Intermittent Hypoxia Inhibits Hepatic CYP1a2 Expression and Delays Aminophylline Metabolism.

Purpose: In this study, we aimed to determine the effects of intermittent hypoxia (IH) on hepatic cytochrome P450 1A2 (CYP1A2) expression and the pharmacokinetics of CYP1A2-mediated aminophylline and warfarin in vitro and in a rabbit model of obstructive sleep apnea. Materials: Human normal liver (LO-2) cells were exposed to 30 min each of 1%, 1-21%, 21%, and 21-1% O2, and then, CYP1A2 expression and drug concentrations were analyzed. We compared the pharmacokinetic parameters of drugs administered to normoxic rabbits and those exposed to 10 min of IH during which the oxygen level fluctuated from 21% to 8%-10% (n = 10 per group). Result: s. The expression of CYP1A2 protein in vitro was significantly reduced in the IH compared with the normoxic cells (0.56 ± 0.11 vs. 1.27 ± 0.17, p < 0.001). Aminophylline was more abundant in cell culture supernatants after 48 h of IH than in those under normoxia. The T 1/2, AUC0-24 h, and Ke values for aminophylline were significantly higher in the IH group. Conclusion: Intermittent hypoxia inhibits hepatic CYP1A2 expression and delays aminophylline metabolism, suggesting that the impact of IH on the expression of CYP enzymes should be closely monitored in clinical practice.

A complete sequence of mitochondrial genome of Neolamarckia cadamba and its use for systematic analysis.

Neolamarckia cadamba is an important tropical and subtropical tree for timber industry in southern China and is also a medicinal plant because of the secondary product cadambine. N. cadamba belongs to Rubiaceae family and its taxonomic relationships with other species are not fully evaluated based on genome sequences. Here, we report the complete sequences of mitochondrial genome of N. cadamba, which is 414,980 bp in length and successfully assembled in two genome circles (109,836 bp and 305,144 bp). The mtDNA harbors 83 genes in total, including 40 protein-coding genes (PCGs), 31 transfer RNA genes, 6 ribosomal RNA genes, and 6 other genes. The base composition of the whole genome is estimated as 27.26% for base A, 22.63% for C, 22.53% for G, and 27.56% for T, with the A + T content of 54.82% (54.45% in the small circle and 54.79% in the large circle). Repetitive sequences account for ~ 0.14% of the whole genome. A maximum likelihood (ML) tree based on DNA sequences of 24 PCGs supports that N. cadamba belongs to order Gentianales. A ML tree based on rps3 gene of 60 species in family Rubiaceae shows that N. cadamba is more related to Cephalanthus accidentalis and Hymenodictyon parvifolium and belongs to the Cinchonoideae subfamily. The result indicates that N. cadamba is genetically distant from the species and genera of Rubiaceae in systematic position. As the first sequence of mitochondrial genome of N. cadamba, it will provide a useful resource to investigate genetic variation and develop molecular markers for genetic breeding in the future.

Immune Mechanism, Gene Module, and Molecular Subtype Identification of Astragalus Membranaceus in the Treatment of Dilated Cardiomyopathy: An Integrated Bioinformatics Study.

Astragalus membranaceus has complex components as a natural drug and has multilevel, multitarget, and multichannel effects on dilated cardiomyopathy (DCM). However, the immune mechanism, gene module, and molecular subtype of astragalus membranaceus in the treatment of DCM are still not revealed. Microarray information of GSE84796 was downloaded from the GEO database, including RNA sequencing data of seven normal cardiac tissues and ten DCM cardiac tissues. A total of 4029 DCM differentially expressed genes were obtained, including 1855 upregulated genes and 2174 downregulated genes. GO/KEGG/GSEA analysis suggested that the activation of T cells and B cells was the primary cause of DCM. WGCNA was used to obtain blue module genes. The blue module genes are primarily ADCY7, BANK1, CD1E, CD19, CD38, CD300LF, CLEC4E, FLT3, GPR18, HCAR3, IRF4, LAMP3, MRC1, SYK, and TLR8, which successfully divided DCM into three molecular subtypes. Based on the CIBERSORT algorithm, the immune infiltration profile of DCM was analyzed. Many immune cell subtypes, including the abovementioned immune cells, showed different levels of increased infiltration in the myocardial tissue of DCM. However, this infiltration pattern was not obviously correlated with clinical characteristics, such as age, EF, and sex. Based on network pharmacology and ClueGO, 20 active components of Astragalus membranaceus and 40 components of DMCTGS were obtained from TCMSP. Through analysis of the immune regulatory network, we found that Astragalus membranaceus effectively regulates the activation of immune cells, such as B cells and T cells, cytokine secretion, and other processes and can intervene in DCM at multiple components, targets, and levels. The above mechanisms were verified by molecular docking results, which confirmed that AKT1, VEGFA, MMP9, and RELA are promising potential targets of DCM.

Analysis of Transcriptional Responses of the Inflorescence Meristems in Jatropha curcas Following Gibberellin Treatment.

Jatropha curcas L. seeds an oilseed plant with great potential for biodiesel production. However, low seed yield, which was limited by its lower female flowers, was a major drawback for its utilization. Our previous study found that the flower number and female-to-male ratio were increased by gibberellin treatment. Here, we compared the transcriptomic profiles of inflorescence meristem at different time points after gibberellic acid A3 (GA3) treatment. The present study showed that 951 differentially expressed genes were obtained in response to gibberellin treatment, compared with control samples. The 6-h time point was an important phase in the response to exogenous gibberellin. Furthermore, the plant endogenous gibberellin, auxin, ethylene, abscisic acid, and brassinolide-signaling transduction pathways were repressed, whereas the genes associated with cytokinin and jasmonic acid signaling were upregulated for 24-h time point following GA3 treatment. In addition, the floral meristem determinacy genes (JcLFY, JcSOC1) and floral organ identity genes (JcAP3, JcPI, JcSEP1-3) were significantly upregulated, but their negative regulator (JcSVP) was downregulated after GA3 treatment. Moreover, the effects of phytohormone, which was induced by exogenous plant growth regulator, mainly acted on the female floral differentiation process. To the best of our knowledge, this data is the first comprehensive analysis of the underlying transcriptional response mechanism of floral differentiation following GA3 treatment in J. curcas, which helps in engineering high-yielding varieties of Jatropha.

Housefly maggot-treated composting as sustainable option for pig manure management.

In traditional composting, large amounts of bulking agents must be added to reduce the moisture of pig manure, which increases the cost of composting and dilutes the N, P and K content in organic fertilizers. In this study, maggot treatment was used in composting instead of bulking agents. In experiment of selecting an optimal inoculum level for composting, the treatment of 0.5% maggot inoculum resulted in the maximum yield of late instar maggots, 11.6% (maggots weight/manure weight). The manure residue became noticeably granular by day 6 and its moisture content was below 60%, which was suitable for further composting without bulking agents. Moreover, in composting experiment with a natural compost without maggot inoculum and maggot-treated compost at 0.5% inoculum level, there were no significant differences in nutrient content between the two organic fertilizers from the two treatments (paired Student's t15=1.0032, P=0.3317). Therefore, maggot culturing did not affect the characteristics of the organic fertilizer. The content of TNPK (total nitrogen+total phosphorus+total potassium) in organic fertilizer from maggot treatment was 10.72% (dry weight), which was far more than that of organic fertilizer made by conventional composting with bulking agents (about 8.0%). Dried maggots as feed meet the national standard (GB/T19164-2003) for commercial fish meal in China, which contained 55.32 ± 1.09% protein; 1.34 ± 0.02% methionine; 4.15 ± 0.10% lysine. This study highlights housefly maggot-treated composting can be considered sustainable alternatives for pig manure management to achieve high-quality organic fertilizer and maggots as feed without bulking agents.

[Effect of aeration intensity on the nitrogen and phosphorus removal performance of AOA membrane bioreactors].

The ability of simultaneous phosphorus and nitrogen removal of sequencing batch membrane bioreactor run in anaerobic/oxic/ anoxic mode (AOA MBR) was examined under three aeration intensities [2.5, 3.75 and 5.0 m3 x (m2 x h)(-10]. The results showed that the averaged removals of COD were over 90% at different aeration intensities. And the higher aeration intensity was, the more ammonia nitrogen removal rate achieved. The removal rates of NH4(+) under the three aeration intensities were 84.7%, 90.6% and 93.8%, respectively. Total nitrogen removal rate increased with the increasing aeration intensity. But excessive aeration intensity reduced TN removal. The removal rates of TN under the three aeration intensities were 83.4%, 87.4% and 80.6%, respectively. Aeration intensity affected the denitrifying phosphorus ability of the AOA MBR. The ratio of denitrification phosphorus removal under the three aeration intensities were 20%, 30.2% and 26.7%, respectively.