Cognitive Control Architecture for the Practical Realization of UAV Collision Avoidance.

A highly intelligent system often draws lessons from the unique abilities of humans. Current humanlike models, however, mainly focus on biological behavior, and the brain functions of humans are often overlooked. By drawing inspiration from brain science, this article shows how aspects of brain processing such as sensing, preprocessing, cognition, obstacle learning, behavior, strategy learning, pre-action, and action can be melded together in a coherent manner with cognitive control architecture. This work is based on the notion that the anti-collision response is activated in sequence, which starts from obstacle sensing to action. In the process of collision avoidance, cognition and learning modules continuously control the UAV's repertoire. Furthermore, simulated and experimental results show that the proposed architecture is effective and feasible.

UFObow: A single-wavelength excitable Brainbow for simultaneous multicolor ex-vivo and in-vivo imaging of mammalian cells.

Brainbow is a genetic cell-labeling technique that allows random colorization of multiple cells and real-time visualization of cell fate within a tissue, providing valuable insights into understanding complex biological processes. However, fluorescent proteins (FPs) in Brainbow have distinct excitation spectra with peak difference greater than 35 nm, which requires sequential imaging under multiple excitations and thus leads to long acquisition times. In addition, they are not easily used together with other fluorophores due to severe spectral bleed-through. Here, we report the development of a single-wavelength excitable Brainbow, UFObow, incorporating three newly developed blue-excitable FPs. We have demonstrated that UFObow enables not only tracking the growth dynamics of tumor cells in vivo but also mapping spatial distribution of immune cells within a sub-cubic centimeter tissue, revealing cell heterogeneity. This provides a powerful means to explore complex biology in a simultaneous imaging manner at a single-cell resolution in organs or in vivo.

C1M2: a universal algorithm for 3D instance segmentation, annotation, and quantification of irregular cells.

Cell instance segmentation is a fundamental task for many biological applications, especially for packed cells in three-dimensional (3D) microscope images that can fully display cellular morphology. Image processing algorithms based on neural networks and feature engineering have enabled great progress in two-dimensional (2D) instance segmentation. However, current methods cannot achieve high segmentation accuracy for irregular cells in 3D images. In this study, we introduce a universal, morphology-based 3D instance segmentation algorithm called Crop Once Merge Twice (C1M2), which can segment cells from a wide range of image types and does not require nucleus images. C1M2 can be extended to quantify the fluorescence intensity of fluorescent proteins and antibodies and automatically annotate their expression levels in individual cells. Our results suggest that C1M2 can serve as a tissue cytometry for 3D histopathological assays by quantifying fluorescence intensity with spatial localization and morphological information.

Three-dimensional mapping of hepatic lymphatic vessels and transcriptome profiling of lymphatic endothelial cells in healthy and diseased livers.

Rationale: Hepatic lymphatics are essential for liver homeostasis and immune function. However, the 3D structure and spatial distribution of hepatic lymphatic vessels (LVs) need to be confirmed. Moreover, the molecular information of hepatic lymphatic endothelial cells (LyECs) needs to be further studied. The bottleneck is the lack of specific markers or labeling methods for hepatic lymphatic endothelial cells (LyECs) Methods: Here, we proposed a method for the spatiotemporal sequential injection of antibodies (STSI-Ab) to selectively label hepatic LyECs in vivo. In addition, we also developed an efficient hepatic LyEC sorting method and performed deep transcriptome sequencing on hepatic LyECs. Results: The STSI-Ab method achieved selective labeling of the mouse hepatic lymphatic network. Three-dimensional fluorescence imaging results of the STSI-Ab mouse liver lobe clearly showed that hepatic LVs entangled with the portal vein but were not present in the central vein. The imaging data inspired a novel hepatic lobule structure model with an added set of LVs in the portal area. Furthermore, deep transcriptome sequencing of isolated hepatic LyECs and Masson's trichrome staining results suggested that hepatic LyECs might be an important source of collagen fibers deposited in the portal area during the process of liver fibrosis and bile duct ligation (BDL). Conclusions: We proposed an STSI-Ab method for selectively labeling hepatic LVs, distinguishing the hepatic LVs from other vessels, and mapping their 3D structure. This study opens an avenue for understanding hepatic lymphatic structure and it will be very beneficial to the study of hepatic LyEC functions.

Mesoscale visualization of three-dimensional microvascular architecture and immunocyte distribution in intact mouse liver lobes.

Rational: The complex vascular architecture and diverse immune cells of the liver are critical for maintaining liver homeostasis. However, quantification of the network of liver vasculature and immunocytes at different scales from a single hepatic lobule to an intact liver lobe remains challenging. Methods: Here, we developed a fast and fluorescence-preserving transparency method, denoted liver-CUBIC, for systematic and integrated analysis of the microcirculation and the three-dimensional distribution of dendritic cells (DCs)/macrophages in intact liver lobes. Results: Whole-mount imaging at mesoscale revealed that the hepatic classical lobule preferred the oblate ellipsoid morphology in the mouse liver and exhibited hepatic sinusoids with heterogeneous arrangement and intricate loop structure. Liver fibrosis not only induces sinusoidal density increase but also promotes sinusoidal arrangement with increased sinusoidal branch and loop structure. Meanwhile, we found that CD11c+ DCs followed a lognormal distribution in the hepatic lobules, skewing toward lobular boundary in steady state. CCl4-induced chronic liver injury promoted CD11c+ DC rearrangement at the lobular border before the formation of liver fibrosis. Furthermore, through whole-mount imaging of tumor-immune cell-vascular crosstalk in intact lobes based on liver-CUBIC, we characterized an accumulation of CX3CR1+CCR2+F4/80+ macrophages at metastatic foci in early colorectal liver metastases. Importantly, colorectal cells secrete CCL2 to mobilize CX3CR1+CCR2+F4/80+ macrophages to accumulate at liver micrometastases, and the interruption of CCL2-induced macrophage accumulation inhibits early colonization of metastasis in the liver. Conclusions: Our investigation of the sinusoidal network and DC/macrophage arrangements through the liver-CUBIC approach and whole-mount imaging provide a powerful platform for understanding hepatic circulatory properties and immune surveillance in the liver.

Comparative Analysis of the Fecal Bacterial Microbiota of Wintering Whooper Swans (Cygnus Cygnus).

There are many and diverse intestinal microbiota, and they are closely related to various physiological functions of the body. They directly participate in the host's food digestion, nutrient absorption, energy metabolism, immune response, and many other physiological activities and are also related to the occurrence of many diseases. The intestinal microbiota are extremely important for maintaining normal physical health. In order to explore the composition and differences of the intestinal microbiota of whooper swans in different wintering areas, we collected fecal samples of whooper swans in Sanmenxia, Henan, and Rongcheng, Shandong, and we used the Illumina HiSeq platform to perform high-throughput sequencing of bacterial 16S rRNA genes. Comparison between Sanmenxia and Rongcheng showed no significant differences in ACE, Chao 1, Simpson, and Shannon indices (p > 0.05). Beta diversity results showed significant differences in bacterial communities between two groups [analysis of similarity (ANOSIM): R = 0.80, p = 0.011]. Linear discriminant analysis effect size (LEfSe) analysis showed that at the phylum level, the relative abundance of Actinobacteria was significantly higher in Sanmenxia whooper swans than Rongcheng whooper swans. At the genus level, the amount of Psychrobacter and Carnobacterium in Sanmenxia was significantly higher in Rongcheng, while the relative abundance Catellicoccus and Lactobacillus was significantly higher in Rongcheng than in Sanmenxia. This study analyzed the composition, characteristics, and differences of the intestinal microbiota of the whooper swans in different wintering environments and provided theoretical support for further exploring the relationship between the intestinal microbiota of the whooper swans and the external environment. And it played an important role in the overwintering physiology and ecology, population management, and epidemic prevention and control of whooper swans.

Extrinsic factors, endocrine mechanisms, and behavioral indicators of migratory restlessness in wintering whooper swans (Cygnus cygnus).

Extrinsic factors, endocrine mechanisms, and behavioral indicators of migratory restlessness were studied in wintering whooper swans (Cygnus cygnus) in the Sanmenxia Swan National Wetland Park in western Henan Province, central China. First, the fecal glucocorticoid metabolite (FGM) concentration was established and related to mean air temperature or photo period (day length) using simple linear or non-linear regression models. After a model selection procedure, the best fitted model revealed that an increase of FGM concentration was associated with an increase in the squared mean air temperature (R2 = 0.88). Other models showed an increasing FGM concentration to correspond with increasing values of day length, squared day length, and mean air temperature-however without statistical support. In a second step, behavioral frequencies of seven behaviors were condensed into three behavioral principal components (PCs) using principal components analysis. Behavioral PCs largely corresponded to three activity phases described for wintering whooper swans in central China and were correlated with the FGM concentration using Spearman's rank-order correlations. Results revealed a significant correlation between FGM and behavioral PC2 (positive factor loadings from vigilance and preening, negative loading from foraging). Finally, we tested for an effect of behavioral PCs on changes in winter home range size using a set of multiple linear regression models. Results of averaged model parameter estimates showed only the behavioral PC3 (positive factor loadings from fighting and calling, negative loading from locomotion) had a marginal significant effect on home range size. Results confirmed findings of previous studies on migratory restlessness in whooper swans. However, due to the small sample size (N = 15 weeks) the effect of PC3 on home range size was weak and should be viewed with caution.

Targeted immunomodulation of inflammatory monocytes across the blood-brain barrier by curcumin-loaded nanoparticles delays the progression of experimental autoimmune encephalomyelitis.

It is difficult to carry out early diagnosis and treatment of Multiple sclerosis (MS) because of the complex pathogenesis elicited by diversified autoantigens. Monocytes play important roles in the process of MS, especially as most of the amplified inflammatory monocytes cross the BBB to promote neuron injury and recruit more immune cells to infiltrate the central nervous system (CNS). Here, we propose monocytes as an effective immunotherapy target for MS. We used High-density lipoprotein-mimicking peptide-phospholipid scaffold (HPPS) as a carrier to improve the bioavailability of curcumin. Curcumin-loaded HPPS (Cur-HPPS) were taken up specifically and efficiently by monocytes through the scavenger receptor class B type I (SR-B1) receptor. This delivery hindered inflammatory monocytes across the BBB in EAE mice, inhibited the proliferation of microglia, and restricted the infiltration of other effector immune cells, resulting in the reduction of EAE morbidity from 100% to 30%. It attributed to the immunomodulatory effect of Cur-HPPS on inflammatory monocytes, which inhibited NF-κB activation and downregulated the expression of adhesion-and migration-related molecules. Meanwhile, infiltrated monocytes in the CNS of EAE mice characterize early inflammation. Therefore, targeted modulation of monocytes with HPPS carrying therapeutic and/or imaging agents offers a novel strategy for MS diagnosis and treatment.

Production and characterisation of novel phosphate glass fibre yarns, textiles, and textile composites for biomedical applications.

This work presents manufacturing, processing and characterisation of the phosphate glass fibre (PGF) products for biomedical applications, including multifilament PGF strands, yarns and textiles, and PGF textile composites. The multifilament production of PGF strands was achieved using a 50-nozzle bushing. PGF yarns, with a linear density of 87 tex, a twist angle of 14° and a tensile strength of 0.29 N/tex, were produced by combining 8 fibre strands using the ring-spinning method. PGF textiles, with a width of 15 mm and a thickness of 0.36 mm, were prepared using an inkle loom. The maximum flexural strength and modulus of unidirectional (UD) composites with a fibre volume fraction of ~17% were 262 ±â€¯11 MPa and 10.4 ±â€¯0.2 GPa, respectively. PGF textile composites with a fibre volume fraction of ~21% exhibited mechanical properties of 176 ±â€¯13 MPa for flexural strength and 8.6 ±â€¯0.6 GPa for flexural modulus. Despite the UD and textile composites having almost an equivalent amount of fibres in the 0 direction, the crimp of the yarns was found to contribute to the significantly lower flexural properties of the textile composites in comparison with the unidirectional (UD) composites. Additionally, the processing conditions such as processing temperature and time were found to have a strong effect on the mechanical properties of the resultant composite products. The number-average molecular weight of PLA was also found to reduce by 13% and 19% after the production of PLA films and PLA plates, respectively, in comparison with the as-received PLA pellets.

Captive breeding of wildlife resources-China's revised supply-side approach to conservation.

The conservation and utilization of wild animals in China often raises public concerns. Thus, the Chinese government is increasingly exploring sustainable development of wildlife resources, and has implemented a series of measures, such as the modification of the Wildlife Protection Law (WPL), implementation of captive breeding licenses, an animal marking system, forest certification, and other actions to regulate captive breeding and utilization of wildlife. At the same time, the government tries to meet the Chinese traditional demand for wildlife products. We first introduce wildlife utilization as an internationally accepted conservation tool, and describe market-based wildlife farming as a legal substitute for wild-hunted animals. Second, we highlight the importance of wildlife products in Chinese culture and economy and review some successful examples of wildlife utilization in China, showing that the supply-side approach is a viable alternative to classical conservation. Subsequently, we outline benefits of, and drawbacks to, China's 'conservation through utilization' approach, resulting in the implementation of China's new, revised WPL. We discuss merits and shortcomings of China's revised WPL and respond to recent national and international criticism on China's supply-side approach to conservation. We strongly propose that captive breeding is a feasible approach to China's wildlife conservation-utilization dilemma, and much work is needed to promote the progress, such as legislation restructure, government attention, duties clarification, and so on. © 2019 The Wildlife Society.

Laser speckle contrast imaging of blood flow in the deep brain using microendoscopy.

Poor blood flow circulation can occur in the subcortical regions of the brain in many brain diseases. However, the limitations of light penetration imaging techniques hinder the detection of blood flow in deep brain tissues in vivo. Hence, in this Letter, we present a gradient index lens-based laser speckle contrast imaging system for time-lapse blood flow detection in subcortical regions of the brain. We monitored the hemodynamic changes in the thalamus of mouse models of acute hypoxia and transient middle cerebral artery occlusion as a proof of concept for practical applications.

Effects of breeding center, age and parasite burden on fecal triiodothyronine levels in forest musk deer.

The objective of this study was to evaluate the effects of sex, breeding center and age on fecal triiodothyronine levels in captive forest musk deer Moschus berezovskii, and to explore the age-intensity model of gastrointestinal parasites. Furthermore, the association between fecal triiodothyronine levels and parasite egg shedding was also analyzed. We collected musk deer fecal samples from two breeding centers located in Shaanxi and Sichuan province, China. Enzyme-linked immunosorbent assays were utilized to estimate the fecal triiodothyronine concentrations and profiles, and fecal parasite eggs or oocysts were counted using the McMaster technique. Female deer from both breeding centers consistently showed higher triiodothyronine concentrations than those observed in males, which indicates that a distinct physiology pattern occurs by sex. The triiodothyronine concentration in Sichuan breeding center was significantly higher than that in Shaanxi center for both sexes, suggesting that differences in environment, diet and management practices are likely to affect the metabolism. In addition, a negative relationship between triiodothyronine concentrations and age was found (r = - 0.75, p < 0.001), and parasite egg shedding was also negatively associated with age (r = - 0.51, p < 0.001), by which we can infer that older animals evolves a more developed immune system. Finally, a positive association between parasite egg shedding and triiodothyronine levels was found, which could be explained by the additional energy metabolism resulting from parasitic infection. Results from this study might suggest metabolic and immunological adaptations in forest musk deer. These baseline data could be used to unveil metabolic status and establish parasite control strategies, which has great potential in captive population management as well as their general health evaluations.

How much can we trust GPS wildlife tracking? An assessment in semi-free-ranging Crested Ibis Nipponia nippon.

GPS tracking has been increasingly used for wildlife studies in recent decades, but its performance has not been fully assessed, especially for newly developed lightweight transmitters. We assessed the performance of eight GPS transmitters developed in China by attaching them to Crested Ibises Nipponia nippon confined to two acclimation cages mimicking real habitats. We calculated the distance between GPS locations and the centroid of the cages as the positioning error, and used the 95% (95th percentile) positioning errors to define the accuracy. The positioning success averaged 92.0%, which is much higher than that of previous studies. Locations were not evenly distributed by Location Class (LC), with the LC A and B locations accounting for 88.7%. The observed 95% positioning error in the locations of LC A (9-39 m) and B (11-41 m) was quite accurate, while up to 6.9-8.8% of poor-quality locations were detected in LC C and D with >100 m or even >1, 000 m positioning error. Positioning success and accuracy were different between the test sites, probably due to the difference in vegetation structure. Thus, we argue that the tested transmitters could provide a large proportion of high-quality data for fine-scale studies, and a number of poor-quality locations that need attention. We suggest that the HPOD (horizontal dilution of precision) or PDOP (positional dilution of precision) be reported instead of the LC as a measurement of location accuracy for each location to ensure identification and filtering of implausible locations.

Application of reminiscence treatment on older people with dementia: a case study in Pingtung, Taiwan.

Reminiscence therapy has been utilized for many years in the treatment of dementia in older people. Purposes of the research included examining different methods of promoting interactivity, social participation, cognitive function improvement in those with dementia, and the effectiveness in reducing symptoms of depression following group treatment. This study used pretest and posttest electroencephalography (EEG) measurements to test reminiscence therapy efficacy on participants. This research organized a social group work with 12 elderly clients with dementia (mild to moderate stage) selected from among 90 residents of an older persons care facility in Pingtung. Eleven agreed to join the study, and 10 completed successfully all treatment sessions. Eight sessions of reminiscence cooking lessons were conducted. The effectiveness of interventions was evaluated by comparing presession and postsession EEG, mental health status, depression scale, and feeling of participation scale scores. Significant differences in values, particularly for EEG, were found between the two sets of scores. The average value of participants' fast waves rose from 43.88 to 55.12, whereas average slow-wave values fell from 56.12 to 44.13. After analysis using the Wilcoxon matched paired signed rank test, significant differences were noted. Findings and suggestions include the following: (a) The rise in Mini-Mental State Examination and reduction in depression scale scores, although noted, were not significant, and (b) the self-achievement, emotional stability, family atmosphere, and physical needs of participants were met. The authors recommend that reminiscence group work be promoted in the home for older persons and that childhood cooking sessions twice each week may be the ideal format for reminiscence group work.

Relationship between CYP3A activity and breast cancer susceptibility in Chinese Han women.

BACKGROUND: Breast cancer is the most frequent type of tumor in women. The main cause of breast cancer remains unknown. Extensive studies have shown that endogenous steroid hormones, especially estrogens, are important in the development and the progression of breast cancer, and the carcinogenesis of estrogens is related to their major oxidative metabolites, 16alpha-hydroxyestrogens and 4-hydroxyestrogens. CYP3A plays a major role in the 4- and 16alpha-hydroxylation of estrogens. Furthermore, CYP3A is present in human mammary epithelial cells and expressed higher and more frequently in malignant breast cells than in the adjacent normal breast tissue. Hence, it will be significant to perform more work to determine the association between CYP3A activity and breast cancer susceptibility. AIMS: To evaluate the relationship of CYP3A activity to breast cancer susceptibility in Chinese Han women using the plasma 1-hydroxymidazolam (1-OHMDZ) to midazolam (MDZ) ratio as the marker of CYP3A activity. METHODS: One hundred and twenty-nine Chinese Han female breast tumor patients and 121 healthy unrelated female volunteers were enrolled in the current study. After an overnight fast, each subject was administered a single oral dose (7.5 mg) of midazolam. Blood samples (5 ml) were drawn at 1 h after the drug administration. The concentration of parent MDZ and its major metabolite 1-OH-MDZ was measured in all the plasma samples using high-performance liquid chromatography. RESULTS: Complete chromatographic data on plasma ratios of 1-OHMDZ to MDZ for 103 cases of breast cancer and 114 controls were available. The plasma concentration ratios of 1-OHMDZ to MDZ were 0.4520+/-0.2318 and 0.3298+/-0.1610 for the malignant cases and the controls, respectively. A higher CYP3A activity was found in the breast cancer cases than in the controls ( P<0.001), and the CYP3A activity of patients with lymph-node metastasis was higher than that of patients without lymph-node metastasis ( P=0.028). CYP3A activity in estrogen receptor or progesterone receptor positive cases was the same as in estrogen receptor or progesterone receptor negative cases ( P=0.124, 0.175). CONCLUSIONS: Our results indicate that high CYP3A activity may contribute to breast cancer disease genesis and may promote breast cancer to lymph-node metastasis.

Inhibitory effect of troleandomycin on the metabolism of omeprazole is CYP2C19 genotype-dependent.

1. Eighteen healthy CYP2C19 genotyped male subjects were administered a 20-mg oral dose of omeprazole (OP) alone or received troleandomycin (TAO) 500 mg daily for 2 days before the dose of OP was administered. Blood samples were obtained and OP 5-hydroxyomeprazole (5-OH-OP) and OP sulfone in plasma were determined by reversed-phase HPLC. 2. The mean C(max), AUC and CL for OP in poor metabolizers (PMs) were greater with TAO than without TAO. The C(max) and AUC of 5-OH-OP in PMs were significantly (p < 0.05) less with TAO than without TAO. The differences in 5-OH-OP between heterozygous extensive metabolizers (EMs) with TAO versus without TAO were similar to those observed in PMs, except for the AUC. However, in homozygous EMs, there were no statistical differences for the effect of TAO. 3. The effect of TAO on the metabolism of OP and its two principal metabolites differs in different genotype groups of CYP2C19. CYP3A4 not only plays a dominant role in the formation of OP sulfone, but also it contributes to the 5-hydroxylation of OP. Both CYP2C19 and CYP3A contribute to the further elimination of 5-OH-OP and OP sulfone.

The distribution and gender difference of CYP3A activity in Chinese subjects.

AIMS: To investigate the distribution of CYP3A activity in the Chinese population, and to test for gender-related differences in CYP3A activity. METHODS: Using midazolam as a probe drug, CYP3A activity in 202 Chinese healthy subjects (104 men) was measured by plasma 1'-hydroxymidazolam:midazolam (1'-OH-MDZ:MDZ) ratio at 1 h after oral administration of 7.5 mg midazolam. The different phases of the menstrual cycle including preovulatory, ovulatory and luteal phases of 66 women phenotyped with midazolam were recorded. The concentrations of 1'-OH-MDZ and MDZ in plasma were measured by HPLC RESULTS: A 13-fold variation of CYP3A activity (log1'-OH-MDZ:MDZ: range -0.949-0.203) was shown. The CYP3A activity was normally distributed as indicated by the frequency distribution histogram, the probit plot and the Kolmogorov-Smirnov test (P > 0.05). The CYP3A activity of women was higher than that of men (median: -0.36 vs -0.43, P < 0.05; 95% CI for difference: -0.127, -0.012). There was a significant difference in CYP3A activity between the three phases of the menstrual cycle. The activity was highest in the preovulatory phase and decreased sequentially in the ovulatory and luteal phases (P < 0.05). CONCLUSIONS: A normal distribution of CYP3A activity was observed in the Chinese population. The CYP3A activity is higher in female subjects than in males. CYP3A activity differed across the phases of the menstrual cycle.

Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects.

OBJECTIVE: This study was designed to define the effect of low-dose aspirin administration on the activity of cytochrome P450 (CYP) in normal human subjects. METHODS: Aspirin, 50 mg daily, was given for 14 days to 18 nonsmoking healthy male volunteers. A modified 5-drug cocktail procedure consisting of caffeine, mephenytoin, metoprolol, chlorzoxazone, and midazolam was performed to simultaneously assess in vivo activity of CYP1A2, CYP2C19, CYP2D6, CYP2E1, and CYP3A, respectively. The activities were assessed on 4 occasions including at baseline, after 7 and 14 daily doses of aspirin, and at 7 days after discontinuation of aspirin. Concentrations of parent drugs and corresponding metabolites in biologic samples were assayed by reversed-phase HPLC. RESULTS: Both 7-day and 14-day aspirin intake increased the activity of CYP2C19 significantly, as indicated by 4-hydroxymephenytoin urinary recovery (P <.001). Induction of low-dose aspirin on CYP2C19 was time-dependent. CYP3A activity indices increased moderately but significantly by both 7-day and 14-day aspirin treatment (P <.05), but the percentage changes in CYP3A activity indices were not significant. Low-dose aspirin had no effect on CYP1A2, CYP2D6, and CYP2E1 in vivo activity by either 7-day or 14-day treatment. CONCLUSIONS: The effect of low-dose aspirin on CYPs was enzyme-specific. Both 7-day and 14-day low-dose aspirin induced the in vivo activities of CYP2C19 but did not affect the activities of CYP1A2, CYP2D6, and CYP2E1. The effect of low-dose aspirin on CYP3A activity awaits further confirmation. When low-dose aspirin is used in combination with drugs that are substrates of CYP2C19, doses of the latter should be adjusted to ensure their efficacy.

Phenotype distribution and gender-related differences of CYP2E1 activity in a Chinese population.

1. The aim was to investigate the phenotype distribution characteristic and gender-related differences of CYP2E1 activity in a healthy Chinese population. 2. Two hundred and three healthy Chinese subjects (105 men, 98 women) were enrolled in this study. 3. CYP2E1 activity was determined by plasma 6-hydroxychlorzoxazone-to-chlorzoxazone concentration ratio (CHZ-MR) 4h after chlorzoxazone dosing. The concentrations of 6-hydroxychlorzoxazone and chlorzoxazone in plasma were detected by reversed-phase HPLC. 4. The results showed an almost 9-fold variation of CYP2E1 activity at a range of from 0.23 to 1.99. The coefficient of variation CY % was demonstrated with skewness and kurtosis of the ratios in the studied population were 44%, 0.96 and 1.10, respectively. 5. CYP2E1 activity was normally distributed in logarithmic form of 6-OH-CHZ/CHZ as evaluated by Kolmogorov-Smirnov test of normality (p = 0.20). Probit plots of the CYP2E1 activity index of men shifted to the right as compared with that of women. The mean CHZ-MR in men was significantly higher than that in women (0.76 +/- 0.30 versus 0.60 +/- 0.28, p < 0.001), and this difference still existed when normalized by weight (0.73 +/- 0.28 versus 0.66 +/- 0.32, p = 0.016). Body weight correlated positively with CYP2E1 activity in the total group(r < 0.212, p < 0.01).

Phenotypic polymorphism of CYP2A6 activity in a Chinese population.

AIMS: To investigate the distribution characteristics of CYP2A6 activity in a Chinese population and to examine the sex-related differences in CYP2A6 activities. METHODS: One hundred and twenty healthy volunteers, 63 men and 57 women, were included in the study. Cytochrome P450 (CYP) 2A6 activity was measured using the ratio of urinary 7-hydroxycoumarin (7-OHC) excreted in 8 h after a coumarin dose. The concentrations of 7-OHC in urine were determined using high performance liquid chromatography. RESULTS: A 300-fold interindividual variation of CYP2A6 activity was shown in the studied Chinese population. The coefficient of variation of CYP2A6 activity was 27.2%. A Kolmogorov-Smirnov test indicated a non-normal distribution of CYP2A6 activity ( P<0.001). Probit plots of CYP2A6 activity revealed a bimodal distribution with breakpoint of activity index near 0.47. The percentage of poor metabolizers (PMs) was 13.3% (95% confidence interval 7.3%-19.4%) in this population. Residual analysis also supported bimodality ( P<0.01). The CYP2A6 activities of females were obviously higher than those of males when the activity index was less than 0.74, although no statistically significant difference in the activity index of CYP2A6 between males and females was found. However, there was no sex-related difference in the incidence of PMs ( P>0.5). CONCLUSIONS: There are pronounced interindividual variations and phenotypic polymorphism of CYP2A6 activities in the Chinese population.