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Background: Non-optimum temperatures are associated with a considerable mortality burden. However, there is a lack of evaluation of labour productivity losses related to premature deaths due to non-optimum temperatures. This study aimed to quantify the labour productivity burden associated with premature deaths related to non-optimum temperatures and explore the potential socio-economic vulnerabilities. Methods: Daily all-cause mortality data were collected from 1,066 locations in 7 countries (Australia, Brazil, Canada, Chile, New Zealand, South Korea, and Thailand). Productivity-Adjusted Life-Year (PALY) loss due to each premature death was calculated to measure the labour productivity loss, by multiplying the years of working life lost by the proportion of the equivalent full-time (EFT) workers. A two-stage times series design and the generalized linear regression model with a quasi-Poisson family were applied to assess the association between non-optimum temperatures and the PALY loss due to premature deaths. Results: We observed a U-shaped relationship between temperature and PALY lost due to premature mortality. We estimated that 2.51% (95% eCI: 2.05%, 2.92%) of PALY losses could be attributed to non-optimal temperatures, with cold-related deaths contributing 1.26% (95% eCI: 0.94%, 1.54%) and heat-related deaths contributing 1.25% (95% eCI: 0.96%, 1.51%). Cold temperature contributed to the most PALYs lost in those aged 45–54 and 55–64, while heat-related losses predominated among the 15–44 age group. We also observed that the fractions of PALY lost attributed to extreme heat were positively associated with the relative deprivation index, while negatively associated with GDP per capita. Conclusion: This multi-country study highlights that non-optimum temperatures led to a considerable labour productivity loss and socioeconomically disadvantaged communities experience greater losses.

Study region: The study region of this paper is the Wusuli River basin, which is comprised of nine sub-basins. The basin is located on the border between China and Russia. Study focus: We investigated the hydrological connectivity of the Wusuli River basin, an international boundary river that has received little attention. The spatial and temporal evolution of hydrological connectivity over the last 38 years was characterized using a geostatistical connectivity function combined with the remote sensing technique. In particular, some key sub-basins were identified to help strengthen China-Russian cooperation on ecological protection of the basin. New hydrological insights for the region: The results show that the hydrological connectivity in the northwestern region of the Wusuli River basin was unstable with several surges from 1984 to 2021. Analyzed from a temporal perspective, the effective range of hydrological connectivity is expanding and connectivity is showing an overall upward trend due to increased fluctuations in rainfall. Analyzed from a spatial perspective, the connectivity of the right bank of the Wusuli River is better than that of the left bank due to the influence of topography. Stable connectivity pathways are a must for efficient hydrological connectivity within a watershed. Another finding is that the capacity of the Wusuli River basin to resist extreme rainfall is weakening.

The optimization design problem of nuclear reactor radiation shield is a typical multi-objective optimization problem with almost 10 sub-objectives and the sub-objectives are always demanded to be under tolerable limits. In this paper, a design method combining multi-objective optimization algorithms with paralleling discrete ordinate transportation code is developed and applied to shield design of the Savannah nuclear reactor. Three approaches are studied for light-weighted and compact design of radiation shield. Comparing with directly optimization with 10 objectives and the single-objective optimization, the approach by setting sub-objectives representing weight and volume as optimization objectives while treating other sub-objectives as constraints has the best performance, which is more suitable to reactor shield design.

Background: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. Objectives: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality. Methods: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates. Results: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0–7 (0.9 °C). An IQR increase in inter-day TV0–7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0–7 and inter-day TV0–7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type. Conclusions: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.

Assessing the association between temperature frequency and mortality can provide insights into human adaptation to local ambient temperatures. We collected daily time-series data on mortality and temperature from 757 locations in 47 countries/regions during 1979–2020. We used a two-stage time series design to assess the association between temperature frequency and all-cause mortality. The results were pooled at the national, regional, and global levels. We observed a consistent decrease in the risk of mortality as the normalized frequency of temperature increases across the globe. The average increase in mortality risk comparing the 10th to 100th percentile of normalized frequency was 13.03% (95% CI: 12.17–13.91), with substantial regional differences (from 4.56% in Australia and New Zealand to 33.06% in South Europe). The highest increase in mortality was observed for high-income countries (13.58%, 95% CI: 12.56–14.61), followed by lower-middle-income countries (12.34%, 95% CI: 9.27–15.51). This study observed a declining risk of mortality associated with higher temperature frequency. Our findings suggest that populations can adapt to their local climate with frequent exposure, with the adapting ability varying geographically due to differences in climatic and socioeconomic characteristics.

Due to the effects of global climate change, the permafrost temperature in the Qinghai-Tibet Plateau (QTP) has rapidly increased over the past decades. The development of thermokarst landforms is one distinctive indicator of permafrost degradation, while the change of the rate of permafrost degradation in recent 10 years has not been systematically investigated in QTP. In this paper, the annual average growth rate (AAGR) of ground deformation, the change of thaw slump areas, and the change of active layer thickness (ALT) of thermokarst landforms are monitored integrating SAR (synthetic aperture radar) and optical images for years 2007 to 2020 in Qilian Mountain, northern QTP. The ground deformation rate and seasonal amplitude were estimated by InSAR method, and the descending and ascending InSAR data are compared the validate the results. Based on the deformation results, AAGR was introduced to evaluate the permafrost degradation degree. Moreover, the ALT were estimated based on the seasonal deformation amplitude and Stefan model. The spatio-temporal characteristics of ground deformation and its relationship with thaw slump and temperature are explored. Experimental results show that the deformation rate increased about 150 % from 2007 to 10 to 2017–20. The maximum AAGR of deformation rate in the study area can reach 20.6 %. The thaw slump area has an obvious trend of expansion from 2009 to 2015, and its distribution agreed well with the deformation map. The ALT results ranged from 0.5 m to 2.8 m, indicating an obvious increase trend from 2007 to 2020. Based on the estimated increased ground deformation, thaw slump area, and ALT, it is inferred that frozen ground was undergoing serious degradation in the last 10 years. This study demonstrates the capability of multi-temporal InSAR in observing the accelerated permafrost thaw-freezing process and monitoring the permafrost parameters.

The optimal allocation of agricultural water and land resources is of great significance in ensuring sustainable food production and economic benefits of farmers. However, agriculture, as an important carbon cycle ecosystem, has paid limited attention to carbon sequestration in the optimal allocation of water and land resources. Therefore, this study developed a new water-carbon-economy coupling model (WCECM) for optimal allocation of agricultural water and land resources. In this model, the minimum water scarcity, maximum carbon sequestration and maximum economic benefits are taken as the optimization objectives. In addition, surface water volume and groundwater volume and planting area etc. were defined as constraints, respectively. Then, the model was solved using the Non-dominated Sorting Genetic Algorithm III (NSGA-III) and the Entropy-weighted-TOPSIS evaluation method. The developed model was demonstrated in the largest Farm, Youyi Farm, which is one of commercial grain production base in China to analyze the optimization of water and land resources from 2010 to 2019. We found that the new WCECM, based on the simulation of a complex coupled water-carbon-economy system, can realize the optimal allocation of agricultural water and land resources to protect regional water resources, increase carbon sequestration and adjust the agricultural planting structure. In detail, through the multi-objective optimization model, the planting structure and the allocation ratio of surface water and groundwater irrigation water consumption are more suitable for this study area. After the optimization, the area planted with Rice was significantly reduced, the area planted with Maize was increased, and the area planted with Soybean did not change significantly compared with the first two crops. The planting structure has changed from focusing on paddy cultivation to dryland cultivation, with the ratio of Rice area, Maize area and Soybean area being 3:6:1. The water consumption is constrained within manageable limits, with an average annual irrigation water consumption of 2.01 × 108 m3. The amount of carbon sequestered has increased significantly, with an average annual increase of 7.8 × 108 kg. Meanwhile, the optimized economic benefits increased slightly, with a value of ¥2.35 billion. In short, optimization of water and land resources is beneficial for improving farmers' incomes, increasing carbon sequestration in agriculture, and conserving water resources.

Land degradation is a major impediment to achieving sustainable development. However, there is currently no harmonized global map of land degradation status and hotspots. This paper aims to obtain the status and hotspots map of global land degradation by multiple methods and indicators to give essential references for land degradation neutrality. The results show that there are significant differences in the distribution and degree of land degradation between the different methods and indicators. Validation through observation points reveals that most of the methods and indicators can reflect land degradation in arid and semi-arid areas, while there are suitable methods or indicators in tropical and high-latitude areas. The degree of degradation has a large difference after overlay analysis, which shows that there are shortcomings of different methods and indicators for monitoring the degree of land degradation. However, the overlay of land degradation extent displays a high consistency, reflecting the current state of global land degradation to a certain extent. These areas with high overlay value can be recognized as hotspots of land degradation. It is also found there are consistent water-energy change characteristics in the hotspot area, such as increased land surface temperature and air temperature and decreased soil moisture and precipitation. These results conclude that studies on the degree of land degradation need to be considered in an integrated manner about the regional background. The combination of multiple methods and indicators is recommended for land degradation extent studies in large areas. Comparison of different methods and indicators is important guidance for global land degradation research. Accelerating ecological monitoring and restoration of land degradation hotspots is the first step towards land degradation neutrality.

Porcine circovirus type 2 (PCV2) is one of the most serious pathogens in pig herds worldwide. The Capsid protein (Cap), a structural protein of PCV2, is involved in the host's immune response; it induces neutralizing-antibody production and has good immunogenicity. The main PCV2 subtype currently prevalent in the Chinese pig herd is PCV2d. In this study, We constructed a recombinant Bacillus subtilis (B. subtilis) capable of secreting Cap protein, named pHT43-Cap/B. subtilis; we concentrated the supernatant of the recombinant bacteria and observed virus-like particles (VLPs) of PCV2d formed by Cap protein under transmission electron microscopy, named PCV2d-VLPs. The immunocompetence of the pHT43-Cap/B. subtilis and PCV2d-VLPs were then assessed by oral administration and by intramuscular injection into mice, respectively. The results showed that the levels of PCV2d-Cap protein-specific IgG in the serum and of PCV2d-Cap protein-specific sIgA in the small intestinal fluid of pHT43-Cap/B. subtilis immunized mice were elevated compared to the control group, both of them highly significant (p

The bamboo structure has received more and more attention as a green, renewable construction with an increasing focus on environmental issues. Cracking at joints or openings and brittle fracture of bamboo are urgent problems in bamboo structures, leading to reduced rigidity, decreased load capacity, and even endangering structural safety. This research aims to explore the mechanism of self-tapping screw reinforcement in improving the brittle fracture characteristic of bamboo laminate. To achieve an optimal effect of reinforcement, fracture tests of bamboo laminated with different numbers of self-tapping screws and screw positions were conducted to study their impact on fracture behaviors. Through the analysis of the ultimate load, the deformation capacity, the initial energy release rate, and the energy release rate caused by the self-tapping screws reinforcement, a model for calculating the energy release rate of bamboo laminate with self-tapping screws is established. Based on the model, the load-bearing capacity of steel-bamboo connections with self-tapping screws can be reasonably estimated.

The inferior short-circuit current density (JSC) of the conjugated block copolymers (CBCs) based single component organic solar cells (SCOSCs), compared with that of binary all-polymer systems, is the main reason for their limited power conversion efficiency (PCE). To improve the JSC of SCOSCs by enhancing the light-harvesting ability, we designed and synthesized three narrower bandgap acceptor monomers with different chlorine-substituted terminals, and incorporated them into the CBCs. As the position of chlorine substitution altered, the blend morphology, the device performance, and the physical mechanism changed accordingly. It is worth noting that the PB-b-PYCl-2-based SCOSCs exhibited a significantly improved JSC, accompanied by the best PCE of 13.42 %, and good thermal stability. This study illustrated the terminal chlorination strategy is a promising way to modify the device performance of the SCOSCs.

High-intensity pulsed magnetic field was applied to modify the microstructure and mechanical propertis of quenched 8Cr4Mo4V bearing steel under the cryogenic environment. The microstructual transformation in 8Cr4Mo4V bearing steel was investigated by X-ray diffraction (XRD), Vibrating sample magnetometer (VSM) and Electron Backscatter Diffraction (EBSD) and so on. The results revealed that individual deep cryogenic treatment (DCT) promote the transformation from retained austenite (RA) in quenched steel to martensite. However, this phase transformation will be inhibited by coupling high-intensity magnetic field with deep cryogenic treatment (MDCT). For instance, the relative reduction of RA content in DCT samples was 10 ± 2%, while that in MDCT samples was 3 ± 3%. Furthermore, the modified Williamson-Hall method was utilized to estimate the dislocation characteristics based on XRD profile analysis. It exhibited that the proportion of edge dislocation significantly decrease from 61.8% to 43.7% by DCT, while this type of dislocation remains almost unchanged after MDCT. Moreover, the microhardness of quenched 8Cr4Mo4V steel became more uniform after MDCT than that of DCT. It can be indicated that the martensite transformation is blocked and carbon cluster is dissolved under the condition of coupling pulsed magnetic field treatment.

Enrichment of phosphopeptides is a crucial step in phosphoproteomics study. At present, combination of multiple affinity chromatography is regard as an efficient phosphopeptide enrichment strategy. Therefore, designing and preparing composites with multiple affinity sites is of great significance. Herein, the Oxid-Ti3C2Tx/UIO-66-NH2 composites with multiple affinity sites are rapidly synthesized by dielectric barrier discharge (DBD) technology at low temperature and atmospheric pressure. The in-situ nucleation of UIO-66-NH2 and TiO2 can be flexibly regulated through the feed ratio of MOF precursors and the DBD duration individually. The UIO-66-NH2 has large specific surface area, high porosity and plentiful Zr-O clusters. Oxid-Ti3C2Tx provides abundant exposed Ti sites and Ti-O clusters. Based on these, Oxid-Ti3C2Tx/UIO-66-NH2 composites exhibited high sensitivity (0.1 fmol μL−1), satisfactory selectivity (BSA: α-casein = 100: 1, molar ratio) and superior repeatability for phosphopeptide enrichment. In addition, the composites performed well in biological samples like nonfat milk (24 phosphopeptides), human saliva (15 endogenous phosphopeptides) and human serum (all 4 endogenous phosphopeptides), demonstrating a huge application potential in phosphoproteomics study. More importantly, this study opens a new path to synthesize MXene/MOF composites with controllable oxidation degree and flexible compositions regulation efficiently, revealing its broad application prospects in various fields.

Study region: Second Songhua River basin (SSRB), Northeast China. Study focus: Accurately assessing future flood risks is the premise and foundation of flood control and water resources management. At present, studies are still lacking in assessing future watershed flood risks that consider climate change and social development in Northeast China and the relative flood risk assessment framework. This study proposed an integrated flood assessment framework containing the AHP, entropy weight, and GCM downscaling methods, which was implemented in the SSRB, a typical watershed in Northeast China, to estimate future basin flood risks under climate change and social development. New hydrological insights for the region: The flood risk in the SSRB will increase significantly in the mid-term (2051–2075) and long-term (2076–2100) future. The areas under the four scenarios with greater than high-risk levels will expand by 28.9 %, 105.6 %, 165.6 %, and 156.7 %, respectively, compared to the historical scenario. The newly added areas mainly located in the lower reaches. Precipitation changes are the primary reason for the future flood risks. The increased GDP under a higher forcing degree will also significantly increase the flood risk in the long-term future in the lower reaches. Based on these above findings, extreme precipitation forecasting and flood management in downstream areas in the basin need to be enhanced. Energy-saving and emission-reduction measures should be simultaneously implemented.

This study analyzed the growth performance, digestive enzyme activities and intestinal microbial community in HC group (fed with Chironomid larvae), HH group (fed with Chironomid larvae plus Earthworms) and QY group (fed with Earthworms) of juvenile Chinese giant salamander (Andrias davidianus) after farming for 60 days. The results showed that diet can affect the growth performance, digestive enzyme activities and intestinal mcirobiota composition of juvenile Chinese giant salamander. The growth performance in juvenile Chinese giant salamander of HC group was significantly higher than that of HH group and QY group. The ether extract content in muscles of juvenile Chinese giant salamander of HH group and QY group was significantly lower than that of HC group. The intestinal digestive enzyme activities in juvenile Chinese giant salamander of HC group were significantly lower than that of HH group and QY group. The intestinal microbial richness and diversity in juvenile Chinese giant salamander of HH group and QY group were significantly higher than that of HC group. The most dominant phylum of HC group and HH group was Firmicutes but QY group was Bacteroidota, and the most dominant genus of HC group was Clostridium_sensu_stricto_1 but HH group and QY group was Bacteroides. The 24 specific bacterial groups with different classification levels had significant differences in three diet groups of juvenile Chinese giant salamander and these specific bacteria were concentrated in Firmicutes, Proteobacteria and Bacteroidota. Thus, the above studies indicated that Chironomid larvae as diet can increase the growth performance of juvenile Chinese giant salamander, while the addition of Earthworms as diet can enhance digestive ability and change microbiota composition in intestine of juvenile Chinese giant salamander.

To achieve the goals of national emission reduction, carbon peak and carbon neutralization, different provinces will face extremely limited and strict carbon emission space. How to allocate these limited carbon emission spaces is not only related to the realization of emission reduction targets, but also the development of the social economy. There are significant differences in resource endowments and development stages among provinces in China, and the industrial structure is very different. The allocation of carbon quotas under the path of carbon neutrality is particularly important. Based on the carbon-neutral path simulated by existing research, this paper selects population size, GDP value, historical cumulative carbon emissions and carbon emission efficiency indicators calculated by the Super-SBM model from the perspective of fairness and efficiency to allocate carbon quotas in each province. The results show that Guangdong has the largest proportion of 8 %, Jiangsu ranks second with 5 %, and Henan ranks third with nearly 5 %. Xinjiang, Qinghai and Ningxia has the lowest proportion of quotas, 1.7 %, 0.88 % and 0.72 % respectively. Overall, well-developed provinces (Guangdong, Jiangsu) and populous provinces (Henan, Shandong, Sichuan) have an advantage in distribution due to higher carbon emission efficiency and larger population size. In some underdeveloped regions, carbon quotas are low due to low economic development levels, small population scale and low carbon emission efficiency. Meanwhile, in some high emission provinces, such as Inner Mongolia, Ningxia, Shanxi and Xinjiang, due to the high historical cumulative carbon emissions per capita, the quota is less.

Global warming has been changing the planet’s climate pattern, leading to increasing frequency, intensity and duration of extreme weather events and natural disasters. These climate-changing events affect various health outcomes adversely through complicated pathways. This paper reviews the main signs of climate change so far, e.g., suboptimal ambient temperature, sea-level rise and other conditions, and depicts the interactive pathways between different climate-changing events such as suboptimal temperature, wildfires, and floods with a broad range of health outcomes. Meanwhile, the modifying effect of socioeconomic, demographic and environmental factors on the pathways is summarised, such that the youth, elderly, females, poor and those living in coastal regions are particularly susceptible to climate change. Although Earth as a whole is expected to suffer from climate change, this review article discusses some potential benefits for certain regions, e.g., a more liveable environment and sufficient food supply. Finally, we summarise certain mitigation and adaptation strategies against climate change and how these strategies may benefit human health in other ways. This review article provides a comprehensive and concise introduction of the pathways between climate change and human health and possible solutions, which may map directions for future research.

Background: Wildfire imposes a high mortality burden on Brazil. However, there is a limited assessment of the health economic losses attributable to wildfire-related fine particulate matter (PM2.5). Methods: We collected daily time-series data on all-cause, cardiovascular, and respiratory mortality from 510 immediate regions in Brazil during 2000–2016. The chemical transport model GEOS-Chem driven with Global Fire Emissions Database (GFED), in combination with ground monitored data and machine learning was used to estimate wildfire-related PM2.5 data at a resolution of 0.25° × 0.25°. A time-series design was applied in each immediate region to assess the association between economic losses due to mortality and wildfire-related PM2.5 and the estimates were pooled at the national level using a random-effect meta-analysis. We used a meta-regression model to explore the modification effect of GDP and its sectors (agriculture, industry, and service) on economic losses. Results: During 2000–2016, a total of US$81.08 billion economic losses (US$5.07 billion per year) due to mortality were attributable to wildfire-related PM2.5 in Brazil, accounting for 0.68% of economic losses and equivalent to approximately 0.14% of Brazil’s GDP. The attributable fraction (AF) of economic losses due to wildfire-related PM2.5 was positively associated with the proportion of GDP from agriculture, while negatively associated with the proportion of GDP from service. Conclusion: Substantial economic losses due to mortality were associated with wildfires, which could be influenced by the agriculture and services share of GDP per capita. Our estimates of the economic losses of mortality could be used to determine optimal levels of investment and resources to mitigate the adverse health impacts of wildfires.

Highly sensitive detection of melanoma-derived exosomal PD-L1 plays a key role in non-invasive diagnosis of melanoma. Here, we proposed a self-calibrated magnetic aptamer sensor (sCMAS) for sensitive detection of melanoma exosomal PD-L1, using the dual lanthanide-assisted luminescence as well as the ratiometric fluorescent probe strategy to overcome limitations caused by systematic or environmental factors, thereby providing a more stable and liable detection output. Generally, the sCMAS employs the Tb-based nanoparticles (TbNps), which were immobilized on magnetic Fe3O4 microparticles, for stable luminescent reference signal report and the BHHCT-Eu3+ complex for detection signal report of the specific exosomal PD-L1 recognition. Particularly, the dual time-resolved luminescent elements were bridged through the PD-L1-responsive aptamer and its complementary DNA hybridization chain. Recognition of exosomes with the aptamer expelled the detection signal (BHHCT-Eu3+) only, leading to an exosome concentration-dependent liner increase of reference signal/detection signal ratio value in a broad concentration range (1.05 × 105–1.05 × 1010 particles/mL), and an extremely low calculated detection limitation of 1.88 × 102 particles/mL. Further, sCMAS allowed a rapid and efficient differentiation of the health samples from melanoma samples, even those early metastatic melanoma cases. Promisingly, this sCMAS developed in this work would provide a vast opportunity for future evaluation of tumor markers (exosomes, cells, proteins, etc.), and will provide a powerful tool in liquid biopsies.

Nitrification waste has been a main hazard factor in many fire and explosion accidents; however, its thermal characteristics, which provide critical information for hazard control, have not been extensively studied. Accordingly, this study investigated the thermokinetic parameters and gas emission behaviors of nitrification waste by using thermogravimetric analysis coupled with Fourier transform infrared spectrometry (TG-FTIR). A reaction environment with various oxygen contents (0%, 15%, 21%, and 30%) was created.Both integral method (Starink method)and differential method (Friedman method) were adopted to analyze the activation energy of nitrification waste. The results revealed that the thermal decomposition of nitrification waste could be divided into three stages and that the activation energy of this waste was a quadratic function of the oxygen content. The results of this study can improve the understanding of the thermal behavior of nitrification waste and can thus serve as a reference for the effective prevention of related thermal hazards.

Background: Wildfire-related fine particulate matter (PM2.5) has many adverse health impacts, but its impacts on human epigenome are unknown. We aimed to evaluate the associations between long-term exposure to wildfire-related PM2.5 and blood DNA methylation, and whether the associations differ from those with non-wildfire-related PM2.5. Methods: We studied 479 Australian women comprising 132 twin pairs and 215 of their sisters. Blood-derived DNA methylation was measured using the HumanMethylation450 BeadChip array. Data on 3-year (year of blood collection and previous two years) average wildfire-related and non-wildfire-related PM2.5 at 0.01°×0.01° spatial resolution were created by combining information from satellite observations, chemical transport models, and ground-based observations. Exposure data were linked to each participant’s home address, assuming the address did not change during the exposure window. For DNA methylation of each cytosine-guanine dinucleotide (CpG), and for global DNA methylation represented by the average of all measured CpGs or CpGs in repetitive elements, we evaluated their associations with wildfire- or non-wildfire-related PM2.5 using a within-sibship analysis controlling for factors shared between siblings and other important covariates. Differentially methylated regions (DMRs) were defined by comb-p and DMRcate. Results: The 3-year average wildfire-related PM2.5 (range: 0.3 to 7.6 µg/m3, mean: 1.6 µg/m3) was negatively, but not significantly (p-values greater than 0.05) associated with all seven global DNA methylation measures. There were 26 CpGs and 33 DMRs associated with wildfire-related PM2.5 (Bonferroni adjusted p-value

Accurate estimates of the causal effect of air pollution on health outcomes, are critical when calculating attributable disease burdens. Brazil has a large population exposed to fast-growing emissions of air pollutants, however no national level studies have been conducted to examine the causal effect of PM2.5 exposure on health outcomes. This study proposes a novel approach, to accurately estimate the causal relationship between daily PM2.5 exposure and hospitalisations, across 1,814 Brazilian cities during 2000–2015. A variant of the difference-in-differences (DID) approach was applied under a counterfactual framework. Daily time series data were divided into panels. Seasonality and long-term trend were controlled using indicators for the panel. Variables which do not change within a short-period were controlled using a dummy variable for the day. Controls for variables which vary day by day, were included in the model. We found the proposed model exhibited competitive power performance in detecting causal associations between short-term PM2.5 exposure and hospitalisations in Brazil. A 10 μg/m3 increase in PM2.5 concentrations over four days (lag 0–3) was associated with a 1.06 % (95 % CI: 0.94 to 1.17) increase in all-cause hospitalisations and accounted for 1.26 % (95 % CI: 1.12–1.39) of total hospitalisations. Larger effects were found for children aged 0–4 years and the elderly aged 80+ years, suggesting policies should be developed to minimise the exposure of these age groups.

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

MiR-30a-5p plays an important role in various cardiovascular diseases, but its effect in atherosclerosis has not been reported. Apolipoprotein E-deficient (Apo E−/−) mice were used to investigate the role of miR-30a-5p in atherosclerosis, and the underlying mechanism was investigated in vivo and in vitro. The fluorescence in situ hybridization test revealed that miR-30a-5p was expressed in Apo E−/− mice lesions. Nevertheless, in RAW264.7 macrophages, the expression of miR-30a-5p was reduced by lipopolysaccharide (LPS) or oxidized low-density lipoprotein. MiR-30a-5p-ago-treated Apo E−/− mice significantly reduced lesion areas in the aorta and aortic root, reduced levels of lipoprotein and pro-inflammatory cytokines, and increased levels of anti-inflammatory cytokines. The ratio of M1/M2 macrophages was decreased in miR-30a-5p-ago-treated Apo E−/− mice and LPS-treated RAW264.7 macrophages by the regulation of Smad-1/2 phosphorylation. MiR-30a-5p reduced lipid uptake in oxidized low-density lipoprotein-treated macrophages by regulating the expression of PPAR-γ, ABCA1, ABCG1, LDLR, and PCSK9. Ubiquitinated ligase NEDD4L was identified as a target of miR-30a-5p. Interestingly, knockdown of NEDD4L decreased the M1/M2 ratio and oxidized low-density lipoprotein uptake in macrophages by inhibiting the ubiquitination of PPAR-γ and phosphorylation of Smad-1/2 and regulating ABCA1, ABCG1, LDLR, and PCSK9. We demonstrated a novel effect and mechanism of miR-30a-5p in atherosclerosis.

It is well known that the outer membrane proteins (OMPs) of Gram-negative bacteria are potential vaccine candidates against bacterial infections, whereas systematic research on the protective efficacy of OMP components is rarely reported. In the present study, we constructed forty OMP recombinant plasmids of Aeromonas hydrophila and evaluated their immune protection against A. hydrophila infection in zebrafish. Our results showed that the transcriptions of many immune-related genes were induced after DNA vaccine immunization. The nine DNA vaccines (pcDNA3.1 (+) plasmid carrying recombinant rAHA_2145, rpilQ, rAHA_1130, rtamA, rAHA_2144, rhgpB, rAHA_3766, rgspD and rAHA_2785 genes) enhanced the survival rates of zebrafish to higher than 50% after challenged with virulent A. hydrophila. Furthermore, after the prime-boost vaccination, these nine DNA vaccines could enhance the host immune response and relative percent survival rates (RPSs) of zebrafish to higher than 60%. Taken together, these OMPs-based DNA vaccines can elicit immune responses and enhance immune protection in zebrafish against A. hydrophila infection, especially the DNA vaccines encoded by rAHA_2144 and rpilQ, which RPSs of zebrafish were 82.4% and 70.2%, respectively after the prime-boost vaccination.

Italy is among the countries with the highest ozone concentration in Europe. However, the mortality burden of ozone and related economic loss has not been fully characterized. This study aimed to estimate the ozone-mortality association in Italy and evaluate attributable mortality burden and related economic loss in 2015–2019. We collected daily all-cause mortality data stratified by age and sex from 2015 to 2019 in 107 provinces of Italy. A two-stage time-series framework was applied to estimate the association between daily maximum eight-hour average ozone and mortality as well as economic loss. An overall increase in the risk of mortality (RR=1.0043, 95% CI: 1.0029, 1.0057) was associated with every 10 µg/m3 increase in ozone. Generally, a total of 70,060 deaths and $65 billion economic loss were attributed to ozone exposure, corresponding to 3.11% of mortality and about 0.5% of the national GDP during the study period, respectively. The highest ozone-related mortality burden (30,910 deaths) and economic loss ($29.24 billion) were observed in the hot season. This nationwide study suggested considerable mortality burden and economic loss were associated with exposure to ozone. More actions and policies should be proposed to reduce ozone levels and help the public protect their health.

Endometriosis is a chronic, inflammatory, estrogen-dependent gynecological disease characterized by the growth of endometrial stromal cells and glands outside the uterine cavity in response to hormones, which commonly occurs in reproductive-age women. Zearalenone (ZEA) is a toxic metabolite produced by Fusarium, which acts as estrogen activity because of the similarity of its structure to estrogen. In this study, we used an endometriosis mouse model: 15 days after ovariectomy, endometrial fragments were sutured on the pelvic wall, and exogenous estrogen was supplied using an estrogen-releasing silicone tube embedded subcutaneously. Mice were treated with different doses of ZEA by gavage for 21 days. The results show that ZEA significantly inhibited the growth of ectopic endometrium in a dose-dependent manner. The proliferation of cells decreased while apoptosis increased in the ectopic tissues of ZEA-treated mice compared to the vehicle group. The expression of estrogen receptor-α and its downstream targets MUC1 and p-AKT decreased, indicating an impaired estrogen signaling activity by ZEA treatment. In addition, the decreased expression of pro-inflammatory cytokine Tnf-α, Il-1β, and Il-6, the lower number of macrophages and neutrophils cells, and the inhibited NF-κB signaling pathway suggest the inflammatory response in the ectopic endometrium was also suppressed by ZEA treatment. However, when the exogenous estrogen supply is removed, ZEA, in turn, plays an estrogen-like role that promotes cell proliferation in the ectopic endometrium. In summary, our data suggest ZEA acts as an antagonist in endometriotic tissue when estrogen is sufficient but turns to estrogenic activity in the absence of estrogen in the development of endometriosis. ZEA also inhibits ectopic tissue growth by inhibiting inflammatory response in the endometriosis model.

Summary: Background: Increased mortality risk is associated with short-term temperature variability. However, to our knowledge, there has been no comprehensive assessment of the temperature variability-related mortality burden worldwide. In this study, using data from the MCC Collaborative Research Network, we first explored the association between temperature variability and mortality across 43 countries or regions. Then, to provide a more comprehensive picture of the global burden of mortality associated with temperature variability, global gridded temperature data with a resolution of 0·5° × 0·5° were used to assess the temperature variability-related mortality burden at the global, regional, and national levels. Furthermore, temporal trends in temperature variability-related mortality burden were also explored from 2000–19. Methods: In this modelling study, we applied a three-stage meta-analytical approach to assess the global temperature variability-related mortality burden at a spatial resolution of 0·5° × 0·5° from 2000–19. Temperature variability was calculated as the SD of the average of the same and previous days’ minimum and maximum temperatures. We first obtained location-specific temperature variability related-mortality associations based on a daily time series of 750 locations from the Multi-country Multi-city Collaborative Research Network. We subsequently constructed a multivariable meta-regression model with five predictors to estimate grid-specific temperature variability related-mortality associations across the globe. Finally, percentage excess in mortality and excess mortality rate were calculated to quantify the temperature variability-related mortality burden and to further explore its temporal trend over two decades. Findings: An increasing trend in temperature variability was identified at the global level from 2000 to 2019. Globally, 1 753 392 deaths (95% CI 1 159 901–2 357 718) were associated with temperature variability per year, accounting for 3·4% (2·2–4·6) of all deaths. Most of Asia, Australia, and New Zealand were observed to have a higher percentage excess in mortality than the global mean. Globally, the percentage excess in mortality increased by about 4·6% (3·7–5·3) per decade. The largest increase occurred in Australia and New Zealand (7·3%, 95% CI 4·3–10·4), followed by Europe (4·4%, 2·2–5·6) and Africa (3·3, 1·9–4·6). Interpretation: Globally, a substantial mortality burden was associated with temperature variability, showing geographical heterogeneity and a slightly increasing temporal trend. Our findings could assist in raising public awareness and improving the understanding of the health impacts of temperature variability. Funding: Australian Research Council, Australian National Health & Medical Research Council.

Finding glycoproteins related to both biomarkers and therapeutic targets is essential prerequisite. Unfortunately, the glycoproteins are hard to directly detect by mass spectrometry due to their low abundance and abundant of interferents. Herein, we report a systematic integration of enrichment and comparative analysis strategy using the hydrophilic magnetic covalent organic frameworks (COFs) as the platform to fish the glycopeptides from normal and colorectal cancer (CRC) cell lysates by bottom-up methods. The layer of COF was controlled growth on the surface of Fe3O4 nanoparticles and the hydrophilicity increased with L-cysteine (L-Cys) was modified. The Fe3O4@PVP/PEI@COF-L-Cys nanoparticles have exhibited the excellent selectivity (IgG/BSA, 1:2000) and high sensitivity (0.1 fmol) for glycopeptide enrichment. A total of 214 glycopeptides and 597 glycosites belonged to 289 glycoproteins were enriched in FHC cell lysate by magnetic COFs. And 711 glycopeptides, 824 glycosites belonged to 440 N-glycoproteins were enriched in HT-29 cell lysate. Furthermore, the differential glycoproteins were comparatively analyzed through gene ontology for verifying biomarkers (LGALS3BP, PDIA3, etc.), therapeutic targets (TM9SF3, etc.), CRC pathological process, and differential glycoprotein’s function. This strategy bridges the enrichment technology and clinical requirements, has great potential for helping illuminate the mapping of CRC differential glycoproteomics.

Nitric oxide (NO) is tightly associated with plant response against cadmium (Cd) stress in rice since NO impacts Cd accumulation via modulating cell wall components. In the present study, we investigated that whether and how NO regulates Cd accumulation in root in two rice lines with different Cd accumulation ability. The variation of polysaccharides in root cell wall (RCW) of a high Cd-accumulating rice line Lu527–8 and a normal rice line Lu527–4 in response to Cd stress when exogenous NO supplied by sodium nitroprusside (SNP, a NO donor) was studied. Appreciable amounts of Cd distributed in RCW, in which most Cd ions were bound to pectin for the two rice lines when exposed to Cd. Exogenous NO upregulated the expression of OsPME11 and OsPME12 that were involved in pectin demethylesterification, resulting in more low methyl-esterified pectin and therefore stronger pectin-Cd binding. Exogenous NO also enhanced the concentration of hemicellulose and the amount of Cd ions in it. These results demonstrate that NO-induced more Cd binding in RCW in the two rice lines through promoting pectin demethylesterification and increasing hemicellulose accumulation. Higher OsPMEs expression and more hemicellulose synthesis contributed to more Cd immobilization in RCW of the high Cd-accumulating rice line Lu527–8. The main findings of this study reveal the regulation of NO on cell wall polysaccharides modification under Cd stress and help to elucidate the physiological and molecular mechanism of NO participating in Cd responses of rice.

The leaves of Lindera aggregate (Sims) Kosterm. are traditionally used as healthy tea for the prevention and treatment of hyperlipidemia in Chinese. The aim of this study was to evaluate the antihyperlipidemic effects and potential mechanisms of the aqueous extracts from L. aggregate leaves (AqLA-L) on normal and hypercholesterolemic (HCL) mice. HCL mice were induced by high fat diet (HFD) and orally administrated with or without AqLA-L for ten days. The results showed that AqLA-L (0.3, 0.6, 1.2 g/kg) significantly reduced serum TG, ALT, but elevated fecal TG in normal mice. AqLA-L (0.3, 0.6, 1.2 g/kg) also remarkably lowered serum TC, TG, LDL, N-HDL, ALT, GLU, APOB, hepatic GLU and increased serum HDL, APOA-I, fecal TG levels in HCL mice. These results revealed that AqLA-L treatment regulated the disorders of the serum lipid and liver function, reduced hepatic GLU contents both in normal and HCL mice. The potential mechanisms for cholesterol-lowering effects of AqLA-L might be up-regulation of cholesterol 7-alpha-hydroxylase (CYP7A1) and ATP-binding cassette transporter A1 (ABCA1), as well as down-regulation of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). The data indicated that AqLA-L has potential therapeutic value in treatment of hyperlipidemia with great application security. Keywords: Lindera aggregate leaves, Hypercholesterolemic mice, Lipids, Cholesterol metabolism

Summary: Background: Climate change is increasing the risks of injuries, diseases, and deaths globally. However, the association between ambient temperature and renal diseases has not been fully characterized. This study aimed to quantify the risk and attributable burden for hospitalizations of renal diseases related to ambient temperature. Methods: Daily hospital admission data from 1816 cities in Brazil were collected during 2000 and 2015. A time-stratified case-crossover design was applied to evaluate the association between temperature and renal diseases. Relative risks (RRs), attributable fractions (AFs), and their confidence intervals (CIs) were calculated to estimate the associations and attributable burden. Findings: A total of 2,726,886 hospitalizations for renal diseases were recorded during the study period. For every 1°C increase in daily mean temperature, the estimated risk of hospitalization for renal diseases over lag 0–7 days increased by 0·9% (RR = 1·009, 95% CI: 1·008–1·010) at the national level. The associations between temperature and renal diseases were largest at lag 0 days but remained for lag 1–2 days. The risk was more prominent in females, children aged 0–4 years, and the elderly ≥ 80 years. 7·4% (95% CI: 5·2–9·6%) of hospitalizations for renal diseases could be attributable to the increase of temperature, equating to 202,093 (95% CI: 141,554–260,594) cases. Interpretation: This nationwide study provides robust evidence that more policies should be developed to prevent heat-related hospitalizations and mitigate climate change. Funding: China Scholarship Council, and the Australian National Health and Medical Research Council

Background: The health impact of short-term heat exposure is well documented. However, limited studies explored the association between life-time summer heat exposure and lung function. Objective: To examine the association between life-time summer heat exposure and lung function among young adults. Methods: We conducted a retrospective cohort study among 1928 college students in Shandong, China from September 4, 2020 to November 15, 2020. Life-time summer heat exposure for participants were estimated based on the nearest station meteorological data after the participant’s birth date and divided by their learning phases. Lung function indicators included forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). A multiple linear regression model was conducted to examine the associations between summer heat exposure and lung function. Stratification analysis by cooling facilities and respiratory diseases history were also conducted. Results: The study subjects had a slight majority of women (58.8%), age 19.2 ± 0.6 years. Each 1 °C increase in life-time summer mean temperature was associated with 1.07% [95% confidence interval (CI): −1.95–0.18%] decrease in FVC and 0.88% (95 %CI: −1.71, −0.05%) decrease in FEV1. Participants with respiratory diseases and non-cooling facility users were more susceptible to summer heat exposure. The usage of fan and air condition could effectively reduce the deleterious heat effects on lung function. Conclusion: Life-time summer heat exposure is significantly associated with the reduction of lung function in young adults. Cooling facilities are necessary for pre-school children to reduce heat effects. Fan and air-condition are effective cooling facilities, especially for people with respiratory diseases.

Enrichment of exosomes with high structural and functional integrity is a critically important step before downstream applications in biological and clinical domains. In this work, dynamic biological interfaces functionalized fructose-responsive immunomagnetic beads (Fr-IMBs) were fabricated by incorporating the dynamic biological interfaces composed of dopamine and 4-carboxyphenylboronic acid with immunomagnetic beads. These fabricated Fr-IMBs were successfully applied to capture the MCF-7 exosomes with a high capture efficacy of 91.0%. After incubation with fructose, the molecular structure of the dopamine-boronic acid complexation can be rearranged and the antibody (anti-CD63) bound exosomes were released competitively, with a yield greater than 79.8%. Those exosomes that underwent both immunomagnetic separation and fructose triggered release remained their good bioactivity to promote MCF-7 cell migration. Better yet, exosomes enriched by Fr-IMBs possessed higher purity and better preservation of tumor-related molecular information of the exosomal proteins than those obtained through the ultracentrifugation approach, as proved by the comparative proteomics. These proposed sugar-responsive immunomagnetic beads may serve as biofriendly candidates in enriching useful biomarkers (e.g., cells, nucleic acids, proteins, etc.) efficiently from complex biological samples with high purity.

miR-34, whose mimic was used on phase I clinical trial, has been extensively reported since its dysfunction in various cancers including non-small-cell lung cancer (NSCLC). However, the roles of miR-34 family members in the progression of lung squamous carcinoma (SCC) in patients who have occupational-exposure experience are unclear yet. Here, we comprehensively investigated the expression levels of miR-34 family members in SCC patients and compared the roles of them in SCC in vitro and vivo. The results showed that the average levels of miR-34a and miR-34b/c were decreased in patients. The analysis of miR-34a to miR-34b/c levels in patients graded different stages or metastases or recurrence showed that miR-34b/c was reduced earlier and more significantly than miR-34a. In vitro assays demonstrated that both miR-34a and miR-34b/c inhibits SCC cells proliferation, migration and invasion via Notch1 pathway, while miR-34b/c effects more than miR-34a does. As miR-34a was significantly decreased in cancer recurrence, the further analysis of relationship between miR-34a and stem cell adhesion molecular CD44 showed that miR-34a was significantly correlated with CD44 levels in patients. Knockdown of CD44 significantly blocked miR-34a mediated inhibition of cell migration and invasion. Treating the purified CD44hi cells with miR-34 overexpression lentivirus inhibited the tumor outgrowth. By contrast, anti-miR-34 facilitated tumor development of CD44low cells. Our study showed that miR-34 family members are negative regulator for SCC development, even though the inhibition is mediated by multiple and complicated signal pathways, which provides theoretical basis for SCC treatment and a biomarker candidate for SCC prognosis.

Residual cancer after incomplete ablation remains a major problem for radiofrequency ablation (RFA). We aimed to investigate the synergetic treatment efficacy of RFA combined with ultrasonic cavitation for liver tumor. Sixty rabbits with VX2 liver tumor were randomly divided into three groups. Group A was control group without any treatment. Combined ultrasonic cavitation with RFA was performed for group B1. Group B2 underwent RFA alone. The histopathological results were compared at the 5th, 11th, and 18th day of experiment, and the survival time and metastasis were assessed. The tumor volume growth rate, percentage of necrosis area, microvessel density, and apoptosis index showed significant differences among these groups at the 5th day, 11th day, and 18th day of experiment (P < .05). In contrast, the difference of metastatic score was not significant at the 5th and 11th day (P > .05). At the 18th day, the metastatic score of group A was significant higher than that of group B1 (P < .05), whereas the differences between group A and group B2, or group B1 and group B2 were not significant (P > .05). The median/range interquartile of survival time in groups A, B1, and B2 were 25/8 days, 50/19 days, and 48/20 days, respectively, and there was significant difference between groups A and B1 or B2 (P < .05). The difference between groups B1 and B2 was not significant (P > .05). Ultrasonic cavitation after incomplete RFA for liver tumor improved the antitumor effect, which could be considered as a potentially useful combined therapeutic strategy for liver malignancy. Keywords: Radiofrequency ablation, Ultrasound, Liver neoplasms, Residual cancer, Microbubbles

Based on the characteristics of hydrodynamics and sediment transport in the bar area in the Modaomen Estuary, a flume experiment was performed to study the evolution of the longitudinal profile of the mouth bar. The mouth bar evolution was investigated under the impacts of floods with different return periods as well as flood-wave interaction. The results showed that floods with different return periods had significant influences on the evolution of the river mouth bar. Particularly on the inner slope of the mouth bar, the sediment was substantially active and moveable. The inner slope and the bar crest tended to be remarkably scoured. The erosion was intensified with the increase of the magnitude of floods. Moreover, the bar crest moved seawards, while the elevation of the bar crest barely changed. Under the flood-wave interaction, a remarkable amount of erosion on the inner and outer slopes of the mouth bar was also found. The seaward displacement of the bar crest under the interaction of floods and waves was less than it was under only the impact of floods, while more deposition was found on the crest of the mouth bar in this case. Keywords: Modaomen, Mouth bar, Wave, Flood, Flume experiment, Sediment transport

Environmental factors play an important role in the development of ulcerative colitis (UC). However, only few studies have examined the effects of air pollution on UC occurrence. We conducted a time–series analysis to explore the association between short-term exposure to fine particulate matter (PM2.5) and outpatient visits for UC in Beijing, China. In total, 84,000 outpatient visits for UC were retrieved from the Beijing Medical Claim Data for Employees between January 1, 2010 and June 30, 2012. Measurements of daily PM2.5 concentrations were obtained from the United States Embassy air-monitoring station. A generalized additive model with quasi-Poisson link was applied to examine the association between PM2.5 concentrations and outpatient visits for UC stratified by sex, age, and season. We found that short-term exposure to PM2.5 was significantly associated with increased daily outpatient visits for UC at lag 0 day. A 10 μg/m3 increase in PM2.5 concentration at lag 0 day corresponded to a 0.32% increase in outpatient visits for UC (95% confidence interval (CI), 0.05–0.58%; P = 0.019). There was a clear concentration–response association between daily outpatient visits for UC and PM2.5 concentrations. The PM2.5 effects were significant across all sex and season subgroups, without evidence of effect modification by sex (P = 0.942) or season (P = 0.399). The association was positive in patients younger than 65 years old but negative in those 65 years old or older, although the difference was not significant (P = 0.883). In conclusion, our study demonstrated that short-term exposure to ambient PM2.5 was significantly associated with an increased risk of daily outpatient visits for UC, especially in younger people. Additional studies are warranted to confirm our findings.

The core device of dense wavelength division multiplexing (DWDM) system is a wavelength division multiplexer/demultiplexer, among which the arrayed waveguide grating (AWG) device has the most superior optical performances. The optical performances of AWG are mainly affected by the structure parameters such as the waveguide spacing, the width and length of the tapered waveguide and the number of arrayed waveguides. Taking the 40-channel AWG as the research object, by combining theory with simulation, this paper analyzed the influence mechanisms and laws of AWG structure parameters on its optical performances including insertion loss, loss non-uniformity, adjacent crosstalk, and 3 dB bandwidth. Then, the sensitivities analysis of AWG optical performance was carried out by using the direct derivation method and the finite difference method in the sensitivities analysis method, so as to obtain the influence degree of each structure parameter on the optical performances. Finally, based on the influence rules and sensitivities of structure parameters on optical performances, this paper adopted some methods to optimize the structure parameters of AWG, and optimized the insertion loss, loss non-uniformity, adjacent crosstalk, and 3 dB bandwidth to about 1 dB, 0.35 dB, −30 dB, and 0.42 nm, respectively. The research methods and conclusions of this paper can provide references for the optimization of optical performances and layout design of other types of AWG.

Background: Premature birth is associated with high prevalence of neurodevelopmental impairments in surviving infants. The putative role of cerebellar and brainstem dysfunction remains poorly understood, particularly in the absence of overt structural injury. Method: We compared in-utero versus ex-utero global, regional and local cerebellar and brainstem development in healthy fetuses (n ​= ​38) and prematurely born infants without evidence of structural brain injury on conventional MRI studies (n ​= ​74) that were performed at two time points: the first corresponding to the third trimester, either in utero or ex utero in the early postnatal period following preterm birth (30–40 weeks of gestation; 38 control fetuses; 52 premature infants) and the second at term equivalent age (37–46 weeks; 38 control infants; 58 premature infants). We compared 1) volumetric growth of 7 regions in the cerebellum (left and right hemispheres, left and right dentate nuclei, and the anterior, neo, and posterior vermis); 2) volumetric growth of 3 brainstem regions (midbrain, pons, and medulla); and 3) shape development in the cerebellum and brainstem using spherical harmonic description between the two groups. Results: Both premature and control groups showed regional cerebellar differences in growth rates, with the left and right cerebellar hemispheres showing faster growth compared to the vermis. In the brainstem, the pons grew faster than the midbrain and medulla in both prematurely born infants and controls. Using shape analyses, premature infants had smaller left and right cerebellar hemispheres but larger regional vermis and paravermis compared to in-utero control fetuses. For the brainstem, premature infants showed impaired growth of the superior surface of the midbrain, anterior surface of the pons, and inferior aspects of the medulla compared to the control fetuses. At term-equivalent age, premature infants had smaller cerebellar hemispheres bilaterally, extending to the superior aspect of the left cerebellar hemisphere, and larger anterior vermis and posteroinferior cerebellar lobes than healthy newborns. For the brainstem, large differences between premature infants and healthy newborns were found in the anterior surface of the pons. Conclusion: This study analyzed both volumetric growth and shape development of the cerebellum and brainstem in premature infants compared to healthy fetuses using longitudinal MRI measurements. The findings in the present study suggested that preterm birth may alter global, regional and local development of the cerebellum and brainstem even in the absence of structural brain injury evident on conventional MRI.

Few large multicity studies have assessed acute effect of tropospheric ozone pollution on pneumonia risk. We aimed to examine the relation between day-to-day changes in ozone concentrations and hospital admissions for pneumonia in China. We conducted a national time-series study in 184 major Chinese cities from 2014 to 2017. City-specific relation between ozone concentrations and pneumonia admissions was evaluated using an over-dispersed generalized additive model. Random-effects meta-analysis was conducted to pool the city-specific estimates. Two-pollutant models were fitted to test the robustness of the relations. We also investigated potential effect modifiers. Overall, we observed increased admissions for pneumonia associated with ozone exposure. The national-average estimates per 10-μg/m3 increase in ozone were 0.14% (95% CI: 0.03%–0.25%) at lag 0 day in the whole year, 0.30% (95% CI: 0.17%–0.43%) at lag 0 day in the warm season, and 0.20% (95% CI: 0.05%–0.34%) at lag 1 day in the cool season. Two-pollutant models indicated that the ozone effects were not confounded by PM2.5, SO2, NO2 or CO. The association between ozone and pneumonia was stronger in the elderly. Ozone levels and gross domestic product per capita reduced the effects of ozone, and smoking enhanced the effects of ozone. In conclusion, we estimated an increase in daily pneumonia admissions associated with ozone exposure in China. As the first national study in China to report acute effect of ozone on pneumonia hospitalizations, our findings are incredibly meaningful in terms of both ozone pollution related policy development and pneumonia prevention. Keywords: Air pollution, Pneumonia, Ozone, Time-series study

Objective: Melatonin has a protective role in adults with cardiovascular disease, but the effects of melatonin in children with cardiac dysfunction are not well understood. This study was designed to explore the variations in melatonin, myeloperoxidase, and caspase-3 levels in children suffering from heart failure. Methods: Seventy-two pediatric patients with heart failure and twelve healthy children were enrolled in this study. A modified Ross scoring system was used to evaluate clinical cardiac function. Patients with a score of >2 points were included in the study and were divided into three groups according to severity of heart failure: mild (score: 3–6), moderate (score: 7–9), and severe (score: 10–12). Echocardiographic parameters, laboratory data, and serum levels of melatonin, myeloperoxidase, and caspase-3 were measured and analyzed in all patients. Results: Compared with patients with mild and moderate heart failure, patients in the severe heart failure group had significantly decreased left ventricular ejection fraction (p 2 pontos foram incluídas no estudo e foram divididos em três grupos de acordo com a gravidade da insuficiência cardíaca: leve (escore: 3-6), moderada (escore: 7-9) e grave (escore: 10-12). Os parâmetros ecocardiográficos, dados laboratoriais e níveis séricos de melatonina, mieloperoxidase e caspase 3 foram medidos e analisados em todos os pacientes. Resultados: Em comparação aos pacientes com insuficiência cardíaca de gravidade leve e moderada, os pacientes no grupo de insuficiência cardíaca grave apresentaram redução significativa da fração de ejeção do ventrículo esquerdo (p

Summary: Recognition of the host plant is a prerequisite for infection by pathogenic bacteria. However, how bacterial cells sense plant-derived stimuli, especially chemicals that function in regulating plant development, remains completely unknown. Here, we have identified a membrane-bound histidine kinase of the phytopathogenic bacterium Xanthomonas campestris, PcrK, as a bacterial receptor that specifically detects the plant cytokinin 2-isopentenyladenine (2iP). 2iP binds to the extracytoplasmic region of PcrK to decrease its autokinase activity. Through a four-step phosphorelay, 2iP stimulation decreased the phosphorylation level of PcrR, the cognate response regulator of PcrK, to activate the phosphodiesterase activity of PcrR in degrading the second messenger 3′,5′-cyclic diguanylic acid. 2iP perception by the PcrK-PcrR remarkably improves bacterial tolerance to oxidative stress by regulating the transcription of 56 genes, including the virulence-associated TonB-dependent receptor gene ctrA. Our results reveal an evolutionarily conserved, inter-kingdom signaling by which phytopathogenic bacteria intercept a plant hormone signal to promote adaptation to oxidative stress. : How pathogenic bacteria use receptors to recognize the signals of the host plant is unknown. Wang et al. have identified a bacterial receptor histidine kinase that specifically senses the plant hormone cytokinin. Through a four-step phosphorelay, cytokinin perception triggers degradation of a second messenger, c-di-GMP, to activate the bacterial response to oxidative stress. Keywords: histidine kinase, ligand, cytokinin, autokinase activity, phosphorelay, response regulator, two-component signal transduction system, Xanthomonas campestris pv. campestris, virulence, oxidative stress

We report the first preliminary and extensive study on the solution self-assembly behaviors of poly(vinylidene fluoride)–b-polystyrene (PVDF–PS) block copolymers. The two PVDF–PS polymers we examined have the same length of PVDF block with number averaged repeating unit of 180, but distinctly different lengths of PS block with number averaged repeating unit of 125 and 1202. The self-assembly experiments were carried out in a series of mixture solutions containing a good solvent N,N-dimethylformamide and a selective solvent with different ratios. Our results showed that the self-assembly process was greatly affected by the two factors we examined, i.e. the length of the PS block and the solvent composition. We hope that our study could stimulate more research on the self-assembly of PVDF-containing polymers in solution. Keywords: Self-assembly, Block copolymers, Poly(vinylidene fluoride)

Wheat and maize are increasingly used as alternative crops to sunflower monocultures that dominate the Hetao Irrigation District in China. Shifts from sunflower monocultures to alternate cropping systems may have significant effects on below-ground microbial communities which control nutrient cycling and influence plant productivity. In this research, rhizosphere bacterial communities were compared among sunflower, wheat and maize cropping systems by 454 pyrosequencing. These cropping systems included 2 years wheat (cultivar Yongliang 4) and maize (cultivar Sidan 19) monoculture, more than 20 years sunflower (cultivar 5009) monoculture, and wheat-sunflower and maize-sunflower rotation. In addition, we investigated rhizosphere bacterial communities of healthy and diseased plants at maturity to determine the relationship between plant health and rotation effect. The results revealed taxonomic information about the overall bacterial community. And significant differences in bacterial community structure were detected among these cropping systems. Eight of the most abundant groups including Proteobacteria, Bacteroidetes, Acidobacteria, Gemmatimonadetes, Chloroflexi, Actinobacteria, Planctomycetes and Firmicutes accounted for more than 85% of the sequences in each treatment. The wheat-wheat rhizosphere had the highest proportion of Acidobacteria, Bacteroidetes and the lowest proportion of unclassified bacteria. Wheat-sunflower cropping system showed more abundant Acidobacteria than maize-sunflower and sunflower monoculture, exhibiting some influences of wheat on the succeeding crop. Maize-maize rhizosphere had the highest proportion of γ-Proteobacteria, Pseudomonadales and the lowest proportion of Acidobacteria. Sunflower rotation with wheat and maize could increase the relative abundance of the Acidobacteria while decrease the relative abundance of the unclassified phyla, as was similar with the health plants. This suggests some positive impacts of rotation with wheat and maize on the bacterial communities within a single field. These results demonstrate that different crop rotation systems can have significant effects on rhizosphere microbiomes that potentially alter plant productivities in agricultural systems.

Background: The sea cucumber lysozyme belongs to the family of invertebrate lysozymes and is thought to be a key defense factor in protecting aquaculture animals against bacterial infection. Recently, evidence was found that the sea cucumber lysozyme exerts broad spectrum antimicrobial action in vitro against Gram-negative and Gram-positive bacteria, and it also has more potent antimicrobial activity independent of its enzymatic activity. To explore the antimicrobial role of this non-enzymatic lysozyme and model its structure to novel antimicrobial peptides, the peptide from the C-terminal amino acid residues 70–146 of the sea cucumber lysozyme in Stichopus japonicus (SjLys-C) was heterologously expressed in Escherichia coli Rosetta(DE3)pLysS. Results: The fusion protein system led to over-expression of the soluble and highly stable product, an approximate 26 kDa recombinant SjLys-C protein (rSjLys-C). The present study showed that rSjLys-C displayed strong antimicrobial activity against the tested Gram-positive and Gram-negative bacteria. In particular, the heat-treated rSjLys-C exhibited more inhibitive activity than the native rSjLys-C. The structural analysis of SjLys-C showed that it is a typical hydrophilic peptide and contains a helix-loop-helix motif. The modeling of SjLys-C molecular structures at different temperatures revealed that the tertiary structure of SjLys-C at 100°C underwent a conformational change which is favorable for enhancing antimicrobial activity. Conclusion: These results indicate that the expressed rSjLys-C is a highly soluble product and has a strong antimicrobial activity. Therefore, gaining a large quantity of biologically active rSjLys-C will be used for further biochemical and structural studies and provide a potential use in aquaculture and medicine.