Serum 25-hydroxyvitamin D and bone mineral density among children and adolescents in a Northwest Chinese city

Although vitamin D is essential for bone health, little is known about prevalence of vitamin D deficiency and low bone mineral density (BMD) among children, especially those in developing countries. It also remains unclear whether serum 25-hydroxyvitamin D [25(OH)D] is associated with BMD among children. We investigated these questions among children and adolescents in Yinchuan (latitude: 38° N), Ningxia, an economically underdeveloped province in Northwest China. A total of 1582 children (756 boys and 826 girls), aged 6–18 years, were recruited from schools using the stratified random sampling method in fall 2015. Serum 25(OH)D concentrations were measured by enzyme-linked immunosorbent assay, and BMD was quantified by dual-energy X-ray absorptiometry. Vitamin D deficiency (defined as serum 25(OH)D ≤ 37.5 nmol/L) was present in 35.5% of study subjects. There were no clear patterns of differences in serum 25(OH)D concentrations across the four age groups compared (6–9 years, 10–13 years, 14–16 years, and 17–18 years). The prevalence of low total body less head (TBLH) BMD (defined as a Z-score of ≤ −2.0 standard deviations away from the mean BMD values of the Chinese pediatric reference population) among children examined was 1.8% and was not significantly different among the four age groups considered. Linear regression analysis revealed that age, weight, and height were significantly and positively associated with TBLH BMD and that the strongest determinant of TBLH BMD was age in boys and weight in girls. There were no significant correlations between serum 25(OH)D concentrations and BMD obtained for total body and at various skeletal sites (r ranged from −0.005 to 0.014) regardless of whether children evaluated were sufficient, insufficient, or deficient in vitamin D. In conclusion, more than one-third of children and adolescents in a Northwest Chinese city were deficient in vitamin D but only <2% of them developed low BMD

milR20 negatively regulates the development of fruit bodies in Pleurotus cornucopiae

The mechanism underlying the development of fruit bodies in edible mushroom is a widely studied topic. In this study, the role of milRNAs in the development of fruit bodies of Pleurotus cornucopiae was studied by comparative analyses of the mRNAs and milRNAs at different stages of development. The genes that play a crucial role in the expression and function of milRNAs were identified and subsequently expressed and silenced at different stages of development. The total number of differentially expressed genes (DEGs) and differentially expressed milRNAs (DEMs) at different stages of development was determined to be 7,934 and 20, respectively. Comparison of the DEGs and DEMs across the different development stages revealed that DEMs and its target DEGs involved in the mitogen-activated protein kinase (MAPK) signaling pathway, protein processing in endoplasmic reticulum, endocytosis, aminoacyl-tRNA biosynthesis, RNA transport, and other metabolism pathways, which may play important roles in the development of the fruit bodies of P. cornucopiae. The function of milR20, which targeted pheromone A receptor g8971 and was involved in the MAPK signaling pathway, was further verified by overexpression and silencing in P. cornucopiae. The results demonstrated that the overexpression of milR20 reduced the growth rate of mycelia and prolonged the development of the fruit bodies, while milR20 silencing had an opposite effect. These findings indicated that milR20 plays a negative role in the development of P. cornucopiae. This study provides novel insights into the molecular mechanism underlying the development of fruit bodies in P. cornucopiae

Detection of Favorable QTL Alleles and Candidate Genes for Lint Percentage by GWAS in Chinese Upland Cotton

Improving cotton yield is a major breeding goal for Chinese upland cotton. Lint percentage is an important yield component and a critical economic index for cotton cultivars, and raising the lint percentage has a close relationship to improving cotton lint yield. To investigate the genetic architecture of lint percentage, a diversity panel consisting of 355 upland cotton accessions was grown, and the lint percentage was measured in four different environments. Genotyping was performed with specific-locus amplified fragment sequencing (SLAF-seq). Twelve single-nucleotide polymorphisms (SNPs) associated with lint percentage were detected via a genome-wide association study (GWAS), in which five SNP loci distributed on chromosomes At3 (A02) and At4 (A08) and contained two major-effect QTLs, which were detected in the best linear unbiased predictions (BLUPs) and in more than three environments simultaneously. Furthermore, favorable haplotypes (FHs) of two major-effect QTLs and 47 putative candidate genes in the two linkage disequilibrium (LD) blocks of these associated loci were identified. The expression levels of these putative candidate genes were estimated using RNA-seq data from ten upland cotton tissues. We found that Gh_A02G1268 was very highly expressed during the early fiber development stage, whereas the gene was poorly expressed in the seed. These results implied that Gh_A02G1268 may determine the lint percentage by regulating seed and fiber development. The favorable QTL alleles and candidate genes for lint percentage identified in this study will have high potential for improving lint yield in future Chinese cotton breeding programs

REG1A and RUNX3 Are Potential Biomarkers for Predicting the Risk of Diabetic Kidney Disease

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Clinical features are traditionally used to predict DKD, yet with low diagnostic efficacy. Most of the recent biomarkers used to predict DKD are based on transcriptomics and metabolomics; however, they also should be used in combination with many other predictive indicators. The purpose of this study was thus to identify a simplified class of blood biomarkers capable of predicting the risk of developing DKD. The Gene Expression Omnibus database was screened for DKD biomarkers, and differentially expressed genes (DEGs) in human blood and kidney were identified via gene expression analysis and the Least Absolute Shrinkage and Selection Operator regression. A comparison of the area under the curve (AUC) profiles on multiple receiver operating characteristic curves of the DEGs in DKD and other renal diseases revealed that REG1A and RUNX3 had the highest specificity for DKD diagnosis. The AUCs of the combined expression of REG1A and RUNX3 in kidney (AUC = 0.929) and blood samples (AUC = 0.917) of DKD patients were similar to each other. The AUC of blood samples from DKD patients and healthy individuals obtained for external validation further demonstrated that REG1A combined with RUNX3 had significant diagnostic efficacy (AUC=0.948). REG1A and RUNX3 expression levels were found to be positively and negatively correlated with urinary albumin creatinine ratio and estimated glomerular filtration rate, respectively. Kaplan-Meier curves also revealed the potential of REG1A and RUNX3 for predicting the risk of DKD. In conclusion, REG1A and RUNX3 may serve as biomarkers for predicting the risk of developing DKD

The Metacaspase Gene <i>PoMCA</i>1 Enhances the Mycelial Heat Stress Tolerance and Regulates the Fruiting Body Development of <i>Pleurotus ostreatus</i>

Pleurotus ostreatus is one of the most cultivated edible mushrooms worldwide, of which the fruiting body development is a highly complex process involving the precise genetic regulatory network and suitable environmental factors. Metacaspases play important roles in developmental processes and programmed cell death (PCD) induced by some environmental stress in many organisms. In this study, a type I metacaspase, PoMCA1, was identified via the analysis of the enzyme domain and alignment with homologous metacaspases. PoMCA1 overexpression and RNAi mutants were generated via Agrobacterium tumefaciens-mediated transformation (ATMT) into the P. ostreatus mycelium. The roles of the PoMCA1 gene in heat stress and fruiting body development were examined. The results show that both of the overexpression transformants were more tolerant to heat stress than the wild-type strain, while the opposite phenomenons were found for the two RNAi strains. Compared with the wild-type strain, the overexpression strain OE-7 had faster formation of the fruiting body, while the two RNAi strains produced significantly more primordia and young fruiting bodies, and presented morphological deformities and slower fruiting body development. All of the results suggest that the PoMCA1 gene is involved in the positive regulation of heat stress tolerance and fruiting body development in P. ostreatus

QSAR and Classification Study on Prediction of Acute Oral Toxicity of N-Nitroso Compounds

To better understand the mechanism of in vivo toxicity of N-nitroso compounds (NNCs), the toxicity data of 80 NNCs related to their rat acute oral toxicity data (50% lethal dose concentration, LD50) were used to establish quantitative structure-activity relationship (QSAR) and classification models. Quantum chemistry methods calculated descriptors and Dragon descriptors were combined to describe the molecular information of all compounds. Genetic algorithm (GA) and multiple linear regression (MLR) analyses were combined to develop QSAR models. Fingerprints and machine learning methods were used to establish classification models. The quality and predictive performance of all established models were evaluated by internal and external validation techniques. The best GA-MLR-based QSAR model containing eight molecular descriptors was obtained with Q2loo = 0.7533, R2 = 0.8071, Q2ext = 0.7041 and R2ext = 0.7195. The results derived from QSAR studies showed that the acute oral toxicity of NNCs mainly depends on three factors, namely, the polarizability, the ionization potential (IP) and the presence/absence and frequency of C&ndash;O bond. For classification studies, the best model was obtained using the MACCS keys fingerprint combined with artificial neural network (ANN) algorithm. The classification models suggested that several representative substructures, including nitrile, hetero N nonbasic, alkylchloride and amine-containing fragments are main contributors for the high toxicity of NNCs. Overall, the developed QSAR and classification models of the rat acute oral toxicity of NNCs showed satisfying predictive abilities. The results provide an insight into the understanding of the toxicity mechanism of NNCs in vivo, which might be used for a preliminary assessment of NNCs toxicity to mammals

Metabolic Activation and Carcinogenesis of Tobacco-Specific Nitrosamine N’-Nitrosonornicotine (NNN): A Density Function Theory and Molecular Docking Study

N&rsquo;-nitrosonornicotine (NNN) is one of the tobacco-specific nitrosamines (TSNAs) that exists widely in smoke and smokeless tobacco products. NNN can induce tumors in various laboratory animal models and has been identified by International Agency for Research on Cancer (IARC) as a human carcinogen. Metabolic activation of NNN is primarily initiated by cytochrome P450 enzymes (CYP450s) via 2&prime;-hydroxylation or 5&prime;-hydroxylation. Subsequently, the hydroxylating intermediates undergo spontaneous decomposition to generate diazohydroxides, which can be further converted to alkyldiazonium ions, followed by attacking DNA to form various DNA damages, such as pyridyloxobutyl (POB)-DNA adducts and pyridyl-N-pyrrolidinyl (py-py)-DNA adducts. If not repaired correctly, these lesions would lead to tumor formation. In the present study, we performed density functional theory (DFT) computations and molecular docking studies to understand the mechanism of metabolic activation and carcinogenesis of NNN. DFT calculations were performed to explore the 2&prime;- or 5&prime;- hydroxylation reaction of (R)-NNN and (S)-NNN. The results indicated that NNN catalyzed by the ferric porphyrin (Compound I, Cpd I) at the active center of CYP450 included two steps, hydrogen abstraction and rebound reactions. The free energy barriers of the 2&prime;- and 5&prime;-hydroxylation of NNN are 9.82/8.44 kcal/mol (R/S) and 7.99/9.19 kcal/mol (R/S), respectively, suggesting that the 2&prime;-(S) and 5&prime;-(R) pathways have a slight advantage. The free energy barriers of the decomposition occurred at the 2&prime;-position and 5&prime;-position of NNN are 18.04/18.02 kcal/mol (R/S) and 18.33/19.53 kcal/mol (R/S), respectively. Moreover, we calculated the alkylation reactions occurred at ten DNA base sites induced by the 2&prime;-hydroxylation product of NNN, generating the free energy barriers ranging from 0.86 to 4.72 kcal/mol, which indicated that these reactions occurred easily. The docking study showed that (S)-NNN had better affinity with CYP450s than that of (R)-NNN, which was consistent with the experimental results. Overall, the combined results of the DFT calculations and the docking obtained in this study provide an insight into the understanding of the carcinogenesis of NNN and other TSNAs