Expression and clinical significance of <i>Pax6</i> gene in retinoblastoma

AIM: To discuss the expression and clinical significance of <i>Pax6 </i>gene in retinoblastoma(Rb). <p>METHODS: Totally 15 cases of fresh Rb organizations were selected as observation group and 15 normal retinal organizations as control group. Western-Blot and reverse transcriptase polymerase chain reaction(RT-PCR)methods were used to detect <i>Pax6</i> protein and <i>Pax6 </i>mRNA expressions of the normal retina organizations and Rb organizations. At the same time, Western Blot method was used to detect the <i>Pax6</i> gene downstream MATH5 and BRN3b differentiation gene protein level expression. After the comparison between two groups, the expression and clinical significance of <i>Pax6</i> gene in Rb were discussed. <p>RESULTS: In the observation group, average value of mRNA expression of <i>Pax6</i> gene was 0.99±0.03; average value of <i>Pax6</i> gene protein expression was 2.07±0.15; average value of BRN3b protein expression was 0.195±0.016; average value of MATH5 protein expression was 0.190±0.031. They were significantly higher than the control group, and the differences were statistically significant(<i>P</i><0.05). <p>CONCLUSION: Abnormal expression of <i>Pax6</i> gene is likely to accelerate the occurrence of Rb

A diffusive gradients in thin-films technique for the assessment of bisphenols desorption from soils

Abstract Desorption/adsorption of bisphenols (BPs) in soils affects their mobility and availability. However, the kinetics of these processes have not been well studied, due to the lack of appropriate means of measurement. Diffusive gradients in thin-films (DGT) technique can assess kinetic processes in soils and have recently been developed for measuring three BPs (BPA, BPB and BPF). DGT was deployed for 2.5 h to 20 d in five soils with different soil properties. Non-linear increase in mass accumulation by DGT with time indicated poor resupply of BPs from soil solid to solution phase. By fitting the data with DIFS (DGT-induced fluxes in soils) model, values for the labile partition coefficient (Kdl), response time (tc) and rates of exchange (k1 and k-1) of BPs between soil solid and solution phases were obtained. The derived values of Kdl showed that most of the BPs in the soil could participate in labile exchange. Average response times of 1–2 h implied that the supply of BPs to DGT was limited by their desorption rate. Soils with more binding sites (higher DOM, CEC and Fe oxides) could resupply BPs more quickly, highlighting the danger of just considering partition effects

Imaging characterization of myocardial function, fibrosis, and perfusion in a nonhuman primate model with heart failure-like features

INTRODUCTION: The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model. METHODS: The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF \u3c 65% (termed as HFrEF, RESULTS: No LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, CONCLUSION: Our preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology

Topographic beta spiral and onshore intrusion of the Kuroshio Current

Author Posting. © American Geophysical Union, 2018. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 45 (2018): 287–296, doi:10.1002/2017GL076614.The Kuroshio intrusion plays a vitally important role in carrying nutrients to marginal seas. However, the key mechanism leading to the Kuroshio intrusion remains unclear. In this study we postulate a mechanism: when the Kuroshio runs onto steep topography northeast of Taiwan, the strong inertia gives rise to upwelling over topography, leading to a left-hand spiral in the stratified ocean. This is called the topographic beta spiral, which is a major player regulating the Kuroshio intrusion; this spiral can be inferred from hydrographic surveys. In the world oceans, the topographic beta spirals can be induced by upwelling generated by strong currents running onto steep topography. This is a vital mechanism regulating onshore intruding flow and the cross-shelf transport of energy and nutrients from the Kuroshio Current to the East China Sea. This topographic beta spiral reveals a long-term missing link between the oceanic general circulation theory and shelf dynamic theory.Strategic Priority Research Program of the Chinese Academy of Sciences Grant Numbers: XDA11020104, XDA110203052; National Natural Science Foundation of China (NSFC) Grant Numbers: 41576023, 41376030, 41476019; Foundation for Innovative Research Groups of NSFC Grant Number: 41421005; NSFC-Shandong Joint Fund for Marine Science Research Centers Grant Number: U1406401; Aoshan Sci-Tec Innovative Project of Qingdao National Laboratory for Marine Science and Technology Grant Number: 2016ASKJ02; National Key Research and Development Program of China Grant Numbers: 2017YFC1404000, 2016YFC1401601; National Key research and development Plan Sino-Australian Center for Healthy Coasts Grant Number: 2016YFE01015002018-07-1

Aurora-A down-regulates IkappaBα via Akt activation and interacts with insulin-like growth factor-1 induced phosphatidylinositol 3-kinase pathway for cancer cell survival

<p>Abstract</p> <p>Background</p> <p>The mitotic Aurora-A kinase exerts crucial functions in maintaining mitotic fidelity. As a bona fide oncoprotein, Aurora-A aberrant overexpression leads to oncogenic transformation. Yet, the mechanisms by which Aurora-A enhances cancer cell survival remain to be elucidated.</p> <p>Results</p> <p>Here, we found that Aurora-A overexpression was closely correlated with clinic stage and lymph node metastasis in tongue carcinoma. Aurora-A inhibitory VX-680 suppressed proliferation, induced apoptosis and markedly reduced migration in cancer cells. We further showed that insulin-like growth factor-1, a PI3K physiological activator, reversed VX-680-decreased cell survival and motility. Conversely, wortmannin, a PI3K inhibitor, combined with VX-680 showed a synergistic effect on inducing apoptosis and suppressing migration. In addition, Aurora-A inhibition suppressed Akt activation, and VX-680-induced apoptosis was attenuated by Myr-Akt overexpression, revealing a cross-talk between Aurora-A and PI3K pathway interacting at Akt activation. Significantly, we showed that suppression of Aurora-A decreased phosphorylated Akt and was associated with increased IkappaBα expression. By contrast, Aurora-A overexpression upregulated Akt activity and downregulated IkappaBα, these changes were accompanied by nuclear translocation of nuclear factor-κB and increased expression of its target gene Bcl-xL. Lastly, Aurora-A overexpression induced IkappaBα reduction was abrogated by suppression of Akt either chemically or genetically.</p> <p>Conclusion</p> <p>Taken together, our data established that Aurora-A, via activating Akt, stimulated nuclear factor-κB signaling pathway to promote cancer cell survival, and promised a novel combined chemotherapy targeting both Aurora-A and PI3K in cancer treatment.</p

Imaging characterization of myocardial function, fibrosis, and perfusion in a nonhuman primate model with heart failure-like features

IntroductionThe availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model.MethodsThe NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF &lt; 65% (termed as HFrEF, n = 10) and LVEF ≥ 65% with diastolic dysfunction (termed as HFpEF, n = 10). Another group of ten healthy monkeys was used as the healthy control. All monkeys underwent a CMR study to measure global longitudinal strain (GLS), myocardial extracellular volume (ECV), and late gadolinium enhancement (LGE). In healthy controls and HFpEF group, quantitative perfusion imaging scans at rest and under dobutamine stress were performed and myocardial perfusion reserve (MPR) was subsequently obtained.ResultsNo LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, p &lt; 0.001), as well as for stress perfusion (2.40 ± 0.34 ml/min/g in healthy controls vs. 1.28 ± 0.24 ml/min/g in HFpEF group, p &lt; 0.01) and corresponding MPR (1.83 ± 0.3 vs. 1.35 ± 0.29, p &lt; 0.01). After adjusting for age, ECV (p = 0.01) and MPR (p = 0.048) still showed significant differences among the three groups.ConclusionOur preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology