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Aldosterone-producing adenoma (APA), the main cause of endocrine hypertension, has recently been reported to be associated with other diseases, such as metabolic syndrome, but the detailed mechanism underlying this association remains unclear. Here, we used untargeted metabolomics and compared the abundance of serum metabolites between essential hypertension (EHT) and APA patients, as well as the serum metabolites of APA patients before and after adrenalectomy. Our results revealed 44 differential metabolites between APA and EHT patients and 39 differential metabolites between pre- and postoperative APA patients. Several metabolites involved in cardiovascular disease, obesity, and diabetes were dysregulated in APA patients compared to EHT patients, including arachidonic acid metabolites [e.g., 5(S)-HpETE and 12-HETE], amino acids (e.g., L-carnitine, taurine, and L-arginine), nucleotide metabolites (e.g., hypoxanthine) and cholesterol 3-sulfate. Importantly, the levels of hypoxanthine and cholesterol 3-sulfate, two metabolites that promote the development of atherosclerotic lesions and obesity, were originally increased in APA patients, but those elevated levels were reversed by adrenalectomy. Conversely, levels of L-carnitine and (3-carboxypropyl) trimethylammonium cation, two metabolites participating in lipid metabolism, were decreased in APA patients but increased postoperatively. We conclude that APA might participate in cardiovascular and metabolic diseases by regulating serum metabolites.

Abstract: In recent years, the incidence of erectile dysfunction (ED) has continued to rise worldwide. Since pharmacotherapy is still the most common and effective method for the treatment of ED at present, many methods and drugs have been designed or developed for the treatment of ED. Oral phosphodiesterase-5 inhibitors and androgen supplement therapy are currently the common therapeutics for ED; however, some patients have poor response to these drugs because of the multiple pathogenic mechanisms of ED. Researchers are trying to find other treatment ways. On the one hand, many new strategies and concepts such as targeted therapy are also integrated into clinical or preclinical research; on the other hand, some combined therapies which have synergistic effects with reduced dose of single drug and less adverse effects are also developed. This review article summarized the efficacy of the latest first-line, second-line drugs and adjuvant therapies for the treatment of ED, as well as the application of comprehensive treatments, which will help doctors to not only deeply understand the mechanism of ED but select the suitable therapeutics for those patients.

Exosomes secreted by cancer cells play important roles in tumor progression by interacting with cell receptors. Renal cancer derived exosomes contain miRNAs which are associated with cell proliferation and invasion. Micro RNA 9-5 (miR-9-5) is highly expressed in the serum of renal cancer patients with advanced (tumor size - node - metastasis) TNM stage and Fuhrman grade. miR-9-5p is extensively expressed in exosomes derived from renal cancer cells. Overexpression of miR-9-5p promotes proliferation and invasion of A-704 (a cancer cell line of human kidney) cells via targeting and deregulating SOCS4 mRNA. Inhibition of the Janus kinase (JAK)/signaling transducer and activator of transcription (STAT) pathway by SOCS4 will be reduced, which leads to phosphorylation of STAT3 and JAK. Activated cytokine signaling promotes cell proliferation and invasion, and inhibits apoptosis. Moreover, overexpression of SOCS4 reduces miR-9-5p levels and plays an opposite role in cell. To conclude, exosomal miR-9-5p plays important roles in renal cancer both in vivo and in vitro, indicating it may be used as biomarker for diagnosis and for monitoring the efficacy if therapy.

In laser forming, phase transformations in the heat affected zone take place under steep cooling rates and temperature gradients, and have a significant affect on the laser forming process and final mechanical properties of products. In this work, phase transformations during laser forming of AISI 1010 steel are experimentally and numerically investigated and the transient volume fraction of each available phase is calculated by coupling the thermal history from finite element analysis with a phase transformation kinetic model. Consequently, the flow stresses of material are obtained from the constitutive relationship of the phases, and the laser forming process is modeled considering the effect of work hardening, recrystallization and phase transformation. A series of carefully controlled experiments are also conducted to validate the theoretically predicted results.

Jackson’s Problem Frame (PF) approach emphasizes the importance of modeling and analyzing the world outside of computer before drifting into designing solutions. Furthermore, it uses problem diagram to vividly capture requirements, problem domains, and their relation in an intuitive and structural way. After visualizing the problem, it provides a solid foundation for communication between software stakeholders, decreasing the possibility of mismatch between customer’s real needs and software system developers’ understanding of customer needs. Thus PF approach is a useful tool in Requirement Engineering (RE). While today’s development activities of complex system invariably deeply roots in large scare problem context and involves various kinds of stakeholder who have different perspectives or viewpoints on the problem they are addressing. It is vital to explicitly represent and analyze these viewpoints, their relationships, then integrate them into a complete and consistent form to ease further overall architecture design and development. This paper explores the integration of viewpoint concepts with problem frames methodology which aim at providing a more flexible and practical way to express requirements from different classes of stakeholders and the problem context they concerned, then, we integrate these viewpoint based sub-problem together to provide basis for subsequent phrases in software life cycle.

The reduction rate of Mo oxide in slag by iron-carbon melt under different stirring conditions, reaction temperatures and slag composition has been investigated. Results indicate that the reduction of Mo oxide is a fast reaction; both stirring and temperature have evident influence upon the reaction; while the initial concentration of Mo oxide and content of fluoride in slag have also some influence upon the reaction. The reduction of Mo oxide is an apparent first order reaction. At 1440-1500 °C, the reduction rate of Mo oxide is mainly controlled by Mo transfer in slag, with its diffusion activation energy of 223 kJ/mol. At 1500-1590 °C, the transfer of Mo in metal turns to be the main limiting step, with its diffusion activation energy of 81.5 kJ/mol

Virtual Welede-Joint Design, a systematic modeling approach, has been developed in this project to predict the relationship of welding process, microstructure, properties, residual stress, and the ultimate weld fatique strength. This systematic modeling approach was applied in the welding of high strength steel. A special welding wire was developed in this project to introduce compressive residual stress at weld toe. The results from both modeling and experiments demonstrated that more than 10x fatique life improvement can be acheived in high strength steel welds by the combination of compressive residual stress from the special welding wire and the desired weld bead shape from a unique welding process. The results indicate a technology breakthrough in the design of lightweight and high fatique performance welded structures using high strength steels.

In laser forming, phase transformation and grain structural evolution in the heat affected zone (HAZ) take place under steep cooling rates and temperature gradients, and have a significant effect on the laser forming process and final mechanical properties of products. In this work, microstructure evolution during laser forming of AISI 1010 steel is experimentally and numerically investigated and the transient constitutive property of phases and grain size are calculated by coupling the thermal history from finite element analysis with a phase transformation kinetic model. Phase volume fraction and grain distribution are predicted. Consequently, the flow stress of material is obtained from the constitutive relationship of the phases, and the laser forming process is modeled considering the effect of work hardening, recrystallization and phase transformation. A series of carefully controlled experiments are also conducted to validate the theoretically predicted results.In laser forming, phase transformation and grain structural evolution in the heat affected zone (HAZ) take place under steep cooling rates and temperature gradients, and have a significant effect on the laser forming process and final mechanical properties of products. In this work, microstructure evolution during laser forming of AISI 1010 steel is experimentally and numerically investigated and the transient constitutive property of phases and grain size are calculated by coupling the thermal history from finite element analysis with a phase transformation kinetic model. Phase volume fraction and grain distribution are predicted. Consequently, the flow stress of material is obtained from the constitutive relationship of the phases, and the laser forming process is modeled considering the effect of work hardening, recrystallization and phase transformation. A series of carefully controlled experiments are also conducted to validate the theoretically predicted results.

Welding practice has traditionally been treated as an art and in most cases experience based trial‐and‐error experimentation has been the major approach to establish a feasible welding procedure. In recent years, significant progress has been made in understanding welding phenomena based on numerical modeling. Recent modeling efforts include simulation of the weld pool formation, weld microstructure evolution, and welding induced residual stress and distortion. The numerical models based on interdisciplinary applied sciences (e.g. heat transfer and fluid flow, materials science, mechanical engineering, and fracture mechanics) have provided detailed insights into welding process and guidance in design of high performance welded‐joints and cost effective welding process. The concept of “Virtual Welding,” which is a simulation package based on interdisciplinary applied science and multi‐scale numerical models, is proposed in this paper. Examples are provided to demonstrate the applications of “Virtual Weldin...