FRET-based polymer materials for detection of cellular microenvironments

Effective detection of cellular microenvironments and understanding of physiological activities in living cells remain a considerable challenge.In recent years,fluore scence(or Forster)resonance energy trans fe r(FRET)technology has emerged as a valuable method for real-time imaging of intracellular environment with high sensitivity,specificity and spatial resolution.Particularly,polymer-based imaging systems show enhanced stability,improved biodistribution,increased dye payloads,and amplified signal/noise ratio compared with small molecular sensors.This review summarizes the recent progress in FRET-based polymeric systems for probing the physiological environments in cells.

Application and prospects of high-throughput screening for in vitro neurogenesis

Over the past few decades,high-throughput screening(HTS)has made great contributions to new drug discovery.HTS technology is equipped with higher throughput,minimized platforms,more automated and computerized operating systems,more efficient and sensitive detection devices,and rapid data processing systems.At the same time,in vitro neurogenesis is gradually becoming important in establishing models to investigate the mechanisms of neural disease or developmental processes.However,challenges remain in generating more mature and functional neurons with specific subtypes and in establishing robust and standardized three-dimensional(3D)in vitro models with neural cells cultured in 3D matrices or organoids representing specific brain regions.Here,we review the applications of HTS technologies on in vitro neurogenesis,especially aiming at identifying the essential genes,chemical small molecules and adaptive microenvironments that hold great prospects for generating functional neurons or more reproductive and homogeneous 3D organoids.We also discuss the developmental tendency of HTS technology,e.g.,so-called next-generation screening,which utilizes 3D organoid-based screening combined with microfluidic devices to narrow the gap between in vitro models and in vivo situations both physiologically and pathologically.

The biogenesis and secretion of exosomes and multivesicular bodies(MVBs):Intercellular shuttles and implications in human diseases

Exosomes carry and transmit signaling molecules used for intercellular communication.The generation and secretion of exosomes is a multistep interlocking process that allows simultaneous control of multiple regulatory sites.Protein molecules,mainly RAB GTPases,cytoskeletal proteins and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor(SNARE),are specifically regulated in response to pathological conditions such as altered cellular microenvironment,stimulation by pathogenic factors,or gene mutation.This interferes with the smooth functioning of endocytosis,translocation,degradation,docking and fusion processes,leading to changes in the secretion of exosomes.Large numbers of secreted exosomes are disseminated by the flow of body fluids and absorbed by the recipient cells.By transmitting characteristic functional proteins and genetic information produced under disease conditions,exosomes can change the physiological state of the recipient cells and their microenvironment.The microenvironment,in turn,affects the occurrence and development of disease.Therefore,this review will discuss the mechanism by which exosome secretion is regulated in cells following the formation of mature secretory multivesicular bodies(MVBs).The overall aim is to find ways to eliminate disease-derived exosomes at their source,thereby providing an important new basis for the clinical treatment of disease.