Aloe-emodin: Progress in Pharmacological Activity, Safety, and Pharmaceutical Formulation Applications.

Aloe-emodin (AE) is an anthraquinone derivative and a biologically active component sourced from various plants, including Rheum palmatum L. and Aloe vera. Known chemically as 1,8-dihydroxy-3-hydroxymethyl-anthraquinone, AE has a rich history in traditional medicine and is esteemed for its accessibility, safety, affordability, and effectiveness. AE boasts multiple biochemical and pharmacological properties, such as strong antibacterial, antioxidant, and antitumor effects. Despite its array of benefits, AE's identity as an anthraquinone derivative raises concerns about its potential for liver and kidney toxicity. Nevertheless, AE is considered a promising drug candidate due to its significant bioactivities and cost efficiency. Recent research has highlighted that nanoformulated AE may enhance drug delivery, biocompatibility, and pharmacological benefits, offering a novel approach to drug design. This review delves into AE's pharmacological impacts, mechanisms, pharmacokinetics, and safety profile, incorporating insights from studies on its nanoformulations. The goal is to outline the burgeoning research in this area and to support the ongoing development and utilization of AE-based therapies.

Integrated Transcriptomics and Metabolomics Analysis Reveals the Effects of Cutting on the Synthesis of Flavonoids and Saponins in Chinese Herbal Medicine Astragalus mongholious.

Astragali Radix, derived from the roots of Astragalus mongholicus, is a traditional Chinese medicine containing flavonoids and saponins as its key ingredients. With a shortage in the wild sources of the herbal plant, it is especially important to explore a cultivation mode for A. mongholicus for medicinal purposes. Cutting, a physical environmental stress method, was used in this study with the objective of improving the quality of this herbal legume. We found that cutting of the top 1/3 of the aboveground part of A. mongholicus during the fruiting period resulted in a significant increase in the content of flavonoids and saponins, as well as in root growth, including length, diameter, and dry weight. Furthermore, the leaves were sampled and analyzed using a combined transcriptome and metabolome analysis approach at five different time points after the treatment. Sixteen differentially expressed unigenes (DEGs) involved in the biosynthesis of flavonoids were identified; these were found to stimulate the synthesis of flavonoids such as formononetin and calycosin-7-O-ß-D-glucoside. Moreover, we identified 10 DEGs that were associated with the biosynthesis of saponins, including astragaloside IV and soyasaponin I, and found that they only regulated the mevalonic acid (MVA) pathway. These findings provide new insights into cultivating high-quality A. mongholicus, which could potentially alleviate the scarcity of this valuable medicinal plant.

Genome-Wide Analysis of Glycerol-3-Phosphate Acyltransferase (GPAT) Family in Perilla frutescens and Functional Characterization of PfGPAT9 Crucial for Biosynthesis of Storage Oils Rich in High-Value Lipids.

Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the first step in triacylglycerol (TAG) biosynthesis. However, GPAT members and their functions remain poorly understood in Perilla frutescens, a special edible-medicinal plant with its seed oil rich in polyunsaturated fatty acids (mostly α-linolenic acid, ALA). Here, 14 PfGPATs were identified from the P. frutescens genome and classified into three distinct groups according to their phylogenetic relationships. These 14 PfGPAT genes were distributed unevenly across 11 chromosomes. PfGPAT members within the same subfamily had highly conserved gene structures and four signature functional domains, despite considerable variations detected in these conserved motifs between groups. RNA-seq and RT-qPCR combined with dynamic analysis of oil and FA profiles during seed development indicated that PfGPAT9 may play a crucial role in the biosynthesis and accumulation of seed oil and PUFAs. Ex vivo enzymatic assay using the yeast expression system evidenced that PfGPAT9 had a strong GPAT enzyme activity crucial for TAG assembly and also a high substrate preference for oleic acid (OA, C18:1) and ALA (C18:3). Heterogeneous expression of PfGPAT9 significantly increased total oil and UFA (mostly C18:1 and C18:3) levels in both the seeds and leaves of the transgenic tobacco plants. Moreover, these transgenic tobacco lines exhibited no significant negative effect on other agronomic traits, including plant growth and seed germination rate, as well as other morphological and developmental properties. Collectively, our findings provide important insights into understanding PfGPAT functions, demonstrating that PfGPAT9 is the desirable target in metabolic engineering for increasing storage oil enriched with valuable FA profiles in oilseed crops.

Integrated metabolic and transcriptional analysis reveals the role of carotenoid cleavage dioxygenase 4 (IbCCD4) in carotenoid accumulation in sweetpotato tuberous roots.

BACKGROUND: Plant carotenoids are essential for human health, having wide uses in dietary supplements, food colorants, animal feed additives, and cosmetics. With the increasing demand for natural carotenoids, plant carotenoids have gained great interest in both academic and industry research worldwide. Orange-fleshed sweetpotato (Ipomoea batatas) enriched with carotenoids is an ideal feedstock for producing natural carotenoids. However, limited information is available regarding the molecular mechanism responsible for carotenoid metabolism in sweetpotato tuberous roots. RESULTS: In this study, metabolic profiling of carotenoids and gene expression analysis were conducted at six tuberous root developmental stages of three sweetpotato varieties with different flesh colors. The correlations between the expression of carotenoid metabolic genes and carotenoid levels suggested that the carotenoid cleavage dioxygenase 4 (IbCCD4) and 9-cis-epoxycarotenoid cleavage dioxygenases 3 (IbNCED3) play important roles in the regulation of carotenoid contents in sweetpotato. Transgenic experiments confirmed that the total carotenoid content decreased in the tuberous roots of IbCCD4-overexpressing sweetpotato. In addition, IbCCD4 may be regulated by two stress-related transcription factors, IbWRKY20 and IbCBF2, implying that the carotenoid accumulation in sweeetpotato is possibly fine-tuned in responses to stress signals. CONCLUSIONS: A set of key genes were revealed to be responsible for carotenoid accumulation in sweetpotato, with IbCCD4 acts as a crucial player. Our findings provided new insights into carotenoid metabolism in sweetpotato tuberous roots and insinuated IbCCD4 to be a target gene in the development of new sweetpotato varieties with high carotenoid production.

The effect of ethical leadership on service recovery performance: A moderated mediation model of organizational virtuousness and trait mindfulness.

In the present study, we first examined the relationship between ethical leadership and frontline employees' (FLEs') service recovery performance (SRP) and then tested the mediating role of organizational virtuousness in the relationship between ethical leadership and SRP in service contexts. Finally, we examined the moderating effect of FLE trait mindfulness on the direct relationship between ethical leadership and organizational virtuousness, as well as the indirect relationship between ethical leadership and SRP, via organizational virtuousness. Three-waved survey data collected from 273 supervisor-employee dyads in different service sector organizations supported our hypothesized relationships. In addition to important theoretical implications, the study carries useful practical implications, particularly for managers who are concerned about improving SRP in the service contexts.

Identification and Functional Characterization of Acyl-ACP Thioesterases B (GhFatBs) Responsible for Palmitic Acid Accumulation in Cotton Seeds.

In spite of increasing use in the food industry, high relative levels of palmitic acid (C16:0) in cottonseed oil imposes harmful effects on human health when overconsumed in the diet. The limited understanding of the mechanism in controlling fatty acid composition has become a significant obstacle for breeding novel cotton varieties with high-quality oil. Fatty acyl-acyl carrier protein (ACP) thioesterase B (FatBs) are a group of enzymes which prefer to hydrolyze the thioester bond from saturated acyl-ACPs, thus playing key roles in controlling the accumulation of saturated fatty acids. However, FatB members and their roles in cotton are largely unknown. In this study, a genome-wide characterization of FatB members was performed in allotetraploid upland cotton, aiming to explore the GhFatBs responsible for high accumulations of C16:0 in cotton seeds. A total of 14 GhFatB genes with uneven distribution on chromosomes were identified from an upland cotton genome and grouped into seven subfamilies through phylogenetic analysis. The six key amino acid residues (Ala, Trys, Ile, Met, Arg and Try) responsible for substrate preference were identified in the N-terminal acyl binding pocket of GhFatBs. RNA-seq and qRT-PCR analysis revealed that the expression profiles of GhFatB genes varied in multiple cotton tissues, with eight GhFatBs (GhA/D-FatB3, GhA/D-FatB4, GhA/D-FatB5, and GhA/D-FatB7) having high expression levels in developing seeds. In particular, expression patterns of GhA-FatB3 and GhD-FatB4 were positively correlated with the dynamic accumulation of C16:0 during cotton seed development. Furthermore, heterologous overexpression assay of either GhA-FatB3 or GhD-FatB4 demonstrated that these two GhFatBs had a high substrate preference to 16:0-ACP, thus contributing greatly to the enrichment of palmitic acid in the tested tissues. Taken together, these findings increase our understanding on fatty acid accumulation and regulation mechanisms in plant seeds. GhFatBs, especially GhA-FatB3 and GhD-FatB4, could be molecular targets for genetic modification to reduce palmitic acid content or to optimize fatty acid profiles in cotton and other oil crops required for the sustainable production of healthy edible oil.

Genome-wide identification, evolutionary and functional analyses of KFB family members in potato.

BACKGROUND: Kelch repeat F-box (KFB) proteins play vital roles in the regulation of multitudinous biochemical and physiological processes in plants, including growth and development, stress response and secondary metabolism. Multiple KFBs have been characterized in various plant species, but the family members and functions have not been systematically identified and analyzed in potato. RESULTS: Genome and transcriptome analyses of StKFB gene family were conducted to dissect the structure, evolution and function of the StKFBs in Solanum tuberosum L. Totally, 44 StKFB members were identified and were classified into 5 groups. The chromosomal localization analysis showed that the 44 StKFB genes were located on 12 chromosomes of potato. Among these genes, two pairs of genes (StKFB15/16 and StKFB40/41) were predicted to be tandemly duplicated genes, and one pair of genes (StKFB15/29) was segmentally duplicated genes. The syntenic analysis showed that the KFBs in potato were closely related to the KFBs in tomato and pepper. Expression profiles of the StKFBs in 13 different tissues and in potato plants with different treatments uncovered distinct spatial expression patterns of these genes and their potential roles in response to various stresses, respectively. Multiple StKFB genes were differentially expressed in yellow- (cultivar 'Jin-16'), red- (cultivar 'Red rose-2') and purple-fleshed (cultivar 'Xisen-8') potato tubers, suggesting that they may play important roles in the regulation of anthocyanin biosynthesis in potato. CONCLUSIONS: This study reports the structure, evolution and expression characteristics of the KFB family in potato. These findings pave the way for further investigation of functional mechanisms of StKFBs, and also provide candidate genes for potato genetic improvement.

Astaxanthin from Haematococcus pluvialis alleviates obesity by modulating lipid metabolism and gut microbiota in mice fed a high-fat diet.

Obesity is a global chronic disease epidemic that is attributed to the abnormal accumulation of lipids in adipose tissue. Astaxanthin (AST) from Haematococcus pluvialis, a natural carotenoid, exhibits antioxidant, anti-lipogenic, anti-diabetic and other potent effects. Herein, we evaluated the effect of AST to illuminate its efficacy and mechanisms in high-fat diet-fed mice. AST supplementation not only significantly decreased body weight and lipid droplet accumulation in the liver but also modulated liver function and serum lipid levels. Lipidomic analysis revealed that 13 lipids might be potential biomarkers responsible for the effects of AST in lipid reduction, such as total free fatty acids (FFAs), triacylglycerols (TGs) and cholesterol esters (CEs). The gut microbiota sequencing results indicated that AST alleviated HFD-induced gut microbiota dysbiosis by optimizing the ratio of Firmicutes to Bacteroides and inhibiting the abundance of obesity-related pathogenic microbiota while promoting the abundance of probiotics related to glucose and lipid metabolism. In addition, qRT-PCR demonstrated that AST could regulate the gene expressions of the AMPK/SREBP1c pathway by downregulating lipogenesis correlated-genes and upregulating the lipid oxidant related-gene. The present study revealed the new function of AST in regulating lipid metabolism, which provided a theoretical basis for the development of high-quality AST functional food and the application of diet active substances in obesity, as demonstrated in mice.

Advanced treatment of chicken farm flushing wastewater by integrating Fenton oxidation and algal cultivation process for algal growth and nutrients removal.

Algae based wastewater treatment has been considered as the most promising win-win strategy for nutrients removal and biomass accumulation. However, the poor linking between traditional wastewater treatment and algal cultivation limits the achievement of this goal. In this study, a novel combination of Fenton oxidation and algal cultivation (CFOAC) system was investigated for the treatment of chicken farm flushing wastewater (CFFW). Fenton oxidation (FO) was adopted to reduce the excessive ammonia nitrogen, which might inhibit the algal growth. The results showed that single FO pretreatment removed 70.5 %, 96.7 %, 86.1 %, and 96.2 % of TN, TAN, TP, and COD, respectively. The highest biomass (235.8 mg/L/d) and lipid (77.3 mg/L/d) productivities were achieved on optimized CFOAC system after 7 days batch cultivation. Accordingly, the nutrients removal efficiencies increased to almost 100 %. Further fatty acid profile analysis showed that algae grown on optimal CFOAC system accumulated a high level of total lipids (32.8 %) with C16-C18 fatty acid as the most abundant compositions (accounting for over 60.6 %), which were propitious to biodiesel production. In addition, this CFOAC system was magnified from 1 L flask to 50 L horizontal pipe photobioreactor (HPPB) in semi-continuously culture under optimal conditions. The average biomass and lipid productivities were 995.7 mg/L/d and 320.6 mg/L/d, respectively, when cultured at 6 days hydraulic retention time with 1/3 substitution every two days. These findings proved that the novel CFOAC system is efficient in nutrients removal, algal cultivation, and biomass production for advanced treatment of CFFW.

Ectopic overexpression of a type-II DGAT (CeDGAT2-2) derived from oil-rich tuber of Cyperus esculentus enhances accumulation of oil and oleic acid in tobacco leaves.

BACKGROUND: Engineering triacylglycerol (TAG) accumulation in vegetative tissues of non-food crops has become a promising way to meet our increasing demand for plant oils, especially the renewable production of biofuels. The most important target modified in this regard is diacylglycerol acyltransferase (DGAT) enzyme responsible for the final rate-limiting step in TAG biosynthesis. Cyperus esculentus is a unique plant largely accumulating oleic acid-enriched oil in its underground tubers. We speculated that DGAT derived from such oil-rich tubers could function more efficiently than that from oleaginous seeds in enhancing oil storage in vegetative tissues of tobacco, a high-yielding biomass crops. RESULTS: Three CeDGAT genes namely CeDGAT1, CeDGAT2-1 and CeDGAT2-2 were identified in C. esculentus by mining transcriptome of developing tubers. These CeDGATs were expressed in tissues tested, with CeDGAT1 highly in roots, CeDGAT2-1 abundantly in leaves, and CeDGAT2-2 predominantly in tubers. Notably, CeDGAT2-2 expression pattern was in accordance with oil dynamic accumulation during tuber development. Overexpression of CeDGAT2-2 functionally restored TAG biosynthesis in TAG-deficient yeast mutant H1246. Oleic acid level was significantly increased in CeDGAT2-2 transgenic yeast compared to the wild-type yeast and ScDGA1-expressed control under culture with and without feeding of exogenous fatty acids. Overexpressing CeDGAT2-2 in tobacco led to dramatic enhancements of leafy oil by 7.15- and 1.7-fold more compared to the wild-type control and plants expressing Arabidopsis seed-derived AtDGAT1. A substantial change in fatty acid composition was detected in leaves, with increase of oleic acid from 5.1% in the wild type to 31.33% in CeDGAT2-2-expressed tobacco and accompanied reduction of saturated fatty acids. Moreover, the elevated accumulation of oleic acid-enriched TAG in transgenic tobacco exhibited no significantly negative impact on other agronomic traits such as photosynthesis, growth rates and seed germination except for small decline of starch content. CONCLUSIONS: The present data indicate that CeDGAT2-2 has a high enzyme activity to catalyze formation of TAG and a strong specificity for oleic acid-containing substrates, providing new insights into understanding oil biosynthesis mechanism in plant vegetative tissues. Overexpression of CeDGAT2-2 alone can significantly increase oleic acid-enriched oil accumulation in tobacco leaves without negative impact on other agronomy traits, showing CeDGAT2-2 as the desirable target gene in metabolic engineering to enrich oil and value-added lipids in high-biomass plants for commercial production of biofuel oils.

Transcriptome sequencing and characterization of Astragalus membranaceus var. mongholicus root reveals key genes involved in flavonoids biosynthesis.

BACKGROUND: Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao is a traditional medicinal herb of Leguminosae since it contains bioactive compounds such as flavonoids, which have significant pharmacological effects on immunity and antioxidant. However, the scanty genomic and transcriptome resources of Astragalus membranaceus have hindered further exploration of its biosynthesis and accumulation mechanism. OBJECTIVE: This project aim to further improve our understanding of the relationship between transcriptional behavior and flavonoids content of A. mongholicus. METHODS: The accumulation of flavonoids and related gene expression in five different developmental stages (A: vegetative, B: florescence, C: fruiting, D: fruit ripening and E: defoliating stages) of A. mongholicus root were studied by combining UV spectrophotometry and transcriptomic techniques. The de novo assembly, annotation and functional evaluation of the contigs were performed with bioinformatics tools. RESULTS: After screening and assembling the raw data, there were a total of 158,123 unigenes with an average length of 644.89 bp were finally obtained, which has 8362 unigenes could be jointly annotated by NR, SwissProt, eggNOG, GO, KEGG and Pfam databases. KEGG enrichment analysis was performed on differentially expressed genes(DEGs)in the four groups (A vs. B, B vs. C, C vs. D, D vs. E). The results showed that many DEGs in each group were significantly enriched to flavonoids biosynthesis related pathways. Among them, a number of 86 were involved in the biosynthesis of isoflavonoid (12), flavonoid (5) and phenylpropanoid (69). Further analysis of these DEGs revealed that the expression levels of key genes such as PAL, 4CL, CCR, COMT, DFR, etc. were all down-regulated at the fruiting stage, and then raised at the fruit ripening stage. This expression pattern was similar to the accumulation trend of total flavonoids content. CONCLUSIONS: In summary, this comprehensive transcriptome dataset allowed the identification of genes associated with flavonoids metabolic pathways. The results laid a foundation for the biosynthesis and regulation of flavonoids. It also provided a scientific basis for the most suitable harvest time and resource utilization of A. mongholicus.

A novel deep intronic COL2A1 mutation in a family with early-onset high myopia/ocular-only Stickler syndrome.

PURPOSE: To identify the genetic defect causing early-onset high myopia (eoHM)/ocular-only Stickler syndrome (ocular-STL) in a large Chinese family. METHODS: Genomic DNA and clinical data from a four-generation family with eoHM/ocular-STL were collected. Whole-exome sequencing was performed on one affected member in initial screening. Linkage scan based on microsatellite markers was carried out initially from candidate loci associated with autosomal dominant eoHM and Stickler syndrome. Sanger sequencing was used to detect potential variants. The pathogenicity of candidate variants was evaluated using mini genes ex vivo. RESULTS: Eight patients and five unaffected members in the family participated in the study, in which the patients had high myopia with other variable ocular phenotypes but without extraocular abnormalities. Whole exome sequencing did not detect any potential pathogenic variant in all genes known to associate with the disease. The eoHM/ocular-STL in the family was mapped to markers around COL2A1 by candidate loci linkage scan, with a maximum lod score of 3.31 for D12S1590 at θ = 0. A novel deep intronic variant, c.86-50C > G in intron 1 of COL2A1, was detected by Sanger sequencing and co-segregated with eoHM/ocular-STL in the family. Ex vivo splicing test using mini genes confirmed that the variant created a new splicing acceptor 49 bp before the canonical splicing site of exon 2, resulted in addition of 49 bp fragment in the transcript (from c.86-49 to c.86-1) and premature termination. CONCLUSIONS: Linkage study, bioinformatics prediction, and ex vivo transcript analysis suggest a novel deep intronic variant adjacent to 5-prime of exon 2 of COL2A1, affecting exon 2 splicing, as a potential cause of ocular-STL in a large family. To our knowledge, this is the first report of an intronic variant around exon 2 as a cause of ocular-STL while a series of variants in the coding region of exon 2, a dispensable alternative-splicing exon for extraocular tissues, in COL2A1 have been reported to cause Stickler syndrome-related ocular phenotype alone.

[Expression of yeast acyl-delta9 desaturase for fatty acid biosynthesis in tobacco].

Palmitoleic acid (16:1delta9), an unusual monounsaturated fatty acid, is highly valued for human nutrition, medication and industry. Plant oils containing large amounts of palmitoleic acid are the ideal resource for biodiesel production. To increase accumulation of palmitoleic acid in plant tissues, we used a yeast (Saccharomyees cerevisiae) acyl-CoA-delta9 desaturase (Scdelta9D) for cytosol- and plastid-targeting expression in tobacco (Nicotiana tabacum L.). By doing this, we also studied the effects of the subcellular-targeted expression of this enzyme on lipid synthesis and metabolism in plant system. Compared to the wild type and vector control plants, the contents of monounsaturated palmitoleic (16:1delta9) and cis-vaccenic (18:1delta11) were significantly enhanced in the Scdelta9D-transgenic leaves whereas the levels of saturated palmitic acid (16:0) and polyunsaturated linoleic (18:2) and linolenic (18:3) acids were reduced in the transgenics. Notably, the contents of 16:1delta9 and 18:1delta11 in the Scdelta9D plastidal-expressed leaves were 2.7 and 1.9 folds of that in the cytosolic-expressed tissues. Statistical analysis appeared a negative correlation coefficient between 16:0 and 16:1delta9 levels. Our data indicate that yeast cytosolic acyl-CoA-delta9 desaturase can convert palmitic (16:0) into palmitoleic acid (16:1delta9) in high plant cells. Moreover, this effect of the enzyme is stronger with the plastid-targeted expression than the cytosol-target expression. The present study developed a new strategy for high accumulation of omega-7 fatty acids (16:1delta9 andl8:1delta11) in plant tissues by protein engineering of acyl-CoA-delta9 desaturase. The findings would particularly benefit the metabolic assembly of the lipid biosynthesis pathway in the large-biomass vegetative organs such as tobacco leaves for the production of high-quality biodiesel.

A wheat (Triticum aestivum) protein phosphatase 2A catalytic subunit gene provides enhanced drought tolerance in tobacco.

BACKGROUND AND AIMS: Multiple copies of genes encoding the catalytic subunit (c) of protein phosphatase 2A (PP2A) are commonly found in plants. For some of these genes, expression is up-regulated under water stress. The aim of this study was to investigate expression and characterization of TaPP2Ac-1 from Triticum aestivum, and to evaluate the effects of TaPP2Ac-1 on Nicotiana benthamiana in response to water stress. METHODS: TaPP2Ac-1 cDNA was isolated from wheat by in silico identification and RT-PCR amplification. Transcript levels of TaPP2Ac-1 were examined in wheat responding to water deficit. Copy numbers of TaPP2Ac-1 in wheat genomes and subcellular localization in onion epidermal cells were studied. Enzyme properties of the recombinant TaPP2Ac-1 protein were determined. In addition, studies were carried out in tobacco plants with pCAPE2-TaPP2Ac-1 under water-deficit conditions. KEY RESULTS: TaPP2Ac-1 cDNA was cloned from wheat. Transcript levels of TaPP2Ac-1 in wheat seedlings were up-regulated under drought condition. One copy for this TaPP2Ac-1 was present in each of the three wheat genomes. TaPP2Ac-1 fused with GFP was located in the nucleus and cytoplasm of onion epidermis cells. The recombinant TaPP2Ac-1 gene was over-expressed in Escherichia coli and encoded a functional serine/threonine phosphatase. Transgenic tobacco plants over-expressing TaPP2Ac-1 exhibited stronger drought tolerance than non-transgenic tobacco plants. CONCLUSIONS: Tobacco plants with pCAPE2-TaPP2Ac-1 appeared to be resistant to water deficit, as shown by their higher capacity to maintain leaf relative water content, leaf cell-membrane stability index, water-retention ability and water use efficiency under water stress. The results suggest that the physiological role of TaPP2Ac-1 is related to drought stress response, possibly through its involvement in drought-responding signal transduction pathways.