Chemiluminescent Nanomicelles for Imaging Hydrogen Peroxide and Self-Therapy in Photodynamic Therapy

Hydrogen peroxide is a signal molecule of the tumor, and its overproduction makes a higher concentration in tumor tissue compared to normal tissue. Based on the fact that peroxalates can make chemiluminescence with a high efficiency in the presence of hydrogen peroxide, we developed nanomicelles composed of peroxalate ester oligomers and fluorescent dyes, called peroxalate nanomicelles (POMs), which could image hydrogen peroxide with high sensitivity and stability. The potential application of the POMs in photodynamic therapy (PDT) for cancer was also investigated. It was found that the PDT-drug-loaded POMs were sensitive to hydrogen peroxide, and the PDT drug could be stimulated by the chemiluminescence from the reaction between POMs and hydrogen peroxide, which carried on a self-therapy of the tumor without the additional laser light resource

Identification of co-expressed gene networks promoting CD8+ T cell infiltration and having prognostic value in uveal melanoma

Abstract Current immunotherapies are unsatisfactory against uveal melanoma (UM); however, elevated CD8+ T cell infiltration level indicates poor prognosis in UM. Here, we aimed to identify co-expressed gene networks promoting CD8+ T cell infiltration in UM and created a prognostic hazard model based on the identified hub genes. Raw data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Stromal-immune comprehensive score (ESTIMATE) was used to evaluate the immune-infiltration landscape of the tumor microenvironment. Single-Sample Gene Set Enrichment Analysis (ssGSEA) and Weighted Correlation Network Analysis (WGCNA) were used to quantify CD8+ T cell infiltration level and identify hub genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to analyze the biological processes. Least absolute shrinkage and selection operator (LASSO) Cox regression were used to establish a prognostic model, which was further validated. Finally, pan-cancer analysis evaluated these genes to be associated with CD8+ T cell infiltration in other tumors. In conclusion, the proposed four-gene (PTPN12, IDH2, P2RX4, and KDELR2) prognostic hazard model had satisfactory prognostic ability. These hub genes may promote CD8+ T cell infiltration in UM through antigen presentation, and CD8+ T cell possibly function as Treg, resulting in poor prognosis. These findings might facilitate the development of novel immunotherapies

Construction of Dual-Biofunctionalized Chitosan/Collagen Scaffolds for Simultaneous Neovascularization and Nerve Regeneration

Biofunctionalization of artificial nerve implants by incorporation of specific bioactive factors has greatly enhanced the success of grafting procedures for peripheral nerve regeneration. However, most studies on novel biofunctionalized implants have emphasized the promotion of neuronal and axonal repair over vascularization, a process critical for long-term functional restoration. We constructed a dual-biofunctionalized chitosan/collagen composite scaffold with Ile-Lys-Val-Ala-Val (IKVAV) and vascular endothelial growth factor (VEGF) by combining solution blending, in situ lyophilization, and surface biomodification. Immobilization of VEGF and IKVAV on the scaffolds was confirmed both qualitatively by staining and quantitatively by ELISA. Various single- and dual-biofunctionalized scaffolds were compared for the promotion of endothelial cell (EC) and Schwann cell (SC) proliferation as well as the induction of angiogenic and neuroregeneration-associated genes by these cells in culture. The efficacy of these scaffolds for vascularization was evaluated by implantation in chicken embryos, while functional repair capacity in vivo was assessed in rats subjected to a 10 mm sciatic nerve injury. Dual-biofunctionalized scaffolds supported robust EC and SC proliferation and upregulated the expression levels of multiple genes and proteins related to neuroregeneration and vascularization. Dual-biofunctionalized scaffolds demonstrated superior vascularization induction in embryos and greater promotion of vascularization, myelination, and functional recovery in rats. These findings support the clinical potential of VEGF/IKVAV dual-biofunctionalized chitosan/collagen composite scaffolds for facilitating peripheral nerve regeneration, making it an attractive candidate for repairing critical nerve defect. The study may provide a critical experimental and theoretical basis for the development and design of new artificial nerve implants with excellent biological performance

GM‐CSF signalling in Th17‐cell pathogenicity: The culprit in autoimmune uveitis promoted by sleep loss

Abstract Sleep loss (SL) is a health problem that affects autoimmune and inflammatory diseases. However, the relationship between SL, the immune system and autoimmune diseases remains unclear. This commentary summarizes and discusses the key findings of the study by Liu et al. published in Clinical and Translational Medicine. In this study, they analysed the effects of SL on autoimmune uveitis using mass cytometry, single‐cell RNA sequencing, and flow cytometry. They identified changes in the composition and function of human and mouse immune cells following SL that primarily involved effector CD4+ T cells and myeloid cells. Furthermore, they demonstrated that SL promoted Th17 differentiation, pathogenicity, and Interleukin‐23 (IL‐23)–Th17– granulocyte macrophage colony stimulating factor (GM‐CSF) feedback mechanism in autoimmunity. Finally, they attenuated SL‐induced EAU exacerbation using anti‐GM‐CSF treatment, providing a novel therapeutic approach for SL‐related autoimmune diseases

Research on the Increase of Mineral Dissociation Degree by High Pressure Water Jet

The traditional grinding technology of ball mill has many problems, such as high energy consumption, unable to maintain the original crystal shape, and it is difficult to obtain high quality and high purity ultrafine powder. The high-pressure water jet mineral dissociation technology is a new technology which is developed in response to these requirements. The experiment shows that the water jet technology has a strong ability of ultrafine grinding. With the increase of jet velocity, the crushing effect is more obvious. The high-pressure water jet pulverization is superior to ball milling for the separation of rare earth minerals, which has the characteristics of high dissociation degree and relatively uniform particle size. The water jet pulverization is more beneficial to the separation and recovery of rare earth minerals