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Introduction Innate lymphoid cells (ILCs) are a group of immune cells that exhibit lymphoid characteristics yet lack antigen-specific receptors found on T and B cells (1). Group 3 ILCs (ILC3s) [...], Group 3 innate lymphoid cells (ILC3s) are key players in intestinal homeostasis. ER stress is linked to inflammatory bowel disease (IBD). Here, we used cell culture, mouse models, and human specimens to determine whether ER stress in ILC3s affects IBD pathophysiology. We show that mouse intestinal ILC3s exhibited a 24-hour rhythmic expression pattern of the master ER stress response regulator inositol-requiring kinase 1[alpha]/X-box-binding protein 1 (IRE1[alpha]/XBP1). Proinflammatory cytokine IL-23 selectively stimulated IRE1[alpha]/XBP1 in mouse ILC3s through mitochondrial ROS (mtROS). IRE1[alpha]/XBP1 was activated in ILC3s from mice exposed to experimental colitis and in inflamed human IBD specimens. Mice with Ire1[alpha] deletion in ILC3s ([Ire1[alpha].sup.[DELTA]Rorc]) showed reduced expression of the ER stress response and cytokine genes including Il22 in ILC3s and were highly vulnerable to infections and colitis. Administration of IL-22 counteracted their colitis susceptibility. In human ILC3s, IRE1 inhibitors suppressed cytokine production, which was upregulated by an IRE1 activator. Moreover, the frequencies of intestinal [XBP1s.sup.+] ILC3s in patients with Crohn's disease before administration of ustekinumab, an anti-IL-12/IL- 23 antibody, positively correlated with the response to treatment. We demonstrate that a noncanonical mtROS-IRE1[alpha]/XBP1 pathway augmented cytokine production by ILC3s and identify [XBP1s.sup.+] ILC3s as a potential biomarker for predicting the response to anti-IL-23 therapies in IBD.

Porous tantalum metal is a new orthopedic implant material made of tantalum metal that has been processed by porous treatment. This material has various advantages, including high hardness, good ductility, good biocompatibility, and strong bone integration ability. Porous tantalum metal has performed well in clinical application, demonstrating excellent medium‐ to long‐term curative effects. The use of implant products made of porous tantalum metal, such as porous tantalum rods, porous tantalum hip prostheses, and porous tantalum augments (MAs), is gradually increasing in the clinical application of hip surgery, and these products have achieved excellent therapeutic effects in the middle and late stages of various hip diseases. In recent years, the combined application of porous tantalum metal and three‐dimenional (3D) printing technology to create personalized 3D‐printed porous tantalum metal has led to new development directions for the treatment of complex hip joint surgical diseases. This review presents a summary of the application of porous tantalum metal in hip surgery in recent years, including clinical treatment effects and existing problems. In addition, the prospect of progress in this field is promoted. [ABSTRACT FROM AUTHOR]

Traumatic osteonecrosis of the femoral head (TONFH) refers to ischemic osteonecrosis is resulting from an acute mechanical interruption of the blood supply to the femoral head. The early diagnosis and optimal treatment have been central focuses of research and continue to undergo improvement. Reliable animal models are essential for advancing research into the treatment of the disease. This review aims to provide a comprehensive overview of tetrapod models (rats, rabbits, dogs, and sheep) and bipod models (emus, ostriches), as well as various modeling methods (traumatic hip dislocation, dissection of the round ligament and ligature of the femoral neck, femoral neck fracture (FNF), reduction and internal fixation after femoral neck fracture, and highly selective disruption of the anterior-superior retinacular vessels). This review examines the advantages, disadvantages, and applicability of each model. Based on blood flow analysis, it proposes a more reliable direction for TONFH modeling: simulating partial blood flow injury in the context of FNF., (© 2025 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background & Aims: Perianal fistulizing Crohn's disease (PCD) is a common and debilitating complication with elusive pathophysiology. We examined mucosal cells from patients with PCD and related conditions using a multi-omics approach., Methods: We recruited patients with PCD (n = 24), CD without perianal disease (NPCD, n = 10), and idiopathic perianal fistulas (IPF, n = 29). Biopsies were taken from fistula tracts, fistula opening, and rectal mucosa. Single-cell RNA-sequencing (scRNA-seq), mass cytometry (CyTOF), spatial transcriptomics (ST), immunohistochemistry, and integrated analysis were performed., Results: ScRNA-seq, CyTOF, and ST unraveled immune and non-immune cell compartments in PCD and IPF fistula tracts. PCD fistulas showed hyperactivated pathogenic pathways including interferon (IFN)G response and TNF signaling in myeloid and stromal cells. Intestinal cells from PCD patients also expressed greater levels of IFNG-responsive and EMT genes compared to NPCD patients. Furthermore, both fistula tracts and ileal mucosa from PCD patients harbored expanded IFNG+ pathogenic Th17 cells, which expressed elevated inflammatory mediators. CyTOF also identified skewed immune cell phenotypes in the fistula tracts, fistula opening, and rectum in PCD patients including expanded Th17 cells, increased pathogenic myeloid cells, and altered T cell exhaustion markers. Further analysis also revealed cellular modules associated with anti-TNF therapy in PCD patients., Conclusion: Multi-omics analysis revealed immune, stromal, and epithelial cell landscapes of PCD, which highlight the pathogenic role of hyperactivated IFNG signaling in both fistula tracts and luminal mucosa. This study identified IFNG as a potential therapeutic target for PCD., Competing Interests: Conflict-of-interest statement Marco Colonna, MD received research grants from Pfizer and Aclaris Therapeutics, unrelated to the data in the study. Matthew Ciorba, MD has received grants unrelated to the current content from AbbVie, Takeda, Pfizer, and Janssen. Parakkal Deepak, MBBS MS received research support under a sponsored research agreement unrelated to the data in the study and/or consulting from Johnson and Johnson, Pfizer, AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, CorEvitas LLC, Sandoz, Takeda Pharmaceuticals, Direct Biologics, Prometheus Biosciences, Lilly, Teva Pharmaceuticals, Merck, ExeGI Pharmaceuticals, AGMB, Landos Pharmaceuticals, Tr1X, and Boehringer Ingelheim.

Background: Gliomas, originating from the most common non-neuronal cells in the brain (glial cells), are the most common brain tumors and are associated with high mortality and poor prognosis. Glioma cells exhibit a tendency to disrupt normal cell-cycle regulation, leading to abnormal proliferation and malignant growth. This study investigated the predictive potential of GJC1 in gliomas and explored its relationship with the cell cycle., Methods: Retrospective analysis of RNA-seq and single-cell sequencing data was conducted using the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. The differential expression of GJC1 in gliomas with various pathological features and in different non-neuronal cell groups was analyzed. Functional data were examined using gene set variation analysis (GSVA). Furthermore, CellMiner was used to evaluate the relationship between GJC1 expression and predicted treatment response across these databases., Results: GJC1 expression was enriched in high-grade gliomas and 1p/19q non-codeletion gliomas. GJC1 enrichment was observed in classical and mesenchymal subtypes within the TCGA glioma subtype group. In single-cell subgroup analysis, GJC1 expression was higher in glioma tissues compared to other non-neuronal cells. Additionally, the TCGA classical subtype of glioma cells exhibited more GJC1 expression than the other subgroups. GJC1 emerged as an independent prognostic factor for overall survival in glioma. GSVA unveiled potential mechanisms by which GJC1 may impact cell-cycle regulation in glioma. Finally, a significant correlation was observed between GJC1 expression and the sensitivity of multiple anti-cancer drugs., Conclusion: These findings confirmed GJC1 as a novel biomarker and provided insights into the differential gene expression in non-neuronal cells and the impact of the cell cycle on gliomas. Consequently, GJC1 may be used to predict glioma prognosis and has potential therapeutic value., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ji, Chen, Lin, Ma, Yang, Zhao, Chen and Yang.)