As extracellular vesicles that play an active role in intercellular communication by transferring cellular materials to recipient cells, exosomes offer great potential as a natural therapeutic drug delivery vehicle. The inflammatory responses in various disease models can be attenuated through introduction of super-repressor IκB (srIκB), which is the dominant active form of IκBα and can inhibit translocation of nuclear factor κB into the nucleus. An optogenetically engineered exosome system (EXPLOR) that we previously developed was implemented for loading a large amount of srIκB into exosomes. We showed that intraperitoneal injection of purified srIκB-loaded exosomes (Exo-srIκBs) attenuates mortality and systemic inflammation in septic mouse models. In a biodistribution study, Exo-srIκBs were observed mainly in the neutrophils, and in monocytes to a lesser extent, in the spleens and livers of mice. Moreover, we found that Exo-srIκB alleviates inflammatory responses in monocytic THP-1 cells and human umbilical vein endothelial cells.

The lung is highly vulnerable during sepsis, yet its functional deterioration accompanied by disturbances in the pulmonary microcirculation is poorly understood. This study aimed to investigate how the pulmonary microcirculation is distorted in sepsis-induced acute lung injury (ALI) and reveal the underlying cellular pathophysiologic mechanism.Using a custom-made intravital lung microscopic imaging system in a murine model of sepsis-induced ALI, we achieved direct real-time visualisation of the pulmonary microcirculation and circulating cellsin vivo. We derived the functional capillary ratio (FCR) as a quantitative parameter for assessing the fraction of functional microvasculature in the pulmonary microcirculation and dead space.We identified that the FCR rapidly decreases in the early stage of sepsis-induced ALI. The intravital imaging revealed that this decrease resulted from the generation of dead space, which was induced by prolonged neutrophil entrapment within the capillaries. We further showed that the neutrophils had an extended sequestration time and an arrest-like dynamic behaviour, both of which triggered neutrophil aggregates inside the capillaries and arterioles. Finally, we found that Mac-1 (CD11b/CD18) was upregulated in the sequestered neutrophils and that a Mac-1 inhibitor restored the FCR and improved hypoxaemia.Using the intravital lung imaging system, we observed that Mac-1-upregulated neutrophil aggregates led to the generation of dead space in the pulmonary microcirculation that was recovered by a Mac-1 inhibitor in sepsis-induced ALI.

easy processability. [8][9][10][11][12][13][14][15][16] Flexible organic transistors are usually fabricated on thin fl exible polymeric substrates. [17][18][19][20][21] They show good fl exibility with small bending radius of a few hundreds of micrometers. Although bending stability is important for large-area electronics in smart applications, it is still insuffi cient in itself to realize human-friendly electronic devices. Such devices require integration with curvilinear surfaces or fl exible and stretchable surfaces. [ 1,22 ] Device elasticity under tensile stress, i.e., stretchability, beyond fl exibility and bendability, is additionally required in a wide range of future electronic applications.Over the past few years, considerable research efforts have been applied to the development of stretchable electronics. Stretchable electronics are typically achieved through two approaches: geometrically structuring conventional brittle materials to have wavy or mesh forms, [ 3,23 ] or using of elastic conductive interconnections to integrate rigid circuit elements. [ 24,25 ] These are based on the strategy that the active material is not to be subjected to signifi cant deformations, and the overall electronic devices can be stretchable. However, these approaches unfortunately limit the fabrication of high-density integrated circuits. Because the interconnections of the wavy or mesh structures and the elastomeric composite are bulky, the distance between unit devices is limited to be reduced. Moreover, structuring whole devices using a buckling process is diffi cult during device miniaturization, and the methods require complex and expensive processing steps for the fabrication of wavy and mesh geo metries. For these reasons, stretchable electronic devices, which consist solely of intrinsically stretchable materials, need to be developed as the ultimate concept device. The development of intrinsically stretchable electronic materials faces several challenges, particularly in the development of stretchable active materials that can retain their electronic semiconducting properties under tensile stress. [26][27][28] Here, we describe the development of an intrinsically stretchable and transparent organic semiconducting material for use in stretchable organic thin fi lm transistors (OTFTs). The stretchable and transparent active material was designed to have the structure of 1D organic semiconducting Despite the considerable efforts applied toward developing stretchable electronics, few intrinsically stretchable semiconductors have been reported that retain the original electrical characteristics under stretching. This study introduces an intrinsically stretchable and transparent organic semiconducting layer by blending self-assembled nanowires (NWs) of an organic semiconductor with an elastomeric and transparent polymer. Blends of poly(3-hexylthio phene) (P3HT) NWs and poly(dimethylsiloxane) (PDMS) yield P3HT NW networks embedded in the PDMS matrix. Interestingly, it is found that the vertical distribution of P3HT NWs...

Although intermolecular charge transport is known to occur via π–π stacking, the influence of π–π stacking on the mechanical properties of polymers has received little attention compared with other dynamic noncovalent interactions. Herein, we demonstrate a method to enhance stretchability via lowering crystallinity and increasing π–π stacking of thiophene-based random copolymer chains, which causes π–π stacking-induced polymer networks to form within the fully conjugated semiconducting polymer matrix. The polymer networks contain coiled amorphous chains that aid energy dissipation when the polymer film is subjected to strain; furthermore, the π–π stacking prevents the chains from irreversible sliding out of place due to the applied strain and provides interchain charge transport. Consequently, we are able to improve the polymer’s mechanical properties such as elongation at break, tensile strength, and toughness along with charge mobility. Additionally, our polymer shows great tolerance to a 40% strain without a decrease in mobility while maintaining a stable electrical performance even after 5000 stretching cycles at 30% strain.

Lysyl-tRNA synthetase (KRS) can be released from cancer cells to cause inflammation, but the mechanism of KRS secretion is unknown. Kim et al. demonstrate that KRS is cleaved by caspase-8, which exposes a binding motif for syntenin and facilitates the secretion of KRS in exosomes.