Selenium Alleviates Cerebral Ischemia/Reperfusion Injury by Regulating Oxidative Stress, Mitochondrial Fusion and Ferroptosis.

To clarify the potential role of selenium (Se) on cerebral ischemia/reperfusion (I/R) injury, we utilized mouse middle cerebral artery occlusion (MCAO) followed by reperfusion as an animal model and oxygen-glucose deprivation and reoxygenation (OGD/R) to treat N2a cells as a cell model, respectively. MCAO model was established in mice and then divided into different groups with or without Se treatment. TTC staining was used to observe whether the cerebral I/R modeling was successful, and the apoptosis level was determined by TUNEL staining. The expression of GPx-4 and p22phox was assessed by western blot. In vitro experiments, the OGD/R induced oxidative stress in N2a cells was assessed by levels of GSH/GSSG, malondialdehyde, superoxide dismutase and iron content, respectively. QRT-PCR was used to detect the mRNA levels of Cox-2, Fth1, Mfn1 and mtDNA in N2a cells. JC-1 staining and flow cytometry was performed to detect the mitochondrial membrane potential. Se treatment alleviated cerebral I/R injury and improved the survival rate of mice. Additionally, Se treatment apparently attenuated oxidative stress and inhibited iron accumulation in MCAO model mice and OGD/R model of N2a cells. In terms of its mechanism, Se could up-regulate Mfn1 expression to alleviate oxidative stress and ferroptosis by promoting mitochondrial fusion in vivo and vitro. These findings suggest that Se may have great potential in alleviating cerebral I/R injury.

A review of current air quality indexes and improvements under the multi-contaminant air pollution exposure.

The air quality is one of the major concerns in the urban environment due to the rapid changes in pollutant emissions driven by complex and intensive human activities. Therefore, quantification of the urban air quality has become an essential need for both urban residents and authorities to quickly assess air quality conditions. To reach this aim, the air quality index (AQI) is the primary way to better understand the urban air quality. However, the varied AQIs in different countries are difficult to directly compare due to the varied calculation methods. Thus, this research presents an updated review of the major AQIs worldwide by dividing them into two categories: single- and multi-contaminant-oriented AQIs. Single-contaminant-oriented AQIs are based on the maximum value of individual pollutants and are applied in most countries with location-dependent standards, such as the United States, China, the United Kingdom and New South Wales, Australia. However, these may greatly underestimate the impact of multiple contaminants, be difficult to dynamically update or to be compared internationally. Moreover, multi-contaminant-oriented AQIs are available in the literature, which consider the combined effects of exposure to multiple contaminants. Among these AQIs, arithmetic pollutant aggregation simply integrates pollutants in a linear or nonlinear way, and weighted pollutant aggregation further assigns varied weights from different perspectives. Combining the advantages and disadvantages of the existing AQIs, the general air quality health index (GAQHI) is proposed as a pollutant-aggregated, local health-based AQI paradigm suitable for the present complex multi-contaminant situation. It provides a direction for the construction of a more accurate, consistent and comparable AQI system and can help both researchers and governments improve human well-being and achieve sustainable development.

Multicontaminant air pollution in Chinese cities.

OBJECTIVE: To investigate multicontaminant air pollution in Chinese cities, to quantify the urban population affected and to explore the relationship between air pollution and urban population size. METHODS: We obtained data for 155 cities with 276 million inhabitants for 2014 from China's air quality monitoring network on concentrations of fine particulate matter measuring under 2.5 µm (PM2.5), coarse particulate matter measuring 2.5 to 10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2) and ozone (O3). Concentrations were considered as high, if they exceeded World Health Organization (WHO) guideline limits. FINDINGS: Overall, 51% (142 million) of the study population was exposed to mean annual multicontaminant concentrations above WHO limits - east China and the megacities were worst affected. High daily levels of four-contaminant mixtures of PM2.5, PM10, SO2 and O3 and PM2.5, PM10, SO2 and NO2 occurred on up to 110 days in 2014 in many cities, mainly in Shandong and Hebei Provinces. High daily levels of PM2.5, PM10 and SO2 occurred on over 146 days in 110 cities, mainly in east and central China. High daily levels of mixtures of PM2.5 and PM10, PM2.5 and SO2, and PM10 and SO2 occurred on over 146 days in 145 cities, mainly in east China. Surprisingly, multicontaminant air pollution was less frequent in cities with populations over 10 million than in smaller cities. CONCLUSION: Multicontaminant air pollution was common in Chinese cities. A shift from single-contaminant to multicontaminant evaluations of the health effects of air pollution is needed. China should implement protective measures during future urbanization.

Reduction of wheat photosynthesis by fine particulate (PM2.5) pollution over the North China Plain.

The negative impact of rapid urbanization in developing countries has led to a deterioration of urban and regional air quality. Much attention has been given to the impact of fine particulate pollution on urban public health. However, very little attention has been given to its impact on the regional ecosystem such as the agricultural ecosystem. Thus, we evaluate the direct impact of air pollution on the reduction of wheat photosynthesis by fine particulate matter (PM2.5) pollution in the world's most heavily polluted area, the North China Plain, using remote sensing observations and ground measurements. We found the following to be true: (1) Heavy PM2.5 pollution could significantly reduce wheat photosynthesis and cause an expositional relationship between the PM2.5 concentration and wheat photosynthesis (R2 = 0.9824, P < 0.05); (2) Heavy PM2.5 pollution makes up 2% for the reduction in wheat photosynthesis at all wheat-plant farmlands in the North China Plain, approximately covering an area of 354,400 km2; (3) Increasing heavy PM2.5 pollution significantly reduced wheat photosynthesis by 87% in wheat-planted farmland during 1999-2011. We hope the results presented here could draw attention to the effect of PM2.5 pollution on the agricultural ecosystem and encourage further studies to evaluate the feedback of atmospheric pollution on the agricultural ecosystem using remote sensing. Abbreviation: Northern China Plain (NCP); normalized difference vegetation index (NDVI); The Moderate Resolution Imaging Spectroradiometer (MODIS); fine particulate matter (PM2.5).

Up-Regulation of TAB3 Is Involved in Neuronal Apoptosis After Intracerebral Hemorrhage.

Human transforming growth factor ß-activated kinase (TAK1)-binding protein 3 (TAB3) is a regulator of NF-κB which has been mainly found in a variety of cancers. While TAB3 is highly expressed in brain tissue, little is known about the function of TAB3 in central nervous system. Our group established an animal ICH model with autologous whole blood injected into brain, and also a cell ICH model with hemin stimulation. Our Western blot result showed up-regulation of TAB3 during neuronal apoptosis in the model of intracerebral hemorrhage (ICH), which was also approved by immunofluorescence and immunohistochemistry result. Besides, increasing TAB3 level was accompanied by the increased expression of active-caspase-3, active-caspase-8, and decreased expression of Bcl-2. Furthermore, in in vitro study, the level of neuronal apoptosis was decreased by applying TAB3- RNA interference in PC12 cells. All the results above suggested that TAB3 probably participates in the process of neuronal apoptosis following ICH.

O-GlcNAcylation of histone deacetylases 1 in hepatocellular carcinoma promotes cancer progression.

Hepatocellular carcinoma (HCC) is a malignant tumor originating in the liver. Previous studies have indicated that O-GlcNAc transferase (OGT) and histone deacetylase-1 (HDAC1) play important roles in the pathogenesis of HCC. In the present study, we investigated the physical link between OGT and HDAC1. The O-GlcNAcylation of HDAC1 is overexpressed in HCC. We found that HDAC1 has two major sites of O-GlcNAcylation in its histone deacetylase domain. HDAC1 O-GlcNAcylation increases the activated phosphorylation of HDAC1, which enhances its enzyme activity. HDAC1 O-GlcNAc mutants promote the p21 transcription regulation through affecting the acetylation levels of histones from chromosome, and then influence the proliferation of HCC cells. We also found that mutants of O-GlcNAcylation site of HDAC1 affect invasion and migration of HepG2 cells. E-cadherin level is highly up-regulated in HDAC1 O-GlcNAc mutant-treated liver cancer cells, which inhibit the occurrence and development of HCC. Our findings suggest that OGT promotes the O-GlcNAc modification of HDAC1in the development of HCC. Therefore, inhibiting O-GlcNAcylation of HDAC1 may repress the progression of HCC.

Upregulated Expression of Karyopherin α2 is Involved in Neuronal Apoptosis Following Intracerebral Hemorrhage in Adult Rats.

Karyopherin α2 (KPNA2) plays a central role in nucleocytoplasmic transport. It is involved in controlling the flow of genetic information and the modulation of diverse cellular activities. Here we explored the KPNA2's roles during the pathophysiological processes of intracerebral hemorrhage (ICH). An ICH rat model was built and evaluated according to behavioral testing. Using Western blot, immunohistochemistry, and immunofluorescence, significant upregulation of KPNA2 was found in neurons in brain areas surrounding the hematoma following ICH. Increasing KPNA2 level was found to be accompanied by the upregulation of active caspase-3, Bax, and decreased expression of Bcl-2. Besides, KPNA2 co-localized well with active caspase-3 in neurons, indicating its potential role in neuronal apoptosis. What's more, knocking down KPNA2 by RNA-interference in PC12 cells reduced active caspase-3 expression. Thus, KPNA2 may play a role in promoting the brain secondary damage following ICH.

SMAD4 is Involved in the Development of Endotoxin Tolerance in Microglia.

Initial exposure of macrophages to LPS induces hyporesponsiveness to a second challenge with LPS, a phenomenon termed LPS tolerance. Smad4 plays important roles in the induction of LPS tolerance. However, the function of Smad4 in microglia remains unknown. Here we show that expression of Smad4 was highly up-regulated in LPS-tolerized mouse cerebral cortex. Smad4 was mostly colocalized with microglia, rarely with neurons. Using a microglia cell line, BV2, we find that LPS activates endogenous Smad4, inducing its migration into the nucleus and increasing its expression. Smad4 significantly suppressed TLR-triggered production of proinflammatory cytokines (IL-6), increased anti-inflammatory cytokine in LPS-tolerized microglia. Moreover, IL-6 concentrations in culture supernatants after second LPS challenge are higher in SMAD4 small interfering RNA (siRNA) BV2 cells than control siRNA BV2 cells, indicating failure to induce tolerance in absence of Smad4 signaling. In our study, we conclude that both in vivo and in vitro, Smad4 signaling is required for maximal induction of endotoxin tolerance.

A New Role Discovered for IGTP: The Protective Effect of IGTP in ICH-Induced Neuronal Apoptosis.

Interferon gamma-induced GTPase (IGTP), which is also named Irgm3, has been widely described in regulating host resistance against intracellular pathogens. Previous researches have demonstrated that IGTP exerts beneficial function during coxsackievirus B3 (CVB3) infection. However, little information is available regarding the role of IGTP in central nervous system. Here, our study revealed that IGTP may have an essential role during ICH-induced neuronal apoptosis. We found the expression level of IGTP adjacent to hematoma was strongly increased after ICH, accompanied with the up-regulation of proliferating cell nuclear antigen (PCNA), active-caspase-3, p-GSK-3ß, and Bax. IGTP was also observed to be co-localized with PCNA in astrocytes and active-caspase-3 in neurons, indicating its association with astrocyte proliferation and neuronal apoptosis after ICH. Finally, in vitro study, knocking down IGTP with IGTP-specific siRNA promoted active-caspase-3, p-GSK-3ß, and Bax expression, and led to more severe neuronal apoptosis after ICH. All these results above suggested that IGTP might play a critical role in protecting neurons from apoptosis after ICH.

MEKK1 Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage.

The JNKs have been implicated in a variety of biological functions in mammalian cells, including apoptosis and the responses to stress. However, the physiological role of these pathways in the intracerebral hemorrhage (ICH) has not been fully elucidated. In this study, we identified a MAPK kinase kinase (MAPKKK), MEKK1, may be involved in neuronal apoptosis in the processes of ICH through the activation of JNKs. From the results of western blot, immunohistochemistry and immunofluorescence, we obtained a significant up-regulation of MEKK1 in neurons adjacent to the hematoma following ICH. Increasing MEKK1 level was found to be accompanied with the up-regulation of p-JNK 3, p53, and c-jun. Besides, MEKK1 co-localized well with p-JNK in neurons, indicating its potential role in neuronal apoptosis. What's more, our in vitro study, using MEKK1 siRNA interference in PC12 cells, further confirmed that MEKK1 might exert its pro-apoptotic function on neuronal apoptosis through extrinsic pathway. Thus, MEKK1 may play a role in promoting the brain damage following ICH.

Quantifying the characteristics of particulate matters captured by urban plants using an automatic approach.

It is widely accepted that urban plant leaves can capture airborne particles. Previous studies on the particle capture capacity of plant leaves have mostly focused on particle mass and/or size distribution. Fewer studies, however, have examined the particle density, and the size and shape characteristics of particles, which may have important implications for evaluating the particle capture efficiency of plants, and identifying the particle sources. In addition, the role of different vegetation types is as yet unclear. Here, we chose three species of different vegetation types, and firstly applied an object-based classification approach to automatically identify the particles from scanning electron microscope (SEM) micrographs. We then quantified the particle capture efficiency, and the major sources of particles were identified. We found (1) Rosa xanthina Lindl (shrub species) had greater retention efficiency than Broussonetia papyrifera (broadleaf species) and Pinus bungeana Zucc. (coniferous species), in terms of particle number and particle area cover. (2) 97.9% of the identified particles had diameter ≤10 µm, and 67.1% of them had diameter ≤2.5 µm. 89.8% of the particles had smooth boundaries, with 23.4% of them being nearly spherical. (3) 32.4%-74.1% of the particles were generated from bare soil and construction activities, and 15.5%-23.0% were mainly from vehicle exhaust and cooking fumes.

The role of N-glycan modification of TNFR1 in inflammatory microglia activation.

Accumulating evidences demonstrated that microglia activation and the autocrine loop of tumor necrosis factor-α (TNFα) greatly contribute to the pathogenesis of several CNS diseases. TNFα exerts its biological effects by interacting with two different receptors: TNF receptor 1 (TNFR1) and TNFR2. The classic proinflammatory activity of TNFα is mainly mediated by TNFR1. In the present study, we found that TNFR1 was modificated by N-glycosylation on Asn151 and Asn202 in microglia. The N-glycosylation of TNFR1 could facilitate its capability of binding to TNFα and further promote the formation of TNFα autocrine loop in microglia stimulated by TNFα, resulting in excessive microglia activation and CNS inflammation. All these processes were related to TNFR1-mediated NF-κB pathways. Elimination of N-glycosylation did not affect the subcellular transportation and cell surface localization of TNFR1, but suppressed ligand-binding affinity. These findings indicated that the N-glycosylation of TNFR1 played an important role during microglia activation in CNS inflammation. By this study, we aimed to provide some valuable experimental evidence for a better understanding of the significance of protein glycosylation in microglia inflammatory activation and CNS disease.

Up-Regulation of KPNB1 Involves in Neuronal Apoptosis Following Intracerebral Hemorrhage in Adult Rats.

Kpnb1, also known as Importin ß1, is a member of the Karyopherin protein family which plays a important role in nuclear import and export pathways. Its expression has been shown to be responsive to stress, such as heat shock, ethanol and oxidative stress. Previous studies demonstrated that Kpnb1 had anti-apoptotic in cervical cancer. These together prompted us to explore whether Kpnb1 has some association with neuron apoptosis in the pathophysiology of intracerebral hemorrhage (ICH). In our study, an ICH model was established by injecting into the right basal ganglia of adult rats with their autologous whole blood and assessed by behavioral tests. We found Kpnb1 were significantly up-regulated adjacent to the hematoma following ICH by Western blot and immunohistochemistry. Double immunofluorenscence manifested Kpnb1 was strikingly increased in neurons, not astrocytes or microglia. Furthermore, we also found that kpnb1 had co-localizations with active-caspase-3 which is a neuronal apoptosis marker suggesting its role in neuronal apoptosis. What's more, our in vitro study, using Kpnb1 RNA interference in PC12 cells, further indicated that Kpnb1 might exert its pro-apoptotic function on neuronal apoptosis. Therefore, Kpnb1 may play a role in the neuronal apoptosis following ICH.

Meteorological and urban landscape factors on severe air pollution in Beijing.

UNLABELLED: Air pollution gained special attention with the rapid development in Beijing. In January 2013, Beijing experienced extreme air pollution, which was not well examined. We thus examine the magnitude of air quality in the particular month by applying the air quality index (AQI), which is based on the newly upgraded Chinese environmental standard. Our finding revealed that (1) air quality has distinct spatial heterogeneity and relatively better air quality was observed in the northwest while worse quality happened in the southeast part of the city; (2) the wind speed is the main determinant of air quality in the city-when wind speed is greater than 4 m/sec, air quality can be significantly improved; and (3) urban impervious surface makes a contribution to the severity of air pollution-that is, with an increase in the fraction of impervious surface in a given area, air pollution is more severe. The results from our study demonstrated the severe pollution in Beijing and its meteorological and landscape factors. Also, the results of this work suggest that very strict air quality management should be conducted when wind speed less than 4 m/sec, especially at places with a large fraction of urban impervious surface. IMPLICATIONS: Prevention of air pollution is rare among methods with controls on meteorological and urban landscape conditions. We present research that utilizes the latest air quality index (AQI) to compare air pollution with meteorological and landscape conditions. We found that wind is the major meteorological factor that determines the air quality. For a given wind speed greater than 4 m/sec, the air quality improved significantly. Urban impervious surface also contributes to the severe air pollution: that is, when the fraction of impervious surface increases, there is more severe air pollution. These results suggest that air quality management should be conducted when wind speed is less than 4 m/sec, especially at places with a larger fraction of urban impervious surface.

Global synergy of carbon and pollution emissions among countries with different income levels and development stages.

The world was drift away on the sustainable development goals (SDGs), whatever global countries claimed fighting for. It's thus essential to illustrate the status of development and environmental quality simultaneously. Resource consumption and energy consumption as the basic needs in supporting human societal development, are commonly used, because they come from the same source and are most directly observed in the open air. We thus examined nexus of carbon and pollution emissions, which also directly indicate residents' livelihood and lifestyle. The possibility of the nexus shifts among income levels with population stack analysis was further investigated. Our findings indicate that the diverse nexus is strongly correlated with development levels, with urban areas being the primary contributor to high carbon and/or pollution emissions despite occupying only 0.5% of global territory. We conclude that expecting leapfrog stages of the nexus is unrealistic, as cross-income-level change requires approximately 80% of the population to significant change its livelihood and lifestyle. Therefore, we recommend setting science-based targets for decoupling carbon and pollution emissions from development are necessary, but should be adapted and tailored to each country's local practice.

Reducing air pollution does not necessarily reduce related adults' mortality burden: Variations in 177 countries with different economic levels.

Prolonged exposure to PM2.5 is associated with increased mortality. However, reducing air pollution concentrations does not necessarily reduce the related burden of deaths. Here, we aim to estimate the variations in PM2.5-related mortality due to contributions from key factors - PM2.5 concentration, population exposure, and healthcare levels - for 177 countries from 2000 to 2018 at the 1-km grid scale according to the Global Mortality Exposure Model (GEMM) model. We find that global reductions in PM2.5-related deaths mainly come from high and upper-middle income countries, where lowered air pollutant concentration and better healthcare can offset mortality burdens caused by increasing exposed populations. Changes in population exposure to PM2.5 contribute the most (54 %) to change in global related deaths over the examined period, followed by changes in healthcare (-42 %) and pollution concentrations (4 %). The impacts vary across countries and regions within them due to other drivers, which are significantly influenced by development status. Policies aiming at reducing PM2.5 associated health risks need to account for country-specific balances of these key socioeconomic drivers.

Determination of the role of hippocampal astrocytes in the bilateral common carotid artery stenosis mouse model by RNA sequencing.

INTRODUCTION: Bilateral common carotid artery stenosis (BCAS) is used experimentally to model vascular dementia (VaD). Previous studies have primarily focused on the degradation of brain white matter after BCAS. However, hippocampal abnormalities are equally important, and hippocampal astrocytes are specifically involved in neural circuits that regulate learning and memory. Whether hippocampal astrocytes participate in the pathogenesis of BCAS-induced VaD has not been well studied. Therefore, in the present study, we attempted to explore the role of hippocampal astrocytes in BCAS. METHODS: Two months after BCAS, behavioral experiments were conducted to investigate changes in neurological function in sham and BCAS mice. A ribosome-tagging approach (RiboTag) profiling strategy was used to isolate mRNAs enriched in hippocampal astrocytes, and the RNA was sequenced and analyzed using transcriptomic methods. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was utilized to validate the results of RNA sequencing. Immunofluorescence analyses were conducted to evaluate the number and morphology of hippocampal astrocytes. RESULTS: We observed significant short-term working memory impairment in BCAS mice. Moreover, the RNA obtained through RiboTag technology was specific to astrocytes. Transcriptomics approaches and subsequent validation studies revealed that the genes that showed expression changes in hippocampal astrocytes after BCAS were mainly involved in immune system processes, glial cell proliferation, substance transport and metabolism. Furthermore, the number and distribution of astrocytes in the CA1 region of the hippocampus tended to decrease after modeling. CONCLUSION: In this study, comparisons between sham and BCAS mice showed that the functions of hippocampal astrocytes were impaired in BCAS-induced chronic cerebral hypoperfusion-related VaD.

The impacts of urban structure on PM2.5 pollution depend on city size and location.

Many cities across the world face the challenge of severe fine particulate matter (PM2.5) pollution. Among the many factors that affect PM2.5 pollution, there is an increasing interest in the impacts of urban structure. However, quantifying these impacts in China has been difficult due to differences of study area and scale in existing research, as well as limited sample sizes. Here, we conducted a continental study focusing on 301 prefectural cities in mainland China to investigate the effects of urban structure, including urban size and urban compactness, on PM2.5 concentrations. Based on PM2.5 raster and land cover data, we used quantile regression and a general multilinear model to estimate the effects and relative contributions of urban size and urban compactness on urban PM2.5 pollution, with explicit consideration for pollution level, urban size and geographical location. We found: (1) nationwide, the larger and more compact that cities were, the heavier the PM2.5 pollution tended to be. Additionally, this relationship became stronger with increasing levels of pollution. (2) In general, urban size played a more important role than urban form, and there were no significant interactive effects between the two metrics on urban PM2.5 concentrations at the national scale. (3) The impacts of urban size and form varied by city size and geographical location. The impacts of urban size were only significant for small or medium-large cities but not for large cities. Among large cities, only urban form had a significantly positive effect on urban PM2.5 concentrations. The further north and west that cities were, the more dependent PM2.5 pollution was on urban form, whereas the further south and east that cities were, the greater the impact of urban size. These results provide insights into how urban design and planning can be used to alleviate air pollution.

Beyond city expansion: multi-scale environmental impacts of urban megaregion formation in China.

Environmental degradation caused by rapid urbanization is a pressing global issue. However, little is known about how urban changes operate and affect environments across multiple scales. Focusing on China, we found urbanization was indeed massive from 2000 to 2015, but it was also very uneven, exhibiting high internal city dynamics. Urban areas in China as a whole became less green, warmer, and had exacerbated PM2.5 pollution. However, environmental impacts differed in newly developed versus older areas of cities. Adverse impacts were prominent in newly urbanized areas, while old urban areas generally showed improved environmental quality. In addition, regional environmental issues are emerging as cities expand, connect and interact to form urban megaregions. To turn urbanization into an opportunity for, rather than an obstacle to, sustainable development, we must move beyond documenting urban expansion to understand the environmental consequences of both internal city dynamics and the formation of urban megaregions.