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Background: Mean perfusion pressure (MPP) has recently emerged as a potential biomarker for personalized management of tissue perfusion in critically ill patients. However, its association with the occurrence of acute kidney injury (AKI) in septic patients and the optimal MPP range remain uncertain. Therefore, this study aims to investigate the relationship between MPP and AKI in critically ill patients with sepsis., Methods: We identified 5867 patients with sepsis from the MIMIC-IV database who met the inclusion and exclusion criteria. The exposure variable was the first set of MPP measured within 24 h after ICU admission with invasive hemodynamic monitoring. The primary outcome was the incidence of AKI at 7 days following ICU admission according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Secondary outcomes included in-hospital mortality, lengths of ICU, and hospital stay. Optimal cut-off point for MPP were determined using the Youden index, and multivariable logistic regression was employed to examine the association between MPP and AKI. Subgroup analyses were conducted to enhance result robustness. Kaplan-Meier survival analysis was utilized to evaluate in-hospital mortality rates categorized by MPP., Results: A total of 5,867 patients with sepsis were included in this study, and the overall incidence of AKI was 82.3%(4828/5867). Patients were categorized into low MPP (< 63 mmHg) and high MPP (≥ 63 mmHg) groups using the optimal ROC curve-derived cut-off point. The incidence of AKI in the low MPP group was higher than that in the high MPP group (87.6% vs. 78.3%, P < 0.001). Multivariable logistic regression analysis adjusted for confounding factors revealed that each 1 mmHg increase in MPP as a continuous variable was associated with a 2% decrease in AKI incidence within 7 days of ICU admission (OR:0.98, 95%CI:0.97-0.99, P < 0.001). When MPP was used as a categorical variable, patients in the high MPP group had a lower risk of AKI than those in the low MPP group (OR:0.71, 95%CI:0.61-0.83, P = 0.001). Subgroup analyses demonstrated a consistent association between MPP and AKI risk across all variables assessed (P for interaction all > 0.05). Kaplan-Meier curve analysis demonstrated a higher survival rate during hospitalization in the high MPP group compared to the low MPP group (Log-rank test, P < 0.0001)., Conclusions: Lower levels of MPP are associated with an increased incidence of AKI at 7 days in critically ill patients with sepsis., (© 2024. The Author(s).)

Firework (FW) events occur during various festivals worldwide and substantially negatively influence both air quality and human health. However, the effects of FWs on the chemical properties and formation of organic aerosols are far from clear. In this study, fine particulate matter (PM 2.5 ) samples were collected in a suburban area in Qingdao, China during the Chinese Spring Festival. The concentrations of chemical species (especially carbonaceous components) in PM 2.5 were measured using a combination of several state-of-the-art techniques. Our results showed that mass concentrations of water-soluble sulfate, potassium and chloride ions, and organic carbon drastically increased and became the predominant components in PM 2.5 during FW events. Correspondingly, both the number and fractional contributions of sulfur (S)-containing subgroups (e.g., CHOS and CHONS compounds) and some chlorine (Cl)-containing organic (e.g., CHOSCl and CHONSCl) compounds identified using ultrahigh-resolution Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) increased. The S- and Cl-containing compounds unique to the FW display period were identified, and their chemical characterization, sources, and formation mechanisms were elucidated by combining FT-ICR MS and quantum chemical calculations. Our results suggest that FW emissions play notable roles in both primary and secondary organic aerosol formation, especially for CHOS- and Cl-containing organic compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The widespread occurrence of emerging brominated flame retardant tetrabromobisphenol S (TBBPS) has become a major environmental concern. In this study, a nanoscale zero-valent iron (nZVI) impregnated organic montmorillonite composite (nZVI-OMT) was successfully prepared and utilized to degrade TBBPS in aqueous solution. The results show that the nZVI-OMT composite was very stable and reusable as the nZVI was well dispersed on the organic montmorillonite. Organic montmorillonite clay layers provide a strong support, facilitate well dispersion of the nZVI chains, and accelerate the overall TBBPS transformation with a degradation rate constant 5.5 times higher than that of the original nZVI. Four major intermediates, including tribromobisphenol S (tri-BBPS), dibromobisphenol S (di-BBPS), bromobisphenol S (BBPS), and bisphenol S (BPS), were detected by high-resolution mass spectrometry (HRMS), indicating sequential reductive debromination of TBBPS mediated by nZVI-OMT. The effective elimination of acute ecotoxicity predicted by toxicity analysis also suggests that the debromination process is a safe and viable option for the treatment of TBBPS. Our results have shown for the first time that TBBPS can be rapidly degraded by an nZVI-OMT composite, expanding the potential use of clay-supported nZVI composites as an environmentally friendly material for wastewater treatment and groundwater remediation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Owing to the potential influence of light-absorbing organic carbon (OC), also termed "brown carbon" (BrC), on the planetary radiation budget, many studies have focused on its absorption in single-sized ranges of particulate matter (PM). However, the size distribution and organic tracer-based source apportionment of BrC absorption have not been extensively investigated. In this study, size-resolved PM samples were collected using multi-stage impactors from eastern Nanjing during each season in 2017. The light absorption of methanol-extractable OC at 365 nm (Abs 365 , Mm -1 ) was determined using spectrophotometry, and a series of organic molecular markers (OMMs) was measured using a gas chromatography-mass spectrometer. Fine PM with an aerodynamic diameter <2.1 μm (PM 2.1 ) dominated Abs 365 (79.8 ± 10.4%) of the total size ranges with maxima and minima in winter and summer, respectively. The distributions of Abs 365 shifted to larger PM sizes from winter to spring and summer due to lower primary emissions and increased BrC chromophores in dust. Except for low-volatility (p o, * L  < 10 -10  atm) polycyclic aromatic hydrocarbons (PAHs), the non-polar OMMs, including n-alkanes, PAHs, oxygenated PAHs, and steranes, showed a bimodal distribution pattern. Secondary products of biogenic precursors and biomass burning tracers presented a unimodal distribution peaking at 0.4-0.7 μm, while sugar alcohols and saccharides were enriched in coarse PM. Their seasonal variations in average concentrations reflected intense photochemical reactions in summer, more biomass burning emissions in winter, and stronger microbial activity in spring and summer. Positive matrix factorization was used for the source apportionment of Abs 365 in fine and coarse PM samples. Biomass burning contributed an average of 53.9% to the Abs 365 of PM 2.1 extracts. The Abs 365 of coarse PM extracts was associated with various dust-related sources where the aging processes of aerosol organics could occur., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: An increasing body of evidence supports an essential role for endoplasmic reticulum stress (ERS) in colorectal cancer (CRC). In this study, we developed an ERS-related genes (ERSRGs) model to aid in the prognostic evaluation and treatment of CRC patients., Methods: The training set and validation set data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. ERSRGs were obtained from the GeneCards database. A prognostic risk scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) along with univariate Cox regression analysis. To further predict the probability of survival for patients at 1, 2, and 3 years, a nomogram was devised. The advantages of the prognostic risk score model in screening patients' sensitive to chemotherapy and immunotherapy were analyzed by drug sensitivity analysis and immune correlation analysis. Finally, hub genes associated with poor prognosis in the risk model were screened by Protein-protein interaction (PPI) network and their expression was validated using clinical specimens., Results: A risk model for overall survival (OS) was developed using 16 ERSRGs associated with prognosis. Through analyses, we demonstrated a high degree of reliability for the prognostic risk scoring model. The constructed nomograms performed well in predicting patient survival over 1, 3, and 5 years. The calibration curve and decision curve analysis (DCA) supported a high degree of accuracy for the model. Patients in the low-risk group had a lower IC50 for the common chemotherapy drug, 5-FU, and responded better to immunotherapy. hub poor prognostic genes were validated in CRC clinical specimens., Conclusion: We have identified and validated a new ERS prognostic marker that can accurately predict the survival status of CRC patients for clinicians and better provide personalized treatment plans., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Combining technology with finance is the focus of supporting economic structure adjustment, and environmental benefits are also the proper meaning of the policy. Using the panel data of 274 cities in China from 2006 to 2017, this paper examines the impact of the Science and Technology Finance Policy (STFP) on carbon emission intensity in pilot cities and the transmission mechanisms through the difference-in-differences method and further explores the impact of STFP on the carbon emission intensity in neighboring cities. The results show that (1) STFP has significantly reduced carbon emission intensity in pilot cities and has dynamic effects, which gradually increase over time. There is significant heterogeneity in the carbon emission reduction effect of STFP, which produces stronger policy effects in first and second-tier cities and cities with higher information levels. (2) STFP achieves carbon emission reduction effects through three main pathways: the total factor productivity improvement effect, innovative elements agglomeration effect, and industrial structure optimization effect. (3) The STFP and national e-commerce demonstration policy have an interactive effect, and the two jointly contribute to the reduction in carbon emission intensity. From the perspective of a spatial effect, STFP has a radiation effect; that is, STFP not only reduces local carbon emission intensity but also curbs the carbon emission intensity in neighboring areas.

Hourly PM 2.5 speciation data have been widely used as an input of positive matrix factorization (PMF) model to apportion PM 2.5 components to specific source-related factors. However, the influence of constant source profile presumption during the observation period is less investigated. In the current work, hourly concentrations of PM 2.5 water-soluble inorganic ions, bulk organic and elemental carbon, and elements were obtained at an urban site in Nanjing, China from 2017 to 2020. PMF analysis based on observation data during specific pollution (firework combustion, sandstorm, and winter haze) and emission-reduction (COVID-19 pandemic) periods was compared with that using the whole 4-year data set (PMF whole ). Due to the lack of data variability, event-based PMF solutions did not separate secondary sulfate and nitrate. But they showed better performance in simulating average concentrations and temporal variations of input species, particularly for primary source markers, than the PMF whole solution. After removing event data, PMF modeling was conducted for individual months (PMF month ) and the 4-year period (PMF 4-year ), respectively. PMF month solutions reflected varied source profiles and contributions and reproduced monthly variations of input species better than the PMF 4-year solution, but failed to capture seasonal patterns of secondary salts. Additionally, four winter pollution days were selected for hour-by-hour PMF simulations, and three sample sizes (500, 1000, and 2000) were tested using a moving window method. The results showed that using short-term observation data performed better in reflecting immediate changes in primary sources, which will benefit future air quality control when primary PM emissions begin to increase., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Size-segregated ambient particulate matter (PM) samples were collected seasonally in suburban Nanjing of east China from 2016 to 2017 and chemically speciated. In both fine (< 2.1 µm, PM 2.1 ) and coarse (> 2.1 µm, PM >2.1 ) PM, organic carbon (OC) accounted for the highest fractions (26.9% ± 10.9% and 23.1% ± 9.35%) of all measured species, and NO 3 - lead in average concentrations of water-soluble inorganic ions (WSIIs). The size distributions of measured components were parameterized using geometric mean diameter (GMD). GMD values of NO 3 - , Cl - , OC, and PM for the whole size range varied from < 2.1 µm in winter to > 2.1 μm in warm seasons, which was due to the fact that the size distributions of semi-volatile components (e.g., NH 4 NO 3 , NH 4 Cl, and OC) had a dependency on the ambient temperature. Unlike OC, elemental carbon (EC), and elements, NH 4 + , NO 3 - , and SO 4 2- exhibited an increase trend in GMD values with relative humidity, indicating that the hygroscopic growth might also play a role in driving seasonal changes of PM size distributions. Positive matrix factorization was performed using compositional data of fine and coarse particles, respectively. The secondary formation of inorganic salts contributing to the majority (> 70%) of fine PM and 20.2% ± 19.9% of speciated coarse PM. The remaining coarse PM content was attributed to a variety of dust sources. Considering that coarse and fine PM had comparable mass concentrations, more attention should be paid to local dust emissions in future air quality plans., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: The number of  neuroendocrine tumors (NETs) is gradually increasing worldwide, and those located in the small intestine (siNETs) are the most common. As some biological and clinical characteristics of tumors of the jejunum and the ileum differ, there is a need to assess the prognosis of individuals with siNETs of the jejunum and ileum separately. We generated a predictive nomogram by assessing individuals with siNETs from the Surveillance, Epidemiology, and End Results (SEER) database., Methods: We used univariate Cox regression analysis to determine both the overall survival (OS) and the cancer-specific survival (CSS) of 2501 patients with a pathological confirmation of siNETs of the jejunum and ileum. To predict 3-, 5-, and 10-year OS of siNETs, a nomogram was generated based on a training cohort and validated with an external cohort. Accuracy and clinical practicability were evaluated separately by Harrell's C-indices, calibration plots, and decision curves. The correlation was examined between dissected lymph nodes and positive lymph nodes., Results: Dissection of 7 or more lymph nodes significantly improved patient OS and was found to be a protective factor for patients with siNETs. In Cox regression analyses, age, primary site, tumor size, N stage, M stage, and regional lymph node examination were significant predictors in the nomogram. A significant positive correlation was found between dissected lymph nodes and positive lymph nodes., Conclusions: Patients with 7 or more dissected lymph nodes showed an accurate tumor stage and a better prognosis. Our nomogram accurately predicted the OS of patients with siNETs., (© 2022. The Society for Surgery of the Alimentary Tract.)

Background: Acetaminophen (APAP) overdose can cause severe liver injury and APAP-induced liver injury (AILI) is one of the leading causes of acute liver failure (ALF). Bruton's tyrosine kinase (BTK) is a key tyrosine kinase in immune responses, which plays an important role in many inflammatory diseases. However, its effect on AILI is still not clear. Here, we aimed to assess the effect of BTK on AILI and explore its underlying mechanism., Methods: In our study, western blot and immunohistochemistry were used to detect the expression of BTK in AILI. The C57BL/6 mice were used to check the protective effect of BTK inhibition on AILI and the activation of BTK was confirmed in mice macrophages treated with APAP. Immunofluorescence, immunohistochemistry, oxygen consumption rate (OCR) detection, polymerase chain reaction (PCR), flow cytometry and western blot were used to determine the role of BTK in mitochondrial dynamics and function of macrophages and the underlying mechanisms in AILI., Results: Our results showed that BTK upregulated in AILI. BTK inhibition protected mice from AILI and BTK was activated in mice macrophages in response to APAP. Mechanically, BTK inhibition promoted mitochondrial fusion and restored mitochondrial function through phospholipase C gamma 2 (PLCγ2)-reactive oxygen species (ROS)-Optic Atrophy 1(OPA1) pathway in macrophages and finally suppressed the release of proinflammatory cytokines., Conclusions: In conclusion, we found that BTK inhibition protected mice from AILI by restoring the mitochondrial function of macrophages through the improvement of the mitochondrial dynamic imbalance via PLCγ2-ROS-OPA1 signaling pathway, which indicated that BTK might be a potential therapeutic target of AILI., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The Comprehensive Air-quality Model with extensions (CAMx) was used to explore the sensitivity of PM 2.5 and O 3 concentrations to four selected meteorological factors: wind speed, temperature, water vapor mixing ratio (Q), and planetary boundary layer height (PBLH) during two pollution episodes over the North China Plain (NCP). We also investigated the impact pathways of different meteorological factors on the formation of PM 2.5 and O 3. It is found that PM 2.5 was more sensitive to the selected meteorological factors in the southeastern NCP, where high anthropogenic emissions and severe air pollution occur. Large variations were observed along the Taihang Mountains, where the height of the terrain changes dramatically. The sensitivity of O 3 to wind speed, PBLH, temperature, and Q was mainly determined by the inhibition effects of PM 2.5 in winter, while in summer, the complex chemical reactions were dominant. Significant diurnal variations of process analysis (PA) results were observed under various meteorological conditions. Higher temperature generally enhance heterogeneous chemistry and transport of NO 3 - through the top boundary layer during night-time in winter, however, in summer, the heterogeneous chemistry of NO 3 - and NH 4 + during daytime were the major pathways to the increased PM 2.5 due to increased temperature. Moreover, temperature alter PM 2.5 concentrations through affecting vertical diffusivity and relative humidity, and alter O 3 concentrations by affecting the gas phase chemistry and mass fluxes through the top boundary layer. Q mainly affects the rate of chemical reactions of PM 2.5 and O 3 . The different impact pathways suggest that it is essential to consider variations in meteorological factors, in addition to the direct impacts of wind speed and PBLH, more attention should be paid to the complex impacts of temperature and Q, when developing emission control strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Air pollution is the result of enormous emissions and unfavorable meteorological conditions. The role of meteorology, particularly extremely unfavorable meteorological events (EUMEs), in processing atmospheric PM 2.5 pollution has not been fully addressed. This work examined the variations of PM 2.5 mass and its chemical components associated with various meteorological parameters and three EUMEs based on meteorological observations and analysis combined with one-year long in situ measurement in 2018 in the suburban area of Tianjin, China. Analysis shows that the polluted days in 2018 were mostly related to the increase in sulfate, nitrate, and ammonium (SNA). Temperature between -2 to 13 °C is more favorable for the formation of SNA, while high temperature exceeding 28 °C is favorable for the formation of organic carbon and sulfate. Most of the ions and carbon components showed significant increase in concentrations when relative humidity exceeded 80%. The maximum decreasing rate of PM 2.5 concentrations due to increase in wind speed and planetary boundary height could be 15.35 μg m -3 (m s -1 ) -1 , and 34.37 μg m -3 (100 m) -1 , respectively. EUMEs showed significant impacts on PM 2.5 components, in which PM 2.5 concentrations showed the most significant increase under temperature inversion (TI) events, and surface-based TI (SBTI) events usually have much stronger impacts on PM 2.5 concentrations than elevated TI (ELTI). Nitrate was found to be the most sensitive component to EUMEs, especially under multiple EUMEs. The synthetic effects of multiple EUMEs could result in an increase of nitrate by 35.53 μg m -3 (523.3%). In addition, OC and sulfate are more sensitive to heat wave events. Our analysis provides improved understanding of the formation of PM 2.5 pollution with respect to meteorology, particularly EUMEs. Based on such information, more attention may be needed on the collaborative prediction of EUMEs and air pollution episodes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Metabolic-associated fatty liver disease (MAFLD) is a common type of chronic liver disease characterized by excessive lipid accumulation in hepatocytes, but the pathogenesis is still unclear. Neutrophils, the most abundant immune cells in the human body, defend against pathogens and regulate the inflammatory response. Recent studies have indicated that excessive liver infiltration of neutrophils is a significant histological hallmark of MAFLD, and neutrophils and their derived granule proteins participate in different stages of MAFLD, including hepatic steatosis, inflammation, fibrosis, cirrhosis and hepatocellular carcinoma. Hence, in this review, we summarize the role of neutrophils in the occurrence and progression of MAFLD and provide a perspective for the clinical application of neutrophils in MAFLD diagnosis and treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Acetaminophen (APAP) is a widely applied drug for the alleviation of pain and fever, which is also a dose-depedent toxin. APAP-induced acute liver injury has become one of the primary causes of liver failure which is an increasingly serious threat to human health. Neutrophils are the major immune cells in human serving as the first barrier against the invasion of pathogen. It has been reported that neutrophils patriciate in the occurrence and development of APAP-induced liver injury. However, evolving evidences suggest that neutrophils also contribute to tissue repair and actively orchestrate resolution of inflammation. Here, we addressed the complex roles in APAP-induced liver injury on the basis of brief introduction of neutrophil's activation, recruitment and migration., (© 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

Hepatitis B virus (HBV) infection is a major public health problem. The high levels of HBV DNA and HBsAg are positively associated with the development of secondary liver diseases, including hepatocellular carcinoma (HCC). Current treatment with nucleos(t)ide analogues mainly reduces viral DNA, but has minimal, if any, inhibitory effect on the viral antigen. Although IFN reduces both HBV DNA and HBsAg, the serious associated side effects limit its use in clinic. Thus, there is an urgent demanding for novel anti-HBV therapy. In our study, viral parameters were determined in the supernatant of HepG2.2.15 cells, HBV-expressing Huh7 and HepG2 cells which transfected with HBV plasmids and in the serum of HBV mouse models with hydrodynamic injection of pAAV-HBV1.2 plasmid. RT-qPCR and Southern blot were performed to detect 35kb mRNA and cccDNA. RT-qPCR, Luciferase assay and Western blot were used to determine anti-HBV effects of MLN4924 and the underlying mechanisms. We found that treatment with MLN4924, the first-in-class neddylation inhibitor currently in several phase II clinical trials for anti-cancer application, effectively suppressed production of HBV DNA, HBsAg, 3.5kb HBV RNA as well as cccDNA. Mechanistically, MLN4924 blocks cullin neddylation and activates ERK to suppress the expression of several transcription factors required for HBV replication, including HNF1α, C/EBPα and HNF4α, leading to an effective blockage in the production of cccDNA and HBV antigen. Our study revealed that neddylation inhibitor MLN4924 has impressive anti-HBV activity by inhibiting HBV replication, thus providing sound rationale for future MLN4924 clinical trial as a novel anti-HBV therapy., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

In this study, hourly concentrations of PM 2.5 water-soluble inorganic ions, bulk organic carbon (OC), and elemental carbon (EC) were monitored from 1/1/2017 to 12/31/2017 and validated using filter-based offline analysis at an urban site in Nanjing, China. Compared with 2013 or before, the annual average of PM 2.5 concentration (36.5 ± 32.9 μg m -3 ) in 2017 decreased by more than 40%, NO 3 - (12.8 ± 11.4 μg m -3 ) became the most abundant water-soluble ion instead of SO 4 2- (9.29 ± 6.07 μg m -3 ), and the relative contribution of OC (5.92 ± 3.40 μg m -3 ) and EC (2.95 ± 1.53 μg m -3 ) to bulk PM 2.5 (24.9 ± 9.31%) increased substantially, indicating the effectiveness of the control policy for reducing gaseous precursor emissions. Based on the diurnal variations of water-soluble ions and gaseous pollutants, NH 4 + , SO 4 2- , and NO 3 - were secondarily formed and NH 4 NO 3 dominated the composition of ammonium salts in PM 2.5 . The diurnal changes of OC, EC, and OC/EC ratios reflected prominent influences from local traffic patterns. Positive matrix factorization was performed using hourly data of PM 2.5 components (PMF 1-h ), of which the results were justified by comparing to those using 23-h averaged data (PMF 23-h ). Given that the secondary ion formation was still the dominant source (68.2%) of PM 2.5 , and the average PM 2.5 concentration in urban Nanjing remained higher than Tier II limit (35 μg m -3 ) of the Chinese National Ambient Air Quality Standard, controlling emissions of PM 2.5 precursor gases should be continued after the completion of Air Pollution Prevention and Control Action Plan in 2017., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hepatocellular carcinoma (HCC) is an aggressive malignancy with high rates of metastasis and relapse. Isoquercitrin (ISO), a natural flavonoid present in the Chinese bayberry and other plant species, reportedly exerts notable inhibitory effects on tumor cell proliferation, though the mechanism is unknown. In the present study, we exposed HepG2 and Huh7 human liver cancer cells to ISO and examined the roles of autophagy and apoptosis in ISO-mediated cell death. We found that ISO exposure inhibited cell viability and colony growth, activated apoptotic pathway, and triggered dysregulated autophagy by activating the AMPK/mTOR/p70S6K pathway. Autophagy inhibition using 3-methyladenine (3-MA) or Atg5-targeted siRNA decreased the Bax/Bcl-2 ratio, caspase-3 activation, and PARP cleavage and protected cells against ISO-induced apoptosis. Moreover, autophagy inhibition reversed the upregulation of AMPK phosphorylation and downregulation of mTOR and p70S6K phosphorylation elicited by ISO. By contrast, application of a broad-spectrum caspase inhibitor failed to inhibit autophagy in ISO-treated cells. These data indicate that ISO simultaneously induced apoptosis and autophagy, and abnormal induction of autophagic flux contributed to ISO-triggered caspase-3-dependent apoptosis.

N-containing aromatic compounds (NACs) are an important group of light-absorbing molecules in the atmosphere. They are often observed in combustion emissions, but their chemical formulas and structural characteristics remain uncertain. In this study, red oak wood and charcoal fuels were burned in cookstoves using the standard water boiling test (WBT) procedure. Submicron aerosol particles in the cookstove emissions were collected using quartz (Q f ) and polytetrafluoroethylene (PTFE) filter membranes positioned in parallel. A back-up quartz filter (Q b ) was also installed downstream of the PTFE filter to evaluate the effect of sampling artifact on NACs measurements. Liquid chromatography-mass spectroscopy (LC-MS) techniques identified seventeen NAC chemical formulas in the cookstove emissions. The average concentrations of total NACs in Q b samples (0.37 ± 0.31 - 1.79 ± 0.77 μg m -3 ) were greater than 50% of those observed in the Q f samples (0.51 ± 0.43 - 3.91 ± 2.06 μg m -3 ), and the Q b to Q f mass ratios of individual NACs had a range of 0.02 - 2.71, indicating that the identified NACs might have substantial fractions remaining in the gas-phase. In comparison to other sources, cookstove emissions from red oak or charcoal fuels did not exhibit unique NAC structural features, but had distinct NACs composition. However, before identifying NACs sources by combining their structural and compositional information, the gas-particle partitioning behaviors of NACs should be further investigated. The average contributions of total NACs to the light absorption of organic matter at λ = 365 nm (1.10 - 2.57%) in Q f and Q b samples (10.7 - 21.0%) are up to 10 times larger than their mass contributions (Q f 0.31 - 1.01%, Q b 1.08 - 3.31%), so the identified NACs are mostly strong light absorbers. To explain more sample extracts absorption, future research is needed to understand the chemical and optical properties of high molecular weight (e.g., MW > 500 Da) entities in particulate matter., Competing Interests: Competing interests The authors declare that they have no conflict of interest.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally with more than 33 million patients diagnosed, taking more than a million lives. Abundant mutations were observed but the functional consequences of these mutations are largely unknown. We report the mutation spectrum, replication dynamics, and infectivity of 11 patient-derived viral isolates in diverse cell lines, including the human lung cancer cell line Calu-3. We observed 46 mutations, including 9 different mutations in the spike gene. Importantly, these viral isolates show significant and consistent variations in replication dynamics and infectivity in tested cell lines, up to a 1500-fold difference in viral titers at 24 h after infecting Calu-3 cells. Moreover, we show that the variations in viral titers among viral isolates are positively correlated with blood clotting function but inversely correlated with the amount of red blood cell and hemoglobin in patients. Therefore, we provide direct evidence that naturally occurring mutations in SARS-CoV-2 can substantially change its replication dynamics and infectivity in diverse human cell lines, with clinical implications in vivo.

The influence of atmosphere pollution on human health is receiving more and more concerns as strengthened anthropogenic activity had brought excessive pollutant into the atmosphere. To date, the quantitative estimation about the contribution of atmosphere on the accumulation of heavy metal in the edible cereal parts induced by anthropogenic forcing is scarce. Taking the Yangtze River Delta area, China as an example, this study estimates quantitatively the influence of atmosphere on the concentration of heavy metal in the aboveground wheat tissues induced by anthropogenic industrial activity at the regional scale. The results show that the aboveground wheat tissues in the southern Yangtze River Delta area accumulated much more heavy metals than that in the northern area, although there is no significant difference in the geological and climate conditions, soil types, agricultural manages, wheat cultivar and soil heavy metals concentrations (even heavy metals concentrations in wheat root) between the southern area and northern area. The mean concentrations of Pb, Zn, Cu and Cd in wheat grain in southern area have exceeded the thresholds of contamination levels. The present study suggests that the influence of atmosphere on the accumulation of Hg, Cd, Pb, Zn, Cu, Ni and Cr in the aboveground wheat tissues is greatly significant when high amounts of pollutant are measured in the atmosphere. Based on translocation coefficient of the element, it is estimated that atmospheric pollution induced by anthropogenic forcing might lead to the concentration of heavy metals in wheat straw and grain increase by approximately 100% and 354% (Hg), 64% and 293% (Pb), 122% and 160% (Cr), 50% and 38% (Cd) and 14% and 41% (Cu), respectively., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Elemental concentrations of ambient aerosols are commonly sampled over 12-24 h, and the low time resolution puts a great limit on current understanding about the temporal variations and source apportionment based on receptor models. In this work, hourly-resolved concentrations of eighteen elements in PM 2.5 at an urban site in Nanjing, a megacity in Yangtze River Delta of east China, were obtained by using a Xact 625 ambient metals monitor from 12/12/2016 to 12/31/2017. The influence of traffic activities was clearly reflected by the spikes of crustal elements (e.g., Fe, Ca, and Si) in the morning rush hour, and the firework burning and sandstorm events during the sampling periods were tracked by sharp enrichment of Ba, K and Fe, Ca, Si, Ti in PM 2.5 , respectively. To evaluate the advantage of hourly-resolved elements data in identifying impacts from specific emission sources, positive matrix factorization (PMF) analysis was performed with the 1-h data set (PMF 1-h ) and 23-h averaged data (PMF 23-h ), respectively. The 4- and 6-factor PMF 23-h solutions had similar factor profiles and consistent factor contributions as the corresponding PMF 1-h solutions. However, due to the limit in inter-sample variability, PMF analysis with 23-h average data misclassified some major (e.g., K, Fe, Zn, Ca, and Si) and trace (e.g., Pb) elements in factor profiles, resulting in different absolute factor contributions between PMF 23-h and PMF 1-h solutions. These results suggested the use of high time-resolved data to obtain valid and robust source apportionment results., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Pyroptosis is a novel programmed cell death form which is distinct from other types of cell death. As an inherently inflammatory process, it plays a vital role in cellular lysis and release of pro-inflammatory cytokines when hosts defend against infections. Recent studies have reported that pyroptosis was involved in liver diseases and had important functions in the progress and development of liver diseases. Here, we addressed the potential role of pyroptosis in liver diseases on the basis of brief introduction of the morphological characteristics, molecular and pathophysiological mechanisms of pyroptosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This study seeks to understand the compositional details of N-containing aromatic compounds (NACs) emitted during biomass burning (BB) and their contribution to light-absorbing organic carbon (OC), also termed brown carbon (BrC). Three laboratory BB experiments were conducted with two U.S. pine forest understory fuels typical of those consumed during prescribed fires. During the experiments, submicron aerosol particles were collected on filter media and subsequently extracted with methanol and examined for their optical and chemical properties. Significant correlations ( p < 0.05) were observed between BrC absorption and elemental carbon (EC)/OC ratios for individual burns data. However, the pooled experimental data indicated that the BB BrC absorption depends on more than the BB fire conditions as represented by the EC/OC ratio. Fourteen NAC formulas were identified in the BB samples, most of which were also observed in simulated secondary organic aerosol (SOA) from photo-oxidation of aromatic VOCs with NO X . However, the molecular structures associated with the identical NAC formula from BB and SOA are different. In this work, the identified NACs from BB are featured by methoxy and cyanate groups, and are predominately generated during the flaming phase. The mass concentrations of identified NACs were quantified using authentic and surrogate standards, and their contributions to bulk light absorption of solvent extractable OC were also calculated. The contributions of identified NACs to organic matter (OM) and BrC absorption were significantly higher in flaming-phase samples than those in smoldering-phase samples, and correlated with EC/OC ratio ( p < 0.05) for both individual burns and pooled experimental data, indicating that the formation of NACs from BB largely depends on burn conditions. The average contributions of identified NACs to overall BrC absorption at 365 nm ranged from 0.087 ± 0.024 to 1.22 ± 0.54%, 3 - 10 times higher than their mass contributions to OM (0.023 ± 0.0089 to 0.18 ± 0.067%), so the NACs with light absorption identified in this work from BB are likely strong BrC chromophores. Further studies are warranted to identify more light-absorbing compounds to explain the unknown fraction (> 98%) of BB BrC absorption., Competing Interests: Competing interests The authors declare that they have no conflict of interest.

Light-absorbing organic carbon (OC), also referred to as "brown carbon" (BrC), has been intensively investigated in atmospheres impacted by biomass burning. However, other BrC sources (e.g., secondary formation in the atmosphere) are rarely studied in ambient aerosols. In the current work, forty-five PM 2.5 filter samples were collected in Research Triangle Park (RTP), NC, USA from June 1st to July 15th, 2013. The bulk carbonaceous components, including OC, elemental carbon (EC), water soluble OC (WSOC), and an array of organic molecular markers were measured; an ultraviolet/visible spectrometer was used to measure the light absorption of methanol extractable OC and WSOC. The average light absorption per OC and WSOC mass of PM 2.5 samples in summer RTP are 0.36 ± 0.16 m 2 gC -1 and 0.29 ± 0.13 m 2 gC -1 , respectively, lower than the ambient aerosol samples impacted by biomass burning and/or fossil fuel combustion (0.7-1.6 m 2 gC -1 ) from other places. Less than 1% of the aqueous extracts absorption is attributed to the light-absorbing chromophores (nitroaromatic compounds) identified in this work. To identify the major sources of BrC absorption in RTP in the summer, Positive Matrix Factorization (PMF) was applied to a dataset containing optical properties and chemical compositions of carbonaceous components in PM 2.5 . The results suggest that the formation of biogenic secondary organic aerosol (SOA) containing organosulfates is an important BrC source, contributing up to half of the BrC absorption in RTP during the summertime., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Household cookstove emissions are an important source of carbonaceous aerosols globally. The light-absorbing organic carbon (OC), also termed brown carbon (BrC), from cookstove emissions can impact the Earth's radiative balance, but is rarely investigated. In this work, PM 2.5 filter samples were collected during combustion experiments with red oak wood, charcoal, and kerosene in a variety of cookstoves mainly at two water boiling test phases (cold start CS, hot start HS). Samples were extracted in methanol and extracts were examined using spectrophotometry. The mass absorption coefficients (MAC λ , m 2 g -1 ) at five wavelengths (365, 400, 450, 500, and 550 nm) were mostly inter-correlated and were used as a measurement proxy for BrC. The MAC 365 for red oak combustion during the CS phase correlated strongly to the elemental carbon (EC)/OC mass ratio, indicating a dependency of BrC absorption on burn conditions. The emissions from cookstoves burning red oak have an average MAC λ 2-6 times greater than those burning charcoal and kerosene, and around 3-4 times greater than that from biomass burning measured in previous studies. These results suggest that residential cookstove emissions could contribute largely to ambient BrC, and the simulation of BrC radiative forcing in climate models for biofuel combustion in cookstoves should be treated specifically and separated from open biomass burning., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hepatitis B virus (HBV) is infecting about 364 million people around the world. It can cause various diseases, such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). However, the present anti-viral treatment in clinics is limited; studies for new therapies are highly desired. Autophagy is a crucial and major catabolic process in the maintenance of normal intracellular homeostasis in host cells. Host cells use this unique process to degrade and recycle long-lived proteins, damaged organelles, and various pathogens for keeping the normal physiological functions. Recently, published studies indicated that HBV can induce autophagy in host cells; this autophagic response is involved in viral replication and pathogenesis. Several viral proteins, such as surface and X proteins, are assumed to be responsible for inducing autophagy in HBV infection. This review briefly summarizes some important mechanisms involved in HBV-induced autophagy and provides a novel perspective on therapies of HBV infection and HBV-related HCC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Bacterial multidrug resistance efflux systems serve an important role in antimicrobial resistance. Thus, identifying novel and effective efflux pump inhibitors that are safe with no adverse side effects is urgently required. Silybin is a flavonolignan component of the extract from the milk thistle seed. To order to investigate the mechanism by which silybin inhibits the efflux system of methicillin‑resistant Staphylococcus aureus (MRSA), antimicrobial susceptibility testing and the double‑plate method were used to evaluate the effect of silybin on MRSA41577. The ability of silybin to inhibit the efflux of ciprofloxacin from MRSA was evaluated by performing a fluorescence assay. Reverse transcription‑quantitative polymerase chain reaction analysis revealed that silybin reduced the expression of the quinolone resistance protein NorA (norA) and quaternary ammonium resistance proteins A/B (qacA/B) efflux genes in MRSA. This suggested that silybin may effectively inhibit the efflux system of MRSA41577. Compared with the control, MRSA41577 treated with silybin for 16 h exhibited a 36 and 49% reduction in the expression of norA and qacA/B, respectively. Inhibition of the expression of these genes by silybin restored the sensitivity of MRSA41577 to antibiotics, indicating that efflux pump inhibitors, which act by inhibiting the efflux system of MRSA, may disrupt the MRSA resistance to antibiotics, rendering the bacteria sensitive to these drugs.

This study investigates the composition of organic particulate matter in PM 2.5 in a remote montane forest in the southeastern US, focusing on the role of organic nitrogen (N) in sulfur-containing secondary organic aerosol (nitrooxy-organosulfates) and aerosols associated with biomass burning (nitro-aromatics). Bulk water-soluble organic N (WSON) represented ~ 14% w/w of water-soluble total N (WSTN) in PM 2.5 on average across seasonal measurement campaigns conducted in the spring, summer, and fall of 2015. The largest contributions of WSON to WSTN were observed in spring (~ 18% w/w ) and the lowest in the fall (~ 10% w/w ). On average, identified nitro-aromatic and nitrooxy-organosulfate compounds accounted for a small fraction of WSON, ranging from ~ 1% in spring to ~ 4% in fall, though were observed to contribute as much as 28% w/w of WSON in individual samples that were impacted by local biomass burning. The highest concentrations of oxidized organic N species occurred during summer (average of 0.65 ng N m -3 ) along with a greater relative abundance of higher-generation oxygenated terpenoic acids, indicating an association with more aged aerosol. The highest concentrations of nitro-aromatics (e.g., nitrocatechol and methyl-nitrocatechol), levoglucosan, and aged SOA tracers were observed during fall, associated with aged biomass burning plumes. Nighttime nitrate radical chemistry is the most likely formation pathway for nitrooxy-organosulfates observed at this low NO x site (generally < 1 ppb). Isoprene-derived organosulfate (MW216, 2-methyltetrol derived), which is formed from isoprene epoxydiols (IEPOX) under low NO x conditions, was the most abundant individual organosulfate. Concentration-weighted average WSON / WSOC ratios for nitro-aromatics + organosulfates + terpenoic acids were 1 order of magnitude lower than the overall aerosol WSON / WSOC ratio, indicating the presence of other uncharacterized higher-N-content species. Although nitrooxy-organosulfates and nitro-aromatics contributed a small fraction of WSON, our results provide new insight into the atmospheric formation processes and sources of these largely uncharacterized components of atmospheric organic N, which also helps to advance the atmospheric models to better understand the chemistry and deposition of reactive N., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

Hepatocellular carcinoma remains the sixth most lethal malignancy in the world. While HCC is often diagnosed via current biomarkers at a late stage, early detection of HCC has proven to be very difficult. Recent studies have focused on using exosomal miRNAs in clinical diagnostics and therapeutics, because they have improved stability in exosomes than as free miRNAs themselves. Exosomal miRNAs act through novel mechanisms for inducing cellular responses in a variety of biological circumstances. Dysregulated expression of miRNAs in exosomes can also accelerate HCC progression, including cell proliferation and metastasis, via alteration of a network of genes. Growing evidence demonstrates that exosomal miRNAs can affect many aspects of physiological and pathological conditions in HCC and indicates that miRNAs in exosomes can not only serve as sensitive biomarkers for cancer diagnostics and recurrence but can also potentially be used as therapeutics to target HCC progression. In this review, we summarize the latest findings between exosomal miRNAs and HCC, in order to better comprehend the functions and applications in HCC. Moreover, we discuss critical issues to consider when developing anti-tumor exosomal miRNAs as a novel therapeutic strategy for treating HCC in the clinic.

Secondary organic aerosol (SOA) can affect the atmospheric radiation balance through absorbing light at shorter visible and UV wavelengths. However, the composition and optical properties of light-absorbing SOA is poorly understood. In this work, SOA filter samples were collected during individual chamber experiments conducted with three biogenic and eight aromatic volatile organic compound (VOC) precursors in the presence of NO X and H 2 O 2 . Compared with the SOA generated using the aromatic precursors, biogenic SOA generally exhibits negligible light absorption above 350 nm; the aromatic SOA generated in the presence of NO X shows stronger light absorption than that generated with H 2 O 2 . Fifteen nitroaromatic compound (NAC) chemical formulas were identified and quantified in SOA samples. Their contributions to the light absorption of sample extracts were also estimated. On average, the m-cresol/NO X SOA sample has the highest mass contribution from NACs (10.4 ± 6.74%, w/w), followed by naphthalene/NO X (6.41 ± 2.08%) and benzene/NO X (5.81 ± 3.82%) SOA. The average contributions of NACs to total light absorption were at least two times greater than their average mass contributions at 365 and 400 nm, revealing the potential use of chromophoric NACs as brown carbon (BrC) tracers in source apportionment and air quality modeling studies.

Light-absorbing organic carbon (OC), also termed brown carbon (BrC), from laboratory-based biomass burning (BB) has been studied intensively to understand the contribution of BB to radiative forcing. However, relatively few measurements have been conducted on field-based BB and even fewer measurements have examined BrC from anthropogenic combustion sources like motor vehicle emissions. In this work, the light absorption of methanol-extractable OC from prescribed and laboratory BB and gasoline vehicle emissions was examined using spectrophotometry. The light absorption of methanol extracts showed a strong wavelength dependence for both BB and gasoline vehicle emissions. The mass absorption coefficients at 365 nm (MAC 365 , m 2 g -1 C) - used as a measurement proxy for BrC - were significantly correlated (p < 0.05) to the elemental carbon (EC)/OC ratios when examined by each BB fuel type. No significant correlation was observed when pooling fuels, indicating that both burn conditions and fuel types may impact BB BrC characteristics. The average MAC 365 of gasoline vehicle emission samples is 0.62 ± 0.76 m 2  g -1 C, which is similar in magnitude to the BB samples (1.27 ± 0.76 m 2  g -1 C). These results suggest that in addition to BB, gasoline vehicle emissions may also be an important BrC source in urban areas.

REACCTING (Research on Emissions Air Quality, Climate, and Cooking Technologies in Northern Ghana) was a 200-home cookstove intervention study from 2013 to 2015. Study households were divided into four groups: a control group, a group given two locally made rocket stoves, a group given two Philips forced draft stoves, and a group given a locally made rocket stove and a Philips stove. In a subset of study households, 48-hour PM 2.5 exposure samples were collected for adults and children, as well as in the primary cooking area. Further, weekly ambient background PM 2.5 samples were collected for the first nine months of the study. All PM 2.5 samples were analyzed for elemental and organic carbon (EC/OC), and a subset was also analyzed for organics. Mixed effects modeling was applied to quantify differences in PM exposures between the groups and to assess relationships between exposures and cooking area measurements. Results showed that personal OC exposure for the intervention groups was 56.6% lower than the control group (p≤0.01). Both intervention groups given Philips stoves had significantly lower EC exposure than the control group (60.6% reduction, p≤0.02). Only weak relationships were found between personal and cooking area EC or OC. Source apportionment modeling was performed on both the personal/microenvironment and the ambient organics PM 2.5 data sets to assess the sources of the observed PM. We identified six PM sources. The identified source factors were similar among the data sets, as well as with previous work in Navrongo. Two sources, one characterized by the presence of methoxyphenols, and one by the presence of polyaromatic hydrocarbons and EC, were associated with biomass burning, and accounted for a median of 9.2% of OC and 15.3% of EC personal exposure. Here, we demonstrate the utility of using the cooking-related source apportionment factors within a mixed effects model for more precise estimation of exposures due to cooking, rather than other combustion sources unrelated to the intervention., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Atmospheric aerosols have been shown to be an important input of organic carbon and nutrients to alpine watersheds and influence biogeochemical processes in these remote settings. For many remote, high elevation watersheds, direct evidence of the sources of water soluble organic aerosols and their chemical and optical characteristics is lacking. Here, we show that the concentration of water soluble organic carbon (WSOC) in the total suspended particulate (TSP) load at a high elevation site in the Colorado Rocky Mountains was strongly correlated with UV absorbance at 254 nm (Abs254, r = 0.88 p < 0.01) and organic carbon (OC, r = 0.95 p < 0.01), accounting for >90% of OC on average. According to source apportionment analysis, biomass burning had the highest contribution (50.3%) to average WSOC concentration; SOA formation and motor vehicle emissions dominated the contribution to WSOC in the summer. The source apportionment and backward trajectory analysis results supported the notion that both wildfire and Colorado Front Range pollution sources contribute to the summertime OC peaks observed in wet deposition at high elevation sites in the Colorado Rocky Mountains. These findings have important implications for water quality in remote, high-elevation, mountain catchments considered to be our pristine reference sites.

Objective: To study the inhibition of methicillin-resistant Staphylococcus aureas (MRSA) biofilm by honokiol., Methods: We used triphenyl tetrazolium chloride method to evaluate the inhibition of biofilm formation and mature by honokiol. We used congo red agar and spectrophotometer to detect the influence of honokiol on polysaccharide intercellular adhesion formation and extracellular DNA release. RT-PCR analysis was used to determine the effect of honokiol on expression of icaA, cidA and agrA., Results: Honokiol showed strong antimicrobial activity both on biofilm formation and mature biofilm of MRSA 41573. Minimum inhibitory concentration was 10 μg/mL for biofilm formation and 50 μg/mL for mature biofilm. Minimum bactericidal concentration was 20 μg/mL for biofilm formation and 100 μg/mL for mature biofilm. Honokiol showed synergy effect with vancomycin and it significantly increased the sensitivity of mature biofilm to vancomycin. Polysaccharide intercellular adhesion formation and extracellular DNA release were effectively inhibited by honokiol. Extracellular DNA release decreased by 28.3% when honokiol at 1/8 MIC. After incubated with 1/2 MIC of honokiol for 16 h, the relative expression of icaA, cidA and agrA of MRSA41573 was reduced by 59.1%, 56% and 72.3%, respectively., Conclusion: Honokiol can significantly inhibit biofilm formation of MRSA41573 and its mechanism is mainly the inhibited expression of icaA and cidA to influence the synthesis of polysaccharide intercellular adhesion and extracellular DNA. Moreover, it also affect biofilm formation by QS system.

This work focuses on the mass content of plasticizers in children's backpacks and toys, and their mass transfer from product surfaces to cotton wipes. The mass content of plasticizers in six backpacks and seven toys was measured by extracting them in tetrahydrofuran. Bis(2-ethylhexyl) terephthalate (DEHT) was the most common plasticizer, dominating the composition of plasticizers in four backpacks (average mass content in product polyvinyl chloride, 5.38 ± 1.98%-25.5 ± 3.54%) and six plastic toys (8.17 ± 1.85%-21.2 ± 1.11%). The surface of each product was wiped with three dry and three wet (by isopropanol) cotton wipes, so as to evaluate the mass transfer of plasticizers to clothing and human skin, respectively. DEHT was the most common plasticizer detected on wipe samples. There were strong correlations (backpacks r=0.90; plastic toys r=0.96) between average mass transfer of DEHT to wet wipes and its average mass content in the product. The mass transfers of the five dominant plasticizers in one backpack to both dry and wet wipes were also correlated (both r=1.00) with their mass contents. These results suggest that the mass transfer of plasticizers from products to clothing or human skin is strongly associated with their mass content.

Bacterial resistance is a threat to public health. Bacterial biofilm formation is one of the main reasons for persistent infection caused by bacteria. Biofilm development is a complex process that involves many factors and genes which play various roles in all stages of the biofilm formation. This review focuses on the gene regulatory mechanisms relate to the biofilm formation of Staphylococcus, the most common pathogen that causes nosocomial infection, as well as the latest developments of pharmacological anti-biofilm therapies. We also address new strategy to treat bacterial infection and the development of drugs and vaccines against biofilm resistance.

A variety of single pollutant and multipollutant metrics can be used to represent exposure to traffic pollutant mixtures and evaluate their health effects. Integrated mobile source indicators (IMSIs) that combine air quality concentration and emissions data have recently been developed and evaluated using data from Atlanta, Georgia. IMSIs were found to track trends in traffic-related pollutants and have similar or stronger associations with health outcomes. In the current work, we apply IMSIs for gasoline, diesel and total (gasoline + diesel) vehicles to two other cities (Denver, Colorado and Houston, Texas) with different emissions profiles as well as to a different dataset from Atlanta. We compare spatial and temporal variability of IMSIs to single-pollutant indicators (carbon monoxide (CO), nitrogen oxides (NOx) and elemental carbon (EC)) and multipollutant source apportionment factors produced by Positive Matrix Factorization (PMF). Across cities, PMF-derived and IMSI gasoline metrics were most strongly correlated with CO (r = 0.31-0.98), while multipollutant diesel metrics were most strongly correlated with EC (r = 0.80-0.98). NOx correlations with PMF factors varied across cities (r = 0.29-0.67), while correlations with IMSIs were relatively consistent (r = 0.61-0.94). In general, single-pollutant metrics were more correlated with IMSIs (r = 0.58-0.98) than with PMF-derived factors (r = 0.07-0.99). A spatial analysis indicated that IMSIs were more strongly correlated (r > 0.7) between two sites in each city than single pollutant and PMF factors. These findings provide confidence that IMSIs provide a transferable, simple approach to estimate mobile source air pollution in cities with differing topography and source profiles using readily available data.

Fraxetin is one of the main constituents of the traditional medicinal plant Fraxinus rhynchophylla. The inhibitory effect of fraxetin on various bacterial strains has been extensively reported, however, its mechanism of action on bacterial cells remains to be elucidated. In the present study, the antibacterial mechanism of fraxetin on Staphylococcus aureus was systematically investigated by examining its effect on cell membranes, protein synthesis, nucleic acid content and topoisomerase activity. The results indicated that fraxetin increased the permeability of the cell membrane but did not render it permeable to macromolecules, such as DNA and RNA. Additionally, the quantity of protein, DNA and RNA decreased to 55.74, 33.86 and 48.96%, respectively following treatment with fraxetin for 16 h. The activity of topoisomerase I and topoisomerase II were also markedly inhibited as fraxetin concentration increased. The result of the ultraviolet‑visible spectrophotometry demonstrated that the DNA characteristics exhibited a blue shift and hypochromic effect following treatment with fraxetin. These results indicated that fraxetin had a marked inhibitory effect on S.aureus proliferation. Further mechanistic studies showed that fraxetin could disrupt nucleic acid and protein synthesis by preventing topoisomerase from binding to DNA.

Objective: To study the inhibitory effect of biochanin A on efflux system of Methicillin-resistant Staphylococcus aureus (MRSA)., Methods: Inhibitory effects of biochanin A on efflux system of Strain MRSA41577 were evaluated using double dilution method, two plate method and fluorescence spectrophotometry. Real time PCR and SDS-PAGE were applied to detect the expression of MRSA41577 norA and to analyze the changes of MRSA41577 efflux protein before and after dosing biochanin A in association with liquid chromatography mass spectrometry to determinate protein variation., Results: Biochanin A alone had no inhibitory effect on MRSA41577, but it showed synergy effect with ciprofloxacin in inhibition MRSA41577 in which 40pg/mL biochanin A decreased the minimum inhibitory concentration (MIC) value of ciprofloxacin from 64 microg/mL to 8 microgg/mL. Biochanin A significantly increased the accumulation of ciprofloxacin in MRSA41577 in a time-dependent manner. At 15 min, biochanin A increased ciprofloxacin in MRSA41577 by 83%, which is similar to that of reserpine (positive control). Further mechanism studies indicated that biochanin A could reduce the expression of nor A in ciprofloxacin-treated MRSA41577. After incubated with biochanin A and ciprofloxacin for 16 h, the relative expression of nor A of MRSA41577 was reduced by 65%. SDS-PAGE analysis showed that the total protein profiles of MRSA41577 were significantly changed after treatment with biochanin A for 16h, in which both norA protein and efflux system ABC transporter ATP-binding protein were significantly decreased., Conclusion: Biochanin A could inhibit Methicillin-resistant Staphylococcus aureus efflux system through reducing pathogen' s expression of nor A and norA protein.

To quantify and minimize the influence of gas/particle (G/P) partitioning on receptor-based source apportionment using particle-phase semivolatile organic compound (SVOC) data, positive matrix factorization (PMF) coupled with a bootstrap technique was applied to three data sets mainly composed of "measured-total" (measured particle- + gas-phase), "particle-only" (measured particle-phase) and "predicted-total" (measured particle-phase + predicted gas-phase) SVOCs to apportion carbonaceous aerosols. Particle- (PM2.5) and gas-phase SVOCs were collected using quartz fiber filters followed by PUF/XAD-4/PUF adsorbents and measured using gas chromatography-mass spectrometry (GC-MS). Concentrations of gas-phase SVOCs were also predicted from their particle-phase concentrations using absorptive partitioning theory. Five factors were resolved for each data set, and the factor profiles were generally consistent across the three PMF solutions. Using a previous source apportionment study at the same receptor site, those five factors were linked to summertime biogenic emissions (odd n-alkane factor), unburned fossil fuels (light SVOC factor), road dust and/or cooking (n-alkane factor), motor vehicle emissions (PAH factor), and lubricating oil combustion (sterane factor). The "measured-total" solution was least influenced by G/P partitioning and used as reference. Two out of the five factors (odd n-alkane and PAH factors) exhibited consistent contributions for "particle-only" vs "measured-total" and "predicted-total" vs "measured-total" solutions. Factor contributions of light SVOC and n-alkane factors were more consistent for "predicted-total" vs "measured-total" than "particle-only" vs "measured-total" solutions. The remaining factor (sterane factor) underestimated the contribution by around 50% from both "particle-only" and "predicted-total" solutions. The results of this study confirm that when measured gas-phase SVOCs are not available, "predicted-total" SVOCs should be used to decrease the influence of G/P partitioning on receptor-based source apportionment.

In this study, a medium volume sampler incorporating quartz fiber filters (QFFs) and a polyurethane foam (PUF)/XAD/PUF sandwich (PXP) was used to collect 2-methyltetrols (isoprene tracer) and levoglucosan (biomass burning tracer) in gaseous and particle (PM2.5) phases. The measured gas/particle (G/P) partitioning coefficients (Kp,OMm) of 2-methyltetrols and levoglucosan were calculated and compared to their predicted G/P partitioning coefficients (Kp,OMt) based on an absorptive partitioning theory. The breakthrough experiments showed that gas-phase 2-methyltetrols and levoglucosan could be collected using the PXP or PUF adsorbent alone, with low breakthrough; however, the recoveries of levoglucosan in PXP samples were lower than 70% (average of 51.9–63.3%). The concentration ratios of 2-methyltetrols and levoglucosan in the gas phase to those in the particle phase were often close to or higher than unity in summer, indicating that these polar species are semi-volatile and their G/P partitioning should be considered when applying particle-phase data for source apportionment. The Kp,OMm values of 2-methyltetrols had small variability in summer Denver, which was ascribed to large variations in concentrations of particulate organic matter (5.14 ± 3.29 μg m–3) and small changes in ambient temperature (21.8 ± 4.05 °C). The regression between log Kp,OMm and log Kp,OMt suggested that the absorptive G/P partitioning theory could reasonably predict the measured G/P partitioning of levoglucosan in ambient samples.

This study presents source apportionment results for PM 2.5 from applying positive matrix factorization (PMF) to a 32-month series of daily PM 2.5 compositional data from Denver, CO, including concentrations of sulfate, nitrate, bulk elemental carbon (EC) and organic carbon (OC), and 51 organic molecular markers (OMMs). An optimum 8-factor solution was determined primarily based on the interpretability of the PMF results and rate of matching factors from bootstrapped PMF solutions with those from the base case solution. These eight factors were identified as inorganic ion, n -alkane, EC/sterane, light n -alkane/polycyclic aromatic hydrocarbon (PAH), medium alkane/alkanoic acid, PAH, winter/methoxyphenol and summer/odd n -alkane. The inorganic ion factor dominated the reconstructed PM 2.5 mass (sulfate + nitrate + EC + OC) in cold periods (daily average temperature < 10 °C; 43.7% of reconstructed PM 2.5 mass) whereas the summer/odd n -alkane factor dominated in hot periods (> 20 °C; 53.1%). The two factors had comparable relative contributions of 26.5% and 27.1% in warm periods with temperatures between 10 °C and 20 °C. Each of the seven factors resolved in a previous study (Dutton et al., 2010b) using a 1-year data set from the same location matches one factor from the current work based on comparing factor profiles. Six out of the seven matched pairs of factors are linked to similar source classes as suggested by the strong correlations between factor contributions ( r = 0.89 - 0.98). Temperature-stratified source apportionment was conducted for three subsets of the data in the current study, corresponding to the cold, warm and hot periods mentioned above. The cold period (7-factor) solution exhibited a similar distribution of reconstructed PM 2.5 mass as the full data set solution. The factor contributions of the warm period (7-factor) solution were well correlated with those from the full data set solution ( r = 0.76 - 0.99). However, the reconstructed PM 2.5 mass was distributed more to inorganic ion, n -alkane and medium alkane/alkanoic acid factors in the warm period solution than in the full data set solution. For the hot period (6-factor) solution, PM 2.5 mass distribution was quite different from that of the full data set solution, as illustrated by regression slopes as low as 0.2 and as high as 4.8 of each matched pair of factors across the two solutions.

The Denver Aerosol Sources and Health (DASH) study was designed to evaluate associations between PM 2.5 species and sources and adverse human health effects. The DASH study generated a five-year (2003-2007) time series of daily speciated PM 2.5 concentration measurements from a single, special-purpose monitoring site in Denver, CO. To evaluate the ability of this site to adequately represent the short term temporal variability of PM 2.5 concentrations in the five county Denver metropolitan area, a one year supplemental set of PM 2.5 samples was collected every sixth day at the original DASH monitoring site and concurrently at three additional sites. Two of the four sites, including the original DASH site, were located in residential areas at least 1.9 km from interstate highways. The other two sites were located within 0.3 km of interstate highways. Concentrations of elemental carbon (EC), organic carbon (OC), and 58 organic molecular markers were measured at each site. To assess spatial variability, site pairs were compared using the Pearson correlation coefficient ( r ) and coefficient of divergence (COD), a statistic that provides information on the degree of uniformity between monitoring sites. Biweekly co-located samples collected from July 2004 to September 2005 were also analyzed and used to estimate the uncertainty associated with sampling and analytical measurement for each species. In general, the two near-highway sites exhibited higher concentrations of EC, OC, polycyclic aromatic hydrocarbons (PAHs), and steranes than did the more residential sites. Lower spatial heterogeneity based on r and COD was inferred for all carbonaceous species after considering their divergence and lack of perfect correlations in co-located samples. Ratio-ratio plots combined with available gasoline- and diesel-powered motor vehicle emissions profiles for the region suggested a greater impact to high molecular weight (HMW) PAHs from diesel-powered vehicles at the near-highway sites and a more uniformly distributed impact to ambient hopanes from gasoline-powered motor vehicles at all four sites.

To identify the sources of PM 2.5 - bound carbonaceous species and examine the spatial variability of source contributions in the Denver metropolitan area, positive matrix factorization (PMF) was applied to one year of every sixth day ambient PM 2.5 compositional data, including elemental carbon (EC), organic carbon (OC), and 32 organic molecular markers, from four sites (two residential and two near-traffic). Statistics (median, inner quantiles and 5 th - 95 th percentiles range) of factor contributions, expressed as reconstructed carbonaceous mass (EC + OC), were estimated from PMF solutions of replicate datasets generated by using a stationary block bootstrap technique. A seven-factor solution was resolved for a set of data pooled across the four sites, as it gave the most interpretable results and had the highest rate of neural network factor matching (76.9%). Identified factors were primarily associated with high plant wax, summertime emission, diesel vehicle emission, fossil fuel combustion, motor vehicle emission, lubricating oil combustion and wood burning. Pearson correlation coefficients ( r ) and coefficients of divergence (COD) were used to assess spatial variability of factor contributions. The summertime emission factor exhibited the highest spatial correlation ( r = 0.74 - 0.88) and lowest CODs (0.32 - 0.38) among all resolved factors; while the three traffic dominated factors (diesel vehicle emission, motor vehicle emission and lubricating oil combustion) showed lower correlations ( r = 0.47 - 0.55) and higher CODs (0.41 - 0.53) on average. Average total EC and OC mass were apportioned to each factor and showed a similar distribution across the four sites. Modeling uncertainties were defined as the 5 th - 95 th percentile range of the factor contributions derived from valid bootstrap PMF solutions, and were highly correlated with the median factor contribution in each factor ( r = 0.77 - 0.98). Source apportionment was also performed on site specific datasets; the results exhibited similar factor profiles and temporal variation in factor contribution as those obtained for the pooled dataset, indicating that the four sites are primarily influenced by similar types of sources. On the other hand, differences were observed in absolute factor contributions between PMF solutions for the pooled versus site-specific datasets, likely due to the large uncertainties in EC and OC factor profiles derived from the site specific datasets with limited numbers of observations.

To evaluate the utility and consistency of different speciation data sets in source apportionment of PM(2.5), positive matrix factorization (PMF) coupled with a bootstrap technique for uncertainty assessment was applied to four different 1-year data sets composed of bulk species, bulk species and water-soluble elements (WSE), bulk species and organic molecular markers (OMM), and all species. The five factors resolved by using only the bulk species best reproduced the observed concentrations of PM(2.5) components. Combining WSE with bulk species as PMF inputs also produced five factors. Three of them were linked to soil, road dust, and processed dust, and together contributed 26.0% of reconstructed PM(2.5) mass. A 7-factor PMF solution was identified using speciated OMM and bulk species. The EC/sterane and summertime/selective aliphatic factors had the highest contributions to EC (39.0%) and OC (53.8%), respectively. The nine factors resolved by including all species as input data are consistent with those from the previous two solutions (WSE and bulk species, OMM and bulk species) in both factor profiles and contributions (r = 0.88-1.00). The comparisons across different solutions indicate that the selection of input data set may depend on the PM components or sources of interest for specific source-oriented health study.

Many software tools have been developed for the automated identification of peptides from tandem mass spectra. The accuracy and sensitivity of the identification software via database search are critical for successful proteomics experiments. A new database search tool, PEAKS DB, has been developed by incorporating the de novo sequencing results into the database search. PEAKS DB achieves significantly improved accuracy and sensitivity over two other commonly used software packages. Additionally, a new result validation method, decoy fusion, has been introduced to solve the issue of overconfidence that exists in the conventional target decoy method for certain types of peptide identification software.

Foliar uptake of airborne lead is one of the pathways for Pb accumulation in plant organs. However, the approximate contributions of airborne Pb to plant organs are still unclear. In the present study, aerosols (nine-stage size-segregated aerosols and total suspended particulates), a wild plant species (Aster subulatus) and the corresponding soils were collected and Pb contents and isotopic ratios in these samples were analyzed. Average concentration of Pb was 96.5 ± 63.5 ng m(-3) in total suspended particulates (TSP) and 20.4 ± 5.5 ng m(-3) in the fine fractions of size-segregated aerosols (SSA) (<2.1 μm), higher than that in the coarser fractions (>2.1 μm) (6.38 ± 3.71 ng m(-3)). Enrichment factors show that aerosols and soils suffered from anthropogenic inputs and the fine fractions of the size-segregated aerosols enriched more Pb than the coarse fractions. The order of Pb contents in A. subulatus was roots>leaves>stems. The linear relationship of Pb isotope ratios ((206)Pb/(207)Pb and (208)Pb/(206)Pb) among soil, plant and aerosol samples were found. Based on the simple binary Pb isotopic model using the mean (206)Pb/(207)Pb ratios in TSP and in SSA, the approximate contributions of airborne Pb into plant leaves were 72.2% and 65.1%, respectively, suggesting that airborne Pb is the most important source for the Pb accumulation in leaves. So the combination of Pb isotope tracing and the simple binary Pb isotope model can assess the contribution of airborne Pb into plant leaves and may be of interest for risk assessment of the exposure to airborne Pb contamination., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Effects of different flavonoids on various bacterial strains have been extensively reported; however, the mechanism(s) of their action on bacterial cells remain largely elusive. In this study, the antibacterial mechanism of soybean isoflavone (SI) on Staphylococcus aureus is systematically investigated using 4'6-diamidino-2-phenylindole (DAPI) staining, pBR322DNA decatenation experiment mediated by topoisomerase and agarose gel electrophoresis for direct decatenation. The results of fluorescence microscopy and fluorescence spectrophotometer indicated that DAPI was integrated in Staphylococcus aureus. Additionally, the quantity of both DNA and RNA reduced to 66.47 and 60.18%, respectively, after treated with SI for 28 h. Effects of SI on topoisomerase I and II were also investigated. SI completely inhibited the pBR322DNA unwinding mediated by topoisomerase I and topoisomerase II at the concentration of 6.4 mg/ml and could denature the plasmid DNA at the concentration of 12.8 mg/ml. These results indicate that topoisomerase I and II are the most important targets by SI to restrain bacterial cell division.

Polar organic compounds and elements were quantified in PM(10) aerosols collected in urban and rural areas of Baoji, an inland city of China, during winter and spring 2008. Concentrations of biomass burning markers and high molecular weight n-alkanoic acids (HMW, >C(22:0)) were heavily increased in winter. In contrast, sugars presented in higher levels in the spring, among which sucrose was the most abundant with an average of 219ngm(-3) in winter and 473ngm(-3) in spring respectively. This suggests enhanced biotic activity in the warm season, whereas no obvious trend was observed for sugar alcohols, concentrations of the three sugar alcohols in spring were only 0.94-2.3 times as those in winter, indicating a second pathway of their formation other than fungal spores in cold season. Major crustal elements (i.e., Fe, K, Mn and Ti) in PM(10) aerosols were also observed in larger concentrations in spring samples than those in winter due to an enhancement of coarse particles from soil minerals. By using principal component analysis (PCA) and positive matrix factorization (PMF), sources and their contributions to the PM components were also investigated in this study. Four factors were extracted with both models, and the sources represented by different factors were based on the highest loaded marker species as follows: factor 1, soil and road dust (Fe, Sr and Ti); factor 2, biomass burning (levoglucosan, galactosan and syringic acid); factor 3, microbial emissions (fructose and sucrose); and factor 4, fossil fuel combustion and fungal spores influence (Pb, Zn, arabitol and mannitol). The high correlation between PM(10) and factor 1 suggested that PM(10) pollution in Baoji was dominated by soil and dust re-suspension., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: To investigate the antibacterial activity and mechanism of luteolin on Staphylococcus aureus., Methods: The antibacterial activity and mechanism experiments were carried out by using 2, 3, 5-triphenyl tetrazolium chloride (TTC), determining membrane penetrability, the change of SDS-PAGE protein spectra and 4 6-diamidino-2-phenylindole (DAPI) staining assay., Results: Luteolin could affect the membrane permeability of Staphylococcus aureus, but not destroy the membrane integrity directly. After treated with luteolin for 16 hours, the total content of proteins decreased to 64.54%, the quantity of both DNA and RNA reduced to 48.44% and 39.35% respectively. The activity of DNA topoisomerase I and II was inhibited completely by 1.6 mg/mL luteolin., Conclusion: Luteolin showed obvious antibacterial activity against Staphylococcus aureus. The antibacterial mechanism of luteolin is that it could inhibit the activity of DNA topoisomerase I and II, which resulted in some decrease in the nucleic acid and protein synthesis.