Arecoline-Induced Hepatotoxicity in Rats: Screening of Abnormal Metabolic Markers and Potential Mechanisms.

Arecoline is a pyridine alkaloid derived from areca nut in the Arecaceae family. It has extensive medicinal activity, such as analgesic, anti-inflammatory, and anti-allergic. However, the toxicity of Arecoline limits its application. Most current studies on its toxicity mainly focus on immunotoxicity, carcinogenesis, and cancer promotion. However, there are few systematic studies on its hepatotoxicity and mechanisms. Therefore, this research explored the mechanism of hepatotoxicity induced by Arecoline in rats and analyzed endogenous metabolite changes in rat plasma by combining network toxicology with metabolomics. The differential metabolites after Arecoline exposure, such as D-Lysine, N4-Acetylaminobutanal, and L-Arginine, were obtained by metabolomics study, and these differential metabolites were involved in the regulation of lipid metabolism, amino acid metabolism, and vitamin metabolism. Based on the strategy of network toxicology, Arecoline can affect the HIF-1 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and other concerning pathways by regulating critical targets, such as ALB, CASP3, EGFR, and MMP9. Integration of metabolomics and network toxicology results were further analyzed, and it was concluded that Arecoline may induce hepatotoxicity by mediating oxidative stress, inflammatory response, energy and lipid metabolism, and cell apoptosis.

Assessment of meteorological and air quality drivers of elevated ambient ozone in Beijing via machine learning approach.

Over the past few years, surface ozone (O3) pollution has dominated China's air pollution as particulate matter has decreased. In Beijing, the annual average concentrations of ground-level O3 from 2015 to 2020 regularly increased from 57.32 to 62.72 µg/m3, showing a change of almost 9.4%, with a 1.6% per year increase. The meteorological factors are the primary influencer of elevated O3 levels; however, their importance and heterogeneity of variables remain rarely understood. In this study, we used 13 meteorological factors and 6 air quality (AQ) parameters to estimate their influencing score using the random forest (RF) algorithm to explain and predict ambient O3. Among the meteorological variables and overall, both land surface temperature and temperature at 2 m from the surface emerged as the most influential factors, while NO2 stood out as the highest influencing factor from the AQ parameters. Indeed, it is crucial and imperative to reduce the temperature caused by climate change in order to effectively control ambient O3 levels in Beijing. Overall, meteorological factors alone exhibited a higher coefficient of determination (R2) value of 0.80, compared with AQ variables of 0.58, for the post-lockdown period. In addition, we calculated the number of days O3 concentration levels exceeded the WHO standard and newly proposed peak-season maximum daily 8-h average (MDA8) O3 guideline for Beijing. The exceedance number of days from the WHO standard of MDA8 ambient O3 was observed to be the highest in June, and each studied year crossed peak season guidelines by almost 2 times margin. This study demonstrates the contributions of meteorological variables and AQ parameters in surging ambient O3 and highlights the importance of future research toward devising an optimum strategy to combat growing O3 pollution in urban areas.

Numerical Investigation on Protective Mechanism of Metal Cover Plate for Alumina Armor against Impact of Fragment by FE-Converting-SPH Method.

It is of extreme importance to develop a reliable numerical prediction technique to simulate the ballistic response of ceramic armor subjected to high-velocity impact (HVI) to economize the test cost and shorten the design period. In the present manuscript, a series of experiments on tungsten heavy alloy (WHA) fragment's penetration into 99.5% alumina (AD995) armors are systematically simulated by employing the FE-converting-SPH technique. The numerical results are compared with the experimental counterparts to find that the FE-converting-SPH method is fairly efficient in predicting the depth of penetration, the residual velocity, length and mass of fragment, and reproducing the crack forms of ceramic. The applicability and accuracy of the numerical model in terms of the algorithm, material model parameters and contact definitions are validated. Then, the relevant parameters of the calibrated numerical model are incorporated to explore the influence of cover-layer thickness on the armor performance. A few mechanisms regarding the cover plate have been identified to act on the armor performance, such as the alteration of fracture cone half-angle, proportion of energy absorbed by ceramic, mushrooming deformation of fragment, etc. The result of multi-mechanism superposition is that the best ballistic performance is endued with 1 mm cover-layer armor, which demonstrates a 24.6% improvement over the bi-layer armor with 4.96 g/cm2 area density, only at the cost of 15.7% increase in areal density, when back-plate thickness is held as 2 mm; for a constant area density of 4.96 g/cm2, a 1 mm cover-layer is also expected to be the best choice, with 10.7% improvement in armor performance.

A model to evaluate ozone distribution and reaction byproducts in aircraft cabin environments.

Ozone and byproducts of ozone-initiated reactions are among the primary pollutants in aircraft cabins. However, investigations of the spatial distribution and reaction mechanisms of these pollutants are insufficient. This study established a computational fluid dynamics-based model to evaluate ozone and byproduct distribution, considering ozone reactions in air, adsorption onto surfaces, and byproduct desorption from surfaces. The model was implemented in an authentic single-aisle aircraft cabin and validated by measurements recorded during the aircraft cruise phase. Ozone concentrations in the supply air-dominated area were approximately 50% higher than that in the passenger breathing zone, suggesting that human surfaces represent a significant ozone sink. The deposition velocity onto human bodies was 21.83 m/h, surpassing 3.97 m/h on other cabin interior surface areas. Our model provides a mechanistic tool to analyze ozone and byproduct concentration distributions, which would be useful for assessing passenger health risks and for developing strategies for healthier aircraft cabin environments.

Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network.

Mesaconitine (MA), one of the main diterpenoid alkaloids in Aconitum, has a variety of pharmacological effects, such as analgesia, anti-inflammation and relaxation of rat aorta. However, MA is a highly toxic ingredient. At present, studies on its toxicity are mainly focused on the heart and central nervous system, and there are few reports on the hepatotoxic mechanism of MA. Therefore, we evaluated the effects of MA administration on liver. SD rats were randomly divided into a normal saline (NS) group, a low-dose MA group (0.8 mg/kg/day) and a high-dose MA group (1.2 mg/kg/day). After 6 days of administration, the toxicity of MA on the liver was observed. Metabolomic and network toxicology methods were combined to explore the effect of MA on the liver of SD rats and the mechanism of hepatotoxicity in this study. Through metabonomics study, the differential metabolites of MA, such as L-phenylalanine, retinyl ester, L-proline and 5-hydroxyindole acetaldehyde, were obtained, which involved amino acid metabolism, vitamin metabolism, glucose metabolism and lipid metabolism. Based on network toxicological analysis, MA can affect HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway and FoxO signal pathway by regulating ALB, AKT1, CASP3, IL2 and other targets. Western blot results showed that protein expression of HMOX1, IL2 and caspase-3 in liver significantly increased after MA administration (p < 0.05). Combined with the results of metabonomics and network toxicology, it is suggested that MA may induce hepatotoxicity by activating oxidative stress, initiating inflammatory reaction and inducing apoptosis.

Identification of key volatile organic compounds in aircraft cabins and associated inhalation health risks.

The identification of key VOCs during flights is important in creating a satisfactory aircraft cabin environment. Two VOC databases for the building indoor environment (from 251 occupied residences) and the aircraft cabin environment (from 56 commercial flights) were compared, to determine the common compounds (detection rate (DR) > 70%) in the two environments and the characteristic VOCs (only those with high DR during flights) in aircraft cabins. Possible VOC emission sources in flights were also discussed. As TVOC is usually viewed as a general indicator of air quality, the prediction of TVOC concentration was carried out using BP neural network algorithm, and the average error between the predicted and measured values was 55.35 µg/m3 (R2 = 0.80). Meanwhile, the VOCs' inhalation cancer/non-cancer risks to crew members and passengers were calculated on the basis of detection rates, exposure concentrations, and health risk assessments. Six compounds (i.e., formaldehyde, benzene, tetrachloroethylene, trichloromethane, 1,2-dichloroethane, and naphthalene) were proposed as the key VOCs in the existing aircraft cabin environment, presenting a risk to crew members that is higher than the US EPA proposed acceptable level (evaluated mean value > 1E-06). The estimated lifetime excess cancer/non-cancer risks for passengers were all below the assessment criteria. Based on a summary of various VOC limits in five built environments, hierarchical design of VOC concentration limits is recommended for the aircraft environment.

Effect of deep eutectic solvents-regulated lignin structure on subsequent pyrolysis products selectivity.

The chemical structure of lignin has an important effect on the lignin pyrolysis product distributions. Therefore, it is of great significance to regulate the selectivity of pyrolysis products by modifying the lignin structure. Herein, deep eutectic solvents (DESs) including choline chloride/ethylene glycol (CE), zinc chloride/ethylene glycol (ZE) and choline chloride/acetic acid, treatment of softwood kraft lignin (SKL) is demonstrated. Systematic characterization indicate that the DESs are not only highly conducive to increasing the hydrogen to carbon efficient ratio, reducing the molecular weight and ß-O-4 linkage, but also contributes to the maximum degradation rate and thermal stability of SKL. Noticeably, CE and ZE treatment are significantly improved the amount of H-phenols and C-phenols derived lignin pyrolysis, respectively. In addition, DESs pretreatment are also beneficial to the increment of monomer aromatic hydrocarbons. More importantly, the CE pretreatment contributes to the improvement of bio-oil yield and decrease of char content from lignin pyrolysis.

The Molecular Mechanism of Antioxidation of Huolisu Oral Liquid Based on Serum Analysis and Network Analysis.

Huolisu Oral Liquid (HLS), a well-known traditional Chinese medicine (TCM) prescription, is an over-the-counter drug that is registered and approved by the State Food and Drug Administration (Approval No. Z51020381). HLS has been widely applied in the clinical treatment of cognitive disorders and has effects on delaying aging. The antioxidant effects of HLS are closely related to its antiaging activities, but the underlying mechanisms are unclear. In this study, the potential antioxidant ingredients of HLS were screened based on serum pharmacochemistry and network pharmacology, and the potential mechanisms involved in HLS antioxidant effects were preliminarily explored. Further, the antioxidant effects of HLS were verified by in vivo and in vitro experiments. The results showed that potential antioxidant ingredients could affect the toxic advanced glycation end products-receptor for advanced glycation end products (TAGE-RAGE) signaling, mitogen-activated protein kinase (MAPK) signaling, interleukin (IL)-17 signaling, tumor necrosis factor (TNF) signaling, toll-like receptors (TLRs), cyclic adenosine monophosphate (cAMP) signaling, hypoxia-inducible factor (HIF)-1 signaling, and other related pathways by regulating GAPDH, AKT1, TP53, MAPK1, JUN, and other associated targets. Thus, HLS may reduce inflammation, control the release of inflammatory cytokines, and regulate mitochondrial autophagy and metabolic abnormalities to ultimately play an antioxidant role. This is the first study attempting to construct a multilevel network of "HLS-antioxidant targets" based on serum pharmacochemistry and network pharmacology to explore the relationship between HLS and antioxidation and the molecular mechanisms of antioxidation combined with bioinformatics functional analysis and lays a foundation for further elucidating the antioxidant mechanisms of HLS.

Influencing factors of carbonyl compounds and other VOCs in commercial airliner cabins: On-board investigation of 56 flights.

Volatile organic compounds (VOCs) as a non-negligible aircraft cabin air quality (CAQ) factor influence the health and comfort of passengers and crew members. On-board measurements of carbonyls (short-chain (C1 -C6 )) and other volatile organic compounds (VOCs, long-chain (C6 -C16 )) with a total of 350 samples were conducted in 56 commercial airliner cabins covering 8 aircraft models in this study. The mean concentration for each individual carbonyl compound was between 0.3 and 8.3 µg/m3 (except for acrolein & acetone, average = 20.7 µg/m3 ) similar to the mean concentrations of other highly detected VOCs (long-chain (C6 -C16 ), 97% of which ranged in 0-10 µg/m3 ) in aircraft cabins. Formaldehyde concentrations in flights were significantly lower than in residential buildings, where construction materials are known formaldehyde sources. Acetone is a VOC emitted by humans, and its concentration in flights was similar to that in other high-occupant density transportation vehicles. The variation of VOC concentrations in different flight phases of long-haul flights was the same as that of CO2 concentration except for the meal phase, which indicates the importance of cabin ventilation in diluting the gaseous contaminants, while the sustained and slow growth of the VOC concentrations during the cruising phase in short-haul flights indicated that the ventilation could not adequately dilute the emission of VOCs. For the different categories of VOCs, the mean concentration during the cruising phase of benzene series, aldehydes, alkanes, other VOCs (detection rate > 50%), and carbonyls in long-haul flights was 44.2 µg/m3 , 17.9 µg/m3 , 18.6 µg/m3 , 31.5 µg/m3 , and 20.4 µg/m3  lower than those in short-haul flights, respectively. Carbonyls and d-limonene showed a significant correlation with meal service (p < 0.05). Unlike the newly decorated rooms or new vehicles, the inner materials were not the major emission sources in aircraft cabins. Practical Implications. The on-board measurements of 56 flights enrich the VOC database of cabin environment, especially for carbonyls. The literature review of carbonyls in the past 20 years contributes to the understanding the current status of cabin air quality (CAQ). The analysis of VOC concentration variation for different flight phases, flight duration, and aircraft age lays a foundation for exploring effective control methods, including ventilation and purification for cabin VOC pollution. The enriched VOC data is helpful to explore the key VOCs of aircraft cabin environment and to evaluate the acute/chronic health exposure risk of pollutants for passengers and crew members.

Carbon dioxide in passenger cabins: Spatial temporal characteristics and 30-year trends.

Carbon dioxide (CO2 ) is an important environmental parameter in aircraft cabins. To understand the most recent, real-time CO2 concentration levels and their key influencing factors in aircraft cabins, we conducted in-flight measurements of 52 randomly selected commercial flights with different aircraft types and durations from August 2017 to August 2019. The spatial temporal characteristics of CO2 concentrations on board were analyzed and summarized. For the flight time scale, the CO2 concentrations during the boarding phase (1680 ± 558 ppmv) were notably higher than that in other phases, whereas the condition of the cruising phase was the lowest in most flights. The flight average CO2 concentrations of the cruising phase were 1253 ± 164 ppmv, and the corresponding estimated outside airflow rates were 6.2 ± 1.3 L/s/p in the economy class across all flights. Single-aisle and twin-aisle flights did not show noticeable differences for the same phases. Relatively uniform CO2 concentrations were observed at different positions of the same class. By comparing the results of this study with those previously reported, CO2 concentrations showed a slightly decreasing trend over the last 30 years. This suggested a slightly increased ventilation rate and potentially superior air quality on board.

Systematically explore the potential hepatotoxic material basis and molecular mechanism of Radix Aconiti Lateralis based on the concept of toxicological evidence chain (TEC).

Radix aconiti lateralis (Fuzi) is widely used in China as a traditional Chinese medicine for the treatment of asthenia, pain and inflammation. However, its toxic alkaloids often lead to adverse reactions. Currently, most of the toxicity studies on Fuzi are focused on the heart and nervous system, and more comprehensive toxicity studies are needed. In this study, based on the previous reports of Fuzi hepatotoxicity, serum pharmacochemistry and network toxicology were used to screen the potential toxic components of Heishunpian(HSP), a processed product of Fuzi, and to explore the possible mechanism of HSP-induced hepatotoxicity. The results obtained are expressed based on the toxicological evidence chain (TEC). It was found that 22 potential toxic components screened can affect Th17 cell differentiation, Jak-STAT signaling pathway, glutathione metabolism, and other related pathways by regulating AKT1, IL2, F2, GSR, EGFR and other related targets, which induces oxidative stress, metabolic disorders, cell apoptosis, immune response, and excessive release of inflammatory factors, eventually inducing liver damage in rats. This is the first study on HSP-induced hepatotoxicity based on the TEC concept, providing references for further studies on the toxicity mechanism of Fuzi.

Effect of pre-acetylation of hydroxyl functional groups by choline chloride/acetic anhydride on subsequent lignin pyrolysis.

In this work, an emerging and efficient strategy for the preparation of lignin samples with different acetylation degree by choline chloride/acetic anhydride (ChCl/Aa) treatment of pine kraft lignin (PKL) is reported, and the effects of efficient pre-acetylation of hydroxyl functional groups on subsequent lignin pyrolysis are also systematically investigated. The results show that the ChCl/Aa displays a high acetylation efficiency towards the aliphatic hydroxyl (~99.1%) and phenolic hydroxyl (~94.0%) of PKL, which enhances the hydrogen to carbon effective ratio of PKL. Noticeably, the ChCl/Aa has a slight effect on ß-O-4 of PKL, and the acetylation of hydroxyl is beneficial for the improvement of the maximum degradation rate of PKL. In addition, the acetylation of hydroxyl is also significantly contributed to the increment of the pyrolysis bio-oil yield. Importantly, the relative content of the H-phenols obtained from acetylated lignins pyrolysis shows a positive correlation with the acetylation degree of hydroxyl.

[Evaluation of taste changes of Scutellariae Radix before and after wine-frying based on electronic ongue technology and its application in identification of Scutellariae Radix pieces].

Scutellariae Radix(Huangqin) is a well-known traditional Chinese medicine(TCM) used for the treatment of clearing heat in clinical application. It is bitter-cold by using directly, but the bitter-cold property can be relieved after wine-frying. The study of taste changes before and after wine-frying of Scutellariae Radix is of great significance in identifying Scutellariae Radix and wine-processed Scutellariae Radix and clarifying the traditional theory of wine-processing. In this experiment, 10 batches of Scutellariae Radix and wine-processed Scutellariae Radix were prepared. The contents of 5 flavonoids were determined by high performance liquid chromatography(HPLC), and principal component analysis(PCA) was performed with 5 flavonoids as variables. As a result, the contents were different in different batches of Scutellariae Radix, but Scutellariae Radix and wine-processed Scutellariae Radix could not be distinguished. Five sensory attributes(sour, salty, fresh, sweet, and bitter) were evaluated by artificial tasting, and the response values of 7 sensors(AHS, AHS, PKS, CTS, NMS, CPS, ANS, SCS) representing the taste of pieces were detected by electronic tongue. The correlation between sensory evaluation and response values of the electronic tongue were analyzed, and the results showed that the sensory evaluation of sour, salty, fresh, sweet, bitter and AHS, CTS, NMS, ANS, SCS sensors had different degrees of correlation, indicating that the electronic tongue technology can be used as an alternative to artificial taste and can serve as a means for quantifying the taste, and it can be used to evaluate the taste of TCM pieces. The taste method was used to analyze the response values of the electronic tongue, and the results showed that the bitterness of wine-processed Scutellariae Radix decreased and the salty taste increased. PCA was used to analyze taste changes before and after wine-processed Scutellariae Radix, and the results showed that taste differences between 2 pieces were divided into 2 categories. PCA loading scattering plots showed that response of saltiness and bitterness were the major factors to affect overall taste in Scutellariae Radix and wine-processed Scutellariae Radix. Based on electronic tongue response values, the Fisher discriminant model for Scutellariae Radix and wine-processed Scutellariae Radix was established, which showed that it could effectively discriminate them with a recognition rate of 100%. The experimental results showed that the electronic tongue combined with multivariate statistical analysis can be used to evaluate taste of TCM, at the same time, it could provide a fast and simple method for identifying different processed products.

Structural characterization and comparison of enzymatic and deep eutectic solvents isolated lignin from various green processes: Toward lignin valorization.

In this work, several representative green processes were developed to extract the enzymatic lignin and deep eutectic solvents (DESs) isolated lignin from corn straw. The results revealed that enzymatic lignin and DESs isolated lignin had a relatively low and homogeneous molecular weight and DESs isolated lignin shown a higher purity. Enzymatic and DESs isolated lignin showed good representativeness and similar to original herbal lignin structures accompany few aryl ether linkage cleavages and oxidation phenomenon. Among them, the subcritical CO2-assisted autohydrolysis and ChCl/Lac DESs treatment exhibited a higher severity for lignin preparation, and sequence DESs isolated lignin had a better reactivity. The ß-O-4 ether bonds and carbon-carbon bonds linkage were further broken up during the Lac and DESs sequence treatment. In short, the described processes showed practical significance for lignin extraction and potential valorization, as well as help to develop more novel strategies for the current biorefinery process.

An eight-city study of volatile organic compounds in Chinese residences: Compounds, concentrations, and characteristics.

This study conducted on-site measurements of indoor volatile organic compounds (VOCs) in 251 occupied residences in China, with multiple visits throughout a whole year. Over 1000 samples were collected for measurement of VOCs in 8 cities, covering different climate regions. Overall, the concentrations of total VOCs (TVOCs) in occupied residences are in the range of 104-1151 µg/m3, with 20% of the samples over the Chinese standard of 600 µg/m3. A higher concentration was evident in the summer (mean = 705 µg/m3) compared to other seasons, especially winter (mean = 289 µg/m3). The TVOCs of residences in areas with central heating (severe cold regions and cold regions) are generally higher than those in areas without central heating. In winter, temperature was the dominant factor, whereas in summer, the building infiltration rate was the key factor influencing the indoor TVOC levels. The TVOCs concentration was also found to be directly proportional to the city economy level. Twenty-nine VOC species with a detection frequency higher than 40% were identified in all samples. Toluene is the most common VOC, with the highest detection rate (90%). The median concentration for a single VOC was between 1 and 14 µg/m3. Aldehydes were found to be the largest contributors to total VOCs in the Chinese residential buildings (mass proportion 22%), followed by benzene series (20%), alkenes (18%), and alkanes (15%). Aldehydes, especially long-chain saturated carbonyls, are likely to be the characteristic VOCs in the Chinese dwellings, with Chinese cooking as the major emission source. In addition, n-butane/i-butane showed maximum concentration in some residences (approximately 105 µg/m3 higher than other VOCs) owing to cooking fuel.

[Concentration Levels and Impact Factors of Benzene Series in Chinese Residential Building].

From December 2016 to December 2017, the concentrations of the benzene series (benzene, toluene, xylene, and ethyl-benzene) in air were analyzed in 223 residential buildings in five climatic regions of China during different seasons. The arithmetic average concentrations of benzene, toluene, xylene, and ethyl-benzene were 6.78, 17.4, 17.68, and 9.87 µg·m-3, respectively. Indoor benzene series concentrations in China were slightly higher than that in other countries; the standard limits for indoor benzene series concentrations in China are much higher than those of other countries and organizations. Among the many factors affecting the concentration of the benzene series in the rooms, the relationship between the completion time of decoration, smoking, and cooking frequency and the concentration of benzene homologues was studied. The results showed that the concentration of toluene decreased with the prolongation of decoration time, the concentration of benzene in smoking households was higher than that in non-smoking families, and there was no direct correlation between cooking frequency and indoor concentration of the benzene series. The study provides statistical data on exposure to the benzene series in decorated homes and a discussion of setting values of relevant standards.

The effect of air change rate and temperature on phthalate concentration in house dust.

Semi-volatile organic compounds (SVOCs) are one of the main indoor pollutant categories. Six phthalates (dimethyl phthalate (DMP), diethyl phthalate (DEP), di(isobutyl) phthalate (DiBP), di(nbutyl) phthalate (DnBP), butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP)) in house dust samples were measured in forty residential apartments in Tianjin and Urumqi in four seasons throughout a year. The measured DEHP dust-phase concentration is in the range: 11.9-699.9 µg/g; and showed obvious differences in different seasons, and the maximum can be 2 times higher than minimum. The DiBP and DnBP showed similar phenomenon. The corresponding gas-phase concentration is estimated considering the influencing factors of indoor temperature, air change rate, particle concentration. Then the dust-gas partition coefficient Kd under different season was obtained through the measured dust-phase concentration and estimated gas-phase concentration. From winter to summer, because the increased temperature leads to higher emission rate, the gas-phase concentration is obviously high in spite of the higher air change rate in summer. The estimated DEHP gas-phase concentration showed obvious differences in different seasons, and the maximum can be about 2 times higher than minimum. The DiBP and DnBP showed similar phenomenon. The lower dust-phase concentration in summer is observed due to the temperature-dependency of the dust-gas partition coefficient. Therefore temperature has the greatest impact on the dust concentration, not influence via emission rate, but influences the partition coefficient Kd.