Impact of calcium hydroxide on physical characteristics and leaching stability of metakaolin-based geopolymer waste form containing radioactive borate waste

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Relationship Between Otorhinolaryngologic Diseases and Obesity

ObjectivesObesity rates have been increasing for all population groups worldwide, leading to the increased development of various diseases. This study was designed is to identify the relationships between obesity and several important otorhinolaryngologic diseases, including chronic otitis media (COM), chronic rhinosinusitis, and chronic tonsillitis.MethodsMean body mass index (BMI) was compared in patients with COM, rhinosinusitis, and tonsillitis and in a control group. The relationships among the prevalence rates of overweight and obesity, morbidity period, and BMI were assessed in each group.ResultsMean BMIs in the COM, rhinosinusitis, and tonsillitis groups were 24.45±2.72 kg/m2, 24.68±3.25 kg/m2, and 24.67±3.82 kg/m2, respectively, with each significantly higher than in the control group (23.22±3.01 kg/m2, P0.05 each).ConclusionMean BMI and the prevalence of obesity were elevated in the three groups of patients with representative otorhinolaryngologic inflammatory diseases, including COM, chronic rhinosinusitis, and chronic tonsillitis

A Dual Inhibitor of the Proteasome Catalytic Subunits LMP2 and Y Attenuates Disease Progression in Mouse Models of Alzheimer\u27s Disease

The immunoproteasome (iP) is a variant of the constitutive proteasome (cP) that is abundantly expressed in immune cells which can also be induced in somatic cells by cytokines such as TNF-α or IFN-γ. Accumulating evidence support that the iP is closely linked to multiple facets of inflammatory response, eventually leading to the development of several iP inhibitors as potential therapeutic agents for autoimmune diseases. Recent studies also found that the iP is upregulated in reactive glial cells surrounding amyloid β (Aβ) deposits in brains of Alzheimer\u27s disease (AD) patients, but the role it plays in the pathogenesis of AD remains unclear. In this study, we investigated the effects of several proteasome inhibitors on cognitive function in AD mouse models and found that YU102, a dual inhibitor of the iP catalytic subunit LMP2 and the cP catalytic subunit Y, ameliorates cognitive impairments in AD mouse models without affecting Aβ deposition. The data obtained from our investigation revealed that YU102 suppresses the secretion of inflammatory cytokines from microglial cells. Overall, this study indicates that there may exist a potential link between LMP2/Y and microglia-mediated neuroinflammation and that inhibition of these subunits may offer a new therapeutic strategy for AD

Overcoming evasive resistance from vascular endothelial growth factor a inhibition in sarcomas by genetic or pharmacologic targeting of hypoxia-inducible factor 1α

Increased levels of hypoxia and hypoxia-inducible factor 1α (HIF-1α) in human sarcomas correlate with tumor progression and radiation resistance. Prolonged antiangiogenic therapy of tumors not only delays tumor growth but may also increase hypoxia and HIF-1α activity. In our recent clinical trial, treatment with the vascular endothelial growth factor A (VEGF-A) antibody, bevacizumab, followed by a combination of bevacizumab and radiation led to near complete necrosis in nearly half of sarcomas. Gene Set Enrichment Analysis of microarrays from pretreatment biopsies found that the Gene Ontology category “Response to hypoxia” was upregulated in poor responders and that the hierarchical clustering based on 140 hypoxia-responsive genes reliably separated poor responders from good responders. The most commonly used chemotherapeutic drug for sarcomas, doxorubicin (Dox), was recently found to block HIF-1α binding to DNA at low metronomic doses. In four sarcoma cell lines, HIF-1α shRNA or Dox at low concentrations blocked HIF-1α induction of VEGF-A by 84–97% and carbonic anhydrase 9 by 83–93%. HT1080 sarcoma xenografts had increased hypoxia and/or HIF-1α activity with increasing tumor size and with anti-VEGF receptor antibody (DC101) treatment. Combining DC101 with HIF-1α shRNA or metronomic Dox had a synergistic effect in suppressing growth of HT1080 xenografts, at least in part via induction of tumor endothelial cell apoptosis. In conclusion, sarcomas respond to increased hypoxia by expressing HIF-1α target genes that may promote resistance to antiangiogenic and other therapies. HIF-1α inhibition blocks this evasive resistance and augments destruction of the tumor vasculature. What’s new? Despite their initial promise, anti-angiogenic therapies have been a disappointment in the clinic. One reason is that solid tumors often become resistant to these drugs. Tumors that respond poorly to this type of therapy have increased activation of the hypoxia-induced transcription factor HIF-1α which can enhance tumor survival and progression. In this study, the authors report that this evasive resistance can be overcome by adding low-dose doxorubicin or shRNA to inhibit HIF-1α activity. They are thus developing a clinical trial combining the angiogenesis inhibitor bevacizumab with metronomic doxorubicin in sarcoma patients

Reversibly controlled ternary polar states and ferroelectric bias promoted by boosting square???tensile???strain

Interaction between dipoles often emerges intriguing physical phenomena, such as exchange bias in the magnetic heterostructures and magnetoelectric effect in multiferroics, which lead to advances in multifunctional heterostructures. However, the defect-dipole tends to be considered the undesired to deteriorate the electronic functionality. Here, we report deterministic switching between the ferroelectric and the pinched states by exploiting a new substrate of cubic perovskite, BaZrO3, which boosts square-tensile-strain to BaTiO3 and promotes four-variants in-plane spontaneous polarization with oxygen vacancy creation. First-principles calculations propose a complex of an oxygen vacancy and two Ti3+ ions coins a charge-neutral defect-dipole. Cooperative control of the defect-dipole and the spontaneous polarization reveals ternary in-plane polar states characterized by biased/pinched hysteresis loops. Furthermore, we experimentally demonstrate that three electrically controlled polar-ordering states lead to switchable and non-volatile dielectric states for application of non-destructive electro-dielectric memory. This discovery opens a new route to develop functional materials via manipulating defect-dipoles and offers a novel platform to advance heteroepitaxy beyond the prevalent perovskite substrates

The impact of education on cortical thickness in amyloid-negative subcortical vascular dementia: cognitive reserve hypothesis

Background: The protective effect of education has been well established in Alzheimer's disease, whereas its role in patients with isolated cerebrovascular diseases remains unclear. We examined the correlation of education with cortical thickness and cerebral small vessel disease markers in patients with pure subcortical vascular mild cognitive impairment (svMCl) and patients with pure subcortical vascular dementia (SVaD). Methods: We analyzed 45 patients with svMCl and 47 patients with SVaD with negative results on Pittsburgh compound B positron emission tomographic imaging who underwent structural brain magnetic resonance imaging. The main outcome was cortical thickness measured using surface-based morphometric analysis. We also assessed the volumes of white matter hyperintensities (WMH) and numbers of lacunes as other outcomes. To investigate the correlation of education with cortical thickness, WMH volume, and number of lacunes, multiple linear regression analyses were performed after controlling for covariates, including Mini Mental State Examination, in the svMCl and SVaD groups. Results: In the SVaD group, higher education was correlated with more severe cortical thinning in the bilateral dorsolateral frontal, left medial frontal, and parahippocampal areas, whereas there was no correlation of education with cortical thickness in the svMCl group. There was no correlation between education and cerebral small vessel disease, including WMH and lacunes, in both patients with svMCl and patients with SVaD. Conclusions: Our findings suggest that the compensatory effects of education on cortical thinning apply to patients with SVaD, which might be explained by the cognitive reserve hypothesis

Regulation of Adipose Tissue Stromal Cells Behaviors by Endogenic Oct4 Expression Control

BACKGROUND: To clarify the role of the POU domain transcription factor Oct4 in Adipose Tissue Stromal Cells (ATSCs), we investigated the regulation of Oct4 expression and other embryonic genes in fully differentiated cells, in addition to identifying expression at the gene and protein levels. The ATSCs and several immature cells were routinely expressing Oct4 protein before and after differentiating into specific lineages. METHODOLOGY/PRINCIPAL FINDINGS AND CONCLUSIONS: Here, we demonstrated the role of Oct4 in ATSCs on cell proliferation and differentiation. Exogenous Oct4 improves adult ATSCs cell proliferation and differentiation potencies through epigenetic reprogramming of stemness genes such as Oct4, Nanog, Sox2, and Rex1. Oct4 directly or indirectly induces ATSCs reprogramming along with the activation of JAK/STAT3 and ERK1/2. Exogenic Oct4 introduced a transdifferentiation priority into the neural lineage than mesodermal lineage. Global gene expression analysis results showed that Oct4 regulated target genes which could be characterized as differentially regulated genes such as pluripotency markers NANOG, SOX2, and KLF4 and markers of undifferentiated stem cells FOXD1, CDC2, and EPHB1. The negatively regulated genes included FAS, TNFR, COL6A1, JAM2, FOXQ1, FOXO1, NESTIN, SMAD3, SLIT3, DKK1, WNT5A, BMP1, and GLIS3 which are implicated in differentiation processes as well as a number of novel genes. Finally we have demonstrated the therapeutic utility of Oct4/ATSCs were introduced into the mouse traumatic brain, engrafted cells was more effectively induces regeneration activity with high therapeutic modality than that of control ATSCs. Engrafted Oct4/ATSCs efficiently migrated and transdifferentiated into action potential carrying, functionally neurons in the hippocampus and promoting the amelioration of lesion cavities

Identification of MicroRNA-21 as a Biomarker for Chemoresistance and Clinical Outcome Following Adjuvant Therapy in Resectable Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy.Formalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real-Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52) showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR) for death (HR = 0.316; 95%CI = 0.166–0.600; P = 0.0004) and recurrence (HR = 0.521; 95%CI = 0.280–0.967; P = 0.04). MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells.. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC

Analysis of the Air Transport Network Characteristics of Major Airports

The world's major airports are directly connected to hundreds of airports without intermediate routes. This connectivity can be described as the network in which the airport becomes a node and the route becomes a connection line. In this regard, this study analyzes the air transport network of 1,060 airports using the social network analysis (SNA) methodology. We consolidated the data from three airline alliances and established a network of 1,060 airports and 5,580 routes in 173 countries. Many previous studies on air transport network examined several specific airports or regions and mainly utilized the internal indicators of airports. Conversely, this study conducted a comprehensive analysis covering 173 countries by using air route, which is an external indicator of airports. This study presented the general characteristics of major countries and regions from the perspective of SNA and compared the individual networks of the United States and China, which have the greatest influence on international air logistics within the scope of the entire network analysis. This study can aid in the understanding of air transport networks and logistics connectivity in inter-city and inter-country transport