Chromosome-scale genome assembly of Rhododendron molle provides insights into its evolution and terpenoid biosynthesis.

BACKGROUND: Rhododendron molle (Ericaceae) is a traditional Chinese medicine, which has been used to treat rheumatism and relieve pain since ancient times. The characteristic grayanoids of this plant have been demonstrated to be the chemical basis for the analgesic activity. Moreover, unlike morphine, these diterpenoids are non-addictive. Grayanoids mainly distribute in the leaves, flowers, roots, and fruits of R. molle, with low content. Currently the research on the biosynthesis of grayanoids is hindered, partially due to lack of the genomic information. RESULTS: In the present study, a total of 744 Mb sequences were generated and assembled into 13 chromosomes. An ancient whole-genome duplication event (Ad-ß) was discovered that occurred around 70 million years ago. Tandem and segmental gene duplications led to specific gene expansions in the terpene synthase and cytochrome P450 (CYP450) gene families. Two diterpene synthases were demonstrated to be responsible for the biosynthesis of 16α-hydroxy-ent-kaurane, the key precursor for grayanoids. Phylogenetic analysis revealed a species-specific bloom of the CYP71AU subfamily, which may involve the candidate CYP450s responsible for the biosynthesis of grayanoids. Additionally, three putative terpene biosynthetic gene clusters were found. CONCLUSIONS: We reported the first genome assembly of R. molle and investigated the molecular basis underpinning terpenoids biosynthesis. Our work provides a foundation for elucidating the complete biosynthetic pathway of grayanoids and studying the terpenoids diversity in R. molle.

De novo transcriptome sequencing of Rhododendron molle and identification of genes involved in the biosynthesis of secondary metabolites.

BACKGROUND: Rhododendron molle (Ericaceae) is a traditional Chinese medicinal plant, its flower and root have been widely used to treat rheumatism and relieve pain for thousands of years in China. Chemical studies have revealed that R. molle contains abundant secondary metabolites such as terpenoinds, flavonoids and lignans, some of which have exhibited various bioactivities including antioxidant, hypotension and analgesic activity. In spite of immense pharmaceutical importance, the mechanism underlying the biosynthesis of secondary metabolites remains unknown and the genomic information is unavailable. RESULTS: To gain molecular insight into this plant, especially on the information of pharmaceutically important secondary metabolites including grayanane diterpenoids, we conducted deep transcriptome sequencing for R. molle flower and root using the Illumina Hiseq platform. In total, 100,603 unigenes were generated through de novo assembly with mean length of 778 bp, 57.1% of these unigenes were annotated in public databases and 17,906 of those unigenes showed significant match in the KEGG database. Unigenes involved in the biosynthesis of secondary metabolites were annotated, including the TPSs and CYPs that were potentially responsible for the biosynthesis of grayanoids. Moreover, 3376 transcription factors and 10,828 simple sequence repeats (SSRs) were also identified. Additionally, we further performed differential gene expression (DEG) analysis of the flower and root transcriptome libraries and identified numerous genes that were specifically expressed or up-regulated in flower. CONCLUSIONS: To the best of our knowledge, this is the first time to generate and thoroughly analyze the transcriptome data of both R. molle flower and root. This study provided an important genetic resource which will shed light on elucidating various secondary metabolite biosynthetic pathways in R. molle, especially for those with medicinal value and allow for drug development in this plant.

Meta-analysis found that studies may have overestimated Caesarean section risks for attention-deficit hyperactivity disorder by ignoring confounding factors.

AIM: Epidemiological studies on associations between Caesarean sections (C-sections) and attention-deficit hyperactivity disorder (ADHD) have been inconsistent, and we performed a meta-analysis. METHODS: We systematically searched PubMed and Embase to December 2018 and included nine hospital-based and population registry studies published in 2011-2018. These covered a total study cohort of more than 2.5 million people in eight countries: Australia, Brazil, Denmark, Finland, Germany, Sweden, Turkey and the UK. The analysis provided summary odds ratios (ORs) and 95% confidence intervals (CI) while taking heterogeneity into account. RESULTS: We found that that C-sections were associated with a small increase in the risk of ADHD (OR 1.14, 95% CI 1.11, 1.17, I2 0%) in offspring. In subgroup analyses, the association remained for both infants born after elective C-sections (OR, 1.15, 1.11, 1.19, I2 0%) and emergency C-sections (OR, 1.13, 1.1, 1.17, I2 45.4%). However, these were only marginally significant when we pooled data from siblings from other pregnancies (OR, 1.06, 1.00-1.13, I2 0%), implying that the association was due to confounding. CONCLUSION: The statistically significant association between C-sections and ADHD in children can be partially explained by unmeasured confounding. Further research controlling for important confounders is required before firm conclusions can be drawn.

Short-Term Impact of Sleep Apnea/Hypopnea on the Interaction Between Various Cortical Areas.

INTRODUCTION: Sleep apnea/hypopnea syndrome (SAHS) can change brain structure and function. These alterations are related to respiratory event-induced abnormal sleep, however, how brain activity changes during these events is less well understood. METHODS: To study information content and interaction among various cortical regions, we analyzed the variations of permutation entropy (PeEn) and symbolic transfer entropy (STE) of electroencephalography (EEG) activity during respiratory events. In this study, 57 patients with moderate SAHS were enrolled, including 2804 respiratory events. The events terminated with cortical arousal were independently researched. RESULTS: PeEn and STE were lower during apnea/hypopnea, and most of the brain interaction was higher after apnea/hypopnea termination than that before apnea in N2 stage. As indicated by STE, the respiratory events also affected the stability of information transmission mode. In N1, N2, and rapid eye movement (REM) stages, the information flow direction was posterior-to-anterior, but the anterior-to-posterior increased relatively during apnea/hypopnea. The above EEG activity trends maintained in events with cortical arousal. CONCLUSIONS: These results may be related to the intermittent hypoxia during apnea and the cortical response. Furthermore, increased frontal information outflow, which was related to the compensatory activation of frontal neurons, may associate with cognitive function.