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The characterization of plant extracts is usually accomplished by reverse-phase liquid chromatography, but the development of new complementary approaches, such as HILIC, offers an orthogonal method. In this study, five HILIC stationary phases were evaluated to assess their ability to retain polyphenols. They were selected to cover the main different HILIC mechanisms: bare silica; silica with ethylene bridge; neutral amide; amino; zwitterionic. A total of 31 polyphenol standards were used for the screening, including 9 stilbenes, 8 flavonoids, 6 anthocyanins, and 8 phenolic acids. Three different detections were tested: diode array detector, charged aerosol detector and mass spectrometry. Results indicated that silica supports were not suitable for retaining polyphenols, with no or low retention observed except for anthocyanins. The effectiveness of stationary phases in retention of phenolics following the order related to increased retention: zwitterionic, amide, and amino. The choice of mobile phase also influenced retention. Mobile phases containing TFA as pH modifier limited retention, while formic acid was found to be more effective for polyphenol retention. Ammonium buffers also improved retention but often compromised peak shape. pH changes mainly impacted ionizable compounds, such as phenolic acids, by increasing their retention when they were ionized. DAD was wellsuited for detecting polyphenols that possess aromatic rings, though peak wavelengths depend on the structures of the polyphenols. CAD, while less sensitive than DAD and MS, provided an almost similar response for structurally related compounds, even with gradient elution. MS was the preferred detector for quantification when resolution between compounds was challenging, as it is often the case with natural extracts. The study successfully demonstrated that best HILIC conditions were obtained using an amino stationary phase composed of a polyethylenimine and formic acid-based mobile phase. These conditions were successfully applied to the analysis of stilbenoid-rich extracts from different parts of the vine. The elution order of stilbenoids followed the degree of polymerization. With CAD, the chromatographic profile was more representative of sample composition. It was demonstrated for the first time the interest of a combination of HILIC and CAD for analyzing stilbenes, offering a complementary approach to the classic RP analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Piezoelectric biomaterials hold a pivotal role in the progression of bioelectronics and biomedicine, owing to their remarkable electromechanical properties, biocompatibility, and bioresorbability. However, their technological potential is restrained by certain challenges, including precise manipulation of nanobiomolecules, controlling their growth across nano-to-macro hierarchy, and tuning desirable mechanical properties. We report a high-speed thermal-electric driven aerosol (TEA) printing method capable of fabricating piezoelectric biofilms in a singular step. Electrohydrodynamic aerosolizing and in situ electrical poling allow instantaneous tuning of the spatial organization of biomolecular inks. We demonstrate TEA printing of β-glycine/polyvinylpyrrolidone films, and such films exhibit the piezoelectric voltage coefficient of 190 × 10 -3 volt-meters per newton, surpassing that of industry-standard lead zirconate titanate by approximately 10-fold. Furthermore, these films demonstrate nearly two orders of magnitude improvement in mechanical flexibility compared to glycine crystals. We also demonstrate the ultrasonic energy harvesters based on the biofilms, providing the possibility of wirelessly powering bioelectronics.

Etimicin is a typical aminoglycoside antibiotic (AG). High performance liquid chromatography-evaporation light scattering detector (HPLC-ELSD) method is a commonly used method for determining impurities in Etimicin. However, due to the poor reproducibility, low sensitivity and narrow linear range of the ELSD, high-throughput quantitative analysis of impurities in Etimicin currently poses a challenge. In this study, a sensitive method using hydrophilic interaction liquid chromatography coupled with charged aerosol detector (HILIC-CAD) was developed for the analysis of the impurities in Etimicin. The liquid phase conditions for determination impurities in Etimicin were optimized using Box Behnken design (BBD) and response surface methodology (RSM), resulting in satisfactory separation and optimal CAD output signal. We also studied the influence of CAD parameters on the signal-to-noise ratio and linearity of Etimicin and its impurities. This method has also been proven to be effective in separating impurities from two other typical AGs, Isepamicin and Amikacin. In the method validation, the coefficient of determination (R 2 ) of Etimicin, Isepamicin and Amikacin and their impurities were all greater than 0.999, within the range of 0.5-50 μg/mL. The average recoveries of the impurities of three typical AGs were 99.03 %-101.22 %, RSDs all were less than 2.5 % for intra-day and inter-day precision, with good precision and accuracy. The developed HILIC-CAD quantification method was sensitive, accurate and highly selective for quantitative analysis of impurities in the AGs without need ion-pairing reagents, which is ensure the public medication safety. The method is first reported application of HILIC-CAD method for quantitative analysis of the impurities in AGs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to establish a feasible dissolution method for inhalation aerosols. A method of collecting fine particles was investigated to capture aerosol particles less than 4 μm in diameter for dissolution tests. This dose collection method enabled the aerosol particles to be uniformly distributed on the glass fiber filter, thus considerably reducing particle agglomeration. Budesonide was used as a model drug. The aerodynamic particle size distribution (APSD) of the meter-dose inhaler (MDI) was compared by replacing actuators with different orifice sizes. Dissolution tests were conducted on fine particle doses collected using various actuators, and the dissolution profiles were modeled. The fine particle dose decreased with an increasing orifice size of the actuator. Actuators with different orifice sizes would affect the dissolution behavior of inhaled drugs. This finding was supported by similarity factor f 2 analysis, suggesting the dissolution method has a discriminative capacity. The results of various model fits showed that the dissolution profiles produced by the different actuators could be fitted well using the Weibull mathematical model. The method employed in this study could offer a potential avenue for exploring the relationship between the orifice size of the actuator and the dissolution behavior of inhaled corticosteroids. This dissolution method was simple, reproducible, and suitable for determining the dissolution of inhalation aerosols., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The condensation of amino acids into peptides plays a crucial role in protein synthesis and is thus essential for understanding the origins of life. However, the spontaneous formation of peptides from amino acids in bulk aqueous media is energetically unfavorable, posing a challenge for elucidating plausible abiotic mechanisms. In this study, we investigate the formation of amide bonds between amino acids within highly supersaturated aerosol droplets containing dicyandiamide (DCD), a cyanide derivative potentially present on primordial Earth. Metastable states, i.e. supersaturation, within individual micron-sized droplets are studied using both an optical trap and a linear quadrupole electrodynamic balance. When irradiated with intense visible light, amide bond formation is observed to occur and can be monitored using vibrational bands in Raman spectra. The reaction rate is found to be strongly influenced by droplet size and kinetic modelling suggests that it is driven by the photochemical product of a DCD self-reaction. Our results highlight the potential of atmospheric aerosol particles as reaction environments for peptide synthesis and have potential implications for the prebiotic chemistry of early Earth., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Exhaled breath (EB) aerosol was in principle shown to be a suitable matrix for bioanalysis of volatile but also non-volatile compounds. This attracted particular interest in the field of drug analysis. However, a big gap still exists in the understanding how and which drugs and/or their metabolites are excreted into exhaled breath and could thus actually be detected. The current study aimed to develop an analytical workflow for the qualitative detection of non-volatile drugs in EB aerosol microparticles., Results: The analyte selection covered different drug classes such as antihypertensives, anticonvulsants or opioid analgesics to investigate and understand the excretion of drugs and their metabolites into EB aerosol. A device for collecting aerosol particles from the lung through impaction was used for the non-invasive sampling procedure. Three expiration cycles per participant and device were collected. The sample preparation consisted of a collector extraction with methanol. Qualitative method development and validation were performed using reversed-phase liquid chromatography (LC) coupled to orbitrap-based high-resolution mass spectrometry (HRMS). Qualitative method validation was done according to published recommendations and international guidelines. Parameters such as selectivity, carry-over, limits of detection and identification, recovery, matrix effects, and long-term stability were evaluated. The limits of detection ranged from 100 pg/collector to 10,000 pg/collector. The procedure was finally used to analyze a total of 31 patient EB samples and demonstrated that e.g., tilidine and its metabolite nortilidine as well as tramadol and its active metabolite O-desmethyltramadol can be detected in EB aerosol., Significance and Novelty: The work shows a comprehensive workflow for elucidating drug excretion into exhaled breath aerosol. This bioanalytical strategy and the corresponding novel data from this study are the foundation for further method development and to better understand, which drugs and their metabolites can be addressed by exhaled breath aerosol bioanalysis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Felix Mahfoud reports financial support was provided by German Research Foundation. Felix Mahfoud reports financial support was provided by German Cardiac Society. Felix Mahfoud reports financial support was provided by German Heart Foundation. Felix Mahfoud reports a relationship with Ablative Solutions, Medtronic, ReCor Medical, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Merck, Servier, and Terumo that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Many phenolic compounds (PhCs) in biomass burning and fossil fuel combustion emissions can partition into atmospheric aqueous phases ( e.g. , cloud/fog water and aqueous aerosols) and undergo reactions to form secondary organic aerosols (SOAs) and brown carbon (BrC). Redox-active transition metals, particularly Fe and Cu, are ubiquitous species in atmospheric aqueous phases known to participate in Fenton/Fenton-like chemistry as a source of aqueous ˙OH. However, even though the concentrations of water-soluble Cu are close to those of water-soluble Fe in atmospheric aqueous phases in some areas, unlike Fe, the effects that Cu have on SOA and BrC formation in atmospheric aqueous phases have scarcely been studied and remain poorly understood. We investigated the effects of Cu(II) on PhC reaction rates and BrC formation during the aqueous oxidation of four PhCs (guaiacol, catechol, syringol, and vanillin) by ˙OH generated from Fenton-like chemistry under different pH conditions. While the PhCs reacted when both H 2 O 2 and Cu(II) were present in the absence ( i.e. , dark oxidation) and presence ( i.e. , photooxidation) of light, the reaction rates were at least one order of magnitude higher during photooxidation. Higher PhC reaction rates were measured at higher pH during both dark oxidation and photooxidation as a result of higher ˙OH concentrations produced by Fenton-like chemistry. Only water-soluble BrC was formed during dark oxidation and photooxidation when Cu(II) was present. Mass absorption coefficients (10 3 to 10 4 cm 2 g -1 ) comparable to those of biomass burning BrC were measured during dark oxidation and photooxidation when Cu(II) was present. Light absorption was enhanced at higher pH during dark oxidation and photooxidation, which indicated that higher quantities and/or more absorbing BrC chromophores were formed at higher pH. The effects that Cu(II) had on the PhC reaction rates and the composition of SOAs and BrC formed depended on the PhC base structure ( i.e. , benzenediol vs. methoxyphenol). Overall, these results show how aqueous reactions involving Cu(II), H 2 O 2 , and PhCs can be an efficient source of daytime and nighttime water-soluble BrC and SOAs, which can have significant implications for how the atmospheric fates of PhCs are modeled for areas with substantial concentrations of water-soluble Cu in highly to moderately acidic cloud/fog water and aqueous aerosols.

The goal of the present research was to assess, under controlled laboratory conditions, the accuracy and precision of a prototype device (named 'P.ALP': Ph.D. Air-quality Low-cost Project) developed for PM 2.5 concentration level monitoring. Indeed, this study follows a complementary manuscript (previously published) focusing on the in-field evaluation of the device's performance. Four P.ALP prototypes were co-located with the reference instrument in a calm-air aerosol chamber at the NIOSH laboratories in Pittsburgh, PA (USA), used by the Center for Direct Reading and Sensor Technologies. The devices were tested for 10 monitoring days under several exposure conditions. To evaluate the performance of the prototypes, different approaches were employed. After the data from the devices were stored and prepared for analysis, to assess the accuracy (comparing the reference instrument with the prototypes) and the precision (comparing all the possible pairs of devices) of the P.ALPs, linear regression analysis was performed. Moreover, to find out the applicability field of this device, the US EPA's suggested criteria were adopted, and to assess error trends of the prototype in the process of data acquisition, Bland-Altman plots were built. The findings show that, by introducing ad hoc calibration factors, the P.ALP's performance needs to be further implemented, but the device can monitor the concentration trend variations with satisfying accuracy. Overall, the P.ALP can be involved in and adapted to a wide range of applications because of the inexpensive nature of the components, the small dimensions, and the high data storage capacity.

Lubricating base oils have been extensively employed for producing various industrial and consumer products. Therefore, their environmental and health impacts should be carefully evaluated. Although there have been many reports on pulmonary cytotoxicity and inflammatory responses of inhaled lubricating base oils, their potential influences on pulmonary surfactant (PS) films that play an essential role in maintaining respiratory mechanics and pulmonary immunity remains largely unknown. Here a systematic study on the interactions between an animal-derived natural PS and aerosols of water and representative mineral and vegetable base oils is performed using a novel biophysical assessing technique called constrained drop surfactometry capable of providing in vitro simulations of normal tidal breathing and physiologically relevant temperature and humidity in the lung. It was found that the mineral oil aerosols can impose strong inhibitions to the biophysical property of PS film, while the airborne vegetable oils and water show negligible adverse effects within the studied concentration range. The inhibitory effect is originated from the strong hydrophobicity of mineral oil, which makes it able to disrupt the interfacial molecular ordering of both phospholipid and protein compositions and consequently suppress the formation of condensed phase and multilayer scaffolds in a PS film. ENVIRONMENTAL IMPLICATION: Understanding the biophysical influence of airborne lubricating base oils on pulmonary surfactant (PS) films can provide new insights into the environmental impacts and health concerns of various industrial lubricant products. Here a comparative study on interactions between an animal-derived natural PS film and the aerosols of water and representative mineral and vegetable base oils under the true physiological conditions was conducted in situ using constrained drop surfactometry. We show that the most frequently used mineral base oil can cause strong inhibitions to the PS film by disrupting the molecular ordering of saturated phospholipids and surfactant-associated proteins at the interface., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

β-caryophyllonic acid (BCA), as an important precursor of aqueous secondary organic aerosols (aqSOA), has adverse effects on the atmospheric environment and human health. However, the key atmospheric chemical reaction process in which BCA participates in the formation of aqueous secondary organic aerosols is still unclear. In this study, the reaction mechanism and kinetics of BCA with ·OH and O 3 were investigated by quantum chemical calculations. The initiation reactions between BCA and ·OH include addition and H-abstraction reaction pathways, subsequent intermediates will also react with O 2 , ultimately undergo a cracking reaction to generate small molecular substances. The reaction of BCA with O 3 can generate primary ozone oxides and the Criegee Intermediates oIM3, subsequent main reaction products include keto-BCA, as well as other small molecule aqSOA precursors. The entire reaction process increases the O/C ratio of aqSOA in the aqueous phase and generates products of small molecules such as 4-formylpropionic acid, which plays an important role in the formation of aqSOA. At 298K, the transformation rate constants of BCA initiated by ·OH and O 3 are 1.47 × 10 10  M -1  s -1 and 3.16 × 10 5  M -1  s -1 , respectively, the atmospheric lifetimes of BCA reacting with ·OH range from 0.86 h-5.40 h, while the lifetimes of BCA reacting with O 3 range from 0.44 h-10.04 years. This suggests that BCA primarily reacts with ·OH. However, under higher O 3 concentrations, its ozonolysis becomes significant, promoting the formation of aqSOA. According to the risk assessment, the toxicity of most transformation products (TPs) gradually decreased, but the residual developmental toxicity could not be ignored. In this paper, the atmospheric liquid phase oxidation mechanisms of sesquiterpene unsaturated derived acid were studied from the microscopic level, which has guiding significance for the formation and transformation of aqSOA in atmosphere., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Characterization of aminoglycoside antibiotics like ribostamycin is important due to the complex composition and common toxic impurities. Aerosol detectors are often employed for determination of these non-absorbent analytes. In this work, a robust and cost-effective method was developed for simultaneous detection of ribostamycin and its related substances using high-performance liquid chromatography (HPLC) with a relative new aerosol detector named nano-quantity analyte detector (NQAD). With the introduction of less toxic but more compatible ion-pairs pentafluoropropionic acid (PFPA) and trifluoroacetic acid (TFA) in the eluent, an optimized separation effect was achieved. Compared with the other two aerosol detectors namely ELSD (evaporative light scattering detector) and CAD (charged aerosol detector), method verification and quantitative detection results revealed that NQAD had higher sensitivity than ELSD with a 0.8 μg/mL limit of detection, as well as wider linear range (from 2 μg/mL to 1000 μg/mL) than both CAD (from 2 μg/mL to 200 μg/mL) and ELSD (from 8 μg/mL to 200 μg/mL) detector. The performance of NQAD helped to realize detection of ribostamycin and its impurities with significant concentration differences in a single run. With a cation suppressor to eliminate the ion-suppression caused by the ion-pairs in the eluent, the structure of nine impurities in ribostamycin sample was characterized by liquid chromatography-mass spectrum (LC-MS). Both external standard and area normalization calculation were investigated, and NQAD obtained more accurate results due to its full-range linear response-to-concentration relationship, providing an alternative for routine quality control of multi analyte systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Thermodynamic modeling is still the most widely used method to characterize aerosol acidity, a critical physicochemical property of atmospheric aerosols. However, it remains unclear whether gas-aerosol partitioning should be incorporated when thermodynamic models are employed to estimate the acidity of coarse particles. In this work, field measurements were conducted at a coastal city in northern China across three seasons, and covered wide ranges of temperature, relative humidity and NH 3 concentrations. We examined the performance of different modes of ISORROPIA-II (a widely used aerosol thermodynamic model) in estimating aerosol acidity of coarse and fine particles. The M0 mode, which incorporates gas-phase data and runs the model in the forward mode, provided reasonable estimation of aerosol acidity for coarse and fine particles. Compared to M0, the M1 mode, which runs the model in the forward mode but does not include gas-phase data, may capture the general trend of aerosol acidity but underestimates pH for both coarse and fine particles; M2, which runs the model in the reverse mode, results in large errors in estimated aerosol pH for both coarse and fine particles and should not be used for aerosol acidity calculations. However, M1 significantly underestimates liquid water contents for both fine and coarse particles, while M2 provides reliable estimation of liquid water contents. In summary, our work highlights the importance of incorporating gas-aerosol partitioning when estimating coarse particle acidity, and thus may help improve our understanding of acidity of coarse particles., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Heterogeneous oxidation by gas-phase oxidants is an important chemical transformation pathway of secondary organic aerosol (SOA) and plays an important role in controlling the abundance, properties, as well as climate and health impacts of aerosols. However, our knowledge on this heterogeneous chemistry remains inadequate. In this study, the heterogeneous oxidation of α-pinene ozonolysis SOA by hydroxyl (OH) radicals was investigated under both low and high relative humidity (RH) conditions, with an emphasis on the evolution of molecular composition of SOA and its RH dependence. It is found that the heterogeneous oxidation of SOA at an OH exposure level equivalent to 12 hr of atmospheric aging leads to particle mass loss of 60% at 25% RH and 95% at 90% RH. The heterogeneous oxidation strongly changes the molecular composition of SOA. The dimer-to-monomer signal ratios increase dramatically with rising OH exposure, in particular under high RH conditions, suggesting that aerosol water stimulates the reaction of monomers with OH radicals more than that of dimers. In addition, the typical SOA tracer compounds such as pinic acid, pinonic acid, hydroxy pinonic acid and dimer esters (e.g., C 17 H 26 O 8 and C 19 H 28 O 7 ) have lifetimes of several hours against heterogeneous OH oxidation under typical atmospheric conditions, which highlights the need for the consideration of their heterogeneous loss in the estimation of monoterpene SOA concentrations using tracer-based methods. Our study sheds lights on the heterogeneous oxidation chemistry of monoterpene SOA and would help to understand their evolution and impacts in the atmosphere., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2023. Published by Elsevier B.V.)

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new therapeutic approach for patients with peritoneal cancer. So far, most published studies investigated the administration of established cytostatic agents through PIPAC. This study aimed to evaluate the effect of PIPAC on two breakthrough anti-cancer agents, specifically anti-PD1 pembrolizumab, and anti-HER2 antibody-drug conjugate (ADC) - trastuzumab-deruxtecan. We conducted systematic analyses on samples of pembrolizumab and trastuzumab-deruxtecan at clinically relevant concentrations before and after PIPAC administration using an experimental setup of a hermetic container system, mimicking the abdominal cavity and using identical features as in clinical use. We utilized a range of chromatographic and spectroscopic techniques to explore potential alterations in the primary, secondary, and tertiary structures of the drugs, focusing on post-translational modifications resulting from the aerosolization. Our findings indicate that PIPAC did not compromise the integrity of tested biopharmaceuticals. The size variants of both drugs, assessed by size exclusion chromatography (SEC), remained unchanged. Reversed-phase liquid chromatography (RPLC) and hydrophobic interaction chromatography (HIC) revealed no significant differences in hydrophobicity variants, the average drug-to-antibody ratio (DAR), or DAR distribution before and after PIPAC treatment. Circular dichroism (CD) spectroscopy confirmed that the secondary and tertiary structures were preserved. While pembrolizumab showed no change in charge variants post-PIPAC, trastuzumab-deruxtecan exhibited a non-negligible change in the quantity of charge variants on the monoclonal antibody itself, while the payload remained unchanged. This shift could possibly be related to the metallic composition of the CapnoPen® device (made of nickel and chromium) used in PIPAC and for these experiments. Together, our results suggest that PIPAC does not alter the structure of pembrolizumab and trastuzumab-deruxtecan, paving the way for future clinical trials., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. The authors declare the following competing financial interests: Mateusz Imiołek is an employee of Waters (Milford, MA, USA), a manufacturer of chromatography systems and consumables. ACQUITY, UPLC, Empower and BioResolve are trademarks of Waters Technologies Corporation. Capnopen® is a trademark of Capno pharm GmbH. Milli-Q is a trademark of Merck KGaA. Keytruda is a trademark of Merck Sharp & Dohme, LLC. Enhertu is a trademark of Daiichi Sankyo Company Limited. Accutron is a trademark of Medtron AG. AdvanceBio is a trademark of Agilent Technologies Inc. MAbPac is a trademark of Thermo Fisher Scientific AG. Excel is a trademark of Microsoft Corporation. All other trademarks are the property of their respective owners., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Active pharmaceutical ingredient (API) embedded dry powder for inhalation (AeDPI) shows higher drug loading and delivery dose for directly treating various lung infections. Inspired by the dandelion, we propose a novel kind of AeDPI microparticle structure fabricated by spray freeze drying technology, which would potentially enhance the alveoli deposition efficiency. When inhaling, such microparticles are expected to be easily broken-up into fragments containing API that acts as 'seed' and could be delivered to alveoli aided by the low density 'pappus' composed of excipient. Herein, itraconazole (ITZ), a first-line drug for treating pulmonary aspergillosis, was selected as model API. TPGS, an amphiphilic surfactant, was used to achieve stable primary ITZ nanocrystal (INc) suspensions for spray freeze drying. A series of microparticles were prepared, and the dandelion-like structure was successfully achieved. The effects of feed liquid compositions and freezing parameters on the microparticle size, morphology, surface energy, crystal properties and in vitro aerosol performance were systematically investigated. The optimal sample (SF (-50) D-INc 7 Leu 3 -2) in one-way experiment showed the highest fine particle fraction of ∼ 68.96 % and extra fine particle fraction of ∼ 36.87 %, equivalently ∼ 4.60 mg and ∼ 2.46 mg could reach the lung and alveoli, respectively, when inhaling 10 mg dry powders. The response surface methodology (RSM) analysis provided the optimized design space for fabricating microparticles with higher deep lung deposition performance. This study demonstrates the advantages of AeDPI microparticle with dandelion-like structure on promoting the delivery efficiency of high-dose drug to the deep lung., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Our purpose was to test the hypothesis that ultrasonic cigarettes (u-cigarettes), which operate at relatively low temperatures, produce aerosols that are less harmful than heated-coil pod-style electronic cigarettes (e-cigarettes). The major chemicals in SURGE u-cigarette fluids and aerosols were quantified, their cytotoxicity and cellular effects were assessed, and a Margin of Exposure risk assessment was performed on chemicals in SURGE fluids. Four SURGE u-cigarette flavor variants ("Blueberry Ice," "Watermelon Ice," "Green Mint," and "Polar Mint") were evaluated. Flavor chemicals were quantified in fluids and aerosols using gas chromatography/mass spectrometry. Cytotoxicity and cell dynamics were assessed using the MTT assay, live-cell imaging, and fluorescence microscopy. WS-23 (a coolant) and total flavor chemical concentrations in SURGE were similar to e-cigarettes, while SURGE nicotine concentrations (13-19 mg/mL) were lower than many fourth generation e-cigarettes. Transfer efficiencies of dominant chemicals to aerosols in SURGE ranged from 44-100%. SURGE fluids and aerosols had four dominant flavor chemicals (>1 mg/mL). Toxic aldehydes were usually higher in SURGE aerosols than in SURGE fluids. SURGE fluids and aerosols had aldehyde concentrations significantly higher than pod-style e-cigarettes. Chemical constituents, solvent ratios, and aldehydes varied among SURGE flavor variants. SURGE fluids and aerosols inhibited cell growth and mitochondrial reductases, produced attenuated and round cells, and depolymerized actin filaments, effects that depended on pod flavor, chemical constituents, and concentration. The MOEs for nicotine, WS-23, and propylene glycol were <100 based on consumption of 1-2 SURGE u-cigarettes/day. Replacing the heating coil with a sonicator did not eliminate chemicals, including aldehydes, in aerosols or diminish toxicity in comparisons between SURGE and other e-cigarette pod products. The high concentrations of nicotine, WS-23, flavor chemicals, and aldehydes and the cytotoxicity of SURGE aerosols do not support the hypothesis that aerosols from u-cigarettes are less harmful than those from e-cigarettes.

Nicotine salt-based e-liquids deliver nicotine more rapidly and efficiently to electronic nicotine delivery system (ENDS) users than freebase nicotine formulations. Nicotine salt-based products represent a substantial majority of the United States ENDS market. Despite the popularity of nicotine salt formulations, the chemical and physical characteristics of aerosols produced by nicotine salt e-liquids are still not well understood. To address this, this study reports the harmful and potentially harmful constituents (HPHCs) and particle sizes of aerosols produced by laboratory-made freebase nicotine and nicotine salt e-liquids. The nicotine salt e-liquids were formulated with benzoic acid, citric acid, lactic acid, malic acid, or oxalic acid. The nicotine salt aerosols had different HPHC profiles than the freebase nicotine aerosols, indicating that the carboxylic acids were not innocent bystanders. The polycarboxylic acid e-liquids containing citric acid, malic acid, or oxalic acid produced higher acrolein yields than the monocarboxylic acid e-liquids containing benzoic acid or lactic acid. Across most PG:VG ratios, nicotine benzoate or nicotine lactate aerosols contained the highest nicotine quantities (in %) and the highest nicotine yields (per milligram of aerosol). Additionally, the nicotine benzoate and nicotine lactate e-liquids produced the highest carboxylic acid yields under all tested conditions. The lower acid yields of the citric, malic, and oxalic acid formulations are potentially due to a combination of factors such as lower transfer efficiencies, lower thermostabilities, and greater susceptibility to side reactions because of their additional carboxyl groups serving as new sites for reactivity. For all nicotine formulations, the particle size characteristics were primarily controlled by the e-liquid solvent ratios, and there were no clear trends between nicotine salt and freebase nicotine aerosols that indicated nicotine protonation affected particle size. The carboxylic acids impacted aerosol output, nicotine delivery, and HPHC yields in distinct ways such that interchanging them in ENDS can potentially cause downstream effects.

Nanoparticle formation by Spark Discharge Aerosol Generation offers low-cost fabrication of nanoparticles, without the use of chemicals or vacuum. It produces aerosol particles of a few nanometers in size with high purity. In this work, copper-based -CuO (tenorite) and Cu- nanoparticles are produced, characterized and used to modify face mask air filters, achieving the introduction of antibacterial and antiviral properties. A range of characterization techniques have been employed, down to the atomic level. The majority of the particles are CuO (of a few nanometers in size that agglomerate to form aggregates), the remainder being a small number of larger Cu particles. The particles were deposited on various substrates, mainly fiber filters in order to study them and use them as biocidal agents. On face masks, their antibacterial activity against Escherichia coli (E.coli) results in a 100 % decrease in bacteria cell viability. Their antiviral activity on face masks results in a 90 % reduction of the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) viability, 15 minutes post the application of the virus stock solution. This highlights the effectiveness of this approach, its simplicity, its low cost and its excellent environmental credentials., (© 2024 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

Previous in vitro toxicological assessments have demonstrated that almost no mutagenic and genotoxic activities in electronic cigarette (e-cigarette) and heated tobacco product (HTP) aerosols were detected even at the maximum recommended concentration. To accurately compare the toxicity levels between cigarette smoke and e-cigarette or HTP aerosols, higher exposure concentrations increasing the possibility to detect toxicity in in vitro tests are necessary, while avoiding solvent-induced toxicity. This study aimed to develop a solvent-free extraction method to obtain concentrated aerosol extracts for improved toxicological evaluation. Our novel approach involved squeezing several Cambridge filter pads, which collected aerosol constituents, in closed containers to achieve solvent-free extraction with comparable efficiency to the conventional method using organic solvents. The optimized squeezing method yielded extracts with concentrations approximately 10 times higher than those obtained in conventional extraction methods. Yield comparison of various constituents, such as flavoring compounds, in e-cigarette aerosol extracts revealed similar extraction efficiencies between the squeezing and conventional methods. However, the extraction efficiency for constituents with high log P ow values, predominantly found in HTP aerosol extracts, was unacceptably low using the squeezing method. In addition, solvent-free centrifuging, another type of extraction method, exhibited unsatisfactory results for even e-cigarette aerosols compared with the conventional method. Our findings suggest that the solvent-free squeezing method is suitable for extracting aerosol collected mass from e-cigarette aerosol but not from HTP aerosol. We anticipate that the solvent-free squeezing method will contribute to a deeper understanding of toxicological differences between e-cigarettes and conventional combustible cigarettes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tsuneo Hashizume reports financial support was provided by Japan Tobacco Inc Tobacco Science Research Center. Tsuneo Hashizume reports a relationship with Japan Tobacco Inc Tobacco Science Research Center that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

One major challenge in predicting secondary organic aerosol (SOA) formation in the atmosphere is incomplete representation of biogenic volatile organic compounds (BVOCs) emitted from plants, particularly those that are emitted as a result of stress - a condition that is becoming more frequent in a rapidly changing climate. One of the most common types of BVOCs emitted by plants in response to environmental stress are acyclic terpenes. In this work, SOA is generated from the photooxidation of acyclic terpenes in an oxidation flow reactor and compared to SOA production from a reference cyclic terpene - α-pinene. The acyclic terpenes used as SOA precursors included β-myrcene, β-ocimene, and linalool. Results showed that oxidation of all acyclic terpenes had lower SOA yields measured after 4 days photochemical age, in comparison to α-pinene. However, there was also evidence that the condensed organic products that formed, while a smaller amount overall, had a higher oligomeric content. In particular, β-ocimene SOA had higher oligomeric content than all the other chemical systems studied. SOA composition data from ultra-high performance liquid chromatography with electrospray ionization mass spectrometry (UHPLC-ESI-MS) was combined with mechanistic modeling using the Generator for Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) to explore chemical mechanisms that could lead to this oligomer formation. Calculations based on composition data suggested that β-ocimene SOA was more viscous with a higher glass transition temperature than other SOA generated from acyclic terpene oxidation. This was attributed to a higher oligomeric content compared to other SOA systems studied. These results contribute to novel chemical insights about SOA formation from acyclic terpenes and relevant chemistry processes, highlighting the importance of improving underrepresented biogenic SOA formation in chemical transport models.

Electronic cigarettes (ECs) emit many toxic substances, including metals, that can pose a threat to users and the environment. The toxicity of the emitted metals depends on their oxidation states. Hence, this study examines the oxidation states of metals observed in EC aerosols. X-ray photoelectron spectroscopy analysis of the filters that collected EC aerosols identified the oxidation states of five primary metals (based on surface sample analysis), including chromium(III) (close to 100%) under low power setting while a noticeable amount of chromium(VI) (15%) at higher power settings of the EC, and copper(II) (100%), zinc(II) (100%), nickel(II) (100%), lead(II) (65%), and lead(IV) (35%) regardless of power settings. This observation indicates that the increased temperature due to higher power settings could alter the oxidation states of certain metals. We noted that many metals were in their lesser toxic states; however, inhaling these metals may still pose health risks.

Using respiratory protective equipment is one of the relevant preventive measures for infectious diseases, including COVID-19, and for various occupational respiratory hazards. Because experienced discomfort may result in a decrease in the utilization of respirators, it is important to enhance the material properties to resolve suboptimal usage. We combined several technologies to produce a filtration material that met requirements set by a cross-disciplinary interview study on the usability of protective equipment. Improved breathability, environmental sustainability, and comfort of the material were achieved by electrospinning poly(ethylene oxide) (PEO) nanofibers on a thin foam-formed fabric from regenerated cellulose fibers. The high filtration efficiency of sub-micron-sized diethylhexyl sebacate (DEHS) aerosol particles resulted from the small mean segment length of 0.35 μm of the nanofiber network. For a particle diameter of 0.6 μm, the filtration efficiency of a single PEO layer varied in the range of 80-97 % depending on the coat weight. The corresponding pressure drop had the level of 20-90 Pa for the airflow velocity of 5.3 cm/s. Using a multilayer structure, a very high filtration efficiency of 99.5 % was obtained with only a slightly higher pressure drop. This opens a route toward designing sustainable personal protective media with improved user experience., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

In 2012, the U.S. Food & Drug Administration (FDA) published an established list of 93 harmful and potentially harmful constituents (HPHCs) targeting four tobacco product types (cigarettes, cigarette tobacco, roll-your-own tobacco, smokeless tobacco). In 2016, the FDA finalized the deeming rule to regulate electronic nicotine delivery systems (ENDS). However, knowledge gaps exist regarding whether certain HPHCs are present in ENDS e-liquids and aerosols. We identified and addressed these gaps by conducting literature searches and then experimentally quantifying HPHCs in the e-liquid and aerosol of 37 ENDS brands based on gaps in the literature. The literature searches identified 66 e-liquid HPHCs and 68 aerosol HPHCs that have limited to no information regarding the quantifiability of these constituents. A contracted ISO 17025 accredited laboratory performed the HPHC quantifications. The availability of validated analytical methods in the contracted laboratory determined the HPHCs included in the study scope (63/66 for e-liquids, 64/68 for aerosols). Combining the results from the quantifications and literature searches, 36 (39%) and 34 (37%) HPHCs were found quantifiable (≥limit of quantification [LOQ]) in ENDS e-liquids and aerosols, respectively, with 25 HPHCs being quantifiable in both matrices. Quantifiability results imply potential HPHC transfers between matrices, leaching from components, or formations from aerosol generation. The study results can inform the scientific basis for manufacturers and regulators regarding regulatory requirements for HPHC reporting. The HPHC quantities can also inform evaluations of the public health impact of ENDS and public communications regarding ENDS health risks.

Fentanyl is an extremely potent opioid that is commonly laced into other drugs. Fentanyl poses a danger to users but also to responders or bystanders who may unknowingly ingest a lethal dose (∼2 mg) of fentanyl from aerosolized powder or vapor. Electrochemistry offers a small, simple, and affordable platform for the direct detection of illicit substances; however, it is largely limited to solution-phase measurements. Here, we demonstrate the hands-free capture and electroanalyzation of aerosols containing fentanyl. A novel electrochemical cell is constructed by a microwire (cylindrical working electrode) traversing an ionic liquid film that is suspended within a conductive loop (reference/counter electrode). We provide a quantitative finite element simulation of the resulting electrochemical system. The suspended film maintains a high-surface area:volume, allowing the electrochemical cell to act as an effective aerosol collector. The low vapor pressure (negligible evaporation) of ionic liquid makes it a robust candidate for in-field applications, and the use of a hydrophobic ionic liquid allows for the extraction of fentanyl from solids and sprayed aqueous aerosols.

This study evaluated the health-related weighted ultraviolet radiation (UVR) due to the total ozone content (TOC) and the aerosol optical depth (AOD) changes. Clear-sky Ultraviolet Index (UVI), daily doses, and exposure times for erythema induction (D ery and T ery ) and vitamin D synthesis (D vitD and T vitD ) were computed by a radiative transfer estimator. TOC and AOD data were provided by six Earth System Models (ESMs) from the Coupled Model Intercomparison Project Phase 6 (CMIP6). For projections, we consider four Shared Socioeconomic Pathways scenarios-SSPs (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5)-and two time-slices (near: 2041-2060 and far future: 2081-2100). UVR projections showed pronounced changes for the summer hemispheres in the far future. TOC increases in mid- and high latitudes of the Southern Hemisphere caused decreases in UVR at the summer solstice. However, projections did not indicate sun-safe exposure conditions in South America, Australia, and Southern Africa. On the contrary, exposure around solar noon from 10 to 20 min will still be sufficient to induce erythema in skin type III individuals throughout this century. In southern Argentina and Chile, the UVR insufficiency for vitamin D synthesis at solar noon in skin type III remains the same during this century at the winter solstice. In the Northern Hemisphere, UVI and D ery at the summer solstice should remain high (UVI ≥ 8; D ery  ~ 7.0 kJ m -2 ) in highly populated locations. Above 45 °N, UVR levels cannot be enough to synthesize vitamin D in skin type III during the boreal winter. Our results show that climate change will affect human health through excess or lack of solar UVR availability., (© 2024. The Author(s), under exclusive licence to the European Photochemistry Association, European Society for Photobiology.)

Reconstituted tobacco (RT) is a product made by reprocessing tobacco waste, experiencing a growing demand for heat-not-burn products. The purpose of this study is to analyze the main flavor ingredients in RT aerosol, as well as the transfer behavior of key flavor substances from substrates to aerosol and the concentrations of these compounds in the substrate after heating. First, we demonstrated that the odor of four RT aerosol samples could be distinguished using an electronic nose. Through non-targeted analysis, 93 volatile compounds were detected by gas chromatography-mass spectrometry, and 286 non/semi-volatile compounds were identified by ultra-high-performance liquid electrophoresis chromatography-mass spectrometry in aerosol. Furthermore, we found that the formation of RT aerosol involves primarily evaporation and distillation, however, the total content delivered from unheated RT samples to aerosol remains relatively low due to compound volatility and cigarette filtration. Thermal reactions during heating indicated the pyrolysis of chlorogenic acid to generate catechol and resorcinol, while Maillard reactions involving glucose and proline produced 2,3-dihydro-3,5-dihydroxy-6-methyl-4h-pyran-4-one. The study highlighted that heating RT at approximately 300°C could mitigate the production of harmful substances while still providing a familiar sensory experience with combusted tobacco., (© 2024 Wiley‐VCH GmbH.)

Health and security concerns have made it essential to develop integrated, continuous collection and sensing platforms that are compact and capable of real-time detection. In this study, we numerically investigate the flow physics associated with the single-step collection and enrichment of aerosolized polystyrene microparticles into a flowing liquid using a stratified air-water flow in a U-shaped microchannel. We validate our simulation results by comparing them to experimental data from the literature. Additionally, we fabricate an identical microfluidic device using PDMS-based soft lithography and test it to corroborate the previously published experimental data. Diversion and entrapment efficiencies are used as evaluation metrics, both of which increase with increasing particle diameter and superficial air inlet velocity. Overall, our ANSYS Fluent two-dimensional (2D) and three-dimensional (3D) multiphase flow simulations exhibit a good agreement with our experimental data and data in the literature (average deviation of ∼11%) in terms of diversion efficiency. Simulations also found the entrapment efficiency to be lower than the diversion efficiency, indicating discrepancies in the literature in terms of captured particles. The effect of the Dean force on the flow physics was also investigated using 3D simulations. We found that the effect of the Dean flow was more dominant relative to the centrifugal force on the smaller particles (e.g., 0.65 μm) compared to the larger particles (e.g., 2.1 μm). Increasing the superficial air inlet velocity also increases the effect of the centrifugal forces relative to the Dean forces. Overall, this experimentally validated multiphase model decouples and investigates the multiple and simultaneous forces on aerosolized particles flowing through a curved microchannel, which is crucial for designing more efficient capture devices. Once integrated with a microfluidic-based biosensor, this stratified flow-based microfluidic biothreat capture platform should deliver continuous sensor-ready enriched biosamples for real-time sensing.

Lateral flow assays (LFAs) are currently the most popular point-of-care diagnostics, rapidly transforming disease diagnosis from expensive doctor checkups and laboratory-based tests to potential on-the-shelf commodities. Yet, their sensitive element, a monoclonal antibody, is expensive to formulate, and their long-term storage depends on refrigeration technology that cannot be met in resource-limited areas. In this work, LCB1 affibodies (antibody mimetic miniproteins) were conjugated to bovine serum albumin (BSA) to afford a high-avidity synthetic capture (LCB1-BSA) capable of detecting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and virus like particles (VLPs). Substituting the monoclonal antibody 2B04 for LCB1-BSA (stable up to 60 °C) significantly improved the thermal stability, shelf life, and affordability of plasmonic-fluor-based LFAs (p-LFAs). Furthermore, this substitution significantly improved the sensitivity of p-LFAs toward the spike protein and VLPs with precise quantitative ability over 2 and 3 orders of magnitude, respectively. LCB1-BSA sensors could detect VLPs at 100-fold lower concentrations, and this improvement, combined with their robust nature, enabled us to develop an aerosol sampling technology to detect aerosolized viral particles. Synthetic captures like LCB1-BSA can increase the ultrasensitivity, availability, sustainability, and long-term accuracy of LFAs while also decreasing their manufacturing costs.

The production of e-cigarette aerosols through vaping processes is known to cause the formation of various free radicals and reactive oxygen species (ROS). Despite the well-known oxidative potential and cytotoxicity of fresh vaping emissions, the effects of chemical aging on exhaled vaping aerosols by indoor atmospheric oxidants are yet to be elucidated. Terpenes are commonly found in e-liquids as flavor additives. In the presence of indoor ozone (O 3 ), e-cigarette aerosols that contain terpene flavorings can undergo chemical transformations, further producing ROS and reactive carbonyl species. Here, we simulated the aging process of the e-cigarette emissions in a 2 m 3 FEP film chamber with 100 ppbv of O 3 exposure for an hour. The aged vaping aerosols, along with fresh aerosols, were collected to detect the presence of ROS. The aged particles exhibited 2- to 11-fold greater oxidative potential, and further analysis showed that these particles formed a greater number of radicals in aqueous conditions. The aging process induced the formation of various alkyl hydroperoxides (ROOH), and through iodometric quantification, we saw that our aged vaping particles contained significantly greater amounts of these hydroperoxides than their fresh counterparts. Bronchial epithelial cells exposed to aged vaping aerosols exhibited an upregulation of the oxidative stress genes, HMOX-1 and GSTP1 , indicating the potential for inhalation toxicity. This work highlights the indirect danger of vaping in environments with high ground-level O 3 , which can chemically transform e-cigarette aerosols into new particles that can induce greater oxidative damage than fresh e-cigarette aerosols. Given that the toxicological characteristics of e-cigarettes are mainly associated with the inhalation of fresh aerosols in current studies, our work may provide a perspective that characterizes vaping exposure under secondhand or thirdhand conditions as a significant health risk.

Secondary aerosols constitute a significant fraction of atmospheric aerosols, yet our understanding of their formation mechanism and fate is very limited. In this work, the secondary organic aerosol (SOA) formation and aging of ambient air of Delhi are studied using a potential aerosol mass (PAM) reactor, an oxidation flow reactor (OFR), coupled with aerosol chemical speciation monitor (ACSM), proton transfer reaction time of flight mass spectrometer (PTR-ToF-MS), and scanning mobility particle sizer with counter (SMPS + C). The setup mimics atmospheric aging of up to several days with the generation of OH radicals. Variations in primary volatile organic compounds (VOCs) and oxygenated volatile organic compounds (OVOCs) as a function of photochemical age were investigated. Primary VOCs such as benzene, toluene, xylene, trimethyl benzene, etc. decrease and OVOCs like formic acid, formaldehyde, acetone, ethanol, etc. increase substantially upon oxidation in OFR. The highest organic aerosol (OA) enhancement was observed for the 4.2 equivalent photochemical days of aging i.e., 1.84 times the ambient concentration, and net OA loss was observed at very high OH exposure, typically after 8.4 days of photochemical aging due to heterogeneous oxidation followed by fragmentation/evaporation. In ambient air, OA enhancement is highest during nighttime due to the high concentrations of precursor VOCs in the atmosphere. SMPS + C results demonstrated substantial new particle formation upon aging and decrement in preexisting aerosol mass. This is the first experimental study conducting an in-situ evaluation of potential SOA mass generated from the ambient aerosols in India., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Oily particles pollution poses a tremendous threat to people's health, so it is urgent to develop air filtration materials with the ability of removing fine oily particles effectively. In this study, a nylon 6 multi-stage structured nanofiber membrane (PA6 MSNM) for effective air filtration of fine oily particles was designed and fabricated by adding a certain amount of tetrabutylammonium hexafluorophosphate (TBAHP) via one-step electrospinning. The PA6 MSNMs were composed of coarse trunk fibres and fine branching fibres. Benefiting from the properties of small pore size and high porosity, the resulting PA6 MSNMs exhibited high average filtration efficiency of 99.80% for oily aerosol particles of 0.20-4.59 μm, a low pressure drop of 251 Pa, and the high quality factor of 0.0248 Pa -1 . More importantly, its filtration efficiencies for oily aerosol particles of 0.25 and 0.30 μm were up to 99.99% and 100.00%, respectively. It is expected that the multi-stage electrospun nanofiber membranes would have wide application prospects in air filtration, particularly for filtering oily particles.

Layer-by-Layer (LbL) assembly of polyelectrolytes on a solid core particle is a well-established technique used to deliver drugs, proteins, regenerative medicines, combinatorial therapy, etc. It is a multifunctional delivery system which can be engineered using various core template particles and coating polymers. This study reports the development and in-vitro evaluation of LbL assembled particles for non-invasive inhaled delivery to the lungs. The LbL assembled particles were prepared by successively coating polyelectrolyte macromolecules, glycol chitosan and bovine serum albumin on 0.5- and 4.5-μm polystyrene particles. The LbL assembly of polyelectrolytes was confirmed by reversible change in zeta potential and sequential increase in the particle size after accumulation of the layer. The prepared LbL particles were further assessed for aerodynamic properties using two distinct nebulizers, and toxicity assessment in normal lung cells. The in-vitro aerosolization study performed using next generation impactor coupled with Pari LC Plus and Aeroeclipse nebulizer showed that both the LbL assembled 0.5 and 4.5-μm particles had MMAD <5 μm confirming suitable aerodynamic properties for non-invasive lung delivery. The in-vitro cytotoxicity, and TEER integrity following treatment with the LbL assembled particles in normal lung epithelial and fibroblasts showed no significant cytotoxicity rendering the LbL assembled particles safe. This study extends the efficiency of LbL assembled particles for novel applications towards delivery of small and large molecules into the lungs., Competing Interests: Declaration of competing interest All authors declare no conflict of interest in this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nitrogen dioxide (NO 2 ) hydrolysis in deliquesced aerosol particles forms nitrous acid and nitrate and thus impacts air quality, climate, and the nitrogen cycle. Traditionally, it is considered to proceed far too slowly in the atmosphere. However, the significance of this process is highly uncertain because kinetic studies have only been made in dilute aqueous solutions but not under high ionic strength conditions of the aerosol particles. Here, we use laboratory experiments, air quality models, and field measurements to examine the effect of the ionic strength on the reaction kinetics of NO 2 hydrolysis. We find that high ionic strengths ( I ) enhance the reaction rate constants ( k I ) by more than an order of magnitude compared to that at infinite dilution ( k I =0 ), yielding log 10 ( k I / k I =0 ) = 0.04 I or rate enhancement factor = 10 0.04 I . A state-of-the-art air quality model shows that the enhanced NO 2 hydrolysis reduces the negative bias in the simulated concentrations of nitrous acid by 28% on average when compared to field observations over the North China Plain. Rapid NO 2 hydrolysis also enhances the levels of nitrous acid in other polluted regions such as North India and further promotes atmospheric oxidation capacity. This study highlights the need to evaluate various reaction kinetics of atmospheric aerosols with high ionic strengths.

The aging process of atmospheric aerosols usually leads to a mixture of inorganic salts and organic compounds of anthropogenic origin. In organic compounds, polyhydroxy organic acids are important components, however, the study on composition and hygroscopic properties of the mixture containing inorganics and polyhydroxy organic acids is scanty. In this study, gluconic acid, the proxy of polyhydroxy organic acids, is mixed with the representative nitrate (Mg(NO 3 ) 2 , Ca(NO 3 ) 2 ) to form aerosols. ATR-FTIR and optical microscopy are employed to study the component changes and hygroscopicity as a function of relative humidity. As relative humidity fluctuates, the FTIR-ATR spectra display that the internal mixed gluconic acid (CH 2 (CH) 4 (OH) 5 COOH) and nitrate can react to release acidic gases, forming relevant gluconate and further affecting the hygroscopicity. The specific presentation is particles cannot be recovered to their original size after the dehydration-hydration process and there will be some disparities in GF for mixed particles. For the gluconic acid-Ca(NO 3 ) 2 /Mg(NO 3 ) 2 mixtures with molar ratios of 1:1, higher degree of reaction resulting in the production of large amounts of gluconate should be responsible to the lower hygroscopicity compared to ZSR model. For 1:2 gluconic acid-nitrate mixed systems (with higher nitrate content), the hygroscopicity of mixtures are higher than the ZSR prediction. A possible reason could be 'salt-promoting effect' on the organic fractions of the surplus inorganic salt in the mixture. These data can improve the chemical composition list evaluation, in turn hygroscopic properties and phase state of atmospheric aerosol, and then the climate effect., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Leveraging the extensive surface area of the lungs for gene therapy, the inhalation route offers distinct advantages for delivery. Clinical nebulizers that employ vibrating mesh technology are the standard choice for converting liquid medicines into aerosols. However, they have limitations when it comes to delivering mRNA through inhalation, including severe damage to nanoparticles due to shearing forces. Here, we introduce a microfluidic aerosolization platform (MAP) that preserves the structural and physicochemical integrity of lipid nanoparticles, enabling safe and efficient delivery of mRNA to the respiratory system. Our results demonstrated the superiority of the MAP over the conventional vibrating mesh nebulizer, as it avoided problems such as particle aggregation, loss of mRNA encapsulation, and deformation of the nanoparticle morphology. Notably, aerosolized nanoparticles generated by the microfluidic device led to enhanced transfection efficiency across various cell lines. In vivo experiments with mice that inhaled these aerosolized nanoparticles revealed successful lung-specific mRNA transfection without observable signs of toxicity. This MAP may represent an advancement for the pulmonary gene therapy, enabling precise and effective delivery of aerosolized nanoparticles.

The potential of fine excipient materials to improve the aerodynamic performance of carrier-based dry powder inhalation (DPI) formulations is well acknowledged but not fully elucidated. To improve the understanding of this potential, we studied two fine excipient materials: micronized lactose particles and silica microspheres. Inhalation formulations, each composed of a coarse lactose carrier, one of the two fine excipient materials (0.0-15.0 % w/w), and a spray-dried drug (fluticasone propionate) material (1.5 % w/w) were prepared. The physical structure, the flow behavior, the aerosolization behavior, and the aerodynamic performance of the formulations were studied. The two fine excipient materials similarly occupied carrier surface macropores. However, only the micronized lactose particles formed agglomerates and appeared to increase the tensile strength of the formulations. At 2.5 % w/w, the two fine excipient materials similarly improved drug dispersibility, whereas at higher concentrations, the micronized lactose material was more beneficial than the silica microspheres. The findings suggest that fine excipient materials improve drug dispersibility from carrier-based DPI formulations at low concentrations by filling carrier surface macropores and at high concentrations by forming agglomerates and/or enforcing fluidization. The study emphasizes critical attributes of fine excipient materials in carrier-based DPI formulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this work, we have investigated the mechanism, thermochemistry and kinetics of the reaction of syn - cis -CH 2 R z CR y CO + O - (where R z , R y = H, CH 3 -) unsaturated Criegee intermediates (CIs) with CF 3 COOH using quantum chemical methods. The rate coefficients for the barrierless reactions were calculated using variable reaction coordinate variational transition state theory (VRC-VTST). For the syn - cis -CH 2 R z CR y CO + O - conformation in which conjugated CC and CO double bonds are aligned with each other, we propose a new pathway for the unidirectional addition of an OC-OH molecule (CF 3 COOH) to the CC double bond of syn - cis -CH 2 R z CR y CO + O - . The rate coefficient for the 1,4-CC addition reaction at 298 K is ∼10 -10 to 10 -11 cm 3 s -1 , resulting in the formation of CF 3 C(O)OCH 2 CR z R y COOH trifluoroacetate alkyl allyl hydroperoxide (TFAAAH) as a new transitory adduct. It can act as a precursor for the formation of secondary organic aerosols (SOAs). This novel TFAAAH hydroperoxide was identified through a detailed quantum chemical study of the 1,4-addition mechanism and will provide new insights into the significance of the 1,4-addition reaction of unsaturated Cls with trace tropospheric gases on -CR z CH 2 vinyl carbon atoms.

Respiratory viruses, such as influenza and severe acute respiratory syndrome coronavirus 2, represent a substantial public health burden and are largely transmitted through respiratory droplets and aerosols. Environmental factors such as relative humidity (RH) and temperature impact virus transmission rates, and a precise mechanistic understanding of the connection between these environmental factors and virus transmission would improve efforts to mitigate respiratory disease transmission. Previous studies on supermicrometer particles observed RH-dependent phase transitions and linked particle phase state to virus viability. Phase transitions in atmospheric aerosols are dependent on size in the submicrometer range, and actual respiratory particles are expelled over a large size range, including submicrometer aerosols that can transmit diseases over long distances. Here, we directly investigated the phase transitions of submicrometer model respiratory aerosols. A probe molecule, Nile red, was added to particle systems including multiple mucin/salt mixtures, a growth medium, and simulated lung fluid. For each system, the polarity-dependent fluorescence emission was measured following RH conditioning. Notably, the fluorescence measurements of mucin/NaCl and Dulbecco's modified Eagle's medium particles indicated that liquid-liquid phase separation (LLPS) also occurs in submicron particles, suggesting that LLPS can also impact the viability of viruses in submicron particles and thus affect aerosol virus transmission. Furthermore, the utility of fluorescence-based measurements to study submicrometer respiratory particle physicochemical properties in situ is demonstrated.

The majority of commercially available monoclonal antibody (mAb) formulations are stabilized with one of three non-ionic surfactants: polysorbate 20 (PS20), polysorbate 80 (PS80), or poloxamer 188 (P188). All three surfactants are susceptible to degradation, which can result in functionality loss and subsequent protein aggregation or free fatty acid particle formation. Consequently, quantitative, and qualitative analysis of surfactants is an integral part of formulation development, stability, and batch release testing. Due to the heterogeneous nature of both polysorbates and poloxamer, online isolation of all the compounds from the protein and other excipients that may disturb the subsequent liquid chromatography with charged aerosol detection (LC-CAD) analysis poses a challenge. Herein, we present an analytical method employing LC-CAD, utilizing a combination of anion and cation exchange columns to completely remove proteins online before infusing the isolated surfactant onto a reversed-phase column. The method allows high throughput analysis of polysorbates within 8 minutes and poloxamer 188 within 12 minutes, providing a separation of the surfactant species of polysorbates (unesterified species, lower esters, and higher esters) and poloxamer 188 (early eluters and main species). Accuracy and precision assessed according to the International Council for harmonisation (ICH) guideline were 96 - 109 % and ≤1 % relative standard deviation respectively for all three surfactants in samples containing up to 110 mg/mL mAb. Subsequently, the method was effectively applied to quantify polysorbate 20 and polysorbate 80 in nine commercial drug products with mAb concentration of up to 180 mg/mL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Multidrug-resistant tuberculosis (MDR-TB) has posed a serious threat to global public health, and antimicrobial peptides (AMPs) have emerged to be promising candidates to tackle this deadly infectious disease. Previous study has suggested that two AMPs, namely D-LAK120-A and D-LAK120-HP13, can potentiate the effect of isoniazid (INH) against mycobacteria. In this study, the strategy of combining INH and D-LAK peptide as a dry powder formulation for inhalation was explored. The antibacterial effect of INH and D-LAK combination was first evaluated on three MDR clinical isolates of Mycobacteria tuberculosis (Mtb). The minimum inhibitory concentrations (MICs) and fractional inhibitory concentration indexes (FICIs) were determined. The combination was synergistic against Mtb with FICIs ranged from 0.25 to 0.38. The INH and D-LAK peptide at 2:1 mole ratio (equivalent to 1: 10 mass ratio) was identified to be optimal. This ratio was adopted for the preparation of dry powder formulation for pulmonary delivery, with mannitol used as bulking excipient. Spherical particles with mass median aerodynamic diameter (MMAD) of around 5 µm were produced by spray drying. The aerosol performance of the spray dried powder was moderate, as evaluated by the Next Generation Impactor (NGI), with emitted fraction and fine particle fraction of above 70 % and 45 %, respectively. The circular dichroism spectra revealed that both D-LAK peptides retained their secondary structure after spray drying, and the antibacterial effect of the combination against the MDR Mtb clinical isolates was successfully preserved. The combination was found to be effective against MDR Mtb isolates with KatG or InhA mutations. Overall, the synergistic combination of INH with D-LAK peptide formulated as inhaled dry powder offers a new therapeutic approach against MDR-TB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Both latent and multidrug-resistant tuberculosis (TB) have been causing significant concern worldwide. A novel drug, pretomanid (PA-824), has shown a potent bactericidal effect against both active and latent forms of Mycobacterium tuberculosis (MTb) and a synergistic effect when combined with pyrazinamide and moxifloxacin. This study aimed to develop triple combination spray dried inhalable formulations composed of antitubercular drugs, pretomanid, moxifloxacin, and pyrazinamide (1:2:8 w/w/w), alone (PaMP) and in combination with an aerosolization enhancer, L-leucine (20 % w/w, PaMPL). The formulation PaMPL consisted of hollow, spherical, dimpled particles (<5 μm) and showed good aerosolization behaviour with a fine particle fraction of 70 %. Solid-state characterization of formulations with and without L-leucine confirmed the amorphous nature of moxifloxacin and pretomanid and the crystalline nature of pyrazinamide with polymorphic transformation after the spray drying process. Further, the X-ray photoelectron spectroscopic analysis revealed the predominant surface composition of L-leucine on PaMPL dry powder particles. The dose-response cytotoxicity results showed pyrazinamide and moxifloxacin were non-toxic in both A549 and Calu-3 cell lines up to 150 µg/mL. However, the cell viability gradually decreased to 50 % when the pretomanid concentration increased to 150 µg/mL. The in vitro efficacy studies demonstrated that the triple combination formulation had more prominent antibacterial activity with a minimum inhibitory concentration (MIC) of 1 µg/mL against the MTb H37Rv strain as compared to individual drugs. In conclusion, the triple combination of pretomanid, moxifloxacin, and pyrazinamide as an inhalable dry powder formulation will potentially improve treatment efficacy with fewer systemic side effects in patients suffering from latent and multidrug-resistant TB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Dispersing Multi-Walled Carbon Nanotubes (MWCNTs) into concrete at low (<1 wt% in cement) concentrations may improve concrete performance and properties and provide enhanced functionalities. When MWCNT-enhanced concrete is fragmented during remodelling or demolition, the stiff, fibrous and carcinogenic MWCNTs will, however, also be part of the respirable particulate matter released in the process. Consequently, systematic aerosolizing of crushed MWCNT-enhanced concretes in a controlled environment and measuring the properties of this aerosol can give valuable insights into the characteristics of the emissions such as concentrations, size range and morphology. These properties impact to which extent the emissions can be inhaled as well as where they are expected to deposit in the lung, which is critical to assess whether these materials might constitute a future health risk for construction and demolition workers. In this work, the impact from MWCNTs on aerosol characteristics was assessed for samples of three concrete types with various amounts of MWCNT, using a novel methodology based on the continuous drop method. MWCNT-enhanced concretes were crushed, aerosolized and the emitted particles were characterized with online and offline techniques. For light-weight porous concrete, the addition of MWCNT significantly reduced the respirable mass fraction (RESP) and particle number concentrations (PNC) across all size ranges (7 nm - 20 μm), indicating that MWCNTs dampened the fragmentation process by possibly reinforcing the microstructure of brittle concrete. For normal concrete, the opposite could be seen, where MWCNTs resulted in drastic increases in RESP and PNC, suggesting that the MWCNTs may be acting as defects in the concrete matrix, thus enhancing the fragmentation process. For the high strength concrete, the fragmentation decreased at the lowest MWCNT concentration, but increased again for the highest MWCNT concentration. All tested concrete types emitted <100 nm particles, regardless of CNT content. SEM imaging displayed CNTs protruding from concrete fragments, but no free fibres were detected., Competing Interests: Declaration of competing interest: No competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Recently, extreme wildfires occur frequently around the world and emit substantial brown carbon (BrC) into the atmosphere, whereas the molecular compositions and photochemical evolution of BrC remain poorly understood. In this work, primary smoke aerosols were generated from wood smoldering, and secondary smoke aerosols were formed by the OH radical photooxidation in an oxidation flow reactor, where both primary and secondary smoke samples were collected on filters. After solvent extraction of filter samples, the molecular composition of dissolved organic carbon (DOC) was determined by Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS). The molecular composition of dissolved BrC was obtained based on the constraints of DOC formulae. The proportion of dissolved BrC fractions accounted for approximately 1/3-1/2 molecular formulae of DOC. The molecular characteristics of dissolved BrC showed higher levels of carbon oxidation state, double bond equivalents, and modified aromaticity index than those of DOC, indicating that dissolved BrC fractions were a class of organic structures with relatively higher oxidation state, unsaturated and aromatic degree in DOC fractions. The comparative analysis suggested that aliphatic and olefinic structures dominated DOC fractions (contributing to 70.1%-76.9%), while olefinic, aromatic, and condensed aromatic structures dominated dissolved BrC fractions (contributing to 97.5%-99.9%). It is worth noting that dissolved BrC fractions only contained carboxylic-rich alicyclic molecules (CRAMs)-like structures, unsaturated hydrocarbons, aromatic structures, and highly oxygenated compounds. CRAMs-like structures were the most abundant species in both DOC and dissolved BrC fractions. Nevertheless, the specific molecular characteristics for DOC and dissolved BrC fractions varied with subgroups after aging. The results highlight the similarities and differences in the molecular compositions and characteristics of DOC and dissolved BrC fractions with aging. This work will provide insights into understanding the molecular composition of DOC and dissolved BrC in smoke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

To ensure the high quality of biopharmaceutical products, it is imperative to implement specialized unit operations that effectively safeguard the structural integrity of large molecules. While lyophilization has long been a reliable process, spray drying has recently garnered attention for its particle engineering capabilities for the pulmonary route of administration. However, maintaining the integrity of biologics during spray drying remains a challenge. To address this issue, we explored a novel dehydration system based on aerosol-assisted room-temperature drying of biological formulations recently developed at Princeton University, called Rapid Room-Temperature Aerosol Dehydration. We compared the quality attributes of the bulk powder of biopharmaceutical products manufactured using this drying technology with that of traditional spray drying. For all the fragment antigen-binding formulations tested, in terms of protein degradation and aerosol performance, we were able to achieve a better product quality using this drying technology compared to the spray drying technique. We also highlight areas for improvement in future prototypes and prospective commercial versions of the system. Overall, the offered dehydration system holds potential for improving the quality and diversity of biopharmaceutical products and may pave the way for more efficient and effective production methods in the biopharma industry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Smoking-related diseases remain a significant public health concern, and heated tobacco products (HTPs) have emerged as a potential alternative to cigarettes. While several studies have confirmed that HTP aerosols contain lower levels of harmful and potentially harmful constituents (HPHCs) than cigarette smoke, less is known about constituents that are intrinsically higher in HTP aerosols. This study provides a comprehensive comparative assessment of an HTP aerosol produced with Tobacco Heating System 2.2 (THS) and comparator cigarette (CC) smoke aiming at identifying all unique or increased compounds in THS aerosol by applying a broad set of LC-MS and GC × GC-MS methods. To focus on differences due to heating versus burning tobacco, confounding factors were minimized by using the same tobacco in both test items and not adding flavorants. Of all analytical features, only 3.5%-corresponding to 31 distinctive compounds-were significantly more abundant in THS aerosol than in CC smoke. A notable subset of these compounds was identified as reaction products of glycerol. The only compound unique to THS aerosol was traced back to its presence in a non-tobacco material in the test item and not a direct product of heating tobacco. Our results demonstrate that heating a glycerol-containing tobacco substrate to the temperatures applied in THS does not introduce new compounds in the resulting aerosol compared to CC smoke which are detectable with the method portfolio applied in this study. Overall, this study contributes to a better understanding of the chemical composition of HTP aerosols and their potential impact on human health., (© 2024. The Author(s).)

Frequent outbreaks of viral diseases have brought substantial negative impacts on society and the economy, and they are very difficult to detect, as the concentration of viral aerosols in the air is low and the composition is complex. The traditional detection method is manually collection and re-detection, being cumbersome and time-consuming. Here we propose a virus aerosol detection method based on microfluidic inertial separation and spectroscopic analysis technology to rapidly and accurately detect aerosol particles in the air. The microfluidic chip is designed based on the principles of inertial separation and laminar flow characteristics, resulting in an average separation efficiency of 95.99% for 2 μm particles. We build a microfluidic chip composite spectrometer detection platform to capture the spectral information on aerosol particles dynamically. By employing machine-learning techniques, we can accurately classify different types of aerosol particles. The entire experiment took less than 30 min as compared with hours by PCR detection. Furthermore, our model achieves an accuracy of 97.87% in identifying virus aerosols, which is comparable to the results obtained from PCR detection.

Alkene ozonolysis can produce stabilized Criegee intermediates (SCIs), which play a key role in oligomers' formation. Though styrene and isoprene coexist in the ambient atmosphere as important anthropogenic and biogenic secondary organic aerosol (SOA) precursors, respectively, their cross-reactions have not received attention. This study investigated the interactions of SCIs from styrene and isoprene ozonolysis for the first time. The high-resolution Orbitrap mass spectrometer was used to determine the unique ion mass spectra of the isoprene-styrene-O 3 mixture. The results show that the signal intensities of new ions account for >8.4% of total ions in the mass spectra of the styrene-isoprene-O 3 mixed system. Styrene and isoprene ozonolysis can produce characteristic C 7 -SCI and C 4 -SCI, respectively. C 7 -SCI and C 4 -SCI can be involved in the cross-reactions, and the results of tandem mass spectra directly confirmed both C 7 -SCI and C 4 -SCI as chain units. The O/C and H/C ratios of cross-products are in the range of 0.38-1.07 and 1.00-1.50, respectively, which are consistent with cross-reaction products. Adding a C 7 -SCI unit reduces the oligomer's volatility by 1.3-1.4 orders of magnitude lower than adding a C 4 -SCI unit. Thus, C 4 -SCI can compete with C 7 -SCI to react with styrene-derived RO 2 /RC(O)OH to produce more volatile cross-products, while the less volatile cross-products can be formed when isoprene-derived RO 2 /RC(O)OH reacted with C 7 -SCI instead of C 4 -SCI. The SOA yield of the mixed system is lower than that of the single styrene-O 3 system but higher than that of the single isoprene-O 3 system. Ambient particles were also collected, and 5 possible SCI-related cross-products were identified. This study illustrates the effects of SCI-related cross-reactions on SOA components and physicochemical properties, providing a basis for future research on SCI-related cross-reactions that frequently occur in the ambient atmosphere., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Sea-salt aerosols (SSA) are one of the key natural aerosols in our atmosphere, consisting predominantly of sodium chloride (NaCl). Throughout their atmospheric transport, these aerosols undergo complex internal mixing, giving rise to a rich variety of inorganic and organic species, including dicarboxylic acids. This study investigates firstly the composition and deliquescence properties of coarse particles containing pure malonic acid (MA 2 , CH 2 (COOH) 2 ) and internally mixed NaCl and MA 2 , by means of an acoustic levitation system coupled with a Raman microspectrometer. Secondly, we report here the first experimental observation and characterization of the products arising from photochemical reactions under UV-Visible irradiation (338 ≤ λ ≤ 414 nm) in the absence of an oxidant under acoustic levitation conditions in MA 2 and NaCl/MA 2 aerosols. Furthermore, the impact of photodegradation on the hygroscopic properties of these particles is examined. We confirmed the irreversible formation of monosodium malonate (NaMA, HOOCCH 2 COONa), which coexists with NaCl or MA 2 on non-irradiated particles. We also demonstrated the formation of oxalic acid (OA 2 , HOOC-COOH) within irradiated MA 2 droplets and the appearance of glyoxylic acid (GlyA, HCOCOOH) in NaCl containing droplets. The photolysis process exerts a marked effect on the hygroscopic properties of the particles, resulting in a shift in deliquescence transitions toward higher relative humidity (RH) values. This study contributes to the understanding of the intricate physicochemical processes involved in SSA during their atmospheric transport. Likewise, this work sheds light on the impacts of these types of aerosols on cloud formation and climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Mineral aerosol particles significantly impact environmental risk prediction of liquid crystal monomers (LCMs). In this work, we investigated the reaction mechanisms and kinetics of three typical LCMs (4-cyano-3,5-difluorophenyl 4-ethylbenzoate (CEB-2F), 4-cyano-3-fluorophenyl 4-ethylbenzoate (CEB-F), and 4-cyanophenyl 4-ethylbenzoate (CEB)) with ozone (O 3 ) in the atmospheric gas, liquid, and particle phases employing density functional theory (DFT). Here, O 3 is prone to add to the benzene ring without F atom(s) in the selected LCMs. The ozonolysis products are aldehydes, carboxylic acids, epoxides, and unsaturated hydrocarbons containing aromatic rings. Those products undergo secondary ozonolysis to generate small molecular compounds such as glyoxal, which is beneficial for generating secondary organic aerosol (SOA). Titanium dioxide (TiO 2 ), an essential component of mineral aerosol particles, has good adsorption properties for LCMs; however, it slightly reduces the reactivity with O 3 . At 298 K, the reaction rate constant of the selected LCMs reacting with O 3 in the gas and atmospheric liquid phases is (2.74‒5.53) × 10 -24 cm 3 /(mol·sec) and 5.58 × 10 -3 ‒39.1 L/(mol·sec), while CEB-2F reacting with O 3 on (TiO 2 ) 6 cluster is 1.84 × 10 -24 cm 3 /(mol·sec). The existence of TiO 2 clusters increases the persistence and long-distance transportability of LCMs, which enlarges the contaminated area of LCMs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Pulmonary delivery of protein-based therapeutics, including antibodies, is a promising option for treating respiratory diseases. Spray drying is a widely used method for producing dry powder formulations with mannitol being a commonly used excipient for these inhalation formulations. There is limited research available concerning the utilization of mannitol as an excipient in the spray drying of proteins and its impact on aerosol performance. This study highlights the importance to understand mannitol's potential role and impact in this context. To investigate the impact of mannitol on physical stability and aerosolization of spray-dried protein formulations, bovine serum albumin (BSA) was employed as a model protein and formulated with different concentrations of mannitol via spray drying. The spray-dried solids were characterized for their particle size using Malvern mastersizer and aerodynamic particle size using next generation impactor (NGI). Additionally, the solids were characterized with solid-state Fourier-transform infrared spectroscopy (ssFTIR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and solid-state nuclear magnetic resonance spectroscopy (ssNMR) to analyze the change in their secondary structure, crystallinity, particle morphology, and protein-excipient interaction, respectively. Size exclusion chromatography (SEC) was used to investigate changes in monomer content resulting from storage under stressed condition of 40 °C. Protein formulations containing more than 33 % mannitol by weight showed crystallization tendencies, causing an increase in monomer loss over time. ssNMR data also showed mixing heterogeneity of BSA and mannitol in the formulations with high mannitol contents. Futhermore, fine particle fraction (FPF) was found to decrease over time for the formulations containing BSA: Mannitol in the ratios of 2:1, 1:2, and 1:5, due to particle agglomeration induced by crystallization of mannitol. This study underscores the significant influence of excipients such as mannitol on the aerosol performance and storage stability of spray-dried protein formulations., Competing Interests: Declaration of competing interest Eric Munson is a partial owner of Kansas Analytical Services, a company that provides solid state NMR service to the pharmaceutical industry. All data here was collected at Purdue University., (Copyright © 2023 Elsevier B.V. All rights reserved.)