Evaluating the Kinetics and Molecular Mechanism for Biomimetic Metabolic Activation of PAHs by Surface-Enhanced Raman Scattering Spectroscopy.

Biomimetic cytochrome P450 for chemical activation of environmental carcinogens is an efficient in vitro model for evaluating their mutagenicity and ultimately acquiring the metabolites that cannot be easily accessed by conventional routes of organic synthesis. Different kinds of mutagen derived from polyaromatic hydrocarbons (PAHs) by metalloporphyrin/oxidant model systems have been reported, but the underlying molecular mechanisms are poorly understood. Herein, we have for the first time demonstrated an effective surface-enhanced Raman scattering (SERS) protocol to study the dynamics and biomimetic metabolic behaviors of pyrene (Pyr) in the presence of various oxygen donors. Quantitative information on the relative concentration of Pyr and its metabolites in the biomimetic system can be extracted from the SERS spectra. On the basis of our results, we conclude that the oxidative metabolism of Pyr is highly influenced by the types and concentrations of oxygen donors, leading to the formation of 1-hydroxypyrene and dioxygenated products. Besides, the addition of an appropriate amount of an organic solvent can promote the formation of secondary oxidation products. These results offer valuable insights into the dynamics of PAHs metabolism and the regulation of their metabolic pathways in biomimetic activation. In comparison to traditional liquid chromatography-mass spectrometry, the present SERS approach is more suitable for high-throughput evaluation of the metabolic process and kinetics of PAHs. We anticipate that this approach will enable a more general and comprehensive tracking of metabolic dynamics and molecular mechanisms involved in the biomimetic activation of other xenobiotics, such as procarcinogens, promutagens, and drugs.

[Antibiotic bone cement covered reconstruction plate for infected anterior pelvic ring fractures].

OBJECTIVE: To explore the clinical efficacy of antibiotic bone cement covered reconstruction steel plate in the treatment of infected anterior pelvic ring fracture. METHODS: From January 2017 to March 2022, 11 patients with infected anterior pelvic ring fracture were treated with antibiotic bone cement covered reconstruction steel plate including 7 males and 4 females and the age ranged from 27 to 49 years old. The pelvic fractures were classified according to the Tile typology: 4 cases of C1 type, 4 cases of C2 type, and 3 cases of C3 type. Among them, 2 cases of infected anterior ring were infected after internal fixation of anterior ring, and 9 patients were infected with infected anterior ring due to incomplete early debridement, which was classified as infected according to the injury severity score(ISS) for 24 to 38 scores. The anterior ring was internally fixed by extended debridement, irrigation, and antibiotic bone cement covered reconstruction plate, and the posterior ring fractures were all closed reduction and internally fixed with sacroiliac screws. RESULTS: All 11 cases obtained follow-up from 13 to 20 months. Among them, 2 patients had recurrence of postoperative infection, 1 case was re-dissected and replaced with antibiotic bone cement-coated internal fixation, and 1 case had a milder infection without accumulation of the medullary cavity, and the infection was controlled by retaining the plate and replacing the antibiotic bone cement only after dissecting. Two cases developed incisional oozing, which healed after removal of the internal fixation three months postoperatively. All patients did not show pelvic fracture redisplacement or reinfection during the follow-up period. All 11 cases eventually healed bony. At the final follow-up, according to the Matta score, the fracture reduction was excellent in 6 cases, good in 4, and possible in 1. According to the Majeed functional score, it was excellent in 6, good in 3, and possible in 2. CONCLUSION: Antibiotic bone cement covered reconstruction plate is effective in the treatment of infected anterior pelvic ring fracture, with high intraoperative safety and low recurrence rate of infection, which is conducive to the early postoperative rehabilitation and significantly shortens the course of the disease.

Identification and Visualization of Polystyrene Microplastics/Nanoplastics in Flavored Yogurt by Raman Imaging.

The contamination of food by microplastics has garnered widespread attention, particularly concerning the health risks associated with small-sized microplastics. However, detecting these smaller microplastics in food poses challenges attributed to the complexity of food matrices and instrumental and method limitations. Here, we employed Raman imaging for visualization and identification of polystyrene particles synthesized in polymerization reactions, ranging from 400 to 2600 nm. We successfully developed a quantitative model of particle size and concentration for polystyrene, exhibiting excellent fit (R2 of 0.9946). We established procedures for spiked flavored yogurt using synthesized polystyrene, providing fresh insights into microplastic extraction efficiency. Recovery rates calculated from models validated the method's feasibility. In practical applications, the assessment of the size, type, shape, and quantity of microplastics in unspiked flavored yogurt was conducted. The most common polymers found were polystyrene, polypropylene, and polyethylene, with the smallest polystyrene sizes ranging from 1 to 10 µm. Additionally, we conducted exposure assessments of microplastics in branded flavored yogurt. This study established a foundation for developing a universal method to quantify microplastics in food, covering synthesis of standards, method development, validation, and application.

Study on the Correlations between Quality Indicators of Dry-Aged Beef and Microbial Succession during Fermentation.

Dry-aged beef has been long favored by people due to its unique flavor and taste. However, the inner relationship between its overall quality formation and microbial changes during dry aging has not yet received much attention and research. To deeply reveal the forming mechanism of the unique flavor and taste of dry-aged beef, correlations between its three main quality indicators, i.e., texture, free amino acids (FAAs), volatile flavor compounds (VFCs), and microbial succession were analyzed in this study. The results showed that Staphylococcus spp. and Macrococcus spp. were key strains that influenced the total quality of dry-aged beef and strongly correlated with chewiness, hardness, and sweet FAAs (Ala), providing beef with unique palatability and taste. Additionally, among VFCs, Staphylococcus spp. and Macrococcus spp. showed a strong correlation with octanal and heptanal, and meanwhile, those highly correlated with nonanal, pentanol, and oct-1-en-3-ol were Debaryomyces spp., Psychrobacter spp., and Brochothrix spp., respectively, providing beef with a unique flavor. Staphylococcus spp. was proposed to be the dominant genus for dry-aged beef. This study provides valuable reference for the understanding of the role of microorganisms involved in dry aging.

Microscopic Raman-based rapid detection of submicron/nano polypropylene plastics in tea and tea beverages.

Polypropylene (PP) is suitable for a broad range of applications and represents the most extensively utilized plastic in food packaging. Micro- and nano-PP plastics are prevalent categories of microplastics (MPs). However, the majority of MPs particles currently utilized in laboratory studies are man-made polystyrene (PS) spheres, and there has been limited research on micrometer- and nanoscale PP plastic particles. This study aims to employ a top-down approach in crafting micro/nanoparticle (M/NPs) models of PP particles, ensuring their enhanced relevance to real-world environments. Micro/nano PP particles, featuring a negatively charged particle size ranging from 203 to 2101 nm, were synthesized through variations in solution concentration and volume. Simultaneously, the devised MPs model was employed to develop a Raman-based qualitative and quantitative detection method for micro/nano PP particles, considering diverse sizes and concentrations. This method integrates Raman spectroscopy and microscopy to measure PP particles with varying sizes, utilizing the coffee ring effect. The Limit of detection (LOD) for 203 nm PP reached 31.25 µg/mL, while those for 382-2101 nm PP were approximately 3.9 µg/mL. The method underwent quantitative analysis by introducing 203 nm PP nanospheres into real food media (i.e., tea beverages, tea leaves), revealing a minimum LOD of approximately 31.25 µg/mL.

Raman silent region - based method for detection of pesticides with cyano group.

Based on the fact that not all chemical substances possess good Raman signals, this article focuses on the Raman silent region signals of pesticides with cyano group. Under the optimized conditions of methanol-water (1:1, v/v) as the solvent, irradiation at 302 nm light source for 20 min, and the use of 0.5 mol/L KI as the aggregating agent, Surface-enhanced Raman spectroscopy (SERS) method for azoxystrobin detection was developed by the Raman silent region signal of 2230 cm-1, and verified by detecting the spiked grapes with different concentrations of azoxystrobin. Other four pesticides with cyano group also could be identified at the peak of 2180 cm-1, 2205 cm-1, 2125 cm-1, and 2130 cm-1 for acetamiprid, phoxim, thiacloprid and cymoxanil, respectively. When azoxystrobin or acetamiprid was mixed respectively with chlorpyrifos without cyano group, their SERS signals in the Raman silent region of chlorpyrifos were not interfered, while mixed with cymoxanil in different ratios (1:4, 1:1 and 4:1), respectively, each two pesticides with cyano group could be distinguished by the changes in the Raman silent region. In further, four pesticides with or without cyano group were mixed together in 1:1:1:1 (acetamiprid, cymoxanil, azoxystrobin chlorpyrifos), and each pesticide still could be identified even at 0.5 mg/L. The results showed that the SERS method combined with UV irradiation may provide a new way to monitor the pesticides with C≡N performance in the Raman silent region without interference from the food matrix.

Degradation of carbofuran and acetamiprid in wolfberry by dielectric barrier discharge plasma: Kinetics, pathways, toxicity and molecular dynamics simulation.

Carbofuran and acetamiprid pose the highest residual risk among pesticides found in wolfberries. This study aimed to degrade these pesticides in wolfberries using a multi-array dielectric barrier discharge plasma (DBD), evaluate the impact on safety and quality and explore their degradation mechanism. The results showed that DBD treatment achieved 90.6% and 80.9% degradation rates for carbofuran and acetamiprid, respectively, following a first-order kinetic reaction. The 120 s treatment successfully reduced pesticide contamination to levels below maximum residue limits. Treatment up to 180 s did not adversely affect the quality of wolfberries. QTOF/MS identification and degradation pathway analysis revealed that DBD broke down the furan ring and carbamate group of carbofuran, while replacing the chlorine atom and oxidizing the side chain of acetamiprid, leading to degradation. The toxicological evaluation showed that the degradation products were less toxic than undegraded pesticides. Molecular dynamics simulations revealed the reactive oxygen species (ROS) facilitated the degradation of pesticides through dehydrogenation and radical addition reactions. ROS type and dosage significantly affected the breakage of chemical bonds associated with toxicity (C4-O5 and C2-Cl1). These findings deepen insights into the plasma chemical degradation of pesticides.

Effect of tannic acid binding on the thermal degradation behavior and product toxicity of boscalid.

The effect of tannic acid (TA) binding on the thermal degradation of boscalid was studied in this work. The results revealed that TA binding has a significant impact on boscalid degradation. The degradation rate constant of bound boscalid was reduced, and its corresponding half-life was significantly prolonged compared to the free state. Four identical degradation products were detected in both states through UHPLC-Q-TOF-MS, indicating that degradation products were not affected by TA binding. Based on DFT and MS analysis, the degradation pathways of boscalid included hydroxyl substitution of chlorine atoms and cleavage of CN and CC bonds. The toxicity of B2 and B3 exceeded that of boscalid. In summary, the binding of TA and boscalid significantly affected the thermal degradation rate of boscalid while preserving the types of degradation products. This study contributed to a fundamental understanding of the degradation process of bound pesticide residues in complex food matrices.

A breakthrough in periodontitis treatment: Revealing the pharmacodynamic substances and mechanisms of Kouqiangjie formula.

ETHNOPHARMACOLOGY RELEVANCE: Periodontitis, a complex inflammatory disease, significantly affects people's lives. Traditional Chinese multi-herbal formulas, composed of various herbs, exhibit their therapeutic efficacy holistically. Kouqiangjie Formula (KQJF), comprising 12 herbs including Rhizoma smilacis glabrae, Polygonatum sibiricum Delar. ex Redoute, Taraxacum mongolicum Hand.-Mazz, etc., has been clinically proven to effectively treat periodontitis. However, the potential active substances conferring these effects and their mechanisms of action remain unclear. AIM OF THE STUDY: The current investigation endeavours to utilize Ultra Performance Liquid Chromatography Quadrupole Time of Flight Mass Spectrometry (UPLC-Q-TOF-MS), network pharmacology, and in vivo animal experiment confirmation to explore the plausible bioactive compounds and operational mechanisms underpinning KQJF's therapeutic impact on periodontitis. MATERIALS AND METHODS: Using the UPLC-Q-TOF-MS technique, we deciphered the chemical constituents of KQJF. Network pharmacology was employed to earmark key bioactive elements, forecast principal targets, and operational pathways which were later substantiated through molecular docking. Experimental validations were carried out in a periodontitis animal model using a range of techniques, including micro-CT, H&E staining, qRT-PCR, and protein blotting procedures, providing comprehensive verification of our initial assumptions. RESULTS: Utilizing UPLC-Q-TOF-MS, we characterized 87 individual chemical constituents in KQJF. Network pharmacology revealed that 14 components, including senkyunolide A, glycycoumarin, licoflavonol, glycyrin, senkyunolide I, and senkyunolide H, form the key therapeutic basis of KQJF in targeting periodontitis. Significant targets and pathways were discerned as AKT1, MMP9, JUN, PTGS2, CASP3, TLR4, IL1ß, BCL2, PPARG, and pathways such as the TNF signaling pathway, NF-κB signaling pathway, osteoclast differentiation, and Wnt signaling pathway. Molecular docking demonstrated robust binding activity between these crucial targets and the key active ingredients. In vivo experimentation corroborated that, compared with the model group, KQJF significantly ameliorated symptoms and micro-CT imaging parameters of periodontitis in the rat model, down-regulating the expression of AKT1, MMP9, JUN, PTGS2, CASP3, TLR4, and IL1ß, while up-regulating the expression of BCL2 and PPARG. CONCLUSION: In summary, this study has pioneered a comprehensive exploration of the potential therapeutic constituents, targets, and mechanisms of KQJF for periodontitis treatment, adopting a synergistic strategy of "chemical component analysis-network pharmacology screening-in vivo animal experiment validation". This provides experimental evidence for the clinical application of KQJF and further in-depth research. Additionally, it presents an effective strategy for the research of other Chinese herbal formulations.

Self-Assembled Integrated Nanozyme Cascade Biosensor with Dual Catalytic Activity for Portable Urease Analysis.

In this work, a novel nanozyme (Cu@Zr) with all-in-one dual enzyme and fluorescence properties is designed by simple self-assembly. A nanozyme cascade sensor with disodium phenyl phosphate (PPDS) as substrate was first established by exploiting the dual enzymatic activities of phosphatase and laccase. Specifically, phosphatase cleaves the P-O bond of PPDS to produce colorless phenol, which is then oxidized by laccase and complexed with the chromogenic agent 4-aminoantipyrine (4-AP) to produce red quinoneimine (QI). Strikingly, the NH3 produced by the urease hydrolysis of urea can interact with Cu@Zr, accelerating the electron transfer rate and ultimately leading to a significantly improved performance of the cascade reaction. Moreover, the fluorescence at 440 nm of Cu@Zr is further quenched by the inner filter effect (IFE) of QI. Thus, the colorimetric and fluorescence dual-mode strategy for sensitive urease analysis with LODs of 3.56 and 1.83 U/L was established by the proposed cascade sensor. Notably, a portable swab loaded with Cu@Zr was also prepared for in situ urease detection with the aid of a smartphone RGB readout. It also provides a potentially viable analytical avenue for environmental and biological analysis.

High-intensity ultrasound promoted the maturation of high-salt liquid-state soy sauce: A mean of enhancing quality attributes and sensory properties.

High-intensity ultrasound was used as a means to promote maturation of soy sauce. The optimal conditions for ultrasound treatment were 90℃ at an ultrasound intensity of 39.48 W/cm2 for 60 min. The total reducing sugars and soluble salt-free solids content was significantly increased after ultrasound-assisted maturation. The free amino acid content was significantly decreased, mainly due to the Maillard reaction (MR). The promoted MR produced several types of flavor compounds, including esters, pyrazines, and ketones, which imparted an attractive aroma to the maturated soy sauce. The proportion of peptides with a molecular weight of 1-5 kDa provided umami as an important flavor characteristic, and the content in the ultrasound-matured soy sauce (10.19 %) was significantly higher than that in the freshly prepared soy sauce (8.34 %) and the thermally treated sample (8.89 %). Ultrasound-assisted maturation would improve product quality and meanwhile, shorten the duration and reduce the cost for the soy sauce industry.

Molecular and proteomic response of Pseudomonas fluorescens biofilm cultured on lettuce (Lactuca sativa L.) after ultrasound treatment at different intensity levels.

Ultrasonic treatment is widely used for surface cleaning of vegetables in the processing of agricultural products. In the present study, the molecular and proteomic response of Pseudomonas fluorescens biofilm cultured on lettuce was investigated after ultrasound treatment at different intensity levels. The results show that the biofilm was efficiently removed after ultrasound treatment with intensity higher than 21.06 W/cm2. However, at an intensity of less than 18.42 W/cm2, P. fluorescens was stimulated by ultrasound leading to promoted bacterial growth, extracellular protease activity, extracellular polysaccharide secretion (EPS), and synthesis of acyl-homoserine lactones (AHLs) as quorum-sensing signaling molecules. The expression of biofilm-related genes, stress response, and dual quorum sensing system was upregulated during post-treatment ultrasound. Proteomic analysis showed that ultrasound activated proteins in the flagellar system, which led to changes in bacterial tendency; meanwhile, a large number of proteins in the dual-component system began to be regulated. ABC transporters accelerated the membrane transport of substances inside and outside the cell membrane and equalized the permeability conditions of the cell membrane. In addition, the expression of proteins related to DNA repair was upregulated, suggesting that bacteria repair damaged DNA after ultrasound exposure.

Diversity for endoribonuclease nsp15-mediated regulation of alpha-coronavirus propagation and virulence.

IMPORTANCE: Understanding the role of the endoribonuclease non-structural protein 15 (nsp15) (EndoU) in coronavirus (CoV) infection and pathogenesis is essential for vaccine target discovery. Whether the EndoU activity of CoV nsp15, as a virulence-related protein, has a diverse effect on viral virulence needs to be further explored. Here, we found that the transmissible gastroenteritis virus (TGEV) and feline infectious peritonitis virus (FIPV) nsp15 proteins antagonize SeV-induced interferon-ß (IFN-ß) production in human embryonic kidney 293 cells. Interestingly, compared with wild-type infection, infection with EnUmt-TGEV or EnUmt-FIPV did not change the IFN-ß response or reduce viral propagation in immunocompetent cells. The results of animal experiments showed that EnUmt viruses did not reduce the clinical presentation and mortality caused by TGEV and FIPV. Our findings enrich the understanding of nsp15-mediated regulation of alpha-CoV propagation and virulence and reveal that the conserved functions of nonstructural proteins have diverse effects on the pathogenicity of CoVs.

Rapid magnetization and removal of microplastics from environment and food based on magnetic metal-organic framework Fe3O4@SiO2@MIL-53(Al).

Microplastics (MPs) are now not only emerging as pollutants in the environment, but their current state of contamination in food is also a cause for concern. It is necessary to focus how to control, reduce, and even remove MPs. In this study, a magnetic metal-organic framework (MOF) material, Fe3O4@SiO2@MIL-53(Al), was synthesized and applied to simulate the magnetization and removal of four types of MPs. Fe3O4@SiO2@MIL-53(Al) was characterized by various means to demonstrate its successful synthesis as a core-shell nanomaterial. The conditions of the method were optimized by examining the effect of time, the mass ratio of material to MPs, temperature, and pH on the removal effect. The removal rates of four MPs were 54.10-94.17%, and the maximum adsorption capacities of Fe3O4@SiO2@MIL-53(Al) that can be adsorbed were 10511.45-44390.24 mg g-1. Notably, the material can effectively magnetize and remove MPs from liquid food containing alcohol with highest efficiency of 97.10 ± 1.21%. Potential adsorption mechanisms were analyzed using kinetic, isothermal, and thermodynamic models, and electrostatic attraction and hydrogen bonding were found to play a dominant role in the adsorption process. In addition, not only can Fe3O4@SiO2@MIL-53(Al) be reused up to five times to maintain high removal rates, but it can also be used in food systems. Therefore, Fe3O4@SiO2@MIL-53(Al) not only has the advantages of ease of use and stability, but also can efficiently and quickly magnetize and remove many common MPs in more complex matrices such as food.

Exposure to ambient oxidant pollution associated with ceramide changes and cardiometabolic responses.

Evidence of impact of ambient oxidant pollution on cardiometabolic responses remains limited. We aimed to examine associations of oxidant pollutants with cardiometabolic responses, and effect modification by ceramides. During 2019-2020, 152 healthy adults were visited 4 times in Beijing, China, and indicators of ceramides, glucose homeostasis, and vascular function were measured. We found significant increases in ceramides of 13.9% (p = 0.020) to 110.1% (p = 0.005) associated with an interquartile increase in oxidant pollutants at prior 1-7 days. Exposure to oxidant pollutants was also related to elevations in insulin and reductions in adiponectin, and elevations in systolic and diastolic blood pressure. Further, stratified analyses revealed larger changes in oxidant pollutant related cardiometabolic responses among participants with higher ceramide levels compared to those with lower levels. Our findings suggested cardiometabolic effects associated with exposure to oxidant pollutants, which may be modified by ceramide levels.

Ag decoration on Na2Ti3O7 nanowires for improved SERS and PHE performance.

Na2Ti3O7 (NTO) is recognized as an authenticated promising photocatalyst and surface-enhanced Raman scattering (SERS) active material, although its performance is limited by its high carrier recombination rate, wide band gap and inadequate utilization of visible light. In this study, to solve these issues, sea urchin-shaped NTO nanowires directly grown on a substrate were fabricated, and then Ag nanoparticles were decorated on NTO nanowires using sputtering equipment. The as-prepared Ag-NTO substrates exhibited different morphologies and high SERS activity, which was confirmed by finite-difference time-domain (FDTD) simulations, showing that appropriate Ag decoration can bring more nanogaps and thus enhance the electromagnetic field (EM) contribution. We visualized the charge transfer (CT) mechanism in SERS and further investigated the catalytic hydrogen production process similarly induced by photogenerated CT. The optimal SERS substrate (Ag-NTO-3) was adopted to verify the photocatalytic hydrogen evolution (PHE) activity, and the hydrogen evolution rate of Ag-NTO-3 was 106.7 µmol h-1 (twice that of pristine NTO). Photoelectrochemical measurements and photoluminescence (PL) analysis were used to elucidate the potential enhancement mechanisms for the photocatalytic performance and CT process. This study can provide a valuable reference for performance and mechanism studies of SERS substrates and photocatalysts.

Temperature-Dependent Phonon Scattering and Photoluminescence in Vertical MoS2/WSe2 Heterostructures.

Transition metal dichalcogenide (TMD) monolayers and their heterostructures have attracted considerable attention due to their distinct properties. In this work, we performed a systematic investigation of MoS2/WSe2 heterostructures, focusing on their temperature-dependent Raman and photoluminescence (PL) characteristics in the range of 79 to 473 K. Our Raman analysis revealed that both the longitudinal and transverse modes of the heterostructure exhibit linear shifts towards low frequencies with increasing temperatures. The peak position and intensity of PL spectra also showed pronounced temperature dependency. The activation energy of thermal-quenching-induced PL emissions was estimated as 61.5 meV and 82.6 meV for WSe2 and MoS2, respectively. Additionally, we observed that the spectral full width at half maximum (FWHM) of Raman and PL peaks increases as the temperature increases, and these broadenings can be attributed to the phonon interaction and the expansion of the heterostructure's thermal coefficients. This work provides valuable insights into the interlayer coupling of van der Waals heterostructures, which is essential for understanding their potential applications in extreme temperatures.

Recent advance in probiotics for the elimination of pesticide residues in food and feed: mechanisms, product toxicity, and reinforcement strategies.

The extensive utilization of pesticides in agriculture has resulted in the presence of pesticide residues in food and feed, which poses a significant threat to human health. Various physical and chemical methods have been proposed to remove pesticides, but most of these methods are either costly or susceptible to secondary contamination. Consequently, the utilization of microorganisms, such as probiotics, for eliminating pesticides, has emerged as a promising alternative. Probiotics, including lactic acid bacteria, yeasts, and fungi, have demonstrated remarkable efficiency and convenience in eliminating pesticide residues from food or feed. To promote the application of probiotic decontamination, this review examines the current research status on the utilization of probiotics for pesticide reduction. The mechanisms involved in microbial decontamination are discussed, along with the toxicity and potential health risks of degradation products. Furthermore, the review explores strategies to enhance probiotic detoxification and outlines prospects for future development.

Pro-inflammation and pro-atherosclerotic responses to short-term air pollution exposure associated with alterations in sphingolipid ceramides and neutrophil extracellular traps.

Air pollution has been associated with the development of atherosclerosis; however, the pathophysiological mechanisms underlying pro-atherosclerotic effects of air pollution exposure remain unclear. We conducted a prospective panel study in Beijing and recruited 152 participants with four monthly visits from September 2019 to January 2020. Linear mixed-effect models were applied to estimate the associations linking short-term air pollution exposure to biomarkers relevant to ceramide metabolism, pro-inflammation (neutrophil extracellular traps formation and systemic inflammation) and pro-atherosclerotic responses (endothelial stimulation, plaque instability, coagulation activation, and elevated blood pressure). We further explored whether ceramides and inflammatory indicators could mediate the alterations in the profiles of pro-atherosclerotic responses. We found that significant increases in levels of circulating ceramides of 9.7% (95% CIs: 0.7, 19.5) to 96.9% (95% CIs: 23.1, 214.9) were associated with interquartile range increases in moving averages of ambient air pollutant metrics, including fine particulate matter (PM2.5), black carbon, particles in size fractions of 100-560 nm, nitrogen dioxide, carbon monoxide and sulfur dioxide at prior up to 7 days. Higher air pollution levels were also associated with activated neutrophils (increases in citrullinated histone H3, neutrophil elastase, double-stranded DNA, and myeloperoxidase) and exacerbation of pro-atherosclerotic responses (e.g., increases in vascular endothelial growth factor, lipoprotein-associated phospholipase A2, matrix metalloproteinase-8, P-selectin, and blood pressure). Mediation analyses further showed that dysregulated ceramide metabolism and potentiated inflammation could mediate PM2.5-associated pro-atherosclerotic responses. Our findings extend the understanding on potential mechanisms of air pollution-associated atherosclerosis, and suggest the significance of reducing air pollution as priority in urban environments.

Exploring the binding mechanism and adverse toxic effects of degradation metabolites of pyrethroid insecticides to human serum albumin: Multi-spectroscopy, calorimetric and molecular docking approaches.

Pyrethroid insecticides (PIs), a class of structurally similar non-persistent organic pollutants, can be degraded and metabolized to more toxic, and longer half-life products. In this study, the binding interaction mechanisms between human serum albumin (HSA) and the main degradation metabolites of PIs, 3-phenoxybenzoic acid (3-PBA) and 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), were studied by theoretical simulation and experimental verification. Steady state fluorescence spectra showed that the fluorescence quenching mechanism was static. According to the binding constant, 4-F-3-PBA (1.53 × 105 L mol-1) was bound more strongly to HSA than 3-PBA (1.42 × 105 L mol-1) in subdomain ⅡA (site I). It was found by isothermal titration calorimetry that the metabolites and HSA spontaneously combined mainly through hydrogen bond and van der Waals interaction. Ultraviolet absorption spectra and circular dichroism spectra showed that the metabolites caused slight changes in the microenvironment and conformation of HSA. The above results were proved by molecular docking. The toxicity properties of the metabolites were further analyzed by software, and 4-F-3-PBA was found to be more toxic than 3-PBA. Considering the high exposure level of these metabolites in food, the environment and human body, it is necessary to further explore the toxicity of PIs metabolites.