In vivo bioorthogonal labeling of rare-earth doped nanoparticles for improved NIR-II tumor imaging by extracellular vesiclemediated targeting

The development of efficient contrast agents for tumor-targeted imaging remains a critical challenge in the clinic.Herein,we proposed a tumor-derived extracellular vesicle(EV)-mediated targeting approach to improve in vivo tumor imaging using ternary downconversion nanoparticles(DCNPs)with strong near infrared II(NIR-II)luminescence at 1,525 nm.The EVs were metabolically engineered with azide group,followed by in vivo labeling of DCNPs through copper-free click chemistry.By taking advantage of the homologous targeting property of tumor derived EVs,remarkable improvement in the tumor accumulation(6.5%injection dose(ID)/g)was achieved in the subcutaneous colorectal cancer model when compared to that of individual DCNPs via passive targeting(1.1%ID/g).Importantly,such bioorthogonal labeling significantly increased NIR-II luminescence signals and prolonged the retention at tumor sites.Our work demonstrates the great potential of EVs-mediated bioorthogonal approach for in vivo labeling of NIR-II optical probes,which provides a robust tool for tumor-specific imaging and targeted therapy.

Enhancement of pacemaker induced stochastic resonance by an autapse in a scale-free neuronal network

An autapse is an unusual synapse that occurs between the axon and the soma of the same neuron. Mathematically, it can be described as a self-delayed feedback loop that is defined by a specific time-delay and the so-called autaptic coupling strength. Recently, the role and function of autapses within the nervous system has been studied extensively. Here, we extend the scope of theoretical research by investigating the effects of an autapse on the transmission of a weak localized pacemaker activity in a scale-free neuronal network. Our results reveal that by mediating the spiking activity of the pacemaker neuron, an autapse increases the propagation of its rhythm across the whole network, if only the autaptic time delay and the autaptic coupling strength are properly adjusted. We show that the autapse-induced enhancement of the transmission of pacemaker activity occurs only when the autaptic time delay is close to an integer multiple of the intrinsic oscillation time of the neurons that form the network. In particular, we demonstrate the emergence of multiple resonances involving the weak signal, the intrinsic oscillations, and the time scale that is dictated by the autapse. Interestingly, we also show that the enhancement of the pacemaker rhythm across the network is the strongest if the degree of the pacemaker neuron is lowest. This is because the dissipation of the localized rhythm is contained to the few directly linked neurons, and only afterwards, through the secondary neurons, it propagates further. If the pacemaker neuron has a high degree, then its rhythm is simply too weak to excite all the neighboring neurons, and propagation therefore fails.