Yang Pu

Extracellular vesicles (EVs) are a collective term for nanoscale or microscale vesicles secreted by cells that play important biological roles. Mesenchymal stem cells are a class of cells with the potential for self-healing and multidirectional differentiation. In recent years, numerous studies have shown that EVs, especially those secreted by mesenchymal stem cells, can promote the repair and regeneration of various tissues and, thus, have significant potential in regenerative medicine. However, due to the rapid clearance capacity of the circulatory system, EVs are barely able to act persistently at specific sites for repair of target tissues. Hydrogels have good biocompatibility and loose and porous structural properties that allow them to serve as EV carriers, thereby prolonging the retention in certain specific areas and slowing the release of EVs. When EVs are needed to function at specific sites, the EV-loaded hydrogels can stand as an excellent approach. In this review, we first introduce the sources, roles, and extraction and characterization methods of EVs and describe their current application status. We then review the different types of hydrogels and discuss factors influencing their abilities to carry and release EVs. We summarize several strategies for loading EVs into hydrogels and characterizing EV-loaded hydrogels. Furthermore, we discuss application strategies for EV-loaded hydrogels and review their specific applications in tissue regeneration and repair. This article concludes with a summary of the current state of research on EV-loaded hydrogels and an outlook on future research directions, which we hope will provide promising ideas for researchers.

Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate the composition of ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs from malignant epithelial cells and discover 42 cell types, including 26 immune cell and 16 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and analyse the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we link the cancer cell transcriptomes to the somatic mutations and identify several markers significantly associated with patients' survival, which may be relevant to precision care of ESCC patients. These results reveal the immunosuppressive status in the ESCC TME and further our understanding of ESCC.

Aberrant lysine lactylation (Kla) is associated with various diseases which are caused by excessive glycolysis metabolism. However, the regulatory molecules and downstream protein targets of Kla remain largely unclear. Here, we observed a global Kla abundance profile in colorectal cancer (CRC) that negatively correlates with prognosis. Among lactylated proteins detected in CRC, lactylation of eEF1A2K408 resulted in boosted translation elongation and enhanced protein synthesis which contributed to tumorigenesis. By screening eEF1A2 interacting proteins, we identified that KAT8, a lysine acetyltransferase that acted as a pan-Kla writer, was responsible for installing Kla on many protein substrates involving in diverse biological processes. Deletion of KAT8 inhibited CRC tumor growth, especially in a high-lactic tumor microenvironment. Therefore, the KAT8-eEF1A2 Kla axis is utilized to meet increased translational requirements for oncogenic adaptation. As a lactyltransferase, KAT8 may represent a potential therapeutic target for CRC.

Plastic surgery is a discipline that uses surgical methods or tissue transplantation to repair, reconstruct and beautify the defects and deformities of human tissues and organs. Three-dimensional (3D) bioprinting has gained widespread attention because it enables fine customization of the implants in the patient's surgical area preoperatively while avoiding some of the adverse reactions and complications of traditional surgical approaches. In this paper, we review the recent research advances in the application of 3D bioprinting in plastic surgery. We first introduce the printing process and basic principles of 3D bioprinting technology, revealing the advantages and disadvantages of different bioprinting technologies. Then, we describe the currently available bioprinting materials, and dissect the rationale for special dynamic 3D bioprinting (4D bioprinting) that is achieved by varying the combination strategy of bioprinting materials. Later, we focus on the viable clinical applications and effects of 3D bioprinting in plastic surgery. Finally, we summarize and discuss the challenges and prospects for the application of 3D bioprinting in plastic surgery. We believe that this review can contribute to further development of 3D bioprinting in plastic surgery and provide lessons for related research.

Complete and rapid healing of infected skin wounds remains a challenge in current clinical treatment. In this study, we prepared a self-healing injectable CK hydrogel by crosslinking two natural polysaccharides, carboxymethyl chitosan and oxidized konjac glucomannan, based on the Schiff base bond. To enhance the biological function of the hydrogel, we multi-functionalized hydrogen by loading it with berberine (BBR) and stem cell-derived exosomes (Exo), forming a composite hydrogel, CK@BBR&Exo, which could be injected directly into the wound through a needle and adhered to the wound. Furthermore, the self-healing properties of CK@BBR&Exo increased its usefulness and service life. Additionally, the drug-loaded CK@BBR&Exo hydrogel was versatile, inhibiting bacterial growth, regulating the inflammatory response, and promoting neovascularization in infected skin wounds, thus achieving the rapid healing of infected skin wounds. These results suggest that the CK@BBR&Exo-injectable self-healing hydrogel is an ideal dressing for treating infected skin wounds.