Development of an atomic spectra research platform based on a 30-keV electron beam ion trap.

Electron Beam Ion Traps (EBITs) serve as efficient tools for producing and studying highly charged ions. In response to the diagnostic requirements of upcoming magnetic confinement fusion devices, a medium-energy atomic spectra research platform based on a compact EBIT is developed. This platform achieves a central magnetic field of up to 1.0 T, with electron beam currents reaching 20 mA and electron energies up to 30 keV, similar to the electron temperature on fusion reactors. The developed atomic spectra platform successfully provided spectral data for elements such as argon, xenon, iron, and tungsten. This platform stands as a valuable asset for advancing research in nuclear fusion, particularly concerning impurity spectroscopic diagnostics.

Effect of extreme temperatures on asthma hospital visits: Modification by event characteristics and healthy behaviors.

Although ambient temperature has been linked to asthma exacerbation, impacts associated with extreme temperature events remain unclear. This study aims to identify the events characteristics that elevate risk of asthma hospital visits, and to assess whether healthy behavior changes due to the COVID-19 prevention and control policy may modify the relationships. Data of asthma hospital visits from all medical facilities in Shenzhen, China during 2016-2020 were assessed in relation to extreme temperature events using a distributed lag model. Stratified analysis was conducted by gender, age and hospital department to identify susceptible populations. Through events defined by various duration days and temperature thresholds, we explored the modification by events intensity, length, occurrence time and healthy behaviors. The cumulative relative risk of asthma during heat waves compared to other days was 1.06 (95%CI: 1.00-1.13) and for cold spells was 1.17 (95%CI: 1.05-1.30), and that of males and school-aged children were generally higher than other sub-groups. There were significant effects of heat waves and cold spells on asthma hospital visits when the mean temperature was above 90th percentile (30 °C) and below 10th percentile (14 °C) respectively, and the relative risks were higher when events lasted longer, became stronger, occurred in daytime and in early summer or winter. During the healthy behaviors maintaining period, the risk of heat waves increased whilst the risk of cold spells reduced. Extreme temperatures may pose considerable impact on asthma and the health effect can be modified by the event characteristics and anti-epidemic healthy behaviors. Strategies of asthma control should consider the heightened threats of the intense and frequent extreme temperature events in the context of climate change.

Development and preliminary test of a space-resolved vacuum-ultraviolet spectroscopy in EAST.

The impurity radiation from the divertor region of the EAST tokamak is dominantly in the wavelength range of vacuum ultraviolet (VUV) due to the elevated edge electron temperature. A space-resolved VUV spectroscopy is developed to measure impurity radiation in the divertor region. An eagle-type VUV spectrometer with a focal length of 1 m is adopted in this system, equipped with a spherical grating and a charged-coupled device (CCD) detector. The performance of the VUV spectrometer is preliminarily tested on a synchrotron radiation facility. The wavelength calibration is conducted near 65 nm. It is found that the wavelength range observed by the CCD detector is about 11.07 nm around the central wavelength of about 65 nm. With a linear dispersion of 0.0053 nm/pixel, it is possible to measure the ion temperature lower than 20 eV at the edge region by analyzing the Doppler broadening of a carbon line. These test results show that the performance of the VUV spectrometer is capable of measuring divertor radiation and analyzing the ion temperature of edge impurity ions.

A compact electron beam ion trap in support of high-temperature plasma diagnostics based on conduction-cooled superconducting coils.

Spectroscopic diagnostics of future fusion reactor plasmas require information on impurity line emissions, especially for relevant high-Z metal elements (e.g., tungsten). These materials will be widely used as plasma facing components for their high heat tolerance and low sputtering yield. Based on an electron beam ion trap, a compact impurity spectra platform is developed to mimic the high-temperature environment of a fusion reactor. The proposed platform can deliver a focused e-beam at energies over 30 keV using a confining magnetic field of ∼1.0 T generated by two superconducting coils (NbTi). Cooled by a closed-loop cryocooler, the coils can avoid the usage of a complicated cryogenic system involving the handling of liquid helium. For spectroscopic studies of highly charged ions, a spherically curved crystal spectrometer is proposed to measure a wavelength range around 2-4 Å covering the typical wavelength range expected to be emitted by metal ions in a fusion plasma. This paper reports the design and development progress of the platform.

The effect of PCSK9 inhibitors on brain stroke prevention: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes, their effects on brain stroke risk are unclear. The present meta-analysis aimed to evaluate the effects of PCSK9 inhibitors on brain stroke prevention. METHODS AND RESULTS: We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov for research published until December 30, 2020, to find randomized controlled trials (RCTs) of PCSK9 inhibitors for brain stroke prevention. Relative risk (RR) and 95% confidence intervals (CIs) were used to represent the outcomes. Seven RCTs with 57,440 participants, including 29,850 patients treated with PCSK9 inhibitors and 27,590 control participants, were included. PCSK9 inhibitors were associated with significant reductions in total brain stroke risk (RR, 0.77; 95% CI, 0.67-0.88; P < 0.001) and ischemic brain stroke risk (RR, 0.76; 95% CI, 0.66, 0.89; P < 0.001) in comparison with the control group. There was no significant difference in cardiovascular mortality (RR, 0.95; 95% CI, 0.84-1.07; P = 0.382) and the risk of hemorrhagic brain stroke (RR, 1.00; 95% CI, 0.66-1.51; P = 0.999) between patients treated with PCSK9 inhibitors and controls. PCSK9 inhibitors did not significantly increase the incidence of neurocognitive adverse events (RR, 1.02; 95% CI, 0.81-1.29; P = 0.85). Moreover, subgroup analysis showed no difference in cognitive function disorder risks among different PCSK9 inhibitors and treatment times. CONCLUSIONS: PCSK9 inhibitors significantly reduced the risk of total brain stroke and ischemic brain stroke without increasing the risk of brain hemorrhage and neurocognitive impairment.

Climate change, air pollution, and allergic respiratory diseases: a call to action for health professionals.

Rising emissions of greenhouse gases in the atmosphere have warmed the planet substantially and are also accompanied by poor air quality. The increased prevalence of allergic airway disease worldwide can be partially attributed to those global environmental changes. Climate change and air pollution pose adverse impacts on respiratory allergies, and that the mechanisms are complex and interactive. Adverse weather conditions, such as extreme temperatures, can act directly on the respiratory tract to induce allergic respiratory illnesses. Thunderstorms and floods can alter the production and distribution of aeroallergens while wildfires and dust storms increase air pollution, and therefore indirectly enhance health risks. Concentrations of particulate matter and ozone in the air have been projected to increase with climate warming and air stagnation, and the rising temperatures and CO2 increase pollen, molds, and spores, which escalate the risk of allergic respiratory diseases. The synergistic effects of extreme heat and aeroallergens intensify the toxic effect of air pollutants, which in turn augment the allergenicity of aeroallergens. With the Earth's climate change, migration of humans and plants shift the living environments and allergens of susceptible people. Urban residents are exposed to multiple factors while children are sensitive to environmental exposure. Since climate change may pose many unexpected and persistent effects on allergic respiratory diseases, health professionals should advocate for effective mitigation and adaptation strategies to minimize its respiratory health effects.

Climate change, air pollution, and allergic respiratory diseases: a call to action for health professionals / 中华医学杂志(英文版)

Rising emissions of greenhouse gases in the atmosphere have warmed the planet substantially and are also accompanied by poor air quality. The increased prevalence of allergic airway disease worldwide can be partially attributed to those global environmental changes. Climate change and air pollution pose adverse impacts on respiratory allergies, and that the mechanisms are complex and interactive. Adverse weather conditions, such as extreme temperatures, can act directly on the respiratory tract to induce allergic respiratory illnesses. Thunderstorms and floods can alter the production and distribution of aeroallergens while wildfires and dust storms increase air pollution, and therefore indirectly enhance health risks. Concentrations of particulate matter and ozone in the air have been projected to increase with climate warming and air stagnation, and the rising temperatures and CO2 increase pollen, molds, and spores, which escalate the risk of allergic respiratory diseases. The synergistic effects of extreme heat and aeroallergens intensify the toxic effect of air pollutants, which in turn augment the allergenicity of aeroallergens. With the Earth's climate change, migration of humans and plants shift the living environments and allergens of susceptible people. Urban residents are exposed to multiple factors while children are sensitive to environmental exposure. Since climate change may pose many unexpected and persistent effects on allergic respiratory diseases, health professionals should advocate for effective mitigation and adaptation strategies to minimize its respiratory health effects.

Area-Level Walkability and the Geographic Distribution of High Body Mass in Sydney, Australia: A Spatial Analysis Using the 45 and Up Study.

Improving the walkability of built environments to promote healthy lifestyles and reduce high body mass is increasingly considered in regional development plans. Walkability indexes have the potential to inform, benchmark and monitor these plans if they are associated with variation in body mass outcomes at spatial scales used for health and urban planning. We assessed relationships between area-level walkability and prevalence and geographic variation in overweight and obesity using an Australian population-based cohort comprising 92,157 Sydney respondents to the 45 and Up Study baseline survey between January 2006 and April 2009. Individual-level data on overweight and obesity were aggregated to 2006 Australian postal areas and analysed as a function of area-level Sydney Walkability Index quartiles using conditional auto regression spatial models adjusted for demographic, social, economic, health and socioeconomic factors. Both overweight and obesity were highly clustered with higher-than-expected prevalence concentrated in the urban sprawl region of western Sydney, and lower-than-expected prevalence in central and eastern Sydney. In fully adjusted spatial models, prevalence of overweight and obesity was 6% and 11% lower in medium-high versus low, and 10% and 15% lower in high versus low walkability postcodes, respectively. Postal area walkability explained approximately 20% and 9% of the excess spatial variation in overweight and obesity that remained after accounting for other individual- and area-level factors. These findings provide support for the potential of area-level walkability indexes to inform, benchmark and monitor regional plans aimed at targeted approaches to reducing population-levels of high body mass through environmental interventions. Future research should consider potential confounding due to neighbourhood self-selection on area-level walkability relations.

The epithelial zinc transporter ZIP10 epigenetically regulates human epidermal homeostasis by modulating histone acetyltransferase activity.

BACKGROUND: The skin is the first organ that manifests changes in response to zinc deficiency. However, the molecular mechanism underlying how zinc is involved in skin homeostasis, especially its epigenetic regulation, is largely unknown. OBJECTIVES: In this study we demonstrate the importance of zinc levels and the zinc transporter ZIP10 in the epigenetic maintenance of human epidermal homeostasis. METHODS: Adult human skin, including skin appendages, were stained with anti-ZIP10 antibody. Histone acetyltransferase (HAT) activity was assessed after treating human keratinocytes with ZIP10 small interfering (si)RNAs or the zinc chelator TPEN. ZIP10- or HAT-regulated genes were analysed based on limma bioinformatics analysis for keratinocytes treated with ZIP10 siRNAs or a HAT inhibitor, or using a public database for transcription factors. A reconstituted human skin model was used to validate the role of ZIP10 in epidermal differentiation and the functional association between ZIP10 and HAT. RESULTS: ZIP10 is predominantly expressed in the interfollicular epidermis, epidermal appendages and hair follicles. ZIP10 depletion resulted in epidermal malformations in a reconstituted human skin model via downregulation of the activity of the epigenetic enzyme HAT. This decreased HAT activity, resulting from either ZIP10 depletion or treatment with the zinc chelator TPEN, was readily restored by zinc supplementation. Through bioinformatics analysis for gene sets regulated by knockdown of SLC39A10 (encoding ZIP10) and HAT inhibition, we demonstrated that ZIP10 and HATs were closely linked with the regulation of genes related to epidermal homeostasis, particularly filaggrin and metallothionein. CONCLUSIONS: Our study suggests that ZIP10-mediated zinc distribution is crucial for epidermal homeostasis via HATs. Therefore, zinc-dependent epigenetic regulation could provide alternatives to maintaining healthy skin or alleviating disorders with skin barrier defects.

Initial group dietary education compared to individual education in gestational diabetes mellitus management: Do outcomes differ?

AIMS: To assess the effectiveness of Initial Group versus Initial Individual GDM dietary education in terms of insulin requirements and pregnancy outcomes. METHODS: A retrospective audit of clinical data was conducted where English speaking women who received initial education in a group setting (01-2-2012 to 01-2-2014) (Group), were compared to women who received initial individual education with a dietitian (1-2-2010 to 31-1-2012) (Individual), all followed by one individual dietitian appointment. The same dietary information was provided in both settings. Data collected included: attendance rates, insulin requirements, maternal weight gain, and rates of adverse birth outcomes. Data were compared by t-test or Chi-squared test. Multivariable logistic regression analysis was conducted to determine independent predictors of insulin therapy. RESULTS: Of 743 women; (362 Group and 381 Individual), Group women had a lower HbA1c at GDM diagnosis 5.3 ±â€¯0.6% versus 5.5 ±â€¯0.5% (34 ±â€¯6.6 mmol/mol versus 37 ±â€¯5.5 mmol/mol p < 0.0001). There were no other differences in baseline characteristics. More Group women required insulin (42.0% versus 34.6%, p = 0.048). Group education was found to be an independent predictor of insulin therapy (OR = 1.9 [1.29, 2.75] p < 0.001). CONCLUSIONS: Despite adjusting for all known potential confounders, unlike Individual education, Group education remained a significant predictor of insulin therapy (but resulted in similar therapeutic and pregnancy outcomes to Individual education).

Does Walkability Contribute to Geographic Variation in Psychosocial Distress? A Spatial Analysis of 91,142 Members of the 45 and Up Study in Sydney, Australia.

Walkability describes the capacity of the built environment to promote walking, and has been proposed as a potential focus for community-level mental health planning. We evaluated this possibility by examining the contribution of area-level walkability to variation in psychosocial distress in a population cohort at spatial scales comparable to those used for regional planning in Sydney, Australia. Data on psychosocial distress were analysed for 91,142 respondents to the 45 and Up Study baseline survey between January 2006 and April 2009. We fit conditional auto regression models at the postal area level to obtain smoothed "disease maps" for psychosocial distress, and assess its association with area-level walkability after adjusting for individual- and area-level factors. Prevalence of psychosocial distress was 7.8%; similar for low (7.9%), low-medium (7.9%), medium-high (8.0%), and high (7.4%) walkability areas; and decreased with reducing postal area socioeconomic disadvantage: 12.2% (most), 9.3%, 7.5%, 5.9%, and 4.7% (least). Unadjusted disease maps indicated strong geographic clustering of psychosocial distress with 99.0% of excess prevalence due to unobserved and spatially structured factors, which was reduced to 55.3% in fully adjusted maps. Spatial and unstructured variance decreased by 97.3% and 39.8% after adjusting for individual-level factors, and another 2.3% and 4.2% with the inclusions of area-level factors. Excess prevalence of psychosocial distress in postal areas was attenuated in adjusted models but remained spatially structured. Postal area prevalence of high psychosocial distress is geographically clustered in Sydney, but is unrelated to postal area walkability. Area-level socioeconomic disadvantage makes a small contribution to this spatial structure; however, community-level mental health planning will likely deliver greatest benefits by focusing on individual-level contributors to disease burden and inequality associated with psychosocial distress.

The contribution of area-level walkability to geographic variation in physical activity: a spatial analysis of 95,837 participants from the 45 and Up Study living in Sydney, Australia.

BACKGROUND: Individual-level studies support a positive relation between walkable built environments and participation in moderate-intensity walking. However, the utility of this evidence for population-level planning is less clear as it is derived at much finer spatial scales than those used for regional programming. The aims of this study were to: evaluate if individual-level relations between walkability and walking to improve health manifest at population-level spatial scales; assess the specificity of area-level walkability for walking relative to other moderate and vigorous physical activity (MVPA); describe geographic variation in walking and other MVPA; and quantify the contribution of walkability to this variation. METHODS: Data on sufficient walking, sufficient MVPA, and high MVPA to improve health were analyzed for 95,837 Sydney respondents to the baseline survey of the 45 and Up Study between January 2006 and April 2010. We used conditional autoregressive models to create smoothed MVPA "disease maps" and assess relations between sufficient MVPA to improve health and area-level walkability adjusted for individual-level demographic, socioeconomic, and health factors, and area-level relative socioeconomic disadvantage. RESULTS: Within-cohort prevalence of meeting recommendations for sufficient walking, sufficient MVPA, and high MVPA were 31.7 (95% CI 31.4-32.0), 69.4 (95% CI 69.1-69.7), and 56.1 (95% CI 55.8-56.4) percent. Prevalence of sufficient walking was increased by 1.20 (95% CrI 1.12-1.29) and 1.07 (95% CrI 1.01-1.13) for high and medium-high versus low walkability postal areas, and for sufficient MVPA by 1.05 (95% CrI 1.01-1.08) for high versus low walkability postal areas. Walkability was not related to high MVPA. Postal area walkability explained 65.8 and 47.4 percent of residual geographic variation in sufficient walking and sufficient MVPA not attributable to individual-level factors. CONCLUSIONS: Walkability is associated with area-level prevalence and geographic variation in sufficient walking and sufficient MVPA to improve health in Sydney, Australia. Our study supports the use of walkability indexes at multiple spatial scales for informing population-level action to increase physical activity and the utility of spatial analysis for walkability research and planning.

Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling.

The epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein that is regarded as one of the markers for tumor initiating cells (TIC) in human hepatocellular carcinoma (HCC). Much work has been directed towards targeting these TICs as a mean of placing these master regulators of cell proliferation and drug resistance under control. Human bone marrow-derived mesenchymal stem cells are known to exhibit an innate property of tumor tropism. However, the possible relationship between MSC and TIC is not well understood. In this study, we show that MSC migration to HCC can be effectively inhibited by TACE and γ-secretase inhibitors that stop the activation of EpCAM signaling event. Silencing of EpCAM expression through siRNA and antibody approaches also resulted in impaired MSC migration. By contrast, increase levels of EpICD proteins in HCC cells and HCC mouse xenografts resulted in enhanced MSC migration. Taken together, these findings show that MSC is drawn to the more oncogenic population of HCC, and could potentially serve as a cell-based carrier of therapeutic genes to target EpICD-enriched hepatic tumor cells.

Interferon-inducible T-cell alpha chemoattractant (ITAC) induces the melanocytic migration and hypopigmentation through destabilizing p53 via histone deacetylase 5: a possible role of ITAC in pigment-related disorders.

BACKGROUND: Cell migration plays a major role in the immune response and in tumorigenesis. Interferon-inducible T-cell alpha chemoattractant (ITAC) elicits a strong chemotactic response from immune cells. OBJECTIVES: To examine the effect of ITAC on melanocyte migration and pigmentation and its involvement in related disorders, and to investigate potential key players in these processes. METHODS: Human melanocytes or melanoma cells were treated with ITAC and a migration assay was carried out. Global gene expression analysis was performed to find genes regulated by ITAC treatment. The function of key players involved in ITAC-induced cellular processes was addressed using knockdown or overexpression experiments in combination with ITAC treatment. ITAC expression in the inflammation-associated hypopigmentary disorder, vitiligo, was examined. RESULTS: Among CXCR3 ligands, only ITAC induced melanocyte migration. ITAC treatment upregulated the expression of histone deacetylase 5 (HDAC5) and downregulated that of p53, a known target of HDAC5. Through knockdown or overexpression of HDAC5 and p53, we confirmed that HDAC5 mediates ITAC-induced migration by decreasing levels of p53 via deacetylation. In addition, ITAC treatment could decrease pigmentation in a p53- and HDAC5-dependent manner. Finally, the increased migration of human melanoma cells by ITAC treatment and the increased ITAC expression in the epidermis of vitiligo skin were verified. CONCLUSIONS: This study provides in vitro evidence for the migratory and hypopigmentation effects of ITAC on melanocytic cells, gives translational insights into the roles of ITAC in pathological conditions, and suggests that HDAC5 and its substrate p53 are potent targets for regulating ITAC-induced cellular processes.

Downregulation of pigment epithelium-derived factor is associated with increased epithelial-mesenchymal transition in bladder cancer.

BACKGROUND: Pigment epithelium-derived factor (PEDF) has been reported to inhibit angiogenesis in bladder cancer, but whether it modulates epithelial-mesenchymal transition (EMT) remains unknown. METHODS: We have included 68 samples of non-muscle invasive bladder cancer in this study. Immunohistochemistry was performed in all sample sections for expressions of PEDF, SNAI2, Vimentin and E-cadherin, which were quantified and The EMT Index (EMTi) was calculated by Vimentin/E-cadherin. Levels of expression were studied for correlations with clinicopathological parameters. RESULTS: Patients were grouped with high (EMTi≤1) and low (EMTi>1) EMT level for comparisons of clinicopathological parameters. In the univariate analysis, EMT level was shown to be significantly associated with tumor onset and PEDF level, but not with gender, occurrence, stage, grade, or SNAI2 level. Further multivariate analysis revealed that PEDF level was significantly negatively correlated with EMTi independent of other clinicopathological parameters. CONCLUSIONS: Our results indicate that PEDF may serve as a promising novel modality for the treatment of bladder cancer, as it can inhibit not only angiogenesis but also EMT process of bladder cancer.

Realist theory construction for a mixed method multilevel study of neighbourhood context and postnatal depression.

BACKGROUND: We have recently described a protocol for a study that aims to build a theory of neighbourhood context and postnatal depression. That protocol proposed a critical realist Explanatory Theory Building Method comprising of an: (1) emergent phase, (2) construction phase, and (3) confirmatory phase. A concurrent triangulated mixed method multilevel cross-sectional study design was described. The protocol also described in detail the Theory Construction Phase which will be presented here. METHODS: The Theory Construction Phase will include: (1) defining stratified levels; (2) analytic resolution; (3) abductive reasoning; (4) comparative analysis (triangulation); (5) retroduction; (6) postulate and proposition development; (7) comparison and assessment of theories; and (8) conceptual frameworks and model development. THEORY CONSTRUCTION: The stratified levels of analysis in this study were predominantly social and psychological. The abductive analysis used the theoretical frames of: Stress Process; Social Isolation; Social Exclusion; Social Services; Social Capital, Acculturation Theory and Global-economic level mechanisms. Realist propositions are presented for each analysis of triangulated data. Inference to best explanation is used to assess and compare theories. A conceptual framework of maternal depression, stress and context is presented that includes examples of mechanisms at psychological, social, cultural and global-economic levels. Stress was identified as a necessary mechanism that has the tendency to cause several outcomes including depression, anxiety, and health harming behaviours. The conceptual framework subsequently included conditional mechanisms identified through the retroduction including the stressors of isolation and expectations and buffers of social support and trust. CONCLUSION: The meta-theory of critical realism is used here to generate and construct social epidemiological theory using stratified ontology and both abductive and retroductive analysis. The findings will be applied to the development of a middle range theory and subsequent programme theory for local perinatal child and family interventions.