Optimization of the Fermentation Process of Mulberry Juice by Lactic Acid Bacteria and Changes in Functional Components and Antioxidant Activity during Fermentation

Using mulberry as raw material, single and mixed strains of Lactobacillus plantarum and Bifidobacterium longum were used to ferment mulberry juice, and single-factor and response surface tests were used to investigate the optimal fermentation process of fermented mulberry juice, and to determine and analyze the functional components (total flavonoids, total anthocyanins, total phenols) and antioxidant activities (ABTS+ free radical scavenging rate, DPPH free radical scavenging rate, hydroxyl radical scavenging rate, total antioxidant capacity), etc. The results showed that the optimal fermentation process for fermented mulberry juice was 0.06% strain addition, initial pH6.1, fermentation temperature 37 ℃, and 0.09% oligofructose addition. The fermentation of lactic acid bacteria improved the functional components and antioxidant activity of fermented mulberry juice. Compared with single strain and mixed strain, the fermentation of mixed strain significantly increased (P<0.05) the content of functional compounds in mulberry juice, and the contents of unfermented mulberry juice and mixed strain after 48 h fermentation were 4.18~6.36 mg/mL of total flavonoids, 0.67~1.95 mg/mL of total anthocyanins, 12.62~18.65 mg/mL of total phenols. And 48 h fermentation of the mixed strains significantly improved the antioxidant activity of mulberry juice, with ABTS+ free radical scavenging rate 61.81%~88.17%, DPPH free radical scavenging rate 52.78%~81.64%, hydroxyl radical scavenging rate 37.38%~86.07%, total antioxidant capacity 17.85~29.49 mmol/L. The fermentation of Lactobacillus plantarum and Bifidobacterium longum mixed strains had better organoleptic properties. The study can provide a theoretical reference for the deep processing of mulberry

Morel (Morchella spp.) intake alters gut microbial community and short-chain fatty acid profiles in mice

Morels (Morchella spp.) are highly nutritious and consumed as both edible mushrooms and traditional Chinese medicine. This study aimed to investigate the effects of dietary supplementation with morel mushrooms on the gut bacterial microbiota and short-chain fatty acids (SCFAs) profiles in healthy mice. Healthy mice were randomly assigned to five groups: a control group (0% morel) and four intervention groups supplemented with different levels of morel mushrooms (5% for M5, 10% for M10, 15% for M15, and 20% for M20) over a period of 4 weeks. Fecal samples were collected at the end of the experiment to characterize the microbiota and assess the SCFAs levels. The morel intervention significantly altered the bacterial community composition, increasing Bacteroides, Lachnospiraceae NK4A136 group and Parabacteroides, while decreasing Staphylococcus and the Firmicutes to Bacteroidetes ratio (F/B ratio). Moreover, increased morel intake was associated with weight loss. All SCFAs content was upregulated in the morel-intervention groups. Potential SCFAs-producing taxa identified by regression analysis were distributed in the families Muribaculaceae, Lachnospiraceae, and in the genera Jeotgalicoccus, Gemella, Odoribacter, Tyzzerella 3 and Ruminococcaceae UCG-014. The functional categories involved with SCFAs-production or weight loss may contain enzymes such as beta-glucosidase (K05349), beta-galactosidase (K01190), and hexosaminidase (K12373) after morel intervention. The exploration of the impact of morel mushrooms on gut microbiota and metabolites contributes to the development of prebiotics for improving health and reducing obesity

Effect of high hydrostatic pressure on aroma volatile compounds and aroma precursors of Hami melon juice

High hydrostatic pressure (HHP) treatment is an effective technique for processing heat-sensitive fruits and causes changes in volatile compounds and their precursors while maintaining quality. We investigated the changes and correlations of volatile compounds, related enzyme activities and precursor amino acids, and fatty acids in Hami melon juice under 350–500 MPa pressure. The application of HHP treatment resulted in a considerable reduction of esters and a substantial increase in aldehydes and alcohols in C6 and C9. Activities of lipoxygenase (LOX), alcohol acyltransferase (AAT), and phospholipase A2 (PLA2) were lower than those of the untreated group, alcohol dehydrogenase (ADH) activity was reversed. When compared to fresh cantaloupe juice, there was an increase in both the types and contents of amino acids with lower total fatty acid contents than the control group. Positive correlations were observed among six ester-related substances and eight alcohol-related substances. Additionally, the correlations between volatile compounds and fatty acids were more substantial compared to those between volatile compounds and amino acids. HHP treatment increases Hami melon flavor precursors and is an effective way to maintain the aroma volatile compounds and flavor of Hami melon juice

Structural basis of the farnesoid X receptor/retinoid X receptor heterodimer on inverted repeat DNA

Farnesoid X receptor (FXR) is a ligand-activated transcription factor known as bile acid receptor (BAR). FXR plays critical roles in various biological processes, including metabolism, immune inflammation, liver regeneration and liver carcinogenesis. FXR forms a heterodimer with the retinoid X receptor (RXR) and binds to diverse FXR response elements (FXREs) to exert its various biological functions. However, the mechanism by which the FXR/RXR heterodimer binds the DNA elements remains unclear. In this study, we aimed to use structural, biochemical and bioinformatics analyses to study the mechanism of FXR binding to the typical FXRE, such as the IR1 site, and the heterodimer interactions in the FXR-DBD/RXR-DBD complex. Further biochemical assays showed that RAR, THR and NR4A2 do not form heterodimers with RXR when bound to the IR1 sites, which indicates that IR1 may be a unique binding site for the FXR/RXR heterodimer. Our studies may provide a further understanding of the dimerization specificity of nuclear receptors

Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455.

Aberrant FGFR4 signaling has been documented abundantly in various human cancers. The majority of FGFR inhibitors display significantly reduced potency toward FGFR4 compared to FGFR1-3. However, LY2874455 has similar inhibition potency for FGFR1-4 with IC50 less than 6.4 nM. To date, there is no published crystal structure of LY2874455 in complex with any kinase. To better understand the pan-FGFR selectivity of LY2874455, we have determined the crystal structure of the FGFR4 kinase domain bound to LY2874455 at a resolution of 2.35 Å. LY2874455, a type I inhibitor for FGFR4, binds to the ATP-binding pocket of FGFR4 in a DFG-in active conformation with three hydrogen bonds and a number of van der Waals contacts. After alignment of the kinase domain sequence of 4 FGFRs, and superposition of the ATP binding pocket of 4 FGFRs, our structural analyses reveal that the interactions of LY2874455 to FGFR4 are largely conserved in 4 FGFRs, explaining at least partly, the broad inhibitory activity of LY2874455 toward 4 FGFRs. Consequently, our studies reveal new insights into the pan-FGFR selectivity of LY2874455 and provide a structural basis for developing novel FGFR inhibitors that target FGFR1-4 broadly

Structural insight into the macrocyclic inhibitor TPX-0022 of c-Met and c-Src

c-Met has been an attractive target of prognostic and therapeutic studies in various cancers. TPX-0022 is a macrocyclic inhibitor of c-Met, c-Src and CSF1R kinases and is currently in phase I/II clinical trials in patients with advanced solid tumors harboring MET gene alterations. In this study, we determined the co-crystal structures of the c-Met/TPX-0022 and c-Src/TPX-0022 complexes to help elucidate the binding mechanism. TPX-0022 binds to the ATP pocket of c-Met and c-Src in a local minimum energy conformation and is stabilized by hydrophobic and hydrogen bond interactions. In addition, TPX-0022 exhibited potent activity against the resistance-relevant c-Met L1195F mutant and moderate activity against the c-Met G1163R, F1200I and Y1230H mutants but weak activity against the c-Met D1228N and Y1230C mutants. Overall, our study reveals the structural mechanism underlying the potency and selectivity of TPX-0022 and the ability to overcome acquire resistance mutations and provides insight into the development of selective c-Met macrocyclic inhibitors

Structures of p53/BCL-2 complex suggest a mechanism for p53 to antagonize BCL-2 activity

Abstract Mitochondrial apoptosis is strictly controlled by BCL-2 family proteins through a subtle network of protein interactions. The tumor suppressor protein p53 triggers transcription-independent apoptosis through direct interactions with BCL-2 family proteins, but the molecular mechanism is not well understood. In this study, we present three crystal structures of p53-DBD in complex with the anti-apoptotic protein BCL-2 at resolutions of 2.3–2.7 Å. The structures show that two loops of p53-DBD penetrate directly into the BH3-binding pocket of BCL-2. Structure-based mutations at the interface impair the p53/BCL-2 interaction. Specifically, the binding sites for p53 and the pro-apoptotic protein Bax in the BCL-2 pocket are mostly identical. In addition, formation of the p53/BCL-2 complex is negatively correlated with the formation of BCL-2 complexes with pro-apoptotic BCL-2 family members. Defects in the p53/BCL-2 interaction attenuate p53-mediated cell apoptosis. Overall, our study provides a structural basis for the interaction between p53 and BCL-2, and suggests a molecular mechanism by which p53 regulates transcription-independent apoptosis by antagonizing the interaction of BCL-2 with pro-apoptotic BCL-2 family members

Data_Sheet_2_Morel (Morchella spp.) intake alters gut microbial community and short-chain fatty acid profiles in mice.xlsx

Morels (Morchella spp.) are highly nutritious and consumed as both edible mushrooms and traditional Chinese medicine. This study aimed to investigate the effects of dietary supplementation with morel mushrooms on the gut bacterial microbiota and short-chain fatty acids (SCFAs) profiles in healthy mice. Healthy mice were randomly assigned to five groups: a control group (0% morel) and four intervention groups supplemented with different levels of morel mushrooms (5% for M5, 10% for M10, 15% for M15, and 20% for M20) over a period of 4 weeks. Fecal samples were collected at the end of the experiment to characterize the microbiota and assess the SCFAs levels. The morel intervention significantly altered the bacterial community composition, increasing Bacteroides, Lachnospiraceae NK4A136 group and Parabacteroides, while decreasing Staphylococcus and the Firmicutes to Bacteroidetes ratio (F/B ratio). Moreover, increased morel intake was associated with weight loss. All SCFAs content was upregulated in the morel-intervention groups. Potential SCFAs-producing taxa identified by regression analysis were distributed in the families Muribaculaceae, Lachnospiraceae, and in the genera Jeotgalicoccus, Gemella, Odoribacter, Tyzzerella 3 and Ruminococcaceae UCG-014. The functional categories involved with SCFAs-production or weight loss may contain enzymes such as beta-glucosidase (K05349), beta-galactosidase (K01190), and hexosaminidase (K12373) after morel intervention. The exploration of the impact of morel mushrooms on gut microbiota and metabolites contributes to the development of prebiotics for improving health and reducing obesity.</p

Data_Sheet_1_Morel (Morchella spp.) intake alters gut microbial community and short-chain fatty acid profiles in mice.docx

Morels (Morchella spp.) are highly nutritious and consumed as both edible mushrooms and traditional Chinese medicine. This study aimed to investigate the effects of dietary supplementation with morel mushrooms on the gut bacterial microbiota and short-chain fatty acids (SCFAs) profiles in healthy mice. Healthy mice were randomly assigned to five groups: a control group (0% morel) and four intervention groups supplemented with different levels of morel mushrooms (5% for M5, 10% for M10, 15% for M15, and 20% for M20) over a period of 4 weeks. Fecal samples were collected at the end of the experiment to characterize the microbiota and assess the SCFAs levels. The morel intervention significantly altered the bacterial community composition, increasing Bacteroides, Lachnospiraceae NK4A136 group and Parabacteroides, while decreasing Staphylococcus and the Firmicutes to Bacteroidetes ratio (F/B ratio). Moreover, increased morel intake was associated with weight loss. All SCFAs content was upregulated in the morel-intervention groups. Potential SCFAs-producing taxa identified by regression analysis were distributed in the families Muribaculaceae, Lachnospiraceae, and in the genera Jeotgalicoccus, Gemella, Odoribacter, Tyzzerella 3 and Ruminococcaceae UCG-014. The functional categories involved with SCFAs-production or weight loss may contain enzymes such as beta-glucosidase (K05349), beta-galactosidase (K01190), and hexosaminidase (K12373) after morel intervention. The exploration of the impact of morel mushrooms on gut microbiota and metabolites contributes to the development of prebiotics for improving health and reducing obesity.</p

Top-down Strategy toward Versatile Graphene Quantum Dots for Organic/Inorganic Hybrid Solar Cells

Metal oxide nanocrystals have been pursued for various applications in photovoltaics as a buffer layer. However, it remains a challenging task to adjust their energy levels to achieve a better match of the donor–acceptor system. Herein, we report the fabrication of graphene quantum dots (GQDs) with bright blue photoluminescence by a top-down strategy based on laser fragmentation with posthydrothermal treatment. The GQDs demonstrate appropriate energy level positions and are used as an intermediate buffer layer between TiO₂ and P3HT to form a cascade energy level architecture. The introduction of the GQDs into a bulk heterojunction hybrid solar cell has led to an enhancement of the power conversion efficiency