Gene-to-metabolite network for biosynthesis of lignans in MeJA-elicited Isatis indigotica hairy root cultures.

Root and leaf tissue of Isatis indigotica shows notable anti-viral efficacy, and are widely used as "Banlangen" and "Daqingye" in traditional Chinese medicine. The plants' pharmacological activity is attributed to phenylpropanoids, especially a group of lignan metabolites. However, the biosynthesis of lignans in I. indigotica remains opaque. This study describes the discovery and analysis of biosynthetic genes and AP2/ERF-type transcription factors involved in lignan biosynthesis in I. indigotica. MeJA treatment revealed differential expression of three genes involved in phenylpropanoid backbone biosynthesis (IiPAL, IiC4H, Ii4CL), five genes involved in lignan biosynthesis (IiCAD, IiC3H, IiCCR, IiDIR, and IiPLR), and 112 putative AP2/ERF transcription factors. In addition, four intermediates of lariciresinol biosynthesis were found to be induced. Based on these results, a canonical correlation analysis using Pearson's correlation coefficient was performed to construct gene-to-metabolite networks and identify putative key genes and rate-limiting reactions in lignan biosynthesis. Over-expression of IiC3H, identified as a key pathway gene, was used for metabolic engineering of I. indigotica hairy roots, and resulted in an increase in lariciresinol production. These findings illustrate the utility of canonical correlation analysis for the discovery and metabolic engineering of key metabolic genes in plants

Simulation of temperature distribution and discharge crater of SiCp/Al composites in a single-pulsed arc discharge

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The effect of scutellaria baicalensis and its active ingredients on major depressive disorder: a systematic review and meta-analysis of literature in pre-clinical research

Background: Scutellaria baicalensis, the dry root of scutellaria baicalensis georgi, is a traditional Chinese medicine with long. In clinic, scutellaria baicalensis is commonly used in prescription for the treatment of depression. Additionally, numerous pre-clinical studies have shown that Scutellaria baicalensis and its active constituents are effective for depression. In this study, we aims to systematically review the roles of scutellaria baicalensis in depression and summarize the possible mechanism.Methods: A systematic review and meta-analysis were conducted to analyze the existing studies on the effects of scutellaria baicalensis on depression in animal models. Briefly, we searched electronic databases including Pubmed and Embase for preclinical trial studies from inception to September 2023. The items in each study were evaluated by two independent reviewers, and meta-analyses were performed on scutellaria baicalensis-induced behavioral changes in the study. Finally, random effects model is used to collect data.Results: A total of 49 studies were identified, and 13 studies were included in the final analysis. They all reported the different antidepressant effects of scutellaria baicalensis and the underlying biological mechanisms. Among the included 13 studies, the results of eight articles SPT[SMD = −2.80, 95%CI(-4.03, -1.57), p < 0.01], the results of the nine articles OFT[SMD = −2.38, 95%CI(-3.53, -1.23), p < 0.01], and the results of two articles NSFT[SMD = −2.98, 95%CI(-3.94, -2.02), p < 0.01] were significantly different from the control group. The risk of bias was moderate in all studies, however, there was a significant heterogeneity among studies.Conclusion: These results preliminarily suggest that scutellaria baicalensis can alleviate depressive behaviors and modulate underlying mechanisms, which is expected to be a promising antidepressant

The SPB-Box Transcription Factor AaSPL2 Positively Regulates Artemisinin Biosynthesis in Artemisia annua L.

Artemisinin, an important compound produced by Artemisia annua, is the active ingredient in the treatment of malaria. Jasmonic acid, one of the phytohormones, is an important elicitor of artemisinin biosynthesis by enhancing transcription levels of transcription factors. SPL transcription factors are plant-specific transcription factors of plant growth, development, and secondary metabolism regulation. However, to date, the SPL transcription factors that regulate artemisinin biosynthesis is currently unclear. Here, we show that an SPL transcription factor can positively regulate artemisinin biosynthesis by binding to the promoter of artemisinin biosynthetic pathway genes. We screened AaSPL2 by gene expression profiles analysis in 14 SPL transcription factors. We demonstrated that AaSPL2 can activate the promoter of DBR2 by dual-LUC assy. Moreover, in the AaSPL2 overexpression plants, the artemisinin content was increased by 33–86%, and in the AaSPL2 -RNAi transgenic plants, artemisinin content was decreased by 33–65%. These data suggest that AaSPL2 and DBR2 interact with a “GTAC” cis-element in the DBR2 promoter, mediating the transcriptional activation of DBR2 in response to JA and resulting in the improvement on artemisinin content

Modified quantitative and volumetric response evaluation criteria for patients with hepatocellular carcinoma after transarterial chemoembolization

ObjectiveThis study aimed to investigate the cutoff value of quantitative and volumetric response evaluation criteria for patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) and compare the performance of the modified criteria to one-dimensional criteria in survival prediction.MethodsA retrospective single-center study was performed for treatment-naive patients with HCC who underwent initial TACE between June 2015 and June 2019. Treatment response assessment was performed after the first observation by contrast CT or MRI, with the measurement of diameters by modified Response Evaluation Criteria in Solid Tumors (mRECIST) and volumes by quantitative European Association for Study of the Liver (qEASL). Overall survival (OS) was the primary endpoint of this study. The new cutoff value for volumetric response evaluation criteria was created using restricted cubic splines. The performance of modified qEASL (mqEASL, with the new cutoff value) and mRECIST on survival prediction was compared by Cox regression models in internal and external validation.ResultsA total of 129 patients (mean age, 60 years ± 11 [standard deviation]; 111 men) were included and divided into training (n=90) and validation (n=39) cohorts. The cutoff value for the viable volume reduction was set at 57.0%. The mqEASL enabled separation of non-responders and responders in terms of median OS (p<0.001), 11.2 months (95% CI, 8.5–17.2 months) vs. 31.5 months (95% CI, 25.5–44.0 months). Two multivariate models were developed with independent prognostic factors (tumor response, metastasis, portal vein tumor thrombus, and subsequent treatment) to predict OS. Model 2 (for mqEASL) had a greater Harrel’s C index, higher time-dependent area under the receiving operator characteristic curve (AUROC), and more precise calibration on 6-month survival rates than Model 1 (for mRECIST).ConclusionsWith the modified cutoff value, the quantitative and volumetric response of HCC patients to TACE becomes a precise predictor of overall survival. Further studies are needed to verify this modification before application in clinical practice

Genome-Wide Identification and Characterization of Salvia miltiorrhiza Laccases Reveal Potential Targets for Salvianolic Acid B Biosynthesis

Laccases are widely distributed in plant kingdom catalyzing the polymerization of lignin monolignols. Rosmarinic acid (RA) has a lignin monolignol-like structure and is converted into salvianolic acid B (SAB), which is a representatively effective hydrophilic compound of a well-known medicinal plant Salvia miltiorrhiza and also the final compound of phenolic acids metabolism pathway in the plant. But the roles of laccases in the biosynthesis of SAB are poorly understood. This work systematically characterizes S. miltiorrhiza laccase (SmLAC) gene family and identifies the SAB-specific candidates. Totally, 29 laccase candidates (SmLAC1-SmLAC29) are found to contain three signature Cu-oxidase domains. They present relatively low sequence identity and diverse intron–exon patterns. The phylogenetic clustering of laccases from S. miltiorrhiza and other ten plants indicates that the 29 SmLACs can be divided into seven groups, revealing potential distinct functions. Existence of diverse cis regulatory elements in the SmLACs promoters suggests putative interactions with transcription factors. Seven SmLACs are found to be potential targets of miR397. Putative glycosylation sites and phosphorylation sites are identified in SmLAC amino acid sequences. Moreover, the expression profile of SmLACs in different organs and tissues deciphers that 5 SmLACs (SmLAC7/8/20/27/28) are expressed preferentially in roots, adding the evidence that they may be involved in the phenylpropanoid metabolic pathway. Besides, silencing of SmLAC7, SmLAC20 and SmLAC28, and overexpression of SmLAC7 and SmLAC20 in the hairy roots of S. miltiorrhiza result in diversification of SAB, signifying that SmLAC7 and SmLAC20 take roles in SAB biosynthesis. The results of this study lay a foundation for further elucidation of laccase functions in S. miltiorrhiza, and add to the knowledge for SAB biosynthesis in S. miltiorrhiza

Integrated Transcript and Metabolite Profiles Reveal That EbCHI Plays an Important Role in Scutellarin Accumulation in Erigeron breviscapus Hairy Roots

Scutellarin, a flavonoid 7-O-glucuronide, is an essential bioactive compound of Erigeron breviscapus (Vaniot) Hand.-Mazz. used for the treatment of cerebrovascular diseases. However, due to overexploitation and overuse, E. breviscapus is facing the problems of extinction and habitat degradation. In this study, a correlation analysis between the transcript and metabolite profiles of methyl jasmonate (MeJA)-treated E. breviscapus at different time points indicated that chalcone isomerase (EbCHI) was the primary contributor to scutellarin accumulation during flavonoid biosynthesis. EbCHI was then further characterized as a chalcone isomerase that efficiently converted chalcone to naringenin in vitro. Optimal parameters derived by comparing different culture conditions were successfully used to establish hairy root cultures of E. breviscapus with a maximum transformation rate of 60% in B5 medium. Furthermore, overexpression of EbCHI significantly enhanced scutellarin accumulation in E. breviscapus hairy roots with a maximum content of 2.21 mg g-1 (dw), 10-fold higher than that of natural roots (0.21 mg g-1 dw). This study sheds new light on a method of effective gene-based metabolic engineering by accurate and appropriate strategies and provides a protocol for hairy root cultures that accumulate high levels of scutellarin, providing a promising prospect for relieving the overexploitation and unavailability of E. breviscapus in the future