No abstract

We present here a rhodium-catalyzed asymmetric N−H insertion reaction, which is a concerted process revealed by DFT calculations, for the synthesis of novel axially chiral N-arylindoles by the reaction between indoles and diazonaphthoquinones. The reaction occurs at the N1 rather than C2/C3 positions of indoles, providing the chiral N-arylindoles in good yields and excellent enantiomeric ratios. Furthermore, this protocol is also amenable to the synthesis of chiral N-arylcarbazoles with excellent enantiocontrol.

Sepsis is a life‐threatening inflammatory disease with a high mortality rate and huge implicative costs. Lipopolysaccharide (LPS) from gram‐negative bacteria activates toll‐like receptor 4 (TLR4) and may trigger septic shock. However, potent TLR4 inhibitors TAK‐242 and Eritoran have been terminated in phase III clinical trials because of inadequate efficacy. Inspired by the recently discovered intracellular, noncanonical LPS receptors, it is considered that TLR4‐mediated canonical and caspase‐mediated noncanonical inflammation can be seen as a “parallel circuit” to induce sepsis and endotoxemia. Logically, it is proposed that the dual inhibition of caspase‐4/5/11 and TLR4 can be a potential novel strategy to develop new therapeutics for sepsis. To verify the strategy, two potential compounds are found: Luteolin and Diacerein with substantial antiinflammatory activity in vitro and in vivo. The results show that the survival rate of endotoxemic mice treated by these compounds is increased remarkably. LPS‐induced organ damage is also prevented. Moreover, these compounds result in physical and mental recovery for endotoxemic mice. Notably, Luteolin exhibits better antiinflammatory activity than TAK‐242 at comparable TLR4‐inhibitory levels. These findings indicate that simultaneous inhibition of TLR4 and caspase‐4/5/11 can be an anticipative strategy defeating sepsis and endotoxemia, which can be translated into significant medical and economic benefits.

It is commonly believed that attending to a piece of information would facilitate its subsequent memory. However, it remains unknown whether this consensus must always be true in all cases. Here, we provided a series of demonstrations supporting the striking possibility that attention could sometimes lead to memory weakening. This possibility was tested by directly comparing the memory traces of key features that were initially task-relevant but became outdated once used with baseline irrelevant features that were completely irrelevant throughout the task. Experiments 1–3 consistently showed that the memory traces of fully attended key features were weaker than the ignored irrelevant features, indicating that attention facilitated forgetting of key features. Experiment 4 demonstrated that forgetting of key features was an active process subject to execute control. These findings shed new light on the understanding of the relationship between attention and forgetting.