Divergent Synthetic Approach to Grayanane Diterpenoids.

The total syntheses of nine grayanane diterpenoids, namely, GTX-II (1), GTX-III (2), rhodojaponin III (3), GTX-XV (4), principinol D (5), iso-GTX-II (6), 1,5-seco-GTX-Δ1,10-ene (7), and leucothols B (8) and D (9), that belong to five distinct subtypes, were disclosed in a divergent manner. Among them, six members were accomplished for the first time. The concise synthetic approach features three key transformations: (1) an oxidative dearomatization-induced [5 + 2] cycloaddition/pinacol rearrangement cascade to assemble the bicyclo[3.2.1]octane carbon framework (CD rings); (2) a photosantonin rearrangement to build up the 5/7 bicycle (AB rings) of 1-epi-grayanoids; and (3) a Grob fragmentation/carbonyl-ene process to access four additional subtypes of grayanane skeletons. Density functional theory calculations were performed to elucidate the mechanistic origins of the crucial divergent transformation, which combined with late-stage synthetic findings provided insights into the biosynthetic relationships between these diverse skeletons.

Genome-wide identification, molecular evolution, and expression analysis provide new insights into the APETALA2/ethylene responsive factor (AP2/ERF) superfamily in Dimocarpus longan Lour.

BACKGROUND: The APETALA2/ethylene responsive factor (AP2/ERF) superfamily members are transcription factors that regulate diverse developmental processes and stress responses in plants. They have been identified in many plants. However, little is known about the AP2/ERF superfamily in longan (Dimocarpus longan Lour.), which is an important tropical/subtropical evergreen fruit tree that produces a variety of bioactive compounds with rich nutritional and medicinal value. We conducted a genome-wide analysis of the AP2/ERF superfamily and its roles in somatic embryogenesis (SE) and developmental processes in longan. RESULTS: A genome-wide survey of the AP2/ERF superfamily was carried out to discover its evolution and function in longan. We identified 125 longan AP2/ERF genes and classified them into the ERF (101 members), AP2 (19 members), RAV (four members) families, and one Soloist. The AP2 and Soloist genes contained one to ten introns, whereas 87 genes in the ERF and RAV families had no introns. Hormone signaling molecules such as methyl jasmonate (MeJA), abscisic acid (ABA), gibberellin, auxin, and salicylic acid (SA), and stress response cis-acting element low-temperature (55) and defense (49) boxes also were identified. We detected diverse single nucleotide polymorphisms (SNPs) between the 'Hong He Zi' (HHZ) and 'SI JI MI' (SJM) cultivars. The number of insertions and deletions (InDels) was far fewer than SNPs. The AP2 family members exhibited more alternative splicing (AS) events in different developmental processes of longan than members of the other families. Expression pattern analysis revealed that some AP2/ERF members regulated early SE and developmental processes in longan seed, root, and flower, and responded to exogenous hormones such as MeJA, SA, and ABA, and 2,4-D, a synthetic auxin. Protein interaction predictions indicated that the Baby Boom (BBM) transcription factor, which was up-regulated at the transcriptional level in early SE, may interact with the LALF/AGL15 network. CONCLUSIONS: The comprehensive analysis of molecular evolution and expression patterns suggested that the AP2/ERF superfamily may plays an important role in longan, especially in early SE, and in seed, root, flower, and young fruit. This systematic analysis provides a foundation for further functional characterization of the AP2/ERF superfamily with the aim of longan improvement.

Exploration of the Effect of Blue Light on Functional Metabolite Accumulation in Longan Embryonic Calli via RNA Sequencing.

Light is an important factor that affects the synthesis of functional metabolites in longan embryogenic calli (ECs). However, analysis of the effect of light on functional metabolites in longan ECs via RNA sequencing has rarely been reported and their light regulation network is unclear. The contents of various functional metabolites as well as the enzymatic activities of superoxide dismutase and peroxidase and the level of H2O2 in longan ECs were significantly higher under blue light treatment than under the other treatments (dark, white). In this study, we sequenced three mRNA libraries constructed from longan ECs subjected to different treatments. A total of 4463, 1639 and 1806 genes were differentially expressed in the dark versus blue (DB), dark versus white (DW) and white versus blue (WB) combinations, respectively. According to GO and KEGG analyses, most of the differentially expressed genes (DEGs) identified were involved in transmembrane transport, taurine and hypotaurine metabolism, calcium transport and so forth. Mapman analysis revealed that more DEGs were identified in each DB combination pathway than in DW combination pathways, indicating that blue light exerts a significantly stronger regulatory effect on longan EC metabolism than the other treatments. Based on previous research and transcriptome data mining, a blue light signaling network of genes that affect longan functional metabolites was constructed and HY5, PIF4 and MYC2 were shown to be the key regulatory genes in the network. The results of this study demonstrate that the expression levels of phase-specific genes vary with changes in longan EC functional metabolites.

Trazodone changed the polysomnographic sleep architecture in insomnia disorder: a systematic review and meta-analysis.

Trazodone has been widely prescribed for off-label use as a sleep aid. Identifying how trazodone impacts the performance of polysomnographic sleep architecture in insomnia disorder will provide additional data that can be used to guide clinical application. To assess the efficacy of trazodone in altering the polysomnographic sleep architecture in insomnia disorder so that sleep can be facilitated. PubMed, EMBASE, Web of Science, PsycINFO, Cochrane Library, Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure, Wanfang Database, and the China Science and Technology Journal Database were searched for articles published between inception and June 2022. RCTs in patients with insomnia disorder applying trazodone in one arm of interventions at least 1 week, and reporting PSG parameters in the outcomes were eligible. RoB 2 was used to evaluate the risk of bias. The results of quality of evidence assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. When I2 < 50%, the fixed effects model was used. When I2 ≥ 50%, the random effects model was used. The mean differences (MD) or standardized mean differences (SMD) and odds ratios (OR) with 95% confidence intervals (CIs) were estimated. Eleven randomized controlled trials were selected and participants were 466. Risk of bias was low in 5 trials (45.5%), and was moderate in 6 (54.5%). Compared with the control group, trazodone significantly increased total sleep time (TST, min) (MD = 39.88, 95% CI 14.44-65.32, P = 0.002) and non-rapid eye movement stage 3 (N3, mixed min and %) (SMD = 1.61, 95% CI 0.69-2.53, P = 0.0006); trazodone significantly decreased latency to onset of persistent sleep (LPS, min) (MD = - 19.30, 95% CI - 37.28 to - 1.32, P = 0.04), non-rapid eye movement stage 1 (N1, mixed min and %) (SMD = - 0.62, 95% CI - 1.13 to - 0.12, P = 0.02), the number of awakenings (NAs, including both arousal times and arousal index) (SMD = - 0.67, 95% CI - 0.91 to - 0.42, P < 0.00001), and waking time after persistent sleep onset (WASO, mixed min and %) (SMD = - 0.42, 95% CI - 0.81, - 0.03, P = 0.04), with no obvious effect on non-rapid eye movement stage 2 (N2, mixed min and %) (SMD = - 0.15, 95% CI - 0.41 to 0.11, P = 0.25), rapid eye movement (REM, mixed min and %) (SMD = 0.22, 95% CI - 0.26 to 0.70, P = 0.37), rapid eye movement latency (REML, min) (MD = 2.33, 95% CI - 27.56 to 32.22, P = 0.88), or apnea-hypopnea index (AHI) (MD = - 4.21, 95% CI - 14.02 to 5.59, P = 0.40). Daytime drowsiness (OR = 2.53, 95% CI 1.14-5.64, P = 0.02) and decreased appetite (OR = 2.81, 95% CI 1.14-6.92, P = 0.02) occurred with greater frequency in the trazodone group as compared to the control group, and the differences were significant. The results of quality of evidence were very low in TST, N3 and AHI, were low in LPS, WASO and REM, and were moderate in N1 and NAs. The sources of heterogeneity in TST and N3 were not found out from sensitive and subgroup analysis and there was no high quality of evidence in outcomes by GRADE Assessment. Trials with combination of other therapy could be a problem in this meta-analysis as the possibility of interactions were found from sungroup analysis. Trazodone could improve sleep by changing the sleep architecture in insomnia disorder, but it should be used with caution due to the adverse events that may occur.PROSPERO registration register name: The effect of trazodone on polysomnography sleep architecture in patients with insomnia: a systematic review and meta-analysis protocol; Registration Number CRD42020215332.

Community promotion and application of Wuqinxi combined with brief behavioral therapy for insomnia: A study protocol.

BACKGROUND: Brief behavioral therapy for insomnia (BBT-I) has been proven to be a simple and effective alternative to cognitive behavioral therapy. However, low adherence limits the application in Chinese primary medical institutions, resulting in delayed or irregular treatment for many patients. This study aimed to explore the efficacy of traditional Chinese medicine external treatments on the adherence to behavioral therapy for insomnia in Chinese primary healthcare institutions, with a particular focus on patients who live in regions with weak healthcare systems. METHODS: This randomized controlled clinical trial will be conducted in primary medical institutions and will recruit 98 adult participants with insomnia. BBT-I will be used as the base treatment. The participants will be divided into experimental (combined with Wuqinxi and other traditional Chinese medicine [TCM] external treatment n = 49) and control (combined with trazodone treatment, n = 49) groups, and each group will be treated for 4 consecutive weeks. The severity index of insomnia will be used as the main indicator of disease evaluation, with an 8-point reduction in the score considered as effective and a score <8 considered as cured. The secondary indicators of the disease evaluation will include the Pittsburgh sleep quality index, Zung's self-rating anxiety scale, Zung's self-rating depression scale, treatment adherence, and adverse event reports. All participants will be followed up at the time of enrollment, 4 weeks after treatment, and 3 months after the end of treatment. DISCUSSION: This clinical trial will provide evidence for the efficacy of traditional Chinese medicine external treatment on the adherence to behavioral therapy for insomnia in primary medical institutions. This cheap and accessible model may benefit insomnia patients in medically underserved areas. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100042845. Registered on 30 January 2021, dataset: http://www.chictr.org.cn/showproj.aspx?proj=65691. Official scientific title of the research topic: Wuqinxi and other external treatment of Chinese Medicine combined with brief behavior therapy for insomnia.