RGA1 regulates grain size, rice quality and seed germination in the small and round grain mutant srg5.

BACKGROUND: Generating elite rice varieties with high yield and superior quality is the main goal of rice breeding programs. Key agronomic traits, including grain size and seed germination characteristics, affect the final yield and quality of rice. The RGA1 gene, which encodes the α-subunit of rice G-protein, plays an important role in regulating rice architecture, seed size and abiotic stress responses. However, whether RGA1 is involved in the regulation of rice quality and seed germination traits is still unclear. RESULTS: In this study, a rice mutant small and round grain 5 (srg5), was identified in an EMS-induced rice mutant library. Systematic analysis of its major agronomic traits revealed that the srg5 mutant exhibited a semi-dwarf plant height with small and round grain and reduced panicle length. Analysis of the physicochemical properties of rice showed that the difference in rice eating and cooking quality (ECQ) between the srg5 mutant and its wild-type control was small, but the appearance quality was significantly improved. Interestingly, a significant suppression of rice seed germination and shoot growth was observed in the srg5 mutant, which was mainly related to the regulation of ABA metabolism. RGA1 was identified as the candidate gene for the srg5 mutant by BSA analysis. A SNP at the splice site of the first intron disrupted the normal splicing of the RGA1 transcript precursor, resulting in a premature stop codon. Additional linkage analysis confirmed that the target gene causing the srg5 mutant phenotype was RGA1. Finally, the introduction of the RGA1 mutant allele into two indica rice varieties also resulted in small and round rice grains with less chalkiness. CONCLUSIONS: These results indicate that RGA1 is not only involved in the control of rice architecture and grain size, but also in the regulation of rice quality and seed germination. This study sheds new light on the biological functions of RGA1, thereby providing valuable information for future systematic analysis of the G-protein pathway and its potential application in rice breeding programs.

Integrative Analysis of Transcriptomic and Metabolomic Data for Identification of Pathways Related to Matrine-Induced Hepatotoxicity.

Matrine (MT) is a major bioactive compound extracted from Sophorae tonkinensis. However, the clinical application of MT is relatively restricted due to its potentially toxic effects, especially hepatotoxicity. Although MT-induced liver injury has been reported, little is known about the underlying molecular mechanisms. In this study, transcriptomics and metabolomics were applied to investigate the hepatotoxicity of MT in mice. The results indicated that liver injury occurred when the administration of MT (30 or 60 mg/kg, i.g) lasted for 2 weeks, including dramatically increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), etc. The metabolomic results revealed that steroid biosynthesis, purine metabolism, glutathione metabolism, and pyruvate metabolism were involved in the occurrence and development of MT-induced hepatotoxicity. Further, the transcriptomic data indicated that the downregulation of NSDHL with CYP51, FDFT1, and DHCR7, involved in steroid biosynthesis, resulted in a lower level of cholic acid. Besides, Gstps and Nat8f1 were related to the disorder of glutathione metabolism, and HMGCS1 could be treated as the marker gene of the development of MT-induced hepatotoxicity. In addition, other metabolites, such as taurine, flavin mononucleotide (FMN), and inosine monophosphate (IMP), also made a contribution to the boosting of MT-induced hepatotoxicity. In this work, our results provide clues for the mechanism investigation of MT-induced hepatotoxicity, and several biomarkers (metabolites and genes) closely related to the liver injury caused by MT are also provided. Meanwhile, new insights into the understanding of the development of MT-induced hepatotoxicity or other monomer-induced hepatotoxicity were also provided.

Mechanisms of Cynarine for treatment of non-alcoholic fatty liver disease based on the integration of network pharmacology, molecular docking and cell experiment.

BACKGROUND: Nonalcoholic Fatty Liver Disease (NAFLD) is a chronic Liver Disease prevalent all over the world. It has become more and more common in Japan, China and most western developed countries. The global prevalence rate is 25.24%, and the trend is increasing year by year. Related studies have shown that Cynarine has certain liver protection, lipid lowering and immune intervention effects. So, this study to systematically predict and analyze the mechanism of Cynarine in the treatment of non-alcoholic fatty liver disease (NAFLD) based on the integration of network pharmacology, molecular docking, and cell experiment. METHODS: We performed Heatmap and Venn diagram analyses to identify genes and targets in Cynarine treat NAFLD. The network of Cynarine-therapeutic targets and the protein-protein interaction network (PPI) was constructed. We used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to visualize associated functional pathways. The Sybyl tool was used to dock the Cynarine with key therapeutic targets molecularly. Finally, cell experiments were applied to validate the role of Cynarine in the treatment of NAFLD. RESULTS: The Cynarine could act on 48 targets of NAFLD, and the role of CASP3, TP53, MMP9, ELANE, NOTCH1 were more important. The PPI network showed that immune and inflammation-related targets played a pivotal role. The KEGG analysis found that the PI3K-Akt signaling pathway, cell cycle and MAPK signaling pathway may be the main pathways for Cynarine to prevent and treat NAFLD. Molecular docking studies confirmed that Cynarine has good binding activity with therapeutic targets. Cynarine reduced the fat deposition ability of NAFLD model cells, and effectively reduced the levels of ALT and AST released by liver cells due to excessive lipid accumulation. We also found that Cynarine inhibited the expression of AKT1 and MAPK1. CONCLUSIONS: This study revealed that Cynarine could significantly reduce the fat deposition ability of NAFLD model cells, which may be closely related to the effective regulation of AKT1 and MAPK1 expression by Cynarine.

Allelic Diversification of the Wx and ALK Loci in Indica Restorer Lines and Their Utilisation in Hybrid Rice Breeding in China over the Last 50 Years.

Hybrid rice technology has been used for more than 50 years, and eating and cooking quality (ECQ) has been a major focus throughout this period. Waxy (Wx) and alkaline denaturation (ALK) genes have received attention owing to their pivotal roles in determining rice characteristics. However, despite significant effort, the ECQ of restorer lines (RLs) has changed very little. By contrast, obvious changes have been seen in inbred rice varieties (IRVs), and the ECQ of IRVs is influenced by Wx, which reduces the proportion of Wxa and increases the proportion of Wxb, leading to a decrease in amylose content (AC) and an increase in ECQ. Meanwhile, ALK is not selected in the same way. We investigated Wx alleles and AC values of sterile lines of female parents with the main mating combinations in widely used areas. The results show that almost all sterile lines were Wxa-type with a high AC, which may explain the low ECQ of hybrid rice. Analysis of hybrid rice varieties and RLs in the last 5 years revealed serious homogenisation among hybrid rice varieties.

Overview of Research into mTOR Inhibitors.

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that belongs to the phosphoinositide 3-kinase (PI3K)-related kinase (PIKK) family. The kinase exists in the forms of two complexes, mTORC1 and mTORC2, and it participates in cell growth, proliferation, metabolism, and survival. The kinase activity is closely related to the occurrence and development of multiple human diseases. Inhibitors of mTOR block critical pathways to produce antiviral, anti-inflammatory, antiproliferative and other effects, and they have been applied to research in cancer, inflammation, central nervous system diseases and viral infections. Existing mTOR inhibitors are commonly divided into mTOR allosteric inhibitors, ATP-competitive inhibitors and dual binding site inhibitors, according to their sites of action. In addition, there exist several dual-target mTOR inhibitors that target PI3K, histone deacetylases (HDAC) or ataxia telangiectasia mutated and Rad-3 related (ATR) kinases. This review focuses on the structure of mTOR protein and related signaling pathways as well as the structure and characteristics of various mTOR inhibitors. Non-rapalog allosteric inhibitors will open new directions for the development of new therapeutics specifically targeting mTORC1. The applications of ATP-competitive inhibitors in central nervous system diseases, viral infections and inflammation have laid the foundation for expanding the indications of mTOR inhibitors. Both dual-binding site inhibitors and dual-target inhibitors are beneficial in overcoming mTOR inhibitor resistance.

Radix Asteris: Traditional Usage, Phytochemistry and Pharmacology of An Important Traditional Chinese Medicine.

Radix Asteris (RA), also known as 'Zi Wan', is the dried root and rhizome of Aster tataricus L. f., which has been used to treat cough and asthma in many countries such as China, Japan, Korea and Vietnam. This article summarizes the available information on RA in ancient Chinese medicine books and modern research literature: its botanical properties, traditional uses, chemical composition, pharmacological activity, toxicity and quality control. Studies have shown that RA extracts contain terpenes, triterpenoid saponins, organic acids, peptides and flavonoids, and have various pharmacological activities such as anti-inflammatory, anti-tumor, anti-oxidation, and anti-depression. RA is considered to be a promising medicinal plant based on its traditional use, chemical constituents and pharmacological activities. However, there are few studies on its toxicity and the consistency of its components, which indicates the need for further in-depth studies on the toxicity and quality control of RA and its extracts.

Synchronous Extraction, Antioxidant Activity Evaluation, and Composition Analysis of Carbohydrates and Polyphenols Present in Artichoke Bud.

This study investigated the optimization of ultrasonic-assisted aqueous two-phase synchronous extraction of carbohydrates and polyphenols present in artichoke bud, evaluated their antioxidant activities in vitro, and analyzed the composition of carbohydrates and polyphenols by high-performance liquid chromatography (HPLC). The powder mass, ultrasonic time, ammonium sulfate concentration, and alcohol-water ratio were considered the influencing factors based on the single-factor experiment results, and a dual-response surface model was designed to optimize the synchronous extraction process to extract carbohydrates and polyphenols. The antioxidant activity was evaluated by measuring the scavenging capacity of ABTS+· and DPPH· and the reducing capacity of Fe3+. The optimal process conditions in this study were as follows: the powder mass of 1.4 g, ammonium sulfate concentration of 0.34 g/mL, alcohol-water ratio of 0.4, and ultrasonic time of 43 min. The polyphenol content in artichoke bud was 5.32 ± 0.13 mg/g, and the polysaccharide content was 74.78 ± 0.11 mg/g. An experiment on in vitro antioxidant activity showed that both carbohydrates and polyphenols had strong antioxidant activities, and the antioxidant activity of polyphenols was stronger than that of carbohydrates. The HPLC analysis revealed that the carbohydrates in artichoke bud were mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose, and the molar ratio was 10.77:25.22:2.37:15.74:125.39:48.62:34.70. The polyphenols comprised chlorogenic acid, 4-dicaffeoylquinic acid, caffeic acid, 1,3-dicaffeoylqunic acid, isochlorogenic acid B, isochlorogenic acid A, cynarin, and isochlorogenic acid C, and the contents were 0.503, 0.029, 0.022, 0.017, 0.008, 0.162, 1.621, 0.030 mg/g, respectively. This study also showed that the carbohydrates and polyphenols in artichoke bud could be important natural antioxidants, and the composition analysis of HPLC provided directions for their future research. Carbohydrates and polyphenols in artichoke buds can be separated and enriched using the optimized process technology, and it is an effective means of extracting ingredients from plants.

Investigation of Lonicera japonica Flos against Nonalcoholic Fatty Liver Disease Using Network Integration and Experimental Validation.

Background and objective: Lonicera japonica Flos (LJF) is a well-known traditional herbal medicine that has been used as an anti-inflammatory, antibacterial, antiviral, and antipyretic agent. The potent anti-inflammatory and other ethnopharmacological uses of LJF make it a potential medicine for the treatment of nonalcoholic fatty liver disease (NAFLD). This research is to explore the mechanisms involved in the activity of LJF against NAFLD using network integration and experimental pharmacology. Materials and methods: The possible targets of LJF involved in its activity against NAFLD were predicted by matching the targets of the active components in LJF with those targets involved in NAFLD. The analysis of the enrichment of GO functional annotations and KEGG pathways using Metascape, followed by constructing the network of active components-targets-pathways using Cytoscape, were carried out to predict the targets. Molecular docking studies were performed to further support the involvement of these targets in the activity of LJF against NAFLD. The shortlisted targets were confirmed via in vitro studies in an NAFLD cell model. Results: A total of 17 active components in LJF and 29 targets related to NAFLD were predicted by network pharmacology. Molecular docking studies of the main components and the key targets showed that isochlorogenic acid B can stably bind to TNF-α and CASP3. In vitro studies have shown that LJF down-regulated the TNF-α and CASP3 expression in an NAFLD cell model. Conclusions: These results provide scientific evidence for further investigations into the role of LJF in the treatment of NAFLD.

Glucan, Water-Dikinase 1 (GWD1), an ideal biotechnological target for potential improving yield and quality in rice.

The source-sink relationship determines the overall agronomic performance of rice. Cloning and characterizing key genes involved in the regulation of source and sink dynamics is imperative for improving rice yield. However, few source genes with potential application in rice have been identified. Glucan, Water-Dikinase 1 (GWD1) is an essential enzyme that plays a pivotal role in the first step of transitory starch degradation in source tissues. In the present study, we successfully generated gwd1 weak mutants by promoter editing using CRISPR/Cas9 system, and also leaf-dominant overexpression lines of GWD1 driven by Osl2 promoter. Analysis of the gwd1 plants indicated that promoter editing mediated down-regulation of GWD1 caused no observable effects on rice growth and development, but only mildly modified its grain transparency and seed germination. However, the transgenic pOsl2::GWD1 overexpression lines showed improvements in multiple key traits, including rice yield, grain shape, rice quality, seed germination and stress tolerance. Therefore, our study shows that GWD1 is not only involved in transitory starch degradation in source tissues, but also plays key roles in the seeds, which is a sink tissue. In conclusion, we find that GWD1 is an ideal biotechnological target with promising potential for the breeding of elite rice cultivars via genetic engineering.

The treatment of cardiovascular diseases: a review of ferulic acid and its derivatives.

Ferulic acid, a hydroxyl derivative extracted from plants, is abundant in free state in seeds and leaves, or covalently linked with cell wall polysaccharides, lignin and different polymers. It has various pharmacological activities, including antioxidant and anti-inflammatory effects, regulates immunity, protects the cardiovascular system, and contributes to the prevention of tumors and diabetes. The protective effect on cardiovascular system is the most valuable one in view of clinical application. Here, we are reviewing the research progress concerning the pharmacological effects of ferulic acid and its derivatives on cardiovascular diseases in the past five years, mainly focusing on mechanisms of action and clinical application. This should provide guidance for clinical applications of ferulic acid and its derivatives in the treatment of cardiovascular diseases.