Role of Sprouty2 in prostate carcinogenesis

Prostate cancer (PC) is the most common cancer in men. In the UK alone, there are over 30,000 men diagnosed with PC every year. Loss of SPRY2 and activation of receptor tyrosine kinases are common events in PC. However, the molecular basis of their interaction and clinical impact remains to be fully examined. SPRY2 loss may functionally synergise with aberrant cellular signalling to drive PC and to promote treatment resistant disease. Using a combination of in vitro, pre-clinical in vivo models and clinical PC, this thesis shows the impact of SPRY2 loss upon activation of the ErbB signalling system via a positive feedback regulation of the ErbB-PI3K/AKT cascade. Loss of SPRY2 resulted in hyper-activation of PI3K/AKT signalling to drive proliferation and invasion by enhanced internalisation of EGFR/HER2 and their sustained localisation and signalling at the early endosome in a PTEN-dependent manner. This involves activation of p38 MAPK by PI3K to facilitate clathrin-mediated ErbB receptor endocytosis. Furthermore, this thesis suggests a critical role of PI3K/AKT in PC whereby in vitro and in vivo inhibition of PI3K suppresses proliferation and invasion, supporting PI3K/AKT as a target for therapy particularly in patients with PTEN-haploinsufficiency, low SPRY2 and ErbB expressing tumours. In conclusion, SPRY2 is an important tumour suppressor in PC; its loss drives the PI3K/AKT pathway via functional interaction with the ErbB system

Neighbourhood satisfaction in rural resettlement residential communities: the case of Suqian, China

Against the background of large-scale urbanisation and rural land expropriation, rural resettlement residential housing has been built to accommodate local rural residents in the peripheral areas of China. To explore the context-specific policy implications for improving neighbourhood satisfaction (NS) of residents in rural resettlement residential communities (RRRCs), this paper examines the determinants of NS, and their spatial effects, in rural resettlement residential neighbourhoods using Suqian, in Jiangsu Province, as a case study. This study contributes to the current literature in two ways: it constitutes the first attempt to examine NS among RRRCs; second, our spatial model helps to gain further understanding of horizontal and vertical spatial dependence effects. Our results indicate that income, gender, age, family structure, number of years living in a community, transport and architectural age all have significant effects on NS in RRRCs

Perceived sustainable urbanization based on geographically hierarchical data structures in Nanjing, China

Concentrating on geographically hierarchical data structures and using large-scale satisfaction survey data in Nanjing, this study employs Bayesian spatial multilevel model (MLM) to evaluate Nanjing’s perceived sustainable urbanization. In this study, we consider the geographically hierarchical data structures and the city’s individual perceptions of sustainable urbanization to explore the effect of environment and self-rated health on perceived sustainable urbanization, controlling for individual sociodemographic attributes and household. Through clarifying the spatial dependence and heterogeneity, this paper provides a flexible framework for assessing sustainable urbanization and dealing with the geographical hierarchical data. In particular, by drawing on existing studies, our questionnaire is more representative of the overall characteristics of Nanjing’s population than census data, which can be helpful for understanding whether urbanization is sustainable from individual perspective and further for correcting practices. Based on a survey of 10,077 questionnaires, this paper finds the geographically hierarchical data structures have significantly influenced the evaluation of sustainable urbanization, and the Bayesian spatial MLM is an effective tool for evaluating China’s sustainable urbanization. In particular, this paper takes spatial effects into consideration and compares the geographically hierarchical data. Results show that spatial patterns significantly influence the assessment of sustainable urbanization, and perceived pollution, age, education level, and income are the four key factors influencing individual perceived sustainable urbanization

Intra-Urban Levels, Spatial Variability, Possible Sources and Health Risks of PM2.5 Bound Phthalate Esters in Xi'an

Phthalate esters (PAEs) are abundant semi-volatile organic compounds in fine particulate. PM2.5 bound PAEs can inhale into the body with breath, which can cause negative effects to human health. In this study, total of 266 PM2.5 samples dispersed from nineteen communities in Xi'an, were collected at December, 2013, the heavy pollution periods. Most of them are from residential areas, and four of them are in universities. Much high levels of PAEs were obtained in this study, which were from 271.7 to 2134 ng m(-3) (952.6 ng m(-3) on average). DEHP was the dominant species, with an average of 402.4 ng m(-3), and attributed for 42.2% of the total PAEs, followed by BBZP (146.8 ng m(-3) on average) and accounted for 15.4% of the total PAEs. Relative humidity and ventilation coefficient are the two meteorological factors affect the PAEs pollutions during the sampling periods. PAEs showed a declined trend from the urban to suburban. The principal component analysis (PCA) investigated that the release from plasticizer using in vinyl flooring, inks, synthetic leather, adhesives, and food contact wrapping; and emissions from cosmetics and personal care products, varnish, and volatilization from solid waste landfill or sewage sludge from wastewater treatment plant are the main sources for PAEs (86.8% of total PAEs). The daily inhalation and cancer risk assessment displayed that possible risk for all age group persons in this area, and infants are the most susceptible population

Development and validity of a mentally-passive and mentally-active sedentary time questionnaire in nursing college students

ObjectiveThis study aimed to develop and validate a questionnaire to evaluate nursing college students’ mentally-passive and mentally-active sedentary time (M-PAST) in China.MethodsAn initial M-PAST questionnaire with mentally-passive and mentally-active sedentary behaviors was developed with content validity undertaken through a consensus panel and pilot test where a convenience sample of six nursing students was recruited to assess the relevance, comprehensiveness, and comprehensibility of the refined questionnaire after expert panelists’ responses. A cross-sectional online survey using a self-reported questionnaire was distributed to nursing students by email and then conducted using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to assess the construct validity of the M-PAST questionnaire and factor structures. Finally, the criterion validity was examined by exploring the associations between the M-PAST and the IPAQ sitting time, psychological distress, and insomnia.ResultsEight items regarding learning and leisure were included in the final version of the M-PAST questionnaire. A group of 650 nursing college students in China completed the study. Principal component analysis revealed two factors (i.e., mentally-passive and mentally-active sedentary behaviors), which explained 41.98% of the variance contributing to the questionnaire. The CFA reached the adaptive standard. Cronbach’s α ranged from 0.730 to 0.742. The correlations between M-PAST and IPAQ total sitting time were significant (p < 0.01, r = 0.125–0.396). Mentally-passive sedentary time was associated with psychological distress and insomnia (p < 0.01, r = 0.078–0.163), while no significant associations were found in mentally-active sedentary behaviors.Conclusion and implications for practiceThe M-PAST questionnaire appears to be a reliable and valid tool that reported both mentally-passive and mentally-active sedentary behaviors in nursing college students in China. However, future studies may need to further examine its validity among international nursing college students. This study further confirmed that mentally-passive sedentary behavior was positively associated with psychological distress and insomnia. Effective strategies are needed to reduce nursing college students’ mentally-passive sedentary time to improve their health and wellbeing in China

Next Generation-Targeted Amplicon Sequencing (NG-TAS): an optimised protocol and computational pipeline for cost-effective profiling of circulating tumour DNA

Cancer; Computational pipeline; Deep sequencingCàncer; Segmentació computacional; SeqüenciacióCáncer; Segmentación computacional; SecuenciaciónCirculating tumour DNA (ctDNA) detection and monitoring have enormous potential clinical utility in oncology. We describe here a fast, flexible and cost-effective method to profile multiple genes simultaneously in low input cell-free DNA (cfDNA): Next Generation-Targeted Amplicon Sequencing (NG-TAS). We designed a panel of 377 amplicons spanning 20 cancer genes and tested the NG-TAS pipeline using cell-free DNA from two HapMap lymphoblastoid cell lines. NG-TAS consistently detected mutations in cfDNA when mutation allele fraction was > 1%. We applied NG-TAS to a clinical cohort of metastatic breast cancer patients, demonstrating its potential in monitoring the disease. The computational pipeline is available at https://github.com/cclab-brca/NGTAS_pipelin

Revealing unusual bandgap shifts with temperature and bandgap renormalization effect in phase-stabilized metal halide perovskites

Hybrid organic-inorganic metal halide perovskites are emerging materials in photovoltaics, whose bandgap is one of the most crucial parameters governing their light harvesting performance. Here we present temperature and photocarrier density dependence of the bandgap in two phase-stabilized perovskite thin films (MA0.3FA0.7PbI3 and MA0.3FA0.7Pb0.5Sn0.5I3) using photoluminescence and absorption spectroscopy. Contrasting bandgap shifts with temperature are observed between the two perovskites. By utilizing X-ray diffraction and in situ high pressure photoluminescence spectroscopy, we show that the thermal expansion plays only a minor role on the large bandgap blueshift due to the enhanced structural stability in our samples. Our first-principles calculations further demonstrate the significant impact of thermally induced lattice distortions on the bandgap widening and reveal that the anomalous trends are caused by the competition between the static and dynamic distortions. Additionally, both the bandgap renormalization and band filling effects are directly observed for the first time in fluence-dependent photoluminescence measurements and are employed to estimate the exciton effective mass. Our results provide new insights into the basic understanding of thermal and charge-accumulation effects on the band structure of hybrid perovskites

Protective Roles of Gadd45 and MDM2 in Blueberry Anthocyanins Mediated DNA Repair of Fragmented and Non-Fragmented DNA Damage in UV-Irradiated HepG2 Cells

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