Impact of organic compounds on the stability of influenza A virus in deposited 1-µL droplets.

The composition of respiratory fluids influences the stability of viruses in exhaled aerosol particles and droplets, though the role of respiratory organics in modulating virus stability remains poorly understood. This study investigates the effect of organic compounds on the stability of influenza A virus (IAV) in deposited droplets. We compare the infectivity loss of IAV at different relative humidities (RHs) over the course of 1 h in 1-µL droplets consisting of phosphate-buffered saline (without organics), synthetic lung fluid, or nasal mucus (both containing organics). We show that IAV stability increases with increasing organic:salt ratios. Among the various organic species, proteins are identified as the most protective component, with smaller proteins stabilizing IAV more efficiently at the same mass concentration. Organics act by both increasing the efflorescence RH and shortening the drying period until efflorescence at a given RH. This research advances our mechanistic understanding of how organics stabilize exhaled viruses and thus influence their inactivation in respiratory droplets. IMPORTANCE: This study investigates how the composition of respiratory fluids affects the stability of viruses in exhaled droplets. Understanding virus stability in droplets is important as it impacts how viruses spread and how we can combat them. We focus on influenza A virus (IAV) and investigate how different organic compounds found in lung fluid and nasal mucus protect the virus from inactivation. We demonstrate that the ratio of organics to salt in the fluid is an indicator of IAV stability. Among organics, small proteins are particularly effective at protecting IAV. Their effect is in part explained by the proteins' influence on the crystallization of salts in the droplets, thereby shielding the viruses from prolonged exposure to harmful salt concentrations. Understanding these mechanisms helps us grasp how viruses sustain their infectivity over time in respiratory droplets, contributing to efforts in controlling infectious diseases.

Non-invasive heart failure monitoring: leveraging smart scales and digital biomarkers to improve heart failure outcomes.

Heart failure (HF) is a significant global concern, impacting patient morbidity, mortality, and healthcare costs. Guideline-directed medical therapy and various preventive measures have proven effective in improving clinical outcomes and reducing HF hospitalizations. Recent data indicates that remote HF monitoring facilitates early detection of HF decompensation by observing upstream events and parameters before clinical signs and symptoms manifest. Moreover, these innovative devices have been shown to decrease unnecessary HF hospitalizations and, in some cases, provide predictive insights before an actual HF incident. In this review, we aim to explore the data regarding smart scales and digital biomarkers and summarize both FDA-approved devices and emerging technologies by assessing their clinical utility, mechanism of HF decompensation detection, and ongoing trials. Furthermore, we also discuss the future trend of integrating these devices into routine clinical practice to improve patient clinical outcomes.

Effect of measurement procedure errors on assessing lung fluid via remote dielectric sensing system.

The study assessed the impact of procedural errors on the remote dielectric sensing system (ReDS), a non-invasive lung fluid assessment technology, in an Asian cohort. Healthy volunteers underwent ReDS measurements following manufacturer's instructions, with two consecutive measurements one minute apart. A subset of 20 participants had modified procedure settings. Reliability was measured using intraclass correlation coefficient (ICC). The study included 86 healthy volunteers, and all ReDS measurements fell within the recommended normal range. The intra-rater reliability of ReDS measurements was excellent, with an ICC of 0.968. Among the subset of 20 subjects, deviations in height and weight did not significantly affect ReDS values. However, deviations in chest size by ± 3 cm had a noticeable impact on ReDS measures, and incorrect station selection led to fluctuations in ReDS readings. In conclusion, the ReDS system demonstrated excellent intra-rater reliability and applicability in an Asian cohort. Procedural errors, such as chest size measurement and station selection, significantly influenced ReDS measurements. Adherence to standardized operating procedures is crucial to ensure accurate and consistent results. These findings highlight the importance of adherence to manufacturer instructions when utilizing ReDS for lung fluid assessment, thereby enhancing its reliability and clinical applicability.

Assessing lung fluid status using noninvasive bioelectrical impedance analysis in patients with acute heart failure: A pilot study.

BACKGROUND: Outpatient monitoring of pulmonary congestion in heart failure (HF) patients may reduce hospitalization rates. This study tested the feasibility of non-invasive high-frequency bioelectrical impedance analysis (HF-BIA) for estimating lung fluid status. METHODS: This prospective study included 70 participants: 50 with acute HF (HF group) and 20 without HF (control group). All participants underwent a supine chest CT scan to measure lung fluid content with lung density analysis software. Concurrently, direct segmental multi-frequency BIA was performed to assess the edema index (EI) of the trunk, entire body, and extremities. RESULTS: The correlation coefficients between lung fluid content and EI measured using HF-BIA were r = 0.566 (p < 0.001) and r = 0.550 (p < 0.001) for the trunk and whole body, respectively. In the HF group, the trunk EI (0.402 ± 0.015) and whole body EI (0.402 ± 0.016) were significantly higher than those of the control group (trunk EI, 0.383 ± 0.007; whole body EI, 0.383 ± 0.007; all p < 0.001). The lung fluid content was significantly higher in the HF than that in the control group (23.7 ± 5.3 vs. 15.5 ± 2.8%, p < 0.001). The log value of NT pro-BNP was significantly correlated with trunk EI (r = 0.688, p < 0.001) and whole-body EI (r = 0.675, p < 0.001) measured by HF-BIA, and the lung fluid content analyzed by CT (r = 0.686, p < 0.001). CONCLUSIONS: BIA-based EI measurements of the trunk and whole body significantly correlated with lung fluid content and NT pro-BNP levels. Non-invasive BIA could be a promising screening tool for lung fluid status monitoring in acute HF patients.

Quantification of Bioaccessible and Environmentally Relevant Trace Metals in Structure Ash from a Wildland-Urban Interface Fire.

Wildfires at the wildland-urban interface (WUI) are increasing in frequency and intensity, driven by climate change and anthropogenic ignitions. Few studies have characterized the variability in the metal content in ash generated from burned structures in order to determine the potential risk to human and environmental health. Using inductively coupled plasma optical emission spectroscopy (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS), we analyzed leachable trace metal concentration in soils and ash from structures burned by the Marshall Fire, a WUI fire that destroyed over 1000 structures in Boulder County, Colorado. Acid digestion revealed that ash derived from structures contained 22 times more Cu and 3 times more Pb on average than surrounding soils on a mg/kg basis. Ash liberated 12 times more Ni (mg/kg) and twice as much Cr (mg/kg) as soils in a water leach. By comparing the amount of acid-extractable metals to that released by water and simulated epithelial lung fluid (SELF), we estimated their potential for environmental mobility and human bioaccessibility. The SELF leach showed that Cu and Ni were more bioaccessible (mg of leachable metal/mg of acid-extractable metal) in ash than in soils. These results suggest that structure ash is an important source of trace metals that can negatively impact the health of both humans and the environment.

Characterization and Polydispersity of Volcanic Ash Nanoparticles in Synthetic Lung Fluid.

The inhalation of natural nanoparticles (NPs) emitted from volcanic activity may be a risk to human health. However, the literature rarely reports the fate and response of NPs once in contact with lung fluids. In this work, we studied the particle size distribution of ashfall from Popocatépetl volcano, Mexico. The collected ashes (n = 5) were analyzed with scanning electron microscopy (SEM) to obtain the elemental composition and morphology, and to determine the size of the ash particles using ParticleMetric software (PMS). The PMS reported most of the ash to have submicrometric size (<1 µm) and an average equivalent circle of 2.72 µm. Moreover, to our knowledge, this study investigated for the first time the behavior of ash NPs at different times (0 to 24 h) while in contact with in vitro lung fluid, Gamble Solution (GS) and Artificial Lysosomal Fluid (ALF) using dynamic light scattering (DLS). We found a large variability in the hydrodynamic diameter, with values less than 1 nm and greater than 5 µm. Furthermore, aggregation and disaggregation processes were recognized in GS and ALF, respectively. The results of this study increase the knowledge of the interaction between NPs and lung fluids, particularly within the alveolar macrophage region.

pH-responsive microparticles of rifampicin for augmented intramacrophage uptake and enhanced antitubercular efficacy.

In this study we present pH-responsive rifampicin (RIF) microparticles comprising lecithin and a biodegradable hydrophobic polymer, polyethylene sebacate (PES), to achieve high intramacrophage delivery and enhanced antitubercular efficacy. PES and PES-lecithin combination microparticles (PL MPs) prepared by single step precipitation revealed average size of 1.5 to 2.7 µm, entrapment efficiency âˆ¼ 60 %, drug loading 12-15 % and negative zeta potential. Increase in lecithin concentration enhanced hydrophilicity. PES MPs demonstrated faster release in simulated lung fluid pH 7.4, while lecithin MPs facilitated faster and concentration dependent release in acidic artificial lysosomal fluid (ALF) pH 4.5 due to swelling and destabilization confirmed by TEM. PES and PL (1:2) MPs exhibited comparable macrophage uptake which was âˆ¼ 5-fold superior than free RIF, in the RAW 264.7 macrophage cells. Confocal microscopy depicted intensified accumulation of the MPs in the lysosomal compartment, with augmented release of coumarin dye from the PL MPs, confirming pH-triggered increased intracellular release. Although, PES MPs and PL (1:2) MPs displayed comparable and high macrophage uptake, antitubercular efficacy against macrophage internalised M. tuberculosis was significantly higher with PL (1:2) MPs. This suggested great promise of the pH-sensitive PL (1:2) MPs for enhanced antitubercular efficacy.

Intraluminal chloride regulates lung branching morphogenesis: involvement of PIEZO1/PIEZO2.

BACKGROUND: Clinical and experimental evidence shows lung fluid volume as a modulator of fetal lung growth with important value in treating fetal lung hypoplasia. Thus, understanding the mechanisms underlying these morphological dynamics has been the topic of multiple investigations with, however, limited results, partially due to the difficulty of capturing or recapitulating these movements in the lab. In this sense, this study aims to establish an ex vivo model allowing the study of lung fluid function in branching morphogenesis and identify the subsequent molecular/ cellular mechanisms. METHODS: Ex vivo lung explant culture was selected as a model to study branching morphogenesis, and intraluminal injections were performed to change the composition of lung fluid. Distinct chloride (Cl-) concentrations (5.8, 29, 143, and 715 mM) or Cl- channels inhibitors [antracene-9-carboxylic acid (A9C), cystic fibrosis transmembrane conductance regulator inhibitor172 (CFTRinh), and calcium-dependent Cl- channel inhibitorA01 (CaCCinh)] were injected into lung lumen at two timepoints, day0 (D0) and D2. At D4, morphological and molecular analyses were performed in terms of branching morphogenesis, spatial distribution (immunofluorescence), and protein quantification (western blot) of mechanoreceptors (PIEZO1 and PIEZO2), neuroendocrine (bombesin, ghrelin, and PGP9.5) and smooth muscle [alpha-smooth muscle actin (α-SMA) and myosin light chain 2 (MLC2)] markers. RESULTS: For the first time, we described effective intraluminal injections at D0 and D2 and demonstrated intraluminal movements at D4 in ex vivo lung explant cultures. Through immunofluorescence assay in in vivo and ex vivo branching morphogenesis, we show that PGP9.5 colocalizes with PIEZO1 and PIEZO2 receptors. Fetal lung growth is increased at higher [Cl-], 715 mM Cl-, through the overexpression of PIEZO1, PIEZO2, ghrelin, bombesin, MLC2, and α-SMA. In contrast, intraluminal injection of CFTRinh or CaCCinh decreases fetal lung growth and the expression of PIEZO1, PIEZO2, ghrelin, bombesin, MLC2, and α-SMA. Finally, the inhibition of PIEZO1/PIEZO2 by GsMTx4 decreases branching morphogenesis and ghrelin, bombesin, MLC2, and α-SMA expression in an intraluminal injection-independent manner. CONCLUSIONS: Our results identify PIEZO1/PIEZO2 expressed in neuroendocrine cells as a regulator of fetal lung growth induced by lung fluid.

Inhalation bioacessibility and lung cell penetration of indoor PM2.5-bound PAEs and its implication in risk assessment.

Several studies have evaluated the human exposure of phthalate esters (PAEs) in PM2.5 via inhalation route, however, inhalation bioaccessibility and the lung cell penetration of PAEs were barely considered in risk assessment. In the present study, PM2.5 samples collected from indoor environments were investigated for inhalation bioaccessibility of PAEs using two simulated lung fluids (gamble's solution (GMB) and artificial lysosomal fluid (ALF)). The results showed that the inhalation bioaccessibility of PAEs (except for diethyl phthalate) under healthy state (GMB: 8.9%-62.8%) was lower than that under the inflammatory condition (ALF: 14.5%-67.6%). Lung cell permeation and metabolism of three selected PAEs (diethyl phthalate, di(n-butyl)phthalate and di-2-ethylhexyl phthalate) was tested using equivalent lung cell (A549) model. The inhalation bioavailability obtained by combination of the bioaccessibility of PAEs in indoor PM2.5 and permeability data of A549 cell ranged from 11.7% to 51.1% in health condition, and 13.5%-55.0% in inflammatory state. The calibration parameter (Fc) based on the inhalation bioavailability was established in present study and could provide a reference for a more accurate risk assessment of PM2.5-bound PAEs.

c-JUN-mediated transcriptional responses in lymphatic endothelial cells are required for lung fluid clearance at birth.

Fluid clearance mediated by lymphatic vessels is known to be essential for lung inflation and gas-exchange function during the transition from prenatal to postnatal life, yet the molecular mechanisms that regulate lymphatic function remain unclear. Here, we profiled the molecular features of lymphatic endothelial cells (LECs) in embryonic and postnatal day (P) 0 lungs by single-cell RNA-sequencing analysis. We identified that the expression of c-JUN is transiently upregulated in P0 LECs. Conditional knockout of Jun in LECs impairs the opening of lung lymphatic vessels at birth, leading to fluid retention in the lungs and neonatal death. We further demonstrated that increased mechanical pressure induces the expression of c-JUN in LECs. c-JUN regulates the opening of lymphatic vessels by modulating the remodeling of the actin cytoskeleton in LECs. Our study established the essential regulatory function of c-JUN-mediated transcriptional responses in facilitating lung lymphatic fluid clearance at birth.

Influence of rapidly oscillating inspired O2 and N2 concentrations on pulmonary vascular function and lung fluid balance in healthy adults.

Introduction: Aircrew may experience rapidly oscillating inspired O2/N2 ratios owing to fluctuations in the on-board oxygen delivery systems (OBOG). Recent investigations suggest these oscillations may contribute to the constellation of physiologic events in aircrew of high-performance aircraft. Therefore, the purpose of this study was to determine whether these "operationally-relevant" environmental challenges may cause decrements in measures of pulmonary vascular physiology. Methods: Thirty healthy participants (Age: 29 ± 5 years) were recruited and assigned to one of the three exposures. Participants were instrumented for physiologic monitoring and underwent baseline cardiopulmonary physiology testing (ground level) consisting of a rebreathe method for quantifying pulmonary blood flow (Qc), pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (Dm). Ultrasound was used to quantify "comet tails" (measure of lung fluid balance). After baseline testing, the participants had two 45 min exposures to an altitude of 8,000 ft where they breathed from gas mixtures alternating between 80/20 and 30/70 O2/N2 ratios at the required frequency (30 s, 60 s, or 120 s), separated by repeat baseline measure. Immediately and 45 min after the second exposure, baseline measures were repeated. Results: We observed no changes in Qc, Dm or Vc during the 60 s exposures. In response to the 30 s oscillation exposure, there was a significantly reduced Qc and Vc at the post-testing period (p = 0.03). Additionally, exposure to the 120 s oscillations resulted in a significant decrease in Vc at the recovery testing period and an increase in the Dm/Vc ratio at both the post and recovery period (p < 0.01). Additionally, we observed no changes in the number of comet tails. Conclusion: These data suggest "operationally-relevant" changes in inspired gas concentrations may cause an acute, albeit mild pulmonary vascular derecruitment, reduced distention and/or mild pulmonary-capillary vasoconstriction, without significant changes in lung fluid balance or respiratory gas exchange. The operational relevance remains less clear, particularly in the setting of additional environmental stressors common during flight (e.g., g forces).

Experience with remote dielectric sensing (ReDS) for acute decompensated heart failure complicated by chronic obstructive pulmonary disease.

Remote dielectric sensing (ReDS) is a novel, non-invasive, miniature radar based, and vest testing system to quantify pulmonary edema. ReDS value can represent valuable additions to the fluid management in patients with congestive heart failure. We report a case of relatively lower ReDS value in spite of the obvious clinical volume overload and pulmonary congestion in a patient with acute heart failure and chronic obstructive pulmonary disease. Treatment for congestion to ameliorate his heart failure was accompanied by further decrease in ReDS value below normal ranges. Although ReDS technology is a promising modality to quantify the lung fluid amount, we might have to pay attention to some unique comorbidities including chronic obstructive pulmonary disease, which might attenuate electromagnetic waves and let ReDS values become inappropriately lower. Learning objective: Remote dielectric sensing (ReDS) is a novel, non-invasive, miniature radar based, and vest testing system to detect pulmonary edema, which has a robust correlation with pulmonary fluid content in heart failure patients. However, the applicability of this modality in patients with a variety of comorbidities remains unknown. We should pay attention to unique comorbidities including chronic obstructive pulmonary disease, which might attenuate electromagnetic waves and let ReDS values become inappropriately lower.

A Contact-Free Optical Device for the Detection of Pulmonary Congestion-A Pilot Study.

BACKGROUND: The cost of heart failure hospitalizations in the US alone is over USD 10 billion per year. Over 4 million Americans are hospitalized every year due to heart failure (HF), with a median length of stay of 4 days and an in-hospital mortality rate that exceeds 5%. Hospitalizations of patients with HF can be prevented by early detection of lung congestion. Our study assessed a new contact-free optical medical device used for the early detection of lung congestion. METHODS: The Gili system is an FDA-cleared device used for measuring chest motion vibration data. Lung congestion in the study was assessed clinically and verified via two cardiologists. An algorithm was developed using machine learning techniques, and cross-validation of the findings was performed to estimate the accuracy of the algorithm. RESULTS: A total of 227 patients were recruited (101 cases vs. 126 controls). The sensitivity and specificity for the device in our study were 0.91 (95% CI: 0.86-0.93) and 0.91 (95% CI: 0.87-0.94), respectively. In all instances, the observed estimates of PPVs and NPVs were at least 0.82 and 0.90, respectively. The accuracy of the algorithm was not affected by different covariates (including respiratory or valvular conditions). CONCLUSIONS: This study demonstrates the efficacy of a contact-free optical device for detecting lung congestion. Further validation of the study results across a larger and precise scale is warranted.

Remote Dielectric Sensing to Assess Residual Pulmonary Congestion Following Percutaneous Mitral Valve Repair.

Background and Objectives: Percutaneous mitral valve repair using a MitraClip system is an established therapeutic strategy to treat severe mitral regurgitation, which is recommended by guidelines in Europe and in the United States, whereas residual mitral regurgitation is associated with mortality and morbidity. Accurate assessment of residual mitral regurgitation is crucial for risk stratification and further adequate intervention, whereas its quantification has technical limitations due to "double" regurgitation that is often encountered following valve clipping. Remote dielectric sensing (ReDSTM) is a non-invasive electromagnetic-based technology to quantify lung fluid levels and might be a promising tool to assess the impact of residual mitral regurgitation following MitraClip. Materials and Methods: Following MitraClip, ReDS values measurements and right heart catheterization were performed and correlated. Results: We had 13 patients (median 74 years, 7 men) who underwent successful MitraClip. According to the visual estimation, eight patients had none or mild regurgitation, and five patients had moderate regurgitation. ReDS values were distributed widely between 16% and 33%, irrespective of the severity of regurgitation. ReDS values had a moderate correlation with invasively measured pulmonary artery wedge pressure (r = 0.73, p = 0.004). Conclusions: ReDS value might be a promising tool to assess residual pulmonary congestion following MitraClip, irrespective of the visually estimated severity of residual mitral regurgitation.

Inhalation bioaccessibility of multi-class organic pollutants associated to atmospheric PM2.5: Correlation with PM2.5 properties and health risk assessment.

Inhalation exposure to fine particulate matter (PM2.5) represents a global concern due to the adverse effects in human health. In the last years, scientific community has been adopted the assessment of the PM2.5-bound pollutant fraction that could be released (bioaccessible fraction) in simulated lung fluids (SLFs) to achieve a better understanding of PM risk assessment and toxicological studies. Thus, bioaccessibility of 49 organic pollutants, including 18 polycyclic aromatic hydrocarbons (PAHs), 12 phthalate esters (PAEs), 11 organophosphorus flame retardants (OPFRs), 6 synthetic musk compounds (SMCs) and 2 bisphenols in PM2.5 samples was evaluated. The proposed method consists of a physiologically based extraction test (PBET) by using artificial lysosomal fluid (ALF) to obtain bioaccessible fractions, followed by a vortex-assisted liquid-liquid microextraction (VALLME) and a final analysis by programmed temperature vaporization-gas chromatography-tandem mass spectrometry (PTV-GC-MS/MS). The highest inhalation bioaccessibility ratio was found for bisphenol A (BPA) with an average of 83%, followed by OPFRs, PAEs and PAHs (with average bioaccessibilities of 68%, 41% and 34%, respectively). Correlations between PM2.5 composition (major ions, trace metals, equivalent black carbon (eBC) and UV-absorbing particulate matter (UVPM)) and bioaccessibility ratios were also assessed. Principal Component Analysis (PCA) suggested that PAHs, PAES and OPFRs bioaccessibility ratios could be positively correlated with PM2.5 carbonaceous content. Furthermore, both inverse and positive correlations on PAHs, PAEs and OPFRs bioaccessibilites could be accounted for some major ions and metal (oid)s associated to PM2.5, whereas no correlations comprising considered PM2.5 major ions and metal (oid)s contents and BPA bioaccessibility was observed. In addition, health risk assessment of target PM2.5-associated PAHs via inhalation was assessed in the study area considering both total and bioaccessible concentrations, being averaged human health risks within the safe carcinogenic and non-carcinogenic levels.

Tools for assessing lung fluid in neonates with respiratory distress.

BACKGROUND: Transient tachypnea of the newborn (TTN), as a common cause of neonatal respiratory distress, needs to be distinguished from respiratory distress syndrome (RDS). Various modalities such as lung ultrasonography, cytokine analysis, and electrical cardiometry for the evaluation of lung fluid can be helpful for the exact diagnosis, however, clinical diagnosis has been applied mainly. This study aimed to evaluate the usefulness of the various tools for the diagnosis of TTN and RDS in neonates. METHODS: This study evaluated 22 late-preterm and term infants admitted to the neonatal intensive care unit of Gangnam Severance Hospital because of respiratory distress. Total 9 neonates were diagnosed with TTN and 13 had RDS. In addition to chest radiography, the LUS score was calculated by a neonatologist using the portable ultrasound device. Cytokines in the bronchoalveolar lavage fluid supernatant were measured. Thoracic fluid content was measured using an electrical cardiometry device. RESULTS: We enrolled 22 patients with median gestational age, 37.1 weeks, and birth weight 3100 g. There is no difference in patient characteristics between RDS and TTN group. Lung ultrasound score was significantly higher in RDS than TTN (11 vs 6, p = 0.001). Score 0 is shown in all infants with TTN. Score 1 is shown as significantly more in RDS than TTN. Between the TTN and RDS groups, there were significant differences in the changes of thoracic fluid content (2 vs - 1.5, p < 0.001), IL-1ß levels (2.5 vs 11.3, p = 0.02), and TNF-α levels (20.1 vs 11.2, p = 0.04). CONCLUSION: We found lung ultrasound and electrical cardiometry to be reliable diagnostic tools for assessing infants with respiratory distress among late-preterm and term infants. Further studies with a large number of patients are needed to confirm their clinical usefulness.

Initial Experience to Follow Lung Fluid Levels during Hemodialysis: A Possibility of Remote Dielectric Sensing-Guided Hemodialysis.

Remote dielectric sensing (ReDSTM) is a novel technology that noninvasively quantifies lung fluid levels. Trends in ReDS values following hemodialysis remain uninvestigated. In a 64-year-old man with clinically stable hemodynamics, 2.7 L of fluid was drained during hemodialysis whereas the ReDS value remained almost unchanged (from 32 to 30%). In a 60-year-old woman with unstable hemodynamics, only 1.8 L of fluid was drained during hemodialysis, whereas ReDS value decreased considerably from 37 to 27%. Given our initial experience measuring ReDS values during hemodialysis, the ratio of fluid removal by hemodialysis between systemic plasma and lung fluid might vary in each patient. ReDS value might be a promising marker to determine the degree of fluid removal in addition to the conventional multidisciplinary index, particularly for those with unstable hemodynamics. The implications of ReDS-guided hemodialysis remain a future concern.

Protective role of scutellarin on LPS induced - Acute lung injury and regulation of apoptosis, oxidative stress and reduction of mitochondrial dysfunction.

Lung fluid accumulation was determined using wet/dry lung mass ratio. Rats subjected to LPS-induced acute lung injury (2.8 ± 0.33, P < 0.05) presented with a significantly higher wet to dry lung weight ration ratio than sham rats (1.6 ± 0.23, P < 0.05). These results demonstrate that acutely inured rats' lungs were oedematous. On the other hand, treatment with scutellarin alone and in combination with a JNK inhibitor, SP600125, both significantly attenuated pulmonary edema as shown via reduced wet/dry lung mass ratios (1.7 ± 0.09 and 1.8 ± 0.23; P < 0.05, respectively). These results showed that the interventions were effective against LPS-induced edema of the lungs. However, the difference between treatment groups' weight ratios was not statistically significant (P > 0.05). In the sham control rats, the levels of ROS and SOD production were maintained at a low and at a high concentration, respectively (P < 0.05). However, following LPS infusion, the ROS levels skyrocketed while that of SOD decreased significantly relative to the control rats (P < 0.05). Furthermore, we noted that pre-treatment with scutellarin reduced the ROS levels in LPS-injured rats while the SOD was increased to near control levels (P < 0.05). Moreover, the combined effect of scutellarin and JNK inhibitor SP600125 on the levels of ROS and the SOD activity followed a similar trend to that of scutellarin alone albeit with a lower magnitude of change. Our results also showed that the combinatorial treatment was not significantly different from scutellarin alone in terms of influence on the levels of ROS production and SOD activity (P > 0.05). The effect of Scutellarin on broncho-alveolar lavage fluid (BALF) cytokine secretion The expression of interleukins-1ß, -18 and -6 in the broncho-alveolar lavage fluid were significantly upregulated by LPS infusion (P < 0.05). The rise was, however, attenuated via pre-treatment with scutellarin only or in conjunction with SP600125, a JNK inhibitor (all P < 0.05). On the contrary, we observed that LPS injection caused a reduction of interlekins -4 and -10 secreted in the BALF. Pre-treatment with scutellarin alone (P < 0.05) and not in combination with SP600125 or SP600125 was able to significantly reverse this noted down-regulation (all P > 0.05).

Olivine Dissolution in Simulated Lung and Gastric Fluid as an Analog to the Behavior of Lunar Particulate Matter Inside the Human Respiratory and Gastrointestinal Systems.

With the Artemis III mission scheduled to land humans on the Moon in 2025, work must be done to understand the hazards lunar dust inhalation would pose to humans. In this study, San Carlos olivine was used as an analog of lunar olivine, a common component of lunar dust. Olivine was dissolved in a flow-through apparatus in both simulated lung fluid and 0.1 M HCl (simulated gastric fluid) over a period of approximately 2 weeks at physiological temperature, 37°C. Effluent samples were collected periodically and analyzed for pH, iron, silicon, and magnesium ion concentrations. The dissolution rate data derived from our measurements allow us to estimate that an inhaled 1.0 µm diameter olivine particle would take approximately 24 years to dissolve in the human lungs and approximately 3 weeks to dissolve in gastric fluid. Results revealed that inhaled olivine particles may generate the toxic chemical, hydroxyl radical, for up to 5-6 days in lung fluid. Olivine dissolved in 0.1 M HCl for 2 weeks transformed to an amorphous silica-rich solid plus the ferric iron oxy-hydroxide ferrihydrite. Olivine dissolved in simulated lung fluid shows no detectable change in composition or crystallinity. Equilibrium thermodynamic models indicate that olivine in the human lungs can precipitate secondary minerals with fibrous crystal structures that have the potential to induce detrimental health effects similar to asbestos exposure. Our work indicates that inhaled lunar dust containing olivine can settle in the human lungs for years and could induce long-term potential health effects like that of silicosis.

Iron-Facilitated Organic Radical Formation from Secondary Organic Aerosols in Surrogate Lung Fluid.

Respiratory deposition of secondary organic aerosols (SOA) and iron may lead to the generation of reactive oxygen species and free radicals in lung fluid to cause oxidative stress, but their underlying mechanism and formation kinetics are not well understood. Here we demonstrate substantial formation of organic radicals in surrogate lung fluid (SLF) by mixtures of Fe2+ and SOA generated from photooxidation of isoprene, α-terpineol, and toluene. The molar yields of organic radicals by SOA are measured to be 0.03-0.5% in SLF, which are 5-10 times higher than in water. We observe that Fe2+ enhances organic radical yields dramatically by a factor of 20-80, which can be attributed to Fe2+-facilitated decomposition of organic peroxides, in consistency with a positive correlation between peroxide contents and organic radical yields. Ascorbate mediates redox cycling of iron ions to sustain organic peroxide decomposition, as supported by kinetic modeling reproducing time- and concentration-dependence of organic radical formation as well as additional experiments observing the formation of Fe2+ and ascorbate radicals in mixtures of ascorbate and Fe3+. •OH and superoxide are found to be scavenged by antioxidants efficiently. These findings have implications on the role of organic radicals in oxidative damage and lipid peroxidation.