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Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response, with resident microglia and infiltrating macrophages playing pivotal roles. While previous studies have grouped these two cell types together based on similarities in structure and function, an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes. In this study, we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury. Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury, gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed. Regarding macrophages, our findings highlighted abundant communication with other cells, including fibroblasts and neurons. Both pro-inflammatory and neuroprotective effects of macrophages were also identified; the pro-inflammatory effect may be related to integrin ß2 (Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway. These findings were validated by in vivo experiments. This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury, and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.
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Lithium-sulfur (Li-S) batteries enable a promising high-energy-storage system while facing practical challenges regarding lithium dendrites and lithium polysulfides (LiPSs) shuttling. Herein, a fascinating SO3H-functionalized graphdiyne (SOGDY) was developed by grafting SO3H onto GDY to modify the separator in Li-S batteries. It realizes structure-retained material transformation, that is, SOGDY retains the crystalline all-carbon network and uniform subnanopores from the initial GDY. The abundant SO3H and uniform pores create a rapid Li+ transport relay station, benefit rapid Li+ transport and even lithium deposition, and prevent lithium dendrite growth. The spatial obstruction and strong polar adsorption sites from SO3H effectively inhibit LiPS shuttling. Additionally, SOGDY establishes a fast electron-transfer pathway to facilitate the LiPS conversion. The SOGDY/PP separator exhibited steady cycling at 1 mA cm-2 over 3500 h in the Liâ¥Li symmetric battery and achieved outstanding low-temperature and high-rate performance in the Li-S battery with a high initial specific capacity of 804.5 mA h g-1 and a final capacity of 504.9 mA h g-1 after 500 cycles at 3 C and -10 °C. This work demonstrates that introducing a stable all-carbon network and uniform functionalized nanopores is an effective strategy to modify the Li-S battery separator.
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This paper predicts the network security posture of an ICS, focusing on the reliability of Industrial Control Systems (ICSs). Evidence reasoning (ER) and belief rule base (BRB) techniques are employed to establish an ICS network security posture prediction model, ensuring the secure operation and prediction of the ICS. This model first integrates various information from the ICS to determine its network security posture value. Subsequently, through ER iteration, information fusion occurs and serves as an input for the BRB prediction model, which necessitates initial parameter setting by relevant experts. External factors may influence the experts' predictions; therefore, this paper proposes the Projection Equalization Optimization (P-EO) algorithm. This optimization algorithm updates the initial parameters to enhance the prediction of the ICS network security posture through the model. Finally, industrial datasets are used as experimental data to improve the credibility of the prediction experiments and validate the model's predictive performance in the ICS. Compared with other methods, this paper's prediction model demonstrates a superior prediction accuracy. By further comparing with other algorithms, this paper has a certain advantage when using less historical data to make predictions.
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OBJECTIVE: To investigate personal exposures to nitrogen oxides (NOX) and nitrogen di-oxide (NO2) and the influence of baseline personal characteristics, living environment and daily activity patterns of the participants on the exposures among adults over 35 in Tianjin and Shanghai. METHODS: In this panel study, 91 healthy nonsmoking adults aged over 35 from Tianjin and Shanghai participated in our study. The study was conducted in summer and winter. The participants were followed for three times with an interval of at least two weeks. Only participants in Shanghai were followed once in winter because of the COVID-19 pandemic. Twenty-seven participants completed follow-up visits in both seasons. We measured their 24 h personal exposures to NOX and NO2and collected their baseline and time-activity information through questionnaire/diary. The linear mixed model was used to analyze the associations between potential influencing factors and personal NOX and NO2 exposure levels. RESULTS: There were 349 follow-up visits with valid 24 h personal NO2 and NOX exposure measurements in the two cities. The ave-rage 24 h personal exposures to NO2 and NOX (volume fraction) in Tianjin participants were 18.0×10-9 and 26.2×10-9 in summer, and 31.0×10-9 and 54.9×10-9 in winter, respectively; and the average 24 h personal exposures to NO2 and NOX in Shanghai participants were 38.7×10-9 and 100.0×10-9 in summer, and 45.5×10-9 and 139.2×10-9 in winter, respectively. The results of univariate regression analysis showed that their personal NOX exposure levels were significantly associated with city, season, gender, average daily cooking times, and ambient NO2 concentrations measured at fixed-site monitoring stations. In addition to the above factors, the personal NOX exposure levels were also significantly associated with educational level and the personal NO2 exposure levels were also significantly associated with passive smoking, average daily home time, cooking energy type, residential distance from main traffic road, and use of kitchen ventilators. Multivariate regression analysis showed that the personal exposure levels of NO2 and NOX were significantly lower in Tianjin than that in Shanghai, were significantly lower in summer than that in winter, and were significantly and positively associated with ambient NO2 concentrations measured at fixed-site monitoring stations. In addition, personal NOX exposure levels were significantly lower in females than in males, and personal NO2 exposure levels were significantly positively associated with average daily cooking times and significantly inversely associated with average daily home time. For every interquartile range (IQR) increase (12.7×10-9) in ambient NO2, the personal NO2 exposure levels increased by 27.5% (95%CI: 17.0%-38.9%), and personal NOX exposure levels increased by 16.1% (95%CI: 7.1%-25.8%). CONCLUSION: Season, city and ambient NO2 concentrations are significant influencing factors of personal exposure levels of NO2and NOX. At the same time, the personal exposures levels of NO2are also affected by lifestyle factors. Our study provides scientific evidence for making precise air pollution control decisions and reducing the exposure levels of NOX in the population.
Subject(s)
Air Pollutants , Environmental Exposure , Nitrogen Oxides , Seasons , Humans , China/epidemiology , Female , Adult , Male , Nitrogen Oxides/analysis , Air Pollutants/analysis , Middle Aged , COVID-19/epidemiology , Environmental Monitoring , Surveys and Questionnaires , Nitrogen Dioxide/analysisABSTRACT
BACKGROUND: In the context of climate change and urbanization, the temporal variation of the adverse health effect of extreme temperature has attracted increasing attention. METHODS: The meteorological data and the daily death records of mortality from respiratory diseases of 136 Chinese cities were from 2006 to 2019. Heat wave and cold spell were selected as the indicator events of extreme high temperature and extreme low temperature, respectively. The generalized linear model and time-varying distributed lag model were used to perform a two-stage time-series analysis to evaluate the temporal variation of the mortality risk associated with extreme temperature in the total population, sub-populations (sex- and age- specific) and different regions (climatic zone and relative humidity level). RESULTS: During the study period, relative risk (RR) of respiratory mortality associated with heat wave decreased from 1.22 (95 %CI: 1.07-1.39) to 1.13 (95 %CI: 1.01-1.26) in the total population, and RR of respiratory mortality associated with cold spell decreased from 1.30 (95 %CI: 1.14-1.49) to 1.17 (95 %CI: 1.08-1.26). The impact of heat wave reduced in the males (P = 0.044) and in the females as with cold spell (P < 0.001). The respiratory mortality risk of people over 65 associated with cold spell decreased (P = 0.040 for people aged 65-74 and P < 0.001 for people over 75). The effect of cold spell reduced in cities from tropical or arid zone (P = 0.035). The effects of both heat wave and cold spell decreased in cities with the relative humidity in the first quartile (P = 0.046 and 0.010, respectively). CONCLUSION: The impact of heat wave on mortality of respiratory diseases decreased mainly in males and cities with the lowest relative humidity, while the impact of cold spell reduced in females, people over 65 and tropical and arid zone, suggesting adaptation to extreme temperature of Chinese residents to some extent.
Subject(s)
Cities , Respiratory Tract Diseases , Humans , China/epidemiology , Male , Female , Respiratory Tract Diseases/mortality , Climate Change , Middle Aged , Aged , Adult , Child , Child, Preschool , Infant , Hot Temperature/adverse effects , Adolescent , Humidity , Cold Temperature/adverse effectsABSTRACT
This study compared the inter-individual variability in adaptive responses to six weeks of small-sided games (SSG) and short sprint interval training (sSIT) in young basketball players. Thirty well-trained young athletes (age: 16.4 ± 0.6 years; stature: 190 ± 8.4 cm; weight: 84.1 ± 8.2 kg) voluntarily participated and were randomly assigned to SSG (3 sets of 5 min 3v3 on full length (28 m) and half-width (7.5 m) court, with 2 minutes of passive recovery in-between), sSIT (3 sets of 12 × 5 s sprinting with 20 s recovery between efforts and 2 min of rest between sets), or CON (routine basketball-specific technical and tactical drills) groups, each of ten. Before and after the training period, participants underwent a series of laboratory- and field-based measurements to evaluate their maximum oxygen uptake (VÌO2max), first and second ventilatory threshold (VT1 and VT2), oxygen pulse, peak and average power output (PPO and APO), linear speed, change of direction (COD), countermovement jump (CMJ), and vertical jump (VJ). Both SSG and sSIT sufficiently stimulated adaptive mechanisms involved in enhancement of the mentioned variables (p < 0.05). However, sSIT resulted in lower residuals in percent changes in VÌO2max (p = 0.02), O2pulse (p = 0.005), VT1 (p = 0.001), PPO (p = 0.03), and linear speed (p = 0.01) across athletes compared to the SSG. Moreover, sSIT resulted in more responders than SSG in VÌO2max (p = 0.02, φ = 0.500), O2pulse (p = 0.003, φ = 0.655), VT1 (p = 0.003, φ = 0.655), VT2 (p = 0.05, φ = 0.436), and linear speed (p = 0.05, φ = 0.420). Our results indicate that sSIT creates a more consistent level of mechanical and physiological stimulus than SSG, potentially leading to more similar adaptations across team members.
Subject(s)
Adaptation, Physiological , Athletic Performance , Basketball , Oxygen Consumption , Humans , Basketball/physiology , Adolescent , Athletic Performance/physiology , Oxygen Consumption/physiology , Male , High-Intensity Interval Training/methods , Running/physiologyABSTRACT
The risk of cardiovascular and respiratory diseases attributed to satellite-based PM2.5 has been less investigated. In this study, the attributable risk was estimated in an area of Iran. The predicted air PM2.5 using satellite data and a two-stage regression model was used as the predictor of the diseases. The dose-response linkage between the bias-corrected predictor employing a strong statistical approach and the outcomes was evaluated using the distributed lag nonlinear model. We considered two distinct scenarios of PM2.5 for the risk estimation. Alongside the risk, the attributable risk and number were estimated for different levels of PM2.5 by age and gender categories. The cumulative influence of PM2.5 particles on respiratory illnesses was statistically significant at 13-16 µg/m3 relative to the reference value (median), mostly apparent in the middle delays. The cumulative relative risk of 90th and 95th percentiles were 2.03 (CI 95%: 1.28, 3.19) and 2.25 (CI 95%: 1.28, 3.96), respectively. Nearly 600 cases of the diseases were attributable to the non-optimum values of the pollutant during 2017-2022, of which more than 400 cases were attributed to high values range. The predictor's influence on cardiovascular illnesses was along with uncertainty, indicating that additional research into their relationship is needed. The bias-corrected PM2.5 played an essential role in the prediction of respiratory illnesses, and it may likely be employed as a trigger for a preventative strategy.
Subject(s)
Air Pollutants , Cardiovascular Diseases , Particulate Matter , Respiratory Tract Diseases , Humans , Iran/epidemiology , Particulate Matter/analysis , Cardiovascular Diseases/epidemiology , Male , Female , Middle Aged , Adult , Respiratory Tract Diseases/epidemiology , Aged , Young Adult , Adolescent , Child , Air Pollutants/analysis , Child, Preschool , Infant , Risk , Infant, Newborn , Respiration Disorders/epidemiology , Environmental Exposure/analysisABSTRACT
Gastric cancer presents a formidable challenge, marked by its debilitating nature and often dire prognosis. Emerging evidence underscores the pivotal role of tumor stem cells in exacerbating treatment resistance and fueling disease recurrence in gastric cancer. Thus, the identification of genes contributing to tumor stemness assumes paramount importance. Employing a comprehensive approach encompassing ssGSEA, WGCNA, and various machine learning algorithms, this study endeavors to delineate tumor stemness key genes (TSKGs). Subsequently, these genes were harnessed to construct a prognostic model, termed the Tumor Stemness Risk Genes Prognostic Model (TSRGPM). Through PCA, Cox regression analysis and ROC curve analysis, the efficacy of Tumor Stemness Risk Scores (TSRS) in stratifying patient risk profiles was underscored, affirming its ability as an independent prognostic indicator. Notably, the TSRS exhibited a significant correlation with lymph node metastasis in gastric cancer. Furthermore, leveraging algorithms such as CIBERSORT to dissect immune infiltration patterns revealed a notable association between TSRS and monocytes and other cell. Subsequent scrutiny of tumor stemness risk genes (TSRGs) culminated in the identification of CDC25A for detailed investigation. Bioinformatics analyses unveil CDC25A's implication in driving the malignant phenotype of tumors, with a discernible impact on cell proliferation and DNA replication in gastric cancer. Noteworthy validation through in vitro experiments corroborated the bioinformatics findings, elucidating the pivotal role of CDC25A expression in modulating tumor stemness in gastric cancer. In summation, the established and validated TSRGPM holds promise in prognostication and delineation of potential therapeutic targets, thus heralding a pivotal stride towards personalized management of this malignancy.
Subject(s)
Machine Learning , Neoplastic Stem Cells , Stomach Neoplasms , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Humans , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Prognosis , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Gene Expression ProfilingABSTRACT
Monodispersed microspheres play a major role in optical science and engineering, providing ideal building blocks for structural color materials. However, the method toward high solid content (HSC) monodispersed microspheres has remained a key hurdle. Herein, a facile access to harvest monodispersed microspheres based on the emulsion polymerization mechanism is demonstrated, where anionic and nonionic surfactants are employed to achieve the electrostatic and steric dual-stabilization balance in a synergistic manner. Monodispersed poly(styrene-butyl acrylate-methacrylic acid) colloidal latex with 55 wt% HSC is achieved, which shows an enhanced self-assembly efficiency of 280% compared with the low solid content (10 wt%) latex. In addition, Ag-coated colloidal photonic crystal (Ag@CPC) coating with near-zero refractive index is achieved, presenting the characteristics of metamaterials. And an 11-fold photoluminescence emission enhancement of CdSe@ZnS quantum dots is realized by the Ag@CPC metamaterial coating. Taking advantage of high assembly efficiency, easily large-scale film-forming of the 55 wt% HSC microspheres latex, robust Ag@CPC metamaterial coatings could be easily produced for passive cooling. The coating demonstrates excellent thermal insulation performance with theoretical cooling power of 30.4 W m-2, providing practical significance for scalable CPC architecture coatings in passive cooling.
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Satellite-based exposure of fine particulate matters has been seldom used as a predictor of mortality. PM2.5 was predicted using Aerosol Optical Depths (AOD) through a two-stage regression model. The predicted PM2.5 was corrected for the bias using two approaches. We estimated the impact by two different scenarios of PM2.5 in the model. We statistically found different distributions of the predicted PM2.5 over the region. Compared to the reference value (5 µg/m3), 90th and 95th percentiles had significant adverse effect on total mortality (RR 90th percentile:1.45; CI 95%: 1.08-1.95 and RR 95th percentile:1.53; CI 95%: 1.11-2.1). Nearly 1050 deaths were attributed to any range of the air pollution (unhealthy range), of which more than half were attributed to high concentration range. Given the adverse effect of extreme values compared to the both scenarios, more efforts are suggested to define local-specific reference values and preventive strategies.
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BACKGROUND: Arterial stiffness (AS) is an important predicting factor for cardiovascular disease. However, no epidemiological studies have ever explored the mediating role of biomarkers in the association between ozone and AS, nor weather fish oil modified such association. METHODS: Study participants were drawn from the UK biobank, and a total of 95,699 middle-aged and older adults were included in this study. Ozone was obtained from Community Multiscale Air Quality (CMAQ) model matched to residential addresses, fish oil from self-reported intake, and arterial stiffness was based on device measurements. First, we applied a double robust approach to explore the association between ozone or fish oil intake and arterial stiffness, adjusting for potential confounders at the individual and regional levels. Then, how triglycerides, apolipoprotein B (Apo B)/apolipoprotein A (ApoA) and non-high-density lipoprotein cholesterol (Non-HDL-C) mediate the relationship between ozone and AS. Last, the modifying role of fish oil was further explored by stratified analysis. RESULTS: The mean age of participants was 55 years; annual average ozone exposure was associated with ASI (beta:0.189 [95%CI: 0.146 to 0.233], P < 0.001), and compared to participants who did not consume fish oil, fish oil users had a lower ASI (beta: 0.061 [95%CI: -0.111 to -0.010], P = 0.016). The relationship between ozone exposure and AS was mediated by triglycerides, ApoB/ApoA, and Non-HDL-C with mediation proportions ranging from 10.90% to 18.30%. Stratified analysis showed lower estimates on the ozone-AS relationship in fish oil users (P = 0.011). CONCLUSION: Ozone exposure was associated with higher levels of arterial stiffness, in contrast to fish oil consumption, which showed a protective association. The association between ozone exposure and arterial stiffness was partially mediated by some biomarkers. In the general population, fish oil consumption might provide protection against ozone-related AS.
Subject(s)
Fish Oils , Ozone , Vascular Stiffness , Humans , Ozone/analysis , Ozone/adverse effects , Middle Aged , Fish Oils/administration & dosage , Male , Female , Vascular Stiffness/drug effects , Aged , Dietary Supplements , Air Pollutants/analysis , United Kingdom , Triglycerides/bloodABSTRACT
INTRODUCTION: Despite the high morbidity and mortality, the effective therapies for heart failure with preserved fraction (HFpEF) are limited as the poor understand of its pathophysiological basis. OBJECTIVE: This study was aimed to characterize the cellular heterogeneity and potential mechanisms of HFpEF at single-cell resolution. METHODS: An HFpEF mouse model was induced by a high-fat diet with N-nitro-L-arginine methyl ester. Cells from the hearts were subjected to single-cell sequencing. The key protein expression was measured with Immunohistochemistry and immunofluorescence staining. RESULTS: In HFpEF hearts, myocardial fibroblasts exhibited higher levels of fibrosis. Furthermore, an increased number of fibroblasts differentiated into high-metabolism and high-fibrosis phenotypes. The expression levels of genes encoding certain pro-angiogenic secreted proteins were decreased in the HFpEF group, as confirmed by bulk RNA sequencing. Additionally, the proportion of the endothelial cell (EC) lineages in the HFpEF group was significantly downregulated, with low angiogenesis and high apoptosis phenotypes observed in these EC lineages. Interestingly, the fibroblasts in the HFpEF heart might cross-link with the EC lineages via over-secretion of ANGPTL4, thus displaying an anti-angiogenic function. Immunohistochemistry and immunofluorescence staining then revealed the downregulation of vascular density and upregulation of ANGPTL4 expression in HFpEF hearts. Finally, we predicted ANGPTL4as a potential druggable target using DrugnomeAI. CONCLUSION: In conclusion, this study comprehensively characterized the angiogenesis impairment in HFpEF hearts at single-cell resolution and proposed that ANGPTL4 secretion by fibroblasts may be a potential mechanism underlying this angiogenic abnormality.
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Rechargeable lithium (Li) metal batteries face challenges in achieving stable cycling due to the instability of the solid electrolyte interphase (SEI). The Li-ion solvation structure and its desolvation process are crucial for the formation of a stable SEI on Li metal anodes and improving Li plating/stripping kinetics. This research introduces an interfacial desolvation coating technique to actively modulate the Li-ion solvation structure at the Li metal interface and regulate the participation of the electrolyte solvent in SEI formation. Through experimental investigations conducted using a carbonate electrolyte with limited compatibility to Li metal, the optimized desolvation coating layer, composed of 12-crown-4 ether-modified silica materials, selectively displaces strongly coordinating solvents while simultaneously enriching weakly coordinating fluorinated solvents at the Li metal/electrolyte interface. This selective desolvation and enrichment effect reduce solvent participation to SEI and thus facilitate the formation of a LiF-dominant SEI with greatly reduced organic species on the Li metal surface, as conclusively verified through various characterization techniques including XPS, quantitative NMR, operando NMR, cryo-TEM, EELS, and EDS. The interfacial desolvation coating technique enables excellent rate cycling stability (i.e., 1C) of the Li metal anode and prolonged cycling life of the Li||LiCoO2 pouch cell in the conventional carbonate electrolyte (E/C 2.6 g/Ah), with 80% capacity retention after 333 cycles.
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Background: Stroke and dementia are the leading causes of neurological disease burden. Detrimental effects of air pollution on both conditions are increasingly recognised, while the impacts on the dynamic transitions have not yet been explored, and whether critical time intervals exist is unknown. Methods: This prospective study was conducted based on the UK Biobank. Annual average air pollution concentrations at baseline year 2010 estimated by land-use regression models were used as a proxy for long-term air pollution exposure. Associations between multiple air pollutants (PM2.5, PM2.5-10, and NO2) indicated by air pollution score and the dynamic transitions of stroke and dementia were estimated, and the impacts during critical time intervals were explored. The date cutoff of this study was February 29, 2020. Findings: During a median follow-up of 10.9 years in 413,372 participants, 6484, 3813, and 376 participants developed incident stroke, dementia, and comorbidity of stroke and dementia. For the overall transition from stroke to comorbid dementia, the hazard ratio (HR) for each interquartile range (IQR) increase in air pollution score was 1.38 (95% CI, 1.15, 1.65), and the risks were limited to two time intervals (within 1 year and over 5 years after stroke). As for the transition from dementia to comorbid stroke, increased risk was only observed during 2-3 years after dementia. Interpretation: Our findings suggested that air pollution played an important role in the dynamic transition of stroke and dementia even at concentrations below the current criteria. The findings provided new evidence for alleviating the disease burden of neurological disorders related to air pollution during critical time intervals. Funding: The State Scholarship Fund of China Scholarship Council.
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Here, a strategy to strengthen d-p orbital hybridization by fabricating π backbonding in the catalyst for efficient lithium polysulfides (LiPSs) conversion is reported. A special interface structure of RuOx quantum dots (QDs) anchored on graphdiyne (GDY) nanoboxes (RuOx QDs/GDY) is prepared to enable strong Ru-to-alkyne π backdonation, which effectively regulates the d-electron structures of Ru centers to promote the d-p orbital hybridization between the catalyst and LiPSs and significantly boosts the catalytic performance of RuOx QDs/GDY. The strong affinity with Li ions and fast Li-ion diffusion of RuOx QDs/GDY also enable ultrastable Li metal anodes. Thus, S@RuOx QDs/GDY cathodes exhibit excellent cycling performance under harsh conditions, and Li@RuOx QDs/GDY anodes show an ultralong cycling life over 8800 h without Li dendrite growth. Lithium-sulfur (Li-S) full cells with S@RuOx QDs/GDY cathodes and Li@RuOx QDs/GDY anodes can deliver an impressive areal capacity of 17.8 mA h cm-2 and good cycling stability under the practical conditions of low negative-to-positive electrode capacity (N/P) ratio (N/P = 1.4), lean electrolyte (E/S = 3 µL mg-1 ), and high S mass loading (15.4 mg cm-2 ).
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BACKGROUND: Stroke and dementia are major neurological disorders that contribute significantly to disease burden and are interlinked in terms of risk. Nevertheless, there is currently no study investigating the influence of residential greenspace on the trajectory of these neurological disorders. METHODS: This longitudinal study utilized data from the UK Biobank. Exposure to residential greenspace was measured by the percentage of total greenspace coverage within a 300-meter buffer zone surrounding the participants' residences. A multistate model was employed to illustrate the trajectory of major neurological disorders, and a piecewise Cox regression model was applied to explore the impact of residential greenspace on different time courses of disease transitions. RESULTS: With 422,649 participants and a median follow-up period of 12.5 years, 8568 (2.0 %), 5648 (1.3 %), and 621 (0.1 %) individuals developed incident stroke, dementia, and comorbidity of both conditions, respectively. An increase in residential greenspace by one interquartile range was associated with reduced risks of transitions from baseline to stroke, dementia, and death, as well as from stroke to comorbidity. The corresponding hazard ratios (HRs) were 0.967 (95 % CI: 0.936, 0.998), 0.928 (0.892, 0.965), 0.925 (0.907, 0.942), and 0.799 (0.685, 0.933), respectively. Furthermore, the protective effect of residential greenspace on the transition from stroke or dementia to comorbidity was particularly pronounced within the first year and over 5 years after stroke and during the 2 to 3 years after dementia onset, with HRs of 0.692 (0.509, 0.941), 0.705 (0.542, 0.918), and 0.567 (0.339, 0.949), respectively. CONCLUSION: This study observed a protective role of residential greenspace in the trajectory of major neurological disorders and contributed to identifying critical progression windows. These findings underscore the significance of environment-health interactions in the prevention of neurological disorders.
Subject(s)
Dementia , Stroke , Humans , Longitudinal Studies , UK Biobank , Biological Specimen Banks , Parks, Recreational , Stroke/epidemiology , Dementia/epidemiologyABSTRACT
BACKGROUND: Evidence linking ozone to depression and anxiety disorders remains sparse and results are heterogeneous. It remains unknown whether omega-3 fatty acid, or genetic susceptibility of mental disorders modify the impacts of ozone. The aim is to assess the associations of ambient ozone with depression and anxiety, and further explore the potential modification effects of omega-3 fatty acid and genetic susceptibility. METHODS: In total of 257,534 participants were enrolled from 2006 to 2010 and followed up to 2016. Depression and anxiety were assessed using mental health questionnaires, primary care records and hospital admission records. The annual average concentrations of ozone were calculated and linked to individuals by home address. Dietary intake and plasma concentration were selected to reflect levels of omega-3 fatty acid. Polygenetic risk scores were selected to reflect genetic susceptibility. We examined the associations of ozone and incident mental disorders, and potential modification of omega-3 fatty acid and genetic susceptibility. RESULTS: Incidences of depression (N = 6957) and anxiety (N = 6944) was associated with increase of ozone. Higher levels of omega-3 fatty acid might attenuate the ozone related depression risk. However, the modification effects of genetic susceptibility were not found. CONCLUSIONS: Long-term exposure to ambient ozone increase the risk of mental disorders among the middle aged and older adults, and omega-3 fatty acid could reduce the adverse effects of ozone on mental health. Higher intake of omega-3 fatty acid is a potential strategy to prevent the risks caused by ozone on public mental health.
Subject(s)
Fatty Acids, Omega-3 , Mental Disorders , Ozone , Middle Aged , Humans , Aged , Ozone/toxicity , UK Biobank , Biological Specimen Banks , Mental Disorders/chemically induced , Mental Disorders/epidemiology , Genetic Predisposition to DiseaseABSTRACT
The fast-charging capability of rechargeable batteries is greatly limited by the sluggish ion transport kinetics in anode materials. Here we develop an iodized polyacrylonitrile (I-PAN) anode that can boost the bulk/interphase lithium (Li)-ion diffusion kinetics and accelerate Li-ion desolvation process to realize high-performance fast-charging Li-ion batteries. The iodine immobilized in I-PAN framework expands ion transport channels, compresses the electric double layer, and changes the inner Helmholtz plane to form LiF/LiI-rich solid electrolyte interphase layer. The dissolved iodine ions in the electrolyte self-induced by the interfacial nucleophilic substitution of PF6 - not only promote the Li-ion desolvation process, but also reuse the plated/dead Li formed on the anode under fast-charging conditions. Consequently, the I-PAN anode exhibits a high capacity of 228.5â mAh g-1 (39 % of capacity at 0.5â A g-1 delivered in 18 seconds) and negligible capacity decay for 10000â cycles at 20â A g-1 . The I-PAN||LiNi0.8 Co0.1 Mn0.1 O2 full cell shows excellent fast-charging performance with attractive capacities and negligible capacity decay for 1000â cycles at extremely high rates of 5â C and 10â C (1â C=180â mA g-1 ). We also demonstrate high-performance fast-charging sodium-ion batteries using I-PAN anodes.
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AIMS: The purpose of this study was to evaluate the role of the NLRP3-inflammasome in heart failure with preserved ejection fraction (HFpEF). MAIN METHODS: Serum inflammatory cytokines were detected in patients with heart failure. Correlation analysis was performed to investigate the relationship between serum inflammatory cytokines and left ventricular diastolic function. A 'two-hit' (metabolic stress and mechanical stress) mouse model of HFpEF was established. Furthermore, MCC950 was used to determine the role of NLRP3-inflammasome inhibition in cardiac and pulmonary artery remodelling in HFpEF mice. KEY FINDINGS: Compared with heart failure patients with reduced ejection fraction, patients with HFpEF have significantly elevated serum inflammatory cytokine levels. Serum NLRP3 and interleukin-1ß levels were positively correlated with the diastolic function of HFpEF. In the HFpEF mouse model, the inhibition of the NLRP3-inflammasome by MCC950 improved exercise intolerance, glucose intolerance, and left ventricular diastolic function, but had no significant effect on systolic function. Meanwhile, MCC950 attenuated the release of inflammatory cytokines, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, the potential protective effects of MCC950 are achieved by inhibiting activation of the NLRP3-IL-1ß pathway and cascade expansion of downstream inflammatory cytokines. Additionally, the inhibition of NLRP3-inflammasome by MCC950 reduced pulmonary artery pressure and improved pulmonary artery remodelling in HFpEF. SIGNIFICANCE: The NLRP3-inflammasome plays a considerable role in inflammation and cardiac and pulmonary artery remodelling in HFpEF by activating the cascade reaction of inflammatory cytokines. This study is the first to comprehensively elucidate the role of the NLRP3-inflammasome in HFpEF, and will provide reference for future study.
Subject(s)
Heart Failure , Inflammasomes , Humans , Mice , Animals , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Heart Failure/drug therapy , Sulfones/pharmacology , Sulfones/therapeutic use , Stroke Volume/physiology , Pulmonary Artery/metabolism , Sulfonamides/pharmacology , Disease Models, Animal , CytokinesABSTRACT
PURPOSE: To date, no study has demonstrated the role of transdermal 17ß-estradiol + norethisterone acetate on all of the risk factors for cardiovascular disease in postmenopausal women. To overcome this knowledge gap, a systematic review and meta-analysis were conducted to determine the effects of this combination treatment on BMI, body weight, waist/hip ratio, fibrinogen, factor VII, lipoprotein(a), fasting blood sugar, insulin, HbA1c, TG, LDL-C, HDL-C, and TC in postmenopausal women. METHODS: PubMed/Medline, SCOPUS, Web of Science, Embase, and Google Scholar were searched for relevant articles published between the inception of each database and April 6, 2023. The sample size and mean (SD) were used to calculate overall effect size using a random-effects model. FINDINGS: A total of 10 articles with 14 arms were included in the meta-analysis. On pooled analysis of effect size, fibrinogen (weighted mean difference [WMD], -0.18 g/L; 95% CI, -0.25 to -0.10), factor VII (WMD, -9.58; 95% CI, -12.51 to -6.64), LDL-C (WMD, -13.09 mg/dL; 95% CI, -18.48 to -7.71), and TC (WMD, -12.61 mg/dL; 95% CI, -18.11 to -7.12) were significantly affected with the use of transdermal 17ß-estradiol + norethisterone acetate (all, P < 0.001), but effects on lipoprotein(a), TG, HDL-C, fasting blood sugar, insulin, HbA1c, BMI, body weight, and waist/hip ratio were not significant. IMPLICATIONS: Based on the findings from the present systematic review and meta-analysis, it was concluded that transdermal administration of 17ß-estradiol + norethisterone acetate had beneficial impacts on fibrinogen, factor VII, LDL-C, and TC, suggesting a possible application in the reduction of cardiovascular disease risk.