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Polymethoxylated flavones (PMFs), the main form of flavones in citrus, are derived from the flavone branch of the flavonoid biosynthesis pathway. Flavone synthases (FNSs) are enzymes that catalyze the synthesis of flavones from flavanones. However, the FNS in citrus has not been characterized yet. Here, we identified two type II FNSs, designated CitFNSII-1 and CitFNSII-2, based on phylogenetics and transcriptome analysis. Both recombinant CitFNSII-1 and CitFNSII-2 proteins directly converted naringenin, pinocembrin, and liquiritigenin to the corresponding flavones in yeast. In addition, transient overexpression of CitFNSII-1 and CitFNSII-2 respectively in citrus peel significantly enhanced the accumulation of total PMFs, while virus-induced CitFNSII-1 and CitFNSII-2 genes silencing simultaneously significantly reduced the expression levels of both genes and total PMF content in citrus seedlings. CitFNSII-1 and CitFNSII-2 presented distinct expression patterns in different cultivars as well as different developmental stages. Methyl salicylate (MeSA) treatment reduced the CitFNSII-2 expression as well as the PMFs content in the peel of Citrus sinensis fruit but not affected the CitFNSII-1 expression. These results indicated that both CitFNSII-1 and CitFNSII-2 participated in the flavone biosynthesis in citrus while the regulatory mechanism governing their expression might be specific. Our findings improved the understanding of the PMFs biosynthesis pathway in citrus and laid the foundation for further investigation on flavone synthesis regulation.

Context Nondigestible fermentable carbohydrates (NDFCs) can be fermented by microbiota, thereby yielding metabolites that have a beneficial role in the prevention and treatment of obesity and its complications. However, to our knowledge, no meta-analysis has been conducted to evaluate the effects of NDFCs on obesity. Objective To conduct a meta-analysis of randomized controlled trials (RCTs) to summarize existing evidence on the effects of numerous NDFCs on adiposity and cardiovascular risk factors in adults with overweight or obesity with ≥2 weeks of follow-up. Data Sources The following databases were searched: MEDLINE, Embase, and CINAHL. Data Extraction Seventy-seven RCTs with 4535 participants were identified for meta-analysis from the 3 databases. Data Analysis The findings suggest that increased intake of NDFCs is significantly effective in reducing body mass index by 0.280 kg/m2, weight by 0.501 kg, hip circumference by 0.554 cm, waist circumference by 0.649 cm, systolic blood pressure by 1.725 mmHg, total cholesterol by 0.36 mmol/L, and low-density lipoprotein by 0.385 mmol/L, with evidence of moderate-to-high quality. Conclusion Convincing evidence from meta-analyses of RCTs indicates that increased NDFC intake improves adiposity, blood lipid levels, and systolic blood pressure in people with overweight and obesity.

Cytochrome P450s (CYPs) are the largest family of enzymes in plant and play multifarious roles in development and defense but the available information about the CYP superfamily in citrus is very limited. Here we provide a comprehensive genome-wide analysis of the CYP superfamily in Citrus clementina genome, identifying 301 CYP genes grouped into ten clans and 49 families. The characteristics of both gene structures and motif compositions strongly supported the reliability of the phylogenetic relationship. Duplication analysis indicated that tandem duplication was the major driving force of expansion for this superfamily. Promoter analysis revealed numerous cis-acting elements related to various responsiveness. RNA-seq data elucidated their expression patterns in citrus fruit peel both during development and in response to UV-B. Furthermore, we characterize a UV-B-induced CYP gene (Ciclev10019637m, designated CitF3′H) as a flavonoid 3′-hydroxylase for the first time. CitF3′H catalyzed numerous flavonoids and favored naringenin in yeast assays. Virus-induced silencing of CitF3′H in citrus seedlings significantly reduced the levels of 3′-hydroxylated flavonoids and their derivatives. These results together with the endoplasmic reticulum-localization of CitF3′H in plant suggest that this enzyme is responsible for the biosynthesis of 3′-hydroxylated flavonoids in citrus. Taken together, our findings provide extensive information about the CYP superfamily in citrus and contribute to further functional verification.

Across Eurasia, horse transport transformed ancient societies. Although evidence for chariotry is well dated, the origins of horse riding are less clear. Techniques to distinguish chariotry from riding in archaeological samples rely on elements not typically recovered from many steppe contexts. Here, the authors examine horse remains of Mongolia's Deer Stone-Khirigsuur (DSK) Complex, comparing them with ancient and modern East Asian horses used for both types of transport. DSK horses demonstrate unique dentition damage that could result from steppe chariotry, but may also indicate riding with a shallow rein angle at a fast gait. A key role for chariots in Late Bronze Age Mongolia helps explain the trajectory of horse use in early East Asia.

Selenium-enriched polysaccharide (SeEPS) was prepared by reducing Se(IV) to elemental selenium and organic selenium in polysaccharide medium by the obtained Enterobacter cloacae strain Z0206 under aerobic conditions. In the present study, we focused on investigating the role of short-term supplementation of SeEPS at supernutritional doses in the regulation of growth performance, liver damage, antioxidant capacity, and selenium (Se) accumulation in C57 mice. Thirty-two C57 mice were randomly divided into four groups: the control group was gavaged with equal volume of phosphate-buffered saline, while the sodium selenite (Na2SeO3), selenomethionine (SeMet), and SeEPS groups were gavaged with 0.5 mg Se/kg BW of Na2SeO3, SeMet, and selenium-enriched polysaccharide (n = 8), respectively. We examined liver injury indicators, antioxidant capacity in the serum and liver, selenium deposition at different sites, selenoprotein levels, and selenocysteine-synthesizing and degradation-associated gene expression in mouse livers. SeEPS supplementation dramatically increased average daily weight gain but reduced the feed-to-gain ratio (F/G) of mice (P

To ensure reasonable intake of selenium for humans and provide insights on the development and nutritional analysis of high-quality selenium-enriched food, we established a reliable and highly sensitive method for the determination of selenium species in Z0206 selenium-enriched polysaccharide (Se-EPS). By optimizing the pre-treatment conditions (different enzymes, enzyme combinations, enzymatic time, concentration of enzymes, and centrifugation time), we found that Se-EPS can be effectively hydrolyzed by proteinase K for 18 h, followed by HPLC-ICP-MS determination. The developed method presented high sensitivity with the limit of detection and quantitation in the range of 0.44–2.35 μg L−1 and 1.54–7.21 μg L−1. The relative standard deviation (RSD) was all less than 10% and recovery was greater than 80% except for SeCys2, which further validated the repeatability and accuracy of the proposed method. Under the optimized conditions, we could determine 4 selenium species: elemental selenium (78.37%), seleno-methionine (14.27%), selenocystine (0.03%), and Se-methylselenocysteine (5.22%) in Se-EPS. This work provides new insights into the determination of different selenium species in selenium-enriched food.

Background Microbiota-accessible carbohydrates (MACs) are critical substrates for intestinal microbes; the subsequent production of SCFAs may have some potential benefits for patients with type 2 diabetes mellitus (T2DM). Objectives We conducted a meta-analysis of randomized controlled trials (RCTs) to assess the effects of higher compared with lower MAC intakes on cardiovascular risk factors in T2DM patients and performed an umbrella review of RCTs to evaluate the evidence quality concerning existing dietary T2DM interventions. Methods Publications were identified by searching MEDLINE, EMBASE, and CINAHL. In the meta-analysis, random-effects models were used to calculate pooled estimates, and sensitivity analyses, meta-regression, subgroup analyses, and Egger's test were performed. For the umbrella review, we summarized pooled estimates, 95% CIs, heterogeneity, and publication bias. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) and modified NutriGrade were used to assess the quality of evidence in the meta-analysis and umbrella review, respectively. Results Forty-five RCTs with 1995 participants were included in the meta-analysis. High MAC intake significantly reduced glycated hemoglobin (HbA1c) (weighted mean difference [WMD] -0.436% [-0.556, -0.315]), fasting glucose (WMD -0.835 mmol/L [-1.048, -0.622]), total cholesterol (WMD -0.293 mmol/L [-0.397, -0.190]), triglycerides (WMD -0.118 mmol/L [-0.308, -0.058]), BMI (WMD -0.476 [-0.641, -0.312]), and systolic blood pressure (WMD -3.066 mmHg [-5.653, -0.478]), with a moderate-to-high quality of evidence, compared with low intake. Region, dose, and MAC type were key variables. The umbrella review of all dietary interventions for cardiovascular risk factors in patients with T2DM included 26 meta-analyses with 158 pooled estimates. The evidence quality of MACs, dietary fiber, high-protein diet, ω-3 (n-3), viscous fiber, vitamin D, and vitamin E intake was moderate to high. Conclusions When compared with lower intake, increased MAC intake improved glycemic control, blood lipid, body weight, and inflammatory markers for people with T2DM. This trial was registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/#recordDetails) as CRD42019120531.

Limonin is an important bioactive substance in citrus fruits, especially in seeds, which has great potential in cancer prevention and treatment. In order to explore the anticancer activity based on interaction between limonin and NQO1, Human promyelocytic leukemia cells (HL‐60) were studied in vitro. We found that limonin could inhibit proliferation and promote apoptosis of HL‐60 cells, and the effect was positively correlated with its dosage. Western blot results showed that limonin could activate the endogenous apoptosis pathway mediated by mitochondria via up‐regulating pro‐apoptotic proteins (Bax, cytochrome c, Caspase3, and Caspase9) and down‐regulating anti‐apoptotic proteins (Bcl‐2), thus inhibiting the proliferation of HL‐60 cells and promoting apoptosis, which further proved the anticancer activity of limonin from the molecular mechanism. At the same time, limonin down‐regulated the expression of NQO1, indicating that limonin may indirectly act on the apoptosis pathway by regulating the expression activity of antioxidant enzymes in vivo, thus exerting its inhibitory effect on tumor cells, which provides an idea for the molecular mechanism that natural products can indirectly exert their anticancer effect by regulating the activity of antioxidant enzymes., Limonin, a citrus nutrient factor, was used as the subject material, which showed a proliferation inhibitory effect on HL‐60 cells. Mechanism exploration found that this effect was caused by activating the apoptosis pathway through inhibiting NQO1 expression.

With the development of Energy Internet and Smart Grid, power communication equipment has gradually become an important pillar supporting the information transmission. However, when equipment failure occurs, more and more attention has been paid to the rapid realization of equipment fault research and judgment from a large amount of equipment fault information. Based on the fault data of power communication equipment, a fault model of power communication equipment is designed in this paper. It combines BERT and BiLSTM-CRF model for knowledge extraction, and constructs the equipment fault knowledge graph to realize the visual display of power communication equipment. Through this model, fault knowledge extraction can be realized accurately, and a visual model of fault analysis can be formed, which can effectively improve the fault research speed and work efficiency of maintenance personnel.

In the present study, the effects of root restriction (RR) on the main phenolic metabolites and the related gene expression at different developmental stages were studied at the transcriptomic and metabolomic levels in "Summer Black" grape berries (Vitis vinifera × Vitis labrusca). The results were as follows: seven phenolic acid compounds, three stilbene compounds, nine flavonol compounds, 10 anthocyanin compounds, and 24 proanthocyanidin compounds were identified by ultra-performance liquid chromatography-high-resolution mass spectrometry. RR treatment significantly promoted the biosynthesis of phenolic acid, trans-resveratrol, flavonol, and anthocyanin and also affected the proanthocyanidin content, which was elevated in the early developmental stages and then reduced in the late developmental stages. The functional genes for phenylalanine ammonia-lyase, trans-cinnamate 4-monooxygenase, 4-coumarate-CoA ligase, shikimate O-hydroxycinnamoyl transferase, chalcone synthase, chalcone isomerase, stilbene synthase, flavonoid 3',5'-hydroxylase, anthocyanidin 3-O-glucosyltransferase, and the transcription factors MYBA1, MYBA2, MYBA3, and MYBA22 were inferred to play critical roles in the changes regulated by RR treatment.

Polymethoxylated flavones (PMFs), which accumulate exclusively in fruit peel of citrus, play important physiological and pharmacological roles but the genetic basis for the methylation of flavonoids has not been fully elucidated in citrus. Here we characterize a caffeoyl-CoA O-methyltransferase-like enzyme, designated CrOMT1. The expression pattern of CrOMT1 was highly correlated with the concentration of the three major PMFs in two different citrus fruit tissues during fruit maturation. Exposure of fruit to UV-B radiation sharply increased the level of CrOMT1 transcripts and also led to the accumulation of three PMFs. The potential role of CrOMT1 was studied by testing the catalytic activity of recombinant CrOMT1 with numerous possible substrates in vitro. The enzyme could most efficiently methylate flavones with neighboring hydroxy moieties, with high catalytic efficiencies found with 6-OH- and 8-OH-containing compounds, preferences that correspond precisely with the essential methylation sites involved in the synthesis of the three naturally occurring PMFs in Citrus reticulata. This indicates that CrOMT1 is capable of in vitro methylation reactions required to synthesize PMFs in vivo. Furthermore, transient overexpression of CrOMT1 increased levels of the three major PMFs in fruit, indicating that CrOMT1 is likely to play an essential role in the biosynthesis of PMFs in citrus., Identification of a Citrus reticulata CCoAOMT-like enzyme involved in biosynthesis of polymethoxylated flavones enables further investigation of these secondary metabolites in citrus fruit.

Fruit bagging is a commonly used cultivation measure to protect citrus fruit from insects and adverse environments. The present study aimed to comprehensively investigate the effects of bagging on the physiochemical characteristics of grapefruit. The grapefruit were bagged at approximately 110–120 d after anthesis with a one-layer kraft paper bag with black coating inside (SL), a double-layer kraft paper bag with one black paper as the inner layer (DL), and a three-layer kraft paper bag with two black papers as inner layers (TL), respectively. Ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) technique was used to identify a total of 19 flavonoids, 2 phenylpropanoids, 9 coumarins, and 5 limonoids. By using UPLC, 50 carotenoids were identified. Gas chromatography–mass spectrometry was used to identify 3 soluble sugars, 3 organic acids, and 11 amino acids. In the quantitated components in the peel (albedo and flavedo), the chlorophylls and the carotenoids components (such as luteoxanthin, violaxanthin, 9-cis-violaxanthin, xanthophyll, zeaxanthin and β-carotene) were significantly downregulated by bagging, causing the surface color of bagged fruit to turn yellow earlier but paler than that of the unbagged control, particularly in the three-layer kraft bag treatment. Unlike the peel, the color and the carotenoid content of the juice sacs were less affected. The physiochemical compounds other than pigments, including soluble sugars, organic acids, amino acids, flavonoids, coumarins and limonoids, were minimally affected by bagging treatments. Our results indicated that bagging at approximately 110–120 d after anthesis exerted influence mainly on peel color, but less on sugars, acids, amino acids, flavonoids, limonoids and coumarins of grapefruit.

Citrus fruit are consumed worldwide due to their excellent features, such as delicious taste and health-promoting compounds. However, section drying, a physiological disorder of citrus fruit, often occurs both in the preharvest and postharvest storage, causing a significant reduction in fruit quality and consumer acceptance. In this review, section drying of citrus fruit was divided into three types: granulation, vesicle collapse and both above. The main causes, metabolic changes and mechanisms of section drying were discussed, respectively. Furthermore, the prevention methods of section drying in citrus fruit, including preharvest and postharvest methods, were also summarized. Given the significant influence of section drying in citrus fruit production, the mechanisms and prevention methods of section drying are worth further exploration. A better understanding of section drying may provide guidance for the prevention of this disorder and future breeding of citrus fruit.

The aim of this study is to compare the regulatory abilities of citrus flavonoids on the oscillating expression of circadian genes. Seven varieties of citrus fruits and twenty-five citrus flavonoids were selected and evaluated. Per2 luciferase bioluminescence report system and serum shock were used to induce circadian gene expression in mouse microglia BV-2 cells. In vivo experiments were carried out using C57BL6/J mice to evaluate the regulation of flavonoids on the oscillatory expression of liver biorhythm genes. Lipopolysaccharide was used to interfere the gene oscillating expression. QRT-PCR was performed to detect the expression of circadian rhythm-related genes, including Clock, Bmal1, Per1, Per2, Per3, Cry1, Cry2, Rev-erbα, Rev-erbβ, Rorα, Dbp, and Npas2. The results show that the polymethoxyflavones (PMFs) exerted stronger circadian gene regulatory capability, while the flavonoids containing glycosides showed no biological activity. Also, all tested flavonoids decreased LPS-induced nitric oxide release, but only polymethoxyflavones inhibited circadian rhythm disorder. PMFs inhibited Nlrp3 inflammasome-related genes and proteins, including Nlrp3, IL-1β, ASC, and Caspase1, while other flavonoids only affected IL-1β and Caspase1 expression. This mechanism was preliminarily verified using the Nlrp3 inhibitor INF39.

Macrophages with the M1 phenotype are a type of immune cell with exciting prospects for cancer therapy; however, when these macrophages infiltrate into tumours, many of them are induced by the tumour microenvironment to transform into the M2 type, which can enable tumour defence against external therapeutic strategies, assisting in tumour development. Macrophages have strong plasticity and functional heterogeneity, and their phenotypic transformation is complex and still poorly understood in relation to cancer therapy. Recent material advances in inorganic nanomaterials, especially inorganic elements in vivo, have accelerated the development of macrophage regulation-based cancer treatments. This review summarizes the basics of recent research on macrophage phenotype transformation and discusses the current challenges in macrophage type regulation. Then, the current achievements involving inorganic material-based macrophage regulation and the related anticancer effects of induced macrophages and their extracellular secretions are reviewed systematically. Importantly, inorganic nanomaterial-based macrophage phenotype regulation is flexible and can be adapted for different types of cancer therapies, presenting a possible novel approach for the generation of immune materials for cancer therapy.

In this study, a unique citrus species (Citrus australasica) was selected, and its fruit characteristics, phenolic compounds and ability to inhibit inflammation were preliminarily studied. Finger lime fruits showed distinctive features in shape, size, weight, colour, total soluble solids, water-soluble pectin, sugar and acids contents. Combining UPLC-HRMS and UPLC-DAD analysis, 31 phenolics, 1 secoiridoid derivative and 1 neolignan glycoside were preliminarily identified and quantified. The phenolics composition of finger limes showed cultivar and tissue specificity. Antioxidant evaluation showed that extracts from finger lime cultivar of ‘XiangBin’ exhibited better antioxidant capacities than cultivar of ‘LiSiKe’, especially in peel. LPS-induced NO-releasing model was performed in the mouse microglia BV-2 cell line. Results illustrated that finger limes inhibited the NO-releasing and the inflammation-related cytokines including IL-1β, IL-6 and TNFα elevation. QRT-PCR revealed that finger lime extracts alleviated LPS-induced upregulation of iNOS, IL-6, JAK2, TNFα, TLR2, TLR4, IL-1β, NF-κB and LPS-induced downregulation of IκBα. This study may expand our knowledge on the physiochemical characteristics and bioactive properties of citrus fruits.

Ponkan (Citrus reticulata Blanco cv. Ponkan) is one of the widely grown and economically important citrus fruit species in China. Present study investigated the dynamic changes of Ponkan fruit’ storability in different storage period and under alternating temperature during the postharvest transportation and shelf life, aiming to find out an efficient and energy-saving transportation scheme for Ponkan fruit at different storage stage. The results showed that, the elongation of storage time and the higher transport temperature led to the increase of decay rate. The juice yield continued to decrease, without affecting by the transportation temperatures. The rind color turn yellow rapidly (with the citrus color index (CCI) increased from 3.61 to 9.25) during the first two months, and remained stable during the following period. The higher transportation temperature accelerated the rind color development. The total soluble solids (TSS) increased during the first month (from 11.21% to 13.25%), remained stable in the second and third months, and then decreased slightly in the fourth month, which was not evidently influenced by the transportation temperature. The titratable acidity (TA) showed a continuous decline which was accelerated by the high transportation temperature. The ethanol and aldehyde contents continue to increase and were not significantly affected by the transportation temperature. The total flavonoids content decreased during the transportation and shelf life of the newly harvested Ponkan fruit, while remained stable and was not significantly affected by the transportation temperature in the four months of storage. The alternating temperature of transportation affected the storability of Ponkan fruit at different storage periods. These finding provided a theoretical basis for the selection of transportation temperature from economic perspective.

To explore the antioxidant capacity of citrus flavonoids under different evaluation systems, chemical and biological methods were engaged to determine the antioxidant abilities of flavanones and polymethoxyflavones. Results showed that flavanones exhibited good antioxidant activity, while polymethoxyflavones had a weak ability to scavenge free radicals. Both flavanones and polymethoxyflavones exerted the ability to inhibit H2O2-induced oxidative stress, but the effective concentration of polymethoxyflavones was lower. Further exploration showed that neohesperidin and tangeretin selectively regulated antioxidant enzyme activity, both in vitro and in vivo. Tangeretin also maintained the expression of antioxidant enzymes in L02 cells and in ICR mice liver. The mechanism exploration showed that both neohesperidin and tangeretin promoted the expression of NRF2 and inhibit the expression of KEAP1, but tangeretin could inhibit the ubiquitination of NRF2 by inhibiting CUL3. The mechanism was verified by CUL3 gene silencing. This study demonstrates a novel antioxidant mechanism of natural products.

In this study, the pectin-based edible coatings encapsulating carvacrol/2-hydroxypropyl-β-cyclodextrin inclusion complex (CAR/HPβCD-IC) were fabricated and their antifungal activities were investigated. The inclusion complex of CAR/HPβCD was demonstrated to be successfully synthesized by the characterization of UV–vis spectroscopy, fluorescence emission spectroscopy, FT-IR, 1H NMR, TGA and DSC. The fluorescence emission spectra analysis suggested that stoichiometric ratio of carvacrol and HPβCD for forming the inclusion complex was 1:1. The aqueous solubility and thermal stability of carvacrol were significantly enhanced after inserting into HPβCD cavity. Furthermore, the inclusion complex exhibited strong antifungal activities against pathogens of Botrytis cinerea and Alternaria alternata. On the other hand, an edible active coating was prepared by the addition of CAR/HPβCD-IC into pectin matrix. The steady rheology results of film-coatings indicated that the apparent viscosity of edible coatings was decreased with the addition of CAR/HPβCD-IC. In contrast, CAR/HPβCD-IC increased the thermal stability of pectin. In addition, the pectin/CAR/HPβCD-IC coating as an active packaging material suppressed the colony growth of B. cinerea and A. alternata in vitro. Results from the present study demonstrated that the pectin-based edible coating encapsulating CAR/HPβCD-IC was a promising coating material for food preservation.

‘Shatangju’ (Citrus reticulata) is a loose-skin mandarin cultivar with delicious taste quality. However, its fruit size varied greatly which might affect the storage results. This study investigated the physiochemical characteristics of ‘Shatangju’ fruit with different sizes after a long-term storage, and found that small fruit tended to have a longer shelf life. According to the results, the fruit with a higher transverse diameter tended to contain more seeds and had lower edible rate. The storability of ‘Shatangju’ fruit decreased with the increase of fruit size, in that the big fruit suffered more severe vesicle collapse after storage. Correspondingly, the physiochemical characteristics of the flesh varied among stored fruit of different sizes. The stored larger fruit tended to have higher content of cellulose, hemicellulose and lignin, as well as a lower content of soluble sugars, organic acids, and amino acids in the flesh, which led to the bad texture and tasteless flavor. We also found that the vesicle collapse of ‘Shatangju’ fruit was a very complicated syndrome involving a series of physiochemical changes rather than simple water loss. The results of the present study provided guidance for the classification and storage of ‘Shatangju’ fruit after harvest.

Apple (Malus pumila Mill.) is a popular fruit with high economic values and various biological activities that are beneficial to human health. In this study, 35 apple cultivars were collected and were evaluated for their basic quality indexes, phenolic compositions, antioxidant activity, anti-tumour, and anti-diabetic activities. The compositions of phenolics were detected by using high-performance liquid chromatography (HPLC) and high-resolution mass spectroscopy (HRMS) assays. The antioxidant activities of peel and pulp extracts from 35 apple cultivars were evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and ferric reducing antioxidant power (FRAP) assay. Results showed that the contents of phenolic acids and proanthocyanidins showed significant correlations with the antioxidant activities. Phenolic-rich extracts significantly inhibited HepG2 cell proliferation, with the inhibition activity varied significantly between cultivars. &lsquo, Gold Delicious&rsquo, pulp extract, &lsquo, Xiboliyabaidian&rsquo, peel and pulp extracts showed protective effects on H2O2-induced injury of human umbilical vein endothelial cells (HUVEC). &lsquo, Red Fuji&rsquo, peel extract, &lsquo, peel and pulp extracts, as well as &lsquo, peel extract, significantly increased glucose consumption of HepG2 cells, in a dose-dependent manner. This research may provide theoretical guidance for further nutritional investigation of the apple resources.

Polymethoxyflavones (PMFs) are special flavonoids in citrus fruits that have been suggested to be beneficial to human health. However, whether PMFs in citrus fruit alter human gut microbiota is not well understood. The aim of the present study was to investigate the effects of PMF-rich fraction from Ougan (Citrus reticulata cv. Suavissima) on gut microbiota and evaluate the intestinal metabolic profile of PMFs in Institute of Cancer Research mice. The main components of the PMF-rich fraction were nobiletin, tangeretin, and 5-demethylnobiletin. The composition of the gut microbiota was analyzed using 16S ribosomal DNA sequencing. The results showed that after oral administration, the composition of mice gut microbiota was significantly altered. The relative abundance of two probiotics, Lactobacillus and Bifidobacterium, were found to increase significantly. A total of 21 metabolites of PMFs were detected in mice intestinal content by high performance liquid chromatography electrospray ionization tandem mass spectrometry, and they were generated through demethylation, demethoxylation, hydroxylation, and glucuronidation. Our results provided evidence that PMFs have potential beneficial regulatory effects on gut microbiota that in turn metabolize PMFs, which warrants further investigation in human clinical trials.