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Optimizing the energy utilization of nutrients and ensuring maximum benefits are continuous goals for livestock producers. The net energy (NE) value of feed reflects its nutritional value in the precision feeding system. An experiment was conducted to determine the apparent metabolizable energy (AME) and NE values of 3 types of dephenolized cottonseed protein (DCP) for Hy Line Brown hens aged 42 to 45 weeks using the reference diet substitution method. A reference diet based on corn soybean meal was used to meet the nutritional needs of Hy Line Brown laying hens. To render the crude protein and energy values of the 3 test diets similar, 10.5%, 12%, and 16% of the gross energy yielding ingredients from the reference diet were replaced with DCP 1, DCP 2, and DCP 3, respectively. The birds were fed 4 diets during a 7-d adaptation period. After the dietary adaptation period, 2 birds per replicate from each treatment group were placed in an individual open circuit respiratory calorimetry chamber for a 3-d experimental period. Daily O

Photodynamic therapy (PDT) is proved to be a promising modality for clinical cancer treatment. However, it also suffers from a key obstacle in association with its oxygen-dependent nature which greatly limits its effective application against hypoxic tumors. Herein, on the basis of the unique property of calcium peroxide (CaO

Drug-induced liver injury (DILI) is a type of

Recent work by Kephart et al.

Chirality-based nanomaterials, especially semiconductors nanoparticles (NPs), are the emerging research in biomedicine field. Herein, chiral manganese dioxide (L/D-MnO

Summary Background In the context of climate change and deforestation, Brazil is facing more frequent and unprecedented wildfires. Wildfire-related PM2·5 is associated with multiple adverse health outcomes; however, the magnitude of these associations in the Brazilian context is unclear. We aimed to estimate the association between daily exposure to wildfire-related PM2·5 and cause-specific hospital admission and attributable health burden in the Brazilian population using a nationwide dataset from 2000 to 2015. Methods In this nationwide time-series analysis, data for daily all-cause, cardiovascular, and respiratory hospital admissions were collected through the Brazilian Unified Health System from 1814 municipalities in Brazil between Jan 1, 2000, and Dec 31, 2015. Daily concentrations of wildfire-related PM2·5 were estimated using the 3D chemical transport model GEOS-Chem at a 2·0° latitude by 2·5° longitude resolution. A time-series analysis was fitted using quasi-Poisson regression to quantify municipality-specific effect estimates, which were then pooled at the regional and national levels using random-effects meta-analyses. Analyses were stratified by sex and ten age groups. The attributable fraction and attributable cases of hospital admissions due to wildfire-related PM2·5 were also calculated. Findings At the national level, a 10 μg/m3 increase in wildfire-related PM2·5 was associated with a 1·65% (95% CI 1·51–1·80) increase in all-cause hospital admissions, a 5·09% (4·73–5·44) increase in respiratory hospital admissions, and a 1·10% (0·78–1·42) increase in cardiovascular hospital admissions, over 0–1 days after the exposure. The effect estimates for all-cause hospital admission did not vary by sex, but were particularly high in children aged 4 years or younger (4·88% [95% CI 4·47–5·28]), children aged 5–9 years (2·33% [1·77–2·90]), and people aged 80 years and older (3·70% [3·20–4·20]) compared with other age groups. We estimated that 0·53% (95% CI 0·48–0·58) of all-cause hospital admissions were attributable to wildfire-related PM2·5, corresponding to 35 cases (95% CI 32–38) per 100 000 residents annually. The attributable rate was greatest for municipalities in the north, south, and central-west regions, and lowest in the northeast region. Results were consistent for all-cause and respiratory diseases across regions, but remained inconsistent for cardiovascular diseases. Interpretation Short-term exposure to wildfire-related PM2·5 was associated with increased risks of all-cause, respiratory, and cardiovascular hospital admissions, particularly among children (0–9 years) and older people (≥80 years). Greater attention should be paid to reducing exposure to wildfire smoke, particularly for the most susceptible populations. Funding Australian Research Council and Australian National Health and Medical Research Council.

Although obesity reflected by BMI can enhance the association of air pollution with increase blood pressures (BP) and prevalent hypertension in susceptible population, there remains lack evidence on interactive effects of different obesity indices and air pollutants on BP and prevalent hypertension in rural adults. 39,259 individuals were recruited from the Henan Rural Cohort. Concentrations of air pollutants (PM1, PM2.5, PM10 and NO2) were evaluated by a spatio-temporal model based on satellites data. Independent associations of air pollutants and obesity reflected by BMI, WC, WHR, WHtR, BFP and VFI on BP indicators (SBP, DBP, MAP and PP) and prevalent hypertension were analyzed by linear regression and logistic regression models, respectively. Furthermore, their additive effects were quantified by RERI, AP and S. Six obesity indices enhanced the associations of four air pollutants and BP indicators. Individuals with high PM1 concentrations plus obesity classified by BMI, WC, WHR, WHtR, BFP and VFI had a 4.18-fold (95% CI: 3.86, 4.53), 3.58-fold (95% CI: 3.34, 3.84), 3.53-fold (95% CI: 3.28, 3.81), 4.02-fold (95% CI: 3.72, 4.35), 3.89-fold (95% CI: 3.59, 4.23), 3.87-fold (95% CI: 3.62, 4.14) increase in prevalent hypertension, respectively, compared to non-obese individuals with low PM1 concentrations; similar results were observed for combined effect of PM2.5, PM10 or NO2 and obesity indices on prevalent hypertension. The significant values of RERI, AP and S indicated additive effects of air pollutants and obesity indices on hypertension. Obesity amplified the effects of exposure to high levels of air pollutants on increased BP values and prevalent hypertension, implying that obese individuals may be susceptible to elevate BP and prevalent hypertension in relation to air pollution exposure. CLINICAL TRIAL REGISTRATION: The Henan Rural Cohort study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699, http://www.chictr.org.cn/showproj.aspx?proj=11375).

Funder: Natural Environment Research Council, Long-term ozone (O3) exposure may lead to non-communicable diseases and increase mortality risk. However, cohort-based studies are relatively rare, and inconsistent exposure metrics impair the credibility of epidemiological evidence synthetization. To provide more accurate meta-estimations, this study updates existing systematic reviews by including recent studies and summarizing the quantitative associations between O3 exposure and cause-specific mortality risks, based on unified exposure metrics. Cross-metric conversion factors were estimated linearly by decadal observations during 1990-2019. The Hunter-Schmidt random-effects estimator was applied to pool the relative risks. A total of 25 studies involving 226,453,067 participants (14 unique cohorts covering 99,855,611 participants) were included in the systematic review. After linearly unifying the inconsistent O3 exposure metrics , the pooled relative risks associated with every 10 nmol mol-1 (ppbV) incremental O3 exposure, by mean of the warm-season daily maximum 8-h average metric, were as follows: 1.014 with 95% confidence interval (CI) ranging 1.009-1.019 for all-cause mortality; 1.025 (95% CI: 1.010-1.040) for respiratory mortality; 1.056 (95% CI: 1.029-1.084) for COPD mortality; 1.019 (95% CI: 1.004-1.035) for cardiovascular mortality; and 1.074 (95% CI: 1.054-1.093) for congestive heart failure mortality. Insignificant mortality risk associations were found for ischemic heart disease, cerebrovascular diseases, and lung cancer. Adjustment for exposure metrics laid a solid foundation for multi-study meta-analysis, and widening coverage of surface O3 observations is expected to strengthen the cross-metric conversion in the future. Ever-growing numbers of epidemiological studies supported the evidence for considerable cardiopulmonary hazards and all-cause mortality risks from long-term O3 exposure. However, evidence of long-term O3 exposure-associated health effects was still scarce, so more relevant studies are needed to cover more populations with regional diversity.

Background MAP2K1 mutations, otherwise known as MEK mutations, are rare oncogenic alterations that have been implicated in MAPK pathway activation. The impact of MAP2K1 mutations in colorectal cancer on EGFR antibody response has not been characterized. Patients and Methods Antitumor activity was assessed in mouse xenograft models with SW48 cell lines harboring MAP2K1 mutation, and protein expression of the RAS signaling pathway was studied by Western blot analysis. We retrospectively identified patients with MAP2K1-mutated metastatic colorectal cancer patients treated at City of Hope Comprehensive Cancer Center between 2015 and 2020 using next-generation sequencing. Patients’ tumor characteristics, treatment response, and outcome are described. Additional patients with the MAP2K1 mutation were identified from The Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center oncogenomic databases. Results Antitumor activity in mouse xenograft models demonstrated efficacy with combination therapy with EGFR and MEK inhibition with either BRAF or ERK inhibitors. Five patients treated at City of Hope between 2015 and 2020 harbored a MAP2K1 mutation at a frequency of 1%. APC and TP53 were common coalterations. All disease was RAS and BRAF wild type, except 1 case that harbored a concurrent KRAS mutation. Four RAS/BRAF wild-type MAP2K1-mutated patients was treated with anti-EGFR, anti-EGFR + MEK and BRAF inhibitors, and anti-EGFR + ERK inhibitors. All 4 patients experienced disease progression. Conclusion MAP2K1 mutation in colorectal cancer is associated with poor response to EGFR inhibition. EGFR inhibition with or without MEK, BRAF, or ERK inhibitors did not result in any clinical benefit in our limited experience.

The objective of the following study was to investigate the effects of naturally oxidized corn oil on the antioxidant capacity and lipid metabolism of broilers. A total of 450, 1-day-old Arbor Acres male broilers were randomly divided into 5 treatments with 6 replicate cages and 15 birds/cage. The dietary treatment array consisted of ratios of naturally oxidized corn oil to non-oxidized corn oil from 0:100, 25:75, 50:50, 75:25, and 100:0, respectively. Serum, liver, and abdominal fat samples were taken at 42 d. The results showed that the liver organ index, liver catalase (CAT) activity, malondialdehyde (MDA) content, and the serum aspartate aminotransferase (AST) content had significant quadratic relationships with the ratio of naturally oxidized corn oil (P0.05). Inflammatory infiltrating cells appeared in the liver of the 50% and 75% oxidized corn oil group. The percentage of abdominal fat, and serum free fatty acids (FFA) content increased linearly with the increased proportion of oxidized corn oil (P0.05). The mRNA expression of NADH quinone oxidoreductase 1 (NQO-1), nuclear factor kappa B (NF-κB), toll-like receptor-4 (TLR-4), peroxisome proliferators activate receptor-α (PPARα), carnitine acyltransferase (CPT1), and acyl-coenzyme oxidase (ACO) of the liver increased linearly while oxidized corn oil increased in the diet (P0.05). Diets containing 100% oxidized corn oil significantly changed the mRNA expression of liver Caveolin compared with other treatment groups (P0.05). Taken together, this study demonstrated that naturally oxidized corn oil could change liver lipid metabolism and accelerate lipid deposition of broilers by upregulating PPARα.

The projection of excess mortality due to diurnal temperature range (DTR) in future has not been evaluated yet in China. Based on daily cause-specific mortality data from 266 cities in China, this study aimed to examine the association between DTR and mortality, which help project the future mortality burden attributable to DTR by considering the modification effects of altitude and population migration. We first found that every 10 °C increase in the DTR would result in a 3.3 % (95 % confidence interval: 2.6 %-4.1 %) excess risk of non-accidental mortality. The unit risk of DTR-associated cause-specific mortality at moderate or high altitudes was significantly lower than at lower altitudes, especially for cardiovascular disease. Subsequently, DTR-associated excess mortality in 2017 in China was 233,154 deaths (with a population-weighted attributable fraction of 2.9 %). Furthermore, we projected DTR-attributable additional mortality in the future, with the associated mortalities to be 221,860 deaths in 2050-2059 (2050s) and 132,305 deaths in 2090-2099 (2090s), under the SSP1-2.6 scenario. Meanwhile, the regional inequalities were exacerbated by 18 % in 2050s and 13 % in 2090s when considering the modification effects of city altitude. Future population migration would increase excess mortality in most areas in central and southern China, and reduce the disease burden in most areas in eastern, western, and northern China. Our findings underpinned that regional strategies should be adopted to mitigate excess mortality attributable to global climate change.

This study aims to investigate how surrounding greenspace density and proximity were associated with children's lung function. Between 2013 and 2015, spirometry and a parental survey were performed with children from four primary schools in two Chinese cities. Forced expiratory volume in 1 s (FEV

The effects of fine particulate matter (PM) on de novo hypertensive disorders of pregnancy (HDP) were inconsistent during the first and second trimesters. This study aimed to assess the trimester-specific effects of PM

Lack of evidence exists on whether air pollution exposure may affect ovarian reserve, especially for Chinese women.To explore the association between exposure to various air pollutants and anti-Müllerian hormone (AMH), a predictor of ovarian reserve, over different exposure windows in Shandong Province, China.We enrolled 18,878 women who had AMH measurements in the Center for Reproductive Medicine, Shandong University during 2010-2019. Daily average concentrations of ambient particulate matter with diameters ≤1 μm/2.5 μm/10 μm (PMThe level of AMH changed by -8.8% (95% confidence interval (CI): -12.1%, -5.3%), -2.1% (95% CI: -3.5%, -0.6%), -1.9% (95% CI: -3.3%, -0.5%), and -4.5% (95% CI: -7.1%, -1.9%) per 10 μg/mWe found that ovarian reserve was negatively associated with air pollution exposure for women, particularly from the primary to secondary follicle stage. The effect estimate increased by the reduction in the diameter of PMs, which also varied across population sub-groups.

The health and environmental impacts of bushfires results in substantial economic costs to society. The present analysis sought to estimate the burden of bushfires in Australia over 10 years from 2021 to 2030 inclusive. A dynamic model with yearly cycles was constructed to simulate follow-up of the entire Australian population from 2021 to 2030, capturing deaths and years of life lived. Estimated numbers of bushfire-related-deaths, costs of related-hospitalizations, and broader economic costs were derived from published sources. A 5% annual discount rate was applied to all costs incurred and life years lived from 2022 onwards. Over the 10 years from 2021 to 2030, the modelled analysis predicted that 2418 [95% confidence interval (CI) 2412 - 2422] lives would be lost to bushfires, as well as 8590 [95% CI 8573 - 8606] years of life lost (discounted). Healthcare costs arising from deaths for smoke-related conditions, hospitalizations amounted to AUD $110 million [95% CI 91-129 million] (discounted). The impact on gross domestic product (GDP) totaled AUD $17.2 billion. A hypothetical intervention that reduces the impact of bushfires by 10% would save $11 million in healthcare costs and $1.9 billion in GDP. The health and economic burden of bushfires in Australia looms large during 2021 and 2030. This underscores the importance of actions to mitigate bushfire risk. The findings are useful for the future design and delivery and help policy makers to make informed decisions about investment in strategies to reduce the incidence and severity of future bushfires.

Long-term exposure to air pollutants is likely to be associated with mental disorders, but relevant studies remain limited and inconsistent, and evidence to assess causality is particularly lacking, especially in developing countries. In addition, there are few studies on the role of physical activity in this relationship. We investigated the causal relationship between air pollutant exposure and mental health among Chinese adults and whether physical activity could play a positive role in this relationship. Using the balanced panel data for 2014 and 2016 from the China Family Panel Study, a representative Chinese national cohort study, we selected and validated appropriate instrumental variable to explore the causal relationship between air pollution and mental health and explored the moderating effect of physical activity using an instrumental variable fixed effects model (IVFE) in a counterfactual causal inference framework. PM

Bushfire smoke is a major ongoing environmental hazard in Australia. In the summer of 2019-2020 smoke from an extreme bushfire event exposed large populations to high concentrations of particulate matter (PM) pollution. In this study we aimed to estimate the effect of bushfire-related PM of less than 2.5 μm in diameter (PMWe estimated concentrations of PMWithin the three subregions, between 110 and 134 days were identified as extreme bushfire smoke days within the subregions of Sydney. Bushfire-related PMBushfire PM

Temperature fluctuations can affect human health independent of the effect of mean temperature. However, no study has evaluated whether short-term temperature fluctuations could affect DNA methylation.Peripheral blood DNA methylation for 479 female siblings of 130 families were analysed. Gridded daily temperatures data were obtained, linked to each participant's home address, and used to calculate nine different metrics of short-term temperature fluctuations: temperature variabilities (TVs) within the day of blood draw and preceding one to seven days (TV 0-1 to TV 0-7), diurnal temperature range (DTR), and temperature change between neighbouring days (TCN). Within-sibship design was used to perform epigenome-wide association analyses, adjusting for daily mean temperatures, and other important covariates (e.g., smoking, alcohol use, cell-type proportions). Differentially methylated regions (DMRs) were further identified. Multiple-testing comparisons with a significant threshold of 0.01 for cytosine-guanine dinucleotides (CpGs) and 0.05 for DMRs were applied.Among 479 participants (mean age ± SD, 56.4 ± 7.9 years), we identified significant changes in methylation levels in 14 CpGs and 70 DMRs associated with temperature fluctuations. Almost all identified CpGs were associated with exposure to temperature fluctuations within three days. Differentially methylated signals were mapped to 68 genes that were linked to human diseases such as cancer (e.g., colorectal carcinoma, breast carcinoma, and metastatic neoplasms) and mental disorder (e.g., schizophrenia, mental depression, and bipolar disorder). The top three most significantly enriched gene ontology terms were Response to bacterium (TV 0-3), followed by Hydrolase activity, acting on ester bonds (TCN), and Oxidoreductase activity (TV 0-3).Short-term temperature fluctuations were associated with differentially methylated signals across the human genome, which provides evidence on the potential biological mechanisms underlying the health impact of temperature fluctuations. Future studies are needed to further clarify the roles of DNA methylation in diseases associated with temperature fluctuations.

Little evidence exists concerning the associations of greenspace with childhood lipid profiles and dyslipidemias, especially in developing countries and regions. We aimed to investigate the associations of greenspace surrounding schools with lipid levels and dyslipidemia prevalence among Chinese children and teenagers. We obtained baseline information and health data of 10,408 children and teenagers (aged 6-18 years) who studied from 94 schools in China. We measured levels of four blood lipids: triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Dyslipidemias were defined using standard recommendations. Greenness surrounding schools were assessed using two satellite-based greenness indices, Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Vegetation Index (SAVI) at 300-, 500-, and 1000-m circular buffers based on each school's latitude and longitude. We used random forest model combined with meteorological and remote sensing data to estimate air pollution levels surrounding each school. We used generalized linear mixed models to estimate the associations of greenness with lipid levels and dyslipidemias prevalence. We also performed sub-group and mediation analyses. An interquartile range (IQR) increase in NDVI

Summary Background Exposure to temperature variability has been associated with increased risk of mortality and morbidity. We aimed to evaluate whether the association between short-term temperature variability and hospitalisation was affected by local socioeconomic level in Brazil. Methods In this time-series study, we collected city-level socioeconomic data, and daily hospitalisation and weather data from 1814 Brazilian cities between Jan 1, 2000, and Dec 31, 2015. All-cause and cause-specific hospitalisation data was from the Hospital Information System of the Unified Health System in Brazil. City-specific daily minimum and maximum temperatures came from a 0·25° × 0·25° Brazilian meteorological dataset. We represented city-specific socioeconomic level using literacy rate, urbanisation rate, average monthly household income per capita (using the 2000 and 2010 Brazilian census), and GDP per capita (using statistics from the Brazilian Institute of Geography and Statistics for 2000–15), and cities were categorised according to the 2015 World Bank standard. We used quasi-Poisson regression to do time-series analyses and obtain city-specific associations between temperature variability and hospitalisation. We pooled city-specific estimates according to different socioeconomic quartiles or levels using random-effect meta-analyses. Meta-regressions adjusting for demographic and climatic characteristics were used to evaluate the modification effect of city-level socioeconomic indicators on the association between temperature variability and hospitalisation. Findings We included a total of 147 959 243 hospitalisations (59·0% female) during the study period. Overall, we estimated that the hospitalisation risk due to every 1°C increase in the temperature variability in the current and previous day (TV0–1) increased by 0·52% (95% CI 0·50−0·55). For lower-middle-income cities, this risk was 0·63% (95% CI 0·58–0·69), for upper-middle-income cities it was 0·50% (0·47–0·53), and for high-income cities it was 0·39% (0·33–0·46). The socioeconomic inequality in vulnerability to TV0–1 was especially evident for people aged 0–19 years (effect estimate 1·21% [1·11–1·31] for lower-middle income vs 0·52% [0·41–0·63] for high income) and people aged 60 years or older (0·60% [0·50–0·70] vs 0·43% [0·31–0·56]), and for hospitalisation due to infectious diseases (1·62% [1·46–1·78] vs 0·56% [0·30–0·82]), respiratory diseases (1·32% [1·20–1·44] vs 0·55% [0·37–0·74]), and endocrine diseases (1·21% [0·99–1·43] vs 0·32% [0·02–0·62]). Interpretation People living in less developed cities in Brazil were more vulnerable to hospitalisation related to temperature variability. This disparity could exacerbate existing health and socioeconomic inequalities in Brazil, and it suggests that more attention should be paid to less developed areas to mitigate the adverse health effects of short-term temperature fluctuations. Funding None.