Genome-Wide Identification and Characterization of the Medium-Chain Dehydrogenase/Reductase Superfamily of Trichosporon asahii and Its Involvement in the Regulation of Fluconazole Resistance.

The medium-chain dehydrogenase/reductase (MDR) superfamily contains many members that are widely present in organisms and play important roles in growth, metabolism, and stress resistance but have not been studied in Trichosporon asahii. In this study, bioinformatics and RNA sequencing methods were used to analyze the MDR superfamily of T. asahii and its regulatory effect on fluconazole resistance. A phylogenetic tree was constructed using Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans, and T. asahii, and 73 MDRs were identified, all of which contained NADPH-binding motifs. T. asahii contained 20 MDRs that were unevenly distributed across six chromosomes. T. asahii MDRs (TaMDRs) had similar 3D structures but varied greatly in their genetic evolution at different phylum levels. RNA-seq and gene expression analyses revealed that the fluconazole-resistant T. asahii strain upregulates xylitol dehydrogenase, and downregulated alcohol dehydrogenase and sorbitol dehydrogenase concluded that the fluconazole-resistant T. asahii strain was less selective toward carbon sources and had higher adaptability to the environment. Overall, our study contributes to our understanding of TaMDRs, providing a basis for further analysis of the genes associated with drug resistance in T. asahii.

Elevated serum lead and cadmium levels associated with increased risk of dyslipidemia in children aged 6 to 9 years in Shenzhen, China.

Exposure to heavy metals can influence on metabolism, but studies have not fully evaluated young children. We investigated the association between levels of serum lead (Pb), cadmium (Cd), chromium (Cr), and arsenic (As) and risk of dyslipidemia in children. A total of 4513 children aged 6 to 9 years at 19 primary schools in Shenzhen were enrolled. Overall, 663 children with dyslipidemia were matched 1:1 with control by sex and age, and levels of serum Pb, Cd, Cr, and As were detected by inductively coupled plasma-mass spectrometry. Demographic characteristics and lifestyle were covariates in the logistic regression to determine the association of heavy metal levels with risk of dyslipidemia. Serum Pb and Cd levels were significantly higher in children with dyslipidemia than controls (133.08 vs. 84.19 µg/L; 0.45 vs. 0.29 µg/L; all P < 0.05), but this association was not found in Cr and As. We found significant upward trends for the odds ratios (ORs) of dyslipidemia associated with increasing quartiles of Pb and Cd levels (highest quartile of serum Pb OR 1.86, 95% confidence interval (CI) 1.46-2.38; Cd OR 2.51, 95% CI 1.94-3.24). Elevated serum Pb and Cd levels were associated with increased risk of dyslipidemia among children.

Effect of Exposure to Paternal Smoking on Overweight and Obesity in Children: Findings from the Children Lifeway Cohort in Shenzhen, Southern China.

INTRODUCTION: Paternal smoking associated with childhood overweight and obesity has been a concern, but studies have not investigated smoking exposure and smoking details. We investigated the association of exposures from paternal smoking as well as smoking details on offspring overweight/obesity. METHODS: A total of 4,513 children (aged 7-8 years) in Shenzhen were enrolled. Four different exposures from paternal smoking as well as smoking quantity, duration of smoking, and age of starting smoking details were the exposure variables and demographic characteristics, and circumstances of birth, dietary intake, lifestyle, and nonpaternal-smoking exposure were covariates in the logistic regression analysis to determine the effect of paternal smoking on childhood overweight/obesity, estimating odds ratios (ORs), and 95% confidence intervals (CIs). RESULTS: Paternal smoking was positively associated with childhood overweight/obesity (p < 0.05). Moreover, only preconception exposure, and both pre- and postconception exposure were significantly associated with childhood overweight/obesity (OR 1.54 [95% CI: 1.14-2.08] and OR 1.73 [95% CI: 1.14-2.61], respectively), restricted to boys but not girls. Furthermore, for children with only preconception paternal-smoking exposure, the dose-response relation was positive between smoking quantity, duration of smoking, age at starting, and overweight/obesity for boy offspring (p trend <0.001). We did not find any significant association between only postnatal exposure to paternal smoking and childhood overweight/obesity (p > 0.05). CONCLUSIONS: Our findings suggest that paternal smoking is associated with boys' overweight/obesity, and this association may be due to the paternal-smoking exposure before conception rather than the postnatal exposure to paternal smoking. Reducing paternal-smoking exposure before conception might help reduce overweight/obesity in boys.

Breakfast preferences and consumption location among children at a median age of 7 in Shenzhen: Implications for managing overweight and obesity.

BACKGROUND: Breakfast is commonly described as the most important meal of the day; however, we have little information regarding its relevance for childhood overweight and obesity in southern mainland China. This study aimed to assess the association between breakfast preferences, consumption location and overweight and obesity for children in Shenzhen. METHODS: Among 6126 children (median age 7.2 years) at primary schools, 3504 were finally included after a questionnaire survey and physical examination. Ten commonly consumed foods/beverages for breakfast in southern China were exposure variables, and consumption location, total energy demographic and other dietary characteristics were covariates in logistic regression to determine the effect of breakfast preferences on overweight and obesity, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Probability of overweight/general obesity was inversely associated with children eating plain congee for breakfast (adjusted OR 0.689, 95% CI 0.566-0.838), restricted to boys after stratification. Probability of overweight/general obesity and central obesity was positively associated with usually eating steamed rice roll for breakfast (OR 1.309, 95% CI 1.090-1.571 and OR 1.351, 95% CI 1.064-1.717, respectively), but the effect on overweight/obesity remained statistically significant for only boys after stratification. Eating steamed rice roll for breakfast and eating out for breakfast had an additive interaction on overweight/obesity. Additionally, eating bread for breakfast had a mild favorable effect on overweight/obesity but only for girls. CONCLUSIONS: Keeping a healthy weight might benefit children who eat plain congee or bread for breakfast in China. However, frequent consumption of steamed rice roll for breakfast and especially eating out could contribute to overweight and obesity. Thus, we need to promote a healthier breakfast pattern among children in southern China to reduce the odds of obesity.

Optimal number of beams for stereotactic body radiotherapy of lung and liver lesions.

PURPOSE: The aim of this study was to determine the optimal number of coplanar and noncoplanar external beams in the setting of stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Spherical targets were delineated within 2 separate extracranial sites, the lung and liver, with diameters varying from 2 cm to 7 cm to cover the range of volumes used in SBRT. Treatment plans were created for all target volumes using 5 to 15 geometrically optimized coplanar and noncoplanar conformal beams. Dose gradient and normal tissue complication probability (NTCP) were evaluated for each set of beam configurations and for each target size. RESULTS: For all lung and liver target volumes, the dose gradient improved with an increase in beam number from 5 to 15 for both coplanar and noncoplanar beam configurations. NTCP decreased as the beam number increased from 5 to 9 beams for all target sizes for both coplanar and noncoplanar beams. There is no significant improvement in NTCP when more than 9 beams were used for treatment planning regardless of target size. CONCLUSION: Based on dosimetric criteria, the optimal number of external beams is 13 to 15 for SBRT using either coplanar or noncoplanar beam bouquets. Simple biologic models indicate that the optimal number of beams is 9 for SBRT of lung and liver lesions >2 cm, whereas smaller lesions may benefit from plans using up to 13 beams.

Geometrically based optimization for extracranial radiosurgery.

For static beam conformal intracranial radiosurgery, geometry of the beam arrangement dominates overall dose distribution. Maximizing beam separation in three dimensions decreases beam overlap, thus maximizing dose conformality and gradient outside of the target volume. Webb proposed arrangements of isotropically convergent beams that could be used as the starting point for a radiotherapy optimization process. We have developed an extracranial radiosurgery optimization method by extending Webb's isotropic beam arrangements to deliverable beam arrangements. This method uses an arrangement of N maximally separated converging vectors within the space available for beam delivery. Each bouquet of isotropic beam vectors is generated by a random sampling process that iteratively maximizes beam separation. Next, beam arrangement is optimized for critical structure avoidance while maintaining minimal overlap between beam entrance and exit pathways. This geometrically optimized beam set can then be used as a template for either conformal beam or intensity modulated extracranial radiosurgery. Preliminary results suggest that using this technique with conformal beam planning provides high plan conformality, a steep dose gradient outside of the tumour volume and acceptable critical structure avoidance in the majority of clinical cases.