A Prediction Model for Deciphering Intratumoral Heterogeneity Derived from the Microglia/Macrophages of Glioma Using Non-Invasive Radiogenomics.

Microglia and macrophages play a major role in glioma immune responses within the glioma microenvironment. We aimed to construct a prognostic prediction model for glioma based on microglia/macrophage-correlated genes. Additionally, we sought to develop a non-invasive radiogenomics approach for risk stratification evaluation. Microglia/macrophage-correlated genes were identified from four single-cell datasets. Hub genes were selected via lasso-Cox regression, and risk scores were calculated. The immunological characteristics of different risk stratifications were assessed, and radiomics models were constructed using corresponding MRI imaging to predict risk stratification. We identified eight hub genes and developed a relevant risk score formula. The risk score emerged as a significant prognostic predictor correlated with immune checkpoints, and a relevant nomogram was drawn. High-risk groups displayed an active microenvironment associated with microglia/macrophages. Furthermore, differences in somatic mutation rates, such as IDH1 missense variant and TP53 missense variant, were observed between high- and low-risk groups. Lastly, a radiogenomics model utilizing five features from magnetic resonance imaging (MRI) T2 fluid-attenuated inversion recovery (Flair) effectively predicted the risk groups under a random forest model. Our findings demonstrate that risk stratification based on microglia/macrophages can effectively predict prognosis and immune functions in glioma. Moreover, we have shown that risk stratification can be non-invasively predicted using an MRI-T2 Flair-based radiogenomics model.

LC-MS based metabolomics analysis of okara fermented by Bacillus subtilis DC-15: Insights into nutritional and functional profile.

Recent studies emphasize the improved nutritional and functional status of fermented okara; however, little is known about the metabolite change during fermentation and how it alters metabolic pathways. A metabolomics approach based on untargeted LC-MS reveals metabolic changes in okara fermented by Bacillus subtilis DC-15. We identified 761 differential metabolites, with the highest abundances found in amino acids, dipeptides, fatty acids, small molecule sugars, and vitamins. Moreover, these identified metabolites were mapped to their respective biosynthesis pathways in order to gain a better understanding of the biochemical reactions triggered by fermentation. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, 485 metabolites were enriched to metabolism-related pathways. They include 37 carbohydrate metabolites, 79 amino acid metabolites, and 22 lipid metabolites. As a result of okara fermentation, we observed a gradual enrichment of metabolites and stabilization of the compounds.

Unveiling of dietary and gut-microbiota derived B vitamins: Metabolism patterns and their synergistic functions in gut-brain homeostasis.

Nutrition-gut cross-talk holds a vital position in sustaining intestinal function, and micronutrient metabolism has emerged as the foremost metabolic pathway to preserve gut homeostasis. Among micronutrients, B vitamins have evolved prior to DNA/RNA and are known for their vital roles for major evolutionary transitions in extant organisms. Despite their universal requirement and critical role, not all the three domains of life are endowed with a natural ability for de novo B vitamins synthesis. The human gut microbiome constitutes prototrophs and auxotroph which are entirely dependent on dietary intake and gut microbial production of B vitamins. The syntrophic metabolism involving cross-feeding of B vitamins and community-wide exchange between commensal bacteria elicit important changes in the diversity and composition of the human gut microbiome. Hereto, we discuss the B-vitamins sharing among prototrophic and auxotrophic gut bacteria, their absorption in small intestine and transport in distal gut, functional role in relation to the gut homeostasis and symptoms linked to their deficiency. We also briefly explore their potential involvement as psychobiotics in brain energetic metabolism (kynurenines/tryptophan pathway) for neurological functions and highlight their deficiency related malfunctioning.

Identification of Immunological Characteristics and Immune Subtypes Based on Single-Sample Gene Set Enrichment Analysis Algorithm in Lower-Grade Glioma.

Few breakthroughs have been achieved in the treatment of lower-grade glioma (LGG) in recent decades. Apart from the conventional pathological and histological classifications, subtypes based on immunogenomics would provide reference for individualized treatment and prognosis prediction. Our study identified four immunotypes of lower-grade glioma (clusters A, B, C, and D) by bioinformatics methods in TCGA-LGG and two CGGA datasets. Cluster A was an "immune-cold" phenotype with the lowest immune infiltration and longest survival expectation, whereas cluster D was an "immune-rich" subtype with the highest immune infiltration and poor survival expectation. The expression of immune checkpoints increased along with immune infiltration degrees among the clusters. It was notable that immune clusters correlated with a variety of clinical and immunogenomic factors such as age, WHO grades, IDH1/2 mutation, PTEN, EGFR, ATRX, and TP53 status. In addition, LGGs in cluster D were sensitive to cisplatin, gemcitabine, and immune checkpoint PD-1 inhibitors. RTK-RAS and TP53 pathways were affected in cluster D. Functional pathways such as cytokine-cytokine receptor interaction, antigen processing and presentation, cell adhesion molecules (CAMs), and ECM-receptor interaction were also enriched in cluster D. Hub genes were selected by the Matthews correlation coefficient (MCC) algorithm in the blue module of a gene co-expression network. Our studies might provide an immunogenomics subtyping reference for immunotherapy in LGG.

Iodine-doped covalent organic frameworks with coaxially stacked cruciform anthracenes for high Hall mobility.

Cruciform anthracene building blocks are designed to construct an electroactive two-dimensional covalent organic framework (COF). Upon doping with iodine, cationic radicals are produced on the COF to exhibit structure-enhanced charge transfer properties with a low activation energy (0.13 eV) and a high Hall mobility (10.5 cm2 V-1 s-1).

Protective Prognostic Biomarkers Negatively Correlated with Macrophage M2 Infiltration in Low-Grade Glioma.

Tumor-associated Macrophages (TAMs) play a vital role in the progression of glioma. Macrophage M2 has been confirmed to promote immunosuppression and proliferation of low-grade glioma (LGG). Here, we searched for genes negatively correlated with Macrophages M2 by bioinformatical methods and investigated their protective ability for prognosis. LGG and adjacent normal samples were screened out in TCGA and three GEO datasets. 326 overlapped differentially expressed genes were calculated, and their biological functions were investigated by Go and KEGG analyses. Macrophage M2 accounted for the highest proportion among all 22 immune cells by CIBERSORT deconvolution algorithm. The proportion of Macrophage M2 in LGG was also higher than that in normal tissue according to several deconvolution algorithms. 43 genes in the blue module negatively correlated with Macrophage M2 infiltration were identified by weighted gene coexpression network analysis (WGCNA). Through immune infiltration and correlation analysis, FGFBP3, VAX2, and SHD were selected and they were enriched in G protein-coupled receptors' signaling regulation and cytokine receptor interaction. They could prolong the overall and disease-free survival time. Univariate and multivariate Cox regression analyses were applied to evaluate prognosis prediction ability. Interestingly, FGFBP3 and AHD were independent prognostic predictors. A nomogram was drawn, and its 1-year, 3-year, and 5-year survival prognostic value was verified by ROC curves and calibration plots. In conclusion, FGFBP3, VAX2, and SHD were protective prognostic biomarkers against Macrophage M2 infiltration in low-grade glioma. The FGFBP3 and SHD were independent factors to effectively predict long-term survival probability.

Functionalization of soy residue (okara) by enzymatic hydrolysis and LAB fermentation for B2 bio-enrichment and improved in vitro digestion.

The utilization of major edible soy-waste (okara) remains a challenge due to its poor digestion, nutritional imbalance (lack of B-vitamins), and undesirable off-flavors. Herein, fresh okara was enzymatically hydrolyzed and then fermented using the B2-overproducing Lactiplantibacillus plantarum UFG169 strain. SEM micrographs showed the microporous and honeycombed structures on the surface of okara. The off-flavors were reduced, and the essential amino acids content was significantly increased in fermented okara. The higher ß-glucosidase activity, increased aglycone isoflavones, and in situ riboflavin (B2) were associated with the enhanced antioxidant potential of the fermented okara. The in vitro digestion of okara resulted in reduced particle size, higher protein digestibility, improved aggregation, lower protein molecular chains, and increased polyphenols. Overall, our study indicated the improved nutrition and digestibility of B2 bio-enriched okara.

Riboflavin Bioenriched Soymilk Alleviates Oxidative Stress Mediated Liver Injury, Intestinal Inflammation, and Gut Microbiota Modification in B2 Depletion-Repletion Mice.

Epidemiological evidence emphasizes that ariboflavinosis can lead to oxidative stress, which in turn may mediate the initiation and progression of liver injury and intestinal inflammation. Although vitamin B2 has gained worldwide attention for its antioxidant defense, the relationship between B2 status, oxidative stress, inflammatory response, and intestinal homeostasis remains indistinct. Herein, we developed a B2 depletion-repletion BALB/c mice model to investigate the ameliorative effects of B2 bioenriched fermented soymilk (B2FS) on ariboflavinosis, accompanied by oxidative stress, inflammation, and gut microbiota modulation in response to B2 deficiency. In vivo results revealed that the phenotypic ariboflavinosis symptoms, growth rate, EGRAC status, and hepatic function reverted to normal after B2FS supplementation. B2FS significantly elevated CAT, SOD, T-AOC, and compromised MDA levels in the serum, simultaneously up-regulated Nrf2, CAT, and SOD2, and down-regulated Keap1 gene in the colon. The histopathological characteristics revealed significant alleviation in the liver and intestinal inflammation, confirmed by the downregulation of inflammatory (IL-1ß and IL-6) and nuclear transcription (NF-κB) factors after B2FS supplementation. B2FS also increased the abundance and diversity of gut microbiota, increased the relative abundance of Prevotella and Absiella, as well as decreased Proteobacteria, Fusobacteria, Synergistetes, and Cyanobacteria in strong conjunction with antioxidant, anti-inflammatory properties, and gut homeostasis along with the remarkable increase in cecal SCFAs content. We hereby reveal that B2FS can effectively alleviate deleterious ariboflavinosis associated with oxidative stress mediated liver injury, chronic intestinal inflammation, and gut dysbiosis in the B2 depletion-repletion mice model via activation of the Nrf2 signaling pathway.

Effects of okara and vitamin B2 bioenrichment on the functional properties and in vitro digestion of fermented soy milk.

Due to highly nutritious and well-known prebiotic nature, okara (soy by-product) can improve the physiological benefits of probiotic consumption by enhancing the physicochemical stability and bioavailability of bacteria and metabolites, partially in food matrices and then in gastrointestinal tract. Initially, vitamin B2 producing probiotic Lactobacillus plantarum UFG10 was immobilized with 4% okara for soy milk fermentation. SEM micrographs showed firm adherence of UFG10 to okara surface depicting efficient immobilization. Soy milk fermented with okara immobilized UFG10 showed enhanced ß-glucosidase activity, stimulating the biotransformation of isoflavones from glucosides (daidzin, from 27.78 to 9.84 µg/mL; genistin, from 32.58 to 8.33 µg/mL) to aglycones (daidzein, from 0.19 to 30.84 µg/mL; genistein, from 1.42 to 33.10 µg/mL) and higher B2 production (1.53 µg/mL, 12 h) confirmed by HPLC. Okara addition and B2 enrichment could yield relatively higher antioxidant strength than control soy milk. PLSR correlation revealed the effects of okara and B2 on the functional properties of soy milk. After okara immobilization, soy milk showed higher soy protein digestibility after in vitro digestion for 225 min, higher aggregation, and lower protein molecular chains, qualitatively confirmed with Atomic force microscope. Okara immobilized bacterial cells exhibited relatively greater resistance up to 55.1% (p < 0.05) in simulated GIT, indicating okara as an ideal substrate for an efficient immobilization which ultimately improved the fate of soy B2 and protein bioaccessibility and functional products such as isoflavones for micro structural design of soy milk with improved nutrition and digestibility.

Effects of roasting level on physicochemical, sensory, and volatile profiles of soybeans using electronic nose and HS-SPME-GC-MS.

We applied oven-roasting on soybean in order to investigate their physicochemical, sensory, and volatile profiles using electronic nose and HS-SPME-GC-MS. Results revealed a temperature dependent kinetic on the physicochemical index except fat content. Roasting at 200 °C for 20 min decreased the protein dispersibility index about 38%; while, lipoxygenase and peroxidase were entirely inactivated. The primary heat sensitive amino acids were methionine, arginine, and cysteine. Electronic nose showed certain capacity to discriminate varying roasted soybeans. Out of 41 volatile compounds identified in soybean headspace, 2,5-dimethylpyrazine showed the highest abundance of 411.18 µg/Kg. Regression model suggested the association of hexanal and aliphatic alcohols with beany flavor, while pyrazines, heterocycles, and furanoids showed a positive correlation with roasted flavor. The selected flavor markers can be used to predict the development of flavor in roasted soybeans. Our study emphasized the effect of roasting level on nutritive value and flavor profiles of soybeans.

A recent update on the multifaceted health benefits associated with ginger and its bioactive components.

Due to recent lifestyle shifts and health discernments among consumers, synthetic drugs are facing the challenge of controlling disease development and progression. Various medicinal plants and their constituents are recognized for their imminent role in disease management via modulation of biological activities. At present, research scholars have diverted their attention on natural bioactive entities with health-boosting perception to combat the lifestyle-related disarrays. In particular, Zingiber officinale is a medicinal herb that has been commonly used in food and pharmaceutical products. Its detailed chemical composition and high value-added active components have been extensively studied. In this review, we have summarized the pharmacological potential of this well-endowed chemo preventive agent. It was revealed that its functionalities are attributed to several inherent chemical constituents, including 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 6-hydroshogaol, and oleoresin, which were established through many studies (in vitro, in vivo, and cell lines). In this review, we also focused on the therapeutic effects of ginger and its constituents for their effective antioxidant properties. Their consumption may reduce or delay the progression of related diseases, such as cancer, diabetes, and obesity, via modulation of genetic and metabolic activities. The updated data could elucidate the relationship of the extraction processes with the constituents and biological manifestations. We have collated the current knowledge (including the latest clinical data) about the bioactive compounds and bioactivities of ginger. Their detailed mechanisms, which can lay foundation for their food and medical applications are also discussed.

Morin as an imminent functional food ingredient: an update on its enhanced efficacy in the treatment and prevention of metabolic syndromes.

Flavonoids represent polyphenolic plant secondary metabolites with a general structure of a 15-carbon skeleton comprising two phenyl rings and a heterocyclic ring. Over 5000 natural flavonoids (flavanones, flavanonols, and flavans) from various plants have been characterized. Several studies provide novel and promising insights into morin hydrate for its different biological activities against a series of metabolic syndromes. The present review is a rendition of its sources, chemistry, functional potency, and protective effects on metabolic syndromes ranging from cancer to brain injury. Most importantly this systematic review article also highlights the mechanisms of interest to morin-mediated management of metabolic disorders. The key mechanisms (anti-oxidative and anti-inflammatory) responsible for its therapeutic potential are well featured after collating the in vitro and in vivo study reports. As a whole, based on the prevailing information rationalizing its medicinal use, morin can be identified as a therapeutic agent for the expansion of human health.

Hypoxia-activated ROS burst liposomes boosted by local mild hyperthermia for photo/chemodynamic therapy.

Single reactive oxygen species (ROS)-mediated therapy, photodynamic therapy (PDT) or chemodynamic therapy (CDT) is severely hindered in hypoxic solid tumor. Herein, to address the urgent challenge, a hypoxia-activated ROS burst liposome has been fabricated to achieve synergistic PDT/CDT that is initiated by the structural dissociation of poly(metronidazole) liposome in hypoxic tumor microenvironment (TME). The therapeutic enhancement of our ROS-blasting treatment is simultaneously regulated by external light-initiated PDT and endogenous iron oxide nanoclusters-triggered CDT, which is synergistically boosted and amplified by localized mild hyperthermia under 808/660 nm coirradiation. More importantly, in vitro and in vivo experiments demonstrate that electron-affinic poly(aminoimidazole) product from hypoxia-responsive transition of poly(metronidazole) polymers could efficiently enhance hypoxic cell apoptosis and induce solid tumor ablation. Thus, this work offers a potential hypoxia-activated ROS burst-PDT/CDT strategy with a superior antitumor efficacy, highlighting a promising clinical application.

Riboflavin-overproducing lactobacilli for the enrichment of fermented soymilk: insights into improved nutritional and functional attributes.

The influence of riboflavin (B2)-overproducing lactobacilli on the antioxidant status, isoflavone conversion, off-flavor reduction, amino acid profile, and viscosity of B2-bio-enriched fermented soymilk was investigated. Results showed that B2 in fermented soymilk was notably increased from 0.2 to 3.8 µg/mL for Lactobacillus fermentum UFG169 and to 1.9 µg/mL for Lactobacillus plantarum UFG10. The apparent viscosity significantly changed with rising acidity and agglutination of protein. The off-flavor volatile substances (hexanal and nonanal) were significantly reduced in fermented soymilk. Furthermore, a large amount of glucoside form isoflavones was deglycosylated into bioactive aglycones after 4 h up to 32 h. B2 content and isoflavones significantly improved the antioxidant status of soymilk. Partial least squares regression analysis correlated the strain activity and fermentation time with the improved nutritional and functional soymilk qualities. This study demonstrated the strategy for strain development for B2-bio-enriched fermentation to extend the health-promoting benefits of soymilk and soy-related foods. KEY POINTS: • B2-enriched fermentation enhanced the nutrition and functional status of soymilk. • Fermentation time significantly affected the apparent viscosity of fermented soymilk. • Off-flavor volatile substances were significantly reduced or even diminished. • Increased B2and bioactive isoflavones contributed to improved antioxidant potential.

Central rather than brachial pressures are stronger predictors of cardiovascular outcomes: A longitudinal prospective study in a Chinese population.

The purpose of this study was to assess the association of blood pressure (BP) measurements with the risk of cardiovascular disease (CVD) and examine whether central systolic BP (CSBP) predicts CVD better than brachial BP measurements (SBP and pulse pressure [PP]). Based on a cross-sectional study conducted in 2009-2010 with follow-up in 2016-2017 among 35- to 64-year-old subjects in China, we evaluated the performance of non-invasively predicted CSBP over brachial BP measurements on the first CVD events. Each BP measurement, individually and jointly with another BP measurement, was entered into the multivariate Cox proportional-hazards models, to examine the predictability of central and brachial BP measurements. Mean age of participants (n = 8710) was 50.1 years at baseline. After a median follow-up of 6.36 years, 187 CVD events occurred. CSBP was a stronger predictor for CVD than brachial BP measurements (CSBP, 1-standard deviation increment HR = 1.49, 95%CI: 1.31-1.70). With CSBP and SBP entering into models jointly, the HR for CSBP and SBP was 1.28 (1.04-1.58) and 1.22 (0.98-1.50), respectively. With CSBP and PP entering into models jointly, the HR for CSBP and PP was 1.51 (1.28-1.78) and 0.98 (0.83-1.15), respectively. For subgroup analysis, the association of CSBP with CVD was stronger than brachial BP measurements in women, those with hypertension and obesity. In the middle-aged Chinese population, noninvasively estimated CSBP may offer advantages over brachial BP measurements to predict CVD events, especially for participants with higher risk. These findings suggest prospective assessment of CSBP as a prevention and treatment target in further trials.