Achieving robust and durable cellular immunity remains a key challenge in the development of subunit vaccines, primarily due to inefficient antigen cross-presentation and inadequate immune activation. Here, we engineered a series of nano-emulsions by conjugating human serum albumin (HSA) with fatty acids of varying chain lengths. Through systematic screening, the palmitic acid-modified nano-emulsion was identified as the most effective carrier, exhibiting intrinsic self-adjuvant properties and a strong capacity to elicit cellular immune responses. Notably, this formulation enables cascade-targeted delivery, trafficking sequentially from lymph nodes to antigen-presenting cells (APCs), and ultimately to the endoplasmic reticulum (ER). Upon co-delivery of the model antigen ovalbumin (OVA) and a stimulator of interferon genes (STING) agonist, the nano-emulsion facilitates both efficient antigen cross-presentation and precise intracellular activation of the STING pathway. This synergistic mechanism significantly enhances CD8+ T cell responses and promotes durable memory formation, resulting in potent antitumor efficacy in murine models. Collectively, this study presents a safe and versatile nano-emulsion platform that overcomes key barriers in subunit vaccine delivery, offering a promising strategy for next-generation vaccine design.
© 2025 The Authors.

Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma resembling developing skeletal muscle, but tumors are found in sites devoid of skeletal muscle, suggesting a non-myogenic cell of origin. We previously described an endothelial progenitor cell-derived model of RMS by activating a conditional, constitutively active Smoothened mutant (SmoM2) with aP2-Cre. We sought to further identify the endothelial progenitor cell of origin in our aP2-Cre;R26SmoM2 model using mice with more endothelial-specific Cre recombinase expression. Using lineage tracing of embryonic endothelial progenitor cells and mature, adult endothelial cells, we show that a selected subset of endothelial progenitor cells can transform into RMS. These endothelial progenitor cells have a specific window during embryogenesis with a capacity for transformation into RMS that is dictated by the presence of primary cilia and Sonic Hedgehog signaling pathway competency. These findings deepen our understanding of endothelial differentiation and the connections between normal development and oncogenesis in children.
Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.

Abstract Pancreatic cancer is one of the most invasive malignant tumors, with poor drug efficacy. Sonodynamic therapy (SDT) has emerged as a promising tumor treatment method. However, cancer-associated fibroblasts (CAFs) limit the efficacy of SDT and contribute to poor therapeutic response. Therefore, developing SDT strategies targeting CAFs in combination with chemotherapy to reshape the drug-resistant tumor microenvironment is critical for enhancing drug therapeutic outcomes in pancreatic cancer. Here, we constructed a CAF-targeted SDT-chemotherapy system named FnBPA5-IR-CF3@Dox, which can actively accumulate in CAFs and achieve effective SDT effect. Upon ultrasound irritation, FnBPA5-IR-CF3@Dox eliminates CAFs at pancreatic tumor sites, resulting in reduction of tumor interstitial fluid pressure, downregulation of interstitial fibrosis, enhanced CD8 + T cell infiltration into tumors, and improved drug penetration to tumor sites. This CAFs-targeted SDT combined with chemotherapy strategy significantly enhances chemotherapy efficacy and inhibits pancreatic cancer progression. It suggests that CAFs-targeted SDT combined with chemotherapy represents a promising approach for tumor microenvironment reprogramming in clinical pancreatic cancer treatment.

Interleukin-6 (IL-6) plays a central role in sepsis-induced cytokine storm involving immune hyperactivation and early neutrophil activation. Programmed death protein-1 (PD-1) is associated with sepsis-induced immunosuppression and lymphocyte apoptosis. However, the effects of simultaneous blockade of IL-6 and PD-1 in a murine sepsis model are not well understood.
In this study, sepsis was induced in male C57BL/6 mice through cecal ligation and puncture (CLP). IL-6 blockade, PD-1 blockade, or combination of both was administered 24 h after CLP. Peripheral blood count, cytokine level, lymphocyte apoptosis in the spleen, neutrophil infiltration in the lungs and liver, and survival rate were measured. The mortality rate of the IL-6/PD-1 group was lower, though not statistically significant (p = 0.164), than that of CLP mice (75.0% vs. 91.7%). The IL-6/PD-1 group had lower neutrophil percentage and platelet count compared with the CLP group; no significant difference was observed in other cytokine levels. The IL-6/PD-1 group also showed reduced T lymphocyte apoptosis in the spleen and decreased neutrophil infiltration in the liver and lungs.
IL-6/PD-1 dual blockade reduces neutrophil infiltration, lymphocyte apoptosis, and bacterial burden while preserving tissue integrity in sepsis. Although the improvement in survival was not statistically significant, these findings highlight its potential as a therapeutic approach in sepsis.
© 2025. The Author(s).

Urinary neutrophils are a hallmark of urinary tract infection (UTI), yet the mechanisms governing their activation, function, and efficacy in controlling infection remain incompletely understood. Tamm-Horsfall glycoprotein (THP), the most abundant protein in urine, uses terminal sialic acids to bind an inhibitory receptor and dampen neutrophil inflammatory responses. We hypothesized that neutrophil modulation is an integral part of THP-mediated host protection. In a UTI model, THP-deficient mice showed elevated urinary tract bacterial burdens, increased neutrophil recruitment, and more severe tissue histopathological changes compared with WT mice. Furthermore, THP-deficient mice displayed impaired urinary NETosis during UTI. To investigate the effect of THP on NETosis, we coupled in vitro fluorescence-based NET assays, proteomic analyses, and standard and imaging flow cytometry with peripheral human neutrophils. We found that THP increases proteins involved in respiratory chain, neutrophil granules, and chromatin remodeling pathways; enhances NETosis in an ROS-dependent manner; and drives NET-associated morphologic features including nuclear decondensation. These effects were observed only in the presence of a NETosis stimulus and could not be solely replicated with equivalent levels of sialic acid alone. We conclude that THP is a critical regulator of NETosis in the urinary tract, playing a key role in host defense against UTI.