Catalytic Asymmetric Peroxidation of α,β-Unsaturated Nitroalkenes by a Bifunctional Organic Catalyst

A new enantioselective peroxidation of α,β-unsaturated nitroalkenes was realized with an easily accessible acid–base bifunctional organic catalyst derived from cinchona alkaloids. This reaction provides unprecedented easy access to optically active chiral peroxides, as illustrated by the asymmetric synthesis of β-peroxy nitro compounds

Catalytic Enantioselective Peroxidation of α,β-Unsaturated Aldehydes for the Asymmetric Synthesis of Biologically Important Chiral Endoperoxides

We have developed an unprecedented highly enantioselective catalytic peroxidation of enals. Critical to this development is the discovery that varying the structure of the hydroperoxide has a significant impact on the enantioselectivity of the organocatalytic asymmetric peroxidation. This novel transformation enabled the development of an enantioselective route toward the core structure shared by all members of the stolonoxide family of anticancer natural products, a connected <i>trans</i>-3,6-disubstituted-1,2-dioxane and <i>trans</i>-2,5-disubstituted-tetrahydrofuran ring system. Our route also features an unprecedented cyclization cascade of a chiral bis­(epoxy)­hydroperoxide. The new methodology and synthetic strategy established in this work should be applicable to the enantioselective synthesis of a broad range of chiral 1,2-dioxolanes and 1,2-dioxanes, thereby facilitating biological and medicinal chemistry studies of peroxy natural products

Eurotium cristatum, a Probiotic Fungus from Fuzhuan Brick Tea, and Its Polysaccharides Ameliorated DSS-Induced Ulcerative Colitis in Mice by Modulating the Gut Microbiota

Eurotium cristatum is a potential probiotic fungus that is used to enhance Fuzhuan tea quality through fermentation and could reduce obesity by modulating gut dysbiosis. This study aimed to investigate the effects and possible mechanisms of killed E. cristatum (KEC) and its polysaccharides (ECP) in ulcerative colitis (UC) relief. KEC and ECP were administered to mice with dextran sulfate sodium-induced UC. The results showed that UC severity, intestinal inflammation, and tight junction protein levels were greatly improved. Furthermore, 16S rRNA sequencing results showed that Escherichia coli, Enterococcus faecium, Clostridium perfringens, Bacteroides caccae, Rothia aeria, and Prevotella melaninogenica were depleted, while Alistipes finegoldii and Bacteroides stercorirosoris were enriched. A fecal microbial transplantation trial confirmed that KEC and ECP ameliorated UC by regulating gut dysbiosis. Thus, this research suggests that KEC and ECP are novel, potent, food-based anti-inflammatory agents that relieve UC by modulating gut dysbiosis

Quantitative Validation and Application of the Photo-Cross-Linking Selection for Double-Stranded DNA-Encoded Libraries

The DNA-encoded compound library (DEL) technology has accelerated the target hits discovery in new drug development. While affinity-based DEL selection can distinguish high-affinity ligands, moderate-affinity ligands are also potential drug candidates with further modifications. Herein, we designed a photo-cross-linking selection method for DELs with double-stranded DNA (dsDELs) to screen moderate-affinity ligands. We constructed two photo-cross-linking libraries with linkers of different lengths that connect a diazirine group to the DNA encoded compound. The diazirine group can be activated by UV irradiation and thus bond with the target protein in a reachable distance. In the model selection, the feasibility of the photo-cross-linking screening system was verified by qPCR and NGS technology. Both high-affinity and moderate-affinity ligands were successfully selected from the libraries

Eurotium cristatum, a Probiotic Fungus from Fuzhuan Brick Tea, and Its Polysaccharides Ameliorated DSS-Induced Ulcerative Colitis in Mice by Modulating the Gut Microbiota

Eurotium cristatum is a potential probiotic fungus that is used to enhance Fuzhuan tea quality through fermentation and could reduce obesity by modulating gut dysbiosis. This study aimed to investigate the effects and possible mechanisms of killed E. cristatum (KEC) and its polysaccharides (ECP) in ulcerative colitis (UC) relief. KEC and ECP were administered to mice with dextran sulfate sodium-induced UC. The results showed that UC severity, intestinal inflammation, and tight junction protein levels were greatly improved. Furthermore, 16S rRNA sequencing results showed that Escherichia coli, Enterococcus faecium, Clostridium perfringens, Bacteroides caccae, Rothia aeria, and Prevotella melaninogenica were depleted, while Alistipes finegoldii and Bacteroides stercorirosoris were enriched. A fecal microbial transplantation trial confirmed that KEC and ECP ameliorated UC by regulating gut dysbiosis. Thus, this research suggests that KEC and ECP are novel, potent, food-based anti-inflammatory agents that relieve UC by modulating gut dysbiosis

Supplemental_PDF - Laparoscopic Microwave Ablation of Hepatocellular Carcinoma at Liver Surface: Technique Effectiveness and Long-Term Outcomes

Supplemental_PDF for Laparoscopic Microwave Ablation of Hepatocellular Carcinoma at Liver Surface: Technique Effectiveness and Long-Term Outcomes by Tao Wang, Xiao-Yu Zhang, Xiaojie Lu, and Bo Zhai in Technology in Cancer Research & Treatment</p

Quantitative Validation and Application of the Photo-Cross-Linking Selection for Double-Stranded DNA-Encoded Libraries

The DNA-encoded compound library (DEL) technology has accelerated the target hits discovery in new drug development. While affinity-based DEL selection can distinguish high-affinity ligands, moderate-affinity ligands are also potential drug candidates with further modifications. Herein, we designed a photo-cross-linking selection method for DELs with double-stranded DNA (dsDELs) to screen moderate-affinity ligands. We constructed two photo-cross-linking libraries with linkers of different lengths that connect a diazirine group to the DNA encoded compound. The diazirine group can be activated by UV irradiation and thus bond with the target protein in a reachable distance. In the model selection, the feasibility of the photo-cross-linking screening system was verified by qPCR and NGS technology. Both high-affinity and moderate-affinity ligands were successfully selected from the libraries

Quantitative Validation and Application of the Photo-Cross-Linking Selection for Double-Stranded DNA-Encoded Libraries

The DNA-encoded compound library (DEL) technology has accelerated the target hits discovery in new drug development. While affinity-based DEL selection can distinguish high-affinity ligands, moderate-affinity ligands are also potential drug candidates with further modifications. Herein, we designed a photo-cross-linking selection method for DELs with double-stranded DNA (dsDELs) to screen moderate-affinity ligands. We constructed two photo-cross-linking libraries with linkers of different lengths that connect a diazirine group to the DNA encoded compound. The diazirine group can be activated by UV irradiation and thus bond with the target protein in a reachable distance. In the model selection, the feasibility of the photo-cross-linking screening system was verified by qPCR and NGS technology. Both high-affinity and moderate-affinity ligands were successfully selected from the libraries

Table_3_Effect of gut microbiome regulated Taohong Siwu Decoction metabolism on glioma cell phenotype.xlsx

IntroductionTo establish a new model for exploring the mechanism of the gut microbiome and drug metabolism, we explored whether Taohong Siwu Decoction acts after metabolism by intestinal flora under the premise of clarifying the interaction between intestinal flora and drug metabolism.MethodsTaohong Siwu Decoction (TSD) was fed to germ-free mice and conventional mice, respectively. The serum from both groups of mice was removed and co-cultured with glioma cells in vitro. The co-cultured glioma cells were compared separately for changes at the RNA level using RNA-seq technology. The genes of interest in the comparison results were selected for validation.ResultsThe differences in the phenotypic alterations of glioma cells between serum from TSD-fed germ-free mice and normal mice were statistically significant. In vitro experiments showed that Taohong Siwu Decoction-fed normal mouse serum-stimulated glioma cells, which inhibited proliferation and increased autophagy. RNA-seq analysis showed that TSD-fed normal mouse serum could regulate CDC6 pathway activity in glioma cells. The therapeutic effect of TSD is significantly influenced by intestinal flora.ConclusionThe treatment of tumors by TSD may be modulated by intestinal flora. We established a new method to quantify the relationship between intestinal flora and the regulation of TSD efficacy through this study.</p

Table_4_Effect of gut microbiome regulated Taohong Siwu Decoction metabolism on glioma cell phenotype.xlsx

IntroductionTo establish a new model for exploring the mechanism of the gut microbiome and drug metabolism, we explored whether Taohong Siwu Decoction acts after metabolism by intestinal flora under the premise of clarifying the interaction between intestinal flora and drug metabolism.MethodsTaohong Siwu Decoction (TSD) was fed to germ-free mice and conventional mice, respectively. The serum from both groups of mice was removed and co-cultured with glioma cells in vitro. The co-cultured glioma cells were compared separately for changes at the RNA level using RNA-seq technology. The genes of interest in the comparison results were selected for validation.ResultsThe differences in the phenotypic alterations of glioma cells between serum from TSD-fed germ-free mice and normal mice were statistically significant. In vitro experiments showed that Taohong Siwu Decoction-fed normal mouse serum-stimulated glioma cells, which inhibited proliferation and increased autophagy. RNA-seq analysis showed that TSD-fed normal mouse serum could regulate CDC6 pathway activity in glioma cells. The therapeutic effect of TSD is significantly influenced by intestinal flora.ConclusionThe treatment of tumors by TSD may be modulated by intestinal flora. We established a new method to quantify the relationship between intestinal flora and the regulation of TSD efficacy through this study.</p