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The purpose of this experiment was to investigate the anti-hepatic fibrosis effect of Aronia melanocarpa polysaccharide (AMP) on TAA-induced liver fibrosis mice and its mechanism, as well as the changes in intestinal flora in vivo. This was established with a dose of 200 mg/kg TAA (i.p) once every three days, lasting for eight weeks. Colchicine with 0.4 mg/kg, and AMP (200 and 400 mg/kg) were given by intragastric administration (i.g) after 28 days of intraperitoneal injection of TAA. AMP treatment significantly inhibited the activities of liver injury markers ALT and AST in serum. Histopathological staining demonstrated that AMP significantly reversed TAA-induced hepatocyte necrosis and collagen deposition. In addition, AMP treatment block TGF- β1/Smads pathway inhibited the production of ECM and alleviates liver fibrosis. Furthermore, AMP treatment enhanced the phosphorylation of PI3K/AKT and decreased the expression of its downstream apoptosis-related proteins in liver, thus effectively alleviating TAA-induced liver fibrosis. In addition, 16S rDNA gene sequencing analysis showed that AMP treatment helped restore the imbalanced ecosystem of gut microbes, increased the proportion of Bacteroidetes and Proteobacteria, and increased species richness. Above findings clearly show that AMP is an effective method for treating liver fibrosis, possibly by improving the gut microbiota.

The high cost of wound healing treatment, the slow recovery of wounds, and the uncertainty of being affected by the body's physiological activities constitute a serious burden on public health. In this work, we report the preparation and characterization of chitosan (CS), PVP, and dihydroquercetin (DHQ) nanofiber film used as wound excipients, as well as in vivo and in vitro evaluations, and verify that the film is effective in wounds. The results show that the prepared film has good morphology, thermal stability and hydrophilicity. In vitro studies have shown that it has antibacterial activity against S.aureus and E.coli, and the DPPH free radical scavenging rate proves that the fiber film has antioxidant activity. MTT cytotoxicity test proved that the film is non-toxic to Hacat cells. Animal experiments have proved that wounds treated with CS-PVP-DHQ nanofiber film heal faster. This article also studied the composite nanofiber film by inducing autophagy pathway and increasing the expression of pan-keratin, vascular endothelial growth factor VEGF and CD31 to promote wound healing. Therefore, the nanofiber film herein show great potential in wound healing applications.

Lithium metal battery is one of the most promising candidates for high power portable electronic devices and long-range electric vehicles, due to its ultra-high theoretical energy density when compared with the current commercial Li-ion batteries. Meanwhile, the metallic lithium also brings safety concern because Li+ ions tend to form lithium dendrite on the uneven surface of anode, and subsequently cause short circuit, fire or explosion of the battery. In this review, we summarized the formation mechanism of lithium dendrite and the corresponding inhibiting strategies via functional separators in lithium metal batteries. The lithium dendrite inhibiting strategies via functional separators can be classified into three catalogs: (i) block the growth of lithium dendrite by mechanical barrier, (ii) redistribute the Li+ ion flux when passing through the separator and (iii) induce the uniform deposition of Li+ ions on anode by nucleation sites. The recent advances of the above strategies are reviewed and discussed, existing critical problems and future perspective of functional separators for lithium dendrite inhibition are also discussed.

Background: DNA methylation at the fifth position of cytosine (5mC) is a common epigenetic alteration affecting a range of cellular processes. In recent years, 5-hydroxymethylcytosine (5hmC), an oxidized form of 5mC, has risen broad interests as a potential biomarker for lung cancer diagnosis and survival. Methods: We analyzed the epigenome-wide 5hmC profiles of paired lung tumor and adjacent normal tissues, using the TET-Assisted Bisulfite (TAB) array – Infinium MethylationEPIC BeadChip (EPIC) approach. The differentially methylated CpG sites were identified, and the biological relevance of 5hmC was assessed by differential methylation regions (DMR) analysis and gene set analysis (GSA). Results: We observed global hypomethylation of 5hmC comparing tumor to normal tissues, and hypermethylated 5hmC were enriched in CpG islands and gene upstream. Comparison of 5hmC and 5modC (total methylation: 5mC + 5hmC) profiling showed low correlation, and only a small proportion of the significant 5hmC loci overlapped with the significant total methylation loci. GSA analysis suggested that 5hmC was mainly involved in biological processes such as cellular process, biological regulation, and metabolic process. Conclusion: This is the first study to analyze the epigenome-wide 5hmC profiles among paired lung tumor and normal tissues. We observed global hypomethylation of 5hmC in lung cancers, and hypermethylated 5hmC enriched in CpG islands and gene upstream. We found that the genome-wide 5hmC levels do not correlate with the total methylation, and the GSA suggested different biological functions of 5hmC compared to 5modC. Overall, our results demonstrate the potential of 5hmC as a novel biomarker for lung cancer. Keywords: Lung neoplasms, Epigenomics, Biomarkers, Methylation, 5-Hydroxymethylcytosine

Environmental metal exposures have been associated with multiple deleterious health endpoints. DNA methylation (DNAm) may provide insight into the mechanisms underlying these relationships. Toenail metals are non-invasive biomarkers, reflecting a medium-term time exposure window.This study examined variation in leukocyte DNAm and toenail arsenic (As), cadmium (Cd), lead (Pb), manganese (Mn), and mercury (Hg) among elderly men in the Normative Aging Study, a longitudinal cohort.We repeatedly collected samples of blood and toenail clippings. We measured DNAm in leukocytes with the Illumina HumanMethylation450 K BeadChip. We first performed median regression to evaluate the effects of each individual toenail metal on DNAm at three levels: individual cytosine-phosphate-guanine (CpG) sites, regions, and pathways. Then, we applied a Bayesian kernel machine regression (BKMR) to assess the joint and individual effects of metal mixtures on DNAm. Significant CpGs were identified using a multiple testing correction based on the independent degrees of freedom approach for correlated outcomes. The approach considers the effective degrees of freedom in the DNAm data using the principal components that explain95% variation of the data.We included 564 subjects (754 visits) between 1999 and 2013. The numbers of significantly differentially methylated CpG sites, regions, and pathways varied by metals. For example, we found six significant pathways for As, three for Cd, and one for Mn. The As-associated pathways were associated with cancer (e.g., skin cancer) and cardiovascular disease, whereas the Cd-associated pathways were related to lung cancer. Metal mixtures were also associated with 47 significant CpG sites, as well as pathways, mainly related to cancer and cardiovascular disease.This study provides an approach to understanding the potential epigenetic mechanisms underlying observed relations between toenail metals and adverse health endpoints.

Background: Exploring the associations of air pollution and weather variables with blood leukocyte distribution is critical to understand the impacts of environmental exposures on the human immune system. Objectives: As previous analyses have been mainly based on data from cell counters, which might not be feasible in epidemiologic studies including large populations of long-stored blood samples, we aimed to expand the understanding of this topic by employing the leukocyte distribution estimated by DNA methylation profiles. Methods: We measured DNA methylation profiles in blood samples using Illumina HumanMethylation450 BeadChip from 1519 visits of 774 Caucasian males participating in the Normative Aging Study. Leukocyte distribution was estimated using Houseman's and Horvath's algorithms. Data on air pollution exposure, temperature, and relative humidity within 28 days before each blood draw was obtained. Results: After fully adjusting for potential covariates, PM2.5, black carbon, particle number, carbon monoxide, nitrogen dioxide, sulfur dioxide, temperature, and relative humidity were associated with the proportions of at least one subtype of leukocytes. Particularly, an interquartile range-higher 28-day average exposure of PM2.5 was associated with 0.147-, 0.054- and 0.101-unit lower proportions (z-scored) of plasma cells, naïve CD8+ T cells, and natural killers, respectively, and 0.059- and 0.161-unit higher proportions (z-scored) of naïve CD4+ T cells and CD8+ T cells, respectively. Conclusions: Our study suggests that short-term air pollution exposure, temperature, and relative humidity are associated with leukocyte distribution. Our study further provides a successful attempt to use epigenetic patterns to assess the influences of environmental exposures on human immune profiles. Keywords: Air pollution, Weather variations, DNA methylation, Leukocyte distribution, Epigenetic epidemiology, Environmental health

In this work ZnO/ZnSe composites were successfully synthesized via solvothermal method and characterized by a series of experiments for investigating into their compositions, morphologies, microstructures and the activities of photocatalytic reduction of CO2. The methanol rates of bare ZnO and ZnSe respectively were 763.9 μmol/gcat/h and 503.88 μmol/gcat/h. However, the sample of 3 wt% ZnO/ZnSe performed better photocatalytic activity up 1581.82 μmol/gcat/h compared to bare ZnO and ZnSe. In the as-prepared photocatalyst the nanosheet of ZnSe benefited the light harvest; suitable deposition of ZnO on the ZnSe nanosheet constructed a type II heterojunction for transferring the photo-generated electron to reduce CO2.

BackgroundThe viral entry of SARS-CoV-2 requires host-expressed TMPRSS2 to facilitate the viral spike (S) protein priming.ObjectivesTo test the hypothesis that Mg treatment leads to DNA methylation changes in TMPRSS2.MethodsThis study is nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), a double-blind 2×2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center. Target doses for both Mg and placebo arms were personalized.ResultsWe found that 12-week of personalized Mg treatment significantly increased 5-mC methylation at cg16371860 (TSS1500, promoter) by 7.2% compared to placebo arm (decreased by 0.1%) in those aged < 65 years old. The difference remained statistically significant after adjusting for age, sex and baseline methylation as well as FDR correction (FDR-adjusted P =0.014). Additionally, Mg treatment significantly reduced 5-hmC level at cg26337277 (close proximity to TSS200 and 5’UTR, promoter) by 2.3% compared to increases by 7.1% in the placebo arm after adjusting for covariates in those aged < 65 years old (P=0.003). The effect remained significant at FDR of 0.10 (adjusted P value=0.088).ConclusionAmong individuals aged younger than 65 years with the Ca:Mg intake ratios equal to or over 2.6, reducing Ca:Mg ratios to around 2.3 increased 5-mC modifications (i.e. cg16371860) and reduced 5-hmC modifications (i.e. cg26337277) in the TMPRSS2 gene. These findings, if confirmed, provide another mechanism for the role of Mg intervention for the prevention of COVID-19 and treatment of early and mild disease by modifying the phenotype of the TMPRSS2 genotype.

Background Airborne particulate matter (PM) may induce epigenetic changes that potentially lead to chronic diseases. Histone modifications regulate gene expression by influencing chromatin structure that can change gene expression status. We evaluated whether traffic-derived PM exposure is associated with four types of environmentally inducible global histone H3 modifications. Methods The Beijing Truck Driver Air Pollution Study included 60 truck drivers and 60 office workers examined twice, 1–2 weeks apart, for ambient PM10 (both day-of and 14-day average exposures), personal PM2.5, black carbon (BC), and elemental components (potassium, sulfur, iron, silicon, aluminum, zinc, calcium, and titanium). For both PM10 measures, we obtained hourly ambient PM10 data for the study period from the Beijing Municipal Environmental Bureau's 27 representatively distributed monitoring stations. We then calculated a 24 h average for each examination day and a moving average of ambient PM10 measured in the 14 days prior to each examination. Examinations measured global levels of H3 lysine 9 acetylation (H3K9ac), H3 lysine 9 tri-methylation (H3K9me3), H3 lysine 27 tri-methylation (H3K27me3), and H3 lysine 36 tri-methylation (H3K36me3) in blood leukocytes collected after work. We used adjusted linear mixed-effect models to examine percent changes in histone modifications per each μg/m3 increase in PM exposure. Results In all participants each μg/m3 increase in 14-day average ambient PM10 exposure was associated with lower H3K27me3 (β=−1.1%, 95% CI: −1.6, −0.6) and H3K36me3 levels (β=−0.8%, 95% CI: −1.4, −0.1). Occupation-stratified analyses showed associations between BC and both H3K9ac and H3K36me3 that were stronger in office workers (β=4.6%, 95% CI: 0.9, 8.4; and β=4.1%, 95% CI: 1.3; 7.0 respectively) than in truck drivers (β=0.1%, 95% CI: −1.3, 1.5; and β=0.9%, 95% CI: −0.9, 2.7, respectively; both pinteraction Conclusions Our results suggest a possible role of global histone H3 modifications in effects of traffic-derived PM exposures, particularly BC exposure. Future studies should assess the roles of these modifications in human diseases and as potential mediators of air pollution-induced disease, in particular BC exposure.

The pedestrian mode is an important component of urban networks, and greatly affects the performance of the sidewalks and crosswalks, as well as the entire network traffic operations by interacting with other traffic modes (automobile, bicycle, transit). There have been many studies concerning different aspects of pedestrian behaviors, such as pedestrian walking speed, pedestrian delay, gap acceptance, signal compliance, route choice, etc. The Highway Capacity Manual (HCM) included the pedestrian mode in the HCM 1994 (update to the HCM 1985) and the HCM, 2010 provided several basic technical methodologies for evaluating the pedestrian level of service (LOS) of different urban street facilities. However, it does not fully cover the pedestrian operation in a great detail and it is missing some important findings in recent studies. The objective of this paper is to provide an overview of pedestrian operations in urban networks, to identify the important aspects of pedestrian operation analysis and to provide recommendations for pedestrian facilities in the HCM on the basis of a summary of available U.S. and international literature. The following topics will be discussed: pedestrian movement models, pedestrian delay estimation, pedestrian-vehicle interactions, and pedestrian travel time estimation. The major features of pedestrian movement along urban segments are the walking speed and available space, which were well examined in past studies. Pedestrian delay is one important measure of pedestrian operation, and its estimation models at signalized/unsignalized intersections are presented with respect to different scenarios. Modifications to the delay model in the HCM, 2010 are highlighted. Pedestrian-vehicle interactions highly affect traffic operations. Both driver and pedestrian behaviors in such an interaction were observed in the field and were examined quantitatively. Pedestrian jaywalking behavior was also observed and its impact on traffic is discussed. Pedestrian route choice at the strategic level and crossing location selection at the operational level jointly determine the pedestrian moving path and further affect the travel time at path-level. A model for estimating pedestrian travel time in an urban network is developed and presented. Such a model can be used to evaluate the facility performance as well as serve for pedestrian route selection. This paper identifies the important aspects of pedestrian operation analysis in an urban network and provides several recommendations to the HCM.

Pedestrian and driver behaviors as well as their interactions, are essential in planning, designing and operating highway facilities. Pedestrian crossing outside of a marked or unmarked crosswalk (i.e. jaywalking), is one of those pedestrian behaviors that may highly affect safety and operations. Unlike permissible crossings at crosswalks, jaywalking events are not often anticipated by drivers, which may result in less driver reaction time and different vehicle operation dynamics. It is important to understand pedestrian crossing behavior outside of crosswalks, as well as driver yielding behavior towards them. To date, limited quantitative and behavioral research has been conducted to investigate this interaction or simulate it microscopically. This paper aims to explore both pedestrian jaywalking behavior (gap acceptance and speeds) and the corresponding driver reactions (yielding behavior) for modeling the vehicle–pedestrian interactions (VPI) outside the crosswalks in a micro-simulation environment. The study also quantifies the differences between vehicle–jaywalker and vehicle-permissible crossing. An observational study and an instrumented vehicle study were conducted on the campus of the University of Florida to collect data from pedestrian and driver perspectives, respectively. Crossing speed, yield acceptance and delay of jaywalking crossings and permissible crossings were observed in the study and these attributed can be used for replicating pedestrian operations in simulators. Moreover, behaviors of driver approaching jaywalkers versus pedestrians crossing at designated crosswalks were compared on the basis of yield rates, and vehicle speed profiles. Vehicle yield dynamics were analyzed to model the driver reactions towards jaywalkers. Lastly, it was found that the locations of jaywalking events are highly concentrated and influenced by the crossing environment, such as pedestrian and vehicular volume, bus stops presence and crossing distance. This paper establishes several quantitative relationships describing interactions between pedestrians crossing outside of crosswalks and approaching drivers, which provide the basis and assumptions for modeling such interactions in a micro-simulation environment for traffic operational analyses.

How to balance ecosystem health and economic development is essential to study sustainability of urban ecosystems. Many methods for assessing urban sustainability have been developed, among which ecological footprint analysis (EFA) has been widely applied as a promising policy and planning tool. This paper proposed a modified EFA with the local ecological footprint being justified by adapting equivalence and yield factors in context of net primary productivity (NPP) from the Miami model. Biodiversity reserves were also incorporated using GIS technology and synthetic assessment of attributes to reflect various ecological functions. In addition, ecological footprint deficit (EFD), implying that the productive land cannot sustain current levels of consumption for a given population, was used to reveal the extent of ecological debt, while the ecological footprint variation index (EFVI) was proposed to describe the tradeoffs between real consumption and the carrying capacity of a specific region. A case study of urban areas in the middle stream of the Yangtze River Basin showed that the per capita EFD of the Wanjiang urban belt, central Poyang Lake urban agglomeration, suburban Poyang Lake urban agglomeration, Wuhan megalopolis, Jingmen–Jingzhou–Yichang urban agglomeration, central Changsha–Zhuzou–Xiangtan urban agglomeration, and suburban Changsha–Zhuzou–Xiangtan urban agglomeration increased by 64.83%, 178.05%, 214.82%, 59.08%, 71.68%, 100.62%, and 91.06% between 2000 and 2010, respectively. The local ecological footprint pressure index (EFPI) was classified into five levels. The Poyang lake urban agglomeration was found to be in a slight deficit, while all others were in a severe deficit in 2010. Calculations of EFVI also revealed that the booming urbanization occurred at great cost to the deteriorating ecosystems between 2000 and 2010. Accordingly, relevant influence factors were investigated using a forward stepwise regression method, which indicated that ecological deficit was positively correlated with GDP, population density, and emission of industrial waste, but negatively correlated with the tertiary industry.

article i nfo Background: Accelerated telomere shortening may cause cancer via chromosomal instability, making it a poten- tially useful biomarker. However, publications on blood telomere length (BTL) and cancer are inconsistent. We prospectively examined BTL measures over time and cancer incidence. Methods: We included 792 Normative Aging Study participants with 1-4 BTL measurements from 1999 to 2012. We used linear mixed-effects models to examine BTL attrition by cancer status (relative to increasing age and decreasing years pre-diagnosis), Cox models for time-dependent associations, and logistic regression for cancer incidence stratified by years between BTL measurement and diagnosis. Findings: Age-related BTL attrition was faster in cancer cases pre-diagnosis than in cancer-free participants (pdifference= 0.017); all participants had similar age-adjusted BTL 8-14 years pre-diagnosis, followed by deceler- ated attrition in cancer cases resulting in longer BTL three (p = 0.003) and four (p = 0.012) years pre-diagnosis. Longer time-dependent BTL was associated with prostate cancer (HR = 1.79, p = 0.03), and longer BTL mea- sured ≤4 years pre-diagnosis with any (OR = 3.27, p b 0.001) and prostate cancers (OR = 6.87, p b 0.001). Interpretation: Age-related BTL attrition was faster in cancer cases but their age-adjusted BTL attrition began decelerating as diagnosis approached. This may explain prior inconsistencies and help develop BTL as a cancer detection biomarker. © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license

Pesticide exposure has repeatedly been associated with cancers. However, molecular mechanisms are largely undetermined. In this study, we examined whether exposure to diazinon, a common organophosphate that has been associated with cancers, could induce DNA methylation alterations. We conducted genome-wide DNA methylation analyses on DNA samples obtained from human hematopoietic K562 cell exposed to diazinon and ethanol using the Illumina Infinium HumanMethylation27 BeadChip. Bayesian-adjusted t-tests were used to identify differentially methylated gene promoter CpG sites. We identified 1069 CpG sites in 984 genes with significant methylation changes in diazinon-treated cells. Gene ontology analysis demonstrated that some genes are tumor suppressor genes, such as TP53INP1 (3.0-fold, q-value

Pressurised liquid extraction (PLE) of three major flavones (hesperidin, nobiletin, and tangeretin) from the peels of Citrus reticulata ‘Chachi’ (Guangchenpi) was investigated. These flavones were quantified and analysed by liquid chromatography–diode array detector–electrospray ionisation mass spectrometry (LC–DAD–ESI/MS). The PLE procedure was optimised, validated and compared with other conventional extraction techniques. PLE gained the best result due to the highest extraction efficiency within the shortest extraction time. The optimal conditions of PLE were employing 70% methanol as extraction solvent at a temperature of 160 °C and extraction pressure of 1500 psi, using one extraction cycle with a static extraction time of 20 min. MS coupling with an ESI interface in the positive ion mode was used as the detection technique. This is the first report on combining PLE with LC–DAD–ESI/MS for the extraction and quantification of flavones in Citrus reticulata ‘Chachi’.