This review presents comprehensive discussions on the recent development in supramolecular materials based on luminogens with aggregation-induced emission (AIE) characteristics.

The Hippo signalling pathway plays important roles in animal development, physiology and tumorigenesis. Understanding how the activity of this pathway is regulated by the cellular microenvironment remains a major challenge. Here we elucidate a molecular mechanism by which hypoxia deactivates Hippo signalling. We demonstrate that the E3 ubiquitin ligase SIAH2 stimulates YAP by destabilizing LATS2, a critical component of the Hippo pathway, in response to hypoxia. Loss of SIAH2 suppresses tumorigenesis in a LATS2-dependent manner in a xenograft mouse model. We further show that YAP complexes with HIF1α and is essential for HIF1α stability and function in tumours in vivo. LATS2 is downregulated in human breast tumours and negatively correlates with SIAH2 expression levels, indicating that the SIAH2-LATS2 pathway may have a role in human cancer. Our data uncover oxygen availability as a microenvironment signal for the Hippo pathway and have implications for understanding the regulation of Hippo signalling in tumorigenesis.

Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly population. Accumulation, aggregation, and deposition of amyloid-␤ (A␤) peptides generated through proteolytic cleavage of amyloid precursor protein (APP) are likely initiating events in the pathogenesis of AD. While A␤ production is accelerated in familial AD, increasing evidence indicates that impaired clearance of A␤ is responsible for late-onset AD. Because A␤ is mainly generated in neurons, these cells are predicted to have the highest risk of encountering A␤ among all cell types in the brain. However, it is still unclear whether they are also involved in A␤ clearance. Here we show that receptor-mediated endocytosis in neurons by the low-density lipoprotein receptor-related protein 1 (LRP1) plays a critical role in brain A␤ clearance. LRP1 is known to be an endocytic receptor for multiple ligands including A␤. Conditional knock-out of Lrp1 in mouse forebrain neurons leads to increased brain A␤ levels and exacerbated amyloid plaque deposition selectively in the cortex of amyloid model APP/PS1 mice without affecting A␤ production. In vivo microdialysis studies demonstrated that A␤ clearance in brain interstitial fluid is impaired in neuronal Lrp1 knock-out mice. Because the neuronal LRP1-deletion did not affect the mRNA levels of major A␤ degrading enzymes, neprilysin and insulin-degrading enzyme, the disturbed A␤ clearance is likely due to the suppression of LRP1-mediated neuronal A␤ uptake and degradation. Together, our results demonstrate that LRP1 plays an important role in receptormediated clearance of A␤ and indicate that neurons not only produce but also clear A␤.