Search

• Fixed-point analysis is carried out to characterize coalescence/breakup and interphase force model. • Iterative screening methodology for coalescence/breakup and interphase force models has been established. • A set of optimal closure models has been screened based on the proposed methodology and show superiority. The Euler–Euler two fluid approach has been widely adopted in computational multi-fluid dynamic (CMFD) simulation of nucleate boiling flow. Accurate prediction of bubble size and interphase forces are desired to properly model interphase momentum transfer in the CMFD simulation. Bubble dynamics, including nucleation, coalescence/breakup and condensation, should be modeled to calculate bubble size variation. In the meantime, modeling of interphase forces is crucial to predict distribution of void fraction. Numerous closure models have been developed for bubble dynamics and interphase forces. Diverse model combinations were reported depending on the specific application. As a step forward to converge the diversity, efforts are dedicated to establish a methodology to iteratively screen the closure models for nucleate flow boiling at elevated pressures based on the DEBORA experiment. In the proposed methodology, the closure models for each physics are first evaluated and sorted based on the predicted value in fixed-point analysis and its effect on CMFD results observed in separate-effect analysis. The second part of the methodology is iterative screening. To achieve accurate bubble size prediction, the optimal coalescence model is identified for each breakup model. With the optimal coalescence counterpart, the optimal breakup model is then identified. For the interphase force models, the optimal lift force model is first determined based on the CMFD simulation with the same drag force model and without wall lubrication force model. The optimal wall lubrication force and drag force model are selected in sequence. Utilized one single case of DEBORA experiments, the optimal set of the coalescence/breakup models, i.e., Prince et al.'s and Luo et al.'s models, and the interphase models, i.e., Tomiyama et al.'s models for drag and lift force, Lubchenko et al.'s model for wall lubrication force and Burns et al.'s model for turbulence dispersion force has been selected. Validation of the model combination based on more DEBORA experiment datasets and Bartolomei et al.'s experiment shows promising prediction accuracy. [Display omitted] [ABSTRACT FROM AUTHOR]

Epidemiological surveys suggest that adult hypercholesterolemia has an intrauterine origin and exhibits gender differences. Our previous study demonstrated that adult rats with intrauterine growth retardation (IUGR) offspring rats induced by prenatal caffeine exposure (PCE) had a higher serum total cholesterol (TCH) level. In this study, we aimed to analyze the influencing factors, underlying mechanism and interactions affecting hypercholesterolemia in adult offspring with caffeine exposure during pregnancy. Pregnant rats were administered caffeine (120 mg/kg d) from gestational day 11 until delivery. Offspring rats fed a normal diet or a high-fat diet (HFD) were euthanized at postnatal week 24, and blood and liver samples were collected. The results showed that PCE could increase the serum levels of TCH and low-density lipoprotein-cholesterol (LDL-C), and the hepatic expression of HMG CoA reductase (HMGCR) and apolipoprotein B (ApoB), but decreased the high-density lipoprotein-cholesterol (HDL-C) level and the hepatic expression of scavenger receptor B1 (SR-B1) and LDL receptor (LDLR). Furthermore, PCE, HFD and gender interact with each other to influence the serum cholesterol phenotype and expression of hepatic cholesterol metabolic genes. These results suggest that the hypercholesterolemia in adult offspring rats induced by PCE mainly resulted from enhanced synthesis and the weakened reverse transport of cholesterol in the liver, furthermore HFD could aggravate this effect, which is caused by hepatic cholesterol metabolic disorders. Moreover, cholesterol metabolism in female rats was more sensitive to neuroendocrine changes and HFD than that in males. This study confirmed the influencing factors (such as a HFD and female gender) of hypercholesterolemia in IUGR offspring providing theoretical and experimental bases for the effective prevention of fetal-originated hypercholesterolemia. [ABSTRACT FROM AUTHOR]

The hypothalamic–pituitary–adrenal (HPA) axis is one of the most important neuroendocrine axes and plays an important role in stress defense responses before and after birth. Prenatal exposure to xenobiotics, including environmental toxins (such as smoke, sulfur dioxide and carbon monoxide), drugs (such as synthetic glucocorticoids), and foods and beverage categories (such as ethanol and caffeine), affects fetal development indirectly by changing the maternal status or damaging the placenta. Certain xenobiotics (such as caffeine, ethanol and dexamethasone) may also affect the fetus directly by crossing the placenta into the fetus due to their lipophilic properties and lower molecular weights. All of these factors probably result in intrauterine programming alteration of the HPA axis, which showed a low basal activity but hypersensitivity to chronic stress. These alterations will, therefore, increase the susceptibility to adult neuropsychiatric (such as depression and schizophrenia) and metabolic diseases (such as hypertension, diabetes and non-alcoholic fatty liver disease). The “over-exposure of fetuses to maternal glucocorticoids” may be the main initiation factor by which the fetal HPA axis programming is altered. Meantime, xenobiotics can directly induce abnormal epigenetic modifications and expression on the important fetal genes (such as hippocampal glucocorticoid receptor, adrenal steroidogenic acute regulatory protein, et al) or damage by in situ oxidative metabolism of fetal adrenals, which may also be contributed to the programming alteration of fetal HPA axis. [ABSTRACT FROM AUTHOR]

Prenatal caffeine exposure (PCE) induces developmental toxicity of multi-organ and susceptibility to multi-disease in offspring. However, the effects of PCE on osteoarthritis susceptibility in adult offspring and its intrauterine programming mechanism remain to be further investigated. Here, we found that PCE induced susceptibility to osteoarthritis in male adult offspring rats, which was related to the inhibited function of cartilage matrix synthesis from fetuses to adults. Meanwhile, PCE consistently downregulated the H3K9ac and expression levels of transforming growth factor β receptor 1 (TGFβR1), and then blocked TGFβ signaling pathway, which contributed to the suppressed cartilage matrix synthesis. Moreover, the high level of corticosterone caused by PCE reduced the H3K9ac level on TGFβR1 promoter region through acting on glucocorticoids receptor (GR) and recruiting histone deacetylase 2 (HDAC2) into the nucleus of fetal chondrocytes. Taken together, PCE induced osteoarthritis susceptibility in male adult offspring rats, which was attributed to the low-functional programming of TGFβR1 induced by corticosterone via GR/HDAC2 signaling. • Prenatal caffeine exposure (PCE) caused osteoarthritis susceptibility in offspring. • The low-expressional TGFβR1 contributed to the inhibited cartilage matrix synthesis. • PCE induced-high corticosterone decreased H3K9ac of TGFβR1 via GR/HDAC2 signaling. [ABSTRACT FROM AUTHOR]

This study intends to explore the role of Vaspin and cholesterol metabolism in the process of osteoarthritis (OA) and its mechanism in vitro and in vivo. In vitro , chondrocytes were treated with interleukin-1β (IL-1β, 20 ng/mL) in combination with Vaspin at different concentrations for 48 h. The expressions of Aggrecan (ACAN), Collagen 2a1 (Col2a1), A Disintegrin And Metalloproteinase with Thrombo Spondin type 1 motifs 5 (ADAMTS 5), and Matrix metalloproteinase 13 (MMP13) were detected. In vivo , the expression of liver X receptor (LXRα) and other Cholesterol efflux related genes were detected in the rat OA knee cartilage-induced by papain. In vitro , in a concentration-dependent manner, Vaspin reversed the decreased expression of ACAN and Col2a1, and the increased expression of ADAMTS 5 and MMP13 caused by IL-1β. Besides, Vaspin promoted the expression of LXRα and other Cholesterol efflux related genes in a concentration-dependent manner in chondrocytes. However, miR155 mimics reversed the Vaspin-induced expression changes of cholesterol efflux pathway in chondrocytes. In vivo , the expression of LXRα and other Cholesterol efflux related genes were decreased in the rat OA knee cartilage-induced by papain. Besides, the level of Vaspin was reduced and the miroRNA155 (miR155) expression was increased in OA knee cartilage of rats. In conclusion, the decreased expression of Vaspin inhibited the expression of Cholesterol efflux pathway via miR155/LXRα. Finally, the inhibited Cholesterol efflux pathway led to the cholesterol accumulation and OA in cartilage. [ABSTRACT FROM AUTHOR]

This study investigated the role and mechanism of action of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the pathogenesis of renal interstitial fibrosis (RIF), and its involvement in the anti-RIF effect of norcantharidin (NCTD). Mice with unilateral ureteral obstruction and BUMPT mouse proximal tubular cells exposed to transforming growth factor (TGF)-β1 were used as in vivo and in vitro models of RIF, respectively. NCTD was administered to mice by intraperitoneal injection (0.075 mg kg−1·day−1). Hematoxylin–eosin and Masson's trichrome staining were performed to assess pathologic changes in the kidney. Immunohistochemistry, western blotting, and real-time PCR were performed to evaluate the expression of TWEAK and the fibrotic factors fibronectin (FN) and collagen type I (Col-I). The role of TWEAK in RIF and in the anti-RIF effect of NCTD was evaluated by TWEAK overexpression and neutralization with a specific antibody, and specific inhibitor of Mothers against decapentaplegic homolog (Smad)3 (SIS3) was used to examine the involvement of TGF-β1/Smad3 signaling. TWEAK was mainly expressed in renal tubules in mice; the level was markedly elevated in both in vivo and in vitro RIF models. TWEAK overexpression in BUMPT cells increased the levels of phosphorylated Smad3, FN, and Col-I, which were reduced by treatment with SIS3. NCTD suppressed FN and Col-I expression by blocking TWEAK-mediated Smad3 phosphorylation. Upregulation of TWEAK contributes to RIF by promoting Smad3 phosphorylation, while NCTD inhibits this process. [ABSTRACT FROM AUTHOR]