Equisetin protects from atherosclerosis in vivo by binding to STAT3 and inhibiting its activity.

Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound isolated from fungus of marine sponge origin, which has antibacterial, anti-inflammatory, lipid-lowering, and weight loss effects. Whether EQST has anti-atherosclerotic activity has not been reported. In this study, we revealed that EQST displayed anti- atherosclerosis effects through inhibiting macrophage inflammatory response, lipid uptake and foam cell formation in vitro, and finally ameliorated high-fat diet (HFD)-induced atherosclerosis in AopE-/- mice in vivo. Mechanistically, EQST directly bound to STAT3 with high-affinity by forming hydrophobic bonds at GLN247 and GLN326 residues, as well as hydrogen bonds at ARG325 and THR346 residues. EQST interacted with STAT3 physically, and functionally inhibited the transcription activity of STAT3, thereby regulating atherosclerosis. Therefore, these results supports EQST as a candidate for developing anti-atherosclerosis therapeutic agent.

Underreporting of non-study cigarette use by study participants confounds the interpretation of results from ambulatory clinical trial of reduced nicotine cigarettes.

BACKGROUND: As part of its comprehensive plan to significantly reduce the harm from tobacco products, the US Food and Drug Administration is establishing a product standard to lower nicotine in conventional cigarettes to make them "minimally addictive or non-addictive". Many clinical studies have investigated the potential impact of such a standard on smoking behavior and exposure to cigarette constituents. These ambulatory studies required participants who smoke to switch to reduced nicotine study cigarettes. In contrast to clinical trials on pharmaceuticals or medical devices, participants had ready access to non-study conventional nicotine cigarettes and high rates of non-study cigarette use were consistently reported. The magnitude of non-compliance, which could impact the interpretation of the study results, was not adequately assessed in these trials. METHODS: We conducted a secondary analysis of data from a large, randomized trial of reduced nicotine cigarettes with 840 participants to estimate the magnitude of non-compliance, i.e., the average number of non-study cigarettes smoked per day by study participants assigned to reduced nicotine cigarettes. Individual participants' non-study cigarette use was estimated based on his/her urinary total nicotine equivalent level, the nicotine content of the study cigarette assigned and the self-reported number of cigarettes smoked, using a previously published method. RESULTS: Our analysis showed that (1) there is a large variation in the number of non-study cigarettes smoked by participants within each group (coefficient of variation 90-232%); (2) participants in reduced nicotine cigarette groups underreported their mean number of non-study cigarettes smoked per day by 85-91%; and (3) the biochemical-based estimates indicate no reduction in the mean number of total cigarettes smoked per day for any group assigned to reduced nicotine cigarettes after accounting for non-study cigarettes. CONCLUSIONS: High levels of non-compliance, in both the rate and magnitude of non-study cigarette use, are common in ambulatory reduced nicotine cigarette trials where participants have access to conventional nicotine non-study cigarettes. The potential impact of high non-compliance on study outcomes should be considered when interpreting the results from such ambulatory studies.

Covalent organic framework-based immunosensor to detect plasma Latexin reveals novel biomarker for coronary artery diseases.

It is a great challenge to develop an efficient and rapid method to detect of biomarkers of cardiovascular disease. In this research, a differential pulse voltammetry (DPV)-based ultrasensitive immunosensor for the detection of plasma Latexin (LXN) has been established. With the aim to increase the surface area of the bare glassy carbon electrode (GCE), multi-walled carbon nanotube-graphene oxide has been developed. Covalent organic frameworks (COFs) are dropped with gold nanoparticles (AuNPs), secondary antibody and thionine (Thi-Ab2-Au-COFs) act as the signal probe with high electronic conductivity. Under the ideal conditions, the immunosensor displayed a broad linear response range from 0.01 ng mL-1 to 100 ng mL-1, with a detection limit of 50 pg mL-1 (S/N = 3). The immunosensor also demonstrates outstanding sensitivity, repeatability, and stability. Finally, we utilized the designed immunosensor to detect plasma LXN in coronary artery disease (CAD) patients, and the data showed that plasma LXN was significantly increased in CAD patients with a good performance of ROCAUC (AUC 0.871, 95 % CI 0.725-1.0, p = 0.002), indicating plasma LXN is a potential biomarker of cardiovascular disease. This immunosensor is a promising strategy for screening CAD patients in clinical practice.

A Randomized, Controlled Study to Assess Changes in Biomarkers of Exposures Among Adults Who Smoke That Switch to Oral Nicotine Pouch Products Relative to Continuing Smoking or Stopping All Tobacco Use.

The purpose of this open-label, randomized, controlled, in-clinic, 5-parallel-group study was to assess biomarkers of exposure (BoE) to select harmful and potentially harmful constituents in adults who smoke (N = 144) switching to oral tobacco products (on!® mint nicotine pouches; test products) compared to continuing smoking cigarettes (CS) and completely quitting all tobacco products (NT). Changes in 20 BoE to select harmful and potentially harmful constituents, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), were evaluated. Adult smokers smoked their usual brand of cigarettes for 2 days (baseline assessments) and then were randomly assigned to ad libitum use of 2, 4, or 8 mg test products, CS, or NT for 7 days. Analysis of covariance was used to assess the Day 7 BoE levels between each group using test products, CS, and NT. The creatinine-adjusted total urinary NNAL and other 18 of 19 BoE levels (except nicotine equivalents [NEs]) were significantly lower (P < .05) on Day 7, among all test product groups compared to CS. Geometric least-square means were reduced for all biomarkers of exposure, except NEs, in test product groups by approximately 42%-96% compared to the CS group, and reductions were comparable to the NT group. The geometric least-square means for urinary NE between the test product and the CS groups, although not significantly different, the Day 7 mean change relative to the CS group were 49.9%, 65.8%, and 101% for the 2, 4, and 8 mg test product groups, respectively. The substantial reduction in harmful and potentially harmful constituent exposure suggests complete switching from cigarettes to test products may present a harm reduction opportunity for adults who smoke.

The effects of inactivated SARS-CoV-2 vaccination and subsequent infection of pregnant mice on the behaviors of offspring.

The mass inoculation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines to induce herd immunity is one of the most effective measures we can deploy in the fight against coronavirus disease 2019 (COVID-19). Pregnant women are prone to a higher risk of COVID-19, and maternal infection is a risk factor for a range of neurological disorders leading to abnormal behavior in adulthood. However, there are limited clinical data to support whether vaccination or infection post-immunization in pregnant women can affect the behavioral cognition of fetuses in adulthood. In this study, human angiotensin-converting enzyme 2 pregnant mice (F0 generation) were immunized with CoronaVac and then infected with SARS-CoV-2. Subsequently, we analyzed the behavioral cognition of their adult offspring (F1 generation) using the open-field test and Morris water maze test. The adult F1 generation did not exhibit any impairments in spontaneous locomotor activity or spatial reference memory.

Nicotine pharmacokinetics and subjective responses after using nicotine pouches with different nicotine levels compared to combustible cigarettes and moist smokeless tobacco in adult tobacco users.

RATIONALE: Oral tobacco-derived nicotine products include on!® nicotine pouches (NPs) which are tobacco-leaf free and available in multiple flavors and nicotine levels. Switching completely to NPs from cigarettes and moist smokeless tobacco (MST) has the potential to reduce harm for adult tobacco consumers. However, the dependence potential of NPs is not established. Therefore, we characterized the abuse potential of NPs with different nicotine levels compared to cigarettes and MST. OBJECTIVES: To evaluate nicotine pharmacokinetics (PK) and subjective effects of NPs (ranging from 1.5 to 8 mg nicotine) compared to own brand cigarettes (OBCs) and MST (OBMST). METHODS: We used a randomized, in-clinic, partial single-blind, 7-way crossover design to assess nicotine PK and subjective effects in dual users of cigarettes and MST. RESULTS: The mean nicotine Cmax for NPs increased with nicotine level, ranging from 3.5 ng/mL (1.5 mg NP) to 15.4 ng/mL (8 mg NP), compared with 12.2 ng/mL for OBCs and 9.8 ng/mL for OBMST. Nicotine tmax was much longer for all NPs and OBMST (32.5-34.4 min) compared to OBCs (8.5 min). Reductions in urges to smoke after use of the 2 mg, 3.5 mg, and 8 mg NPs were not statistically different (p > 0.05) relative to OBC. Also, NPs resulted in lower ratings of positive subjective effects relative to OBCs and OBMST. CONCLUSIONS: Overall, based on the study results and literature reported nicotine PK values for cigarettes and MST, the abuse potential of NPs is not likely to be higher than OBCs and OBMST. NPs may be potentially acceptable switching products for users of cigarettes and MST products.

A Randomized, Controlled Study to Assess Biomarkers of Exposure in Adult Smokers Switching to Oral Nicotine Products.

This open-label, randomized, controlled, in-clinic, 6-parallel-group study evaluated changes in biomarkers of exposure (BoEs) to select harmful and potentially harmful constituents in adult smokers (N = 213) not planning to quit smoking. Adult smokers were randomized to continue smoking (CS), reduce smoking by 50% and dual use oral tobacco-derived nicotine (OTDN) products (VERVE chews/discs), stop smoking and exclusively use discs or chews, or stop using all tobacco products (NT). The primary objective compared 24-hour urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; a biomarker for the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) in dual and exclusive use of discs and chews to continue smoking and NT on day 7. NNAL levels on day 7 were significantly lower (P < .05) among dual and exclusive users of discs/chews compared to continue smoking; median percent reductions were ≈30% and ≈73%, respectively. NNAL levels were not significantly different between those who used discs/chews and the NT group. Many of the additional secondary biomarkers of exposure were significantly lower in dual users (10/19) and exclusive users of discs/chews (17/19) compared to the continue smoking group. Overall, reductions in secondary biomarkers of exposure were greater in exclusive users than dual users. The 24-hour urinary nicotine equivalents were significantly lower (P < .05) among exclusive users of discs/chews compared to continue smoking. The discs/chews appeared to be well tolerated. These results demonstrate that while switching completely to discs/chews substantially reduces exposure to select harmful and potentially harmful constituents, dual use with 50% reduction in cigarette consumption also reduces exposure. oral tobacco-derived nicotine products like discs/chews may present a harm reduction opportunity for adult smokers, particularly those not intending to quit smoking.

Biomarkers of Exposure and Biomarkers of Potential Harm in Adult Smokers Who Switch to e-Vapor Products Relative to Cigarette Smoking in a 24-week, Randomized, Clinical Trial.

INTRODUCTION: Long-term health effects of e-vapor products (EVPs) are not well-established. We compared biomarkers of exposure (BoE) to select harmful and potentially harmful constituents and biomarkers of potential harm (BoPH) in adult smokers who switched to EVPs versus continued smoking for 24 weeks. METHODS: Adult smokers (n = 450, >10 cigarettes per day for ≥10 years) were randomly assigned to continue smoking (control) or switch to one of two cartridge-based EVPs (test 1: classic; test 2: menthol, 4% nicotine). BoE and BoPH were measured at baseline and 12 weeks. The results presented here are from a subset of 150 control and EVP subjects (switchers with exhaled carbon monoxide <8 ppm and <10% baseline cigarettes per day) followed for 24 total weeks. RESULTS: Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and carboxyhemoglobin were significantly reduced (p < .0001) in tests 1 and 2 at 24 weeks. Urinary nicotine equivalents were not statistically significantly different between the control and EVP groups. At week 24, statistically significant reductions (p < .05) were observed for white blood cell counts, 11-dehydrothromboxane ß2, and sICAM in both test groups, and there were several significant changes in measures of pulmonary function. High-density lipoprotein cholesterol and 8-epi-prostaglandin-F2α were directionally favorable in both EVP groups versus control. CONCLUSIONS: We demonstrate that significant reductions of selected harmful and potentially harmful constituents in EVP aerosol results in significant reductions in BoEs and favorable changes in BoPHs after switching to EVPs for 24 weeks. These changes approached those reported for smoking cessation, suggesting that switching to exclusive use of the EVPs may be less harmful than continuing smoking. IMPLICATIONS: Cigarette smoking causes serious diseases. Switching from cigarettes to a noncombustible product is a potential harm reduction pathway for adult smokers unable or unwilling to quit. Long-term health effects of e-vapor products (EVPs) compared with continued smoking have not been extensively studied. We present biomarker of exposure evidence on select harmful and potentially harmful constituents and biomarkers of potential harm related to inflammation and oxidative stress in adult smokers switching to two EVPs. This study demonstrates significant reductions in biomarkers of exposure (except for nicotine) accompanied with favorable changes in various biomarkers of potential harm, including pulmonary function. The totality of evidence suggests that exclusive EVP use may present lower health risks compared with smoking cigarettes.

Nicotine pharmacokinetics and subjective response among adult smokers using different flavors of on!® nicotine pouches compared to combustible cigarettes.

RATIONALE: on!® nicotine pouches (NPs) are oral tobacco-derived nicotine products that are tobacco-leaf free and are available in a variety of flavors and nicotine strengths. Switching completely to NPs from cigarettes may present the potential to reduce harm in adult smokers (AS) unable or unwilling to quit smoking. We characterized the abuse potential of six different flavor variants of NPs compared to cigarettes. OBJECTIVES: The objective of this study was to evaluate the nicotine pharmacokinetics (PK) and subjective effects of different flavor variants of NPs compared to participants' own brand cigarettes (OBCs) in AS. METHODS: In this single-blind, randomized, 7-way crossover study, we assessed nicotine PK, subjective measures (using well-established questionnaires), and product use behavior associated with six flavors of 4 mg NPs and OBCs in AS that remained in clinic for the duration of the test period. RESULTS: Nicotine Cmax values ranged from 9.0 to 11.5 ng/mL for the NPs and 16.3 ng/mL for OBCs. The tmax ranged from 30.1 to 34.9 min for ONPs and 7.5 min for OBCs. Use of NPs resulted in lower ratings of urge to smoke or craving a cigarette. All the NPs were considered pleasant, but not as much as OBCs. Flavor did not appear to influence the nicotine PK or subjective responses. CONCLUSIONS: Based on the nicotine PK parameters and subjective responses, we conclude that NPs, regardless of flavor, likely have lower abuse potential than cigarettes. Overall, this study suggests that the NPs may be potentially acceptable switching products for adult smokers.

Characterization of the Abuse Potential in Adult Smokers of a Novel Oral Tobacco Product Relative to Combustible Cigarettes and Nicotine Polacrilex Gum.

Novel noncombustible tobacco products offer adult smokers (ASs) alternatives to combustible cigarettes lower on the continuum of risk; however, the abuse potential of such products has not been well studied. The objective of this study was to evaluate the abuse potential of 2 chewable tobacco-derived nicotine containing products, VERVE Chews Blue Mint (test 1) and Green Mint (test 2), in ASs compared with own-brand cigarettes (CIGS) and nicotine polacrilex gum (GUM) using subjective measures and nicotine pharmacokinetics. ASs used the test products during a 5-day at-home trial prior to completing an in-clinic 4-period randomized crossover study. During the study ASs used test products, CIGS, and GUM once on separate days. Responses to Tobacco/Nicotine Withdrawal and Direct Effects of Product questionnaires were documented, and blood samples were collected to assess nicotine pharmacokinetics during each product use. Nicotine pharmacokinetic parameters (Cmax and AUC) were statistically significantly lower with use of test products compared with CIGS and statistically significantly higher compared with GUM. No appreciable differences were noted between the 2 flavors for any of the end points measured. Reductions in maximum urge to smoke and maximum responses to the question "Is the Product 'Pleasant' Right Now?" for the test products were statistically significantly lower than CIGS but comparable to GUM. Similar results were observed for responses to other items in the 2 questionnaires. The test products, under the conditions of this study, carry lower abuse potential than own-brand cigarettes and similar to nicotine polacrilex gum.

Application of online two-dimensional high-performance liquid chromatography as purification procedure to determine the origin of 19-norandrosterone in urine by gas chromatography-combustion-isotope ratio mass spectrometry.

19-Norandrosterone (19-NA) is the main metabolite of nandrolone and/or its precursors, which can be found naturally in human urine in trace amount. Gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) confirmation procedure can be used to identify a potential exogenous origin of 19-NA in urine sample. Sample purification for GC-C-IRMS analysis is crucial to the whole confirmation procedure because the concentration of 19-NA in the urine to be tested is very low. Online two-dimensional high-performance liquid chromatography (2D-HPLC) clean-up procedure with high separation capacity is used to isolate and enrich 19-NA as a sample pretreatment process. Linearity, lowest detectable concentration, uncertainty, and selectivity of the method are validated according to the World Anti-doping Agency's (WADA) requirement. Isotope fractionation effect was not observed during the 2D-HPLC purification process. The validated method provides a high efficient and convenient confirmation procedure to determine the origin of 19-NA.

Discrimination of wild and domestic deer musk using isotope ratio mass spectrometry.

Musk is the dried secretion of the musk pod (sac) of adult male musk deer, and has been used as perfume and traditional medicine for thousands of years. Steroid was regarded as 1 of the most important active compounds in musk. In order to protect the wild musk deer, musk deer farming has been carried out in China, India, and Nepal. However, it is hard to differentiate the 2 origins of musk by morphological identification. No other method has been reported so far for the discrimination of wild and domestic deer musk. The establishment of a reliable discrimination method has become an urgent work. In the present study, 6 batches of wild deer musk and 14 batches of domestic deer musk were collected. Analysis of steroid components in musk was carried out with GC-MS/MS. Androgen, progestin, estrogen, and sterol were detected in those samples. Large diversity was observed in the concentrations of steroids in musk. No obvious difference could be observed in steroid concentrations between wild and domestic deer musk by principal component analysis and cluster analysis. Furthermore, the δ13 C values of steroids were determined by gas chromatography/combustion coupled with isotopic ratio mass spectrometry. There were significant differences (P < .01) in steroid δ13 C values between wild origin musk and domesticated origin musk. Isotopic ratio mass spectrometry can be used to discriminate wild and domestic deer musk.

Fundamental study of sterilization effects on marine Vibrio sp. in a cylindrical water chamber with supply of only underwater shock waves.

The effect of shock sterilization on marine Vibrio sp. is investigated by carrying out a bio-experiment based on a bubble-shockwave interaction. In the experiments, underwater shock waves with different strength and frequencies are produced by a high-voltage power supply in a cylindrical water chamber. The bio-experimental results show marine Vibrio sp. is completely inactivated in a short time by a 1.0-Hz electric discharge. However, a high sterilization effect requires a strong and high frequency of the bubble motion, and it also depends on the lifetime of the bubble. Subsequently, by an experiment with an air gap to prevent the underwater shock waves entering the cell suspension, it is found that the introduction of a strong shock pressure is not entirely required to obtain the effective sterilization. On the other hand, the direct effect of the sterilization by rebound shock wave resulting from the bubble-shock wave interaction is examined in the experiments. The results suggest that free radicals mainly contribute to killing marine bacteria, and direct mechanical effects of the bubble motion are not responsible. In addition, the creation of the OH radical is indirectly confirmed by measuring the H2O2 concentration. Finally, the Herring equation is solved to investigate the condition of free radical generation when considering the effect of thermal conductivity at the bubble interface. As a result, the effective sterilization conditions based on the bubble-shock wave interaction are clearly obtained.

Steroid profile and IRMS analysis of musk administration for doping control.

Musk, the dried secretion of the musk pod (sac) of adult male musk deer, has been used as traditional Chinese Medicine (TCM) in China and south-east Asian countries for thousands of years. Due to the anabolic steroid component in this TCM, musk preparations have been included in the list of medical products containing prohibited substances employed for doping by the State Food and Drug Administration of China. The application of musk pod formulation was claimed to be responsible for some adverse analytical findings (AAFs) in the 2011 FIFA Women's World Cup. Our preliminary study has suggested that musk ingestion did not lead to AAFs of doping control with the single dosage of 100 mg. However, the influences of musk administration in large and multi dosage are still unclear. The aim of this study is to further investigate the influences of musk administration for doping control. Wild and domestic deer musk samples were collected. The concentrations and δ13 C-values of steroids in musk were analyzed. In an excretion study, 200 and 100 mg of wild and domestic deer musk samples were administrated by 29 subjects, respectively. Fluctuations in steroid profile could be observed, and the ratio of 5α-androstane-3α,17ß-diol to 5ß-androstane-3α,17ß-diol was more sensitive than other parameters. In the IRMS test, the ∆Δδ13 C-value between endogenous reference compound and etiocholanolone was a sensitive parameter, and AAFs were obtained. It is the first time to confirm with excretion study that musk administration could lead to positive result of doping control. Copyright © 2017 John Wiley & Sons, Ltd.

IRMS detection of testosterone manipulated with 13C labeled standards in human urine by removing the labeled 13C.

Isotope ratio mass spectrometry (IRMS) is applied to confirm testosterone (T) abuse by determining the carbon isotope ratios (δ(13)C value). However, (13)C labeled standards can be used to control the δ(13)C value and produce manipulated T which cannot be detected by the current method. A method was explored to remove the (13)C labeled atom at C-3 from the molecule of androsterone (Andro), the metabolite of T in urine, to produce the resultant (A-nor-5α-androstane-2,17-dione, ANAD). The difference in δ(13)C values between Andro and ANAD (Δδ(13)CAndro-ANAD, ‰) would change significantly in case manipulated T is abused. Twenty-one volunteers administered T manipulated with different (13)C labeled standards. The collected urine samples were analyzed with the established method, and the maximum value of Δδ(13)CAndro-ANAD post ingestion ranged from 3.0‰ to 8.8‰. Based on the population reference, the cut-off value of Δδ(13)CAndro-ANAD for positive result was suggested as 1.2‰. The developed method could be used to detect T manipulated with 3-(13)C labeled standards.

Impact of progesterone administration on doping test of endogenous steroids.

Progesterone (PROG) is a naturally occurring progestagen, which has been used to prevent preterm birth, control persistent anovulatory bleeding, and treat premenstrual syndrome in clinical practices. Studies on the metabolism of PROG have demonstrated that PROG is the precursor of other steroids such as 5ß-pregnane-3α,20α-diol (PD), testosterone (T), and 17-hydroxyprogesterone. PD is the most commonly used endogenous reference compound (ERC) in the isotope ratio mass spectrometry (IRMS) analysis for doping control. It is expected that the PROG administration could affect the carbon isotope ratios ((13)C/(12)C, expressed as δ (13)C-value) of PD and T metabolites, and lead to the false-negative or false-positive results in doping test. The influences of oral and intramuscular administration of PROG on the urinary steroid profile and carbon isotope ratios of steroids were investigated in this study. It was demonstrated that the urine concentrations and the δ (13)C-values of PD were affected obviously. The depleted δ (13)C-values of PD could be used to suggest PROG administration. Using PD as ERC may result in the distorted evaluation for suspicious urine sample in IRMS analysis when PROG is ingested. The 5α-androst-16-en-3α-ol and 11ß-hydroxyandrosterone could be used as the alternative ERCs in case of PROG administration. The carbon isotope ratios of androsterone (An) and etiocholanolone (Etio), two T metabolites, remained unchanged throughout the excretion study, which suggested that the δ values of An and Etio could still be used as the urinary markers of T administration even when PROG was administrated.

Cigarettes with different nicotine levels affect sensory perception and levels of biomarkers of exposure in adult smokers.

INTRODUCTION: Few clinical studies involving cigarettes have provided a comprehensive picture of smoke exposure, test article characterization, and insights into sensory properties combined. The purpose of these pilot studies was to determine whether cigarettes with different levels of nicotine but similar tar levels would affect sensory experience or smoking behavior so as to significantly alter levels of selected biomarkers of exposure (BOE). METHODS: In 2 confined, double-blind studies, 120 adult smokers switched from Marlboro Gold cigarettes at baseline to either 1 of 2 lower nicotine cigarettes or 1 of 2 higher nicotine cigarettes and then to the other cigarette after 5 days. Urinary excretion of exposure biomarkers (nicotine equivalents [NE], total and free 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL], 1-hydroxypyrene, and 3-hydroxypropyl mercapturic acid) as well as carboxyhemoglobin and plasma cotinine were measured at baseline, Day 5, and Day 10. Daily cigarette consumption was monitored and sensory characteristics were rated for each cigarette. RESULTS: With higher nicotine yield, urine NE, urine total NNAL, and plasma cotinine increased while nonnicotine BOE decreased without changes in cigarette consumption. In contrast, with lower nicotine yield, urine NE, urine total NNAL, and plasma cotinine dropped while nonnicotine BOE and cigarettes per day increased. Higher nicotine cigarettes were rated harsher and stronger than at baseline while lower nicotine cigarettes were less strong. All 4 test cigarettes were highly disliked. CONCLUSIONS: These studies demonstrate that abrupt increases or decreases in nicotine and the resulting sensory changes impact BOE through changes in intensity or frequency of smoking.

Influences of musk administration on the doping test.

Musk is widely used as a traditional drug in Asia for the treatment of stroke, tumour, and cardiopathy with an oral dosage of 0.03-0.1 g per day. Because of the potential anabolic effect, musk preparations have been included in the list of medical products containing prohibited substances employed for doping. The application of musk pod formulation was regarded as the reason of some adverse analytical findings in the 2011 FIFA Women's World Cup. In order to investigate the influence of musk administration on the doping test, we executed a chemical analysis and excretion study. The gas chromatography/mass spectrometry (GC-MS) analysis demonstrated the diversity of steroid concentrations in musk samples. Furthermore, the δ(13)C-values of steroids from wild deer musk showed more depleted than those of domestic deer musk by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) analysis. Because the steroids from some musk had δ(13)C-values in the range of naturally produced steroids in human body, the possible abuse of this kind of musk is very hard to be detected by isotope ratio mass spectrometry (IRMS) in doping control. Musk grains from wild and domestic deer were administrated for the excretion study respectively. Spot urine samples were collected from two male volunteers before and after 100 mg musk grains administration. The profiles and carbon isotope ratios of urinary steroids were determined by GC-MS and GC/C/IRMS. The ingestion of either wild or domestic deer musk did not lead to the adverse analytical finding of doping control in the single dosage of 100mg.

[Roles of moisture in constructing man-made algal crust with Micocoleus vaginatus].

To explore the roles of moisture in the construction of man-made algal crust with inoculated Micocoleus vaginatus, a laboratory experiment was conducted to study the variations of the microalgal biomass, algal crust thickness, crust compressive strength, and crust microstructure under six moisture doses and four moisture treatment intervals. When M. vaginatus was inoculated to the naked sands without moisture addition, the microalgal biomass was very low, and no algal crust was formed. With increasing dose of moisture, the microalgal biomass, algal crust thickness, and crust compressive strength increased significantly, and the algal filaments and extracellulhr polysaccharides (EPS) had a gradual increase, wrapped around the sands and formed a complex network. After 15 days moisture treatment, stable algal crust was formed, which had the highest microalgal biomass, crust thickness, and crust compressive strength. The optimal moisture dose for M. vaginatus to form man-made algal crust was 3-4 L.m-2.d-1, and the addition of moisture should be continued for 15 d. The availability of the moisture promoted the metabolic processes of M. vaginatus and the synthesis of the algal EPS, which increased the microalgal biomass and its ability to resist desiccation. The moisture availability at early stage was the key factor for M. vaginatus to successfully form algal crust. This study could offer some guidance for the recovery of biological soil crusts in the field.

Discriminating the endogenous and exogenous urinary estrogens in human by isotopic ratio mass spectrometry and its potential clinical value.

Estrogens were prohibited in the food producing animals by European Union (96/22/EC directive) and added to the Report on Carcinogens in United States since 2002. Due to very low concentration in serum or urine (~pg/mL), the method of control its abuse had not been fully developed. The endogenous estrogens were separated from urines of 18 adult men and women. The exogenous estrogens were chemical reference standards and over the counter preparations. Two patients of dysfunctional uterine bleeding (DUB) administered exogenous estradiol and the urines were collected for 72 h. The urinary estrogens were separated by high-performance liquid chromatography (HPLC) and confirmed. The exogenous and exogenous estrogens were analyzed by gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) to determine the (13)C/(12)C ratio (δ(13)C‰). The δ(13)C‰ values of reference standard of E1, E2, and E3 were -29.36±0.72, -27.98±0.35, -27.62±0.51, respectively. The δ(13)C‰ values of the endogenous E1, E2, and E3 were -21.62±1.07, -22.14±0.98, and -21.88±1.16, with P<0.01 (t-test). Two DUB patients' urinary estradiol δ(13)C‰ values was depleted to -28.02±0.33 after the administration. The progesterone, 17α-hydroxyprogesterone, pregnanediol, as well as desogestrel and ethinylestradiol from contraceptives were also determined. Stable carbon isotope analysis can distinguish the endogenous and exogenous urinary estrogen in human.