Identification of pyruvic and maleic acid as potential markers for disease activity and prognosis in chronic urticaria.

BACKGROUND: Population-based studies have highlighted the link between chronic urticaria (CU) and metabolic syndrome, and metabolic alterations have been revealed in CU. However, to our knowledge, a comprehensive metabolomics study on a large cohort of patients with CU has not been reported. OBJECTIVE: We sought to explore the underlying metabolic subtypes and novel metabolite biomarkers for CU diagnosis and therapy. METHODS: Plasma samples from 80 patients with CU and 82 healthy controls were collected for metabolomics quantification and bioinformatics analysis. Another independent cohort consisting of 144 patients with CU was studied to validate the findings. Bone marrow-derived mast cells and mice with IgE-induced passive cutaneous anaphylaxis were used for in vitro and in vivo experiments, respectively. RESULTS: We observed clear metabolome differences between CU patients and healthy controls. Meanwhile, differential metabolites N6-acetyl-l-lysine, l-aspartate, maleic acid, and pyruvic acid were used to construct random forest classifiers and achieved area under receiver operating characteristic curve values greater than 0.85, suggesting their potential as diagnostic biomarkers of CU. More importantly, by exploring the underlying metabolic subtypes of CU, we found that the low abundance of pyruvic acid and maleic acid was significantly related to the activity of CU, poor efficacy of second-generation H1 antihistamines, and short relapse-free time. The results were validated in the independent cohort. Moreover, supplementation with pyruvate or maleate could significantly attenuate IgE-mediated mast cell activation in vitro and in vivo. CONCLUSIONS: Plasma pyruvic acid and maleic acid may be effective biomarkers for predicting disease activity, therapeutic efficacy, and prognosis for patients with CU.

Differential Toxicity of Electronic Cigarette Aerosols Generated from Different Generations of Devices In Vitro and In Vivo.

Electronic cigarettes (e-cigs) have become increasingly popular, especially among youth, raising concerns about their potential health risks. JUUL and Tank devices are two common types of e-cigs that deliver aerosols with varying nicotine levels and flavors. However, the differences in the aerosols generated from different devices and their corresponding cytotoxicity and pulmonary injury effects remain poorly understood. This study addresses these knowledge gaps by characterizing the aerosols of JUUL and Tank e-cig devices and testing their toxic effects on THP-1 and BEAS-2B human cell lines as well as the C57BL/6J mouse model. In our study, the lower-voltage device, the 3.7 V JUUL generates 2.72 mg/puff aerosols by using e-liquid containing 3% nicotine salt (i.e., nicotine benzoate), which is less than the 11.06 mg/puff aerosols generated by the 7.5 V Tank using e-liquid containing 2.4% freebase nicotine. Yet, the cytotoxicity results reveal that JUUL aerosols induced higher toxicity and increased production of pro-inflammation cytokines compared to Tank aerosols per puff. Additionally, we observed that JUUL induced more severe pulmonary inflammation and DNA damage compared to Tank after normalizing for cotinine, a nicotine metabolite, in vivo. Our findings suggest that the device design plays a more important role in e-cig aerosol-induced toxicity than the composition of the e-liquid or voltage. These results provide valuable insights into the health risks associated with various electronic-cig devices and offer an approach for evaluating them.

Environmental justice analysis of wildfire-related PM2.5 exposure using low-cost sensors in California.

The increasing number and severity of wildfires is negatively impacting air quality for millions of California residents each year. Community exposure to PM2.5 in two main population centers (San Francisco Bay area and Los Angeles County area) was assessed using the low-cost PurpleAir sensor network for the record-setting 2020 California wildfire season. Estimated PM2.5 concentrations in each study area were compared to census tract-level environmental justice vulnerability indicators, including environmental, health, and demographic data. Higher PM2.5 concentrations were positively correlated with poverty, cardiovascular emergency department visits, and housing inequities. Sensors within 30 km of actively burning wildfires showed statistically significant increases in indoor (~800 %) and outdoor (~540 %) PM2.5 during the fires. Results indicate that wildfire emissions may exacerbate existing health disparities as well as the burden of pollution in disadvantaged communities, suggesting a need to improve monitoring and adaptive capacity among vulnerable populations.

Integrative lipidomic features identify plasma lipid signatures in chronic urticaria.

Chronic urticaria (CU) is a chronic inflammatory skin disease mainly mediated by mast cells. Lipids exert essential functions in biological processes; however, the role of lipids in CU remains unclear. Nontargeted lipidomics was performed to investigate the differential lipid profiles between CU patients and healthy control (HC) subjects. Functional validation studies were performed in vitro and in vivo including ß-hexosaminidase release examination from mast cells and passive cutaneous anaphylaxis (PCA) mouse model. We detected dramatically altered glycerophospholipids in CU patients compared with HCs. Phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) were increased, while phosphatidylcholine (PC) was reduced in CU patients. The reduction in PC was related to a high weekly urticaria activity score (UAS7), while PS was positively associated with the dermatology life quality index (DLQI). We also identified the differential lipid profiles between chronic spontaneous urticaria (CSU), symptomatic dermographism (SD), and CSU coexist with SD. CU patients were classified into two subtypes (subtype 1 and subtype 2) based on consensus clustering of lipid profiling. Compared with patients in subtype 2, patients in subtype 1 had elevated levels of PC (18:0e/18:2) and PE (38:2), and lower urticaria control test (UCT) scores indicated worse clinical efficiency of secondary generation H1 antihistamines treatment. Importantly, we found that supplementation with PC could attenuate IgE-induced immune responses in mast cells. In general, We described the landscape of plasma lipid alterations in CU patients and provided novel insights into the role of PC in mast cells.

Pharmacogenomics for the efficacy and side effects of antihistamines.

Antihistamines, especially H1 antihistamines, are widely used in the treatment of allergic diseases such as urticaria and allergic rhinitis, mainly for reversing elevated histamine and anti-allergic effects. Antihistamines are generally safe, but some patients experience adverse reactions, such as cardiotoxicity, central inhibition and anticholinergic effects. There are also individual differences in antihistamine efficacy in clinical practice. The concept of individualized medicine has been deeply rooted in people's minds since it was put forward. Pharmacogenomics is the study of the role of inheritance in individual variations in drug response. In recent decades, pharmacogenomics has been developing rapidly, which provides new ideas for individualized medicine. Polymorphisms in the genes encoding metabolic enzymes, transporters and target receptors have been shown to affect the efficacy of antihistamines. In addition, recent evidence suggests that gene polymorphisms influence urticaria susceptibility and antihistamine therapy. Here, we summarize current reports in this area, aiming to contribute to future research in antihistamines and clinical guidance for antihistamines use in individualized medicine.

Efficacy and Safety of Dupilumab in Chinese Patients With Atopic Dermatitis: A Real-World Study.

Background: Atopic dermatitis (AD) is a common skin disease, but treatment of this disease has been challenging. Dupilumab is a new biological agent for AD that has been proven to be safe and effective in clinical trials. Although dupilumab was approved for listing in China in June 2020, real-world data about the application of dupilumab in China are lacking. This study aimed to collect and analyze real-world data on dupilumab among Chinese AD patients. Methods: Demographic and clinical data for 116 AD patients receiving dupilumab treatment were reviewed. The Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) of patients were evaluated every 2 weeks from baseline to 16 weeks of treatment. Any adverse events during treatment were recorded. Results: Among the 116 patients in this study, baseline levels of IgE, eosinophils, and LDH were elevated in 62.79% (n = 86), 45.30% (n = 86), and 54.20% of patients (n = 48), respectively. The SCORAD index and POEM, DLQI, and NRS scores were significantly improved in all patients at 2 weeks (p < 0.0001), 4 weeks (p < 0.01), and 16 weeks (p < 0.001). EASI scores also improved significantly in all patients at 2 weeks (p < 0.01), 4 weeks (> 0.05), and 16 weeks (p < 0.01). However, 11 patients (9.48%) had no response. IgE and LDH levels (p > 0.05), Eosinophil counts (p < 0.01) in blood increased temporarily in the first 4 weeks and then decreased and stabilized during dupilumab treatment. Conjunctivitis was the most common adverse event (2.59%) among the patients. We found that the curative efficacy of dupilumab at 4th weeks was related to the patient's age and course of disease. Nevertheless, there is no relationship between levels of eosinophils, IgE, LDH and the therapeutic efficacy of dupilumab. Conclusion: The real-world data in China showed that dupilumab can effectively treat AD and is well tolerated with a low incidence of adverse events.

Characterization of exhaled e-cigarette aerosols in a vape shop using a field-portable holographic on-chip microscope.

The past decade marked a drastic increase in the usage of electronic cigarettes. The adverse health impact of secondhand exposure due to exhaled e-cig particles has raised significant concerns, demanding further research on the characteristics of these particles. In this work, we report direct volatility measurements on exhaled e-cig aerosols using a field-portable device (termed c-Air) enabled by deep learning and lens-free holographic microscopy; for this analysis, we performed a series of field experiments in a vape shop where customers used/vaped their e-cig products. During four days of experiments, we periodically sampled the indoor air with intervals of ~ 16 min and collected the exhaled particles with c-Air. Time-lapse inline holograms of the collected particles were recorded by c-Air and reconstructed using a convolutional neural network yielding phase-recovered microscopic images of the particles. Volumetric decay of individual particles due to evaporation was used as an indicator of the volatility of each aerosol. Volatility dynamics quantified through c-Air experiments showed that indoor vaping increased the percentage of volatile and semi-volatile particles in air. The reported methodology and findings can guide further studies on volatility characterization of indoor e-cig emissions.

Dynamic Imaging and Characterization of Volatile Aerosols in E-Cigarette Emissions Using Deep Learning-Based Holographic Microscopy.

Various volatile aerosols have been associated with adverse health effects; however, characterization of these aerosols is challenging due to their dynamic nature. Here, we present a method that directly measures the volatility of particulate matter (PM) using computational microscopy and deep learning. This method was applied to aerosols generated by electronic cigarettes (e-cigs), which vaporize a liquid mixture (e-liquid) that mainly consists of propylene glycol (PG), vegetable glycerin (VG), nicotine, and flavoring compounds. E-cig-generated aerosols were recorded by a field-portable computational microscope, using an impaction-based air sampler. A lensless digital holographic microscope inside this mobile device continuously records the inline holograms of the collected particles. A deep learning-based algorithm is used to automatically reconstruct the microscopic images of e-cig-generated particles from their holograms and rapidly quantify their volatility. To evaluate the effects of e-liquid composition on aerosol dynamics, we measured the volatility of the particles generated by flavorless, nicotine-free e-liquids with various PG/VG volumetric ratios, revealing a negative correlation between the particles' volatility and the volumetric ratio of VG in the e-liquid. For a given PG/VG composition, the addition of nicotine dominated the evaporation dynamics of the e-cig aerosol and the aforementioned negative correlation was no longer observed. We also revealed that flavoring additives in e-liquids significantly decrease the volatility of e-cig aerosol. The presented holographic volatility measurement technique and the associated mobile device might provide new insights on the volatility of e-cig-generated particles and can be applied to characterize various volatile PM.

Experimental study on microstructure and mechanical properties of stalk for Glycyrrhiza Glabra.

In this paper, a year-old stalk of Glycyrrhiza glabra was used as the research object. The electronic universal testing machine was used to test the mechanical properties of shearing and bending. The microstructure of the stalk of Glycyrrhiza glabra was observed with a microscope. Mechanical test research indicated that the shearing process included an elastic phase, a yield phase, and a plastic deformation phase. The bending process was divided into elastic deformation stage and plastic deformation stage. In addition, the shearing force, shearing energy, bending force and bending energy all increased with the increase in diameter. As the water content increased, the shearing force and bending force decreased at first, reached the minimum when the water content was about 45%, and then had an upward trend. The shearing energy increased with the water content, and the bending energy, decreased with the water content. The two test factors were statistically significant for both shearing and bending properties. The microscopic test results showed that the phloem, fiber, and pith constitute the microstructure of the licorice stalk. The linear regression model could reflect the correlation between the cross-sectional area of each part and the shearing force and bending force (P < 0.05). Through analysis, it was concluded that the change of the cross-sectional area of the stalk microstructure had an important influence on the mechanical properties of shearing and bending. The results can provide theoretical basis for the design of Glycyrrhiza Glabra stalk harvesting, crushing and processing equipment.

Electronic cigarette aerosols induce oxidative stress-dependent cell death and NF-κB mediated acute lung inflammation in mice.

Electronic cigarette (e-cigarette) use has been linked to recent acute lung injury case clusters in over 2000 patients and dozens of deaths in the United States, however, the mechanism leading to lung injury is not certain although ultrafine particles, heavy metals, volatile organic compounds, and other harmful ingredients have been implicated. To systematically evaluate e-cigarette toxicity, we generated e-cigarette aerosols by varying the puff numbers (20-480), nicotine contents (0-24 mg/mL), and collected e-cigarette samples through an impinger system for biological assays. The calculated samples' concentration ranged from 1.96 to 47.06 mg/mL. THP-1 monocyte-differentiated macrophages, BEAS-2B bronchial epithelial cells, wild-type C57BL/6 mice, and NF-κB-luc transgenic mice were used to test the effects of these samples. E-cigarette samples showed cytotoxicity to THP-1 cells and BEAS-2B in vitro, leading to increased oxidative stress, inflammatory cytokine production with or without nicotine, and cell death. Furthermore, aerosol generated from PG is more toxic than VG. The toxicity of e-cigarette samples is at least partially due to the reactive oxygen species and aldehydes, which are generated during the aerosolization processes by the e-cigarette device. After NF-κB-luc mice exposed with e-cigarette samples by oropharyngeal aspiration, NF-κB expressions were observed in a dose-response fashion with or without nicotine. In addition, the e-cigarette samples induced neutrophil infiltration, IL-1ß production, oxidative stress marker heme oxygenase-1 expression in wild-type C57BL/6 mice. These results suggested that oxidative stress, pro-inflammatory NF-κB pathway activation, and cell death are involved in e-cigarette aerosol-induced acute lung inflammation.

Impacts of electronic cigarettes usage on air quality of vape shops and their nearby areas.

With the rapid growth of the electronic cigarette (e-cig) market, there is an increasing number of vape shops that exclusively sell e-cigs. The use of e-cigs in the vape shop is a primary source of indoor particles, which might transport to its nearby indoor spaces in the multiunit setting. In this study, six pairs of vape shops and neighboring businesses in Southern California were recruited for real-time measurements of particulate pollutants between February 2017 and October 2019. The mean (SD) particle number concentration (PNC) and PM2.5 concentration in the studied vape shops were 2.8 × 104 (2.3 × 104) particles/cm3 and 276 (546) µg/m3, which were substantially higher than those in neighboring businesses and outdoor areas. In addition, 24-h time-weighted average (TWA) nicotine sampling was conducted in the six pairs and three additional pairs. Nicotine was detected in the air of all the studied vape shops and neighboring businesses, in which the mean (SD) concentration was 2.59 (1.02) and 0.17 (0.13) µg/m3, respectively. Inside vape shops, the dilution-corrected vaping density (puffs/h/100 m3) is a strong predictor of the particle concentration, and nicotine concentration highly depends on the air exchange rate (AER). Out of the six studied pairs, PNCs in five vape shops and PM2.5 in two vape shops were significantly correlated with those in their neighboring businesses. This correlation was stronger when the door of the vape shop was closed. When the door was open, environmental electronic vaping (EEV) aerosols, especially smaller particles, could transport from the vape shop to the outdoor environment. Overall, e-cig usage in the vape shop impacts both its own and nearby air quality, raising concerns regarding the risk of exposure to EEV aerosols in the surrounding environments.

Effects of propylene glycol, vegetable glycerin, and nicotine on emissions and dynamics of electronic cigarette aerosols.

An electronic cigarette (e-cig) generates aerosols by vaporizing the e-liquid, which mainly consists of propylene glycol (PG), vegetable glycerin (VG), and nicotine. Understanding the effects of e-liquid main compositions on e-cig aerosols is important for exposure assessment. This study investigated how the PG/VG ratio and nicotine content affect e-cig aerosol emissions and dynamics. A tank-based e-cig device with 10 different flavorless e-liquid mixtures (e.g., PG/VG ratios of 0/100, 10/90, 30/70, 50/50, and 100/0 with 0.0% or 2.4% nicotine) was used to puff aerosols into a 0.46 m3 stainless steel chamber for 0.5 h. Real-time measurements of particle number concentration (PNC), fine particulate matter (PM2.5), and particle size distributions were conducted continuously throughout the puffing and the following 2-h decay period. During the decay period, particle loss rates were determined by a first-order log-linear regression and used to calculate the emission factor. The addition of nicotine in the e-liquid significantly decreased the particle number emission factor by 33%. The PM2.5 emission factor significantly decreased with greater PG content in the e-liquid. For nicotine-free e-liquids, increasing the PG/VG ratio resulted in increased particle loss rates measured by PNC and PM2.5. This pattern was not observed with nicotine in the e-liquids. The particle loss rates, however, were significantly different with and without nicotine especially when the PG/VG ratios were greater than 30/70. Compared with nonvolatile diethyl-hexyl subacute (DEHS) aerosols, e-cig particle concentration decayed faster inside the chamber, presumably due to evaporation. These results have potential implications for assessing human exposure to e-cig aerosols.

Effects of Electronic Cigarettes on Indoor Air Quality and Health.

With the rapid increase in electronic cigarette (e-cig) users worldwide, secondhand exposure to e-cig aerosols has become a serious public health concern. We summarize the evidence on the effects of e-cigs on indoor air quality, chemical compositions of mainstream and secondhand e-cig aerosols, and associated respiratory and cardiovascular effects. The use of e-cigs in indoor environments leads to high levels of fine and ultrafine particles similar to tobacco cigarettes (t-cigs). Concentrations of chemical compounds in e-cig aerosols are generally lower than those in t-cig smoke, but a substantial amount of vaporized propylene glycol, vegetable glycerin, nicotine, and toxic substances, such as aldehydes and heavy metals, has been reported. Exposures to mainstream e-cig aerosols have biologic effects but only limited evidence shows adverse respiratory and cardiovascular effects in humans. Long-term studies are needed to better understand the dosimetry and health effects of exposures to secondhand e-cig aerosols.

Enhanced electrokinetic remediation of lead-contaminated soil by complexing agents and approaching anodes.

Optimizing process parameters that affect the remediation time and power consumption can improve the treatment efficiency of the electrokinetic remediation as well as determine the cost of a remediation action. Lab-scale electrokinetic remediation of Pb-contaminated soils was investigated for the effect of complexant ethylenediaminetetraacetic acid (EDTA) and acetic acid and approaching anode on the removal efficiency of Pb. When EDTA was added to the catholyte, EDTA dissolved insoluble Pb in soils to form soluble Pb-EDTA complexes, increasing Pb mobility and accordingly removal efficiency. The removal efficiency was enhanced from 47.8 to 61.5 % when the EDTA concentration was increased from 0.1 to 0.2 M, showing that EDTA played an important role in remediation. And the migration rate of Pb was increased to 72.3 % when both EDTA and acetic acid were used in the catholyte. The "approaching anode electrokinetic remediation" process in the presence of both EDTA and acetic acid had a higher Pb-removal efficiency with an average efficiency of 83.8 %. The efficiency of electrokinetic remediation was closely related to Pb speciation. Exchangeable and carbonate-bounded Pb were likely the forms which could be removed. All results indicate that the approaching anode method in the presence of EDTA and acetic acid is an advisable choice for electrokinetic remediation of Pb-contaminated soil.