Dietary flavonoids modulate the gut microbiota: A new perspective on improving autism spectrum disorder through the gut-brain axis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unknown etiology. It is associated with various factors and causes great inconvenience to the patient's life. The gut-brain axis (GBA), which serves as a bidirectional information channel for exchanging information between the gut microbiota and the brain, is vital in studying many neurodegenerative diseases. Dietary flavonoids provide anti-inflammatory and antioxidant benefits, as well as regulating the structure and function of the gut microbiota. The occurrence and development of ASD are associated with dysbiosis of the gut microbiota. Modulation of gut microbiota can effectively improve the severity of ASD. This paper reviews the links between gut microbiota, flavonoids, and ASD, focusing on the mechanism of dietary flavonoids in regulating ASD through the GBA.

A gene-encoded aldehyde tag repurposed from RiPP cyclophane-forming pathway.

Gene-encoded aldehyde tag technology has been widely utilized in protein bioorthogonal chemistry and biotechnological application. Herein, we report utilization of the promiscuous rSAM cyclophane synthase SjiB involved in triceptide biosynthesis as a dedicated and highly efficient formylglycine synthase. The new aldehyde tag sequence in this system, YQSSI, is biosynthetically orthogonal to the known aldehyde tag (C/S)x(P/A)xR. The potential use of SjiB/YQSSI aldehyde tag system was further validated in fluorescent labelling of model proteins.

Selecting autochthonous lactic acid bacteria for co-inoculation in Chinese bayberry wine production: Stress response, starter cultures application and volatilomic study.

This study focused on isolating and characterising autochthonous lactic acid bacteria (LAB) from spontaneously fermented Chinese bayberry (CB) and their potential application in CB wine fermentation in co-inoculation with yeast starter cultures. Numerous LAB, including Lactiplantibacillus (Lp.) plantarum (9), Limosilactobacillus (Lb.) fermentum (6), Lactococcus (Lc.) lactis (3), Enterococcus (Ec.) hirae (1), Leuconostoc (Le.) mesenteroides (1), and Weissella (Ws.) cibaria (1), were isolated and identified. The isolated strains Lp. plantarum ZFM710 and ZFM715, together with Lb. fermentum ZFM720 and ZFM722, adapted well to unfavourable fermentation environment, including ethanol, osmolality, and acidity stresses, were selected for producing CB wine by co-inoculation with Saccharomyces cerevisiae. During fermentation, the presence of LAB promoted the development of S. cerevisiae, while the population dynamics of LAB in different groups at different stages showed strain-specific differences. Fermentation trials involving LAB yielded a lower ethanol concentration except for Lp. plantarum ZFM715. Compared to the pure S. cerevisiae fermented sample, the addition of LAB led to a clear modulation in organic acid composition. Lb. fermentum strains in co-fermentation led to significant decreases in each classified group of aroma compounds, while Lp. plantarum ZFM715 significantly increased the complexity and intensity of aroma compounds, as well as the intensities of fruity and floral notes. The study selects interesting strains for the design of starter cultures for use in CB wine production, underlining the interest in the selection of autochthonous LAB in fruit wines, with the aim of improving the adaptation of bacteria to specific environmental conditions and shaping the unique traits of the finished products.

Comparison of phenolic composition and sensory quality among pear beverages made using Saccharomyces cerevisiae and Torulaspora delbrueckii.

The effects of Saccharomyces cerevisiae and Torulaspora delbrueckii on phenolic composition and sensory quality were characterized in the production of alcoholic beverages from selected pear cultivars with diverse biochemical characteristics. The fermentation process generally affected the phenolic composition by increasing the contents of hydroxycinnamic acids and flavan-3-ols and reducing the levels of hydroxybenzoic acids, procyanidins, and flavonols. Although the phenolic compositions and sensory properties of pear beverages depended primarily on pear cultivar selection, the applied yeast strains also played important roles in beverage quality. Fermentation with T. delbrueckii resulted in higher caffeoylquinic acid and quercetin-3-O-glucoside contents, higher rated intensities of 'cooked pear' and 'floral' odors and a sweeter taste than fermentation with S. cerevisiae. Moreover, higher concentrations of hydroxybenzoic acids, hydroxycinnamic acids, and flavonols correlated closely with astringency perception. Applying T. delbrueckii strains and breeding novel pear cultivars are important approaches to produce fermented beverages of high quality.

Metabolic enzyme Suclg2 maintains tolerogenicity of regulatory dendritic cells diffDCs by suppressing Lactb succinylation.

Metabolic reprogramming plays a pivotal role in the differentiation and function of immune cells including dendritic cells (DCs). Regulatory DCs can be generated in regional tissue niches like splenic stroma and act as an important part of stromal control of immune response for the maintenance of immune tolerance. However, the metabolic alterations during splenic stroma-driven regulatory DCs differentiation and the metabolic enzyme involved in regulatory DCs function remain poorly understood. By combining metabolomic, transcriptomic, and functional investigations of mature DCs (maDCs) and diffDCs (regulatory DCs differentiated from activated mature DCs through coculturing with splenic stroma), here we identified succinate-CoA ligase subunit beta Suclg2 as a key metabolic enzyme that reprograms the proinflammatory status of mature DCs into a tolerogenic phenotype via preventing NF-κB signaling activation. diffDCs downregulate succinic acid levels and increase the Suclg2 expression along with their differentiation from mature DCs. Suclg2-interference impaired the tolerogenic function of diffDCs in inducing T cell apoptosis and enhanced activation of NF-κB signaling and expression of inflammatory genes CD40, Ccl5, and Il12b in diffDCs. Furthermore, we identified Lactb as a new positive regulator of NF-κB signaling in diffDCs whose succinylation at the lysine 288 residue was inhibited by Suclg2. Our study reveals that the metabolic enzyme Suclg2 is required to maintain the immunoregulatory function of diffDCs, adding mechanistic insights into the metabolic regulation of DC-based immunity and tolerance.

Aroma characteristics of volatile compounds brought by variations in microbes in winemaking.

Wine is a highly complex mixture of components with different chemical natures. These components largely define wine's appearance, aroma, taste, and mouthfeel properties. Among them, aroma is among the most important indicators of wine's sensory characteristics. The essence of winemaking ecosystem is the process of metabolic activities of diverse microbes including yeasts, lactic acid bacteria, and molds, which result in wines with complicated and diversified aromas. A better understanding of how these microbes affect wine's aroma is a crucial step to producing premium quality wine. This study illustrates existing knowledge on the diversity and classification of wine aroma compounds and their microbial origin. Their contributions to wine characteristics are discussed, as well. Furthermore, we review the relationship between these microbes and wine aroma characteristics. This review broadens the discussion of wine aroma compounds to include more modern microbiological concepts, and it provides relevant background and suggests new directions for future research.

Glycosyltransferase Extl1 promotes CCR7-mediated dendritic cell migration to restrain infection and autoimmunity.

CCR7-triggered DC migration toward draining lymph nodes is critical for the initiation of protective immunity and maintenance of immune tolerance. How to promote CCR7-mediated DC migration to determine T cell responses under inflammatory and homeostatic conditions remains poorly understood. Here we demonstrate that the Extl1 (Exostosin like glycosyltransferase 1) promotes CCR7-triggered DC migration in a heparan sulfate proteoglycans (HSPG)-dependent manner. Mechanistically, Extl1 mediates HSPG production via its glycosyltransferase domain to inhibit C1q expression. Extl1/HSPG axis relieves C1q-mediated restriction of CCR7 surface expression and internalization, and thus enhances CCR7-dependent migratory signaling activation. Consequently, Extl1 is required for DC-mediated Th1 and Th17 responses in immune defense against bacterial infection and for Treg cell development in the prevention of autoimmunity. Our study adds mechanistic insights to the regulation of CCR7-triggered DC migration in immunity and tolerance and provides a potential target for the treatment of infectious and autoimmune diseases.

Innate immune imprints in SARS-CoV-2 Omicron variant infection convalescents.

SARS-CoV-2 Omicron variant infection generally gives rise to asymptomatic to moderate COVID-19 in vaccinated people. The immune cells can be reprogrammed or "imprinted" by vaccination and infections to generate protective immunity against subsequent challenges. Considering the immune imprint in Omicron infection is unclear, here we delineate the innate immune landscape of human Omicron infection via single-cell RNA sequencing, surface proteome profiling, and plasma cytokine quantification. We found that monocyte responses predominated in immune imprints of Omicron convalescents, with IL-1ß-associated and interferon (IFN)-responsive signatures with mild and moderate symptoms, respectively. Low-density neutrophils increased and exhibited IL-1ß-associated and IFN-responsive signatures similarly. Mild convalescents had increased blood IL-1ß, CCL4, IL-9 levels and PI3+ neutrophils, indicating a bias to IL-1ß responsiveness, while moderate convalescents had increased blood CXCL10 and IFN-responsive monocytes, suggesting durative IFN responses. Therefore, IL-1ß- or IFN-responsiveness of myeloid cells may indicate the disease severity of Omicron infection and mediate post-COVID conditions.

Review of phytochemical and nutritional characteristics and food applications of Citrus L. fruits.

Since the dietary regimen rich in fruits is being widely recognized and encouraged, Citrus L. fruits have been growing in popularity worldwide due to their high amounts of health-promoting phytonutrients and bioactive compounds, such as flavonoids, phenolic acids, vitamins, carotenoids, pectins, and fatty acids. The diverse physicochemical properties and multiple utilization of citrus fruits in food industry are associated with their unique chemical compositions. Throughout the world, citrus has been used for producing various value-added and nutritionally enhanced products, including juices, wines, jams, canned citrus, and dried citrus. However, the current studies regarding the phytochemical and nutritional characteristics and food applications of citrus are scattered. This review systematically summarizes the existing bibliography on the chemical characteristics, functional and nutraceutical benefits, processing, and potential applications of citrus. A thorough understanding of this information may provide scientific guidance for better utilizing citrus as a functional fruit and benefit the extension of citrus value chain.

lncRNA-GM targets Foxo1 to promote T cell-mediated autoimmunity.

RNA-RBP interaction is important in immune regulation and implicated in various immune disorders. The differentiation of proinflammatory T cell subset TH17 and its balance with regulatory T cell (Treg) generation is closely related to autoimmune pathogenesis. The roles of RNA-RBP interaction in regulation of TH17/Treg differentiation and autoinflammation remain in need of further investigation. Here we report that lncRNA-GM polarizes TH17 differentiation but inhibits iTreg differentiation by reducing activity of Foxo1, a transcriptional factor that is important in inhibiting TH17 differentiation but promoting Treg generation. lncRNA-GM-deficient mice were protected from experimental autoimmune encephalomyelitis. Mechanistically, lncRNA-GM directly binds to cytoplasmic Foxo1, thus inhibiting its activity through blocking dephosphorylation of Foxo1 by phosphatase PP2A to promote Il23r transcription. The human homolog of lncRNA-GM (AK026392.1) also polarizes human TH17 differentiation. Our study provides mechanistic insight into the interaction of lncRNA and transcriptional factor in determining T cell subset differentiation during T cell-mediated autoimmune diseases.

A Class IIb Bacteriocin Plantaricin NC8 Modulates Gut Microbiota of Different Enterotypes in vitro.

The gut microbiota is engaged in multiple interactions affecting host health. Bacteriocins showed the ability of impeding the growth of intestinal pathogenic bacteria and modulating gut microbiota in animals. Few studies have also discovered their regulation on human intestinal flora using an in vitro simulated system. However, little is known about their effect on gut microbiota of different enterotypes of human. This work evaluated the modification of the gut microbiota of two enterotypes (ET B and ET P) by the class IIb bacteriocin plantaricin NC8 (PLNC8) by using an in vitro fermentation model of the intestine. Gas chromatography results revealed that PLNC8 had no influence on the gut microbiota's production of short-chain fatty acids in the subjects' samples. PLNC8 lowered the Shannon index of ET B' gut microbiota and the Simpson index of ET P' gut microbiota, according to 16S rDNA sequencing. In ET B, PLNC8 enhanced the abundance of Bacteroides, Bifidobacterium, Megamonas, Escherichia-Shigella, Parabacteroides, and Lactobacillus while decreasing the abundance of Streptococcus. Prevotella_9, Bifidobacterium, Escherichia-Shigella, Mitsuokella, and Collinsella were found more abundant in ET P. The current study adds to our understanding of the impact of PLNC8 on the human gut microbiota and lays the groundwork for future research into PLNC8's effects on human intestinal disease.

Effect of Response Surface Methodology-Optimized Ultrasound-Assisted Pretreatment Extraction on the Composition of Essential Oil Released From Tribute citrus Peels.

The traditional hydrodistillation (HD) and ultrasound-assisted pretreatment extraction (UAPE) methods were proposed to obtain essential oil (EO) from Tribute citrus (TC) peels. The Box-Behnken design was employed to optimize the HD and UAPE procedures. Moreover, gas chromatography-mass spectrometry (GC-MS) and electronic nose (E-nose) were applied to identify the discrepancy of the extraction methods. The yield of EO extracted by UAPE (114.02 mg/g) was significantly higher than that by HD (85.67 mg/g) (p < 0.01) undergoing 40 min short time-consuming UPAE. A total of 28 compounds were extracted from the TC peels as terpenes were the predominant components. d-Limonene was the most vital compound in the T. citrus essential oil (TCEO), accounting for 86.38% of the total volatile concentration in HD and 86.75% in UAPE, respectively, followed by α-pinene, sabinene, γ-myrcene, and ß-phellandrene. The chart of radar and graphic of the principal component analysis by E-nose displayed no significance, which was similar to the GC-MS results. This study demonstrated that UAPE is an efficient and short time-consuming method for TCEO extraction, which provides a promising method for the separation of EO from aromatic plant materials.

Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial.

BACKGROUND: There is currently a lack of effective treatments for non-small cell lung cancer (NSCLC) patients harboring HER2 mutations. We examined the efficacy and safety of, and potential resistance mechanism to, pyrotinib, a pan-HER inhibitor, in advanced NSCLC carrying HER2 mutations. METHODS: In this multicenter, single-arm, phase II trial, stage IIIB-IV NSCLC patients harboring HER2 mutations, as determined using next-generation sequencing, were enrolled and treated with pyrotinib at a dose of 400 mg/day. The primary endpoint was 6-month progression-free survival (PFS) rate, and secondary endpoints were objective response rate (ORR), PFS, overall survival (OS), disease control rate (DCR), and safety. The impact of different HER2 mutation types on sensitivity to pyrotinib and the potential of utilizing mutational profile derived from circulating tumor DNA (ctDNA) to predict disease progression were also explored. RESULTS: Seventy-eight patients were enrolled for efficacy and safety analysis. The 6-month PFS rate was 49.5% (95% confidence interval [CI], 39.2-60.8). Pyrotinib produced an ORR of 19.2% (95% CI, 11.2-30.0), with median PFS of 5.6 months (95% CI, 2.8-8.4), and median OS of 10.5 months (95% CI, 8.7-12.3). The median duration of response was 9.9 months (95% CI, 6.2-13.6). All treatment-related adverse events (TRAEs) were grade 1-3 (all, 91.0%; grade 3, 20.5%), and the most common TRAE was diarrhea (all, 85.9%; grade 3, 16.7%). Patients with exon 20 and non-exon 20 HER2 mutations had ORRs of 17.7% and 25.0%, respectively. Brain metastases at baseline and prior exposure to afatinib were not associated with ORR, PFS, or OS. Loss of HER2 mutations and appearance of amplification in HER2 and EGFR were detected upon disease progression. CONCLUSIONS: Pyrotinib exhibited promising efficacy and acceptable safety in NSCLC patients carrying exon 20 and non-exon 20 HER2 mutations and is worth further investigation. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1800020262.

Use of Non-Saccharomyces Yeasts in Berry Wine Production: Inspiration from Their Applications in Winemaking.

Although berries (nongrape) are rich in health-promoting bioactive compounds, and their consumption is associated with a lower risk of diverse chronic diseases, only a fraction of the annual yield of berries is exploited and consumed. Development of berry wines presents an approach to increase the utilization of berries. Alcoholic fermentation is a complex process driven by yeasts, which influence key properties of wine diversification and quality. In winemaking, non-Saccharomyces yeasts were traditionally considered as undesired microorganisms because of their high production of metabolites with negative connotations. However, there has been a recent and growing interest in the application of non-Saccharomyces yeast in many innovative wineries. Numerous studies have demonstrated the potential of these yeasts to improve properties of wine as an alternative or complement to Saccharomyces cerevisiae. The broad use of non-Saccharomyces yeasts in winemaking provides a promising picture of these unconventional yeasts in berry wine production, which can be considered as a novel biotechnological approach for creating value-added berry products for the global market. This review provides an overview of the current use of non-Saccharomyces yeasts in winemaking and their applicative perspective in berry wine production.

Sensory and chemical characterization of Chinese bog bilberry wines using Check-all-that-apply method and GC-Quadrupole-MS and GC-Orbitrap-MS analyses.

The sensory and chemical profiles of commercial bog bilberry (BB) wines were investigated using a multi-analytical approach. Sensory test included scaling and check-all-that-apply (CATA) method with questions on liking of BB wine. The sensory data was correlated with their volatile compound profiles determined using gas chromatography coupled with quadrupole and orbitrap mass spectrometry (GC-Quadrupole/Orbitrap-MS). In general, all BB wines were characterized with "fruity", "blueberry" and "floral" odors and "sour", "mouth puckering" and "sweet" flavors. Samples more frequently characterized as "fruity" and "floral" in CATA were preferred by the panelists (n = 93). High relative proportions of o-cymene, p-cymenene, 1-octen-3-one and 3-ethylphenol in a sample (described as "ginger" and "chili") resulted in a lower liking rating. Similarly, generally disliked sample described with "Chinese herbs" and "licorice" was characterized by compounds 3-methylpentan-1-ol, 1,1,6-trimethyl-1,2-dihydronaphthalene, and 4-vinylphenol. The data will give novel information for berry wine and beverage industry on the quality factors of BB wines linked to higher acceptance.

Enhanced Performance of Membrane Distillation Using Surface Heating Process.

Membrane distillation (MD) is a thermally driven desalination process that has excellent application prospects in seawater desalination or hypersaline wastewater treatment, while severe temperature polarization (TP) and the resulting relatively high energy consumption have become principal challenges limiting the commercial application of MD. Therefore, the design of novel systems to overcome the shortage of conventional MD requires urgent attention. Here, we developed three surface heating vacuum membrane distillation systems, namely, SHVMD-1, SHVMD-2, and SHVMD-3, according to the different positions of the thermal conducting layer in the cell. The distillate flux, TP, and energy performance of these systems under different operating conditions were investigated. All three systems showed stable performance, with a salt rejection >99.98% for 35 g/L NaCl, and the highest flux was close to 9 L/m2·h. The temperature polarization coefficients were higher than unity in SHVMD-2 and SHVMD-3 systems, and the SHVMD-2 system produced the lowest specific energy consumption and the highest thermal efficiency. In addition, we tested the intermittent surface heating process, which can further improve energy performance through reducing specific electrical energy consumption in vacuum membrane distillation. This paper provides a simple and efficient membrane system for the desalination of brines.

Morphologic Change of In Vivo Porcine Liver Under 13 mm Hg Pneumoperitoneum Pressure.

BACKGROUND: Clinically, the total and residual liver volume must be accurately calculated before major hepatectomy. However, liver volume might be influenced by pneumoperitoneum during surgery. Changes in liver volume change also affect the accuracy of simulation and augmented reality navigation systems, which are commonly first validated in animal models. In this study, the morphologic changes in porcine livers in vivo under 13 mm Hg pneumoperitoneum pressure were investigated. MATERIALS AND METHODS: Twenty male pigs were scanned with contrast-enhanced computed tomography without pneumoperitoneum and with 13 mm Hg pneumoperitoneum pressure. RESULTS: The surface area and volume of the liver and the vascular diameter of the aortic lumen, inferior vena cava lumen, and portal vein lumen were measured. There were statistically significant differences in the surface area and volume of the liver (P=0.000), transverse diameter of the portal vein (P=0.038), longitudinal diameter of the inferior vena cava (P=0.033), longitudinal diameter of the portal vein (P=0.036), vascular cross-sectional area of the inferior vena cava (P=0.028), and portal vein (P=0.038) before and after 13 mm Hg pneumoperitoneum pressure. CONCLUSIONS: This study indicated that the creation of pneumoperitoneum at 13 mm Hg pressure in a porcine causes liver morphologic alterations affecting the area and volume, as well as the diameter of a blood vessel.

Effect of Saccharomyces cerevisiae and Schizosaccharomyces pombe strains on chemical composition and sensory quality of ciders made from Finnish apple cultivars.

Composition of volatile compounds and concentrations of sugars and organic acids were studied in apple ciders produced with Saccharomyces cerevisiae and Schizosaccharomyces pombe yeasts using eleven different Finnish apple cultivars. Moreover, sensory quality of selected ciders was studied using check-all-that-apply test with untrained panelists. Seventy-seven volatile compounds were detected in the samples using HS-SPME-GC-MS. In general, the ciders had higher concentrations of higher alcohols, aldehydes, and acetals whereas the juices contained higher contents of C6-alcohols. Simultaneously, fermentation using S. pombe resulted in lower concentrations of malic acid, ethyl pentanoate, ethyl hexanoate, and volatile acids and higher concentrations of residual sugars compared to S. cerevisiae. Ciders made using S. cerevisiae were characterized as 'alcoholic' and 'yeasty' while S. pombe ciders were more frequently described as 'sweet', 'honey-like', and less rated as sour. Besides the strong effect by the yeasts, apple cultivars had significant effects on the compositional and sensorial properties of apple ciders.

Effect of preheated milk proteins and bioactive compounds on the stability of cyanidin-3-O-glucoside.

Native and preheated whey protein isolates (WPI) and casein (at 55 °C-90 °C) were used as protective carriers. Three bioactive compounds, including (-)-Epigallocatechin-3-gallte (EGCG), gallic acid, and vitamin C, were added to enhance the stability of cyanidin-3-O-glucoside (C3G). Under acidic (pH 3.6) and neutral (pH 6.3) conditions, both native and preheated milk proteins showed significant protective effect on C3G. WPI preheated at 85 °C presented the best protective effect on C3G under neutral condition by reducing its thermal, oxidation, and photo degradation rates 25.0%, 38.0%, and 41.1%, respectively. The addition of vitamin C into the protein-anthocyanin solutions accelerated the color loss of C3G, whereas EGCG and gallic acid improved its thermal stability. Among the bioactive compounds, gallic acid provided the most significant protective effect on C3G by further decreasing the thermal degradation rate of C3G 44.6% as a result of the formation of 85 °C preheated WPI-gallic acid-C3G complexes.