The prevention and evaluation of explosions requires suitable standards of measurement. As such, for this study two ignition thresholds, the ignition temperature and the minimum ignition irradiance ...were selected as the assessment criteria. These ignition threshold values were experimentally determined by heating stationary inert silicon carbide particles via thermal radiation with a large spot size in order to ignite quiescent methane-air fuel mixtures. A high-speed Schlieren camera was used to capture the progression of the formation and propagation of the flames throughout the experiments. The results of the experiments show that the irradiance and temperature threshold are directly and inversely proportional to the particle size, respectively. Furthermore, the irradiance and temperature thresholds have similar tendencies within the flammability limits; wherein, the minimum value corresponds to fuel mixtures at a stoichiometric ratio, and increases as the equivalence ratio shifts toward the flammability limits. Irradiance thresholds, though, are more sensitive to changes in equivalence ratio than temperature. The temperature histories of the heated particle determined that when the irradiance is lower than its ignition threshold value, the heated particle-fuel mixture system will arrive at a thermal equilibrium, rather than ignition, due to the inability of the particle to reach the ignition temperature. This study also found that longer ignition times will result in a more drastic deformation of the flame fronts caused by natural convection.
Small cell lung cancer (SCLC) is a rapidly progressing, incurable cancer that frequently spreads to bone. New insights are needed to identify therapeutic targets to prevent or retard SCLC metastatic ...progression. Human SCLC SBC-5 cells in mouse xenograft models home to skeletal and nonskeletal sites, whereas human SCLC SBC-3 cells only pervade nonskeletal sites. Because microRNAs (miRNA) often act as tumor regulators, we investigated their role in preclinical models of SCLC. miRNA expression profiling revealed selective and reduced expression of miRNA (miR)-335 and miR-29a in SBC-5 cells, compared with SBC-3 cells. In SBC-5 cells, miR-335 expression correlated with bone osteolytic lesions, whereas miR-29a expression did not. Overexpression of miR-335 in SBC-5 cells significantly reduced cell migration, invasion, proliferation, colony formation, and osteoclast induction in vitro. Importantly, in miR-335 overexpressing SBC-5 cell xenografts (n = 10), there were minimal osteolytic lesions in the majority of mice and none in three mice. Expression of RANK ligand (RANKL) and insulin-like growth factor-I receptor (IGF-IR), key mediators of bone metastases, were elevated in SBC-5 as compared with SBC-3 cells. Mechanistically, overexpression of miR-335 in SBC-5 cells reduced RANKL and IGF-IR expression. In conclusion, loss of miR-335 promoted SCLC metastatic skeletal lesions via deregulation of IGF-IR and RANKL pathways and was associated with metastatic osteolytic skeletal lesions.
These preclinical findings establish a need to pursue the role of miR-335 in human SCLC with metastatic skeletal disease.
MicroRNAs (miRNAs) are frequently deregulated in human tumors, and play important roles in tumor development and progression. The pathological roles of miRNAs in neurofibromatosis type 1 (NF1) ...tumorigenesis are largely unknown. We demonstrated that miR‐10b was up‐regulated in primary Schwann cells isolated from NF1 neurofibromas and in cell lines and tumor tissues from malignant peripheral nerve sheath tumors (MPNSTs). Intriguingly, a significantly high level of miR‐10b correlated with low neurofibromin expression was found in a neuroectodermal cell line: Ewing’s sarcoma SK‐ES‐1 cells. Antisense inhibiting miR‐10b in NF1 MPNST cells reduced cell proliferation, migration and invasion. Furthermore, we showed that NF1 mRNA was the target for miR‐10b. Overexpression of miR‐10b in 293T cells suppressed neurofibromin expression and activated RAS signaling. Antisense inhibition of miR‐10b restored neurofibromin expression in SK‐ES‐1 cells, and decreased RAS signaling independent of neurofibromin in NF1 MPNST cells. These results suggest that miR‐10b may play an important role in NF1 tumorigenesis through targeting neurofibromin and RAS signaling. (Cancer Sci 2010)
Abstract
Background
Ovarian cancer (OC) is a major cause of cancer-related deaths among women. The aim of this study was to estimate and report data on the current burden of ovarian cancer worldwide ...over the past 30 years.
Method
Based on the data provided by GBD 2019, we collected and interpreted the disease data of ovarian cancer by incidence, mortality, disability-adjusted life-years (DALYs), and used corresponding age-standardized rates as indicators. Also, we categorized the data by attributed risk factors and captured deaths due to high fasting plasma glucose, occupational exposure to asbestos and high body-mass index, respectively. All outcomes in the study were reported using mean values and corresponding 95% uncertainty intervals (95% UI).
Results
Globally, there were 294422 (260649 to 329727) incident cases in 2019, and the number of deaths and DALYs were 198412 (175357 to 217665) and 5.36 million (4.69 to 5.95). The overall burden was on the rise, with a percentage change of 107.8% (76.1 to 135.7%) for new cases, 103.8% (75.7 to 126.4%) for deaths and 96.1% (65.0 to 120.5%) for DALYs. Whereas the age-standardized rates kept stable during 1990–2019. The burden of ovarian cancer increased with age. and showed a totally different trends among SDI regions. Although high SDI region had the declining rates, the burden of ovarian cancer remained stable in high-middle and low SDI regions, and the middle and low-middle SDI areas showed increasing trends. High fasting plasma glucose was estimated to be the most important attributable risk factor for ovarian cancer deaths globally, with a percentage change of deaths of 7.9% (1.6 to 18.3%), followed by occupational exposure to asbestos and high body mass index.
Conclusions
Although the age-standardized rates of ovarian cancer didn’t significantly change at the global level, the burden still increased, especially in areas on the lower end of the SDI range. Also, the disease burden due to different attributable risk factors showed heterogeneous, and it became more severe with age.
This study aimed to evaluate the potential associations of dietary BCAAs (isoleucine, leucine, and valine) with physical function in the elderly Chinese population. A validated semiquantitative food ...frequency questionnaire and anthropometric and physical function measurements were used to collect data. We modeled trends in physical function indicators for BCAA quartiles using multivariate linear regression models. Among 4336 (43.97% men) participants aged 72.73 ± 5.48 years, a higher dietary intake of BCAAs was positively associated with increased handgrip strength (all p trends < 0.001), shorter times for 4-m fast walking (all p trends < 0.001) and repeated chair rises (all p trends < 0.001). No linear association was found between subtypes of amino acids and any physical functions (all p trends > 0.05). Individuals in the highest quartiles of BCAA intake had a reduced risk of developing low muscle strength, and the multiadjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for women and men were 0.50 (0.38−0.65) and 0.67 (0.50−0.91), respectively. Similarly, higher BCAA consumption was associated with a lower risk of developing low physical performance (4-m walking speed: OR = 0.68 0.50−0.93; repeated chair rises: OR = 0.66 0.54−0.81). Higher dietary BCAA intake might be beneficial for physical function in the elderly population.
MicroRNAs (miRNAs) are a new class of small noncoding RNAs of 19-25 nucleotides that function as negative posttranscriptional gene regulators. MiRNAs hybridize to the 3' untranslated region (UTR) of ...target mRNAs and repress translation or mediate mRNA cleavage. MiRNAs critically regulate tumorigenesis and progression by targeting oncogenes, tumor suppressor genes, or genes related to proliferation, angiogenesis, and apoptosis. Different tumor types and tumors at different stages exhibit unique miRNA profiles. MiRNAs show promise as potential biomarkers for cancer diagnostics, progression, and response to treatment. The role of miRNAs in promoting bone metastases is under investigated. We summarize recent findings on the mechanisms by which miRNAs may regulate bone metastatic spread of breast cancer, prostate cancer, lung cancer and multiple myeloma. We review similarities and differences in miRNA profiles that may explain the variety of molecular pathways underling metastatic spread to the skeleton in different cancers. Finally, we discuss the exciting potential of using miRNAs as diagnostics and therapeutic targets to reduce the risk of bone metastases in cancer, from the perspective of data provided by recent pre-clinical and clinical studies.
Lung cancer is the leading cause of malignancy-related mortality worldwide. Metastases, which account for 90% of lung cancer deaths, frequently target the skeleton, leading to rapid deterioration in ...quality of life and premature death. The molecular mechanism underlying this progression, especially the development of bone metastases, is largely unknown. MicroRNAs (miRNAs) are small, endogenous, noncoding RNAs that function as negatively posttranscriptional gene regulators. Changes in miRNAs, which may exhibit either oncogenic or tumor suppressive activity, are common in lung cancer. Over-expressed miRNAs may contribute to oncogenesis by down-regulating tumor suppressors, whereas the loss of selected miRNAs may negatively regulate oncogenes or factors related to tumorigenesis and progression. MiRNAs may activate or repress metastases. Specific miRNA expression profiles may correlate with the response in treatment. We summarize recent findings and patents in the pathological roles of miRNAs in the progression and bone metastases in lung cancer, and discuss the diagnostic and therapeutic options in the clinical management of lung cancer.
•Uncertainty and sensitivity analysis framework for pipe-embedded walls is proposed.•The variables’ ranking is obtained by two different sensitivity analysis methods.•Four key variables are ...identified, and the pipe spacing affects heat accumulation.•The climate zone no longer dominates the thermal radiation of the interior surface.•Pipe location has a slight influence on heat transfer indicators of wall surfaces.
Pipe-embedded building envelope, which is of particular interest to architects and engineers due to its excellent performances and invisibility characteristic, has been regarded as a potential technology for future buildings. Understanding the impacts of multiple uncertainties associated with design, construction, and operational control on its thermal performances is critical to the development of this burgeoning active insulation technology. Aiming at this goal, an in-depth uncertainty analysis (UA) and global sensitivity analysis (GSA) study was numerically conducted to investigate the influence mechanism of 12 different variables on 5 performance indicators in winter conditions. The UA results indicated that a dual-effect, i.e., better indoor thermal comfort and “zero” or even “negative” thermal load of the exterior walls, could be achieved only when relevant variables were properly selected. Due to the increase in the quantities and types of input variables, as well as the internal heat transfer process became more complicated, the importance rankings of variables obtained by two different GSA methods became different. Therefore, the treed Gaussian process method was proven to be more effective in identifying the uncertain variables. The GSA results stated that heat-source temperature, indoor set-point, charging duration, and thermal conductivity of pipe-embedded layer were the four most significant variables. For heat-source temperature and indoor set-point, there always existed an obvious mutual restriction relationship between them among all indicators except exterior surface heating loss. Meanwhile, the suggested value of the charging duration was no less than 6 h, and the optimal range of the thermal conductivity of pipe-embedded layer given by GSA was 0.5–2.75 W/m·℃. Under the blocking effect of the thermal barrier, the uncertainty of the climate zone on interior surface heating load was greatly reduced, and the climate zone was no longer a key variable affecting the cumulative subcooling duration. Besides, it was proved that the pipe spacing had a great influence on the heat accumulation inside the pipe-embedded layer, pipe location had a slight influence on interior surface heating load and exterior surface heating loss, and the pipe diameter did not influence thermal performances. From the perspective of energy density, the optimal range of the pipe spacing was 100–250 mm. Overall, this study highlighted the positive effect of the pipe-embedded system on the development of new-built and existing buildings towards zero-carbon targets, and also provided useful guidance for its further applications and investigations.
Heavy rains and floods cause human, material, and economic damage in cities worldwide. The severity of flooding has intensified due to accelerating urbanization. While much of the existing research ...on flood hazards emphasizes simulation and assessment, the correlation between indicators has yet to be explored. This study employs the Tree Gaussian Process sensitivity analysis method. Through rigorous sampling and correlation analysis, the model identifies critical determinants. Significantly, factors such as the water supply penetration rate (Var3), water pipeline density in built-up areas (Var4), centralized treatment rate of sewage treatment plants (Var6), agricultural land for forestry (Var13), and urban, village, and industrial and mining land (Var15) stand out as primary influencers on the flood-affected populace. These variables reflect a city’s flood management capability and its dedication to resource stewardship and ecological equilibrium, underscoring its critical role in flood risk assessment and strategic mitigation. The study further illuminates that the interplay of these variables can exacerbate flood consequences, suggesting a compounded impact when variables operate in tandem. Recognizing these synergistic effects reveals a more pronounced flood threat than previously estimated, indicating that viewing these factors in silos might underrepresent the risk involved.
The aim of this study is to estimate the educational level differences in the primary and secondary prevention of stroke among the Chinese population. Data were obtained from the China Kadoorie ...Biobank (CKB) survey of 512,891 people aged 30–79 years in 10 geographic regions of China, which was conducted from 2002 to 2008. The Prediction for Atherosclerotic Cardiovascular Disease Risk in China model was used to identify individuals with a high estimated 10-year stroke risk. A total of 8884 participants (1.7%) had established stroke and 218,972 (42.7%) had a high stroke risk. In both primary and secondary prevention, the participants' educational level was positively associated with the control of smoking, blood pressure, consuming a healthy diet, and the use of antiplatelet, BP-lowering medications but negatively associated with higher physical activity levels (all Ptrend < 0.001). In addition, the positive associations were observed with the control of drinking and use of anti-hyperglycaemia medication for primary prevention (all Ptrend < 0.001) and with the use of lipid-lowering medication for secondary prevention (Ptrend = 0.019). The results of the interaction between education level and prevention level showed that, compared with participants in primary prevention, educational level disparities in those with secondary prevention had significantly higher use of antiplatelets and lipid-lowering drugs, achieving the physical activity goal and non-current drinker (all Pfor interaction < 0.05). A higher education level was associated with an increased acceptance of primary and secondary prevention strategies (not smoking or drinking, consuming a healthier diet) except for engaging in a suitable level of physical activity.
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