Unfavorable Role Research Articles

Microglia and Macrophages in the Pathological Central and Peripheral Nervous Systems.

Microglia, the immunocompetent cells in the central nervous system (CNS), have long been studied as pathologically deteriorating players in various CNS diseases. However, microglia exert ameliorating neuroprotective effects, which prompted us to reconsider their roles in CNS and peripheral nervous system (PNS) pathophysiology. Moreover, recent findings showed that microglia play critical roles even in the healthy CNS. The microglial functions that normally contribute to the maintenance of homeostasis in the CNS are modified by other cells, such as astrocytes and infiltrated myeloid cells; thus, the microglial actions on neurons are extremely complex. For a deeper understanding of the pathophysiology of various diseases, including those of the PNS, it is important to understand microglial functioning. In this review, we discuss both the favorable and unfavorable roles of microglia in neuronal survival in various CNS and PNS disorders. We also discuss the roles of blood-borne macrophages in the pathogenesis of CNS and PNS injuries because they cooperatively modify the pathological processes of resident microglia. Finally, metabolic changes in glycolysis and oxidative phosphorylation, with special reference to the pro-/anti-inflammatory activation of microglia, are intensively addressed, because they are profoundly correlated with the generation of reactive oxygen species and changes in pro-/anti-inflammatory phenotypes.

Immunomodulatory Role of the Antimicrobial LL-37 Peptide in Autoimmune Diseases and Viral Infections.

Antimicrobial peptides (AMPs) are produced by neutrophils, monocytes, and macrophages, as well as epithelial cells, and are an essential component of innate immunity system against infection, including several viral infections. AMPs, in particular the cathelicidin LL-37, also exert numerous immunomodulatory activities by inducing cytokine production and attracting and regulating the activity of immune cells. AMPs are scarcely expressed in normal skin, but their expression increases when skin is injured by external factors, such as trauma, inflammation, or infection. LL-37 complexed to self-DNA acts as autoantigen in psoriasis and lupus erythematosus (LE), where it also induces production of interferon by plasmocytoid dendritic cells and thus initiates a cascade of autocrine and paracrine processes, leading to a disease state. In these disorders, epidermal keratinocytes express high amounts of AMPs, which can lead to uncontrolled inflammation. Similarly, LL-37 had several favorable and unfavorable roles in virus replication and disease pathogenesis. Targeting the antiviral and immunomodulatory functions of LL-37 opens a new approach to limit virus dissemination and the progression of disease.

A role of single nucleotide polymorphism in TNF, NOS3 and MMP9 genes at the risk of developing neonatal pneumonia

Neonatal pneumonia is one of the most common causes of infant mortality. Moreover, the diagnosis of this pathology represents a difficult task and requires to seek for additional solutions in clinical and laboratory practice. One of the current and promising ways to diagnose rerlies on search of predictive markers among the innate and adaptive immunity genes involved in disease pathogenesis. We used bioinformatics analysis to select genes playing essential role developing neonatal pneumonia. Next, cord blood samples collected from 234 newborns were examined by real-time polymerase chain reaction for nine polymorphic markers in the TNF, IL10, IL17A, IL17F, IL6, NOS3, and MMP9 genes. The results of statistical analysis showed that heterozygous genotypes in the MMP9 and TNF genes were associated with the risk of developing early neonatal pneumonia, and also the protective role of homozygotes AA in the MMP9 gene and GG in the TNF gene. A search for associations with a risk of intrauterine pneumonia revealed an unfavorable role for heterozygous genotypes in the NOS3 and MMP9 genes. Thus, due to difficulties in diagnosis or in case of developing neonatal pneumonia, it may be recommended to add genetic analysis for assessing polymorphic markers in the MMP9 (rs17576), TNF (rs1800629) and NOS3 (rs1549758) genes along with standard test assays.

High expression of GPNMB indicates an unfavorable prognosis in glioma: Combination of data from the GEO and CGGA databases and validation in tissue microarray.

Glycoprotein non-metastatic melanoma protein B (GPNMB), a transmembrane glycoprotein, has been reported to be involved in tumor progression, but its prognostic value for glioma and the mechanistic effects on glioma progression have not been clearly explored. The present study aimed to investigate the prognostic role of GPNMB in glioma and the potential mechanisms of how GPNMB mediates glioma progression. Differentially expressed genes between the four highest and four lowest GPNMB expression samples in the GSE53733 dataset were first determined. Gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene set enrichment analysis results demonstrated that the significantly enriched pathways in samples with high GPNMB expression compared with those with low GPNMB expression were associated with hypoxia, angiogenesis, migration and invasion. Pearson correlation analysis was conducted to investigate the correlations between GPNMB expression and the markers of hypoxia, angiogenesis, migration and invasion in GSE53733, which were further validated using another mRNA microarray dataset from the Chinese Glioma Genome Atlas (CGGA). In addition, using the CGGA dataset, high GPNMB expression was demonstrated to be significantly associated with advanced WHO grade and short survival time in patients with glioma. Of note, based on the immunohistochemical staining of the tissue microarrays, Kaplan-Meier analysis with the Renyi test and a Cox proportional hazards model were used to validate the unfavorable prognostic role of high GPNMB expression in glioma. In conclusion, high GPNMB expression may be associated with high tumor grade and unfavorable prognosis in glioma. GPNMB expression was demonstrated to correlate with the markers of hypoxia, angiogenesis, migration and invasion, which may be potential mechanisms through which GPNMB mediates glioma progression.

Prognostic value of tissue-infiltrating immune cells in tumor microenvironment of follicular lymphoma: A meta-analysis

BackgroundThe follicular lymphoma (FL) microenvironment is composed of follicular dendritic cells (FDCs), tumor-infiltrating CD4/CD8+ T cells (TILs), follicular regulatory T (Treg) cells, lymphoma-associated macrophages (LAMs), and immune checkpoint–related immune cells, all of which are relevant in the prognosis of FL, but their results remain controversial. Therefore, we performed this systematic review to explore the relationship between the FL microenvironment and prognosis. MethodsRelevant studies were identified from PubMed, EMBASE and the Cochrane Library. Twenty-three trials involving 3336 patients with FL were included for analysis. ResultsThis meta-analysis confirmed the unfavorable prognostic role of high CD21+/CD23+ FDC density in overall survival (OS) and progression-free survival (PFS). CD8+ or granzyme B+ TILs instead of CD4+ TILs are indicators for good OS. FoxP3+ Treg cells was not associated with prognosis, and even in subgroup analysis neither the number of cells nor the infiltration pattern had predictive value. A high degree of CD68+ macrophage infiltration was a negative prognostic factor for OS, but was associated with good prognosis in the rituximab-era subgroup. Although there was no correlation between PD1-positive immune cells and prognosis, subtypes with the follicular helper T (TFH) or exhausted T cell (TEX) phenotype tended to influence prognosis. The HR in the short time to transformation (TTT) analyses suggested that high CD68+ LAM numbers, diffuse pattern of FOXP3+ Treg cells and PD1+ cells, and high PD-L1 cell numbers are adverse factors leading to early transformation. ConclusionsMultiple tissue-infiltratingimmune cells in microenvironment play critical and different roles in FL prognosis.

Associations of Maternal Prepregnancy Body Mass Index and Gestational Weight Gain With Physical Fitness in Childhood

To investigate the potential associations of maternal prepregnancy body mass index (mppBMI) and gestational weight gain (GWG) with physical fitness in children. A random sample of 5125 children and their mothers was evaluated. The mothers provided data contained in their medical booklets and pregnancy ultrasound records. The data from 5 physical fitness tests (eg,20-m shuttle run, 30-m sprint, vertical jump, standing long jump, and small ball throw) were used to assess children's cardiorespiratory fitness, speed, explosive power, and lower and upper body strength, respectively. MppBMI was inversely associated with cardiorespiratory fitness (b = -0.02), lower body strength (b = -1.01), upper body strength (b = -0.07), and speed (b = 0.04). Also, GWG was unfavorably associated with cardiorespiratory fitness (b = -0.02), lower body strength (b = -1.12), upper body strength (b = -0.03), and speed (b = 0.03), after adjusting for sex, birth weight, and children's BMI (all P values < .05). Children of mothers with an mppBMI ≥ 25kg/m2 and excess GWG had almost 30% and 20% increased odds for low performances in physical fitness tests than those of mothers with an mppBMI < 25kg/m2 and adequate GWG, respectively. Antenatal factors such as increased mppBMI and excess GWG could play an unfavorable role in the future health of the offspring.

Favorable and unfavorable roles of microglia and macrophages in the pathologic central nervous system

Favorable and unfavorable roles of microglia and macrophages in the pathologic central nervous system

Uric acid in CKD: has the jury come to the verdict?

Epidemiological studies show that hyperuricemia independently predicts the development of chronic kidney disease (CKD) in individuals with normal kidney function both in the general population and in subjects with diabetes. As a matter of fact, an unfavorable role of uric acid may somewhat be harder to identify in the context of multiple risk factors and pathogenetic mechanisms typical of overt CKD such as proteinuria and high blood pressure. Although the discrepancy in clinical results could mean that urate lowering treatment does not provide a constant benefit in all patients with hyperuricemia and CKD, we believe that the inconsistency in the results from available meta-analysis is mainly due to inadequate sample size, short follow-up times and heterogeneity in study design characterizing the randomized controlled trials included in the analyses. Therefore, available data support the view that hyperuricemia has a damaging impact on kidney function, while preliminary evidence suggests that treatment of so-called asymptomatic hyperuricemia may be helpful to slow or delay the progression of chronic kidney.

Prognostic relevance of the Golgi mannosidase MAN1A1 in ovarian cancer: impact of N-glycosylation on tumour cell aggregation

BackgroundMaturation of complex N-glycans involves the action of Golgi mannosidases and plays a major role in cancer progression. We recently showed a favourable prognostic role of α-mannosidase MAN1A1 in breast cancer mainly caused by alteration of certain adhesion molecules.MethodsWe analysed the protein expression of MAN1A1 in ovarian cancer (n = 204) using western blot and studied the impact of MAN1A1 itself and of MAN1A1-related glycosylation on the prognostic relevance of two adhesion molecules. Functional consequences of mannosidase inhibition using kifunensine and MAN1A1 knock out were investigated in ovarian cancer cells in vitro.ResultsPatients with high MAN1A1 expression in tumours showed significantly shorter RFS than those with low-MAN1A1 levels. Moreover, high MAN1A1 expression correlated significantly with advanced stage, lymph node involvement and distant metastasis. Further, the glycosylated adhesion molecule ALCAM reveals a significant adverse prognostic effect only in the presence of high MAN1A1 expression. In spheroid-formation assays, mannosidase inhibition and especially MAN1A1 knock out led to strong reduction of tumour cell aggregation.ConclusionsOur study demonstrates the unfavourable prognostic role of MAN1A1 in ovarian cancer, probably caused by an altered ability of spheroid formation, and the strong influence of this glycosylation enzyme on the prognostic impact of ALCAM.

Enhanced photocatalytic activity of biosynthesized Au-Ag/TiO2 catalyst by removing excess anchored biomolecules

A green bioreduction method was used to prepare highly efficient supported TiO2 photocatalysts with bimetallic (Au-Ag) nanoparticles at room temperature using Cinnamomum camphora leaf extract as both the protective agent and reducing agent. The resulted Au-Ag/TiO2 exhibits high photocatalytic activity toward the degradation of organic dyes. It was demonstrated that after some of the biomolecules were removed through ionic-liquid extraction and/or calcinations, the Au-Ag/TiO2 photocatalyst exhibits significantly enhanced catalytic performance toward the degradation of methyl orange compared to the pristine untreated catalyst. As a result, 300 mL of 20 mg/mL methyl orange can be fully degraded in 30 min. These can be explained by the sufficient biomolecules could protect the nanoparticles stay in small size, but excess biomolecules played an unfavorable role in hindering the electron transportation during the catalytic reaction. The low-cost preparation, the high activity, together with the good stability and recyclability make this developed Au-Ag/TiO2 a promising photocatalyst toward the degradation of wastewater.

Aerodynamic load spectrum and fatigue behaviour of high‐speed train's equipment cabin

AbstractIn present study, the aerodynamic fatigue behaviour of train equipment cabin was investigated. Pressure sensors were arranged at train passing side. Eight‐grade load spectrum was constructed by means of rain‐flow counting, and fatigue damage was calculated with Miner's rule and Carten‐Dolan rule, both for the matrix metals and welds. For welds, defect detection was considered via visual inspection with nondestructive test (VI‐NDT), pure nondestructive test (P‐NDT), and without nondestructive test (W‐NDT). The result confirms that welds play an unfavourable role rather than matrix metals. Weld damage in W‐NDT exceeds its limit (1.0) to designed mileage. Then, damage influence was studied under tunnel passing, train passing, and running direction. Running direction as the head car contributes 82% to approximately 86% and 70% to approximately 77% of the total damage for matrix metal and welds, respectively. Train passing gives more damage to matrix metals than welds. Tunnel passing contributes 25% to approximately 26% for both matrix metals and welds.

Understanding the Situated Roles of Electronic Medical Record Systems to Enable Redesign: Mixed Methods Study.

BackgroundRedesigning electronic medical record (EMR) systems is needed to improve their usability and usefulness. Similar to other artifacts, EMR systems can evolve with time and exhibit situated roles. Situated roles refer to the ways in which a system is appropriated by its users, that is, the unintended ways the users engage with, relate to, and perceive the system in its context of use. These situated roles are usually unknown to the designers as they emerge and evolve as a response by the users to a contextual need or constraint. Understanding the system’s situated roles can expose the unarticulated needs of the users and enable redesign opportunities.ObjectiveThis study aimed to find EMR redesign opportunities by understanding the situated roles of EMR systems in prenatal care settings.MethodsWe conducted a field-based observational study at a Japanese prenatal care clinic. We observed 3 obstetricians and 6 midwives providing prenatal care to 37 pregnant women. We looked at how the EMR system is used during the checkups. We analyzed the observational data following a thematic analysis approach and identified the situated roles of the EMR system. Finally, we administered a survey to 5 obstetricians and 10 midwives to validate our results and understand the attitudes of the prenatal care staff regarding the situated roles of the EMR system.ResultsWe identified 10 distinct situated roles that EMR systems play in prenatal care settings. Among them, 4 roles were regarded as favorable as most users wanted to experience them more frequently, and 4 roles were regarded as unfavorable as most users wanted to experience them less frequently; 2 ambivalent roles highlighted the providers’ reluctance to document sensitive psychosocial information in the EMR and their use of the EMR system as an accomplice to pause communication during the checkups. To improve the usability and usefulness of EMR systems, designers can amplify the favorable roles and minimize the unfavorable roles. Our results also showed that obstetricians and midwives may have different experiences, wants, and priorities regarding the use of the EMR system.ConclusionsCurrently, EMR systems are mainly viewed as tools that support the clinical workflow. Redesigning EMR systems is needed to amplify their roles as communication support tools. Our results provided multiple EMR redesign opportunities to improve the usability and usefulness of EMR systems in prenatal care. Designers can use the results to guide their EMR redesign activities and align them with the users’ wants and priorities. The biggest challenge is to redesign EMR systems in a way that amplifies their favorable roles for all the stakeholders concurrently.

Theoretical research on TEM mode feedback for compact design of an X-band triaxial klystron amplifier

A relativistic triaxial klystron amplifier (TKA) is considered to be one of the most promising high power microwave (HPM) sources for coherent power combination in high frequency bands. In general investigations, the TEM mode leakage and asymmetric modes' competition are considered to play unfavorable roles in the normal operation of TKA. Therefore, mode reflectors with high reflection efficiency in both the TEM mode and the asymmetric modes are employed and expected to significantly suppress the transmissions of the microwaves between the cavities. So the cavities can be separated from each other, while the long drift length is necessary to achieve the deep modulation. Therefore, the size of TKA is noticeably larger compared to other HPM oscillators, which requires large magnetic coil and huge energy consumption. In our present research, it is found that the TEM mode leakage can be utilized to form positive feedback between the cavities, which is significant for electron beam modulation and furthermore to make the devices more compact. In this paper, the mechanism of TEM mode feedback between the cavities is discussed and the conditions of positive and negative feedback are achieved. Besides, an especially designed reflector with high reflection coefficients in asymmetric modes and low reflection coefficients in the TEM mode is designed to utilize the TEM mode and suppress the asymmetric modes. Based on the above research, a TKA adopting positive TEM mode feedback, whose total length is decreased by 23.6% compared to the previous design, is presented. A high power microwave with a power of 2.25 GW and a frequency of 8.4 GHz is generated with a 690 kV, 9.3 kA electron beam excitation and a 40 kW radio-frequency signal injection. Meanwhile, there is insignificant self-excitation of the parasitic mode in the proposed structure in three-dimensional particle-in-cell simulation, and the relative phase shifts between the injected signals and the output microwaves are kept locked after the amplifier becomes saturated.

Study on photoelectric characteristics of monolayer WS2 films.

It is important to determine the time-dependent evolution of the excited monolayer WS2, which will provide a basis for the reasonable design of optoelectronic devices based on two-dimensional transition metal dichalcogenides. Here, we made a simple and large-area photodetector based on the monolayer WS2, with high light sensitivity and fast response, benefiting from the special dynamics of carrier involving the exciton, trion, and charge. Moreover, we tested the relaxation behavior of the excited monolayer WS2 by employing transient absorption (TA). It was found that the multi-body interaction among exciton would occur after the density of pump photon increases to 3.45 × 1014 photons per cm2. The exciton dissociation accompanying the generation of trion would appear in the photo-induced relaxation process, which would be a benefit for the operation of this photodetector. Increasing the energy of the exciton is good for the generation of carrier by comparing the relaxation behavior of WS2 excited to A and B exciton states. However, the bound exciton relaxation, originating from the capture process of the defect state, would exist and play an unfavorable role during the functioning of devices.

Interleukin 6 gene polymorphism is associated with protein serum level and disease activity in Polish patients with rheumatoid arthritis.

Interleukin 6 (IL-6) is a pro-inflammatory cytokine involved in the development of rheumatoid arthritis (RA). The present study aimed to determine the possible association of the IL6 (rs1800795, G > C) polymorphism with RA susceptibility, disease progression and protein serum levels. Distribution of IL6 alleles and genotypes was similar in RA patients and controls. As expected, patients before induction of anti-tumour necrosis factor agents had significantly higher IL-6 levels as compared with controls (P = 0.002). The CC homozygous patients were characterised with the highest average concentrations of this pro-inflammatory cytokine before treatment (P = 0.028), and they also more frequently presented with more active disease (P = 0.048). These results imply that the IL6 rs1800795 CC homozygosity may play a rather unfavourable role in RA.

Prognostic Significance of Severe Thrombocytopenia in Overall Survival of Patients with Myelodysplastic Syndromes Treated with Azacytidine. a Multicenter Study By the Hellenic MDS Study Group

INTRODUCTIONThe hypomethylating agents 5-azacitidine (5-AZA) and decitabine are recently considered the most preferable treatment option for patients with intermediate-2 and high-risk myelodysplastic syndromes (MDS), by International Prognostic Scoring System (IPSS). 5-AZA responders experience improved survival both in clinical trials (AZA 001) and in the real-life setting. Thrombocytopenia is a common event in MDS, during the course of the disease; recently, severe thrombocytopenia (≤30,000 platelets/μL) has been suggested as an important factor regarding the survival of MDS patients. In the present study, we examined the potential prognostic significance of severe thrombocytopenia, in intermediate-2- and high-risk MDS patients, being treated with 5-AZA, during the first 3 years of treatment. METHODSThis retrospective study included 850 higher-risk patients (intermediate-2- and high-risk), registered in the the Hellenic MDS Registry, treated with 5-AZA from 2010 to 2018 and were followed up for a time period up to 3 years. Complete patient data were available for 225 patients. Biostatistical analysis performed in this study included Kaplan-Meier survival analysis and Cox regression. The level of statistical significance was set at a probability value of less than 0.050 (P<0.050). RESULTSThe current study included 225 patients (159 male and 66 women) with intermediate-2- or high-risk MDS treated with 5-AZA, with a median age of 74 years (range: 47 - 89). WHO diagnosis included 1 (0.4%) case of RCUD, 8 (3.6%) cases of RCMD, 3 (1.3%) cases of RCMD-RS, 43 (19.1%) cases of RAEB-1, and 170 (75.6%) cases of RAEB-2. According to IPSS, 174 (77.3%) patients were classified in the intermediate-2 risk group and 51 (22.7%) patients in the high-risk group. In addition, according to IPSS-R, 24 (10.7%) patients were categorized in the intermediate risk group, 106 (47.1%) patients in the high-risk group, and 95 (42.2%) patients in the very-high risk group. All patients were evaluated regarding response to 5-AZA treatment. The initial response at 6 months was: complete remission (CR) in 40 (18.4%) patients, partial remission (PR) in 24 (11.1%) patients, hematological improvement (HI) in 35 (16.1%) patients; therefore, the initial overall response rate (CR, PR, and HI) was 45.6%. Stable disease (SD) was achieved by 56 (25.8%) MDS patients, while 62 (28.5%) patients showed progression of disease (PD) or treatment failure. Severe thrombocytopenia was not predictive of response, as shown using logistic regression analysis. However, severe thrombocytopenia predicted poor overall survival (OS) in the first 3 years of treatment with 5-AZA, as shown by the Kaplan-Meier analysis (Figure 1; P=0.016). Regarding AML-free survival, a strong trend was observed for thy unfavorable prognostic role of this severe cytopenia (P=0.096). Univariate Cox regression analysis for OS revealed a statistically significant hazard ratio (HR) of 1.6 for MDS patients with severe thrombocytopenia (HR=1.6, 95% CI=1.08, P=0.019). CONCLUSIONSOur study showed that severe thrombocytopenia (≤ 30,000 platelets/μL) in intermediate-2- and high-risk MDS patients, treated with 5-AZA, predicts lower OS rates during the first 3 years of treatment. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Predictive value of microRNA let-7a expression for efficacy and prognosis of radiotherapy in patients with lung cancer brain metastasis: A case-control study.

Background:As a well-known cancer with high mortality, lung cancer has been implied to be closely associated with brain metastasis. Despite notable advances, effective treatment methods are still in urgent need. This study aims to investigate the value of serum microRNA-let-7a (miR-let-7a) expression in predicting efficacy and prognosis of radiotherapy in patients with lung cancer brain metastasis.Methods:To begin with, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed for better understand of the correlation between miR-let-7a and lung cancer. Afterwards, the relationship between serum miR-let-7a expression and radiotherapy efficacy was analyzed by receiver operating characteristic curve analysis. Following successful transfection, RT-qPCR and Western blot assay were utilized for evaluating the involvement of miR-let-7a in regulation of DICER1 expression in lung cancer cell line. Then, whether miR-let-7a was implicated in proliferation and cell cycle distribution of lung cancer cells were confirmed by cell counting kit-8 assay and flow cytometry respectively.Results:Initially, it was revealed that serum miR-let-7a expression was decreased in lung cancer. Later, we found that decreased miR-let-7a displayed an unfavorable role in radiotherapy efficacy and overall survival rate of patients with lung cancer brain metastasis. After the successful transfection, the inverse relationship between miR-let-7a and DICER1 expression was uncovered. Meanwhile, biological behaviors of lung cancer cells were presented to be limited after transfection of overexpressed miR-let-7a.Conclusion:Our findings demonstrated that the lower expression of miR-let-7a in patients with lung cancer brain metastasis was closely related to unfavorable efficacy and prognosis of radiotherapy, and it may be an important predictive biomarker by regulation of DICER1.

Upregulation of Myocardial and Vascular Phosphodiesterase 9A in A Model of Atherosclerotic Cardiovascular Disease.

Atherosclerosis is strongly associated with cardiac dysfunction and heart failure. Besides microvascular dysfunction and diminishment of the cardiac nitric oxide-Protein Kinase G (NO-PKG) pathway, recent evidence suggests that phosphodiesterase 9A (PDE9A) enzyme has an unfavorable role in pathological changes. Here, we characterized a rabbit model that shows cardiac dysfunction as a result of an atherogenic diet, and examined the myocardial PDE9A signaling. Rabbits were divided into Control (normal diet) and HC (atherogenic diet) groups. Cardiac function was evaluated by echocardiography. Vascular function was assessed, along with serum biomarkers. Histological stains were conducted, expression of selected proteins and cyclic guanosine monophosphate (cGMP) levels were determined. Signs of diastolic dysfunction were shown in HC animals, along with concentric hypertrophy and interstitial fibrosis. Endothelial function was diminished in HC rabbits, along with marked reduction in the aortic lumen, and increased left ventricle outflow tract (LVOT) pressures. A significant increase was shown in myocardial PDE9A levels in HC animals with unchanged vasodilator-stimulated phosphoprotein (VASP) phosphorylation and cGMP levels. Upregulation of PDE9A may be associated with early stage of cardiac dysfunction in atherosclerotic conditions. Since PDE9A is involved in cGMP degradation and in deactivation of the cardioprotective PKG signaling pathway, it may become an encouraging target for future investigations in atherosclerotic diseases.

Exploring prognostic genes in ovarian cancer stage-related coexpression network modules.

Identification of meaningful cluster modules of differential genes or representative biomarkers related to the stages of ovarian cancer (OC) is pivotal, which may help to detect mechanisms of OC progression and evaluate OC patients’ prognosis.We downloaded gene expression data and the corresponding clinical information of OC patients from The Cancer Genome Atlas (TCGA) database, which included 379 ovarian cancer patients. Differentially expressed genes (DEGs) of OC patients between stages were picked out using R. There were 731 differential genes between ovarian cancer stage II and stage III (DEGs II-III) and 563 differential genes between ovarian cancer stage III and stage IV (DEGs III-IV), then we performed GO analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, CytoHubba was used to detect the top 20 hub genes in DEGs II-III and DEGs III-IV, followed Cytoscape with search tool for the retrieval of interacting genes (STRING) and MCODE plug-in was utilized to construct protein-protein interaction (PPI) modules of these genes. Three important coexpression modules of DEGs II-III and 3 more meaningful modules of DEGs III-IV were detected from PPI network using molecular complex detection (MCODE) tool. In addition, 5 hub genes in these stage-related DEGs modules with worse overall survival were selected, including COL3A1, COL1A1, COL1A2, KRAS, NRAS. This bioinformatics analysis demonstrated that stage-related prognostic DEGs, such as COL3A1, COL1A1, COL1A2, KRAS, and NRAS might play an unfavorable role in the development as well as metastasis of ovarian cancer. Furthermore, they need to be experimentally verified as a new biomarker to predict OC patient prognosis.

Prediction of notched strength for cylindrical composites pipes under tensile loading conditions

Abstract In this paper, an experimental study has been performed on thick, ±55° filament wound glass/epoxy tubes using quasi-static tests to examine their offshore applications. A new design for the experimental test is developed in which the end tabs and fixture system are made in a way that the stress concentration at the edges of the composite pipe can be reduced. Split disk uniaxial tensile test has been performed on composite pipes with 86 mm of the internal diameter and the thickness of 6.2 mm, in order to evaluate the mechanical properties and to quantify the effect of geometric non-linearities. These pipes can be subjected to different phenomena which can result in introducing a defect in the structure. Two types of pipe specimens are tested which include the composite with notch and the other without notches. The objective of the using a notched specimen is to examine the evolution of the damage and to study the mechanical properties as a function of this damage. The experimental results are described as the influence of the number and the size of notches on the mechanical behavior. These results have shown that the yield stress decreases and yield strain increase with increasing of the notch size and number. The evolution of damage showed that the presence of notches plays an unfavorable role in the integrity of the structure.