R software and other appropriate tools, we conducted a range of analyses, including function enrichment, interactive network creation, gene cluster analysis, and transcriptional and post-transcriptional signature profiling. Candidate hub crosslinks between ED and depression were selected after external validation and molecular experiments. Furthermore, subpopulation location and disease association of hub genes were explored.ResultsA total of 85 common genes were identified between ED and depression. These genes strongly correlate with cell adhesion, redox homeostasis, reactive oxygen species metabolic process, and neuronal cell body. An interactive network consisting of 80 proteins and 216 interactions was thereby developed. Analysis of the proteomic signature of common genes highlighted eight major shared genes: CLDN5, COL7A1, LDHA, MAP2K2, RETSAT, SEMA3A, TAGLN, and TBC1D1. These genes were involved in blood vessel morphogenesis and muscle cell activity. A subsequent transcription factor (TF)–miRNA network showed 47 TFs and 88 miRNAs relevant to shared genes. Finally, CLDN5 and TBC1D1 were well-validated and identified as the hub crosslinks between ED and depression. These genes had specific subpopulation locations in the corpus cavernosum and brain tissue, respectively.ConclusionOur study is the first to investigate common transcriptomic alterations and the shared biological roles of ED and depression. The findings of this study provide insights into the referential molecular mechanisms underlying the co-existence between depression and ED

Phospholipase Cγ2 Signaling Cascade Contribute to the Antiplatelet Effect of Notoginsenoside Fc

Scope: Bleeding, the main drawback of clinically used chemical anti-thrombotic drug is resulted from the unidirectional suppression of platelet activity. Therefore, dual-directional regulatory effect on platelet is the main preponderance of Panax notoginseng over these drugs. The dual-directional regulatory effect should be ascribed to the resourceful Panax notoginseng saponins (PNS). Clarifying the mechanism of main PNS in both inhibiting and promoting platelet aggregation will give a full outlook for the dual-directional regulatory effect. The present study is aimed at explaining the mechanism of Notoginsenoside Fc (Fc), a main PNS, in inhibiting platelet aggregation.Methods: In the in vitro study, after incubating platelets with Fc and m-3M3FBS, platelet aggregation was triggered by thrombin, collagen or ADP. Platelet aggregation was measured by aggregometer. Phospholipase Cγ2 (PLCγ2) and protein kinase C (PKC) activities were studied by western blotting. Diacylglycerol (DAG), thromboxane B2 (TXB2) and 1,4,5-inositol trisphosphate (IP3) concentrations were measured by corresponding ELISA kits. Calcium concentrations ([Ca2+]) were estimated through the fluorescence intensity emitted from Fluo-4. In the in vivo study, thrombus model was induced by FeCl3. The effect of Fc on thrombosis was evaluated by measurement of protein content and observation of injured blood vessel.Results: thrombin, collagen and ADP induced platelet aggregation were all suppressed by incubating platelets with Fc. Platelet PLCγ2 and subsequent DAG-PKC-TXA2 and IP3 were down-regulated by Fc as well. However, the basal [Ca2+] in platelet was not altered by Fc. Nevertheless, thrombin triggered activation of PLCγ2 and subsequent DAG-PKC-TXA2 and IP3-[Ca2+] were all abolished by Fc. Fc also attenuated platelet aggregation and PLCγ2 signaling activation induced by PLC activator, m-3M3FBS. In the in vivo study, FeCl3 induced thrombosis in rat femoral artery was significantly alleviated by administration of Fc.Conclusion: The results above suggested the antiplatelet and antithrombotic effects of Fc are carried out through oppression of PLCγ2 and subsequent DAG-PKC-TXA2 and IP3-[Ca2+]. The present study provided theoretical support for new anti-thrombotic drug exploitation by Panax notoginseng

Axial tensile behavior of hybrid steel-polypropylene fiber reinforced high-strength lightweight concrete

In practical engineering, concrete materials are mainly damaged by tension, especially for high-strength lightweight concrete (HSLC) whose tensile performance is not as satisfactory as ordinary concrete under the same compressive strength. Adding fibers is one of the most effective methods to improve the tensile properties of concrete. In this study, the tensile behavior of hybrid fiber reinforced HSLC was investigated through direct tensile test. The tensile stress-strain curve was obtained and the tensile toughness was calculated. Furthermore, the cracking process was measured and captured synchronously by digital image correlation (DIC) measurement. The results indicated that hybrid fibers enhanced the tensile properties of HSLC at both micro and macro levels. Polypropylene fibers increased the tensile toughness of HSLC by inhibiting the propagation of micro-cracks. Steel fibers improved the peak stress, peak strain, and tensile toughness of HSLC by extending the propagation path of macro-cracks and restraining the increase of the width of macro-cracks. According to the test results, an equation for the axial tensile stress-strain curve of the hybrid fiber reinforced HSLC related to fiber characteristic parameters was formulated, which can be used as a reference for engineering design

INFLUENCE STUDY ON THE LOGO OF AN ENGINE CONNECTING ROD TO ITS FATIGUE STRENGTH

The connecting rod breaked in the logo position at the middle of the connecting rod body, when it was subjected to cyclin load fatigue experiment. The material and manufacturing process of the experimental samples were checked and there was no defect. The three-dimension solid model of the experimental connecting rod was built by 3-D modeling software, and the stress concentration had occurred at the same location logo with the experimental sample connecting rod by using finite element method. Then three schemes were designed and the influence on the distance between the logo words, the height of logo to connecting rod body surface and the positing of the logo to stress were analysis, the results showed that: the stress was reduced by appropriately increasing the spacing between logo words. The depressing logo could greatly reduce the stress comparing with the protruding logo. The positon of the logo had the most influence to the stress, and the stress concentration of the connecting rod disappeared when the logo moved from middle of the connecting rod to the outside of the connecting rod cap

Study on Residual Stress in Disc-Milling Grooving of Blisks

The disc-milling method is expected to increase the grooving efficiency of blisks. However, there are few studies about the residual stress on a blisk during disc-milling grooving. In this study, a single-factor experiment and an orthogonal experiment of blisk disc-milling and grooving were designed to obtain the residual stress. Surface subsurface residual stress were also studied. The results showed that the surface of the milling groove bore compressive stress. Residual stress decreased with increasing spindle speed and increased with increasing feed speed and spindle rotation angle. Moreover, residual stress was most sensitive to spindle rotation angle and least sensitive to feed speed. A higher residual stress produced on the machined surface led to a deeper layer of residual stress

ITRAQ-based quantitative proteomics reveals the proteome profiles of MDBK cells infected with bovine viral diarrhea virus

Abstract Background Bovine viral diarrhea (BVD) which is caused by Bovine viral diarrhea virus (BVDV), is an acute, contagious disease. In spite of the use of vaccines and elimination projects, BVDV still causes severe economic losses to the cattle industry for the past few years. The current study presents a preliminary analysis of the pathogenic mechanisms from the perspective of protein expression levels in infected host cells at different points in time to elucidate the infection process associated with BVDV. Methods We used the isobaric tags for relative and absolute quantitation (iTRAQ) technology coupled with liquid chromatography-tandem mass spectrometric (LC–MS/MS) approach for a quantitative proteomics comparison of BVDV NADL-infected MDBK cells and non-infected cells. The functions of the proteins were deduced by functional annotation and their involvement in metabolic processes explored by KEGG pathway analysis to identify their interactions. Results There were 357 (47.6% downregulated, 52.4% upregulated infected vs. control), 101 (52.5% downregulated, 47.5% upregulated infected vs. control), and 66 (21.2% downregulated, 78.8% upregulated infected vs. control) proteins were differentially expressed (fold change > 1.5 or < 0.67) in the BVDV NADL-infected MDBK cells at 12, 24, and 48 h after infection. GO analysis showed that the differentially expressed proteins (DEPs) are mainly involved in metabolic processes, biological regulation and localization. KEGG enrichment analysis showed that some signaling pathways that involved in the regulation of BVDV NADL-infection and host resistance are significantly (P < 0.05) enriched at different stages of the BVDV NADL-infection, such as Endocytosis signaling pathway, FoxO signaling pathway, Homologous recombination signaling pathway and Lysosome pathway. Conclusions These results revealed that the DEPs in BVDV NADL-infected MDBK cells have a wide range of regulatory effects; in addition, they provide a lot of resources for the study of host cell proteomics after BVDV infection