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.

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.

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.

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."

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.

A tellurium-based small compound ameliorates tumor metastasis by downregulating heparanase expression.

Tellurium is a rare element, and ammonium trichloro (dioxoethylene-o,o') tellurate (AS101) is the most bioactive molecule among several synthetic tellurium compounds. AS101 was found to be immunomodulatory and can modulate types of cytokines. However, the effect of AS101 on tumor metastasis remains unclear. Heparanase, an endo-glucuronidase, cleaves heparin sulfate side chains of proteoglycans on the cell surface, further leading to the degradation of the extracellular matrix. Heparanase also releases angiogenic factors in the extracellular matrix, is overexpressed in tumor cells, and promotes tumor metastasis and angiogenesis. In this study, we investigated the effect of AS101 in 4T1 and CT26 cells, especially heparanase. Heparanase expression was downregulated in 4T1 and CT26 cells after treatment with AS101 in vitro. The protein level involved in the protein kinase-B/mammalian target of rapamycin (AKT/mTOR) signaling pathway also declined. Cell migration assays revealed the inhibitory effect of AS101 on migration. The results of this study indicate that AS101 inhibits tumor migration by downregulating heparanase through the AKT/mTOR signaling pathway and has positive effects in vivo.

Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin.

Estimates of the prevalence of chronic hepatitis B (CHB) in the United States differ significantly, and the contribution of foreign-born (FB) persons has not been adequately described. The aim of this study was to estimate the number of FB persons in the United States living with CHB by their country of origin. We performed a systematic review for reports of HBsAg seroprevalence rates in 102 countries (covering PubMed from 1980 to July 2010). Data from 1,373 articles meeting inclusion criteria were extracted into country-specific databases. We identified 256 seroprevalence surveys in emigrants from 52 countries (including 689,078 persons) and 1,797 surveys in the general populations of 98 countries (including 17,861,035 persons). Surveys including individuals with lower or higher risk of CHB than the general population were excluded. Data were combined using meta-analytic methods to determine country-specific pooled CHB prevalence rates. Rates were multiplied by the number of FB living in the United States in 2009 by country of birth from the U.S. Census Bureau to yield the number of FB with CHB from each country. We estimate a total of 1.32 million (95% confidence interval: 1.04-1.61) FB in the United States living with CHB in 2009; 58% migrated from Asia and 11% migrated from Africa, where hepatitis B is highly endemic. Approximately 7% migrated from Central America, a region with lower CHB rates, but many more emigrants to the United States. This analysis suggests that the number of FB persons living with CHB in the United States may be significantly greater than previously reported. Assuming 300,000-600,000 U.S.-born persons with CHB, the total prevalence of CHB in the United States may be as high as 2.2 million.

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.

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).

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.

Silymarin inhibits in vitro T-cell proliferation and cytokine production in hepatitis C virus infection.

BACKGROUND & AIMS: Silymarin, an extract from the seeds of the milk thistle plant Silybum marianum, has been used for centuries for the treatment of chronic liver diseases. Despite common use by patients with hepatitis C in the United States, its clinical efficacy remains uncertain. The goal of this study was to determine whether silymarin has in vitro effects on immune function that might have implications for its potential effect on hepatitis C virus (HCV)-induced liver disease. METHODS: Freshly isolated peripheral blood mononuclear cells (PBMC) and T cells from HCV-infected and uninfected subjects were tested in vitro for responses to nonspecific and antigenic stimulation in the presence and absence of a standardized preparation of silymarin (MK001). RESULTS: Minimal MK001 toxicity on PBMC was found at concentrations between 5 and 40 microg/mL. MK001 dose dependently inhibited the proliferation and secretion of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-2 by PBMC stimulated with anti-CD3. In addition, MK001 inhibited proliferation by CD4(+) T cells to HCV, Candida, and tetanus protein antigens and by HLA-A2/HCV 1406-1415-specific CD8(+) T cells to allogeneic stimulation. MK001 inhibited T-cell TNF-alpha and IFN-gamma cytokine secretion to tetanus and Candida protein antigens. Finally, MK001 inhibited nuclear factor-kappaB transcriptional activation after T-cell receptor-mediated stimulation of Jurkat T cells, consistent with its ability to inhibit Jurkat T-cell proliferation and secretion of IL-2. CONCLUSIONS: Silymarin's ability to inhibit the proliferation and proinflammatory cytokine secretion of T cells, combined with its previously described antiviral effect, suggests a possible mechanism of action that could lead to clinical benefit during HCV infection.

Diagnosis of depression in former injection drug users with chronic hepatitis C.

GOALS: This study seeks to define the performance characteristics of 2 common depression screening tests and how psychiatric diagnoses affect adherence to treatment. BACKGROUND: Hepatitis C virus is common in former injection drug users (IDU). Many former IDUs have depression, which may complicate treatment, and are often denied therapy. STUDY: Ninety patients with chronic hepatitis C virus and reported IDU were recruited from a Hepatology Clinic in Seattle. Subjects completed the Beck Depression Inventory (BDI) and Patient Health Questionnaire-9 (PHQ-9) before antiviral therapy. A psychiatrist administered the Mini International Neuropsychiatric Interview as the "gold standard." Adherence was measured by self-report of missed doses. RESULTS: The BDI and PHQ-9 were highly correlated (r=0.75). Using a BDI score of ≥20 and a PHQ-9 score of ≥10, 39% and 52%, respectively, were misclassified as being depressed, as compared with the Mini International Neuropsychiatric Interview. Maximal sensitivity (85.7%) and specificity (82.6%) was achieved using a BDI score cutoff of 31, with an area under the curve of 0.82. For the PHQ-9, a cutoff of 14 yielded the best sensitivity (85.7%) and specificity (73.9%) with an area under the curve of 0.84. Adherence to at least 80% of medications was achieved by the majority. CONCLUSIONS: Subjects reported good adherence and outcomes despite a high level of psychiatric comorbidity. The BDI and PHQ-9 were highly correlated but both tended to overdiagnose depression. A high score on BDI or PHQ-9 should not be the sole basis for withholding treatment. These patients should be evaluated by a psychiatrist to make an informed decision.

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.

Ultrafast dynamics in helium nanodroplets probed by femtosecond time-resolved EUV photoelectron imaging.

The dynamics of electronically excited helium nanodroplets are studied by femtosecond time-resolved photoelectron imaging. EUV excitation into a broad absorption band centered around 23.8 eV leads to an indirect photoemission process that generates ultraslow photoelectrons. A 1.58 eV probe pulse transiently depletes the indirect photoemission signal for pump-probe time delays <200 fs and enhances the signal beyond this delay. The depletion is due to suppression of the indirect ionization process by the probe photon, which generates a broad, isotropically emitted photoelectron band. Similar time scales in the decay of the high energy photoelectron signal and the enhancement of the indirect photoemission signal suggest an internal relaxation process that populates states in the range of a lower energy droplet absorption band located just below the droplet ionization potential (IP approximately 23.0 eV). A nearly 70% enhancement of the ultraslow photoelectron signal indicates that interband relaxation plays a more dominant role for the droplet de-excitation mechanism than photoemission.

Infrared spectra of C2H6, C2H4, C2H2, and CO2 aerosols potentially formed in Titan's atmosphere.

Pure and mixed aerosols of ethane, ethylene, acetylene and carbon dioxide were generated in a collisional cooling cell and characterized by Fourier transform infrared spectroscopy between 600 and 4000 cm(-1). Pure ethane, pure ethylene, and mixed ethane/ethylene initially form supercooled liquid droplets, which over time crystallize to their stable solid phases. These droplets are found to be long-lived (up to hours) for pure ethane and mixed ethane/ethylene, but short-lived (up to seconds) for pure ethylene. Acetylene and carbon dioxide form solid aerosol particles. Acetylene particles have a partially amorphous structure, while carbon dioxide particles are crystalline. The structure of the infrared bands of carbon dioxide is strongly determined by the particles' shape due to exciton coupling. The comparison of various mixed systems reveals that acetylene very efficiently induces heterogeneous crystallization. As reported earlier, the co-condensation of acetylene and carbon dioxide can lead to the formation of a metastable mixed crystalline phase. Our preliminary calculations show that this mixed phase has a monoclinic rather than the cubic structure proposed previously.

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.

Pregnancy complications associated with hepatitis C: data from a 2003-2005 Washington state birth cohort.

OBJECTIVE: The objective of the study was to determine the effect of hepatitis C virus (HCV) on selected maternal and infant birth outcomes. STUDY DESIGN: This population-based cohort study using Washington state birth records from 2003 to 2005 compared a cohort of pregnant women identified as HCV positive from birth certificate data (n = 506) to randomly selected HCV-negative mothers (n = 2022) and drug-using HCV-negative mothers (n = 1439). RESULTS: Infants of HCV-positive mothers were more likely to be low birthweight (odds ratio [OR], 2.17; 95% confidence interval [CI] 1.24, 3.80), to be small for gestational age (OR, 1.46; 95% CI, 1.00, 2.13), to need assisted ventilation (OR, 2.37; 95% CI, 1.46, 3.85), and to require neonatal intensive car unit (NICU) admission (OR, 2.91; 95% CI, 1.86, 4.55). HCV-positive mothers with excess weight gain also had a greater risk of gestational diabetes (OR, 2.51; 95% CI, 1.04, 6.03). Compared with the drug-using cohort, NICU admission and the need for assisted ventilation remained associated with HCV. CONCLUSION: HCV-positive pregnant women appear to be at risk for adverse neonatal and maternal outcomes.

Factors predictive of significant hepatic fibrosis in adults with chronic hepatitis B and normal serum ALT.

GOAL: This study examines the prevalence and correlates of significant liver fibrosis among patients with immunotolerant hepatitis B. BACKGROUND: Adults with chronic hepatitis B infection acquired early in life often have normal serum alanine aminotransferase (ALT) activity and high serum hepatitis B virus deoxyribonucleic acid loads (HBV DNA), known as "immunotolerant" hepatitis B. STUDY: We conducted a cross-sectional study of 28 hepatitis B patients with serum HBV DNA titer >10 copies/mL, positive hepatitis B envelope antigen, and persistently normal serum ALT in a tertiary care setting. Liver biopsies were reviewed by a single pathologist who was blinded to other data. The prevalence of significant hepatic fibrosis was determined using the hospital-defined upper limit of normal for ALT and 2 more stringent criteria proposed by recent studies. Statistical analyses were conducted to identify factors associated with hepatic fibrosis. RESULTS: The prevalence of stage 2 fibrosis using the hospital laboratory, more stringent, and most stringent definitions of normal serum ALT, was 32%, 32%, and 13%, respectively, corresponding to negative predictive values of 68%, 68%, and 88%, respectively. Age greater than 30 years (P=0.035), grade 2 liver inflammation (P=0.005), and lower serum HBV DNA level (mean 7.45 vs. 8.42 log10 copies/mL, P<0.001) were independently associated with stage 2 fibrosis on liver biopsy. CONCLUSIONS: These results highlight the need to use stringent definitions of normal serum ALT when making clinical decisions for patients with chronic hepatitis B. Older age and lower serum HBV DNA level predict significant hepatic fibrosis on biopsy. Our findings may guide decisions regarding liver biopsy among patients with immunotolerant hepatitis B.