Long-term effects of chronic exposure to electronic cigarette aerosol on the cardiovascular and pulmonary system in mice: A comparative study to cigarette smoke.

Electronic cigarettes (e-cigarettes) have rapidly gained popularity as alternatives to traditional combustible cigarettes. However, their long-term health impact remains uncertain. This study aimed to investigate the effects of chronic exposure to e-cigarette aerosol (ECA) in mice compared to conventional cigarette smoke (CS) exposure. The mice were exposed to air (control), low, medium, or high doses of ECA, or a reference CS dose orally and nasally for eight months. Various cardiovascular and pulmonary assessments have been conducted to determine the biological and prosthetic effects. Histopathological analysis was used to determine structural changes in the heart and lungs. Biological markers associated with fibrosis, inflammation, and oxidative stress were investigated. Cardiac proteomic analysis was applied to reveal the shared and unique protein expression changes in ECA and CS groups, which related to processes such as immune activation, lipid metabolism, and intracellular transport. Overall, chronic exposure to ECA led to adverse cardiovascular and pulmonary effects in mice, although they were less pronounced than those of CS exposure. This study provides evidence that e-cigarettes may be less harmful than combustible cigarettes for the long-term health of the cardiovascular and respiratory systems in mice. However, further human studies are needed to clarify the long-term health risks associated with e-cigarette use.

Characteristics of second-hand exposure to aerosols from e-cigarettes: A literature review since 2010.

In recent years, the use of electronic vaping products (also named e-cigarettes) has increased due to their appealing flavors and nicotine delivery without the combustion of tobacco. Although the hazardous substances emitted by e-cigarettes are largely found to be much lower than combustible cigarettes, second-hand exposure to e-cigarette aerosols is not completely benign for bystanders. This work reviewed and synthesized findings on the second-hand exposure of aerosols from e-cigarettes and compared the results with those of the combustible cigarettes. In this review, different results were integrated based upon sampling locations such as residences, vehicles, offices, public places, and experimental exposure chambers. In addition, the factors that influence the second-hand exposure levels were identified by objectively reviewing and integrating the impacts of combustible cigarettes and e-cigarettes on the environment. It is a challenge to compare the literature data directly to assess the effect of smoking/vaping on the indoor environment. The room volume, indoor air exchange rate, puffing duration, and puffing numbers should be considered, which are important factors in determining the degree of pollution. Therefore, it is necessary to calculate the "emission rate" to normalize the concentration of pollutants emitted under various experimental conditions and make the results comparable. This review aims to increase the awareness regarding the harmful effects of the second-hand exposure to aerosols coming from the use of cigarettes and e-cigarettes, identify knowledge gaps, and provide a scientific basis for future policy interventions with regard to the regulation of smoking and vaping.

Changes in biomarkers of exposure and withdrawal symptom among Chinese adult smokers after completely or partially switching from combustible cigarettes to an electronic nicotine delivery system.

This study assessed changes in biomarkers of exposure (BoE) after 5 days of completely or partially switching to an electronic nicotine delivery system (ENDS) use, compared with continued use of combustible cigarettes and smoking abstinence among Chinese adult smokers. A randomized, open-label, parallel-arm study was conducted among Chinese adult smokers who were naive ENDS users. Forty-six subjects were randomized to 4 study groups (n = 11-12 per group): exclusive ENDS use, dual use of ENDS and cigarettes, exclusive cigarettes use, and smoking abstinence. Subjects were confined in clinic for 5 consecutive days and product use was ad libitum. Nicotine and its metabolites (cotinine and 3-hydroxycotinine), and BoEs (AAMA, CEMA, HEMA, HMPMA, 3-HPMA, SPMA, exhaled CO, and exhaled NO) were measured. Withdrawal symptom was measured using MNWS throughout the 5-day period. Six urine BoEs of volatile organic compounds decreased by 55.1-84.1% in the exclusive ENDS use group, which is similar to the smoking abstinence group (67.2-87.4%). The level of decrease was 56.8-70.4% in the dual use group and 10.7-39.0% in the cigarettes group. Urine total nicotine exposure had a non-significant increase in the exclusive ENDS use group, and plasma nicotine and cotinine showed a trend of increasing day by day. After completely or partially switching to ENDS use among Chinese smokers, exposure to selected toxicants were significantly decreased. The results of this study add to the body of evidence that exposure to toxic substance decreased among smokers after complete or partial switch from combustible cigarettes to ENDS use. As part of transition to experienced ENDS use, this study found that smokers of the initial stage who have no prior ENDS experience may increase nicotine intake after switching to ENDS use.

Ternary Dry Powder Agglomerate Inhalation Formulation of Melatonin With Air Jet Mixing to Improve In Vitro And In Vivo Performance.

An improved agglomerate formulation with melatonin and fine lactose for dry powder inhalation using Turbuhaler® was developed. Co-grinding lactose with 1 % magnesium stearate prior to air jet mixing served as a key factor to improve the in vitro aerosolization and in vivo efficacy. Elevated mixing pressure facilitated the dispersion and homogenization of the cohesive mixture for even distribution of agglomerate size after spheroidization and subsequent higher emitted dose with lower variation. Magnesium stearate was employed as a tertiary component to adjust the interparticle force for better aerosolization. At optimized mixing pressure, co-grinding lactose with magnesium stearate before jet mixing displayed further improvement of fine particle fraction to 71.6 ± 3.1 %. The superior fine particle deposition efficiency contributed to rapid onset of action and a high bioavailability of 67.0 % after intratracheal administration to rats. Overall, an inhalable melatonin dry powder formulation exhibiting good aerosol property and lung deposition with clinical translation potential was developed.

Inhalation of electronic cigarettes slightly affects lung function and inflammation in mice.

Electronic cigarettes have become increasingly popular, but the results of previous studies on electronic cigarette exposure in animals have been equivocal. This study aimed to evaluate the effects of electronic cigarette smoke (ECS) and cigarette smoke (CS) on lung function and pulmonary inflammation in mice to investigate whether electronic cigarettes are safer when compared to cigarettes. 32 specific pathogen-free BALB/c male mice were randomly grouped and exposed to fresh air (control), mint-flavored ECS (ECS1, 6 mg/kg), cheese-flavored ECS (ECS2, 6 mg/kg), and CS (6 mg/kg). After 3 weeks exposure to ECS or CS, we measured lung function (PIF and Penh) and blood oxygen saturation. The levels of TNF-α and IL-6 in the bronchoalveolar lavage fluid (BALF) and serum were measured using ELISA. HE staining was performed to observe the pathological changes in the lung tissues. The levels of IL-6 in BALF and serum, and TNF-α in BALF, were elevated similarly in the ECS and CS groups compared to the control group. Significant elevation was observed in serum TNF-α levels in the CS group. The total count of cells in BALF were increased after ECS1 exposure and CS exposure. PIF and oxygen saturation decreased, and Penh increased markedly in the CS group but not in the ECS groups. Compared with the ECS groups, mice in the CS group had widened lung tissue septa and increased inflammatory cell infiltration. However, we did not detect significant differences between mint-flavored and cheese-flavored e-cigarettes in our study. Overall, our findings suggested that both ECS and CS impair lung function and histopathology while promoting inflammation. In contrast, ECS has a less negative impact than CS.

Evaluation of the Effects of e-Cigarette Aerosol Extracts and Tobacco Cigarette Smoke Extracts on RAW264.7 Cells.

With the advancement of society, electronic cigarettes (e-cigarettes) have gained popularity among a growing number of individuals. While numerous toxicological studies have suggested that e-cigarettes are a safer alternative to traditional cigarettes, there is also a body of literature presenting contrasting findings. This in vitro study aimed to compare the effects of e-cigarettes and tobacco cigarettes (t-cigarettes) on RAW264.7 cells by using four e-cigarette aerosol extracts (ECA) and cigarette smoking extracts (CS) containing different nicotine concentrations. The results revealed that low concentration of nicotine in CS as well as in ECA with grape, watermelon, and cola flavors could promote cell viability. Conversely, high nicotine concentration in CS and ECA with four flavors decreased cell viability. Furthermore, our study demonstrated that CS significantly reduced the phagocytic capability of RAW264.7 cells and increased the levels of inflammatory cytokines (IL-6, TNF-α, and IL-1ß) and reactive oxygen species (ROS) compared to ECA. Overall, our findings indicate all four e-cigarettes induced less cytotoxicity to RAW264.7 cells and might be safer than t-cigarettes.

The toxic effects of electronic cigarette aerosol and cigarette smoke on cardiovascular, gastrointestinal and renal systems in mice.

Electronic cigarette (EC) has been suggested to be less harmful than cigarette smoking, but the research on the full extent of their harm reduction potential is still lacking. This study aimed to evaluate the influence of EC aerosol and cigarette smoke (CS) on cardiovascular, gastrointestinal, and renal functions in mice after prolonged exposure. Forty-eight C57BL/6J male mice were randomly grouped and then exposed to fresh air (control), mung bean-flavored EC aerosol with low and high dose (EC1L, 6 mg/kg; EC1H, 12 mg/kg), watermelon-flavored EC aerosol with low and high dose (EC2L, 6 mg/kg; EC2H, 12 mg/kg), and finally a cigarette smoke (CS, 6 mg/kg), respectively. After 10 weeks of exposure, the heart rate increased for both the EC and CS groups, and the effect of CS on blood oxygen saturation was significantly higher than that of the EC group (P < 0.01). Proteomic analysis of the heart tissue showed that the overlapped differential expression protein from the EC and CS exposures was Crip2. For the gastrointestinal system, oral mucosa was significantly damaged in CS group. Compare with CS, EC had significantly fewer negative effects on most of the indictors which focused on in this study.

PM1 exposure and spatial transmission of nicotine from the simulated second-hand vapor of pod-based electronic cigarettes.

Electronic cigarettes (E-cigarettes) have gained significant popularity in recent years as a substitute for combustible cigarettes. However, there is growing concern regarding the safety of E-cigarette products for both the users and those exposed passively to second-hand emissions, which contain nicotine and other toxic substances. In particular, the characteristics of second-hand PM1 exposure and the transmission of nicotine from E-cigarettes remain unclear. In this study, the untrapped mainstream aerosols from the E-cigarette and smoke from cigarettes were exhausted by the smoking machines which were operated under standardized puffing regimes to simulate second-hand vapor or smoke exposure. The concentrations and components of PM1 released from cigarettes and E-cigarettes were compared under varying environmental conditions and regulated using a heating, ventilation, and air conditioning (HVAC) system. Additionally, the ambient nicotine concentrations and the size distribution of the generated aerosols were determined at different distances from the release source. Results showed that PM1 accounted for the highest proportion (98 %) of the released particulate matter (PM1, PM2.5, and PM10). The mass median aerodynamic diameter (MMAD) of cigarette smoke (0.5 ± 0.01 µm, geometric standard deviation (GSD) 1.97 ± 0.1) was smaller than that of E-cigarette aerosols (1.06 ± 0.14 µm, GSD 1.79 ± 0.19). The PM1 concentrations and chemical components were effectively reduced when the HVAC system was utilized. Nicotine concentrations in E-cigarette aerosols were comparable to those of combustible cigarette emissions when close to the exposure source (0 m), while they declined more rapidly than cigarette smoke emissions with increasing distance from the source. Furthermore, the maximum nicotine concentrations occurred in 1 µm and 0.5 µm particles in E-cigarette and cigarette emissions, respectively. These results provide a scientific basis for the assessment of E-cigarette and cigarette aerosol passive exposure risks, guiding the development of environmental and human health control measures for these products.

Evaluation of the effects of e-cigarette aerosol extracts and tobacco cigarette smoke extracts on human gingival epithelial cells.

Smoking increases the risk of a number of diseases, including cardiovascular, oral and lung diseases. E-cigarettes are gaining popularity among young people as an alternative to cigarettes, but there is debate over whether they are less harmful to the mouth than e-cigarettes. In this study, human gingival epithelial cells (HGECs) were treated with four commercially available e-cigarette aerosol condensates (ECAC) or commercially available generic cigarette smoke condensates (CSC) with different nicotine concentrations. Cell viability was determined by MTT assay. Cell apoptosis was observed by acridine orange (AO) and Hoechst33258 staining. The levels of type I collagen, matrix metalloproteinase (MMP-1, MMP-3), cyclooxygenase 2 and inflammatory factors were detected by ELISA and RT-PCR. Finally, ROS levels were analyzed by ROS staining. The different effects of CSC and ECAC on HGECs were compared. The results showed that higher nicotine concentration of CS significantly reduced the activity of HGECs. By contrast, all ECAC had no significant effect. The levels of matrix metalloproteinase, COX-2, and inflammatory factors were higher in HGECs treated with CSC than those treated with ECAC. In contrast, the level of type I collagen was higher in HGECs treated with ECAC than those treated with CSC. In conclusion, all four flavors of e-cigarettes were less toxic to HGE cells than tobacco, but further clinical studies are needed to determine whether e-cigarettes are less harmful to oral health than conventional cigarettes.

Evaluation of the Effects of E-Cigarette Aerosol Extracts and Tobacco Cigarette Smoke Extracts on Human Gingival Epithelial Cells.

Smoking increases the risk of a number of diseases, including cardiovascular, oral, and lung diseases. E-cigarettes are gaining popularity among young people as an alternative to cigarettes, but there is debate over whether they are less harmful to the mouth than e-cigarettes. In this study, human gingival epithelial cells (HGECs) were treated with four commercially available e-cigarette aerosol condensates (ECAC) or commercially available generic cigarette smoke condensates (CSC) with different nicotine concentrations. Cell viability was determined by MTT assay. Cell apoptosis was observed by acridine orange (AO) and Hoechst33258 staining. The levels of type I collagen, matrix metalloproteinase (MMP-1, MMP-3), cyclooxygenase 2, and inflammatory factors were detected by ELISA and RT-PCR. Finally, ROS levels were analyzed by ROS staining. The different effects of CSC and ECAC on HGECs were compared. The results showed that higher nicotine concentration of CS significantly reduced the activity of HGECs. By contrast, all ECAC had no significant effect. The levels of matrix metalloproteinase, COX-2, and inflammatory factors were higher in HGECs treated with CSC than those treated with ECAC. In contrast, the level of type I collagen was higher in HGECs treated with ECAC than those treated with CSC. In conclusion, all four flavors of e-cigarettes were less toxic to HGE cells than tobacco, but further clinical studies are needed to determine whether e-cigarettes are less harmful to oral health than conventional cigarettes.

Cigarettes smoking and e-cigarettes using among university students: a cross-section survey in Guangzhou, China, 2021.

BACKGROUND: There is an increase in the use of cigarettes and e-cigarettes worldwide, and the similar trends may be observed in young adults. Since 2014, e-cigarettes have become the most commonly used nicotine products among young adults (Sun et al., JAMA Netw Open 4:e2118788, 2021). With the increase in e-cigarette use and the decrease in use of cigarettes and other tobacco products, however, there is limited information about Chinese smokers, e-cigarettes users and trends in cigarettes and e-cigarettes use among university students. Therefore, our objective was to investigate the using status of cigarettes, e-cigarettes and smoking behavior among the students from 7 universities in Guangzhou, China. METHODS: Students at 7 different universities in Guangzhou were investigated online in 2021 through a cross-sectional survey. A total of 10,008 students were recruited and after screening, 9361 participants were adopted in our statistics. Descriptive analysis, Chi-square analysis, and multiple logistic regression analysis were used to explore the smoking status and influencing factors. RESULTS: The average age of the 9361 university students was 22.4 years (SD = 3.6). 58.3% of participants were male. 29.8% of the participants smoked or used e-cigarettes. Among the smokers and users of e-cigarettes, 16.7% were e-cigarettes only users, 35.0% were cigarettes only users, and 48.3% were dual users. Males were more likely to smoke or use e-cigarettes. Medical students, students from prestigious Chinese universities, and students with higher levels of education were less likely. Students with unhealthy lifestyles (e.g., drinking alcohol frequently, playing video games excessively, staying up late frequently) were more likely to smoke or use e-cigarettes. Emotion can have significant impacts on both cigarettes and e-cigarettes dual users when choosing cigarettes or e-cigarettes to use. More than half of dual users said they would choose cigarettes when they were depressed and e-cigarettes when they were happy. CONCLUSION: We identified factors influencing the use of cigarettes and e-cigarettes among university students in Guangzhou, China. Gender, education level background, specialization, lifestyle habits and emotion all influenced the use of cigarettes and e-cigarettes among university students in Guangzhou, China. Male, low education level, from non-prestigious Chinese universities or vocational schools, non-medical specialization, and presence of unhealthy lifestyles were influencing factors for the use of cigarettes and e-cigarettes among university students in Guangzhou and students with these factors were more likely to smoke or use e-cigarettes. Besides, emotions can influence dual users' choice of products. This study provides more information to better understand young people's preferences for cigarettes and e-cigarettes by elucidating the characteristics of cigarettes and e-cigarettes use, as well as related influencing factors, among university students in Guangzhou. Further research involving more variables connected to the use of cigarettes and e-cigarettes will be required in our future study.

Cytotoxicity and cell injuries of flavored electronic cigarette aerosol and mainstream cigarette smoke: A comprehensive in vitro evaluation.

INTRODUCTION: Although electronic cigarettes (e-cigarettes) have attracted much attention due to their claimed harm-reduction effects compared with conventional cigarettes, the adverse effects of e-cigarette aerosol exposure on human health are still unclear. In this work we compared the cytotoxic effects of combustion cigarettes with four commercially available flavored electronic cigarettes and their main components on ten cell lines. Cell injury mechanism of e-cigarette aerosol and combustible cigarette smoke was also explored using cellular models. METHODS: Eleven kinds of e-cigarettes aerosol condensates (ECSCs) and cigarette smoke constituent's condensates (CSC) were collected by Cambridge filter pad, and the nicotine contents were determined by UPLC to provide an equivalent nicotine dosage. The CCK-8 assay was used to measure the cell viability differences between ECSC and CSC. Based on RNA-seq results, we compared the effects of ECSC and CSC on various cell injury pathways. Oxidative stress and inflammatory responses were further tested by Western Blot, immunofluorescence, and qRT-PCR assays. RESULTS: CSC was found to be more cytotoxic than flavored ECSC and their main components, and BEAS-2B cell line was the most sensitive cells by comparing the IC50 value. With prolonged exposure duration and higher doses, ECSC began to exhibit cytotoxicity at and above 72 µg/mL. The IC50 values of ECSC were 15-fold higher than that of CSC. Transcriptome analyses indicated that cell injury-related processes were enriched after the treatment of CSC. CSC could significantly induce more oxidative stress and inflammatory signals than ECSC. CONCLUSION: ECSCs and their components induced significantly less cytotoxicity than CSC under the laboratory exposure conditions, and CSC caused much severe cell injuries. Our study adds to the body of scientific evidence for a more comprehensive safety evaluation of e-cigarette products as compared to cigarettes.

Chemical analysis of selected harmful and potentially harmful constituents and in vitro toxicological evaluation of leading flavoured e-cigarette aerosols in the Chinese market.

Use of electronic cigarettes (e-cigarettes) has increased significantly over the past decade due to consumer perception that these products represent a less risky alternative to combustible cigarettes. E-liquids generally contain a simple mix of vegetable glycerin, propylene glycerol, nicotine, organic acids, and flavourings. Regulators require that harmful and potentially harmful constituents (HPHCs) that might cause harm to the consumer must be monitored in the aerosol generated by e-cigarettes and in cigarette smoke (CS). To quantify HPHCs in aerosols from commercial flavoured e-cigarettes in Chinese market, this study has systematically compared levels of HPHCs, including eight carbonyls, five volatile organic compounds, four tobacco-specific nitrosamines, 16 polycyclic aromatic hydrocarbons, and seven heavy metals, in the aerosols of four market-leading flavoured e-cigarettes and mainstream CS, alongside in vitro cytotoxicity and mutagenicity assays. The vast majority of HPHCs were either undetected or significantly lower in the e-cigarette aerosols than in commercial CS or reference CS (3R4F). Where HPHCs were detected, there were small variations among the different flavoured e-cigarettes. In the neutral red uptake and Ames assays, aqueous extracts of the e-cigarette aerosols did not induce obvious cytotoxicity or mutagenicity, whereas CS aqueous extract showed dose-related cytotoxicity and mutagenicity. Collectively, these results indicate that use of e-cigarettes might potentially lead to a significant reduction in exposure to harmful substances, with fewer cytotoxic and mutagenic effects, as compared with conventional smoking. Further studies based on human puffing conditions and longer evaluation periods will be needed to substantiate this potential.

Preparation and Study of a Simple Three-Matrix Solid Electrolyte Membrane in Air.

Solid-state lithium batteries have attracted much attention due to their special properties of high safety and high energy density. Among them, the polymer electrolyte membrane with high ionic conductivity and a wide electrochemical window is a key part to achieve stable cycling of solid-state batteries. However, the low ionic conductivity and the high interfacial resistance limit its practical application. This work deals with the preparation of a composite solid electrolyte with high mechanical flexibility and non-flammability. Firstly, the crystallinity of the polymer is reduced, and the fluidity of Li+ between the polymer segments is improved by tertiary polymer polymerization. Then, lithium salt is added to form a solpolymer solution to provide Li+ and anion and then an inorganic solid electrolyte is added. As a result, the composite solid electrolyte has a Li+ conductivity (3.18 × 10-4 mS cm-1). The (LiNi0.5Mn1.5O4)LNMO/SPLL (PES-PVC-PVDF-LiBF4-LAZTP)/Li battery has a capacity retention rate of 98.4% after 100 cycles, which is much higher than that without inorganic oxides. This research provides an important reference for developing all-solid-state batteries in the greenhouse.

Combined biological effects and lung proteomics analysis in mice reveal different toxic impacts of electronic cigarette aerosol and combustible cigarette smoke on the respiratory system.

Combustible cigarettes produce many toxic substances that have been linked to diseases, such as lung cancer and chronic obstructive pulmonary disease. For those smokers unable or unwilling to quit, electronic cigarettes (e-cigarettes) could be used as an alternative to cigarettes. However, the effects and mechanisms of e-cigarette aerosol (ECA) on respiratory function have not been fully elucidated, and in vivo studies of its safety are limited compared to cigarette smoke (CS). In this article, we chose nicotine levels as dosing references and C57BL/6 mice for a 10-week subchronic inhalation toxicity study. A comprehensive set of toxicological endpoints was used to study the effect of exposure. Both CS (6 mg/kg) and ECA (6 or 12 mg/kg) inhalation had decreased the animal's lung function and increased levels of inflammation markers, along with pathological changes in the airways and lungs, with ECA displaying a relatively small effect at the same dose. Proteomic analysis of lung tissue showed greater overall protein changes by CS than that of ECA, with more severe inflammatory network perturbations. Compared with ECA, KEGG analysis of CS revealed upregulation of more inflammatory and virus-related pathways. Protein-protein interactions (PPI) showed that both ECA and CS significantly changed ribosome and complement system-related proteins in mouse lung tissue. The results support that e-cigarette aerosol is less harmful to the respiratory system than cigarette smoke at the same dose using this animal model, thus providing additional evidence for the relative safety of e-cigarettes.

A comparative assessment of e-cigarette aerosol extracts and tobacco cigarette smoke extracts on in vitro endothelial cell inflammation response.

With the development of the times, electronic cigarettes (e-cigarettes) are being received by more and more people. We compared the different effects of e-cigarettes and tobacco cigarettes on human umbilical vein endothelial cells (HUVECs) treated with the typical e-cigarette aerosol extracts (ECA) and cigarette smoking extracts (CS) sourced from commercial retail stores. HUVECs were treated with different kinds of ECA or CS with different nicotinic concentrations (0.03125, 0.125, 0.5, 2, 8, or 32 µg/mL). Cell viability was examined by the MTT assay. The cell apoptosis was investigated by acridine orange (AO) and Hoechst 33258 staining. The RT-PCR and western blot assays were used to analyze the adhesion molecules and inflammation cytokines released by HUVECs. Furthermore, the intracellular reactive oxygen species (ROS) was observed by fluorescence microscopy. Our data showed that the CS (nicotine concentration at 0.125 µg/mL could decrease the viability of HUVECs by 71%, but not the four kinds of ECA. The apoptotic ratio was about 32.5% in the CS group. No matter the levels of adhesion molecules, inflammation cytokines or ROS, they were higher in CS groups than in ECA groups. Overall, the four kinds of e-cigarettes induced significantly less cytotoxicity than the commercially available tobacco cigarettes in HUVECs. The CS showed the most severe impact on HUVECs. ECA might provide a harm reduction measure, especially in cardiovascular risk, after people switch from tobacco cigarettes to e-cigarettes.

Comparison of biological and transcriptomic effects of conventional cigarette and electronic cigarette smoke exposure at toxicological dose in BEAS-2B cells.

Cigarette seriously affects human health, and electronic cigarette (e-cigarette), considered as cigarette substitutes, become popular as its contribution to quit smoking. But scientific evidence about the absolute safety of e-cigarette is insufficient. Previous studies also have indicated that different dosages of cigarette can lead to different biological effects. Thus, the impact of cigarette at toxicological dose such as IC50 compared with that of e-cigarette are highly needed. In this study, we investigated the effects of cigarette smoke condensate (CSC) at toxicological dose compared with e-cigarette smoke condensate (ECSC) in equivalent nicotine level. Nicotine content of CSC and ECSC were determined by UPLC. Human lung epithelial cells (BEAS-2B) were exposed to 0-32 µg/ml of CSC and ECSC for 24 h to determine IC50 of cell viability and morphological assessment. Inflammation, apoptosis, cell cycle analysis and RNA-Seq transcriptome analysis were performed to characterize the differences between CSC and ECSC. We found that acute exposure of BEAS-2B cells to CSC at IC50 leaded to morphological change, inflammatory cytokines production and cell apoptosis, while ECSC did not exert such cell effects in equivalent nicotine level. The transcriptome analysis showed that differentially expressed genes in CSC were far more than that in ECSC, and mainly enriched in the category of cell cycle, DNA repair, cancer, and metabolic related pathways. Such cell cycle arrest was further experimentally confirmed. These results suggested that toxicological dose of ECSC might be much higher than that of CSC. Based on equivalent nicotine content, an acute exposure to CSC had significant impacts on cell effects and gene expression profile compared to ECSC. Our results provided a reference for the safety studies of conventional cigarette and e-cigarette.

Acute and subacute inhalation toxicity assessment of WS-23 in Sprague-Dawley rats.

2-isopropyl-N,2,3-trimethylbutyramide (WS-23) is a well-known artificial synthesis cooling agent widely used in foods, medicines, and tobaccos. As a commonly cooling agent in e-cigarette liquids, WS-23 has led to concerns about the inhalation toxicity with the prosperous of e-cigarettes in recent years. Thus, the aim of this study is to assess the acute and subacute inhalation toxicity of WS-23 in Sprague-Dawley (SD) rats according to the Organization for Economic Cooperation and Development (OECD) guidelines. In the acute toxicity study, there was no mortality and behavioral signs of toxicity at the limit test dose level (340.0 mg/m3 ) in the exposure period and the following 14-day observation period. In the subacute inhalation toxicity study, there was no significant difference observed in the body weights, feed consumption, and relative organ weights. Haematological, serum biochemical, urine, and bronchoalveolar lavage fluid (BALF) analysis revealed the non-adverse effects after 28-day repeated WS-23 inhalation (342.85 mg/m3 ), accompanied by slight changes in few parameters which returned to normal during the 28-day recovery period. The histopathologic examination also did not show any differences in vital organs. In conclusion, the maximum tolerated dose for WS-23 acute inhalation is not less than 340.0 mg/m3 , and the No Observed Adverse Effect Level (NOAEL) of WS-23 subacute inhalation was determined to be over 342.85 mg/m3 .

Fast conversion of lithium (poly)sulfides in lithium-sulfur batteries using three-dimensional porous carbon.

The slow redox kinetics of polysulfide hinders the rapid and complete conversion between soluble polysulfides and Li2S2/Li2S, resulting in unsatisfactory rate and cycle performance in lithium-sulfur batteries. Electrochemical catalysis, one effective method, promotes the reaction kinetics and inhibits the "shuttle effect". Here, we present a three-dimensional ordered macro-porous carbon with abundant cobalt-nitrogen-carbon active sites as a matrix catalyst, leading to accelerated polysulfide redox kinetics. In addition, the interconnected conductive frameworks with ordered macro-porous carbon afford fast ion/electron transport and provide sufficient space to adapt to the volume expansion of the sulfur electrode. Owing to the aforementioned advantages, a lithium-sulfur battery with the matrix catalyst delivers a high specific capacity (1140 mA h g-1 at 0.1C) and a low capacity decay rate (0.0937% per cycle over 500 cycles). Moreover, there is a high rate capacity (349.1 mA h g-1) even at the high current density of 2C and sulfur loading of 3.8 mg cm-2 due to the improved polysulfide redox kinetics by a catalytic effect.

Triptolide reverses the Taxol resistance of lung adenocarcinoma by inhibiting the NF-κB signaling pathway and the expression of NF-κB-regulated drug-resistant genes.

Paclitaxel (or Taxol®) is a first-line chemotherapeutic drug for the treatment of non-small cell lung cancer; however, resistance to the drug is an important factor, which influences the outcome of chemotherapy. The present study aimed to investigate the role of triptolide (TPL) in reversing Taxol­resistant human lung adenocarcinoma and to elucidate the underlying molecular mechanism of resistance reversal mediated by TPL. It was hypothesized that this experimental approach would assist in solving the problem of chemotherapeutic resistance in non­small cell lung cancer, thereby improving the clinical outcomes. The human Taxol­resistant lung adenocarcinoma cell line, A549/Taxol, was established. The resistance index of the cell line was calculated, according to the half maximal inhibitory concentration (IC50) of A549/Taxol IC50 of A549, to be 51.87. The levels of apoptosis and the cell cycle in the A549/Taxol cell line were assessed to confirm the effects of TPL at three different concentrations (0.03, 0.3 and 3 µmol/l) and treatment durations (2, 4, 6 and 12 h) by flow cytometric analysis, and the inhibition of the NF­κB signaling pathway and the expression of NF­κB­regulated drug­resistant proteins were determined by immunofluorescence and western blotting, respectively. The administration of TPL promoted cell apoptosis in the A549/Taxol lung adenocarcinoma Taxol­resistant cell line and also promoted cell cycle regulation. The drug was also able to elicit a reversal of the drug resistance. TPL inhibited the nuclear factor­κB (NF­κB) signaling pathway and the expression of NF­κB­regulated drug­resistant genes, including those for FLICE­like inhibitory protein, X­linked inhibitor of apoptosis protein, Bcl­2, Bcl­xL and cyclo­oxygenase­2. TPL exerted a marked drug­resistance­reversal effect on human lung adenocarcinoma Taxol resistance, and the effect was revealed to be dose­ and time­dependent. In conclusion, TPL exerted its role in the process of resistance reversal by inhibiting the NF­κB signaling pathway, and the transcription and expression of NF-κB-regulated drug-resistant genes.