A novel inhalable nanobody targeting IL-4Rα for the treatment of asthma.

BACKGROUND: Inhalable biologics represent a promising approach to improve the efficacy and safety of asthma treatment. Although several mAbs targeting IL-4 receptor α chain (IL-4Rα) have been approved or are undergoing clinical trials, the development of inhalable mAbs targeting IL-4Rα presents significant challenges. OBJECTIVE: Capitalizing on the distinctive advantages of nanobodies (Nbs) in maintaining efficacy during storage and administration, we sought to develop a novel inhalable IL-4Rα Nb for effectively treating asthma. METHODS: Three IL-4Rα immunized Nb libraries were used to generate specific and functional IL-4Rα Nbs. LQ036, a bivalent Nb comprising 2 HuNb103 units, was constructed with a high affinity and specificity for human IL-4Rα. The efficacy, pharmacokinetics, and safety of inhaled LQ036 were evaluated in B-hIL4/hIL4RA humanized mice. RESULTS: LQ036 inhibited secreted embryonic alkaline phosphatase reporter activity, inhibited TF-1 cell proliferation, and suppressed phosphorylated signal transducer and activator of transduction 6 in T cells from patients with asthma. Crystal structure analysis revealed a binding region similar to dupilumab but with higher affinity, leading to better efficacy in blocking the signaling pathway. HuNb103 competed with IL-4 and IL-13 for IL-4Rα binding. Additionally, LQ036 significantly inhibited ovalbumin-specific IgE levels in serum, CCL17 levels in bronchoalveolar lavage fluid, bronchial mucous cell hyperplasia, and airway goblet cell hyperplasia in B-hIL4/hIL4RA humanized mice. Inhaled LQ036 exhibited favorable pharmacokinetics, safety, and tissue distribution, with higher concentrations observed in the lungs and bronchi. CONCLUSIONS: These findings from preclinical studies establish the safety and efficacy of inhaled LQ036, underscoring its potential as a pioneering inhalable biologic therapy for asthma.

Inhalable Nanofitin demonstrates high neutralization of SARS-CoV-2 virus via direct application in respiratory tract.

Nanofitins are small and hyperthermostable alternative protein scaffolds that display physicochemical properties making them suitable for the development of topical therapeutics, notably for the treatment of pulmonary infectious diseases. Local administration of biologics to the lungs involves a particularly stressful step of nebulization that is poorly tolerated by most antibodies, which limits their application by this delivery route. During the COVID-19 pandemic, we generated anti-SARS-CoV-2 monomeric Nanofitins of high specificity for the spike protein. Hit Nanofitin candidates were identified based on their binding properties with punctual spike mutants and assembled into a linear multimeric construction constituting of four different Nanofitins, allowing the generation of a highly potent anti-SARS-CoV-2 molecule. The therapeutic efficacy of the multimeric assembly was demonstrated both in in vitro and in vivo models. Interestingly, the neutralization mechanism of the multimeric construction seems to involve a particular conformation switch of the spike trimer. In addition, we reported the stability and the conserved activity of the tetrameric construction after nebulization. This advantageous developability feature for pulmonary administration associated with the ease of assembly, as well as the fast generation process position the Nanofitin technology as a potential therapeutic solution for emerging infectious diseases.

Inhalable hybrid nanovaccines with virus-biomimetic structure boost protective immune responses against SARS-CoV-2 variants.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with different antigenic variants, has posed a significant threat to public health. It is urgent to develop inhalable vaccines, instead of injectable vaccines, to elicit mucosal immunity against respiratory viral infections. METHODS: We reported an inhalable hybrid nanovaccine (NVRBD-MLipo) to boost protective immunity against SARS-CoV-2 infection. Nanovesicles derived from genetically engineered 293T cells expressing RBD (NVRBD) were fused with pulmonary surfactant (PS)-biomimetic liposomes containing MPLA (MLipo) to yield NVRBD-MLipo, which possessed virus-biomimetic structure, inherited RBD expression and versatile properties. RESULTS: In contrast to subcutaneous vaccination, NVRBD-MLipo, via inhalable vaccination, could efficiently enter the alveolar macrophages (AMs) to elicit AMs activation through MPLA-activated TLR4/NF-κB signaling pathway. Moreover, NVRBD-MLipo induced T and B cells activation, and high level of RBD-specific IgG and secretory IgA (sIgA), thus elevating protective mucosal and systemic immune responses, while reducing side effects. NVRBD-MLipo also demonstrated broad-spectrum neutralization activity against SARS-CoV-2 (WT, Delta, Omicron) pseudovirus, and protected immunized mice against WT pseudovirus infection. CONCLUSIONS: This inhalable NVRBD-MLipo, as an effective and safe nanovaccine, holds huge potential to provoke robust mucosal immunity, and might be a promising vaccine candidate to combat respiratory infectious diseases, including COVID-19 and influenza.

Influence of saw chain type and wood species on the concentration of wood dust in a forestry operation.

This study examines the impact of chainsaw chain type and tree species on the concentration of inhalable wood dust generated during motor-manual harvesting in forested areas. The effects of conducting real-world measurements of inhalable dust within the operator's breathing zone during forestry work are investigated. Two different chain types were evaluated: the commonly used 3/8" pitch chain (conventional chain) and the 0.325" pitch chain. Additionally, measurements were taken for three tree species: beech, oak, and pine (including both live and standing dead trees after a fire). Results showed that, overall, using the conventional 3/8" chain type yielded the highest concentration of wood dust for all three tree species. Notably, the highest wood dust concentration was observed in the burned Pinus brutia cluster, also with the 3/8" chain pitch. These findings emphasize the importance of understanding how chain type and tree species contribute to wood dust levels.

Exposure to dust and respiratory health among Australian miners.

PURPOSE: Occupational exposure to dust has been recognised as a significant health hazard to mine workers. This study aimed to investigate the association between exposure to inhalable (INH) and respirable (RES) dust and respiratory health among mine workers in Western Australia using an industry-wide exposure database. METHODS: The database comprised cross-sectional surveys conducted by mining companies for the period 2001-2012. The study population consisted of 12,797 workers who were monitored for exposure to INH and RES dust and undertook health assessments including a respiratory questionnaire and spirometry test. RESULTS: Despite the general trend of declining exposure to both INH and RES dust observed over the 12 years period, mine workers reported a higher prevalence of phlegm and cough when exposed to elevated concentrations of INH and RES dust. Logistic regression analysis further confirmed the positive association between INH dust exposure and the prevalence of phlegm with an adjusted odds ratio of 1.033 (95% CI 1.012-1.052). Overall, 6.3% of miners might have potential airway obstruction, and exposure to INH dust was associated with impaired lung function parameters. CONCLUSION: Exposure levels of INH and RES dust particles among mine workers have reduced considerably and were well below currently legislated occupational exposure limits. However, given the reported higher prevalence of phlegm and cough among those with elevated dust concentrations, there is a continued need for effective dust exposure monitoring and control in the mineral mining industry.

Long-term exposures to ambient particulate matter and ozone pollution with lower extremity deep vein thrombosis after surgical operations: a retrospective case-control study in Beijing, China.

BACKGROUND: Lower extremity deep vein thrombosis (LEDVT) after surgical operations is a common and fatal disease leading to unfavorable outcomes including death. Nevertheless, there has been insufficient evidence on the associations between ambient air pollution and LEDVT, particularly studies from developing regions. METHODS: Based on 302 LEDVT cases and 302 controls in a general hospital in Beijing, China, this unmatched retrospective case-control study investigated the associations of fine particulate matter (PM2.5), inhalable particulate matter (PM10), and ozone (O3) with odds of LEDVT. RESULTS: Per 10 µg/m3 increase in PM2.5, PM10, and O3 at 3-month, 6-month, and 2-year average was associated with increased LEDVT odds [odds ratios (ORs) for PM2.5: 1.10 (95%CI: 1.05, 1.14), 1.14 (95%CI: 1.09, 1.18), and 1.30 (95%CI: 1.06, 1.61); ORs for PM10: 1.06 (95%CI: 1.02, 1.10), 1.12 (95%CI: 1.08, 1.16), and 1.29 (95%CI: 1.03, 1.61); ORs for O3: 1.00 (95%CI: 0.96, 1.04), 1.16 (95%CI: 1.02, 1.31), and 2.08 (95%CI: 1.03, 4.18), respectively]. The stratified analyses, exposure-responses curves, and sensitivity analyses further highlighted the robustness of our findings. CONCLUSIONS: Long-term exposures to ambient PM2.5, PM10, and O3 may increase the risk of LEDVT in patients after surgical operations. The results may be implicated in the prevention and control of adverse clinical outcomes of surgical patients associated with ambient air pollution.

Deposition of secondary organic aerosol in human lung model: Effect of photochemically aged aerosol on human respiratory system.

Ultrafine particles (UFP) of Secondary Organic Aerosol (SOA) penetrate deep into the human respiratory system and exert fatal effects on human health. However, there is little data on the potential deposited doses of UFP-generated SOA in the human respiratory tract. This study is to estimate the fraction of aerosol deposition using a multiple-path-particle-dosimetry (MPPD) model. For relevancy of real life, the model employed measured concentrations of toluene-derived fresh and aged SOA produced within serially connected smog chamber and PAM-OFR (Potential Aerosol Mass-Oxidation Flow Reactor) under atmospheric environmental conditions (NOx and relative humidity). The number concentrations and chemical composition of fresh and aged aerosols produced within the chambers were measured using Scanning Mobility Particle Sizer (SMPS) and High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS), while the morphology of individual particles was analyzed using Scanning Electron Microscopy (SEM). The number concentration of aged SOA-w/s was more than double compared to that of fresh SOA-w/s (maximum reached after 10 h) with its size less than 100 nm. The O:C ratio for aged SOA-w/s were 0.96 and 1.15 depending on RH (0.96 at 3% RH and 1.15 at 50% RH), and individual spherical particles containing water were present in agglomerates with its size of less than 1 µm. In all inhalable fresh and aged SOA produced in the two chambers, 5-22% of aerosol is deposited in the Head airways, 4-8% in the tracheobronchial, and 8-34% in the alveolar regions. The predominant deposition of the aged aerosol occurred in the alveoli (in the generation 20th lobe), and the deposition faction in the alveoli was 2-3 times higher in the children group than the adults group. This study presented a quantitative exposure assessment of SOA generated under a realistic simulation and suggested the possibility of evaluating long-term exposure to SOA and potential health effects by determining the potential inhalable aerosol doses and the fraction of deposition in the human respiratory system.

Full-length 16S rRNA gene sequencing and machine learning reveal the bacterial composition of inhalable particles from two different breeding stages in a piggery.

Bacterial loading aggravates the harm of particulate matter (PM) to public health and ecological systems, especially in operations of concentrated animal production. This study aimed to explore the characteristics and influencing factors of bacterial components of inhalable particles at a piggery. The morphology and elemental composition of coarse particles (PM10, aerodynamic diameter ≤ 10 µm) and fine particles (PM2.5, aerodynamic diameter ≤ 2.5 µm) were analyzed. Full-length 16 S rRNA sequencing technology was used to identify bacterial components according to breeding stage, particle size, and diurnal rhythm. Machine learning (ML) algorithms were used to further explore the relationship between bacteria and the environment. The results showed that the morphology of particles in the piggery differed, and the morphologies of the suspected bacterial components were elliptical deposited particles. Full-length 16 S rRNA indicated that most of the airborne bacteria in the fattening and gestation houses were bacilli. The analysis of beta diversity and difference between samples showed that the relative abundance of some bacteria in PM2.5 was significantly higher than that in PM10 at the same pig house (P < 0.01). There were significant differences in the bacterial composition of inhalable particles between the fattening and gestation houses (P < 0.01). The aggregated boosted tree (ABT) model showed that PM2.5 had a great influence on airborne bacteria among air pollutants. Fast expectation-maximization microbial source tracking (FEAST) showed that feces was a major potential source of airborne bacteria in pig houses (contribution 52.64-80.58 %). These results will provide a scientific basis for exploring the potential risks of airborne bacteria in a piggery to human and animal health.

Cytotoxic and Bactericidal Effects of Inhalable Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticles with Traces of Zinc Oxide.

The bactericidal effects of inhalable ciprofloxacin (CIP) loaded-poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) with traces of zinc oxide (ZnO) were investigated against clinical strains of the respiratory pathogens Staphylococcus aureus and Pseudomonas aeruginosa. CIP-loaded PEtOx NPs retained their bactericidal activity within the formulations compared to free CIP drugs against these two pathogens, and bactericidal effects were enhanced with the inclusion of ZnO. PEtOx polymer and ZnO NPs did not show bactericidal activity alone or in combination against these pathogens. The formulations were tested to determine the cytotoxic and proinflammatory effects on airway epithelial cells derived from healthy donors (NHBE), donors with chronic obstructive pulmonary disease (COPD, DHBE), and a cell line derived from adults with cystic fibrosis (CFBE41o-) and macrophages from healthy adult controls (HCs), and those with either COPD or CF. NHBE cells demonstrated maximum cell viability (66%) against CIP-loaded PEtOx NPs with the half maximal inhibitory concentration (IC50) value of 50.7 mg/mL. CIP-loaded PEtOx NPs were more toxic to epithelial cells from donors with respiratory diseases than NHBEs, with respective IC50 values of 0.103 mg/mL for DHBEs and 0.514 mg/mL for CFBE41o- cells. However, high concentrations of CIP-loaded PEtOx NPs were toxic to macrophages, with respective IC50 values of 0.002 mg/mL for HC macrophages and 0.021 mg/mL for CF-like macrophages. PEtOx NPs, ZnO NPs, and ZnO-PEtOx NPs with no drug were not cytotoxic to any cells investigated. The in vitro digestibility of PEtOx and its NPs was investigated in simulated lung fluid (SLF) (pH 7.4). The analysed samples were characterized using Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and UV-Vis spectroscopy. Digestion of PEtOx NPs commenced one week following incubation and was completely digested after four weeks; however, the original PEtOx was not digested after six weeks of incubation. The outcome of this study revealed that PEtOx polymer could be considered an efficient drug delivery carrier in respiratory linings, and CIP-loaded PEtOx NPs with traces of ZnO could be a promising addition to inhalable treatments against resistant bacteria with reduced toxicity.

Use of prototype side stream filtration system to control dust levels in a commercial swine farrowing building.

Swine meat provides an essential global food source. Due to economies of scale, modern U.S. swine production primarily occurs indoors to maintain an optimal environment across the stages of swine production. Indoor concentrations of dust and contaminant gases in swine production buildings increase in the winter months due to reduced ventilation to optimal building temperature. In this study, an engineering control technology designed to recirculate the air in a swine farrowing room through a mobile air handling unit containing high-efficiency particulate filters was presented. A mobile solution could be easily deployed as an intervention method if an infectious disease outbreak occurs at a swine operation. The performance of this control technology was evaluated following deployment in a production farrowing barn for a period of 6 weeks during the winter in the Midwestern United States. Contaminant concentrations of inhalable dust, respirable dust, and carbon dioxide were measured in the room treated by the prototype system and compared to contaminant concentrations measured in an untreated "control" room. Over 6 weeks, the mean inhalable and respirable dust concentrations observed during the study period for the "treatment" room were 2.61 and 0.14 mg/m3, respectively, compared to 3.51 and 0.25 mg/m3, respectively, for the control room. The mobile recirculating ventilation system, operating at a flow rate of 45 m3/min (5 room air exchanges per hour), reduced the inhalable dust by 25% and respirable dust by 48% as measured with a real-time aerosol monitor, when compared to the control room. In addition, no concentration differences in carbon dioxide and relative humidity between the treatment and the control rooms were observed. Inhalable and respirable concentrations of dust were significantly reduced (p = 0.001), which demonstrates an essential improvement of the air quality that may prove beneficial to reduce the burden of disease among both workers and animals.

Inhalable spray-dried polycaprolactone-based microparticles of Sorafenib Tosylate with promising efficacy on A549 cells.

The study developed and evaluated Sorafenib Tosylate (SRT)-loaded polymeric microparticles (MPs) using biodegradable polymer polycaprolactone (PCL) as a potential inhalable carrier for NSCLC. MPs were prepared by spray-drying an oil-in-water (o/w) emulsion. The optimized MPs demonstrated excellent flowability, particle size of 2.84 ± 0.5 µm, zeta potential of -14.0 ± 1.5 mV, and 85.08 ± 5.43% entrapment efficiency. ATR-FTIR/DSC studies revealed a lack of characteristic peaks of the crystalline drug signifying good entrapment of the drug. MPs were spherical and uniform in SEM pictures. The MPs showed a biphasic release pattern up to 72h. The Anderson cascade impactor (ACI) investigation demonstrated the highest drug deposition at stage 4, which revealed that the MPs can reach the lungs' secondary and terminal bronchi. Inhalable MPs had an efficient aerodynamic property with a mass median aerodynamic diameter (MMAD) of 2.63 ± 1.3 µm, a geometric standard deviation (GSD) of 1.93 ± 0.2 µm, and a fine particle fraction (FPF) of 87 ± 2.5%. Finally, in cytotoxicity studies on A549 cancer cells, MPs had an IC50 value of 0.6011 ± 0.8 µM, which was 85.68% lower than free drug. These findings suggest SRT-loaded inhalable PCL-based MPs as a novel NSCLC treatment.

Recent advances in facemask devices for in vivo sampling of human exhaled breath aerosols and inhalable environmental exposures.

Since the COVID-19 pandemic, the unprecedented use of facemasks has been requiring for wearing in daily life. By wearing facemask, human exhaled breath aerosols and inhaled environmental exposures can be efficiently filtered and thus various filtration residues can be deposited in facemask. Therefore, facemask could be a simple, wearable, in vivo, onsite and noninvasive sampler for collecting exhaled and inhalable compositions, and gain new insights into human health and environmental exposure. In this review, the recent advances in developments and applications of in vivo facemask sampling of human exhaled bacteria, viruses, proteins, and metabolites, and inhalable facemask contaminants and air pollutants, are reviewed. New features of facemask sampling are highlighted. The perspectives and challenges on further development and potential applications of facemask devices are also discussed.

Inhalable Antibiotic Resistome from Wastewater Treatment Plants to Urban Areas: Bacterial Hosts, Dissemination Risks, and Source Contributions.

Antibiotic resistance genes (ARGs) are commonly detected in the atmosphere, but questions remain regarding their sources and relative contributions, bacterial hosts, and corresponding human health risks. Here, we conducted a qPCR- and metagenomics-based investigation of inhalable fine particulate matter (PM2.5) at a large wastewater treatment plant (WWTP) and in the ambient air of Hong Kong, together with an in-depth analysis of published data of other potential sources in the area. PM2.5 was observed with increasing enrichment of total ARGs along the coastal-urban-WWTP gradient and clinically relevant ARGs commonly identified in urban and WWTP sites, illustrating anthropogenic impacts on the atmospheric accumulation of ARGs. With certain kinds of putative antibiotic-resistant pathogens detected in urban and WWTP PM2.5, a comparable proportion of ARGs that co-occurred with MGEs was found between the atmosphere and WWTP matrices. Despite similar emission rates of bacteria and ARGs within each WWTP matrix, about 11-13% of the bacteria and >57% of the relevant ARGs in urban and WWTP PM2.5 were attributable to WWTPs. Our study highlights the importance of WWTPs in disseminating bacteria and ARGs to the ambient air from a quantitative perspective and, thus, the need to control potential sources of inhalation exposure to protect the health of urban populations.

In vitro evaluation of the inhalation toxicity of the cosmetic ingredient aluminum chlorohydrate.

Aluminum chlorohydrate (ACH) is a major aerosol component frequently used as the active ingredient in antiperspirants, and in vivo studies have raised a concern about its inhalation toxicity. Still, few studies have addressed its effects on the human respiratory tract. Therefore, we developed a study on ACH inhalation toxicity using an in vitro human alveolar cell model (A549 cells) with molecular and cellular markers of oxidative stress, immunotoxicity, and epigenetic changes. The chemical characterization of ACH suspensions indicated particle instability and aggregation; however, side-scatter analysis demonstrated significant particle uptake in cells exposed to ACH. Exposure of A549 cells to non-cytotoxic concentrations of ACH (0.25, 0.5, and 1 mg/ml) showed that ACH induced reactive oxygen species. Moreover, ACH upregulated TNF, IL6, IL8, and IL1A genes, but not the lncRNAs NEAT1 and MALAT1. Finally, no alterations on the global DNA methylation pattern (5-methylcytosine and 5-hydroxymethylcytosine) or the phosphorylation of histone H2AX (γ-H2AX) were observed. Our data suggest that ACH may induce oxidative stress and inflammation on alveolar cells, and A549 cells may be useful to identify cellular and molecular events that may be associated with adverse effects on the lungs. Still, further research is needed to ensure the inhalation safety of ACH.

Enhanced curcumin loaded nanocellulose: a possible inhalable nanotherapeutic to treat COVID-19.

Nanocellulose/polyvinyl alcohol/curcumin (CNC/PVA/curcumin) nanoparticles with enhanced drug loading properties were developed by the dispersion of nanocellulose in curcumin/polyvinyl alcohol aqueous medium. Due to the physical and chemical nature of sulphuric acid hydrolyzed nanocellulose and the antiviral properties of curcumin, the possibility of using these nanoparticles as an inhalable nanotherapeutic for the treatment of coronavirus disease 2019 (COVID-19) is discussed. The adsorption of curcumin and PVA into nanocellulose, and the presence of anionic sulphate groups, which is important for the interaction with viral glycoproteins were confirmed by Fourier transform infrared (FTIR) spectroscopy. FESEM images showed that the diameter of nanocellulose ranged from 50 to 100 nm, which is closer to the diameter (60-140 nm) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The solubility of poorly water-soluble curcumin was increased from 40.58 ± 1.42 to 313.61 ± 1.05 mg/L with increasing the PVA concentration from 0.05 to 0.8% (w/v) in aqueous medium. This is a significant increase in the solubility compared to curcumin's solubility in carboxymethyl cellulose medium in our previous study. The drug loading capacity increased by 22-fold with the addition of 0.8% PVA to the nanocellulose dispersed curcumin solution. The highest drug release increased from 1.25 ± 0.15 mg/L to 17.11 ± 0.22 mg/L with increasing the PVA concentration from 0 to 0.8% in the drug-loaded medium. Future studies of this material will be based on the antiviral efficacy against SARS-CoV-2 and cell cytotoxicity studies. Due to the particulate nature, morphology and size of SARS-CoV-2, nanoparticle-based strategies offer a strong approach to tackling this virus. Hence, we believe that the enhanced loading of curcumin in nanocellulose will provide a promising nano-based solution for the treatment of COVID-19.

SARS-CoV-2 and Health Care Worker Protection in Low-Risk Settings: a Review of Modes of Transmission and a Novel Airborne Model Involving Inhalable Particles.

Since the beginning of the COVID-19 pandemic, there has been intense debate over SARS-CoV-2's mode of transmission and appropriate personal protective equipment for health care workers in low-risk settings. The objective of this review is to identify and appraise the available evidence (clinical trials and laboratory studies on masks and respirators, epidemiological studies, and air sampling studies), clarify key concepts and necessary conditions for airborne transmission, and shed light on knowledge gaps in the field. We find that, except for aerosol-generating procedures, the overall data in support of airborne transmission-taken in its traditional definition (long-distance and respirable aerosols)-are weak, based predominantly on indirect and experimental rather than clinical or epidemiological evidence. Consequently, we propose a revised and broader definition of "airborne," going beyond the current droplet and aerosol dichotomy and involving short-range inhalable particles, supported by data targeting the nose as the main viral receptor site. This new model better explains clinical observations, especially in the context of close and prolonged contacts between health care workers and patients, and reconciles seemingly contradictory data in the SARS-CoV-2 literature. The model also carries important implications for personal protective equipment and environmental controls, such as ventilation, in health care settings. However, further studies, especially clinical trials, are needed to complete the picture.

Experiment and numerical investigation of inhalable particles and indoor environment with ventilation system.

After the outbreak of COVID-19, the indoor environment has become particularly important in closed spaces, being a common concern in environmental science and public health, and of great significance for the building environment. To improve the indoor air quality and control the spread of viruses, the analysis of inhalable particles in indoor environments is critical. In this research, we study standards focused on inhalable particles and indoor environmental quality, as well as analyzing the movement and diffusion of indoor particles. Based on our analysis, we conduct an experimental study to determine the distribution of indoor inhalable particles of different sizes before and after diffusion under the conditions of underfloor air distribution. Furthermore, the mathematical modeling method is adopted to simulate the indoor flow field, particle trajectories, and pollutant dispersion process. The k-ε two-equation model is applied as the turbulence model in the numerical simulation, while the Lagrangian discrete phase model is adopted to trace the motion of particles and analyze the distribution characteristics of indoor particles. The results demonstrate that fine particles (i.e., those with size less than 0.5 µm) have a significant impact on the indoor particle concentration, while coarse particles (i.e., with size above 2.5 µm) have a greater influence on the total mass concentration of indoor particles. Small-sized particles can easily follow the airflow and diffuse to upper parts of the room. Overall, the effects of indoor particles on indoor air quality, including the potential threat of aerosol transmission of respiratory infectious diseases, are non-negligible. Application of the presented research can contribute to improving the health-related aspects of the building environment.

Low-Flammable Parahydrogen-Polarized MRI Contrast Agents.

Many MRI contrast agents formed with the parahydrogen-induced polarization (PHIP) technique exhibit biocompatible profiles. In the context of respiratory imaging with inhalable molecular contrast agents, the development of nonflammable contrast agents would nonetheless be highly beneficial for the biomedical translation of this sensitive, high-throughput and affordable hyperpolarization technique. To this end, we assess the hydrogenation kinetics, the polarization levels and the lifetimes of PHIP hyperpolarized products (acids, ethers and esters) at various degrees of fluorine substitution. The results highlight important trends as a function of molecular structure that are instrumental for the design of new, safe contrast agents for in vivo imaging applications of the PHIP technique, with an emphasis on the highly volatile group of ethers used as inhalable anesthetics.

Air pollution influence on serum inflammatory interleukins: A prospective study in childhood-onset systemic lupus erythematous patients.

OBJECTIVE: To assess the effect of individual exposure, in real-time, to traffic-related pollutants on serum interleukin levels of childhood-onset lupus erythematous systemic (c-SLE) patients. METHODS: A longitudinal and observational design was conducted in 12 repeated measures of serum samples and clinical evaluations (totaling 108 measurements) of c-SLE patients over 30 consecutive months. Real-time, individual exposure to fine particles (PM2.5) and nitrogen dioxide (NO2) was measured with portable monitors. Generalized estimating equation was used to evaluate the association between exposure to PM2.5 and NO2 and the following serum cytokine levels on the 7 days preceding clinical assessment and serum collection: MCP1, IL-6, IL-8, IL-10, IL-17, IFN-alpha, and TNF-alpha. Disease activity and other risk factors were also controlled. RESULTS: An interquartile range (IQR) increase in PM2.5 daily concentration was significantly associated with increased levels of TNF-alpha on the third, fourth, and seventh day after exposure; IL-10 on the third and fourth day after exposure; IL-17 on the third and seventh day after exposure; and INF-alpha on the third day after exposure (p < 0.05). An IQR increase in 7-day moving average of PM2.5 was associated with a 6.2 pg/mL (95% CI: 0.5; 11.8; p = 0.04) increase in serum IFN-alpha level. An unexpected significant association was observed between an IQR increase in NO27-day cumulative concentration and a decrease of 1.6 pg/mL (95% CI: -2.6; -0.7; p < 0.001) in serum IL-17. CONCLUSION: Real-time exposure to PM2.5 prospectively associated with increased serum TNF-alpha, INF-alpha, IL-10, and IL-17 levels in c-SLE patients.

Inhalable nanovaccine with biomimetic coronavirus structure to trigger mucosal immunity of respiratory tract against COVID-19.

The COVID-19 pandemic caused by SARS-CoV-2 seriously threatens global public health. It has previously been confirmed that SARS-CoV-2 is mainly transmitted between people through "respiratory droplets". Therefore, the respiratory tract mucosa is the first barrier to prevent virus invasion. It is very important to stimulate mucosal immunity to protect the body from respiratory virus infection. Inspired by this, we designed a bionic-virus nanovaccine, which can induce mucosal immunity by nasal delivery to prevent virus infection from respiratory tract. The nanovaccine that mimic virosome is composed of poly(I:C) mimicking viral genetic material as immune adjuvant, biomimetic pulmonary surfactant (bio-PS) liposomes as capsid structure of virus and the receptor binding domains (RBDs) of SARS-CoV-2 as "spike" to completely simulate the structure of the coronavirus. The nanovaccine can be administered by inhaling to imitate the process of SARS-CoV-2 infection through the respiratory tract. Our results demonstrated that the inhalable nanovaccine with bionic virus-like structure has a stronger mucosal protective effect than routine muscle and subcutaneous inoculation. In particular, high titer of secretory immunoglobulin A (sIgA) was detected in respiratory secretions, which effectively neutralize the virus and prevent it from entering the body through the respiratory tract. Through imitating the structure and route of infection, this inhalable nanovaccine strategy might inspire a new approach to the precaution of respiratory viruses.