Effects of chronic electronic cigarettes exposure in inducing respiratory function decline and pulmonary tissue injury - A direct comparison to combustible cigarettes.

BACKGROUND: Electronic cigarette (e-cig) use is increasing worldwide, especially among young individuals. Spirometry measures airflow obstruction and is the primary tool for diagnosing/monitoring respiratory diseases in clinical settings. This study aims to assess the effects of chronic e-cig exposure on spirometric traits, and directly compare to conventional combustible-cigarette (c-cig). METHODS: We employed an e- and c-cig aerosol generation system that resembled human smoking/vaping scenario. Fifty 6-week old C57BL/6 mice were equally divided into five groups and exposed to clean air (control), e-cig aerosol (low- and high-dose), and c-cig aerosol (low- and high-dose), respectively, for 10 weeks. Afterwards, growth trajectory, spirometry and pulmonary pathology were analyzed. RESULTS: Both e- and c-cig exposure slowed down growth and weight gain. Low dose e-cig exposure (1 h exposure per day) resulted in minimal respiratory function damage. At high dose (2 h exposure per day), e-cig exposure deteriorated 7 spirometry traits but by a smaller magnitude than c-cig exposure. For example, comparing to clean air controls, high dose e- and c-cig exposure increased inspiratory resistance by 24.3% (p = 0.026) and 66.7% (p = 2.6e-5), respectively. Low-dose e-cig exposure increased alveolar macrophage count but did not lead to airway remodeling. In contrast, even low-dose c-cig caused alveoli break down and thickening of the small airway, hallmarks of airway obstructive disease. CONCLUSIONS: We conducted well-controlled animal exposure experiments assessing chronic e-cig exposure's effects on spirometry traits. Further, mechanistic study characterized airway remodeling, alveolar tissue lesion and inflammation induced by e- and c-cig exposure. Our findings provided scientific and public health insights on e-cig's health consequences, especially in adolescent users.

Targeting zebrafish and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitor.

Cushing disease caused by adrenocorticotropin (ACTH)-secreting pituitary adenomas leads to hypercortisolemia predisposing to diabetes, hypertension, osteoporosis, central obesity, cardiovascular morbidity, and increased mortality. There is no effective pituitary targeted pharmacotherapy for Cushing disease. Here, we generated germline transgenic zebrafish with overexpression of pituitary tumor transforming gene (PTTG/securin) targeted to the adenohypophyseal proopiomelanocortin (POMC) lineage, which recapitulated early features pathognomonic of corticotroph adenomas, including corticotroph expansion and partial glucocorticoid resistance. Adult Tg:Pomc-Pttg fish develop neoplastic coticotrophs and pituitary cyclin E up-regulation, as well as metabolic disturbances mimicking hypercortisolism caused by Cushing disease. Early development of corticotroph pathologies in Tg:Pomc-Pttg embryos facilitated drug testing in vivo. We identified a pharmacologic CDK2/cyclin E inhibitor, R-roscovitine (seliciclib; CYC202), which specifically reversed corticotroph expansion in live Tg:Pomc-Pttg embryos. We further validated that orally administered R-roscovitine suppresses ACTH and corticosterone levels, and also restrained tumor growth in a mouse model of ACTH-secreting pituitary adenomas. Molecular analyses in vitro and in vivo showed that R-roscovitine suppresses ACTH expression, induces corticotroph tumor cell senescence and cell cycle exit by up-regulating p27, p21 and p57, and downregulates cyclin E expression. The results suggest that use of selective CDK inhibitors could effectively target corticotroph tumor growth and hormone secretion.

Comprehensive two-dimensional gas chromatography mass spectrometry with a solid-state thermal modulator for in-situ speciated measurement of organic aerosols.

Thermal desorption aerosol gas chromatography mass spectrometry is capable of online measuring speciated organics in atmospheric aerosols. Compared to the one-dimensional gas chromatography, comprehensive two-dimensional gas chromatography increases the resolution and the sensitivity, mitigates the unresolved complex mixture and co-elution occurred in one-dimensional gas chromatography. In this study, we report a quartz filter-based thermal desorption aerosol comprehensive two-dimensional gas chromatography mass spectrometry (2D-Q-TAG). It combines a solid-state thermal modulator with a quartz filter-based thermal desorption aerosol gas chromatography mass spectrometry. The solid-state thermal modulator conducts modulation independently from the chromatographic oven without using cryogens or compressed air, which makes the system readily adaptive for field measurement. The 2D-Q-TAG was evaluated using C7-C40 n-alkanes and 16 polycyclic aromatic hydrocarbons (PAHs). It has low limits of detection from 0.001 to 0.104 ng. The instrument was then deployed to measure atmospheric PM2.5 (particulate matter with an equivalent aerodynamic diameter  ≤  2.5 µm) in urban Beijing. It allows in-situ detection of speciated organics in atmospheric aerosols with hourly time resolution. Organic classes including alkanes, furanones, alcohols, aldehydes, ketones, acids, PAHs, oxy-PAHs, and alkyl-naphthalenes were well separated and detected. The total mass concentration of n-alkanes ranged from 122.1 to 629.9 ng/m3. Diurnal variation of n-alkanes was captured due to the high time resolution of the instrument.

Quartz filter-based thermal desorption gas chromatography mass spectrometry for in-situ molecular level measurement of ambient organic aerosols.

Thermal desorption aerosol gas chromatography (TAG) is an effective technique for online chemical characterization of organics in atmospheric fine particulate matter (PM2.5) on the molecular level. Unlike the previously reported impactor- or metal filter-based TAG, in this study, a replaceable quartz filter-based TAG (Q-TAG) was developed to achieve online measurement of organic constituents in ambient PM2.5. A homemade device for automatic online sampling and pretreatment of aerosols was developed and coupled with gas chromatography-mass spectrometry (GC-MS) by a 4-port valve. Performance of the Q-TAG system was evaluated using C7 - C40 n-alkanes to cover a wide range of volatility. C11 - C40 could be measured by Q-TAG. The response of their peaks depends on their volatility and thermal desorption conditions (the desorption time and the flow rate). Under the optimized conditions, good precision (<12%), acceptable linearity (R2> 0.98) and high sensitivity (detection limits from 0.02 to 0.01 ng) of C13 - C40 were obtained. The developed Q-TAG system was applied for online analysis of organic species in ambient PM2.5. The Q-TAG is suitable for detection of semi and low volatile organic species in particulate matter, and its filter can be easily changed, making it a useful tool in molecular characterization of ambient organic aerosols.

Improving thermal desorption aerosol gas chromatography using a dual-trap design.

Thermal desorption aerosol gas chromatography (TAG) is an effective tool for in situ analysis of particulate organic molecules. However, the performance of current TAG is limited by the detectability of low volatile compounds and the matrix effect. In this study, a dual-trap TAG system was developed to address these issues. Thermally desorbed effluent is focused by a weakly retained trap (for low volatile compounds) in a 1 m capillary column conditioned in the GC oven, followed by a strongly retained trap (for high volatile compounds). Then, the focused analytes are desorbed in a reverse flow into the GC column for analysis. Detection over a wide volatility range from C10 to C40 n-alkanes is achieved using the dual-trap TAG. We show that it has lower discrimination of injection, better linearity and higher detectability of n-alkanes. The dual-trap TAG was applied for in-situ measurement of ambient fine particles (PM2.5) in Beijing. Repeatable retention time of n-alkanes was demonstrated during a continuous measurement over two weeks.

[Preliminary study of the ultrasonic measurement of thickness of skin in children].

OBJECTIVE: To collect the data of measuring skin thickness of children of both genders of different ages and parts of body with non-invasive high-frequency ultrasound method. METHODS: Two hundred and twenty-one children from 1 to 18 years of age,without systemic disease or injury in skin, were enrolled in the study and divided into 4 groups: i.e., infant group (112 years of age), pre-school age group (3-6 years of age), school age group (7-12 years for boys and 7-11 years for girls), adolescent age group (13-18 years for boys and 12-18 years for girls), and each group was subdivided into 2 groups according to the gender. The skin thicknesses of children in cheek, chest, abdomen, forearms, fundament and thigh was respectively measured by 13 MHz high-frequency ultrasound. RESULTS: The region with thinnest skin in children was the cheek, and the thickest was the back and buttock. (1) There were no significant differences in thickness of skin in the same region between genders and also among different age groups (P > 0.05). (2) There were also no obvious differences of thickness of the dermis and the whole skin in the same region between male and female, or among infants, pre-school age and school age groups (P > 0.05). In adolescent group, the average thickness of dermis in male was (1.16 +/- 0.04 ) - (1.98 +/- 0.47) mm, the average whole thickness of skin in male was (1.27 +/- 0.12) - (2.20 +/- 0.45) mm, while those of female were (1.00 +/- 0.18) - (1.60 +/- 0.30) mm and (1.10 +/- 0.17) - (1.83 +/- 0.29) mm (P < 0.05). CONCLUSION: It is reliable to measure the skin thickness by 13MHz ultrasound as a non-invasive method. The main factor which determined the thickness of the skin is dermal thickness, especially in males. The significant differences of skin thickness among cheek, back and buttock provide the basis for us to choose the appropriate thickness of skin grafts harvested from different body parts.