In vitro anti-tumor activity in SGC-7901 human gastric cancer cells treated with dandelion extract

Purpose: To investigate the mechanisms of cytotoxicity of a dandelion extract against human gastric cancer cell line SGC-7901 cells.Methods: The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometry, and transwell assays were used to investigate the effects of a dandelion extract on cell proliferation, levels of apoptosis, and cell migration, respectively. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assessed the effects of a dandelion extract on the expression levels of genes regulating proliferation and apoptosis.Results: Dandelion extract exerted strong cytotoxic effects on the cancer cells. After exposure, apoptotic cells increased and cell migration was reduced. RT-qPCR assay revealed that dandelion extract significantly increased anti-proliferative and pro-apoptotic gene expression, including phosphate and tensin homology deleted on chromosome ten (Pten) and Bcl-2 Associated X protein (Bax) mRNA in the gastric cancer cells. The results also indicate that there was decreased pro-proliferative and antiapoptotic gene expression (i.e., extracellular signal-regulated kinase (Erk), Survivin, and B-cell lymphoma 2 (Bcl2) mRNA).Conclusion: The results suggest that dandelion extract is a potent gastric cancer cell proliferation, survival, and migration inhibitor with potential pharmaceutical applications for the prevention of gastric cancer.Keywords: dandelion extract, gastric cancer, cytotoxic effect, migration inhibitio

Structure of a Bmi-1-Ring1B Polycomb Group Ubiquitin Ligase Complex

Polycomb group (PcG) proteins Bmi-1 and Ring1B are core subunits of the PRC1 complex which plays important roles in the regulation of Hox gene expression, X-chromosome inactivation, tumorigenesis and stem cell self-renewal. The RING finger protein Ring1B is an E3 ligase that participates in the ubiquitination of lysine 119 of histone H2A, and the binding of Bmi-1 stimulates the E3 ligase activity. We have mapped the regions of Bmi-1 and Ring1B required for efficient ubiquitin transfer and determined a 2.5 Angstroms structure of the Bmi-1-Ring1B core domain complex. The structure reveals that Ring1B 'hugs' Bmi-1 through extensive RING domain contacts and its N-terminal tail wraps around Bmi-1. The two regions of interaction have a synergistic effect on the E3 ligase activity. Our analyses suggest a model where the Bmi-1-Ring1B complex stabilizes the interaction between the E2 enzyme and the nucleosomal substrate to allow efficient ubiquitin transfer

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

Proton-Boron Fusion Yield Increased by Orders of Magnitude with Foam Targets

A novel intense beam-driven scheme for high yield of the tri-alpha reaction 11B(p,{\alpha})2{\alpha} was investigated. We used a foam target made of cellulose triacetate (TAC, C_9H_{16}O_8) doped with boron. It was then heated volumetrically by soft X-ray radiation from a laser heated hohlraum and turned into a homogenous, and long living plasma. We employed a picosecond laser pulse to generate a high-intensity energetic proton beam via the well-known Target Normal Sheath Acceleration (TNSA) mechanism. We observed up to 10^{10}/sr {\alpha} particles per laser shot. This constitutes presently the highest yield value normalized to the laser energy on target. The measured fusion yield per proton exceeds the classical expectation of beam-target reactions by up to four orders of magnitude under high proton intensities. This enhancement is attributed to the strong electric fields and nonequilibrium thermonuclear fusion reactions as a result of the new method. Our approach shows opportunities to pursue ignition of aneutronic fusion

Cadmium-Induced Oxidative Stress and Apoptotic Changes in the Testis of Freshwater Crab, Sinopotamon henanense

Cadmium (Cd), one of the most toxic environmental and industrial pollutants, is known to exert gonadotoxic and spermiotoxic effects. In the present study, we examined the toxic effect of Cd on the testis of freshwater crab, Sinopotamon henanense. Crabs were exposed to different Cd concentrations (from 0 to 116.00 mg·L−1) for 7 d. Oxidative stress and apoptotic changes in the testes were detected. The activities of SOD, GPx and CAT initially increased and subsequently decreased with increasing Cd concentrations, which was accompanied with the increase in malondialdehyde (MDA) and H2O2 content in a concentration-dependent manner. Typical morphological characteristic and physiological changes of apoptosis were observed using a variety of methods (HE staining, AO/EB double fluorescent staining, Transmission Electron Microscope observation and DNA fragmentation analysis), and the activities of caspase-3 and caspase-9 were increased in a concentration-dependent manner after Cd exposure. These results led to the conclusion that Cd could induced oxidative damage as well as apoptosis in the testis, and the apoptotic processes may be mediated via mitochondria-dependent apoptosis pathway by regulating the activities of caspase-3 and caspase-9

Transcriptional Profiling of the Dose Response: A More Powerful Approach for Characterizing Drug Activities

The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901) across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Pitted-Ground Volcanoes on Mercury

On the planet Mercury, pyroclastic deposits formed by explosive volcanism are developed around rimless volcanic pits that are up to dozens of kilometers in diameters. Some pyroclastic deposits on Mercury, however, host no discernable main eruption centers but feature pitted-ground terrains that each consists of many similar sized and irregularly shaped pits. Individual pits are usually much smaller and shallower than typical volcanoes on Mercury. The origin of these landforms is unknown, but it is indicative of styles of volcanism on Mercury and/or post-volcanic modifications. Here, we investigate the possible origin of these peculiar landforms based on their geological context, morphology, geometry, reflectance spectra, and geophysical background. Reflectance spectra of pyroclastic deposits around such volcanoes are comparable with those erupted from typical volcanic pits on Mercury, suggesting a genetic relation between these pitted-ground terrains with explosive volcanism, and the source magma might have similar compositions. Pitted-ground volcanoes are mainly observed in impact structures, and two cases were formed in high-reflectance smooth plains and channeled lava flows. Most pitted-ground volcanoes are relatively degraded compared with typical volcanoes on Mercury, and some might have been formed in geological recent times judged by both their pristine preservation and crosscutting relationship with impact rays. All pitted-ground volcanoes have unconfined morphology boundaries, and each case is composed by dozens of rimless pits that have similar preservation states and interconnected edges. Such morphological characteristics are unique among volcanic landforms on terrestrial bodies, and they cannot be explained by multiple post-eruption collapses of a main explosive volcano. Pitted-ground volcanoes that are developed in lava flows with the same age have different preservation states, suggesting that the pits were not formed by escape of thermally destabilized volatiles from substrate and subsequent roof collapses. The largest pitted-ground volcano (~3700 km2) is located on the Borealis Planitia, and Bouguer gravity data reveal no larger mass concentration in the subsurface than surrounding terrains, consistent with a paucity of shallow intrusions in the crust of Mercury. Short-term and spatially-clustered explosive eruptions could explain the peculiar morphology and geometry of the pits, suggesting that pits in a given pitted-ground volcano are akin to swarms of monogenetic volcanoes. However, possible magma dynamics for the formation of pitted-ground volcanoes cannot be confirmed until future high-resolution gravity mapping could reveal detailed interior structures beneath these volcanoes. Based on comparative studies with spatially-clustered and similarly aged volcanoes on Earth, we interpret that a combination of pervasive crustal fractures and regional thermal anomaly in the thin mantle of Mercury might have caused such short-term and spatially-clustered explosive eruptions. If this interpretation was true, the heavy degradation state of most pitted-ground volcanoes and the few well-preserved cases are consistent with an overall cooling trend of the mantle, indicating the existence of longstanding heterogeneous thermal structures in the mantle

Physical and Mechanical Properties of Poplar Clones and Rapid Prediction of the Properties by Near Infrared Spectroscopy

In order to understand the physical and mechanical properties of poplar clones, and explore a method for their quick evaluation, the air dry density, modulus of rupture (MOR), modulus of elasticity (MOE), and compressive strength parallel to grains of three new bred poplar clones were explored and the prediction models with the highest accuracy were established by near infrared spectroscopy (NIRs). Clone 50 (Populus deltoides CL. ‘55/65′) had the highest air dry density, MOR, MOE, and compressive strength parallel to grains in the three clones. For clone 50 and 108 (Populus euramericana cv. ‘Guariento’), the mechanical properties of sapwood were better than those of heartwood, and the sapwood of clone 50 also had a better air dry density than that of heartwood. There were significant positive correlations between the air dry density and mechanical properties, with correlation coefficients above 0.68. Prediction models with better effects could be obtained by using information on the cross section for the air dry density and mechanical properties. First derivative+ Savitzky–Golay (S-G) smoothing methods were employed for the air dry density and MOR, and multiple scattering correction (MSC)+ S-G smoothing methods were used when establishing prediction models of MOE and compressive strength parallel to grains