Exploring the Cellular Impact of Size-Segregated Cigarette Aerosols: Insights into Indoor Particulate Matter Toxicity and Potential Therapeutic Interventions.

Exposure to anthropogenic aerosols has been associated with a variety of adverse health effects, increased morbidity, and premature death. Although cigarette smoke poses one of the most significant public health threats, the cellular toxicity of particulate matter contained in cigarette smoke has not been systematically interrogated in a size-segregated manner. In this study, we employed a refined particle size classification to collect cigarette aerosols, enabling a comprehensive assessment and comparison of the impacts exerted by cigarette aerosol extract (CAE) on SH-SY5Y, HEK293T, and A549 cells. Exposure to CAE reduced cell viability in a dose-dependent manner, with organic components having a greater impact and SH-SY5Y cells displaying lower tolerance compared to HEK293T and A549 cells. Moreover, CAE was found to cause increased oxidative stress, mitochondrial dysfunction, and increased levels of apoptosis, pyroptosis, and autophagy, leading to increased cell death. Furthermore, we found that rutin, a phytocompound with antioxidant potential, could reduce intracellular reactive oxygen species and protect against CAE-triggered cell death. These findings underscore the therapeutic potential of antioxidant drugs in mitigating the adverse effects of cigarette aerosol exposure for better public health outcomes.

Influence of Cigarette Aerosol in Alpha-Synuclein Oligomerization and Cell Viability in SH-SY5Y: Implications for Parkinson's Disease.

Although cigarette aerosol exposure is associated with various adverse health issues, its impact on Parkinson's disease (PD) remains elusive. Here, we investigated the effect of cigarette aerosol extract (CAE) on SH-SY5Y cells for the first time, both with and without α-synuclein (α-Syn) overexpression. We found that α-Syn aggravates CAE-induced cell death, oxidative stress, and mitochondrial dysfunction. Fluorescence cross-correlation spectroscopy (FCCS) revealed a dual distribution of α-Syn within the cells, with homogeneous regions indicative of monomeric α-Syn and punctated regions, suggesting the formation of oligomers. Moreover, we observed colocalization of α-Syn oligomers with lysosomes along with a reduction in autophagy activity. These findings suggest that α-Syn overexpression exacerbates CAE-induced intracellular cytotoxicity, mitochondrial dysfunction, and autophagy dysregulation, leading to elevated cell mortality. Our findings provide new insights into the pathogenic mechanisms linking exposure to cigarette aerosols with neurodegenerative diseases.

Exposure to phenols reduces melanogenesis in B16F10 cells and zebrafish.

Phenols, ubiquitous environmental contaminants found in water, soil, and air, pose risks to organisms even at minimal concentrations, and many are classified as hazardous pollutants. Skin pigmentation is a natural shield against ultraviolet-induced DNA damage and oxidative stress, pivotal in reducing skin cancer incidences. Studies on B16F10 melanoma cells and zebrafish offer valuable insights into potential therapeutic avenues for melanoma in the context of phenol exposure. Upon phenol treatment, there was a marked decrease in melanin content and melanogenesis-associated protein expression, such as tyrosinase and the microphthalmia-associated transcription factor (MITF) in these melanoma cells. Additionally, phenols led to diminished p38 phosphorylation, amplified extracellular signal-regulated kinase (ERK) phosphorylation, and curtailed melanin expression in zebrafish. These observations underscore the detrimental impact of phenols on melanogenesis and propose a mechanism of action centered on the ERK/p38 signaling pathway. Consequently, our data spotlight the adverse effects of phenols on melanogenesis."

Water Plays Multifunctional Roles in the Intervening Formation of Secondary Organic Aerosols in Ozonolysis of Limonene: A Valence Photoelectron Spectroscopy and Density Functional Theory Study.

Although water may affect aqueous aerosol chemistry, how it intervenes in the formation of secondary organic aerosols (SOAs) at the molecular level remains elusive. Ozonolysis of limonene is one of the most important sources of indoor SOAs. Here, we report the valence electronic properties of limonene aerosols and SOAs derived from limonene ozonolysis (Lim-SOAs) via aerosol vacuum ultraviolet photoelectron spectroscopy, with a focus on the effects of water on Lim-SOAs. The first vertical ionization energy of limonene aerosols is measured to be 8.79 ± 0.07 eV. While water significantly increases the total photoelectron yield of Lim-SOAs, three photoelectron features attributable to Lim-SOAs each exhibit distinct dependence on the fraction of water in aerosols, implying that different formation pathways and molecular origins are involved in the formation of Lim-SOAs. Combined with density functional theory calculation and mass spectrometry measurements, this study reveals that water, particularly the water dimer, enhances the formation of Lim-SOAs by altering the ozonolysis energetics and pathways by intervening in its Criegee chemistry, acting as both a catalyst and a reactant. The atmospheric implication is discussed.

Aerosol emissions and gravity waves of Taal volcano.

The Taal volcano (14.0 N, 121.0 E) in Philippines erupted in January-February 2020, with a part of aerosols drifted northward and detected by a lidar system at Kaohsiung city (22.37 N, 120.15 E), Taiwan. The aerosol observed on Feb 11 is special for its high-altitude distributions at 4-7 km with discrete structures which can be resolved into a sinusoidal oscillation of ~ 30 min period, suggesting a case of wave event caused by the eruptions. We report in this paper the gravity wave generated by the volcanic eruptions and its effects on aerosol emissions. By studying the temperature and pressure data in the Taal region using radiosonde data, we found atmospheric gravity waves with powers correlated with the optical thickness (AOD) at 550 nm measured by the Moderate Resolution Imaging Spectrometer (MODIS) satellite. This study presents the first observation of modulation of the aerosol emissions by the volcanic gravity waves and a case of coupling of dynamics and chemistry.

Airborne transmission of respiratory viruses.

The COVID-19 pandemic has revealed critical knowledge gaps in our understanding of and a need to update the traditional view of transmission pathways for respiratory viruses. The long-standing definitions of droplet and airborne transmission do not account for the mechanisms by which virus-laden respiratory droplets and aerosols travel through the air and lead to infection. In this Review, we discuss current evidence regarding the transmission of respiratory viruses by aerosols-how they are generated, transported, and deposited, as well as the factors affecting the relative contributions of droplet-spray deposition versus aerosol inhalation as modes of transmission. Improved understanding of aerosol transmission brought about by studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires a reevaluation of the major transmission pathways for other respiratory viruses, which will allow better-informed controls to reduce airborne transmission.

Optical properties of volcanic aerosols from eruptions of Nishinoshima Island observed in Southern Taiwan.

In July-August 2020, the volcano on Nishinoshima Island erupted with a moderate scale. The emitted aerosols arrived in Taiwan in early August and caused hazy air conditions in a few cities. In the city of Kaohsiung (KS) in southern Taiwan, the volcanic aerosols were observed with a combination of the aerosol robotic network (AERONET), several ground monitoring stations, and a lidar system. Increasing aerosol loadings were observed, beginning on 5 August 2020, based on a ground PM10/PM2.5 and the aerosol optical depth (AOD) of AERONET. Lidar measurements showed strong aerosol layers at heights of 0-2 km comparable to AERONET AOD. Optical properties including AOD, Angström exponent (AE), lidar backscattering coefficient, and depolarization ratio are measured with the source investigated using the back and forward trajectory studies.

Evidence and evolution of Criegee intermediates, hydroperoxides and secondary organic aerosols formed via ozonolysis of α-pinene.

α-Pinene, the most abundant monoterpene in the atmosphere, accounts for more than 50% of global monoterpene emission. Though its reaction with ozone has been generally perceived as a major source of secondary organic aerosols (SOAs), direct evidence of its reaction intermediates (RI) and their evolution remain lacking. Here we study the ozonolysis of α-pinene between 180 and 298 K using a long-path, temperature-variable aerosol cooling chamber coupled to a rapid-scan time-resolved Fourier transform infrared spectrometer. The spectroscopic signatures of large Criegee intermediates (CIs) and hydroperoxides (HPs) were found for the first time. The aerosol size evolution during the reaction was also measured. In contrast to a previous perception, we show that temperature plays a determinant role in the ozonolysis kinetics. Finally, we show that the formation of HPs is an energetically favorable pathway to dissipate CIs. This study provides new insights into the ozonolysis of α-pinene and its contribution to SOA formation.

Phthalides serve as potent modulators to boost fetal hemoglobin induction therapy for ß-hemoglobinopathies.

Fetal hemoglobin (HbF) induction therapy has become the most promising strategy for treating ß-hemoglobinopathies, including sickle-cell diseases and ß-thalassemia. However, subtle but critical structural difference exists between HbF and normal adult hemoglobin (HbA), which inevitably leads to reduced binding of the endogenous modulator 2,3-bisphosphoglycerate (2,3-BPG) to HbF and thus increased oxygen affinity and decreased oxygen transport efficiency of HbF. We combined the oxygen equilibrium experiments, resonance Raman (RR) spectroscopy, and molecular docking modeling, and we discuss 2 phthalides, z-butylidenephthalide and z-ligustilide, that can effectively lower the oxygen affinity of HbF. They adjust it to a level closer to that of HbA and make it a more satisfactory oxygen carrier for adults. From the oxygen equilibrium curve measurements, we show that the 2 phthalides are more effective than 2,3-BPG for modulating HbF. The RR spectra show that phthalides allosterically stabilize the oxygenated HbF in the low oxygen affinity conformation, and the molecular docking modeling reveals that the 2 chosen phthalides interact with HbF via the cleft around the γ1/γ2 interface with a binding strength ∼1.6 times stronger than that of 2,3-BPG. We discuss the implications of z-butylidenephthalide and z-ligustilide in boosting the efficacy of HbF induction therapy to mitigate the clinical severities of ß-hemoglobinopathies.

Short-interval exposure to ambient fine particulate matter (PM2.5) exacerbates the susceptibility of pulmonary damage in setting of lung ischemia-reperfusion injury in rodent: Pharmacomodulation of melatonin.

This study tested the hypothesis that exposure to ambient fine particulate matter (PM2.5) pollution increased susceptibility of rat lung to damage from acute ischemia-reperfusion (IR) injury that was reversed by melatonin (Mel) treatment. Male-adult SD rats (n = 30) were categorized into group 1 (normal control), group 2 (PM2.5 only), group 3 (IR only at day 8 after PM2.5 exposure), group 4 (PM2.5 + IR) and group 5 (PM2.5 + IR + Mel), and all animals were sacrificed by day 10 after PM2.5 exposure. Oxygen saturation (%) was significantly higher in group 1 than in other groups and significantly lower in group 4 than in groups 2, 3 and 5 but it did not differ among the latter three groups (p < 0.01). Pulmonary protein expressions of inflammation (MMP-9/TNF-α/NF-kB), oxidative stress (NOX-1/NOX-2/oxidized protein), apoptosis (mitochondrial-Bax/caspase-3/PARP) and fibrosis were lowest in group 1, highest in group 4, significantly higher in group 5 than in groups 2 and 3 (all p < 0.0001), but they did not differ between groups 2 and 3. Inflammatory cell infiltration in lung parenchyma, specific inflammatory cell surface markers (CD14+, F4/88+), allergic inflammatory cells (IgE+, eosinophil+), number of goblet cells, thickness of tracheal epithelial layer and fibrotic area exhibited an identical pattern of protein expressions to inflammation among the five groups (all p < 0.0001). In conclusion, lung parenchymal damage and a rigorous inflammatory response were identified in rodent even with short-term PM2.5 exposure.

Assessing the Impact of Electronic Health Record Interventions on Hepatitis B Screening and Vaccination.

BACKGROUND: Hepatitis B virus (HBV) infection is a major health disparity between Asian Americans, Native Hawaiians, and Pacific Islanders compared with other racial/ethnic groups in the U.S. AIMS: Our aims were to determine the effectiveness of an electronic health record (EHR) data-driven clinical intervention to improve HBV screening and vaccination rates at a community health center primarily serving Asian American patients. METHODS: Using a community-engaged approach, we conducted a study to compare the differences in screening and vaccination rates for 6,429 patient encounters before and after implementation of the EHR intervention. A multivariable logistic regression analysis was conducted to estimate the effect of the intervention. RESULTS: Analyses indicated that patients who visited the clinic after implementing the EHR intervention were more likely to be screened (OR=1.8, p<.001) and vaccinated (OR=2.8, p<.001) for hepatitis B. CONCLUSIONS: Electronic health record interventions implemented using a community-engaged approach may improve delivery of appropriate care to patients at risk for hepatitis B in a community health setting.

Phthalide Derivatives from Angelica Sinensis Decrease Hemoglobin Oxygen Affinity: A New Allosteric-Modulating Mechanism and Potential Use as 2,3-BPG Functional Substitutes.

Angelica sinensis (AS), one of the most versatile herbal medicines remains widely used due to its multi-faceted pharmacologic activities. Besides its traditional use as the blood-nourishing tonic, its anti-hypertensive, anti-cardiovascular, neuroprotective and anti-cancer effects have been reported. Albeit the significant therapeutic effects, how AS exerts such diverse efficacies from the molecular level remains elusive. Here we investigate the influences of AS and four representative phthalide derivatives from AS on the structure and function of hemoglobin (Hb). From the spectroscopy and oxygen equilibrium experiments, we show that AS and the chosen phthalides inhibited the oxygenated Hb from transforming into the high-affinity "relaxed" (R) state, decreasing Hb's oxygen affinity. It reveals that phthalides cooperate with the endogenous Hb modulator, 2,3-bisphosphoglycerate (2,3-BPG) to synergetically regulate Hb allostery. From the docking modeling, phthalides appear to interact with Hb mainly through its α1/α2 interface, likely strengthening four (out of six) Hb "tense" (T) state stabilizing salt-bridges. A new allosteric-modulating mechanism is proposed to rationalize the capacity of phthalides to facilitate Hb oxygen transport, which may be inherently correlated with the therapeutic activities of AS. The potential of phthalides to serve as 2,3-BPG substitutes/supplements and their implications in the systemic biology and preventive medicine are discussed.

Interfacial Solvation and Surface pH of Phenol and Dihydroxybenzene Aqueous Nanoaerosols Unveiled by Aerosol VUV Photoelectron Spectroscopy.

Although the significance of aqueous interfaces has been recognized in numerous important fields, it can be even more prominent for nanoscaled aqueous aerosols because of their large surface-to-volume ratios and prevalent existence in nature. Also, considering that organic species are often mixed with aqueous aerosols in nature, a fundamental understanding of the electronic and structural properties of organic species in aqueous nanoaerosols is essential to learn the interplay between water and organic solutes under the nanoscaled size regime. Here, we report for the first time the vacuum ultraviolet photoelectron spectroscopy of phenol and three dihydroxybenzene (DHB) isomers including catechol, resorcinol, and hydroquinone in the aqueous nanoaerosol form. By evaluating two photoelectron features of the lowest vertical ionization energies originated from the b1(π) and a2(π) orbitals for phenolic aqueous nanoaerosols, their interfacial solvation characteristics are unraveled. Phenolic species appear to reside primarily on/near the aqueous nanoaerosol interface, where they appear only partially hydrated on the aqueous interface with the hydrophilic hydroxyl group more solvated in water. An appreciable proportion of phenol is found to coexist with phenolate at/near the nanoaerosol interface even under a high bulk pH of 12.0, indicating that the nanoaerosol interface exhibits a composition distribution and pH drastically different from those of the bulk. The surface pH of phenol-containing aqueous nanoaerosols is found to be ∼2.2 ± 0.1 units more acidic than that of the bulk interior, as measured at the bulk pH of 12.0. From the photoelectron spectra of DHB aqueous nanoaerosols, the effects of numbers/arrangements of -OH groups are assessed. This study shows that the hydration extents, pH values, deprotonation status, and numbers/relative arrangements of -OH groups are crucial factors affecting the ionization energies of phenolic aqueous nanoaerosols and thus their redox-based activities. The multifaceted implications of the present study in the aerosol science, atmospheric/marine chemistry, and biological science are also addressed.

Molecular Basis of the Antioxidant Capability of Glutathione Unraveled via Aerosol VUV Photoelectron Spectroscopy.

Glutathione (GSH), the most abundant nonenzymatic antioxidant in living systems, actively scavenges various exogenous/endogenous oxidizing species, defending important biomolecules against oxidative damages. Although it is well established that the antioxidant activity of GSH originates from the cysteinyl thiol (-SH) group, the molecular origin that makes the thiol group of GSH a stronger reducing agent than other thiol-containing proteins is unclear. To gain insights into the molecular basis underlying GSH's superior antioxidant capability, here we report, for the first time, the valence electronic structures of solvated GSH in the aqueous aerosol form via the aerosol vacuum ultraviolet photoelectron spectroscopy technique. The pH-dependent electronic evolution of GSH is obtained, and the possible correlations between GSH and its constituting amino acids are interrogated. The valence band maxima (VBMs) for GSH aqueous aerosols are found at 7.81, 7.61, 7.52, and 5.51 ± 0.10 eV at a pH of 1.00, 2.74, 7.00, and 12.00, respectively, which appear to be lower than the values of their corresponding hybrid counterparts collectively contributed from the three isolated constituting amino acids of GSH. An additional photoelectron feature is observed for GSH aqueous aerosols at pH = 12.00, where the thiol group on its Cys residue becomes deprotonated and the relatively well-separated feature allows its vertical ionization energy (VIE) to be determined as 6.70 ± 0.05 eV. Compared to a VIE of 6.97 ± 0.05 eV obtained for a similar thiolate feature observed previously for isolated Cys aqueous aerosols ( Su et al. VUV Photoelectron Spectroscopy of Cysteine Aqueous Aerosols: A Microscopic View of Its Nucleophilicity at Varying pH Conditions . J. Phys. Chem. Lett. 2015 , 6 , 817 - 823 ), a 0.27 eV reduction in the VIE is found for GSH, indicating that the outermost electron corresponding to the nonbonding electron on the thiolate group can be removed more readily from the GSH tripeptide than that from Cys alone. The possible origins underlying the decrease in the VBM of GSH with respect to that of each corresponding hybrid counterpart and the decrease in the VIE of the thiolate feature of GSH with respect to that of the isolated Cys are discussed, providing hints to understand the superior antioxidant capability of GSH from a molecular level.

Resurgence of Vaccine-Preventable Diseases in the United States: Anesthetic and Critical Care Implications.

Vaccine-preventable diseases (VPDs) such as measles and pertussis are becoming more common in the United States. This disturbing trend is driven by several factors, including the antivaccination movement, waning efficacy of certain vaccines, pathogen adaptation, and travel of individuals to and from areas where disease is endemic. The anesthesia-related manifestations of many VPDs involve airway complications, cardiovascular and respiratory compromise, and unusual neurologic and neuromuscular symptoms. In this article, we will review the presentation and management of 9 VPDs most relevant to anesthesiologists, intensivists, and other hospital-based clinicians: measles, mumps, rubella, pertussis, diphtheria, influenza, meningococcal disease, varicella, and poliomyelitis. Because many of the pathogens causing these diseases are spread by respiratory droplets and aerosols, appropriate transmission precautions, personal protective equipment, and immunizations necessary to protect clinicians and prevent nosocomial outbreaks are described.

Particulate Matter Exposure in a Police Station Located near a Highway.

People living or working near roadways have experienced an increase in cardiovascular or respiratory diseases due to vehicle emissions. Very few studies have focused on the PM exposure of highway police officers, particularly for the number concentration and size distribution of ultrafine particles (UFP). This study evaluated exposure concentrations of particulate matter (PM) in the Sinying police station near a highway located in Tainan, Taiwan, under different traffic volumes, traffic types, and shift times. We focused on periods when the wind blew from the highway toward the police station and when the wind speed was greater than or equal to 0.5 m/s. PM2.5, UFP, and PM-PAHs concentrations in the police station and an upwind reference station were measured. Results indicate that PM2.5, UFP, and PM-PAHs concentrations in the police station can be on average 1.13, 2.17, and 5.81 times more than the upwind reference station concentrations, respectively. The highest exposure level for PM2.5 and UFP was observed during the 12:00 PM-4:00 PM shift while the highest PAHs concentration was found in the 4:00 AM-8:00 AM shift. Thus, special attention needs to be given to protect police officers from exposure to high PM concentration.

VUV Photoelectron Spectroscopy of Cysteine Aqueous Aerosols: A Microscopic View of Its Nucleophilicity at Varying pH Conditions.

Cysteine (Cys) is unique due to its highly reactive thiol group. It often regulates the biological function of proteins by acting as the redox site. Despite its biological significance, however, the valence electronic structure of Cys under the aqueous environments remains unavailable. Here, we report the VUV photoelectron spectroscopy of Cys aqueous aerosols via a newly built aerosol VUV photoelectron spectroscopy apparatus. The photoelectron spectra of Cys show distinct band shapes at varying pH conditions, reflecting the altered molecular orbital characters when its dominating form changes. The ionization energy of Cys is determined to be 8.98 ± 0.05 eV at low pH. A new feature at a binding energy of 6.97 ± 0.05 eV is observed at high pH, suggesting that the negative charge on the thiolate group becomes the first electron to be removed upon ionization. This work implies that when Cys is involved in redox processes, the charge transfer mechanism may be entirely altered under different pH conditions.

Subunit disassembly pathway of human hemoglobin revealing the site-specific role of its cysteine residues.

Cysteine residues play a unique role in human hemoglobin (Hb) by affecting its cooperative oxygen binding behavior and the stability of its tetrameric structure. However, how these cysteine residues fulfill their biophysical functions from the molecular level is yet unclear. Here we study the subunit disassembly pathway of human hemoglobin using the sulfhydryl reagent, p-hydroxymercuribenzoate (PMB) and investigate the functional roles of cysteine residues in human hemoglobin. We show evidence from the matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry that all three types of cysteine residues, including the surface-exposed ßCys93 and the shielded αCys104 and ßCys112 are reactive to PMB, resolving an issue long under debate. It is demonstrated that all three types of cysteine residues must be blocked by PMB to accomplish the subunit disassembly, and the PMB-cysteine reactions proceed in a stepwise manner with an order of ßCys93, αCys104, and ßCys112. The PMB reactions with the three different cysteine residues demonstrate strong site-specificity. The possible influence of PMB-cysteine reactions to the stability of various intersubunit salt bridges has been discussed based on the crystallographic structure of hemoglobin, providing insights in understanding the hemoglobin subunit disassembly pathway and the site-specific functional role of each cysteine residue in hemoglobin.

Infrared spectroscopy and modeling of co-crystalline CO2·C2H2 aerosol particles. I. The formation and decomposition of co-crystalline CO2·C2H2 aerosol particles.

Aerosol particles composed of co-crystalline CO(2)·C(2)H(2) were generated in a bath gas cooling cell at cryogenic temperatures and investigated with infrared spectroscopy between 600 and 4000 cm(-1). Similar to results obtained for thin films of the co-crystal [T. E. Gough and T. E. Rowat, J. Chem. Phys. 109, 6809 (1998)], this phase was found to be metastable and decomposed into pure CO(2) and pure C(2)H(2). These decomposed aerosols were characterized through (i) a comparison to experimentally prepared aerosols of mixed CO(2) and C(2)H(2) of known architectures and (ii) the modeling of infrared spectra. A likely architecture after decomposition are C(2)H(2)-CO(2) core-shell particles with a disk-like shape. The co-crystalline CO(2)·C(2)H(2) aerosols prior to decomposition are modeled and analyzed in detail in the subsequent paper (Part II).