MEK inhibition prevents CAR-T cell exhaustion and differentiation via downregulation of c-Fos and JunB.

Clinical evidence supports the notion that T cell exhaustion and terminal differentiation pose challenges to the persistence and effectiveness of chimeric antigen receptor-T (CAR-T) cells. MEK1/2 inhibitors (MEKIs), widely used in cancer treatment due to their ability to inhibit aberrant MAPK signaling, have shown potential synergistic effects when combined with immunotherapy. However, the impact and mechanisms of MEKIs on CAR-T cells remain uncertain and controversial.

An in situ forming cartilage matrix mimetic hydrogel scavenges ROS and ameliorates osteoarthritis after superficial cartilage injury.

Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in clinical settings, posing significant treatment challenges. Here, we fabricated a cartilage extracellular matrix mimic hydrogel (GHC, consisting of Gelatin, Hyaluronic acid, and Chondroitin sulfate) to avoid the exacerbation of cartilage deterioration, which is often driven by the accumulation of reactive oxygen species (ROS) and a pro-inflammatory microenvironment. The GHC hydrogel exhibited multifunctional properties, including in situ formation, tissue adhesiveness, anti-ROS capabilities, and the promotion of chondrogenesis.

A nano-composite hyaluronic acid-based hydrogel efficiently antibacterial and scavenges ROS for promoting infected diabetic wound healing.

Diabetic wound infection brings chronic pain to patients and the therapy remains a crucial challenge owing to the disruption of the internal microenvironment. Herein, we report a nano-composite hydrogel (ZnO@HN) based on ZnO nanoparticles and a photo-trigging hyaluronic acid which is modified by o-nitrobenzene (NB), to accelerate infected diabetic wound healing. The diameter of the prepared ZnO nanoparticle is about 50 nm.

Fibroblasts facilitate lymphatic vessel formation in transplanted heart.

Lymphangiogenesis plays a critical role in the transplanted heart. The remodeling of lymphatics in the transplanted heart and the source of newly formed lymphatic vessels are still controversial, especially the mechanism of lymphangiogenesis remains limited. Heart transplantation was performed among , , , ; and (); mice.

Rewiring mitochondrial metabolism to counteract exhaustion of CAR-T cells.

Short persistence and early exhaustion of T cells are major limits to the efficacy and broad application of immunotherapy. Exhausted T and chimeric antigen receptor (CAR)-T cells upregulate expression of genes associated with terminated T cell differentiation, aerobic glycolysis and apoptosis. Among cell exhaustion characteristics, impaired mitochondrial function and dynamics are considered hallmarks.