Dendritic cell-derived IL-27 p28 regulates T cell program in pathogenicity and alleviates acute graft-versus-host disease

Interleukin 27(IL-27),a heterodimeric cytokine composed of Epstein-Barr virus-induced 3 and p28,is a pleiotropic cytokine with both pro-and anti-inflammatory properties.However,the precise role of IL-27 in acute graft-versus-host disease is not yet fully understood.In this study,utilizing mice with IL-27 p28 deficiency in dendritic cells(DCs),we demonstrated that IL-27 p28 deficiency resulted in impaired Treg cell function and enhanced effector T cell responses,corresponding to aggravated aGVHD in mice.In addition,using single-cell RNA sequencing,we found that loss of IL-27 p28 impaired Treg cell generation and promoted IL1R2^(+)TIGIT^(+)pathogenic CD4+T cells in the thymus at a steady state.Mechanistically,IL-27 p28 deficiency promoted STAT1 phosphorylation and Th1 cell responses,leading to the inhibition of Treg cell differentiation and function.Finally,patients with high levels of IL-27 p28 in serum showed a substantially decreased occurrence of grade II-IV aGVHD and more favorable overall survival than those with low levels of IL-27 p28.Thus,our results suggest a protective role of DC-derived IL-27 p28 in the pathogenesis of aGVHD through modulation of the Treg/Teff cell balance during thymic development.IL-27 p28 may be a valuable marker for predicting aGVHD development after transplantation in humans.

Polymerization-Amplified Photoacoustic Signal by Enhancing Near-Infrared Light-Harvesting Capacity and Thermal-to-Acoustic Conversion

As a frontier imaging technique for biomedical applications,photoacoustic(PA)imaging has been developed rapidly.The development of new design strategies and excellent PA imaging reagents to boost PA conversion is eagerly desirable for high quality PA imaging but complicated to realize.Herein,we develop a new strategy in which PA imaging reagents with better properties can be easily optimized by polymerization.A series of new PA imaging reagents were designed and synthesized.The polymerization strategy can effectively promote the PA signal by specifically increasing the thermal-to-acoustic conversion efficiency.As these materials shared the same building units,the optimized effectiveness of polymerization strategy in terms of near-infrared light-harvesting capacity and thermal-to-acoustic conversion efficiency are discussed,rationally.The polymers with intense intramolecular motion exhibit an amplified PA signal by elevating thermal-to-acoustic conversion and its higher light-harvesting capability at redshifted region.The simultaneously strong PA signal and photothermal conversion efficiency of p-TTmB NPs enable precise PA imaging and effective photothermal therapy.This work highlights a simple and available design guideline of polymerization for amplifying the PA effect and optimizing existing materials.

Robust H_(∞)path tracking control of autonomous vehicles with delay and actuator saturation

The path tracking control problem is investigated in this paper for autonomous vehicles(AVs)with time-varying input delay and actuator saturation.Based on the Lyapunov-Krasovskii function and the characteristic of the saturation nonlinearity,a robust H_(∞)state-feedback path tracking controller is presented,and the corresponding control gain can be obtained by solving the linear matrix inequalities(LMIs).The asymptotic stability and prescribed H_(∞)performance conditions are studied for the closed-loop control system.To reduce the cost of control system,a static robust H_(∞)output-feedback controller is also proposed.In addition,the uncertainty effects of the cornering stiffness and external disturbances are included to improve the robustness of the control scheme.Simulation results are given to verify the effectiveness of the proposed theoretical results.