The first chromosome-level Fallopia multiflora genome assembly provides insights into stilbene biosynthesis.

Fallopia multiflora (Thunb.) Harald, a vine belonging to the Polygonaceae family, is used in traditional medicine. The stilbenes contained in it have significant pharmacological activities in anti-oxidation and anti-aging. This study describes the assembly of the F. multiflora genome and presents its chromosome-level genome sequence containing 1.46 gigabases of data (with a contig N50 of 1.97 megabases), 1.44 gigabases of which was assigned to 11 pseudochromosomes. Comparative genomics confirmed that F. multiflora shared a whole-genome duplication event with Tartary buckwheat and then underwent different transposon evolution after separation. Combining genomics, transcriptomics, and metabolomics data to map a network of associated genes and metabolites, we identified two FmRS genes responsible for the catalysis of one molecule of p-coumaroyl-CoA and three molecules of malonyl-CoA to resveratrol in F. multiflora. These findings not only serve as the basis for revealing the stilbene biosynthetic pathway but will also contribute to the development of tools for increasing the production of bioactive stilbenes through molecular breeding in plants or metabolic engineering in microbes. Moreover, the reference genome of F. multiflora is a useful addition to the genomes of the Polygonaceae family.

Integrated untargeted metabolome, full-length sequencing, and transcriptome analyses reveal insights into the fruit quality at different harvest times of Chaenomeles speciosa.

Chaenomeles speciosa fruit is a homologous medicine and food plant with a long history of multiple uses. It could be harvested near maturity and last for a long time. However, the optimal harvest strategy of Chaenomeles speciosa for various uses is currently unavailable. Here, untargeted metabolome at different harvest times during maturation was investigated for the first time, and 896 metabolites, including sugars, organic acids, amino acids, and phenylpropanoids, were identified. Optimal harvesting methods were proposed for different purposes. During the early maturation stages (before 105 days after full bloom), Ch. speciosa fruit could be harvested as Chinesemedicine. Whereas as snacks and food, Ch. speciosa fruit might be harvested at late maturity (after 120 days after full bloom). In addition, the overall network was revealed by integrating full-length Iso-seq and transcriptomics (RNA-seq) to investigate the association between quality-associated metabolites and Chaenomeles speciosa fruit gene expression during maturation. A few putative genes were captured via screening, dissecting and correlation analysis with the quality-associated metabolites (including d-glucose, catechin, gallocatechin, and succinic acid). Overall, in addition to providing a harvesting strategy for food and medicine, we also investigated the metabolism and gene expression pattern of Chaenomeles speciosa fruit during maturation. This comprehensive data and analyses laid the foundation for further investigating potential regulatory mechanisms during harvest and provided a new possibility for its development and utilization.

Effects of dietary irritants on intestinal homeostasis and the intervention strategies.

Abundant diet components are unexplored as vital factors in intestinal homeostasis. Dietary irritants stimulate the nervous system and provoke somatosensory responses, further inducing diarrhea, gut microbiota disorder, intestinal barrier damage or even severe gastrointestinal disease. We depicted the effects of food with piquancy, high fat, low pH, high-refined carbohydrates, and indigestible texture. The mechanism of dietary irritants on intestinal homeostasis were comprehensively summarized. Somatosensory responses to dietary irritants are palpable and have specific chemical and neural mechanisms. In contrast, even low-dose exposure to dietary irritants can involve multiple intestinal barriers. Their mechanisms in intestinal homeostasis are often overlapping and dose-dependent. Therefore, treating symptoms caused by dietary irritants requires personalized nutritional advice. The reprocessing of stimulant foods, additional supplementation with probiotics or prebiotics, and enhancement of the intestinal barrier are effective intervention strategies. This review provides promising preliminary guidelines for the treatment of symptoms and gastrointestinal injury caused by dietary irritants.

Full-length transcriptome analysis of two chemotype and functional characterization of genes related to sesquiterpene biosynthesis in Atractylodes lancea.

Atractylodes lancea (Thunb.) DC. is an important medicinal plant mainly distributed in China. A. lancea is rich in volatile oils and has a significant effect on various diseases, including coronavirus disease 2019 (COVID-19). Based on the signature constituents of volatile oils, A. lancea is divided into two chemotypes: the Dabieshan and Maoshan chemotype. Gas chromatography-mass spectrometry (GC-MS) results revealed that the hinesol and ß-eudesmol contents in the Dabieshan chemotype were higher than those in the Maoshan chemotype. Next-generation sequencing (NGS) and single-molecule real-time (SMRT) sequencing technologies were combined to investigate the molecular mechanisms of sesquiterpenoid biosynthesis in A. lancea. A total of 42 differentially expressed genes (DEGs) for terpenoid biosynthesis were identified in the two chemotype groups, and nine full-length terpene synthase (TPS) genes were identified. Subcellular localization revealed that AlTPS1 and AlTPS2 proteins were localized in the nucleus and endoplasmic reticulum. They use FPP as a substrate to generate sesquiterpenoids. AlTPS1 catalyzes biosynthesis of elemol while AlTPS2 is observed to perform ß-farnesene synthase activity. This study provides information for understanding the differences in the accumulation of terpenoids in two chemotypes of A. lancea and lays a foundation for further elucidation of the molecular mechanism of sesquiterpenoid biosynthesis.

Impact of pectin with various esterification degrees on the profiles of gut microbiota and serum metabolites.

Colitis is generally affected by multiple factors, including the dysbiosis of intestinal microbiota, and may affect organs outside colon through circulation. Pectin, which is an edible polysaccharide widely present in plant cell walls, has been proved in our previous study to possess preventive potentials against acute ulcerative colitis, especially when the esterification degree is less than 50%. This study aimed to clarify the underlying correlations of gut microbiome and serum metabolites with the preventive effects of pectin with different esterification degrees (H121, L13, and L102) against colitis in mice. MiSeq sequencing data showed that symbiotic bacteria especially beneficial Lactobacillus and Bifidobacterium were enriched by pectin intake. Fiber consumers such as Prevotella and Bacteroides actively responded to L13 pectin, particularly under high dosage (L13-H). In addition, the abnormal abundance of Akkermansia associated with colitis would not appear in mice who had been provided with any of the three pectins before dextran sulfate sodium (DSS) treatment. Furthermore, pre-treatment of H121 and L13 pectins could improve the serum glycerophospholipids such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE). In contrast, lysophosphatidic acid (LPA) contributing to the glycerophospholipid metabolism pathway was enriched only in the L13-H group, which has been previously proved to be associated with the epithelial barrier and intestinal homeostasis. Positive relationships between the glycerophospholipids and the dominant candidates of intestinal bacteria such as Lactobacillus indicated the joint actions of intestinal microbes and serum metabolites as well as the underlying crosstalks among gut microbiome. Therefore, the results of this research suggested that the preventive effects of low-esterified pectin on DSS-induced colitis were likely to be initiated by the enrichment of probiotics in the gut and serum glycerophospholipids. KEY POINTS: • L13 pectin remarkably improved the diversity of the gut microbiome in healthy mice. • Probiotics were enriched and abnormal Akkermansia was restored by L13 and L102 pectins. • Glycerophospholipid metabolism was significantly enriched by H121 and L13 pectins.

Colour, chemical compounds, and antioxidant capacity of Astragali Radix based on untargeted metabolomics and targeted quantification.

INTRODUCTION: Astragali Radix has been used for over 2000 years in traditional Chinese medicine. Its secondary xylem "Jinjing" and secondary phloem "Yulan" are important for evaluating the quality of the Daodi medicinal material in China. However, its systematic characterisation has not been conducted. OBJECTIVE: This study aims to investigate the colour, chemical compounds, and antioxidant capacity of the secondary xylem and phloem of Astragali Radix on the basis of untargeted metabolomics, broadening the application scope of Astragali Radix in food and pharmaceutical industries. METHODS: The L*, a*, and b* of the secondary xylem and phloem were measured by colorimetry, and the chemical compounds were identified and quantified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and high-performance liquid chromatography-diode array detector-evaporative light scattering detection. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays were conducted to evaluate their antioxidant capacity. RESULTS: Thirty-one compounds were identified by UPLC-Q-TOF-MS. The secondary xylem exhibited high parameter b*, flavonoid content, and antioxidant capacity, while the secondary phloem was rich in astragalosides. The colour parameters of well-defined type A significantly varied from those of the other types. Well-defined type A also exhibited the highest antioxidant activity and flavonoid content, followed by middle type A-like, middle type B-like, and yellow shading type B. CONCLUSION: The colour parameters, chemical compounds, and antioxidant capacity among the different transverse sections of secondary xylem and phloem varied. The yellow colour of secondary xylem was correlated to high flavonoid content and antioxidant activity, and well-defined type A of Astragali Radix had better quality than other types.

Bioactive Dietary Fibers Selectively Promote Gut Microbiota to Exert Antidiabetic Effects.

High intake of dietary fibers was found to be inversely associated with type-2 diabetes (T2D), whereas the difference among different dietary fibers on T2D remains unclear. Therefore, we have investigated the effects of different dietary fibers on T2D. Nine types of dietary fibers were used to investigate and evaluate their effects on type-2 diabetic rats via physiology, genomics, and metabolomics. We found that supplementation with ß-glucan, arabinogalactan, guar gum, apple pectin, glucomannan, and arabinoxylan significantly reduced the fasting blood glucose, whereas carrageenan, xylan, and xanthan gum did not affect glycemic control in diabetic rats. Also, bioactive dietary fibers (ß-glucan, arabinogalactan, guar gum, and apple pectin) associated with the increased butyric acid level and abundance of beneficial bacteria (Lachnobacterium, Parabacteroides, Faecalibacterium, Akkermansia, and some butyric acid-producing bacteria), as well as improved host metabolism by decreasing 12α-hydroxylated bile acids, acylcarnitines, and amino acids (leucine, phenylalanine, citrulline, etc.), thereby exert beneficial effects on T2D. It was also found that ß-glucan might attenuate insulin resistance via downregulation of Prevotella copri-mediated biosynthesis of branched-chain amino acids in T2D. Together, our study uncovered the effects of different dietary fibers on T2D, along with their potential mechanism.

A polysaccharide from natural Cordyceps sinensis regulates the intestinal immunity and gut microbiota in mice with cyclophosphamide-induced intestinal injury.

A polysaccharide from Cordyceps sinensis (NCSP) was reported to attenuate intestinal injury and regulate the balance of T helper (Th)1/Th2 cells in immunosuppressed mice. However, whether it influences Th17 and regulatory T (Treg) cells as well as gut ecology remains unknown. In the present study, the intestinal injury mouse model was also established by intraperitoneal injection of cyclophosphamide (Cy) for three consecutive days. NCSP was found to increase the number of CD4+ T cells, stimulate the secretion of interleukins (IL)-17 and IL-21, and the expression of transcription factor (retinoic acid-related orphan receptor (ROR)-γt). The levels of transforming growth factor (TGF)-ß3 and transcription factor (forkhead box (Fox)p-3) were increased in NCSP-treated groups. Moreover, NCSP upregulated the mRNA expression of toll like receptors (TLR-2, -6 and -9), while it downregulated the TLR-4 expression. In addition, NCSP modulated the intestinal microbiota composition and increased the levels of SCFAs. These findings indicated that NCSP may enhance intestinal immunity and have the potential to become a prebiotic to regulate intestinal microbiota.

Hypoglycemic mechanism of polysaccharide from Cyclocarya paliurus leaves in type 2 diabetic rats by gut microbiota and host metabolism alteration.

Diabetes mellitus is a serious threat to human health. Cyclocarya paliurus (Batal.) Iljinskaja (C.paliurus) is one of the traditional herbal medicine and food in China for treating type 2 diabetes, and the C. paliurus polysaccharides (CP) were found to be one of its major functional constituents. This research aimed at investigating the hypoglycemic mechanism for CP. It was found that CP markedly attenuated the symptoms of diabetes, and inhibited the protein expression of Bax, improved the expression of Bcl-2 in pancreas of diabetic rats, normalized hormones secretion and controlled the inflammation which contributed to the regeneration of pancreatic ß-cell and insulin resistance. CP treatment increased the beneficial bacteria genus Ruminococcaceae UCG-005 which was reported to be a key genus for protecting against diabetes, and the fecal short-chain fatty acids levels were elevated. Uric metabolites analysis showed that CP treatment helped to protect with the diabetes by seven significantly improved pathways closely with the nutrition metabolism (amino acids and purine) and energy metabolism (TCA cycle), which could help to build up the intestinal epithelial cell defense for the inflammation associated with the diabetes. Our study highlights the specific mechanism of prebiotics to attenuate diabetes through multi-path of gut microbiota and host metabolism.

Genome survey sequencing of Atractylodes lancea and identification of its SSR markers.

Atractylodes lancea (Thunb.) DC. is a traditional Chinese medicine rich in sesquiterpenes that has been widely used in China and Japan for the treatment of viral infections. Despite its important pharmacological value, genomic information regarding A. lancea is currently unavailable. In the present study, the whole genome sequence of A. lancea was obtained using an Illumina sequencing platform. The results revealed an estimated genome size for A. lancea of 4,159.24 Mb, with 2.28% heterozygosity, and a repeat rate of 89.2%, all of which indicate a highly heterozygous genome. Based on the genomic data of A. lancea, 27,582 simple sequence repeat (SSR) markers were identified. The differences in representation among nucleotide repeat types were large, e.g., the mononucleotide repeat type was the most abundant (54.74%) while the pentanucleotide repeats were the least abundant (0.10%), and sequence motifs GA/TC (31.17%) and TTC/GAA (7.23%) were the most abundant among the dinucleotide and trinucleotide repeat motifs, respectively. A total of 93,434 genes matched known genes in common databases including 48,493 genes in the Gene Ontology (GO) database and 34,929 genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. This is the first report to sequence and characterize the whole genome of A. lancea and will provide a theoretical basis and reference for further genome-wide deep sequencing and SSR molecular marker development of A. lancea.

Hypoglycemic and Hypolipidemic Mechanism of Tea Polysaccharides on Type 2 Diabetic Rats via Gut Microbiota and Metabolism Alteration.

Diabetes mellitus is a serious threat to human health. Tea is cultivated around the world, and its polysaccharide components are reported to be an effective approach for managing type 2 diabetes with fewer adverse effects than medication. To examine the therapeutic effect of tea polysaccharides on diabetes, a type 2 diabetic rat model was generated. We showed that tea polysaccharides remarkably decreased fasting blood glucose and the levels of total cholesterol, total triglyceride, low-density lipoprotein cholesterol, and free fatty acid of type 2 diabetic rats. 16S rRNA sequencing and metabolomics were used to investigate the variation of gut microbiota and the metabolites profiles of diabetic rats after intervention of tea polysaccharides. We found that tea polysaccharides maintained the diversity of gut microbiota and restored the relative abundance of some bacterial genera (Lachnospira, Victivallis, Roseburia, and Fluviicola) which was reduced by diabetes. According to metabolomics analysis, we found that amino acid and other related metabolites was influenced by tea polysaccharides intervention. Correlation analysis among metabolites, gut microbiota, and parameters of hypoglycemic indicated that tea polysaccharides had hypoglycemic and hypolipidemic effect on type 2 diabetes via the modulation of gut microbiota and the improvement of host metabolism.

PEGylated non-ionic surfactant vesicles as drug delivery systems for Gambogenic acid.

Gambogenic acid (GNA), a popular Chinese traditional medicine, has its limitations of coming into use due to its low aqueous solubility and poor bioavailability. In this study, therefore, the PEGylated non-ionic surfactant vesicles drug delivery systems were prepared from biocompatible non-ionic surfactant of Span60, cholesterol and dicetyl phosphate (DCP) by the improved ethanol injection method, and were modified with a polyethylene glycol monostearate15 (PEG15-SA). PEG15-SA, as a biocompatible, non-toxic and non-immunogenic hydrophilic segment, was grafted onto the surface of colloidal niosomes carries to reduce the uptake by the reticuloendothelial system (RES), prolonging the circulation time and attaining higher entrapment efficiency. To our knowledge, this work is the first to report that PEG15-SA was applied to coating of niosomes for encapsulation of GNA. The optimized PEG-GNA-NISVs (P-GNA-NISVs) were characterized in terms of mean vesicles size, polydispersity index (PDI), Zeta potential and entrapment efficiency of the P-GNA-NISVs. The results showed that the mean diameter, PDI, Zeta potential, and the entrapment efficiency of the P-GNA-NISVs were 70.1 nm, 0.166, -44.3 mV and 87.74%, respectively. Furthermore, the release studies of GNA from PEGylated niosomes in vitro and the pharmacokinetics in vivo exhibited a prolonged release profile as studied over 24 h. In conclusion, the result suggests that P-GNA-NISVs prepared in this way not only have higher encapsulation capacity, more colloidal stability but also offer an approach that the PEGylated niosomes is a promising carrier for anticancer GNA.

[Preparation and characterization of non-ionic surfactant vesicle of cantharidin].

OBJECTIVE: To study the preparation of cantharidin entrapped non-ionic surfactant vesicle (noisome)and evaluate its quality. METHOD: The niosome loaded with cantharidin was prepared using injection method by non-ionic surfactants as the carrier. An centrifugation separation method and HPLC analysis method of the cantharidin were established to detect the entrapment efficiency. The optimum preparation technology was established by a orthogonal experiment. The morphology, and particle size were studied to evaluate the preparation. RESULT: The average size of niosomes were (209. 8 +/- 0.5) nm. The entrapment efficiency of the CTD-NS was (27.5% +/- 2.0%) and Zeta potential was (41.5 +/- 0.65) mV. CONCLUSION: The preparation of cantharidin noisome by TweenA and SpanB is practicable and successful. These experiments can be the basement of developing targeting drug delivery system.