Facile and efficient transformation of thiols to disulfides via a radical pathway with N-anomeric amide.

Radical coupling of thiols is an attractive route for the synthesis of disulfides, but this approach should be promoted by strong oxidants and/or metal salts in combination with additives, which limits its substrate scope and application. In this work, the N-anomeric amide was first found to be able to realize the conversion of thiols to sulfur radicals with high efficiency in the absence of an oxidant or any additives for the synthesis of symmetrical disulfides. The protocol features mild reaction conditions, good functional group tolerance, and moderate to excellent yields.

Na2S-Mediated One-Pot Selective Deoxygenation of α-Hydroxyl Carbonyl Compounds including Natural Products.

A practical method for the deoxygenation of α-hydroxyl carbonyl compounds under mild reaction conditions is reported here. The use of cheap and easy-to-handle Na2S·9H2O as the reductant in the presence of PPh3 and N-chlorosuccinimide (NCS) enables the selective dehydroxylation of α-hydroxyl carbonyl compounds, including ketones, esters, amides, imides and nitrile groups. The synthetic utility is demonstrated by the late-stage deoxygenation of bioactive molecule and complex natural products.

Selective synthesis of sulfoxides and sulfones via controllable oxidation of sulfides with N-fluorobenzenesulfonimide.

A practical and mild method for the switchable synthesis of sulfoxides or sulfones via selective oxidation of sulfides using cheap N-fluorobenzenesulfonimide (NFSI) as the oxidant has been developed. These highly chemoselective transformations were simply achieved by varying the NFSI loading with H2O as the green solvent and oxygen source without any additives. The good functional group tolerance makes the strategy valuable.

Advanced mass spectrometry-based multi-omics technologies for exploring the pathogenesis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the primary hepatic malignancies and is the third most common cause of cancer related death worldwide. Although a wealth of knowledge has been gained concerning the initiation and progression of HCC over the last half century, efforts to improve our understanding of its pathogenesis at a molecular level are still greatly needed, to enable clinicians to enhance the standards of the current diagnosis and treatment of HCC. In the post-genome era, advanced mass spectrometry driven multi-omics technologies (e.g., profiling of DNA damage adducts, RNA modification profiling, proteomics, and metabolomics) stand at the interface between chemistry and biology, and have yielded valuable outcomes from the study of a diversity of complicated diseases. Particularly, these technologies are being broadly used to dissect various biological aspects of HCC with the purpose of biomarker discovery, interrogating pathogenesis as well as for therapeutic discovery. This proof of knowledge-based critical review aims at exploring the selected applications of those defined omics technologies in the HCC niche with an emphasis on translational applications driven by advanced mass spectrometry, toward the specific clinical use for HCC patients. This approach will enable the biomedical community, through both basic research and the clinical sciences, to enhance the applicability of mass spectrometry-based omics technologies in dissecting the pathogenesis of HCC and could lead to novel therapeutic discoveries for HCC.

Prediction and Characterisation of the System Effects of Aristolochic Acid: A Novel Joint Network Analysis towards Therapeutic and Toxicological Mechanisms.

Aristolochic acid (AA) is the major active component of medicinal plants from the Aristolochiaceae family of flowering plants widely utilized for medicinal purposes. However, the molecular mechanisms of AA systems effects remain poorly understood. Here, we employed a joint network analysis that combines network pharmacology, a protein-protein interaction (PPI) database, biological processes analysis and functional annotation analysis to explore system effects. Firstly, we selected 15 protein targets (14 genes) in the PubChem database as the potential target genes and used PPI knowledge to incorporate these genes into an AA-specific gene network that contains 129 genes. Secondly, we performed biological processes analysis for these AA-related targets using ClueGO, some of new targeted genes were randomly selected and experimentally verified by employing the Quantitative Real-Time PCR assay for targeting the systems effects of AA in HK-2 cells with observed dependency of concentration. Thirdly, the pathway-based functional enrichment analysis was manipulated using WebGestalt to identify the mostly significant pathways associated with AA. At last, we built an AA target pathway network of significant pathways to predict the system effects. Taken together, this joint network analysis revealed that the systematic regulatory effects of AA on multidimensional pathways involving both therapeutic action and toxicity.

Metabolic phenotyping of the Yersinia high-pathogenicity island that regulates central carbon metabolism.

The high-pathogenicity island (HPI) is an important determinant of the pathogenicity of pathogenic Yersinia microbes. The HPI carries a cluster of virulence genes that chiefly account for the biosynthesis, transportation and regulation of a virulence-associated siderophore, yersiniabactin. This siderophore is also present in uropathogenic E. coli (UTI89) but not in non-uropathogenic E. coli. We sought to perform metabolic phenotyping and to understand how the presence of the HPI influences central carbon metabolism, which remains poorly understood, by combining targeted metabolomics with a genetic approach. Unexpectedly, our results revealed that uropathogenic E. coli (UPEC) with an HPI had superior metabolic homeostasis to a non-UPEC K12 strain without an HPI, thereby allowing UPEC with an HPI to flexibly adapt to a variety of growth environments. In this study, we elucidate the unrecognized regulatory effects of the HPI virulence genes on central carbon metabolism, in addition to their roles in directing yersiniabactin. These regulatory effects may be implicated in differentiating UPEC from non-UPEC.

MS-based metabolomics facilitates the discovery of in vivo functional small molecules with a diversity of biological contexts.

In vivo small molecules as necessary intermediates are involved in numerous critical metabolic pathways and biological processes associated with many essential biological functions and events. There is growing evidence that MS-based metabolomics is emerging as a powerful tool to facilitate the discovery of functional small molecules that can better our understanding of development, infection, nutrition, disease, toxicity, drug therapeutics, gene modifications and host-pathogen interaction from metabolic perspectives. However, further progress must still be made in MS-based metabolomics because of the shortcomings in the current technologies and knowledge. This technique-driven review aims to explore the discovery of in vivo functional small molecules facilitated by MS-based metabolomics and to highlight the analytic capabilities and promising applications of this discovery strategy. Moreover, the biological significance of the discovery of in vivo functional small molecules with different biological contexts is also interrogated at a metabolic perspective.