Determination of 10 mycotoxins in wine, baijiu, and huangjiu of the Chinese market by liquid chromatography tandem mass spectrometry and exposure estimation.

In this study, liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to analyze the prevalence of 10 mycotoxins in 140 samples from the Chinese market, aiming to assess the exposure of Chinese individuals to these mycotoxins through the consumption of wine, baijiu, and huangjiu. Mycotoxins were detected in 98% of the samples, with fumonisins (FBs), deoxynivalenol (DON), and zearalenone (ZEN) exhibiting positive rates exceeding 50%. Regarding the exposure of the Chinese population to mycotoxins resulting from alcoholic beverage consumption, fruit wine intake made a relatively significant contribution to aflatoxin exposure, while baijiu showed a relatively significant contribution to ZEN exposure (1.84%). The analysis of the correlation between grape variety, wine region, and mycotoxin content demonstrated that FBs, ZEN, and DON were significantly influenced by grape variety and wine region. This research holds great significance in protecting human life and health, as well as in the production of safer alcoholic beverages.

Enhancing the flavour quality of Laiyang pear wine by screening sorbitol-utilizing yeasts and co-fermentation strategies.

This study took a novel approach to address the dual challenges of enhancing the ethanol content and aroma complexity in Laiyang pear wine. It focused on sorbitol as a pivotal element in the strategic selection of yeasts with specific sorbitol-utilization capabilities and their application in co-fermentation strategies. We selected two Saccharomyces cerevisiae strains (coded as Sc1, Sc2), two Metschnikowia pulcherrima (coded as Mp1, Mp2), and one Pichia terricola (coded as Tp) due to their efficacy as starter cultures. Notably, the Sc2 strain, alone or with Mp2, significantly increased the ethanol content (30% and 16%). Mixed Saccharomyces cerevisiae and Pichia terricola fermentation improved the ester profiles and beta-damascenone levels (maximum of 150%), while Metschnikowia pulcherrima addition enriched the phenethyl alcohol content (maximum of 330%), diversifying the aroma. This study investigated the efficacy of strategic yeast selection based on sorbitol utilization and co-fermentation methods in enhancing Laiyang pear wine quality and aroma.

Development and validation of a liquid chromatography tandem mass spectrometry method for the determination of 10 mycotoxins in beer of the Chinese market and exposure estimate.

Mycotoxins are important risk factors in beer. In this study, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to determine 10 mycotoxins in beer within 6 min. The method is fast, efficient, and has a simple and quick sample preparation. Validation was conducted based on the performance standards specified in Commission Decision 657/2002/EC, and the results demonstrated excellent linearity (R2 > 0.99), repeatability (RSD < 5 %), quantification limits (0.005-20.246 µg/L), and recovery rates (77 %-118 %). The prevalence of the 10 mycotoxins in 96 beers purchased from the Chinese market was analyzed, and the exposure of the Chinese population to mycotoxins through beer consumption was assessed. Deoxynivalenol (DON) was detected in 93.75 % of the beers, and the incidence of fumonisins (FBs) and zearalenone (ZEN) exceeded 50 %. Beer intake contributed significantly to the exposure of aflatoxins (AFs) and DON, especially in males. Correlation analysis between mycotoxin content in beer, raw materials, and the brewing process revealed that the brewing process significantly affected the content of DON (P < 0.001), while auxiliary materials also had a significant impact on the content of FBs and DON (P < 0.001). This study holds great significance in producing higher quality and safer beer.

Formation of vinylphenolic pyranoanthocyanins by selected indigenous yeasts displaying high hydroxycinnamate decarboxylase activity during mulberry wine fermentation and aging.

The color of mulberry wine is difficult to maintain since the main chromogenic substances, anthocyanins, are severely degraded during fermentation and aging. This study selected Saccharomyces cerevisiae I34 and Wickerhamomyces anomalus D6, both displaying high hydroxycinnamate decarboxylase (HCDC) activity (78.49% and 78.71%), to enhance the formation of stable vinylphenolic pyranoanthocyanins (VPAs) pigments during mulberry wine fermentation. The HCDC activity of 84 different strains from eight regions in China was primarily screened via the deep well plate micro fermentation method, after which the tolerance and brewing characteristics were evaluated via simulated mulberry juice. The two selected strains and a commercial Saccharomyces cerevisiae were then inoculated individually or sequentially into the fresh mulberry juice, while the anthocyanin precursors and VPAs were identified and quantified via UHPLC-ESI/MS. The results showed that the HCDC-active strains facilitated the synthesis of stable pigments, cyanidin-3-O-glucoside-4-vinylcatechol (VPC3G), and cyanidin-3-O-rutinoside-4-vinylcatechol (VPC3R), highlighting its potential for enhancing color stability.

Research progress on the application of different controlling strategies to minimizing ethyl carbamate in grape wine.

Ethyl carbamate (EC) is a probable carcinogenic compound commonly found in fermented foods and alcoholic beverages and has been classified as a category 2A carcinogen by the International Agency for Research on Cancer (IARC). Alcoholic beverages are one of the main sources of EC intake by humans. Therefore, many countries have introduced a standard EC limit in alcoholic beverages. Wine is the second largest alcoholic beverage in the world after beer and is loved by consumers for its rich taste. However, different survey results showed that the detection rate of EC in wine was almost 100%, while the maximum content was as high as 100 µg/L, necessitating EC content regulation in wine. The existing methods for controlling the EC level in wine mainly include optimizing raw fermentation materials and processes, using genetically engineered strains, and enzymatic methods (urease or urethanase). This review focused on introducing and comparing the advantages, disadvantages, and applicability of methods for controlling EC, and proposes two possible new techniques, that is, changing the fermentation strain and exogenously adding phenolic compounds. In the future, it is hoped that the feasibility of this prospect will be verified by pilot-scale or large-scale application to provide new insight into the regulation of EC during wine production. The formation mechanism and influencing factors of EC in wine were also introduced and the analytical methods of EC were summarized.

VabHLH137 promotes proanthocyanidin and anthocyanin biosynthesis and enhances resistance to Colletotrichum gloeosporioides in grapevine.

Proanthocyanidins (PAs) and anthocyanins are involved in the response of plants to various environmental stresses. However, the mechanism behind defense-induced PA biosynthetic regulation is still not completely elucidated, also in grapevine. This study performed a transcriptome sequencing analysis of grape berries infected with Colletotrichum gloeosporioides to highlight the induction of the VabHLH137 factor from the basic helix-loop-helix (bHLH) XII subfamily by the fungus, which appeared to be significantly co-expressed with PA-related genes. The functional analysis of VabHLH137 overexpression and knockdown in transgenic grape calli showed that it positively regulated PA and anthocyanin biosynthesis. Moreover, VabHLH137 overexpression in the grape calli significantly increased resistance to C. gloeosporioides. A yeast one-hybrid and electrophoretic mobility shift assay revealed that VabHLH137 directly bound to the VaLAR2 promoter, enhancing its activity and interacting with VaMYBPAR, a transcriptional activator of PA biosynthesis. Furthermore, transient experiments showed that although the VabHLH137 + VaMYBPAR complex activated VaLAR2 expression, it failed to further enhance VaLAR2 expression compared to VaMYBPAR alone. The findings indicated that VabHLH137 enhanced PA biosynthesis by activating of VaLAR2 expression, providing new insight into the transcriptional regulation of defense-induced PA biosynthesis in grapevine.

Research progress regarding the effect and mechanism of dietary phenolic acids for improving nonalcoholic fatty liver disease via gut microbiota.

Phenolic acids (PAs), a class of small bioactive molecules widely distributed in food and mainly found as secondary plant metabolites, present significant advantages such as antioxidant activity and other health benefits. The global epidemic of nonalcoholic fatty liver disease (NAFLD) is becoming a serious public health problem. Existing studies showed that gut microbiota (GM) dysbiosis is highly associated with the occurrence and development of NAFLD. In recent years, progress has been made in the study of the relationship among PA compounds, GM, and NAFLD. PAs can regulate the composition and functions of the GM to promote human health, while GM can increase the dietary sources of PAs and improve its bioavailability. This paper discussed PAs, GM, and their interrelationship while introducing several representative dietary PA sources and examining the absorption and metabolism of PAs mediated by GM. It also summarizes the effect and mechanisms of PAs in improving and regulating NAFLD via GM and their metabolites. This helps to better evaluate the potential preventive effect of PAs on NAFLD via the regulation of GM and expands the utilization of PAs and PA-rich food resources.

Dietary regulation of the SIgA-gut microbiota interaction.

Gut microbiota (GM) is essential for host health, and changes in the GM are related to the development of various diseases. Recently, secretory immunoglobulin A (SIgA), the most abundant immunoglobulin isotype in the intestinal mucosa, has been found to play an essential role in controlling GM. SIgA dysfunction can lead to changes in the GM and is associated with the development of various GM-related diseases. Although in early stage, recent studies have shown that assorted dietary interventions, including vitamins, amino acids, fatty acids, polyphenols, oligo/polysaccharides, and probiotics, can influence the intestinal SIgA response and SIgA-GM interaction. Dietary intervention can enhance the SIgA response by directly regulating it (from top to bottom) or by regulating the GM structure or gene expression (from bottom to top). Furthermore, intensive studies involving the particular influence of dietary intervention on SIgA-binding to the GM and SIgA repertoire and the precise regulation of the SIgA response via dietary intervention are still exceedingly scarce and merit further consideration. This review summarizes the existing knowledge and (possible) mechanisms of the influence of dietary intervention on the SIgA-GM interaction. Key issues are considered, and the approaches in addressing these issues in future studies are also discussed.

Application of non-Saccharomyces yeasts with high ß-glucosidase activity to enhance terpene-related floral flavor in craft beer.

The rising interest in craft beer urging for novel yeasts that provide diverse attributes. This research aimed to explore the potential of four non-Saccharomyces yeasts with high ß-glucosidase activity in beer fermentation. Fermentation ability, adverse environment resistance and carbohydrate affinity were measured via growth and physiochemical parameters and, based on these results, a Candida glabrata (D18) yeast was selected for subsequent sequential fermentations. Aroma analysis of the fermented beer was then performed using gas chromatography-mass spectrometry, demonstrated that some glucoside-binding terpenes had been significantly increased. In two D18 involved groups, geraniol content increased 51.5/11-fold in the single and mixed fermentations, respectively, while linalool increased 1.36-fold in the mixed fermentation, providing the final beer product with unique floral and fruity characteristics. Principal component analysis and sensory evaluation were also applied to further demonstrate these distinctions. Overall, D18 was found to be a potential yeast for beer fermentation with unique properties.

Survey of the biogenic amines in craft beer from the Chinese market and the analysis of the formation regularity during beer fermentation.

This study evaluated the levels of eight biogenic amines in 59 craft beers of five styles and monitored the changes during beer fermentation, showing that putrescine and tryptamine were the most abundant at maximum values of 46.14 mg/L and 89.97 mg/L, respectively. This research indicated for the first time that dark beer, such as Stout/Porter, displayed the highest total biogenic amine content due to considerable tryptamine accumulation, with a maximum value of 116.95 mg/L. The total biogenic amine level increased gradually during the segmental saccharification and main fermentation stages, representing the two critical control points for their formation during beer fermentation. This study provides a theoretical basis and technical guidance for the safe and standardized production of craft beer and the formulation of biogenic amines limit standards, which is highly significant for protecting the health of consumers.

Fungal Community Composition and Its Relationship with Volatile Compounds during Spontaneous Fermentation of Cabernet Sauvignon from Two Chinese Wine-Growing Regions.

The microbial community structure associated with wine in a wine-growing region is shaped by diverse ecological factors within that region, profoundly impacting the wine flavor. In wine fermentation, fungi contribute more sensory-active biochemical compounds than bacteria. In this study, we employed amplicon sequencing to measure samples from the spontaneous fermentation process of cabernet sauvignon wines from two wine-growing regions in China to study the diversity and structural evolution of fungi during spontaneous fermentation and analyze the correlation between fungi and volatile compounds. The results showed significant differences in fungal community structure and diversity in cabernet sauvignon musts from different geographical origins, and these differences affected the flavor quality of the wines. As alcoholic fermentation progressed, Saccharomyces became the dominant fungal genus and reshaped the fungal community structure, and the diversity of the fungal community decreased. However, the fungal communities of each wine-growing region remained distinct throughout the fermentation process. Furthermore, the correlation between the fungal community and volatile compounds indicated that wine is a product of fermentation involving multiple fungal genera, and the flavor is influenced by a variety of fungi. Our study enhances the comprehension of fungal communities in Chinese wine-growing regions, explaining the regulatory role of wine-related fungal microorganisms in wine flavor.

Ovarian clear cell cancer associated with Trousseau syndrome: A case report and literature review.

RATIONALE: Trousseau syndrome is known as patients with tumors have a combination of multiple thrombi with systemic organ infarction. The incidence of ovarian clear cell cancer associated with Trousseau syndrome is relatively low. We report the case of a 41-year-old woman diagnosed with ovarian clear cell cancer with deep vein thrombosis and cerebral infarction who had a poor prognosis. PATIENT CONCERNS: A 41-year-old woman was brought to our hospital with abdominal pain. Abdominal computerized tomography scan suggested large mass of ovarian origin which was considered an ovarian tumor with pelvic metastasis and peritoneal metastasis. Laboratory analyses indicated an elevated levels of serum tumor marker carbohydrate antigen 125 was 321.9 U/mL and the level of D-dimer was 16.71 mg/L. DIAGNOSIS: The patient underwent pelvic mass aspiration was diagnosed with ovarian clear cell cancer. B-ultrasound revealed thrombosis of the lower limbs. INTERVENTIONS: She underwent 2 neoadjuvant chemotherapies, along with anticoagulation therapy. However, it had a poor therapeutic effect, and the patient suffered from acute cerebral infarction that worsened. OUTCOMES: Chemotherapy and anticoagulation failed to stop the tumor and blood clot progression. The patient died 2 months after cerebral infarction without surgical treatment. LESSONS: Gynecologists should be aware of the need for clinical suspicion of the risk of thrombosis during the treatment period of ovarian cancer and make careful decisions.

Sweet potato extract alleviates high-fat-diet-induced obesity in C57BL/6J mice, but not by inhibiting pancreatic lipases.

Scope and aim: Sweet potato is widely consumed as a healthy and nutritive vegetable containing bioactive constituents for health promotion. This study investigated the beneficial impact of white-fleshed sweet potato extract (SPE) on high fat diet (HFD)-induced obese mice. Methods and results: First, SPE, in which resin glycoside was found as the dominant constituent, was suggested as a potential anti-obesity agent, because 20-70% pancreatic lipase (PL) inhibition was measured with SPE by in vitro turbidity assay and pNPP assay. Hence, next, the effect of SPE on obese mice was detected by oral administration of HFD supplemented with 6% SPE on C57BL/6J mice for 9 weeks. Surprisingly, being the opposite of what was typically observed from a lipase inhibitor such as orlistat, the fecal fat content in SPE-fed obese mice was decreased (p < 0.01). Meanwhile, 6% SPE supplement indeed significantly ameliorated HFD-induced obesity in mice, including body weight gain, fat accumulation, adipocyte enlargement, insulin resistance, and hepatic steatosis (p < 0.05). The improved liver steatosis was found associated with a down-regulating action of SPE on nuclear factor kappa B activation in HFD-fed mice. The anti-obesity influence of SPE was also confirmed on the HepG2 cell model for non-alcoholic fatty liver disease (NAFLD). Conclusion: These results indicate that SPE, as a dietary supplement, has the great potential for weight control and treating hepatic steatosis, possibly through a different action mechanism from that of orlistat.

Indigenous yeast can increase the phenolic acid and volatile ester compounds in Petit Manseng wine.

Introduction: Indigenous yeasts are generally found in grapes, vineyards, and natural environments. Sequential inoculation and fermentation with non-Saccharomyces cerevisiae yeast (H30) and Saccharomyces cerevisiae (YT13) also improve the flavor of wine. Methods: This study sequentially inoculated fermented Petit Manseng and natural grape juice with native H30 and YT13 selected from vineyards in Yantai, China. Results and discussion: The sensory characteristics of Petit Manseng wine were evaluated by detecting the primary organic acids, phenolic acid compounds, and volatile ester compounds. The results showed that the lactic acid content of the natural wine fermented sequentially with H30 and YT13 increased by 490 µg/L compared with the control group, while the ferulic acid content was 1.4 times that of the single-yeast fermentation group. Furthermore, butyrolactone and anthocyanidin propionate were present in the mixed fermentation group, increasing the aroma complexity of Petit Manseng wine and providing high-quality yeast resources that increase the regional characteristics when producing dry white wine.

Hanseniaspora uvarum FS35 degrade putrescine in wine through the direct oxidative deamination pathway of copper amine oxidase 1.

Putrescine is abundant in wine and have toxicological risks for the health of consumers. Certain microbes with oxidative deamination activity are considered to be one of the most effective ways to degrade putrescine. The characterization and possible mechanism of putrescine degradation by Hanseniaspora uvarum FS35 were studied in this work. Hanseniaspora uvarum FS35 was selected from 111 yeast strains by UPLC analysis and exhibited the ability to eliminate > 44.5 mg/L of putrescine after 12 h of culture. Transcriptome analysis showed that by adding putrescine as a nitrogen source, the gene expression level of copper amine oxidase 1 (CuAO1) increased, leading to a coordinated response in the oxidative deamination of putrescine to 4-amino-butanal and subsequent dehydrogenation to 4-amino-butanoate. The purified recombinant protein CuAO1 could degrade 25.8 and 21.8 mg/L of putrescine in Marselan and Cabernet Sauvignon wines, respectively. H. uvarum FS35 was then inoculated sequentially with Saccharomyces cerevisiae into Cabernet Sauvignon grape juice, and the physiochemical indexes and aroma compounds were detected by HPLC and HS-SPME/GC-MS, respectively. wines produced from sequential inoculations showed significantly lower level of putrescine and higher amounts of glycerol, lactic acid, acetic acid, phenylethyl alcohol, ethyl acetate and ß-phenylethyl acetate compared with the control fermentation of commercial S. cerevisiae, which proved the potential of H. uvarum FS35 as a promising strategy to reduce biogenic amines in wines.

Coconut oil and medium-chain fatty acids attenuate high-fat diet-induced obesity in mice through increased thermogenesis by activating brown adipose tissue.

Coconut oil (CO) and its main ingredients, medium-chain fatty acids (MCFA), present many benefits. Whether MCFA and CO play an equally valuable role in anti-obesity remains unclear. This study compared the anti-obesity effects of CO and MCFA [octanoic acid (C8:0) and decanoic acid (C10:0)] to gain insight into the underlying mechanism. Male C57BL/6J mice were fed either a low-fat diet (LFD) or high-fat diet (100% HFD) replaced with 2.5% MCFA (97.5% HFD + 2.5% MCFA) or 5% CO (95% HFD + 5% CO) for 17 weeks. CO and MCFA ameliorated the HFD-induced abnormal body and adipose depot weights, insulin sensitivity, and energy expenditure (EE), which was associated with brown adipose tissue (BAT) thermogenesis. Furthermore, CO enhanced the expression of thermogenesis markers in BAT, which was consistent with increased BAT activity. CO showed a better effect than MCFA in activating BAT to increase thermogenesis and energy metabolism to combat obesity, which may be attributed to the cooperation of MCFA and other substances in CO. This work provides evidence for the anti-obesity effects of CO, which could be a better alternative to lard in daily diet, rather than pure MCFA.

Indigenous Saccharomyces cerevisiae Could Better Adapt to the Physicochemical Conditions and Natural Microbial Ecology of Prince Grape Must Compared with Commercial Saccharomyces cerevisiae FX10.

Indigenous Saccharomyces cerevisiae, as a new and useful tool, can be used in fermentation to enhance the aroma characteristic qualities of the wine-production region. In this study, we used indigenous S. cerevisiae L59 and commercial S. cerevisiae FX10 to ferment Prince (a new hybrid variety from Lion Winery) wine, detected the basic physicochemical parameters and the dynamic changes of fungal communities during fermentation, and analyzed the correlations between fungal communities and volatile compounds. The results showed that the indigenous S. cerevisiae L59 could quickly adapt to the specific physicochemical conditions and microbial ecology of the grape must, showing a strong potential for winemaking. Compared with commercial S. cerevisiae FX10, the wine fermented by indigenous S. cerevisiae L59 contained more glycerol and less organic acids, contributing to a rounder taste. The results of volatile compounds indicated that the indigenous S. cerevisiae L59 had a positive effect on adding rosy, honey, pineapple and other sweet aroma characteristics to the wine. Overall, the study we performed showed that selection of indigenous S. cerevisiae from the wine-producing region as a starter for wine fermentation is conducive to improving the aroma profile of wine and preserving the aroma of the grape variety.

Study on effects of processing technology and storage on the composition of Ampelopsis grossedentata by untargeted metabolomics.

Ampelopsis grossedentata is a traditional medicinal and edible plant rich in bioactive compounds. This paper focus on the white powder on the surface of A. grossedentata, and the effects of processing technology and storage time on the composition of bioactive compounds in Ampelopsis grossedentata extracts (AMP). 33 compounds in AMP were identified and 30 compounds were reported for the first time compared with standards by UHPLC-Q-Orbitrap-MS. Organic acid, phenol, and flavonoids were detected in powder samples. Through comparing the mass spectrum data of three processing samples (traditional method, fermentation and drying-only), five compounds in fermentation samples were higher than other groups, and the content of most compounds of the traditional process was decreased compared with drying-only process. For the storage time research, the powder on the surface was found to be more unstable than leaf parts after 24 h, suggesting that sealing preservation is crucial in the process after powder precipitation.

Glycosylated modification of MUC1 maybe a new target to promote drug sensitivity and efficacy for breast cancer chemotherapy.

Breast cancer, the most common cancer in women, usually exhibits intrinsic insensitivity to drugs, even without drug resistance. MUC1 is a highly glycosylated transmembrane protein, overexpressed in breast cancer, contributing to tumorigenesis and worse prognosis. However, the molecular mechanism between MUC1 and drug sensitivity still remains unclear. Here, natural flavonoid apigenin was used as objective due to the antitumor activity and wide availability. MUC1 knockout (KO) markedly sensitized breast cancer cells to apigenin cytotoxicity in vitro and in vivo. Both genetical and pharmacological inhibition significantly enhanced the chemosensitivity to apigenin and clinical drugs whereas MUC1 overexpression conversely aggravated such drug resistance. Constitutively re-expressing wild type MUC1 in KO cells restored the drug resistance; however, the transmembrane domain deletant could not rescue the phenotype. Notably, further investigation discovered that membrane-dependent drug resistance relied on the extracellular glycosylated modification since removing O-glycosylation via inhibitor, enzyme digestion, or GCNT3 (MUC1 related O-glycosyltransferase) knockout markedly reinvigorated the chemosensitivity in WT cells, but had no effect on KO cells. Conversely, inserting O-glycosylated sites to MUC1-N increased the drug tolerance whereas the O-glycosylated deletant (Ser/Thr to Ala) maintained high susceptibility to drugs. Importantly, the intracellular concentration of apigenin measured by UPLC and fluorescence distribution firmly revealed the increased drug permeation in MUC1 KO and BAG-pretreated cells. Multiple clinical chemotherapeutics with small molecular were tested and obtained the similar conclusion. Our findings uncover a critical role of the extracellular O-glycosylation of MUC1-N in weakening drug sensitivity through acting as a barrier, highlighting a new perspective that targeting MUC1 O-glycosylation has great potential to promote drug sensitivity and efficacy.

Mulberry Ethanol Extract and Rutin Protect Alcohol-Damaged GES-1 Cells by Inhibiting the MAPK Pathway.

Mulberry extract has been proven to have the effect of resisting alcohol damage, but its mechanism is still unclear. In this study, the composition of mulberry ethanol extract (MBE) was identified by LC-MS/MS and the main components of MBE were ascertained by measuring. Gastric mucosal epithelial (GES-1) cells were used to elucidate the mechanism of MBE and rutin (the central part of MBE) helped protect against alcohol damage. The results revealed that phenolics accounted for the majority of MBE, accounting for 308.6 mg/g gallic acid equivalents and 108 substances were identified, including 37 flavonoids and 50 non-flavonoids. The treatment of 400 µg/mL MBE and 320 µM rutin reduced early cell apoptosis and the content of intracellular reactive oxygen species, malondialdehyde and increased glutathione. The qPCR results indicated that the MBE inhibits the expression of genes in the mitogen-activated protein kinase (MAPK) pathway, including p38, JNK, ERK and caspase-3; rutin inhibits the expression of p38 and caspase-3. Overall, MBE was able to reduce the oxidative stress of GES-1 cells and regulated apoptosis-related genes of the MAPK pathway. This study provides information for developing anti-ethanol injury drugs or functional foods.