Micro ribonucleic acid-448 regulates zinc finger e-box binding homeobox 1 to inhibit the growth of breast cancer cells and increase their sensitivity to chemotherapy

Objective: This study aimed to investigate the effect of Zinc Finger E-box Binding Homeobox 1 (ZEB1) regulation by Micro Ribonucleic acid (miR)-448 on Breast Cancer (BC) cells and their sensitivity to chemotherapy. Methods: miR-448 and ZEB1 mRNA levels in BC and normal tissues were detected by qPCR, and ZEB1 protein was detected by Western Blotting (WB). The correlation between miR-448 and tumor metastasis, clinical staging, and ZEB1 expression was analyzed. MCF-7 cells were transfected or co-transfected with the miR-448 mimic, oe-ZEB1, or their negative controls. Changes in miR-448 and ZEB1 expression were detected by qPCR and WB. Cell proliferation was determined by CCK-8 assays, invasion changes were analyzed by Transwell assays, and apoptosis was detected by flow cytometry. Results: miR-448 expression in BC tissues was lower than that in normal tissues, while ZEB1 expression was increased in the former. ZEB1 expression was lower in BC patients with lymph node metastasis than in those without. In patients with clinical stage I–III BC, miR-448 expression decreased with an increase in tumor stage, which was negatively correlated with ZEB1 expression. Upregulation of miR-448 expression can suppress MCF-7 cell proliferation and invasion and promote apoptosis. Upregulation of ZEB1 expression in cells overexpressing miR-448 can partially reverse the inhibition of BC cell growth induced by miR-448. miR-448 can enhance the sensitivity of cells toward paclitaxel and 5-fluorouracil. Conclusions: miR-448 suppresses cell proliferation and invasion and promotes apoptosis by targeting ZEB1. Moreover, it can increase the sensitivity of cells toward paclitaxel and 5-fluorouracil

High quality electron beam generation in a proton-driven hollow plasma wakefield accelerator

Simulations of proton-driven plasma wakefield accelerators have demonstrated substantially higher accelerating gradients compared to conventional accelerators and the viability of accelerating electrons to the energy frontier in a single plasma stage. However, due to the strong intrinsic transverse fields varying both radially and in time, the witness beam quality is still far from suitable for practical application in future colliders. Here we demonstrate efficient acceleration of electrons in proton-driven wakefields in a hollow plasma channel. In this regime, the witness bunch is positioned in the region with a strong accelerating field, free from plasma electrons and ions. We show that the electron beam carrying the charge of about 10% of 1 TeV proton driver charge can be accelerated to 0.6 TeV with preserved normalized emittance in a single channel of 700 m. This high quality and high charge beam may pave the way for the development of future plasma-based energy frontier colliders.Comment: 10 pages, 7 figure

Variations in neonatal mortality, infant mortality, preterm birth and birth weight in England and Wales according to ethnicity and maternal country or region of birth: an analysis of linked national data from 2006 to 2012.

BACKGROUND: Risks of adverse birth outcomes in England and Wales are relatively low but vary across ethnic groups. We aimed to explore the role of mother's country of birth on birth outcomes across ethnic groups using a large population-based linked data set. METHODS: We used a cohort of 4.6 million singleton live births in England and Wales to estimate relative risks of neonatal mortality, infant mortality and preterm birth, and differences in birth weight, comparing infants of UK-born mothers to infants whose mothers were born in their countries or regions of ethnic origin, or elsewhere. RESULTS: The crude neonatal and infant death risks were 2.1 and 3.2 per 1000, respectively, the crude preterm birth risk was 5.6% and the crude mean birth weight was 3.36 kg. Pooling across all ethnic groups, infants of mothers born in their countries or regions of ethnic origin had lower adjusted risks of death and preterm birth, and higher gestational age-adjusted mean birth weights than those of UK-born mothers. White British infants of non-UK-born mothers had slightly lower gestational age-adjusted mean birth weights than White British infants of UK-born mothers (mean difference -3 g, 95% CI -5 g to -0.3 g). Pakistani infants of Pakistan-born mothers had lower adjusted risks of neonatal death (adjusted risk ratio (aRR) 0.84, 95% CI 0.72 to 0.98), infant death (aRR 0.84, 95% CI 0.75 to 0.94) and preterm birth (aRR 0.85, 95% CI 0.82 to 0.88) than Pakistani infants of UK-born Pakistani mothers. Indian infants of India-born mothers had lower adjusted preterm birth risk (aRR 0.91, 95% CI 0.87 to 0.96) than Indian infants of UK-born Indian mothers. There was no evidence of a difference by mother's country of birth in risk of birth outcomes among Black infants, except Black Caribbean infants of mothers born in neither the UK nor their region of origin, who had higher neonatal death risks (aRR 1.71, 95% CI 1.06 to 2.76). CONCLUSION: This study highlights evidence of better birth outcomes among UK-born infants of non-UK-born minority ethnic group mothers, and could inform the design of future interventions to reduce the risks of adverse birth outcomes through improved targeting of at-risk groups

Cardiomyocyte-specific role of miR-24 in promoting cell survival

Cardiomyocyte cell death is a major contributing factor to various cardiovascular diseases and is therefore an important target for the design of therapeutic strategies. More recently, stem cell therapies, such as transplantation of embryonic or induced pluripotent stem (iPS) cell-derived cardiomyocytes, have emerged as a promising alternative therapeutic avenue to treating cardiovascular diseases. Nevertheless, survival of these introduced cells is a serious issue that must be solved before clinical application. We and others have identified a small non-coding RNA, microRNA-24 (miR-24), as a pro-survival molecule that inhibits the apoptosis of cardiomyocytes. However, these earlier studies delivered mimics or inhibitors of miR-24 via viral transduction or chemical transfection, where the observed protective role of miR-24 in cardiomyocytes might have partially resulted from its effect on non-cardiomyocyte cells. To elucidate the cardiomyocyte-specific effects of miR-24 when overexpressed, we developed a genetic model by generating a transgenic mouse line, where miR-24 expression is driven by the cardiac-specific Myh6 promoter. The Myh6-miR-24 transgenic mice did not exhibit apparent difference from their wild-type littermates under normal physiological conditions. However, when the mice were subject to myocardial infarction (MI), the transgenic mice exhibited decreased cardiomyocyte apoptosis, improved cardiac function and reduced scar size post-MI compared to their wild-type littermates. Interestingly, the protective effects observed in our transgenic mice were smaller than those from earlier reported approaches as well as our parallelly performed non-genetic approach, raising the possibility that non-genetic approaches of introducing miR-24 might have been mediated via other cell types than cardiomyocytes, leading to a more dramatic phenotype. In conclusion, our study for the first time directly tests the cardiomyocyte-specific role of miR-24 in the adult heart, and may provide insight to strategy design when considering miRNA-based therapies for cardiovascular diseases

Shared and Distinct Neural Bases of Large- and Small-Scale Spatial Ability: A Coordinate-Based Activation Likelihood Estimation Meta-Analysis

Background: Spatial ability is vital for human survival and development. However, the relationship between large-scale and small-scale spatial ability remains poorly understood. To address this issue from a novel perspective, we performed an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies to determine the shared and distinct neural bases of these two forms of spatial ability.Methods: We searched Web of Science, PubMed, PsycINFO, and Google Scholar for studies regarding “spatial ability” published within the last 20 years (January 1988 through June 2018). A final total of 103 studies (Table 1) involving 2,085 participants (male = 1,116) and 2,586 foci were incorporated into the meta-analysis.Results: Large-scale spatial ability was associated with activation in the limbic lobe, posterior lobe, occipital lobe, parietal lobe, right anterior lobe, frontal lobe, and right sub-lobar area. Small-scale spatial ability was associated with activation in the parietal lobe, occipital lobe, frontal lobe, right posterior lobe, and left sub-lobar area. Furthermore, conjunction analysis revealed overlapping regions in the sub-gyrus, right superior frontal gyrus, right superior parietal lobule, right middle occipital gyrus, right superior occipital gyrus, left inferior occipital gyrus, and precuneus. The contrast analysis demonstrated that the parahippocampal gyrus, left lingual gyrus, culmen, right middle temporal gyrus, left declive, left superior occipital gyrus, and right lentiform nucleus were more strongly activated during large-scale spatial tasks. In contrast, the precuneus, right inferior frontal gyrus, right precentral gyrus, left inferior parietal lobule, left supramarginal gyrus, left superior parietal lobule, right inferior occipital gyrus, and left middle frontal gyrus were more strongly activated during small-scale spatial tasks. Our results further indicated that there is no absolute difference in the cognitive strategies associated with the two forms of spatial ability (egocentric/allocentric).Conclusion: The results of the present study verify and expand upon the theoretical model of spatial ability proposed by Hegarty et al. Our analysis revealed a shared neural basis between large- and small-scale spatial abilities, as well as specific yet independent neural bases underlying each. Based on these findings, we proposed a more comprehensive version of the behavioral model

Organic coating on sulfate and soot particles during late Summer in the Svalbard Archipelago

14 pages, 8 figures, 1 table, supplement https://doi.org/10.5194/acp-19-10433-2019Interaction of anthropogenic particles with radiation and clouds plays an important role in Arctic climate change. The mixing state of aerosols is a key parameter to influence aerosol radiation and aerosol–cloud interactions. However, little is known of this parameter in the Arctic, preventing an accurate representation of this information in global models. Here we used transmission electron microscopy with energy-dispersive X-ray spectrometry, scanning electron microscopy, nanoscale secondary ion mass spectrometry, and atomic forces microscopy to determine the size and mixing state of individual sulfate and carbonaceous particles at 100 nm to 2 µm collected in the Svalbard Archipelago in summer. We found that 74 % by number of non-sea-salt sulfate particles were coated with organic matter (OM); 20 % of sulfate particles also had soot inclusions which only appeared in the OM coating. The OM coating is estimated to contribute 63 % of the particle volume on average. To understand how OM coating influences optical properties of sulfate particles, a Mie core–shell model was applied to calculate optical properties of individual sulfate particles. Our result shows that the absorption cross section of individual OM-coated particles significantly increased when assuming the OM coating as light-absorbing brown carbon. Microscopic observations here suggest that OM modulates the mixing structure of fine Arctic sulfate particles, which may determine their hygroscopicity and optical propertiesThis work was funded by the National Natural Science Foundation of China (41622504, 41575116, 31700475) and the Hundred Talents Program in Zhejiang University. Zongbo Shi acknowledges funding from NERC (NE/S00579X/1)Peer Reviewe

The effect of maternal age and planned place of birth on intrapartum outcomes in healthy women with straightforward pregnancies:secondary analysis of the Birthplace national prospective cohort study

To describe the relationship between maternal age and intrapartum outcomes in 'low-risk' women; and to evaluate whether the relationship between maternal age and intrapartum interventions and adverse outcomes differs by planned place of birth.Prospective cohort study.Obstetric units (OUs), midwifery units and planned home births in England.63 371 women aged over 16 without known medical or obstetric risk factors, with singleton pregnancies, planning vaginal birth.Log Poisson regression was used to evaluate the association between maternal age, modelled as a continuous and categorical variable, and risk of intrapartum interventions and adverse maternal and perinatal outcomes.Intrapartum caesarean section, instrumental delivery, syntocinon augmentation and a composite measure of maternal interventions/adverse outcomes requiring obstetric care encompassing augmentation, instrumental delivery, intrapartum caesarean section, general anaesthesia, blood transfusion, third-degree/fourth-degree tear, maternal admission; adverse perinatal outcome (encompassing neonatal unit admission or perinatal death).Interventions and adverse maternal outcomes requiring obstetric care generally increased with age, particularly in nulliparous women. For nulliparous women aged 16-40, the risk of experiencing an intervention or adverse outcome requiring obstetric care increased more steeply with age in planned non-OU births than in planned OU births (adjusted RR 1.21 per 5-year increase in age, 95% CI 1.18 to 1.25 vs adjusted RR 1.12, 95% CI 1.10 to 1.15) but absolute risks were lower in planned non-OU births at all ages. The risk of neonatal unit admission or perinatal death was significantly raised in nulliparous women aged 40+ relative to women aged 25-29 (adjusted RR 2.29, 95% CI 1.28 to 4.09).At all ages, 'low-risk' women who plan birth in a non-OU setting tend to experience lower intervention rates than comparable women who plan birth in an OU. Younger nulliparous women appear to benefit more from this reduction than older nulliparous women

Joint contribution of socioeconomic circumstances and ethnic group to variations in preterm birth, neonatal mortality and infant mortality in England and Wales: a population-based retrospective cohort study using routine data from 2006 to 2012.

OBJECTIVES: This study aimed to describe the variation in risks of adverse birth outcomes across ethnic groups and socioeconomic circumstances, and to explore the evidence of mediation by socioeconomic circumstances of the effect of ethnicity on birth outcomes. SETTING: England and Wales. PARTICIPANTS: The data came from the 4.6 million singleton live births between 2006 and 2012. EXPOSURE: The main exposure was ethnic group. Socioeconomic circumstances, the hypothesised mediator, were measured using the Index of Multiple Deprivation (IMD), an area-level measure of deprivation, based on the mother's place of residence. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were birth outcomes, namely: neonatal death, infant death and preterm birth. We estimated the slope and relative indices of inequality to describe differences in birth outcomes across IMD, and the proportion of the variance in birth outcomes across ethnic groups attributable to IMD. We investigated mediation by IMD on birth outcomes across ethnic groups using structural equation modelling. RESULTS: Neonatal mortality, infant mortality and preterm birth risks were 2.1 per 1000, 3.2 per 1000 and 5.6%, respectively. Babies in the most deprived areas had 47%-129% greater risk of adverse birth outcomes than those in the least deprived areas. Minority ethnic babies had 48%-138% greater risk of adverse birth outcomes compared with white British babies. Up to a third of the variance in birth outcomes across ethnic groups was attributable to differences in IMD, and there was strong statistical evidence of an indirect effect through IMD in the effect of ethnicity on birth outcomes. CONCLUSION: There is evidence that socioeconomic circumstances could be contributing to the differences in birth outcomes across ethnic groups

Simulation study of a passive plasma beam dump using varying plasma density

A plasma beam dump uses the collective oscillations of plasma electrons to absorb the kinetic energy of a particle beam. In this paper, a modified passive plasma beam dump scheme is proposed using either a gradient or stepped plasma profile to maintain a higher decelerating gradient compared with a uniform plasma. The improvement is a result of the plasma wavelength change preventing the re-acceleration of low energy particles. Particle-in-cell simulation results show that both stepped and gradient plasma profiles can achieve improved energy loss compared with a uniform plasma for an electron bunch of parameters routinely achieved in laser wakefield acceleration