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Oxylipins are a class of low-abundance lipids formed via oxygenation of fatty acids. These compounds include potent signaling molecules (e.g., octadecanoids, eicosanoids) that can exert essential functions in the pathophysiology of inflammatory diseases including asthma. While some oxylipin signaling cascades have been unraveled using LC-MS/MS-based methods, measurements in homogenate samples do not represent the spatial heterogeneity of lipid metabolism. Mass spectrometry imaging (MSI) directly detects analytes from a surface, which enables spatial mapping of oxylipin biosynthesis and migration within the tissue. MSI has lacked the sensitivity to routinely detect low-abundance oxylipins; however, new multiple-reaction-monitoring (MRM)-based MSI technologies show increased sensitivity. In this study, we developed a workflow to apply desorption electrospray ionization coupled to a triple quadrupole mass spectrometer (DESI-MRM) to spatially map oxylipins in pulmonary tissue. The targeted MSI workflow screened guinea pig lung extracts using LC-MS/MS to filter oxylipin targets based on their detectability by DESI-MRM. A panel of 5 oxylipins was then selected for DESI-MRM imaging derived from arachidonic acid (TXB 2 , 11-HETE, 12-HETE), linoleic acid (12,13-DiHOME), and α-linolenic acid (16-HOTrE). To parse this new data type, a custom-built R package (quantMSImageR) was developed with functionality to label regions of interest as well as quantify and analyze lipid distributions. The spatial distributions quantified by DESI-MRM were supported by LC-MS/MS analysis, with both indicating that 16-HOTrE and 12-HETE were associated with airways, while 12,13-DiHOME and arachidonic acid were mapped to parenchyma. This study realizes the potential of targeted MSI to routinely map low-abundance oxylipins with high specificity at scale.

Clinical samples are routinely inactivated before molecular assays to prevent pathogen transmission. Antibody-based assays are sensitive to changes in analyte conformation, but the impact of inactivation on the analyte detectability has been overlooked. This study assessed the effects of commonly used inactivation-methods, Triton X-100 (0.5%) and heat (60 °C, 1 h), on cytokine/chemokine detection in plasma, lung aspirates, and nasopharyngeal samples. Heat significantly reduced analyte detectability in plasma (IL-12p40, IL-15, IL-16, VEGF, IL-7, TNF-β) by 33-99% (p ≤ 0.02), while Triton X-100 minimally affected analytes in plasma and nasopharyngeal samples (11-37%, p ≤ 0.04) and had no significant impact on lung aspirates. Structural analysis revealed that cytokines affected by heat had more hydrophobic residues and higher instability-indices. As the protein-detectability was affected differently in different sample types, the sample environment could also influence protein stability. This underscores the importance of selecting the most suitable inactivation methods for clinical samples to ensure accurate cytokine/chemokine analysis in both clinical and research settings., (© 2024. Crown.)

Pulmonary epithelial lining fluid (ELF) was commonly used for the pharmacokinetic study in lower respiratory tract infections. To characterize the intrapulmonary pharmacokinetic properties of polymyxin B following aerosol delivery, we developed and fully validated a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for quantifying polymyxin B in human bronchoalveolar lavage fluid (BALF). The ELF concentrations were calculated by the BALF values of polymyxin B using urea as a volume normalizer. Chromatographic separation was achieved on a Phonomenex Kinetex XB-C18 column(100 mm × 2.1 mm I.D., 2.6 μm)in acetonitrile and water both containing 0.2 % formic acid. The flow rate was set as 0.4 mL/min for a 3.5 min running time. Protein precipitation was used in preparing BALF samples with polymyxin E1 as an internal standard. Polymyxin B was detected under multiple reaction monitoring conditions using the electrospray ionization interface running in the positive ionization mode. The assay showed a good linear relationship over the tested concentration ranges of 0.0300/0.00306---10.0/1.02 mg/L for polymyxin B1/B2 in bronchoalveolar lavage fluid (R 2  > 0.99). The inter- and inter-day precisions (RSD, %) were < 12.2 %(15.2 % for LLOQ samples)and the accuracies (%) were within the range of 94.3 ∼ 110.4 %. This reliable LC-MS/MS method for detection of polymyxin B was successfully applied to conduct a pulmonary penetration study in patients following aerosol administration., 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. Published by Elsevier B.V.)

A receptor for advanced glycation end products (RAGE) has emerged as a crucial player in various pathological conditions due to its involvement in inflammation and cellular dysfunction. Its soluble isoform, sRAGE, has garnered significant attention for its competitive inhibitory effects and potential therapeutic applications. However, obtaining sRAGE with appropriate glycosylation patterns for binding to glycated proteins has been challenging, often requiring costly expression systems. Here, we present a novel approach for producing and purifying sRAGE from Sus scrofa lungs, bypassing the need for expensive expression systems. Previous protocols for sRAGE extraction faced reproducibility issues due to high viscosity and haemoglobin content of the solution. To address this, we developed a method for selective haemoglobin precipitation using a zinc-containing buffer, enabling purification via various chromatographic methods. Through a combination of chromatographic techniques, we obtained sRAGE in suitable purity, identified using HPLC-MS/MS. Additionally, producing glycated proteins for RAGE receptor activation often involved lengthy protocols or inadequate separation from reactants. Thus, we devised a rapid method for producing and purifying pure BSA glycated with ribose, addressing a critical gap in the field. Functional studies, conducted using Native PAGE, demonstrated the capability of purified proteins to bind to each other., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

This Technical Note presents a comprehensive proteomics workflow for the new combination of Orbitrap and Astral mass analyzers across biofluids, cells, and tissues. Central to our workflow is the integration of Adaptive Focused Acoustics (AFA) technology for cells and tissue lysis to ensure robust and reproducible sample preparation in a high-throughput manner. Furthermore, we automated the detergent-compatible single-pot, solid-phase-enhanced sample Preparation (SP3) method for protein digestion. The synergy of these advanced methodologies facilitates a robust and high-throughput approach for cell and tissue analysis, an important consideration in translational research. This work disseminates our platform workflow, analyzes the effectiveness, demonstrates the reproducibility of the results, and highlights the potential of these technologies in biomarker discovery and disease pathology. For cells and tissues (heart, liver, lung, and intestine) proteomics analysis by data-independent acquisition mode, identifications exceeding 10,000 proteins can be achieved with a 24 min active gradient. In 200 ng injections of HeLa digest across multiple gradients, an average of more than 80% of proteins have a CV less than 20%, and a 45 min run covers ∼90% of the expressed proteome. This complete workflow allows for large swaths of the proteome to be identified and is compatible with diverse sample types.

Ash emission from volcanic eruptions affects the environment, society, and human health. This study shows the total concentration and lung bioaccessible fraction of eight potential toxic metal(loid)s in five Popocatépetl ashfall samples. Mineralogical phases and particle size distribution of the ashfall were analyzed by X-ray diffraction (XRD) and Scanning Electron Microscope (SEM) techniques, respectively. The bioaccessibility test of Gamble solution (GS) and Artificial Lysosomal Fluid (ALF) were conducted to simulate extracellular (pH 7) and intracellular (pH 4.5) conditions, respectively. The studied metal(loid)s showed the following total concentration (mg kg -1 ): 1.98 (As), 0.17 (Cd), 134.09 (Cr), 8.66 (Cu), 697.33 (Mn), 55.35 (Ni), 8.77 (Pb), and 104.10 (Zn). Geochemical indices suggested that some metal(loid)s are slightly enriched compared to the local soil background concentrations. Several mineralogical phases were identified in the collected ashfall deposits, such as plagioclase, pyroxene, and Fe-Ti oxide, among others. According to the risk assessment results, the non-carcinogenic risk related to ashfall exposure returns an HQ > 1 for children. In contrast, the estimation of carcinogenic risk was found to be within the tolerable limit. Metal(loid)s showed low bioaccessibility (< 30%) in GS and ALF, with the highest values found in ALF solution for As (12.18%) and Cu (7.57%). Despite their metal-bioaccessibility, our findings also showed that dominant ash particle size ranged between fine (< 2.5 μm) and extremely fine (< 1 μm), considered highly inhalable fractions. The results obtained in this work indicate that volcanic ashes are bioinsoluble and biodurable, and exhibit low bioaccessibility when in contact with lung human fluids., (© 2024. The Author(s).)

Background: Human lung tissue, as an interface with the environment, is susceptible to various environmental pollutants, including trace metals. However, quantitative data on trace metals in human lung tissues remain poorly described., Methods: This study aimed to characterize the elemental composition of histologically healthy, unaffected parts of human lung tissues, associated with non-infective, non-infiltrative, and non-malignant diseases (n = 60) for essential (Cr, Mn, Fe, Co, Cu, Zn, and Se) and toxic trace elements (Sr, Ni, As, Cd, and Pb). Additionally, we investigated the influence of personal factors (sex, age, and smoking habits) on the examined trace element profiles, as well as between the trace elements correlations in the healthy human lungs., Results: Among the analyzed trace elements, Fe was the most prevalent, while As was the least prevalent in healthy lung tissues. Stratifying by age revealed significantly higher Cr and Co (less Sr, Ni, and Pb) and lower Se levels in older individuals (above 65 years) compared to their younger counterparts. Sex-based differences were also notable, with Cu and Co 1.2- and 2.3-fold higher levels in females than in males. Exploring the impact of smoking habits revealed a striking 10-fold increase in Cd levels in the lung tissues of smokers compared to non-smokers. Correlation analyses showed significant positive associations between concentrations of certain toxic and essential trace elements in healthy lung tissues., Conclusions: This study could contribute to the establishment of baseline intervals for essential and toxic trace elements, valuable for toxicological and clinical assessment, in healthy, unaffected human lungs, and indicates the influence of sex, age, and smoking. However, further larger-scale studies are needed to make more stable conclusions., 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 GmbH. All rights reserved.)

Identifying body fluids and organ tissues is highly significant as they can offer crucial evidence in criminal investigations and aid the court in making informed decisions, primarily through evaluating the biological source and possibly at the activity level up to death or fatal damage. In this study, organ tissue-specific CpG markers were identified from Illumina's methylation EPIC array data of nine organ tissues, including epidermis, dermis, heart, skeletal muscle, blood, kidney, brain, lung, and liver, from autopsies of 10 Koreans. Through the validation test using 43 samples, 18 hypomethylation markers, with two markers for each organ tissue type, were selected to construct a SNaPshot assay. Two multiplex assays involving forward and reverse SBE primers were designed to help investigators accurately determine the organ origin of the analyzed tissue samples through repeated analysis of the same PCR products for markers. The developed multiplex demonstrated high accuracy, achieving 100.0 % correct detection of the presence of nine organ tissue types in 88 samples from autopsies of 10 Asians. However, two lung samples showed additional positive indications of the presence of blood. An interlaboratory comparison using 80 autopsy samples (heart, skeletal muscle, blood, kidney cortex, kidney medulla, brain, lung, and liver) from 10 individuals in Germany revealed overall comparable results with correct detection of the presence of eight organ tissue types in 92.5 % samples (74 of 80 samples). In the case of six samples, it was impossible to determine the correct tissue successfully due to drop-outs of unmethylation signals at target tissue marker loci. One of these lung samples revealed only non-intended off-target signals for blood. The observed differences might be due to differences in sample collection during routine autopsy, technical differences due to the PCR cycler, and the threshold used for signal calling. Indicating the presence of additional tissue type and off-target unmethylation signals seems alleviated by applying more stringent hypomethylation thresholds. Therefore, the developed SNaPshot multiplex assays will be valuable for forensic investigators dealing with organ tissue identification, as well as for prosecutors and defense aiming to establish the circumstances that occurred at the crime scene., Competing Interests: Declaration of Competing Interest The authors have declared no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Context.—: Overexposure to respirable coal mine dust can cause severe lung disease including progressive massive fibrosis (PMF). Field emission scanning electron microscopy with energy dispersive x-ray spectroscopy (FESEM-EDS) has been used for in situ lung dust particle analysis for evaluation of disease etiology. Automating such work can reduce time, costs, and user bias., Objective.—: To develop and test an automated FESEM-EDS method for in situ analysis of inorganic particles in coal miner lung tissue., Design.—: We programmed an automated FESEM-EDS procedure to collect particle size and elemental data, using lung tissue from 10 underground coal miners with PMF and 4 control cases. A statistical clustering approach was used to establish classification criteria based on particle chemistry. Data were correlated to PMF/non-PMF areas of the tissue, using corresponding brightfield microscopy images. Results for each miner case were compared with a separate corresponding analysis of particles recovered following tissue digestion., Results.—: In situ analysis of miner tissues showed higher particle number densities than controls and densities were generally higher in PMF than non-PMF areas. Particle counts were typically dominated by aluminum silicates with varying percentages of silica. Compared to digestion results for the miner tissues, in situ results indicated lower density of particles (number per tissue volume), larger size, and a lower ratio of silica to total silicates-probably due to frequent particle clustering in situ., Conclusions.—: Automated FESEM-EDS analysis of lung dust is feasible in situ and could be applied to a larger set of mineral dust-exposed lung tissues to investigate specific histologic features of PMF and other dust-related occupational diseases., (© 2024 College of American Pathologists.)

Rationale: The application of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to murine lungs is challenging due to the spongy nature of the tissue. Lungs consist of interconnected air sacs (alveoli) lined by a single layer of flattened epithelial cells, which requires inflation to maintain its natural structure. Therefore, a protocol that is compatible with both lung instillation and high spatial resolution is essential to enable multi-omic studies on murine lung disease models using MALDI-MSI., Methods and Results: To maintain the structural integrity of the tissue, murine lungs were inflated with 8% (w/v) gelatin for lipid MSI of fresh frozen tissues or 4% (v/v) paraformaldehyde neutral buffer for N-glycan and peptide MSI of FFPE tissues. Tissues were sectioned and prepared for enzymatic digestion and/or matrix deposition. Glycerol-free PNGase F was applied for N-glycan MSI, while Trypsin Gold was applied for peptide MSI using the iMatrixSpray and ImagePrep Station, respectively. For lipid, N-glycan and peptide MSI, α-cyano-4-hydroxycinnamic acid matrix was deposited using the iMatrixSpray. MS data were acquired with 20 μm spatial resolution using a timsTOF fleX MS instrument followed by MS fragmentation of lipids, N-glycans and peptides. For lipid MSI, trapped ion mobility spectrometry was used to separate isomeric/isobaric lipid species. SCiLS™ Lab was used to visualize all MSI data. For analyte identification, MetaboScape®, GlycoMod and Mascot were used to annotate MS fragmentation spectra of lipids, N-glycans and tryptic peptides, respectively., Conclusions: Our protocol provides instructions on sample preparation for high spatial resolution MALDI-MSI, MS/MS data acquisition and lipid, N-glycan and peptide annotation and identification from murine lungs. This protocol will allow non-biased analyses of diseased lungs from preclinical murine models and provide further insight into disease models., (© 2024 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Laser-induced breakdown spectroscopy (LIBS) imaging continues to gain strength as an influential bioanalytical technique, showing intriguing potential in the field of clinical analysis. This is because hyperspectral LIBS imaging allows for rapid, comprehensive elemental analysis, covering elements from major to trace levels consistently year after year. In this study, we estimated the potential of a multivariate spectral data treatment approach based on a so-called convex envelope method to detect exotic elements (whether they are minor or in trace amounts) in biopsy tissues of patients with occupational exposure-related diseases. More precisely, we have developed an approach called Interesting Features Finder (IFF), which initially allowed us to identify unexpected elements without any preconceptions, considering only the set of spectra contained in a LIBS hyperspectral data cube. This task is, in fact, almost impossible with conventional chemometric tools, as it entails identifying a few exotic spectra among several hundred thousand others. Once this detection was performed, a second approach based on correlation was used to locate their distribution in the biopsies. Through this unique data analysis pipeline to processing massive LIBS spectroscopic data, it was possible to detect and locate exotic elements such as tin and rhodium in a patient's tissue section, ultimately leading to a possible reclassification of their lung condition as an occupational disease. This review will thus demonstrate the potential of this new diagnostic tool based on LIBS imaging in addressing the shortcomings of approaches developed thus far. The proposed data processing approach naturally transcends this specific framework and can be leveraged across various domains of analytical chemistry, where the detection of rare events is concealed within extensive data sets.

Background: Understanding lung deposition dose of black carbon is critical to fully reconcile epidemiological evidence of combustion particles induced health effects and inform the development of air quality metrics concerning black carbon. Macrophage carbon load (MaCL) is a novel cytology method that quantifies lung deposition dose of black carbon, however it has limited feasibility in large-scale epidemiological study due to the labor-intensive manual counting., Objective: To assess the association between MaCL and episodic elevation of combustion particles; to develop artificial intelligence based counting algorithm for MaCL assay., Methods: Sputum slides were collected during episodic elevation of ambient PM 2.5 (n = 49, daily PM 2.5  > 10 µg/m 3 for over 2 weeks due to wildfire smoke intrusion in summer and local wood burning in winter) and low PM 2.5 period (n = 39, 30-day average PM 2.5  < 4 µg/m 3 ) from the Lovelace Smokers cohort., Results: Over 98% individual carbon particles in macrophages had diameter <1 µm. MaCL levels scored manually were highly responsive to episodic elevation of ambient PM 2.5 and also correlated with lung injury biomarker, plasma CC16. The association with CC16 became more robust when the assessment focused on macrophages with higher carbon load. A Machine-Learning algorithm for Engulfed cArbon Particles (MacLEAP) was developed based on the Mask Region-based Convolutional Neural Network. MacLEAP algorithm yielded excellent correlations with manual counting for number and area of the particles. The algorithm produced associations with ambient PM 2.5 and plasma CC16 that were nearly identical in magnitude to those obtained through manual counting., Impact Statement: Understanding lung black carbon deposition is crucial for comprehending health effects of combustion particles. We developed "Machine-Learning algorithm for Engulfed cArbon Particles (MacLEAP)", the first artificial intelligence algorithm for quantifying airway macrophage black carbon. Our study bolstered the algorithm with more training images and its first use in air pollution epidemiology. We revealed macrophage carbon load as a sensitive biomarker for heightened ambient combustion particles due to wildfires and residential wood burning., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Breath exhaled hydrogen cyanide (HCN) has been identified to be associated with several respiratory diseases. Accurately distinguishing the concentration and release rate of different HCN sources is of great value in clinical research. However, there are still significant challenges due to the high adsorption and low concentration characteristics of exhaled HCN. In this study, a two-compartment kinetic model method based on negative photoionization mass spectrometry was developed to simultaneously determine the kinetic parameters including concentrations and release rates in the airways and alveoli. The influences of the sampling line diameter, length, and temperature on the response time of the sampling system were studied and optimized, achieving a response time of 0.2 s. The negative influence of oral cavity-released HCN was reduced by employing a strategy based on anatomical lung volume calculation. The calibration for HCN in the dynamic range of 0.5-100 ppbv and limit of detection (LOD) at 0.3 ppbv were achieved. Subsequently, the experiments of smoking, short-term passive smoking, and intake of bitter almonds were performed to examine the influences of endogenous and exogenous factors on the dynamic parameters of the model method. The results indicate that compared with steady-state concentration measurements, the kinetic parameters obtained using this model method can accurately and significantly reflect the changes in different HCN sources, highlighting its potential for HCN-related disease research., 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.)

Exposure to ambient particulate matter (PM) has been associated with respiratory and cardiovascular outcomes, and nickel has been more frequently associated with these outcomes than other metal constituents of ambient PM. Because of this, we evaluated whether the evidence to date supports causal relationships between exposure to nickel in ambient PM and respiratory or cardiovascular outcomes. We critically reviewed 38 studies in human populations published between 2012 and 2022. Although a large variety of respiratory and cardiovascular outcomes were examined, data were sparse for many. As a result, we focused our evaluation on seven respiratory outcomes and three cardiovascular outcomes that were each examined in ≥3 studies. Of these health outcomes, exposure to nickel in ambient PM has been statistically significantly associated with respiratory mortality, respiratory emergency hospital visits, asthma, lung function (i.e., forced expiratory volume in 1 s, forced vital capacity), cardiovascular mortality, and ischemic heart disease mortality. Studies of the health outcomes of focus are subject to multiple methodological limitations, primarily ecological fallacy (short-term exposure studies), exposure measurement error, confounding, model misspecification, and multiple comparisons issue. While some statistically significant associations were reported, they were not strong, precise, or consistent. Statistically significant findings for long-term exposure to nickel in PM were largely reported in studies that could not establish temporality, despite their cohort study design. Statistically significant findings for short-term exposure to nickel in PM were largely reported in studies that could establish temporality, although this cannot inform causal inference at the individual level due to the aggregate level data used. The biological plausibility of the associations is only supported at high concentrations not relevant to ambient exposures. Overall, the literature to date does not provide adequate support for a causal relationship between nickel in ambient PM and respiratory or cardiovascular outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All of the authors are empoyed by Gradient, an independent risk science consulting firm. The work reported in this paper was conducted by the authors during their normal course of employment, with financial support by NiPERA, Inc., and a draft of this paper was reviewed by members of NiPERA, Inc. at the request of the authors. This paper is the professional work product of the authors, and the opinions and conclusions within are not necessarily those of their employers or the financial sponsor of the work., (Copyright © 2024 GradCo LLC dba Gradient. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Cough represents a natural mechanism that plays an important defensive role in the respiratory tract, but in some conditions, it may become persistent, nonproductive, and harmful. In general, refractory chronic cough (RCC) occurs in about 20% of individuals; hence, we aimed to assess the presence of altered gut-lung communication in RCC patients through a compositional and functional characterization of both gut (GM) and oral microbiota (OM)., Methods: 16S rRNA sequencing was used to characterize both GM and OM composition of RCC patients and healthy controls (HC). PICRUST2 assessed functional changes in microbial communities while gas chromatography was used to evaluate fecal short-chain fatty acid levels and serum-free fatty acid (FFA) abundances., Results: In comparison with HC, RCC patients reported increased saliva alpha-diversity and statistically significant beta-diversity in both GM and OM. Also, a, respectively, significant increased or reduced Firmicutes/Bacteroidota ratio in stool and saliva samples of RCC patients has been shown, in addition to a modification of the abundances of several taxa in both GM and OM. Moreover, a potential fecal over-expression of lipopolysaccharide biosynthesis and lipoic acid metabolism pathways and several differences in serum FFA levels have been reported in RCC patients than in HC., Conclusion: Since differences in both GM and OM of RCC patients have been documented, these findings could provide new information about RCC pathogenesis and also pave the way for the development of novel nutritional or pharmacological interventions for the management of RCC through the restoration of eubiotic gut-lung communication., (© 2024. The Author(s).)

Ultrafine particles (UFPs) are airborne particles with a diameter of less than 100 nm. They are emitted from various sources, such as traffic, combustion, and industrial processes, and can have adverse effects on human health. Long-term mean ambient average particle size (APS) in the UFP range varies over space within cities, with locations near UFP sources having typically smaller APS. Spatial models for lung deposited surface area (LDSA) within urban areas are limited and currently there is no model for APS in any European city. We collected particle number concentration (PNC), LDSA, and APS data over one-year monitoring campaign from May 2021 to May 2022 across 27 locations and estimated annual mean in Copenhagen, Denmark, and obtained additionally annual mean PNC data from 6 state-owned continuous monitors. We developed 94 predictor variables, and machine learning models (random forest and bagged tree) were developed for PNC, LDSA, and APS. The annual mean PNC, LDSA, and APS were, respectively, 5523 pt/cm 3 , 12.0 μm 2 /cm 3 , and 46.1 nm. The final R 2 values by random forest (RF) model were 0.93 for PNC, 0.88 for LDSA, and 0.85 for APS. The 10-fold, repeated 10-times cross-validation R 2 values were 0.65, 0.67, and 0.60 for PNC, LDSA, and APS, respectively. The root mean square error for final RF models were 296 pt/cm 3 , 0.48 μm 2 /cm 3 , and 1.60 nm for PNC, LDSA, and APS, respectively. Traffic-related variables, such as length of major roads within buffers 100-150 m and distance to streets with various speed limits were amongst the highly-ranked predictors for our models. Overall, our ML models achieved high R 2 values and low errors, providing insights into UFP exposure in a European city where average PNC is quite low. These hyperlocal predictions can be used to study health effects of UFPs in the Danish Capital., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Prostate and lung cancers are the most common types of cancer and affect a large part of the population around the world, causing deaths. Therefore, the rapid identification of cancer can profoundly impact reducing cancer-related death rates and protecting human lives. Significant resources have been dedicated to investigating new methods for early disease detection. Cancer biomarkers encompass various biochemical entities, including nucleic acids, proteins, sugars, small metabolites, cytogenetic and cytokinetic parameters, and whole tumor cells in bodily fluids. These tools can be utilized for various purposes, such as risk assessment, diagnosis, prognosis, treatment efficacy, toxicity evaluation, and predicting a return. Due to these versatile and critical purposes, there are widespread studies on the development of new, sensitive, and selective approaches for the determination of cancer biomarkers. This review illustrates the significant lung and prostate cancer biomarkers and their determination utilizing electrochemical sensors, which have the advantage of improved sensitivity, low cost, and simple analysis. Additionally, approaches such as improving sensitivity with nanomaterials and ensuring selectivity with MIPs are used to increase the performance of the sensor. This review aims to overview the most recent electrochemical biosensor applications for determining vital biomarkers of prostate and lung cancers in terms of nanobiosensors and molecularly imprinted polymer (MIP)-based biosensors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Brominated flame retardants (BFRs) are a group of chemicals widely used in various applications to prevent or slow down the spread of fire. However, they have adverse effects on human health. There is a relative scarcity of population-based studies regarding BFRs, particularly their impact on the respiratory system. This study aimed to investigate the influence of BFRs on pulmonary function using data from the National Health and Nutrition Examination Survey. The study found that elevated serum concentrations of certain BFRs were associated with pulmonary ventilatory dysfunction. Adjusted analyses revealed positive correlations between PBDE47, PBDE183, and PBDE209 concentrations and ventilatory dysfunction. The analysis of mixed BFRs showed a positive relationship with pulmonary ventilation dysfunction, with PBDE47 making the most significant contribution. Our study demonstrates that both individual and combined BFRs exposure can lead to impaired pulmonary ventilation function. These findings provide evidence of the adverse effects of BFRs on lung function, emphasizing the importance of further investigating the potential health consequences of these compounds. Further large-scale longitudinal studies are needed to investigate this relationship in the future., (© 2024. The Author(s).)

Rationale: Air pollution and extreme temperature and humidity are risk factors for lung dysfunction, but their interactions are not clearly understood., Objectives: To assess the impact of exposure to air pollutants and meteorological factors on lung function, and the contribution of their interaction to the overall effect., Methods: The peak expiratory flow rates of 135 participants were repeatedly measured during up to four visits. Two weeks before each visit, the concentrations of gaseous pollutants and 19 fine particle components, and the temperature and relative humidity, were continuously monitored in the community where they lived. A Bayesian Kernel machine regression model was used to explore the non-linear exposure-response relationships of the peak expiratory flow rate with pollutant exposure and meteorological factors, and their interactions., Measurements and Main Results: Increased temperature and relative humidity could exacerbate pollutant-associated decline in the peak expiratory flow rate, although their associations with lung dysfunction disappeared after adjustment for pollutant exposure. For example, declines of peak expiratory flow rate associated with interquartile range increase of 3-day cadmium exposure were -0.03 and -0.07 units, when temperature was at 0.1 and 19.5 °C, respectively. Decreased temperature were associated with declines of peak expiratory flow rate after adjustment for pollutant exposure, and had interaction with pollutant exposure on lung dysfunction., Conclusions: High temperature, low temperature, and high humidity were all high-risk factors for lung dysfunction, and their interactions with pollutant levels contributed greatly to the overall effects., 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 Inc. All rights reserved.)

Carbon nanotubes (CNTs) are increasingly being used in industrial applications, but their toxicological data in animals and humans are still sparse. To assess the toxicological dose-response of CNTs and to evaluate their pulmonary biopersistence, their quantification in tissues, especially lungs, is crucial. There are currently no reference methods or reference materials for low levels of CNTs in organic matter. Among existing analytical methods, few have been fully and properly validated. To remedy this, we undertook an inter-laboratory comparison on samples of freeze-dried pig lung, ground and doped with CNTs. Eight laboratories were enrolled to analyze 3 types of CNTs at 2 concentration levels each in this organic matrix. Associated with the different analysis techniques used (specific to each laboratory), sample preparation may or may not have involved prior digestion of the matrix, depending on the analysis technique and the material being analyzed. Overall, even challenging, laboratories' ability to quantify CNT levels in organic matter is demonstrated. However, CNT quantification is often overestimated. Trueness analysis identified effective methods, but systematic errors persisted for some. Choosing the assigned value proved complex. Indirect analysis methods, despite added steps, outperform direct methods. The study emphasizes the need for reference materials, enhanced precision, and organized comparisons.

Objective: Dust exposure is high in several industries. We investigated associations of exposure in paper mills, wood pellet plants, and iron foundries with lung function impairment., Methods: Respirable silica, inhalable paper dust, or inhalable wood dust were collected as personal samples and spirometry was performed. Multiple linear regression analyzed associations with FEV 1 %pred and FVC%pred., Results: Wood pellet workers with high exposure to inhalable dust had lower FEV 1 %pred (95% CI) (-9.4 [-16 to -2.6]) and FVC%pred (-9.8 [-15 to -4.0]) compared with lowest exposure level. Workers at paper mills and foundries had no dose-dependent association but lower FEV 1 %pred and FVC%pred than in workers at wood pellets plants., Conclusions: Increased exposure to inhalable wood dust is associated with decreased lung function. Foundry and paper mill workers have generally lower lung function than wood pellet workers. Spirometry should be considered in workers in industries with airborne particulate matter pollution., Competing Interests: Conflict of interest: None declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Scope: Particulate matter (PM) contains toxic organic matter and heavy metals that enter the entire body through blood flow and may cause mortality. Ganoderma formosanum mycelium, a valuable traditional Chinese medicine that has been used since ancient times, contains various active ingredients that can effectively impede inflammatory responses on murine alveolar macrophages induced by PM particles., Methods and Results: An experimental study assessing the effect of G. formosanum mycelium extract's water fraction (WA) on PM-exposed murine alveolar macrophages using ROS measurement shows that WA reduces intracellular ROS by 12% and increases cell viability by 16% when induced by PM particles. According to RNA-Sequencing, western blotting, and real-time qPCR are conducted to analyze the metabolic pathway. The WA reduces the protein ratio in p-NF-κB/NF-κB by 18% and decreases the expression of inflammatory genes, including IL-1β by 38%, IL-6 by 29%, and TNF-α by 19%. Finally, the identification of seven types of anti-inflammatory compounds in the WA fraction is achieved through UHPLC-ESI-Orbitrap-Elite-MS/MS analysis. These compounds include anti-inflammatory compounds, namely thiamine, adenosine 5'-monophosphate, pipecolic acid, L-pyroglutamic acid, acetyl-L-carnitine, D-mannitol, and L-malic acid., Conclusions: The study suggests that the WA has the potential to alleviate the PM -induced damage in alveolar macrophages, demonstrating its anti-inflammatory properties., (© 2024 Wiley‐VCH GmbH.)

The urban environment during pregnancy may influence child's respiratory health, but scarce evidence exists on systematic evaluation of multiple urban exposures (e.g., air pollution, natural spaces, noise, built environment) on children's lung function, wheezing, and asthma development. We aimed to examine the association of the urban environment during pregnancy with lung function, preschool wheezing, and school-age asthma. We included 5624 mother-child pairs participating in a population-based prospective birth cohort. We estimated 30 urban environmental exposures including air pollution, road traffic noise, traffic, green spaces, blue spaces, and built environment during pregnancy. At 10 years of age, lung function was measured by spirometry. Information on preschool wheezing and physician-diagnosed school-age asthma was obtained from multiple questionnaires. We described single-exposure associations with respiratory outcomes using an exposome-wide association study. We also identified patterns of urban exposures with hierarchical clustering on principal components analysis and examined their associations with respiratory outcomes using multivariate regression models. Single-exposure analyses showed associations of higher particulate matter (PM) with lower mid-expiratory flow (FEF 25-75% ) (e.g., for PM < 2.5 μm of diameter [PM 2.5 ] z-score = -0.06 [-0.09, -0.03]) and higher forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) (e.g., for PM 2.5 FEV 1 0.05 [0.02, 0.08]) after correction for multiple-hypothesis testing. Cluster analysis described three patterns of urban exposures during pregnancy and showed that the cluster characterised by higher levels of air pollution, noise, walkability, street connectivity, and lower levels of natural spaces were associated with lower FEF 25-75% (-0.08 [-0.17, 0.00]), and higher odds of preschool wheezing (1.21 [1.03, 1.43]). This study shows that the characteristics of the urban environment during pregnancy are of relevance to the offspring's respiratory health during childhood., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The replication of the hominine physiological environment was identified as an effectual strategy to develop the physiological model in vitro to perform the intuitionistic assessment of toxicity of contaminations. Herein, we proposed a dynamic interface strategy that accurately mimicked the blood flow and shear stress in human capillaries to subtly evaluate the physiological damages. To proof the concept, the dynamic air-blood barrier (ABB) model in vitro was developed by the dynamic interface strategy and was utilized to assess the toxicity of polyethylene terephthalate microplastics (PET-MPs). The developed dynamic ABB model was compared with the static ABB model developed by the conventional Transwell® system and the animal model, then the performance of the dynamic ABB model in evaluation of the PET-MPs induced pulmonary damage via replicating the hominine ABB. The experimental data revealed that the developed dynamic ABB model in vitro effectively mimicked the physiological structure and barrier functions of human ABB, in which more sophisticated physiological microenvironment enabled the distinguishment of the toxicities of PET-MPs in different sizes and different concentrations comparing with the static ABB model constructed on Transwell® systems. Furthermore, the consistent physiological and biochemical characters adopted dynamic ABB model could be achieved in a quick manner referring with that of the mouse model in the evaluation of the microplastics-induced pulmonary damage. The proposed dynamic interface strategy supplied a general approach to develop the hominine physiological environment in vitro and exhibited a potential to develop the ABB model in vitro to evaluate the hazards of inhaled airborne pollutants., 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 B.V. All rights reserved.)

Background: Evidence on the public health relevance of exposure to livestock farm emissions is increasing. Research mostly focused on chemical air pollution, less on microbial exposure, while endotoxins are suggested relevant bacterial components in farm emissions. Acute respiratory health effects of short-term exposure to livestock-related air pollution has been shown for NH 3 and PM 10 , but has not yet been studied for endotoxin. We aimed to assess associations between lung function and short-term exposure to livestock farming emitted endotoxin in co-pollutant models with NH 3 and PM 10 ., Methods: In 2014/2015, spirometry was conducted in 2308 non-farming residents living in a rural area in the Netherlands. Residential exposure to livestock farming emitted endotoxin during the week prior to spirometry was estimated by dispersion modelling. The model was applied to geo-located individual barns within 10 km of each home address using provincial farm data and local hourly meteorological conditions. Regional week-average measured concentrations of NH 3 and PM 10 were obtained through monitoring stations. Lung function parameters (FEV 1 , FVC, FEV 1 /FVC, MMEF) were expressed in %-predicted value based on GLI-2012. Exposure-response analyses were performed by linear regression modelling., Results: Week-average endotoxin exposure was negatively associated with FVC, independently from regional NH 3 and PM 10 exposure. A 1.1% decline in FVC was estimated for an increase of endotoxin exposure from 10th to 90th percentile. Stratified analyses showed a larger decline (3.2%) for participants with current asthma and/or COPD. FEV 1 was negatively associated with week-average endotoxin exposure, but less consistent after co-pollutant adjustment. FEV 1 /FVC and MMEF were not associated with week-average endotoxin exposure., Conclusions: Lower lung function in non-farming residents was observed in relation to short-term residential exposure to livestock farming emitted endotoxin. This study indicates the probable relevance of exposure to microbial emissions from livestock farms considering public health besides chemical air pollution, necessitating future research incorporating both., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors reports financial support was provided by Netherlands Ministry of Infrastructure and Water Management. All authors reports financial support was provided by Province of Noord-Brabant. All authors reports financial support was provided by Netherlands Ministry of Health Welfare and Sport. All authors reports financial support was provided by Netherlands Ministry of Economic Affairs. All authors reports financial support was provided by Lung Foundation Netherlands. Co-author Gerard Hoek is associate editor at Environmental Research., (Copyright © 2023 Utrecht University. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Systemic inflammation is one potential mechanism underlying negative impact of air pollution on lung function. Levels of inflammation-related proteins have the potential to characterize infants' susceptibility to air pollution induced lung function impairment. This study aimed to examine the interplay between air pollution exposure and inflammation-related proteins on lung function in 6-months-old infants., Methods: In the EMIL birth cohort from Stockholm (n = 82), dynamic spirometry, along with measurement of plasma levels of 92 systemic inflammation-related proteins (Olink Proseek Multiplex Inflammation panel) have been carried out in infants aged six months. Time-weighted average exposure to particles with an aerodynamic diameter of <10 μm (PM 10 ), <2.5 μm (PM 2.5 ), and nitrogen dioxide (NO 2 ) at residential addresses from birth and onwards was estimated via validated dispersion models. To characterize the abnormality of inflammation-related protein profile, for each protein in each infant, we calculated the relative deviance of the protein level from age- and sex-specific median in terms of its age- and sex-specific interquartile range (IQR), followed by computing the absolute value of the smallest relative deviance, "minimum absolute deviance". Using linear regression models, interaction of air pollution and the abnormal inflammatory profile on lung function was estimated on the additive scale., Results: We found joint association of PM exposure and an abnormal inflammatory protein profile in relation to FEV 0.5 and FVC. For 0.1 unit increase in minimum absolute deviance, one IQR increase in PM 10 was associated with 85.9 ml (95% CI: -122.9, -48.9) additional decrease in FEV 0.5, and 72.3 ml (95% CI: -121.5, -23.2) additional decrease in FVC. Similar results were obtained with PM 2.5 exposure, while less apparent for NO 2 ., Conclusions: Early life air pollution exposure and abnormal inflammation-related protein profiles may interact synergistically towards lower lung function in infants., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Layers of pulmonary lipids on an aqueous substrate at non-equilibrium conditions can decrease the surface tension of water to quite low values. This is connected with different relaxation processes occurring at the interface and the associated changes in the surface layer structure. Results of measurements by the combination of methods like surface rheology, ellipsometry, Brewster angle microscopy, and IRRAS for spread layers of lipid mixtures open a possibility to specify the dynamics of structural changes at conditions close to the physiological state. At sufficiently low surface tension values (below 5 mN/m) significant changes in the ellipsometric signal were observed for pure DPPC layers, which can be related to a transition from 2D to 3D structures caused by the layer folding. The addition of other lipids can accelerate the relaxation processes connected with squeezing-out of molecules or multilayer stacks formation hampering thereby a decrease of surface tension down to low values corresponding to the folding of the monolayer., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Exposure to polycyclic aromatic hydrocarbons (PAHs) of high molecular weight from chimney soot can cause cancer among chimney sweepers. These sweepers may also be exposed to high concentrations of nanosized particles, which can cause significant inflammatory responses due to their relatively greater surface area per mass. In this study, the authors aimed to assess the exposure profiles of airborne personal exposure to gaseous and particulate PAHs, and real-time samples of the particle number concentrations (PNCs), particle sizes, and lung-deposited surface areas (LDSAs), for chimney sweepers in Norway. Additionally, the authors aimed to assess the task-based exposure concentrations of PNCs, sizes, and LDSAs while working on different tasks. The results are based on personal samples of particulate PAHs ( n  = 68), gaseous PAHs ( n  = 28), and real-time nanoparticles ( n  = 8) collected from 17 chimney sweepers. Samples were collected during a "typical work week" of chimney sweeping and fire safety inspections, then during a "massive soot" week, where larger sweeping missions took place. Significantly higher PAH concentrations were measured during the "massive soot" week compared to the "typical work week," however, the time-weighted average (TWA) (8-hr) of all gaseous and particulate PAHs ranged from 0.52 to 4.47 µg/m 3 and 0.49 to 2.50 µg/m 3 , respectively, well below the Norwegian occupational exposure limit (OEL) of 40 µg/m 3 . The PNCs were high during certain activities, such as emptying the vacuum cleaner. Additionally, during 2 days of sweeping in a waste sorting facility, the TWAs of the PNCs were 3.6 × 10 4 and 7.1 × 10 4 particles/cm 3 on the first and second days, respectively, which were near and above the proposed nano reference limit TWA value of 4.0 × 10 4 particles/cm 3 proposed by the International Workshop on Nano Reference Values. The corresponding TWAs of the LDSAs were 49.5 and 54.5 µm 2 /cm 3 , respectively. The chimney sweepers seemed aware of the potential health risks associated with exposure, and suitable personal protective equipment was used. However, the PNCs reported for the activities show that when the activities change or increase, the PNCs' TWAs can become unacceptably high.

Background: Quantification of asbestos fibers has been mainly performed in the lung but rarely in other organs. However, this may be relevant to understanding better translocation pathways and the oncogenic effects of asbestos on the human body. Electron microscopy is the best technology available to assess the type of fiber, dimensions, and distribution of asbestos fibers in different tissues and as a biomarker of cumulative dose., Objectives: This scoping review aims to summarize the findings of the studies in which asbestos fibers have been quantified by electron microscopy, occasionally associated with X-ray microanalysis, in normal and pathological tissue of ten abdominal organs., Methods: A scoping review has been performed by searching articles that quantified asbestos fibers in abdominal organs by electron microscopy (Scanning- SEM or Transmission- TEM)., Results: The 12 selected studies included 204 cases, and 325 samples were analyzed. The colon and rectum, kidney, bladder, and abdominal lymph nodes were the organs with at least ten samples available with quantification of asbestos fibers. Asbestos fibers were detected in all the abdominal organs considered: the highest value (152,32 million fibers per gram of dry tissue) was found in the colon and was identified using STEM with EDS., Conclusion: The studies included were heterogeneous in terms of exposure and cases, type of samples, as well as analytical techniques, therefore we cannot confirm a specific pattern of distribution in any organ, based on the low homogeneity of the exposure status. The colon is the organ in which the number of fibers is the highest, probably because of exposure arising from both internal distribution of inhaled fibers and ingestion. Additional studies of the number of asbestos fibers in abdominal organs should be made to achieve better representativity.

Introduction: A child's living environment has a significant impact on their respiratory health, with exposure to poor indoor air quality (IAQ) contributing to potentially lifelong respiratory morbidity. These effects occur throughout childhood, from the antenatal period through to adolescence. Children are particularly susceptible to the effects of environmental insults, and children living in socioeconomic deprivation globally are more likely to breathe air both indoors and outdoors, which poses an acute and long-term risk to their health. Adult respiratory health is, at least in part, determined by exposures and respiratory system development in childhood, starting in utero., Areas Covered: This narrative review will discuss, from a global perspective, what contributes to poor IAQ in the child's home and school environment and the impact that indoor air pollution exposure has on respiratory health throughout the different stages of childhood., Expert Opinion: All children have the right to a living and educational environment without the threat of pollution affecting their health. Action is needed at multiple levels to address this pressing issue to improve lifelong respiratory health. Such action should incorporate a child's rights-based approach, empowering children, and their families, to have access to clean air to breathe in their living environment.

Background: The acid glycoprotein 1 (AGP1) is downregulated in lung cancer. However, the performance of AGP1 in distinguishing benign from malignant lung lesions is still unknown., Methods: The expression of AGP1 in benign diseases and lung cancer samples was detected by Western blot. The receiver operating characteristic curves, bivariate correlation, and multivariate analysis was analyzed by SPSS software., Results: AGP1 expression levels were significantly downregulated in lung cancer and correlated with carcinoembryonic antigen (CEA), CA199, and CA724 tumor biomarkers. The diagnostic performance of AGP1 for distinguishing malignant from benign pulmonary lesions was better than the other four clinical biomarkers including CEA, squamous cell carcinoma-associated antigen, neuron-specific enolase, and cytokeratin 19 fragment 21-1, with an area under the curve value of 0.713 at 88.8% sensitivity. Furthermore, the multivariate analysis indicated that the variates of thrombin time and potassium significantly affected the AGP1 levels in lung cancer., Conclusions: Our study indicates that AGP1 expression is decreased in lung cancer compared to benign samples, which helps distinguish benign and malignant pulmonary lesions., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A screening survey has been carried out to measure the radon concentration in drinking water at various locations of Ajodhya hill and surrounding areas in Purulia district of West Bengal, India, using AlphaGUARD radon monitor. The obtained 222 Rn concentration in ground water varies from 5.71 ± 0.29 to 579.47 ± 23.18 Bq/l with an average of 110.00 ± 6.61 Bq/l. Comparison between our results with the internationally recommended reference levels reveals that drinking of water from the majority of these tube-wells can pose significant health risks to the local people. Correlation study indicates that tube-well depth has significant influence on the radon level in water samples. Using 60 l/yr and 1642.50 l/yr water consumption estimated annual effective radon doses for most of the samples (almost 70% and 96%, respectively) are high compared to the World Health Organization (WHO) and the European Union (EU) Commission prescribed reference dose limit of 100 μSv/yr. Also, the evaluated Excess Lifetime Cancer Risk (ELCR) values associated with the tube-wells are showing serious threat to the health of the locals.The primary goal of this work is to develop a radon profile map of this area and to find out the possible reasons behind the elevated radon level in ground water. This type of work may play a very crucial role to aware the locals in perspective of human exposure to radon. The local health officials and the water quality regulators of India are requested to take necessary steps for protecting the local people from water radon hazard., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Particulate matter (PM) inhaled into human lungs causes oxidative stress and adverse health effects through antioxidant depletion (oxidative potential, OP). However, there is limited knowledge regarding the association between the lung-deposited dose (LDD) of PM and OP in extrathoracic (ET), tracheobronchial (TB), and pulmonary (P) regions of human lungs. Dithiothreitol (DTT) and ascorbic acid (AA) assays were employed to measure the OP of PM size fractions to investigate OP distribution in human lungs and identify the chemical drivers. Quasi-ultrafine particles (quasi-UFP, ≤0.49 μm) exhibited high OP deposition in the TB and P regions, while coarse particles (CP, ≥3.0 μm) dominated in the ET region. A plot of extrinsic (per air volume) and intrinsic (per PM mass) OP versus LDD revealed that the OP for fine and coarse particles was greatest in the ET region, whereas the OP of quasi-UFP was greatest in alveoli. The study also demonstrated that extrinsic OP and PM doses are not strongly related. The decline in OP with increasing PM dose reveals the need for further investigation of the antagonistic effects of the chemical compositions. Overall, the results presented herein help address the gap in knowledge regarding the association between the OP and LDD of ambient particles in specific regions of human lungs., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The geothermal power plants for electricity production currently active in Italy are all located in Mt. Amiata area in the Tuscany region. A cross-sectional survey was conducted in the framework of the regional project "InVETTA-Biomonitoring Survey and Epidemiological Evaluations for the Protection of Health in the Amiata Territories", using objective measures of lung function to investigate the role of hydrogen sulphide (H2S) in affecting the respiratory health of the population living in this area., Methods: 2018 adults aged 18-70 were enrolled during 2017-2019. Home and workplace addresses of participants were geocoded. Dispersion modelling was used to evaluate the spatial variability of exposure to H2S from the geothermal power plants' emissions. We estimated average long-term historical exposure to H2S and more recent exposure indicators. Chronic Obstructive Pulmonary Disease (COPD) was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Multivariable logistic regressions were performed to investigate associations between outcome and exposure., Results: Our findings did not showed any evidence of an association between increasing H2S exposure and lung function impairments. Some risk reductions were observed: a -32.8% (p = 0.003) for FEV1<80% and a -51.7% (p = 0.001) risk decrease for FVC<80% were associated with interquartile increase (13.8 μg/m3) of H2S levels., Conclusion: Our study provides no evidence that chronic exposure to low levels of H2S is associated with decrements in pulmonary function, suggesting that ambient H2S exposure may benefit lung function., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Stoppa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The work shows the effect of counting rules, such as analysis magnification and asbestos fiber dimension to be count (with length ≥5 µm or also asbestos fibers with length <5 µm) in the lung asbestos fiber burden analysis for legal medicine evaluations., Methods: On the same lung tissue samples, two different analyses were carried out to count any asbestos fibers with length ≥1 µm and with length ≥5 µm. Results of the amphibole burden of the two analyses were compared by linear regression analysis on log10-transformed values., Results: The analysis should be carried out at an appropriate magnification and on samples prepared in such a way as they allow the counting of very fine fibers. If the analysis is limited to the asbestos fibers with length ≥5 µm, there is a high risk of not detecting possible residual chrysotile fiber burden and thinner crocidolite asbestos fibers., Conclusions: On average we estimated that 1 amphibole fiber with length ≥5 µm corresponds to ∼8 amphibole fibers with length ≥1 µm in the lung. The values of the Helsinki criteria should be updated taking this into account.

Atmospheric particulate matter (PM) poses great adverse effects through the production of reactive oxygen species (ROS). Various components in PM are acknowledged to induce ROS formation, while the interactions among chemicals remain to be elucidated. Here, we systematically investigate the influence of Brown carbon (BrC) surrogates (e.g., imidazoles, nitrocatechols and humic acid) on hydroxyl radical (OH) generation from transition metals (TMs) in simulated lung fluid. Present results show that BrC has an antagonism (interaction factor: 20-90 %) with Cu 2+ in OH generation upon the interaction with glutathione, in which the concentrations of BrC and TMs influence the extent of antagonism. Rapid OH generation in glutathione is observed for Fe 2+ , while OH formation is very little for Fe 3+ . The compositions of antioxidants (e.g., glutathione, ascorbate, urate), resembling the upper and lower respiratory tract, respond differently to BrC and TMs (Cu 2+ , Fe 2+ and Fe 3+ ) in OH generation and the degree of antagonism. The complexation equilibrium constants and site numbers between Cu 2+ and humic acid were further analyzed using fluorescence quenching experiments. Possible complexation products among TMs, 4-nitrocatechol and glutathione were also identified using quadropule-time-of-flight mass spectrometry. The results suggest atmospheric BrC widely participate in complexation with TMs which influence OH formation in the human lung fluid, and complexation should be considered in evaluating ROS formation mediated by ambient PM., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cooking oil fumes (COFs) comprised of a mixture of cancer-causing volatile organic aldehydes (VOAs), particularly trans, trans-2,4-decadienal (t,t-DDE), 4-hydroxy-hexenal (4-HHE), and 4-hydroxy-nonenal (4-HNE). Monitoring toxic VOAs levels in people exposed to different cooking conditions is vital to predicting the cancer risk. For this purpose, we developed a fast tissue extraction (FaTEx) technique combined with UHPLC-MS/MS to monitor three toxic VOAs in mice lung tissue samples. FaTEx pre-treatment protocol was developed by combining two syringes for extraction and clean-up process. The various procedural steps affecting the FaTEx sample pre-treatment process were optimized to enhance the target VOAs' extraction efficiency from the sample matrix. Under the optimal experimental conditions, results exhibit good correlation coefficient values > 0.99, detection limits were between 0.5-3 ng/g, quantification limits were between 1-10 ng/g, and the matrix effect was <18.1%. Furthermore, the extraction recovery values of the spiked tissue exhibited between 88.9-109.6% with <8.6% of RSD. Cooking oil fume (containing t,t-DDE) treated mice at various time durations were sacrificed to validate the developed technique, and it was found that t,t-DDE concentrations were from 14.8 to 33.8 μg/g. The obtained results were found to be a fast, reliable, and semi-automated sample pre-treatment technique with good extraction efficiency, trace level detection limit, and less matrix effect. Therefore, this method can be applied as a potential analytical method to determine the VOAs in humans exposed to long-term cooking oil fumes., 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.)

The fungus Amanita muscaria is universally recognizable for its iconic appearance; it is also widely regarded as poisonous, inedible, and even deadly. In spite of that, there have been documented cases of use of A. muscaria -containing preparations against various diseases, including cancer, to no apparent ill effect. The search for compounds that can be used to treat cancer among various plants and fungi has been intensifying in recent years. In light of this, we describe an HPLC HILIC analytical method for the evaluation of the content of the anticancer compound ergosterol (ERG) and the neuroactive alkaloids ibotenic acid (IBO) and muscimol (MUS) that contribute significantly to the unpleasant physiological syndrome associated with A. muscaria consumption. A 'homemade' A. muscaria tincture made using 80-proof rye vodka as the solvent, an A. muscaria extract made with a standardized water-ethanol solution as the solvent, and fractions obtained from the second extract via liquid-liquid extraction with nonpolar solvents were analyzed. The study also presents the results of capillary zone electrophoresis with contactless conductivity detection and UHPLC-MS/MS analyses of the IBO and MUS content of the two native A. muscaria extracts and an evaluation of the standardized extract's cytotoxic effect against a small panel of lung cell cultures in vitro. Our results show that the standardized extract has a significant cytotoxic effect and does not contain the compounds of interest in any significant quantity.

Respiratory health problems in poultry production are frequent and knotty and thus attract the attention of farmers and researchers. The breakthrough of gene sequencing technology has revealed that healthy lungs harbor rich microbiota, whose succession and homeostasis are closely related to lung health status, suggesting a new idea to explore the mechanism of lung injury in broilers with pulmonary microbiota as the entry point. This study aimed to investigate the succession of pulmonary microbiota in healthy broilers during the growth cycle. Fixed and molecular samples were collected from the lungs of healthy broilers at 1, 3, 14, 21, 28, and 42 d of age. Lung tissue morphology was observed by hematoxylin and eosin staining, and the changes in the composition and diversity of pulmonary microbiota were analyzed using 16S rRNA gene sequencing. The results showed that lung index peaked at 3 d, then decreased with age. No significant change was observed in the α diversity of pulmonary microbiota, while the β diversity changed regularly with age during the broilers' growth cycle. The relative abundance of dominant bacteria of Firmicutes and their subordinate Lactobacillus increased with age, while the abundance of Proteobacteria decreased with age. The correlation analysis between the abundance of differential bacteria and predicted function showed that dominant bacteria of Firmicutes, Proteobacteria and Lactobacillus were significantly correlated with most functional abundance, indicating that they may involve in lung functional development and physiological activities of broilers. Collectively, these findings suggest that the lung has been colonized with abundant microbiota in broilers when they were just hatched, and their composition changed regularly with day age. The dominant bacteria, Firmicutes, Proteobacteria, and Lactobacillus, play crucial roles in lung function development and physiological activities. It paves the way for further research on the mechanism of pulmonary microbiota-mediated lung injury in broilers., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to particulate matter (PM) has been associated with a wide range of adverse health effects, but it is still unclear how particles from various transport modes differ in terms of toxicity and associations with different human health outcomes. This literature review aims to summarize toxicological and epidemiological studies of the effect of ultrafine particles (UFPs), also called nanoparticles (NPs, <100 nm), from different transport modes with a focus on vehicle exhaust (particularly comparing diesel and biodiesel) and non-exhaust as well as particles from shipping (harbor), aviation (airport) and rail (mainly subway/underground). The review includes both particles collected in laboratory tests and the field (intense traffic environments or collected close to harbor, airport, and in subway). In addition, epidemiological studies on UFPs are reviewed with special attention to studies aimed at distinguishing the effects of different transport modes. Results from toxicological studies indicate that both fossil and biodiesel NPs show toxic effects. Several in vivo studies show that inhalation of NPs collected in traffic environments not only impacts the lung, but also triggers cardiovascular effects as well as negative impacts on the brain, although few studies compared NPs from different sources. Few studies were found on aviation (airport) NPs, but the available results suggest similar toxic effects as traffic-related particles. There is still little data related to the toxic effects linked to several sources (shipping, road and tire wear, subway NPs), but in vitro results highlighted the role of metals in the toxicity of subway and brake wear particles. Finally, the epidemiological studies emphasized the current limited knowledge of the health impacts of source-specific UFPs related to different transport modes. This review discusses the necessity of future research for a better understanding of the relative potencies of NPs from different transport modes and their use in health risk assessment., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Urban air fine particles are a major health-relating problem. However, it is not well understood how the health-relevant features of fine particles should be monitored. Limitations of PM 2.5 (mass concentration of sub 2.5 μm particles), which is commonly used in the health effect estimations, have been recognized and, e.g., World Health Organization (WHO) has released good practice statements for particle number (PN) and black carbon (BC) concentrations (2021). In this study, a characterization of urban wintertime aerosol was done in three environments: a detached housing area with residential wood combustion, traffic-influenced streets in a city centre and near an airport. The particle characteristics varied significantly between the locations, resulting different average particle sizes causing lung deposited surface area (LDSA). Near the airport, departing planes had a major contribution on PN, and most particles were smaller than 10 nm, similarly as in the city centre. The high hourly mean PN (>20 000 1/cm 3 ) stated in the WHO's good practices was clearly exceeded near the airport and in the city centre, even though traffic rates were reduced due to a SARS-CoV-2-related partial lockdown. In the residential area, wood combustion increased both BC and PM 2.5 , but also PN of sub 10 and 23 nm particles. The high concentrations of sub 10 nm particles in all the locations show the importance of the chosen lower size limit of PN measurement, e.g., WHO states that the lower limit should be 10 nm or smaller. Furthermore, due to ultrafine particle emissions, LDSA per unit PM 2.5 was 1.4 and 2.4 times higher near the airport than in the city centre and the residential area, respectively, indicating that health effects of PM 2.5 depend on urban environment as well as conditions, and emphasizing the importance of PN monitoring in terms of health effects related to local pollution sources., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Arsenic exposure is associated with airway inflammation and decreased lung function tests. Whether arsenic exposure associated with lung interstitial changes remains unknown. We conducted this population-based study in southern Taiwan during 2016 and 2018. Our study recruited individuals aged over 20 years, residing in the vicinity of a petrochemical complex and with no history of cigarette smoking. In both the 2016 and 2018 cross-sectional studies, we conducted chest low-dose computed tomography (LDCT) scans, as well as urinary arsenic and blood biochemistry analyses. Lung interstitial changes included lung fibrotic changes that were defined as the presence of curvilinear or linear densities, fine lines, or plate opacity in specific lobes; additionally, other interstitial changes were defined as the presence of ground-glass opacity (GGO) or bronchiectasis on the LDCT images. In both cross-sectional studies conducted in 2016 and 2018, participants with lung fibrotic changes exhibited a statistically significant increase in the mean urinary arsenic concentrations compared to those without fibrotic changes (geometric mean = 100.1 vs. 82.8 μg/g creatinine, p < 0.001 for cross-sectional study 2016, and geometric mean = 105.6 vs. 71.0 μg/g creatinine, p < 0.001 for cross-sectional study 2018). After controlling for age, gender, body mass index, platelet counts, hypertension, aspartate aminotransferase, cholesterol, HbA1c, and educational levels, we observed a significant positive association between a unit increase in log urinary arsenic concentrations and the risk of lung fibrotic changes in both cross-sectional study 2016 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.04-1.90, p = 0.028) and cross-sectional study 2018 (OR = 3.03, 95% CI = 1.38-6.63, p = 0.006). Our study did not find a significant association between arsenic exposure and bronchiectasis or GGO. It is imperative for the government to take significant measures to reduce arsenic exposure levels among individuals living near petrochemical complexes., 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.)

One of the major toxic effects of exposure to ammonia is the resulting pulmonary acute and chronic effects. This study investigated the acute pulmonary effects of exposure to ammonia lower than the recommended threshold limit value (TLV). This cross-sectional study was conducted in 2021 in four chemical fertilizer production industries using ammonia as the main raw material. A total of 116 workers who were exposed to ammonia were investigated. The level of exposure to ammonia was measured by NMAM 6016, and the evaluation of pulmonary symptoms and function parameters was done using the American Thoracic Society and European Respiratory Society protocols in four sessions. The paired-sample t-test, repeated measures test, Chi-square, and Fisher's exact test were run to analyze the collected data. The prevalence rates of pulmonary symptoms, including cough, dyspnea, phlegm, and wheezing, were 24.14, 17.24, 14.66, and 16.38%, respectively, after one exposure shift. It was observed that all pulmonary function parameters were reduced after one exposure shift to ammonia. The results revealed that the parameters of vital capacity, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), the FEV1/FVC ratio, and peak expiratory flow significantly decreased ( p < 0.05) across four exposure shifts. The findings indicated that exposure to ammonia at concentrations lower than one-fifth of TLV could bring about acute pulmonary effects and reduce pulmonary function parameters, similar to the pattern observed in obstructive pulmonary diseases.

The effect of ambient PM 10 and PM 2.5 on lung function modified by body muscle and adipose tissue is not fully understood at present. Our aims were to investigate the association between seasonal average air pollutants and lung function in asthmatic patients modified by body composition indicators. In this cross-sectional study, we recruited 914 doctor-diagnosed asthmatic patients, and performed interaction and stratified analysis using the median values of total body muscle (TBM), total body fat (TBF), and percentage body fat (PBF) as well as body mass index (BMI) =25 as the cutoff points of the high/low body composition groups. The adjusted R 2 values of the developed LUR models of PM 2.5 and PM 10 were 91.4% and 90.5% and also verified by cross-validation, respectively. After adjusting for confounding factors, we found that TBM significantly modified the association between PM 10 and lung function among asthma patients (interaction P value <0.05). In the low TBM group, seasonal average concentrations of PM 10 estimated by the LUR model increased by 10 μg/m 3 , and negative associations with lung function indicators were observed. For obese patients with BMI>25 and high TBF, the increase in PM 10 was associated with the decrease in lung function. The asthma patients with obesity and low total body muscle were more susceptible to adverse effects of PM 10 on lung function., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Qingjin Yiqi granules (QJYQ granules) are hospital preparations derived from ancient prescriptions under the guidance of academician Zhang Boli; they have the effect of invigorating qi and nourishing yin, strengthening the spleen and harmonizing the middle, clearing heat, and drying dampness, and are mainly used for patients with coronavirus disease 2019 (COVID-19) during the recovery period. However, their chemical constituents and pharmacokinetic characteristics in vivo have not been systematically investigated. In this study, 110 chemical constituents of QJYQ granules were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and a fast and sensitive ultra-high-performance liquid chromatography-mass spectrometry method was developed and validated for the target analytes. A rat model of lung-qi deficiency was established by subjecting mice to passive smoking combined with cold baths, and 23 main bioactive components of QJYQ granules were analyzed in normal and model rats after oral administration. The results showed that, compared to the normal group, there were significant differences in the pharmacokinetics of baicalin, schisandrin, ginsenoside Rb1, naringin, hesperidin, liquiritin, liquiritigenin, glycyrrhizic acid, and hastatoside in the model rats (P < 0.05), indicating that the in vivo processes of the above components changed under pathological conditions, suggesting that they may have pharmacological effects as active components. This study has helped identify QJYQ particulate substances and further supports their clinical application.., 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 B.V. All rights reserved.)

Radon ( 222 Rn) and its progeny are responsible for half of the annual dose from natural radiation and the most frequent cause for lung cancer induction after smoking. During inhalation, progeny nuclides accumulate in the respiratory tract while most of the radon gas is exhaled. The decay of progeny nuclides in the lung together with the high radiosensitivity of this tissue lead to equivalent doses implying a significant cancer risk. Here, we use gamma spectroscopy to measure the attachment of radon progeny on an air-ventilated filter system within a radon enriched atmosphere, mimicking the respiratory tract. A mathematical model was developed to describe the measured time-dependent activities of radon progeny on the filter system. We verified a linear relation between the ambient radon activity concentration during exposure and the amount of decay products on the filter system. The measured activities on the filters and its mathematical description are in good agreement. The developed experimental set-up can thus serve to further investigate the deposition of radon progeny in the respiratory tract under varying conditions for determination of dose conversion factors in radiation protection, which we demonstrate by deriving dose estimations in mouse lung., (© 2023. The Author(s).)

Tobacco products contain radioactive 210 Pb and 210 Po which can be transferred from the filler to the mainstream smoke. When inhaled, they can contribute to the radioactive dose to the lungs and are suspected to significantly contribute to lung cancer from smoking. Currently, no data are available on the radioactive risk of the heated tobacco products (HTP). However, due to the relatively high heat involved in some of these devices, there are concerns about the volatility of polonium particles. Here we used data on the 210 Po and 210 Pb content in tobacco smoke along with biokinetic and dosimetric models to compute the effective dose induced by conventional smoking and by using an HTP device (PMI IQOS system). Results show that conventional smoking of one pack per day induces a dose to the lung of about 0.3 mSv/year. This dose decreases by a factor of ten (0.03 mSv/year) for the IQOS system. However, this dose reduction is not obtained by specific countermeasures but by the fact that the IQOS system heats only 15% of the tobacco filler to the target temperature of 330 °C. When heated homogeneously to 300 °C, both conventional and Heets (IQOS) cigarettes release about 80% of the 210 Po from the tobacco, leading to similar doses to lungs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pascal Froidevaux reports financial support was provided by Swiss Federal Office of Public Health., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: We assessed the association of traffic-related air pollution (TRAP) with the incidence of lung, breast, and urinary tract cancer in Halifax, Nova Scotia., Methods: Our case-control study included 2315 cancers and 8501 age-sex-matched controls. Land-use regression was used to estimate TRAP concentrations. Logistic regression was used to assess cancer risk in relation to TRAP, adjusting for community social and material deprivation., Results: There was no association between the risk of lung, breast, or urinary tract cancer in relation to TRAP. Lung cancer risk was significantly increased in the most deprived communities, whereas breast cancer risk was highest in the least deprived communities., Conclusions: In a city characterized by low levels of ambient air pollution, there was no evidence of a linear increased lung, breast, or urinary tract cancer risk in relation to TRAP., Competing Interests: Conflict of interest statement: None declared., (Copyright © 2023 American College of Occupational and Environmental Medicine.)