Catalytic asymmetric construction of chiral indole‐fused rings has become an important issue in the chemical community because of the significance of such scaffolds. In this work, we have ...accomplished the first catalytic asymmetric (4+2) and (4+3) cycloadditions of 2,3‐indolyldimethanols by using indoles and 2‐naphthols as suitable reaction partners under the catalysis of chiral phosphoric acids, constructing enantioenriched indole‐fused six‐membered and seven‐membered rings in high yields with excellent enantioselectivities. In addition, this approach is used to realize the first enantioselective construction of challenging tetrahydroindolocarbazole scaffolds, which are found to show promising anticancer activity. More importantly, theoretical calculations of the reaction pathways and activation mode offer an in‐depth understanding of this class of indolylmethanols. This work not only settles the challenges in realizing catalytic asymmetric cycloadditions of indolyldimethanols but also provides a powerful strategy for the construction of enantioenriched indole‐fused rings.
The first catalytic asymmetric (4+2) and (4+3) cycloadditions of 2,3‐indolyldimethanols enable the construction of enantioenriched indole‐fused rings in high yields with excellent enantioselectivities. This approach led to the first enantioselective construction of challenging tetrahydroindolocarbazole scaffolds, which show promising anticancer activity. Theoretical calculations offer an in‐depth understanding of this class of indolylmethanols.
Recent evidences showed that long noncoding RNAs (lncRNAs) are frequently dysregulated and play important roles in various cancers. Clear cell renal cell carcinoma (ccRCC) is one of the leading cause ...of cancer-related death, largely due to the metastasis of ccRCC. However, the clinical significances and roles of lncRNAs in metastatic ccRCC are still unknown.
lncRNA expression microarray analysis was performed to search the dysregulated lncRNA in metastatic ccRCC. quantitative real-time PCR was performed to measure the expression of lncRNAs in human ccRCC samples. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of lncRNAs on ccRCC cell proliferation, migration, invasion and in vivo metastasis. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and western blot were performed to explore the molecular mechanisms underlying the functions of lncRNAs.
The microarray analysis identified a novel lncRNA termed metastatic renal cell carcinoma-associated transcript 1 (MRCCAT1), which is highly expressed in metastatic ccRCC tissues and associated with the metastatic properties of ccRCC. Multivariate Cox regression analysis revealed that MRCCAT1 is an independent prognostic factor for ccRCC patients. Overexpression of MRCCAT1 promotes ccRCC cells proliferation, migration, and invasion. Depletion of MRCCAT1 inhibites ccRCC cells proliferation, migration, and invasion in vitro, and ccRCC metastasis in vivo. Mechanistically, MRCCAT1 represses NPR3 transcription by recruiting PRC2 to NPR3 promoter, and subsequently activates p38-MAPK signaling pathway.
MRCCAT1 is a critical lncRNA that promotes ccRCC metastasis via inhibiting NPR3 and activating p38-MAPK signaling. Our results imply that MRCCAT1 could serve as a prognostic biomarker and therapeutic target for ccRCC.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC ...intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.
A new class of axially chiral styrene‐based thiourea tertiary amine catalysts, which have unique characteristics such as an efficient synthetic route, multiple chiral elements, and multiple ...activating groups, has been rationally designed. These new chiral catalysts have proven to be efficient organocatalysts, enabling the chemo‐, diastereo‐, and enantioselective (2+4) cyclization of 2‐benzothiazolimines with homophthalic anhydrides in good yields (up to 96 %) with excellent stereoselectivities (all >95:5 dr, up to 98 % ee). More importantly, theoretical calculations elucidated the important role of an axially chiral styrene moiety in controlling both the reactivity and enantioselectivity. This work not only represents the first design of styrene‐based chiral thiourea tertiary amine catalysts and the first catalytic asymmetric (2+4) cyclization of 2‐benzothiazolimines, but also gives an in‐depth understanding of axially chiral styrene‐based organocatalysts.
A new class of axially chiral styrene‐based organocatalysts has been rationally designed. They enable the chemo‐, diastereo‐ and enantioselective (2+4) cyclization of 2‐benzothiazolimines. This work represents the first design of styrene‐based chiral thiourea tertiary amine catalysts and the first catalytic asymmetric (2+4) cyclization of 2‐benzothiazolimines, and it gives an in‐depth understanding of axially chiral styrene‐based organocatalysts.
Numerous efficient synthetic methods for enantioselective indole functionalizations have emerged in recent years. This review summarizes the major achievements in the transition-metal-catalyzed ...enantioselective indole functionalization reactions since 2010 and focuses on C-C bond formation processes, including alkylations, arylations, cycloaddition reactions, and other reactions. It intends to give a compendious overview of the significant progress achieved in this area.
We report herein the three‐component radical addition reaction of SF5Cl, alkene and diazo compounds for the selective formation of α‐alkyl‐α‐SF5 carbonyl compounds. The three‐component addition ...reaction proceeded through the first reaction of SF5 radical with the diazo compound followed by the addition of the in situ generated carbon radical to alkene. The synthetic useful α‐allyl‐α‐SF5 carbonyl compounds were successfully prepared when allyl trimethylsilanes were used as the alkene substrates. Furthermore, the three‐component adducts formed from SF5Cl, α‐diazoacetophenones and vinyl acetates were converted into pentafluorosulfanylfurans. This transformation provided a practical and efficeint method for the synthesis of pentafluorosulfanylfurans.
A three‐component radical reaction of SF5Cl, alkenes, and diazo compounds for synthesis of α‐alkyl‐α‐SF5 carbonyl compounds was developed. Furthermore, the three‐component adducts formed from SF5Cl, α‐diazoacetophenones and vinyl acetates were converted into pentafluorosulfanylfurans.
Toxicity Research of PM2.5 Compositions In Vitro Jia, Yi-Yang; Wang, Qi; Liu, Te
International journal of environmental research and public health,
02/2017, Volume:
14, Issue:
3
Journal Article
Peer reviewed
Open access
According to the published literature, we surmise that particulate matter (PM) concentration, individually, may be less important than components in explaining health effects. PM2.5 (aerodynamic ...diameter <2.5 μm) had similar cytotoxicity (e.g., cell viability reduction, oxidative damage, inflammatory effects and genetic toxicity) on different types of cells. The studies of cells are readily available for detailed mechanistic investigations, which is more appropriate for learning and comparing the mechanism caused by single or mixed ingredients coating a carbon core. No review exists that holistically examines the evidence from all components-based in vitro studies. We reviewed published studies that focus on the cytotoxicity of normal PM2.5. Those studies suggested that the toxicity of mixed compositions differs greatly from the single ingredients in mixed components and the target cells. The cytotoxic responses caused by PM2.5 components have not shown a consistent association with clear, specific health effects. The results may be beneficial for providing new targets for drugs for the treatment of PM2.5-related diseases.
Heck reaction is one of the most important carbon‐carbon bond forming reactions with wide applications in organic synthesis. Considerable advances of enantioselective Heck reaction have been achieved ...in the past decades. This review focuses on recent development of catalytic asymmetric Heck reaction and reductive Heck reaction, which covers intermolecular and intramolecular versions since 2011. The article is organized in terms of the catalysts and olefin substrates.
Recent progress of catalytic asymmetric Heck reactions and reductive Heck reactions since 2011 is described.
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