Mechanical and molecular activation lead to structurally analogous MscL states

The mechanosensitive channel of large conductance MscL gates in response to tension changes in the membrane to allow the exchange of molecules through its pore. Native ligands that bind and modulate MscL are unknown and trapping an activated state has been challenging. Disruption of lipid access to tension-sensitive transmembrane pockets by modification leads to a concerted structural and functional MscL response. However, it is unknown whether there is structural correlation between tension mediated and molecular activation in mechanosensitive channels. Here, we combine HDX mass spectrometry and ESEEM solvent accessibility measurements on MscL, coupled with molecular dynamics under bilayer tension, to investigate the structural changes associated with the two distinctively derived states. Membrane thinning is not sufficient to hydrate the MscL pore, when lipids are trapped in the pockets, under tensions capable to gate the native channel. Tension and molecule stabilised states present analogous MscL structures, suggesting a link between these two distinct activation mechanisms. These findings could hint at synergistic modes of regulation in mechanosensitive ion channels with implications for their multimodality.

Dual functions of CO2 molecular activation and 4f levels as electron transport bridge in erbium single atom composite photocatalysts therefore enhancing visible-light photoactivities

Only when the interfacial charge separation is enhanced and the CO2 activation is improved, can the heterojunction nanocomposite photocatalyst be brought into full play for CO2 reduction reaction (CO2RR). Here,...

RIPK2: New Elements in Modulating Inflammatory Breast Cancer Pathogenesis

Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that is associated with significantly high mortality. In spite of advances in IBC diagnoses, the prognosis is still poor compared to non-IBC. Due to the aggressive nature of the disease, we hypothesize that elevated levels of inflammatory mediators may drive tumorigenesis and metastasis in IBC patients. Utilizing IBC cell models and patient tumor samples, we can detect elevated NF-κB activity and hyperactivation of non-canonical drivers of NF-κB (nuclear factor kappaB)-directed inflammation such as tyrosine phosphorylated receptor-interacting protein kinase 2 (pY RIPK2), when compared to non-IBC cells or patients. Interestingly, elevated RIPK2 activity levels were present in a majority of pre-chemotherapy samples from IBC patients at the time of diagnosis to suggest that patients at diagnosis had molecular activation of NF-κB via RIPK2, a phenomenon we define as “molecular inflammation”. Surprisingly, chemotherapy did cause a significant increase in RIPK2 activity and thus molecular inflammation suggesting that chemotherapy does not resolve the molecular activation of NF-κB via RIPK2. This would impact on the metastatic potential of IBC cells. Indeed, we can demonstrate that RIPK2 activity correlated with advanced tumor, metastasis, and group stage as well as body mass index (BMI) to indicate that RIPK2 might be a useful prognostic marker for IBC and advanced stage breast cancer.

Metal nanoparticles induced photocatalysis

Photocatalysis induced by light absorption of metal nanoparticles (NPs) has emerged as a promising strategy for exploiting efficient visible-light-responsive composites for solar-energy conversion. In this review, we first introduce the light absorption of metal NPs and the mechanisms proposed in metal-induced photocatalysis (MIP). Then, its applications in water splitting, artificial photosynthesis and inert molecular activation are summarized. To address the challenge of low efficiency in this field, strategies in promoting catalytic activity are reviewed, and particular attention is paid to the particle-size effect of metal. Finally, the challenges and possible development directions of MIP are briefly discussed.