Intranasal vaccination with engineered BCG expressing CCL2 induces a stronger immune barrier against Mycobacterium tuberculosis than BCG.

Intradermal Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccination is currently the only licensed strategy for preventing tuberculosis (TB). It provides limited protection against pulmonary TB. To enhance the efficacy of BCG, we developed a recombinant BCG expressing exogenous monocyte chemoattractant CC chemokine ligand 2 (CCL2) called rBCG-CCL2. Co-culturing macrophages with rBCG-CCL2 enhances their abilities in migration, phagocytosis, and effector molecule expression. In the mouse model, intranasal vaccination with rBCG-CCL2 induced greater immune cell infiltration and a more extensive innate immune response in lung compared to vaccination with parental BCG, as determined by multiparameter flow cytometry, transcriptomic analysis, and pathological assessments. Moreover, rBCG-CCL2 induced a high frequency of activated macrophages and antigen-specific T helper 1 (Th1) and Th17 T cells in lungs. The enhanced immune microenvironment responded more effectively to intravenous challenge with Mycobacterium tuberculosis (Mtb) H37Ra, leading to significant reductions in H37Ra burden and pathological damage to the lungs and spleen. Intranasal rBCG-CCL2-vaccinated mice rapidly initiated pro-inflammatory Th1 cytokine release and reduced pathological damage to the lungs and spleen during the early stage of H37Ra challenge. The finding that co-expression of CCL2 synergistically enhances the immune barrier induced by BCG provides a model for defining immune correlates and mechanisms of vaccine-elicited protection against TB.

Size-Dependent Nascent Sea Spray Aerosol Bounce Fractions and Estimated Viscosity: The Role of Divalent Cation Enrichment, Surface Tension, and the Kelvin Effect.

Viscosity, or the "thickness," of aerosols plays a key role in atmospheric processes like ice formation, water absorption, and heterogeneous kinetics. However, the viscosity of sea spray aerosols (SSA) has not been widely studied. This research explored the relationship between particle size and viscosity of authentic SSA particles through particle bounce, atomic force microscopy analysis, and predictive viscosity modeling from molecular composition. The study found that 40 nm SSA particles had estimated viscosities around 104 Pa·s and bounce fractions three times higher than 100 and 200 nm particles with less than 102 Pa·s at a relative humidity (RH) of 60%. Additional studies revealed the Kelvin effect and particle density, influenced by particle size, have a greater impact on size-dependent bounce fractions than changes in RH across impactor stages. While changes in the level of surfactants can impact particle bounce, the increased viscosity in smaller SSA is attributed to the formation of gel-like phase states caused by cation-organic cross-links between divalent calcium ions and organic anions enriched in the smaller particles. This work shows the smallest gel-like SSA particles observed in the field are highly viscous, which has implications for cloud formation, secondary aerosol growth, and pollutant transport in coastal environments.

Siloxane Emissions and Exposures during the Use of Hair Care Products in Buildings.

Cyclic volatile methyl siloxanes (cVMS) are ubiquitous in hair care products (HCPs). cVMS emissions from HCPs are of concern, given the potential adverse impact of siloxanes on the environment and human health. To characterize cVMS emissions and exposures during the use of HCPs, realistic hair care experiments were conducted in a residential building. Siloxane-based HCPs were tested using common hair styling techniques, including straightening, curling, waving, and oiling. VOC concentrations were measured via proton-transfer-reaction time-of-flight mass spectrometry. HCP use drove rapid changes in the chemical composition of the indoor atmosphere. cVMS dominated VOC emissions from HCP use, and decamethylcyclopentasiloxane (D5) contributed the most to cVMS emissions. cVMS emission factors (EFs) during hair care routines ranged from 110-1500 mg/person and were influenced by HCP type, styling tools, operation temperatures, and hair length. The high temperature of styling tools and the high surface area of hair enhanced VOC emissions. Increasing the hair straightener temperature from room temperature to 210 °C increased cVMS EFs by 50-310%. Elevated indoor cVMS concentrations can result in substantial indoor-to-outdoor transport of cVMS via ventilation (0.4-6 tons D5/year in the U.S.); thus, hair care routines may augment the abundance of cVMS in the outdoor atmosphere.

Rapid Nucleation and Growth of Indoor Atmospheric Nanocluster Aerosol during the Use of Scented Volatile Chemical Products in Residential Buildings.

Scented volatile chemical products (sVCPs) are frequently used indoors. We conducted field measurements in a residential building to investigate new particle formation (NPF) from sVCP emissions. State-of-the-art instrumentation was used for real-time monitoring of indoor atmospheric nanocluster aerosol (NCA; 1-3 nm particles) size distributions and terpene mixing ratios. We integrated our NCA measurements with a comprehensive material balance model to analyze sVCP-nucleated indoor NCA dynamics. Our results reveal that sVCPs significantly increase indoor terpene mixing ratios (10-1,000 ppb), exceeding those in outdoor forested environments. The emitted terpenes react with indoor atmospheric O3 and initiate indoor NPF, resulting in nucleation rates as high as ∼105 cm-3 s-1 and condensational growth rates up to 300 nm h-1; these are orders of magnitude higher than those reported during outdoor NPF events. Notably, high particle nucleation rates significantly increase indoor atmospheric NCA concentrations (105-108 cm-3), and high growth rates drive their survival and growth to sizes that efficiently reach the deepest regions of the human respiratory system. We found sVCP-nucleated NCA to cause respiratory exposures and dose rates comparable to or exceeding those from primary aerosol sources such as gas stoves and diesel engines, highlighting their significant impact on indoor atmospheric environments.

Dynamics of nanocluster aerosol in the indoor atmosphere during gas cooking.

Nanocluster aerosol (NCA: particles in the size range of 1-3 nm) are a critically important, yet understudied, class of atmospheric aerosol particles. NCA efficiently deposit in the human respiratory system and can translocate to vital organs. Due to their high surface area-to-mass ratios, NCA are associated with a heightened propensity for bioactivity and toxicity. Despite the human health relevance of NCA, little is known regarding the prevalence of NCA in indoor environments where people spend the majority of their time. In this study, we quantify the formation and transformation of indoor atmospheric NCA down to 1 nm via high-resolution online nanoparticle measurements during propane gas cooking in a residential building. We observed a substantial pool of sub-1.5 nm NCA in the indoor atmosphere during cooking periods, with aerosol number concentrations often dominated by the newly formed NCA. Indoor atmospheric NCA emission factors can reach up to ∼1016 NCA/kg-fuel during propane gas cooking and can exceed those for vehicles with gasoline and diesel engines. Such high emissions of combustion-derived indoor NCA can result in substantial NCA respiratory exposures and dose rates for children and adults, significantly exceeding that for outdoor traffic-associated NCA. Combustion-derived indoor NCA undergo unique size-dependent physical transformations, strongly influenced by particle coagulation and condensation of low-volatility cooking vapors. We show that indoor atmospheric NCA need to be measured directly and cannot be predicted using conventional indoor air pollution markers such as PM2.5 mass concentrations and NO x (NO + NO2) mixing ratios.

Surveillance of common respiratory infections during the COVID-19 pandemic demonstrates the preventive efficacy of non-pharmaceutical interventions.

OBJECTIVE: The emergence of a novel coronavirus, SARS-CoV-2, and its subsequent spread outside of Wuhan, China, led to the human society experiencing a pandemic of coronavirus disease 2019 (COVID-19). While the development of vaccines and pharmaceutical treatments are ongoing, government authorities in China have implemented unprecedented non-pharmaceutical interventions as primary barriers to curb the spread of the deadly SARS-CoV-2 virus. Although the decline of COVID-19 cases coincided with the implementation of such interventions, we searched for evidence to demonstrate the efficacy of these interventions, since artifactual factors, such as the environment, the pathogen itself, and the phases of epidemic, may also alter the patterns of case development. METHODS: We surveyed common viral respiratory infections that have a similar pattern of transmission, tropism, and clinical manifestation, as COVID-19 under a series of non-pharmaceutical interventions during the current pandemic season. We then compared this data with historical data from previous seasons without such interventions. RESULTS: Our survey showed that the rates of common respiratory infections, such as influenza and respiratory syncytial virus infections, decreased dramatically from 13.7% (95% CI, 10.82-16.58) and 4.64% (95% CI, 2.88-7.64) in previous years to 0.73% (95% CI, 0.02-1.44) and 0.0%, respectively, in the current season. CONCLUSIONS: Our surveillance provides compelling evidence that non-pharmaceutical interventions are cost-effective ways to curb the spread of contagious agents, and may represent the only practical approach to limit the evolving epidemic until specific vaccines and pharmaceutical treatments are available.

Optimal vacuum erectile device therapy regimen for penile rehabilitation in a bilateral cavernous nerve crush rat model.

BACKGROUND: Vacuum erectile device (VED) therapy has been widely used in penile rehabilitation after radical prostatectomy; however, there is no consensus on the best regimen. OBJECTIVES: To explore an optimal VED therapy regimen in bilateral cavernous nerve crush (BCNC) rat model. MATERIALS AND METHODS: Adult male rats were used to measure the effects of different durations (1-30 min) of VED treatment on penile length, penile blood gas analysis, and adverse effects. Forty-eight adult male rats were randomly divided into Sham, BCNC, and VED treatment groups (2-3-2-3 min, 4-3-3 min, 5-5 min, and 10 min). Penile length, erectile function, and side effects were detected after VED treatment. Histopathological staining and Western blotting were performed to explore the cellular and molecular changes. RESULTS: Prolongation of the duration of VED treatment significantly decreased the penile oxygen saturation, partial oxygen pressure, and arterial blood ratio (P < 0.05). Compared with the BCNC group, all VED treatment regimens partially reversed BCNC-induced penile shortening and erectile dysfunction (P < 0.0001), with the 4-3-3-min and 5-5-min treatment groups exhibiting more significant improvement than the 10-min and 2-3-2-3-min treatment groups (P < 0.0001). The mechanism may be related to the up-regulation of the smooth muscle cell/collagen ratio, endothelial nitric oxide synthase, and α-smooth muscle actin (all P < 0.0001); and the down-regulation of hypoxia-inducible factor-1α, transforming growth factor-ß1, and apoptosis (all P < 0.0001). The incidence of adverse effects in the 2-3-2-3-min treatment group was the highest. DISCUSSION: The commonly used VED therapy regimens maintained erectile function and penile length of BCNC rat by relieving hypoxia and fibrosis, and no further benefits were observed with increased treatment frequency or prolonged treatment duration. CONCLUSION: Two consecutive 5-min treatments with a short interval is the optimal VED therapy regimen for penile rehabilitation in BCNC rat model.