Comprehensive analysis of hypoxia-related genes for prognosis value, immune status, and therapy in osteosarcoma patients

Osteosarcoma is a common malignant bone tumor in children and adolescents. The overall survival of osteosarcoma patients is remarkably poor. Herein, we sought to establish a reliable risk prognostic model to predict the prognosis of osteosarcoma patients. Patients ’ RNA expression and corresponding clinical data were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus databases. A consensus clustering was conducted to uncover novel molecular subgroups based on 200 hypoxia-linked genes. A hypoxia-risk models were established by Cox regression analysis coupled with LASSO regression. Functional enrichment analysis, including Gene Ontology annotation and KEGG pathway analysis, were conducted to determine the associated mechanisms. Moreover, we explored relationships between the risk scores and age, gender, tumor microenvironment, and drug sensitivity by correlation analysis. We identified two molecular subgroups with significantly different survival rates and developed a risk model based on 12 genes. Survival analysis indicated that the high-risk osteosarcoma patients likely have a poor prognosis. The area under the curve (AUC) value showed the validity of our risk scoring model, and the nomogram indicates the model’s reliability. High-risk patients had lower Tfh cell infiltration and a lower stromal score. We determined the abnormal expression of three prognostic genes in osteosarcoma cells. Sunitinib can promote osteosarcoma cell apoptosis with down-regulation of KCNJ3 expression. In summary, the constructed hypoxia-related risk score model can assist clinicians during clinical practice for osteosarcoma prognosis management. Immune and drug sensitivity analysis can provide essential insights into subsequent mechanisms. KCNJ3 may be a valuable prognostic marker for osteosarcoma development

Nodular and diffuse spindle cell infiltration in keloidal scleroderma: a case report

Keloidal scleroderma is a variant of scleroderma that presents as firm keloidal nodules or plaques. Due to the similarity in morphology and pathology, it is often distinguished from a hypertrophic scar or keloid. We report a case of keloidal scleroderma with rare nodular and diffuse spindle cell infiltration in histopathology. Recognition of this unusual histopathological feature may help clinicians improve their knowledge and avoid misdiagnosis

The role of aryl hydrocarbon receptor in vitiligo: a review

Vitiligo is an acquired autoimmune dermatosis characterized by patchy skin depigmentation, causing significant psychological distress to the patients. Genetic susceptibility, environmental triggers, oxidative stress, and autoimmunity contribute to melanocyte destruction in vitiligo. Due to the diversity and complexity of pathogenesis, the combination of inhibiting melanocyte destruction and stimulating melanogenesis gives the best results in treating vitiligo. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that can regulate the expression of various downstream genes and play roles in cell differentiation, immune response, and physiological homeostasis maintenance. Recent studies suggested that AhR signaling pathway was downregulated in vitiligo. Activation of AhR pathway helps to activate antioxidant pathways, inhibit abnormal immunity response, and upregulate the melanogenesis gene, thereby protecting melanocytes from oxidative stress damage, controlling disease progression, and promoting lesion repigmentation. Here, we review the relevant literature and summarize the possible roles of the AhR signaling pathway in vitiligo pathogenesis and treatment, to further understand the links between the AhR and vitiligo, and provide new potential therapeutic strategies

SENSITIVITY ANALYSIS ON STRESS OF FLEXIBLE HINGES TO DESIGN PARAMETERS BASED ON TAGUCHI METHOD

The flexible hinges in the compliant mechanism,when the cyclic loading with continuous and variable loads,are easily to induce the fatigue crack initiation in its thinnest place due to stress concentration. It ultimately causes fatigue failure in the flexible hinges. Using the elliptical hinge as the research object,this paper analyzed the characteristics of the maximum applied stress in the thinnest place of flexible hinges by using Taguchi Method. Orthogonal experiments were performed upon finding out the controllable factors and noise factors affecting the maximum stress. Sensitivity analysis based on Orthogonal experiments was applied loading to quantitatively analyze the effect of each design variable parameter on the maximum stress. The calculation showed that the change of the maximum stress depends on several design variables parameters,and the geometric parameter plays an important role. This method does not depend on optimization algorithm,can be employed for sensitivity analysis of discrete,non-differential or implicit-expression structures,and provides favorable reference to the robust design of the flexible hinges by improving its fatigue life

Astragaloside IV Enhances Melanogenesis via the AhR-Dependent AKT/GSK-3β/β-Catenin Pathway in Normal Human Epidermal Melanocytes

Astragalus membranaceus root has been widely used for repigmentation treatment in vitiligo, but its mechanism is poorly understood. We sought to investigate the effect of astragaloside IV (AS-IV), a main active extract of the Astragalus membranaceus root, on melanin synthesis in normal human epidermal melanocytes (NHEMs) and to elucidate its underlying mechanisms. Melanin content, tyrosinase activity, qPCR, western blot, and immunofluorescence were employed. Specific inhibitors and small interfering RNA were used to investigate the possible pathway. AS-IV stimulated melanin synthesis and upregulated the expression of melanogenesis-related genes in a concentration-dependent manner in NHEMs. AS-IV could activate the aryl hydrocarbon receptor (AhR), and AS-IV-induced melanogenesis was inhibited in si-AhR-transfected NHEMs. In addition, we showed that AS-IV enhanced the phosphorylation of AKT and GSK-3β and nuclear translocation of β-catenin. AS-IV-induced MITF expression upregulation and melanin synthesis were decreased in the presence of β-catenin inhibitor FH353. Furthermore, AhR antagonist CH223191 inhibited the activation of AKT/GSK-3β/β-catenin signaling, whereas the expression of CYP1A1 (marker of AhR activation) was not affected by the AKT inhibitor in AS-IV-exposed NHEMs. Our findings show that AS-IV induces melanogenesis through AhR-dependent AKT/GSK-3β/β-catenin pathway activation and could be beneficial in the therapy for depigmented skin disorders

ROBUST OPTIMAL DESIGN OF MULTIPLE RESPONSE OF FLEXIBLE HINGE BASED ON THE TAGUCHI AND SATISFACTION FUNCTION METHOD

It is difficult to optimize flexibility robustness because the robust optimization of multiple response for cell injection 3 RRR compliant parallel micro motion platform flexible parts are existed"under"deformation or"over"deformation. a new method is proposed to solve the robust optimization of multiple response which combine the Taguchi method and satisfaction function. Firstly,the hinge motion model compliance of micro-platform multi-directional is established and the response surface test design based on this model. Secondly,the taguchi method is introduced to analyze the stability of multiple response. Finally,the satisfaction function is used to taken the issues of multiple response optimization into maximal value of overall satisfaction and get the robust optimization design plan under the restriction of multiple response flexibility. Examples show that this method can provide a new solution for robust optimal design of the multiple response of flexible hinge

Additional file 2: of CircIBTK inhibits DNA demethylation and activation of AKT signaling pathway via miR-29b in peripheral blood mononuclear cells in systemic lupus erythematosus

Figure S1. a, b Statistical analysis of the cumulative densitometry data for western blot analysis of PTEN expression and AKT phosphorylation in PBMCs from HC transfected with miR-29b mimics. c, d Statistical analysis of the cumulative densitometry data for western blot analysis of PTEN expression and AKT phosphorylation in PBMCs from patients with SLE, transfected with miR-29b inhibitor. e, f Statistical analysis of the cumulative densitometry data for western blot analysis of PTEN/AKT signaling-related proteins in PBMCs from patients with SLE, transfected with miR-29b mimics, circIBTK expression plasmids, NC oligonucleotides or empty vector. g, h Statistical analysis of the cumulative densitometry data for western blot analysis of PTEN/AKT signaling-related proteins in PBMCs from HC transfected with miR-29b inhibitor, circIBTK siRNA or NC oligonucleotides. Three replicate experiments were performed. The cumulative densitometry data were compared using the paired Student’s t test and results were represented as mean ± SD (n = 3). *P < 0.05, **P < 0.01. (PDF 298 kb

Wafer-Level Vacuum-Packaged Electric Field Microsensor: Structure Design, Theoretical Model, Microfabrication, and Characterization

This paper proposes a novel wafer-level vacuum packaged electric field microsensor (EFM) featuring a high quality factor, low driving voltage, low noise, and low power consumption. The silicon-on-insulator (SOI) conductive handle layer was innovatively used as the sensing channel to transmit the external electric field to the surface of the sensitive structure, and the vacuum packaging was realized through anodic bonding between the SOI and glass-on-silicon (GOS). The fabrication process was designed and successfully realized, featured with a simplified process and highly efficient batch manufacturing, and the final chip size was only 5 × 5 mm. A theoretical model for the packaged device was set up. The influence of key parameters in the packaging structure on the output characteristics of the microsensor was analyzed on the basis of the proposed model. Experiments were conducted on the wafer-level vacuum-packaged EFM to characterize its performance. Experimental results show that, under the condition of applying 5 V DC driving voltage, the required AC driving voltage of the sensor was only 0.05 VP, and the feedthrough was only 4.2 mV. The quality factor was higher than 5000 and was maintained with no drop in the 50-day test. The vacuum in the chamber of the sensor was about 10 Pa. A sensitivity of 0.16 mV/(kV/m) was achieved within the electrostatic field range of 0–50 kV/m. The linearity of the microsensor was 1.62%, and the uncertainty was 4.42%

Additional file 1: of CircIBTK inhibits DNA demethylation and activation of AKT signaling pathway via miR-29b in peripheral blood mononuclear cells in systemic lupus erythematosus

Table S1. Clinical characteristics of 42 patients with SLE and 35 healthy controls. (DOCX 16 kb

Inflammatory Markers and the Risk of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

<div><p>Systemic inflammatory factors are inconsistently associated with the pathogenesis of chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis to summarize the evidence supporting the association between systemic inflammation and the risk of COPD. Pertinent studies were retrieved from PubMed, EmBase, and the Cochrane Library until April 2015. A random-effects model was used to process the data, and the analysis was further stratified by factors affecting these associations. Sensitivity analyses for publication bias were performed. We included 24 observational studies reporting data on 10,677 COPD patients and 28,660 controls. Overall, we noted that COPD was associated with elevated serum CRP (SMD: 1.21; 95%CI: 0.92–1.50; P < 0.001), leukocytes (SMD: 1.07; 95%: 0.25–1.88; P = 0.010), IL-6 (SMD: 0.90; 95%CI: 0.48–1.31; P < 0.001), IL-8 (SMD: 2.34; 95%CI: 0.69–4.00; P = 0.006), and fibrinogen levels (SMD: 0.87; 95%CI: 0.44–1.31; P < 0.001) when compared with control. However, COPD was not significantly associated with TNF-α levels when compared with control (SMD: 0.60; 95%CI: -0.46 to 1.67; P = 0.266). Our findings suggested that COPD was associated with elevated serum CRP, leukocytes, IL-6, IL-8, and fibrinogen, without any significant relationship with TNF-α.</p></div