High-Efficiency Effect-Directed Analysis Leveraging Five High Level Advancements: A Critical Review.

Organic contaminants are ubiquitous in the environment, with mounting evidence unequivocally connecting them to aquatic toxicity, illness, and increased mortality, underscoring their substantial impacts on ecological security and environmental health. The intricate composition of sample mixtures and uncertain physicochemical features of potential toxic substances pose challenges to identify key toxicants in environmental samples. Effect-directed analysis (EDA), establishing a connection between key toxicants found in environmental samples and associated hazards, enables the identification of toxicants that can streamline research efforts and inform management action. Nevertheless, the advancement of EDA is constrained by the following factors: inadequate extraction and fractionation of environmental samples, limited bioassay endpoints and unknown linkage to higher order impacts, limited coverage of chemical analysis (i.e., high-resolution mass spectrometry, HRMS), and lacking effective linkage between bioassays and chemical analysis. This review proposes five key advancements to enhance the efficiency of EDA in addressing these challenges: (1) multiple adsorbents for comprehensive coverage of chemical extraction, (2) high-resolution microfractionation and multidimensional fractionation for refined fractionation, (3) robust in vivo/vitro bioassays and omics, (4) high-performance configurations for HRMS analysis, and (5) chemical-, data-, and knowledge-driven approaches for streamlined toxicant identification and validation. We envision that future EDA will integrate big data and artificial intelligence based on the development of quantitative omics, cutting-edge multidimensional microfractionation, and ultraperformance MS to identify environmental hazard factors, serving for broader environmental governance.

PM2.5 Increases Systemic Inflammatory Cells and Associated Disease Risks by Inducing NRF2-Dependent Myeloid-Biased Hematopoiesis in Adult Male Mice.

Although PM2.5 (fine particles with aerodynamic diameter <2.5 µm) exposure shows the potential to impact normal hematopoiesis, the detailed alterations in systemic hematopoiesis and the underlying mechanisms remain unclear. For hematopoiesis under steady-state or stress conditions, nuclear factor erythroid 2-related factor 2 (NRF2) is essential for regulating hematopoietic processes to maintain blood homeostasis. Herein, we characterized changes in the populations of hematopoietic stem progenitor cells and committed hematopoietic progenitors in the lungs and bone marrow (BM) of wild-type and Nrf2-/- C57BL/6J male mice. PM2.5-induced NRF2-dependent biased hematopoiesis toward myeloid lineage in the lungs and BM generates excessive numbers of various inflammatory immune cells, including neutrophils, monocytes, and platelets. The increased population of these immune cells in the lungs, BM, and peripheral blood has been associated with observed pulmonary fibrosis and high disease risks in an NRF2-dependent manner. Therefore, although NRF2 is a protective factor against stressors, upon PM2.5 exposure, NRF2 is involved in stress myelopoiesis and enhanced PM2.5 toxicity in pulmonary injury, even leading to systemic inflammation.

Matrix Thermal Shift Assay for Fast Construction of Multidimensional Ligand-Target Space.

Existing thermal shift-based mass spectrometry approaches are able to identify target proteins without chemical modification of the ligand, but they are suffering from complicated workflows with limited throughput. Herein, we present a new thermal shift-based method, termed matrix thermal shift assay (mTSA), for fast deconvolution of ligand-binding targets and binding affinities at the proteome level. In mTSA, a sample matrix, treated horizontally with five different compound concentrations and vertically with five technical replicates of each condition, was denatured at a single temperature to induce protein precipitation, and then, data-independent acquisition was employed for quick protein quantification. Compared with previous thermal shift assays, the analysis throughput of mTSA was significantly improved, but the costs as well as efforts were reduced. More importantly, the matrix experiment design allowed simultaneous computation of the statistical significance and fitting of the dose-response profiles, which can be combined to enable a more accurate identification of target proteins, as well as reporting binding affinities between the ligand and individual targets. Using a pan-specific kinase inhibitor, staurosporine, we demonstrated a 36% improvement in screening sensitivity over the traditional thermal proteome profiling (TPP) and a comparable sensitivity with a latest two-dimensional TPP. Finally, mTSA was successfully applied to delineate the target landscape of perfluorooctanesulfonic acid (PFOS), a persistent organic pollutant that is hard to perform modification on, and revealed several potential targets that might account for the toxicities of PFOS.

Effect-directed analysis of androgenic compounds from sewage sludges in China.

The safety of municipal sewage sludge has raised great concerns because of the accumulation of large-scale endocrine disrupting chemicals in the sludge during wastewater treatment. The presence of contaminants in sludge can cause secondary pollution owing to inappropriate disposal mechanisms, posing potential risks to the environment and human health. Effect-directed analysis (EDA), involving an androgen receptor (AR) reporter gene bioassay, fractionation, and suspect and nontarget chemical analysis, were applied to identify causal AR agonists in sludge; 20 of the 30 sludge extracts exhibited significant androgenic activity. Among these, the extracts from Yinchuan, Kunming, and Shijiazhuang, which held the most polluted AR agonistic activities were prepared for extensive EDA, with the dihydrotestosterone (DHT)-equivalency of 2.5 - 4.5 ng DHT/g of sludge. Seven androgens, namely boldione, androstenedione, testosterone, megestrol, progesterone, and testosterone isocaproate, were identified in these strongest sludges together, along with testosterone cypionate, first reported in sludge media. These identified androgens together accounted for 55 %, 87 %, and 52 % of the effects on the sludge from Yinchuan, Shijiazhuang, and Kunming, respectively. This study elucidates the causative androgenic compounds in sewage sludge and provides a valuable reference for monitoring and managing androgens in wastewater treatment.

Recent developments in modification of biochar and its application in soil pollution control and ecoregulation.

Soil pollution has become a real threat to mankind in the 21st century. On the one hand, soil pollution has reduced the world's arable land area, resulting in the contradiction between the world's population expansion and the shortage of arable land. On the other hand, soil pollution has seriously disrupted the soil ecological balance and significantly affected the biodiversity in the soil. Soil pollutants may further affect the survival, reproduction and health of humans and other organisms through the food chain. Several studies have suggested that biochar has the potential to act as a soil conditioner and to promote crop growth, and is widely used to remove environmental pollutants. Biochar modified by physical, chemical, and biological methods will affect the treatment efficiency of soil pollution, soil quality, soil ecology and interaction with organisms, especially with microorganisms. Therefore, in this review, we summarized several main biochar modification methods and the mechanisms of the modification and introduced the effects of the application of modified biochar to soil pollutant control, soil ecological regulation and soil nutrient regulation. We also introduced some case studies for the development of modified biochars suitable for different soil conditions, which plays a guiding role in the future development and application of modified biochar. In general, this review provides a reference for the green treatment of different soil pollutants by modified biochar and provides data support for the sustainable development of agriculture.

Dynamic landscape of multi-elements in PM2.5 revealed by real-time analysis.

Metal components in fine particulate matter (PM2.5) are closely associated with many adverse health outcomes. Dynamic changes of metals in PM2.5 are critical for risk assessment due to their temporal variations. Herein, an online method for real-time determination of multi-elements (As, Cd, Cs, Cu, Fe, Mg, Mn, Pb, Rb, Sn, Tl, and V) in PM2.5 was established by directly introducing air samples into inductively coupled plasma mass spectrometry (ICPMS). Meanwhile, a quantified method using metal standard aerosols (Cr, Mo, and W) and high time resolution for 3.3 min online measurement was developed and validated. The limits of detection were in the range of 0.001-6.30 ng/m3 for different metals. Subsequently, the real-time contents of multi-elements in PM2.5 for 12 h over 33 days were measured at different air qualities. Temporal variations of crustal elements like Fe, Mg are similar to PM2.5, whereas toxic elements (Pb, As and Cd) have upward trends at dusk. This denoted the association with various emission sources and different exposure concentrations of metals. In addition to the acquisition of real-time information, online analysis of multi-elements in PM2.5 is beneficial for atmospheric monitoring and provides critical insights into the different exposure risks of metals in PM2.5 at varying times.

Disturbed Gut-Liver axis indicating oral exposure to polystyrene microplastic potentially increases the risk of insulin resistance.

Human uptake abundance of microplastics via various pathways, and they accumulate in human liver, kidney, gut and even placenta (especially with a diameter of 1 µm or less). Recent scientific studies have found that exposure to microplastics causes intestinal inflammation and liver metabolic disorder, but it remains largely unknown that whether the damage and inflammation may cause further development of severe diseases. In this study, we discovered one of such potential diseases that may be induced by the exposure to small-sized microplastics (with a diameter of 1 µm) performing a multi-organ and multi-omics study comprising metabolomics and microbiome approaches. Unlike other animal experiments, the dosing strategy was applied in mice according to the daily exposure of the highly exposed population, which was more environmentally relevant and reflective of real-world human exposure. Our studies on the gut-liver axis metabolism have shown that the crosstalk between the gut and liver ultimately leaded to insulin resistance and even diabetes. We proactively verified this hypothesis by measuring the levels of fasting blood glucose and fasting insulin, which were found significantly elevated in the mice with microplastics exposure. These results indicate the urgent need of large-scale cohort evaluation on epidemiology and prognosis of insulin resistance after microplastics exposure in future.

Illuminating a time-response mechanism in mice liver after PM2.5 exposure using metabolomics analysis.

PM2.5 is recognized as an atmospheric pollutant that seriously jeopardizes human health. Emerging evidence indicates that PM2.5 exposure is associated with metabolic disorders. Existing epidemiology and toxicology studies on the health effects of PM2.5 usually focused on its different components and doses, the effects on susceptible populations, or the effects of indoor and outdoor pollution. The underlying mechanisms of exposure time are poorly understood. Liver, as the central organ involved in various metabolisms, has special signaling pathways non-existed in lung and cardiovascular systems. Exacerbation in liver by the prolonged exposure of PM2.5 leads to hepatic function disorder. It is therefore essential to elucidate the mechanism underlying hepatotoxicity after PM2.5 exposure from the perspective of time-response relationship. In this study, targeted metabolomics was utilized to explore the hepatic injury in mice after PM2.5 exposure. Our results showed that prolonged exposure of PM2.5 would aggravate liver metabolic disorders. The metabolic process was divided into three phases. In phase I, it was found that PM2.5 exposure disturbed the hepatic urea synthesis. In phase II, oxidative damages and inflammations obviously occurred in liver, which would further cause neurobehavioral disorders and fat deposits. In phase III, the changes of metabolites and metabolic pathways indicated that the liver has been severely damaged, with the accelerated biosynthesis and fat metabolism. Finally, using ROC analysis coupled with their biological functions, 4 potential biomarkers were screened out, with which we established a method to classify and diagnose the progress of liver damage in mice after PM2.5 exposure. In this paper, we not only established the time-response relationship of PM2.5, but also provided new insights for the classification and prediction of the toxic injury stages in mice liver, which provides a ground work for the future drug intervention to prevent oxidative damage of PM2.5.

[Isolation, Identification, and Degrading Characteristics of an Oil Resistant Formaldehyde-Degrading Bacterium].

In recent years, the health risks of cooking oil fumes have been widely concerning. Since formaldehyde is one of the major pollutants emitted from cooking oil fumes, the degradation of formaldehyde should be investigated. Due to the advances and innovations in the degradation of pollutants, biodegradation was evaluated in this research. In this study, we screened out the strain of XF-1, which can degrade formaldehyde from cooking oil fume condensates. The strain of XF-1 was identified as Bacillus amyloliquefaciens sp. by a sequence analysis combing morphology, physiological, and biochemical experiments. The degrading characteristics of the strain were further studied. In the medium with a formaldehyde concentration of 100 mg·L-1, the efficiency of XF-1 for degrading formaldehyde was 95.80% within 34 h. When the initial concentration of formaldehyde was <300 mg·L-1, the XF-1 strain could completely degrade the formaldehyde within 120 h. When the formaldehyde concentration was 800 mg·L-1, the degradation rate of the XF-1 strain reached 73.01% at 96 h. The maximum tolerated concentration of formaldehyde was 1500 mg·L-1. According to a single factor experiment (pH, inoculation amount, formaldehyde concentration, and temperature), the influence of each factor on the degradation of formaldehyde was studied. The optimal growth condition of the strain was 30℃ at pH 6 with an inoculum amount of 10%. The degradation specificity of formaldehyde was studied by comparing it with that of other bacillus species. The results showed that XF-1 strain was specific with regard to the function of degrading formaldehyde and was able to withstand a high oil environment. The maximum tolerable oil concentration of XF-1 was 900 g·L-1. By analyzing the extracellular metabolites, it was determined that the metabolic pathway of formaldehyde degradation was the RuMP assimilation pathway. In this paper, a strain of formaldehyde degrading bacteria that was also resistant to oil was screened out and its metabolic mechanism was studied. The results indicated that the bacteria had broad application prospects in the treatment of formaldehyde emitted from cooking oil fumes.

Metabolic profiling of liver tissues in mice after instillation of fine particulate matter.

Human exposure to fine particulate matter (PM2.5) in various environment could lead to a number of adverse health effects. Little is known about the toxic mechanism and the further response caused by PM2.5 exposure. In this study, a metabolomics approach using gas chromatography-mass spectrometry (GC-MS) was adopted to evaluate the liver toxicity induced by different gradient concentrations of PM2.5. A multivariate statistical analysis had shown, a total of 12 endogenous metabolites including amino acids and organic acids were identified as potential biomarkers of PM2.5 and most of them were down-regulated. By analyzing the metabolic pathways using the identified biomarkers, the significantly interfered metabolic pathways when mice were exposed to PM2.5 were found as: glycine, serine and threonine metabolism, aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, alanine, aspartate and glutamate metabolism, methane metabolism, linoleic acid metabolism and valine, and leucine and isoleucine biosynthesis, all of which were closely related to liver metabolism. The findings of this study reveal detailed toxic metabolic effects of PM2.5 in liver tissues, provide ways for assessing the health risk of PM2.5 at molecular level, and further offer insights on the potential mechanism of its toxicity.

[Exhaust Emission Characteristics of Typical Alkanes from Heavy-Duty Diesel Vehicles Based on a Portable Emission Measurement System].

The on-road emissions of typical alkanes from 11 heavy-duty diesel vehicles with different emission standards (from China Ⅰ to China Ⅳ) were tested using a portable emission measurement system(PEMS) and quantified by gas chromatography-mass spectrometry (GC-MS). Our aim was to analyze the emission characteristics of typical alkanes in heavy-duty diesel vehicle exhaust. The results show that the emission standard significantly affected the emission factors (EFs) of n-alkanes and hopanes. Vehicles with higher emission standards had lower EFs. Compared with China Ⅰ vehicles, the total EFs of n-alkanes, 17α(H),21ß(H)-C30 hopane (C30-hopane), and 22S- and 22R-17α(H),21ß(H)-homohopane (22S-C31 and 22R-C31 homohopane) from China Ⅳ vehicles were significantly reduced by 72.23%, 64.95%, 70.78%, and 74.68%, respectively. The peak carbon numbers of gaseous n-alkanes were 17 to 18, while they were 18 to 21 in particulate n-alkanes. The 22S-C31 homohopane/(22S-C31 homohopane + 22R-C31 homohopane) ratios ranged from 0.46 to 0.56, with an average of 0.50, which conform to the characteristics of hopanes in petroleum. The total EFs of n-alkanes had a good linear relationship with the total EFs of C30-hopane, and the R2 was 0.9268. Furthermore, the driving conditions had a great influence on the emissions of n-alkanes and hopanes. Specifically, the EFs of n-alkanes and hopanes on non-highway roads were 1.69 to 2.42 times greater than those on highways.

Changes in the components and biotoxicity of dissolved organic matter in a municipal wastewater reclamation reverse osmosis system.

The characteristics of dissolved organic matter (DOM) and the biotoxicity of these components were investigated in a municipal wastewater reclamation reverse osmosis (mWRRO) system with a microfiltration (MF) pretreatment unit. The MF pretreatment step had little effect on the levels of dissolved organic carbon (DOC) in the secondary effluent, but the addition of chlorine before MF promoted the formation of organics with anti-estrogenic activity. The distribution of excitation emission matrix (EEM) fluorescence constituents exhibited obvious discrepancies between the secondary effluent and the reverse osmosis (RO) concentrate. Using size exclusion chromatography, DOM with low molecular weights of approximately 1.2 and 0.98 kDa was newly formed during the mWRRO. The normalized genotoxicity and anti-estrogenic activity of the RO concentrate were 32.1 ± 10.2 µg4-NQO/mgDOC and 0.36 ± 0.08 mgTAM/mgDOC, respectively, and these values were clearly higher than those of the secondary effluent and MF permeate. The florescence volume of Regions I and II in the EEM spectrum could be suggested as a surrogate for assessing the genotoxicity and anti-estrogenic activity of the RO concentrate.