Synthetic Strategies in the Preparation of Phenanthridinones

Phenanthridinones are important heterocyclic frameworks present in a variety of complex natural products, pharmaceuticals and displaying wide range of pharmacological actions. Its structural importance has evoked a great deal of interest in the domains of organic synthesis and medicinal chemistry to develop new synthetic methodologies, as well as novel compounds of pharmaceutical interest. This review focuses on the synthesis of phenanthridinone scaffolds by employing aryl-aryl, N-aryl, and biaryl coupling reactions, decarboxylative amidations, and photocatalyzed reactions.

Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability

ABSTRACTThe majority of the non-coding regions in the human genome do not harbor any annotated element and are even not marked with any epigenomic signal or protein binding. An understudied aspect of these regions is their possible roles in stabilizing the 3D chromatin organization. To illuminate their “structural importance”, we chose to start with the non-coding regions forming many 3D contacts (referred to as hubs) and identified dozens of hubs essential for cell viability. Hi-C and single cell transcriptomic analyses showed that their deletion could significantly alter chromatin organization and impact gene expression located distal in the genome. This study revealed the 3D structural importance of non-coding loci that are not associated with any functional element, providing a new mechanistic understanding of the disease-associated genetic variations (GVs). Furthermore, our analyses also suggested a powerful approach to develop “one-drug-multiple-targets” therapeutics targeting the disease-specific non-coding regions.

‘And makes it indistinct / As water is in water’: The melting away of the heroic subject in Antony and Cleopatra and All for Love

Premising the structural importance of water imagery in William Shakespeare’s Antony and Cleopatra, Antony’s ‘liquefaction’ reflects the core of his interiority, which is identified with his love affair with Cleopatra. Their desire requires a third party, Rome, in relation to which a seemingly self-enclosing erotic universe is built, and against which Antony fights for ascendancy, as a ghostly heroic self. In John Dryden’s All for Love, the historical flux vanishes, Antony’s heroic past figures as a residue and history as an embarrassment to love. In contrast with Shakespeare’s heroes, the lovers’ domestication foregrounds the compatibility of love and eros within marriage.

Fault tree analysis of large-scale blackout accidents

Fault tree analysis method is used to analyze the large-scale blackout accidents. Minimum cut sets and minimum path sets of large-scale blackout accidents are calculated, and the structural importance degree of the accidents is analyzed according to the minimum path sets. Direct factors that cause large-scale blackout accidents are determined. Effective measures are put forward to prevent large-scale blackouts, and the theoretical basis is put forward to prevent large-scale blackouts.