Although endogenous neural stem cells represent a promising target for noninvasive spinal cord injury repair, inflammatory lesion environments frequently trigger their death. Our prior work identified necroptosis as a key death pathway for endogenous neural stem cells migrating to spinal cord injury lesions. Rapamycin-insensitive companion of mTOR (Rictor; a core component of the mechanistic target of rapamycin complex 2 [mTORC2] complex) regulates neural stem cell self-renewal and differentiation, and our preliminary data implicate it in spinal cord injury repair; however, its role in promoting endogenous neural stem cell survival post-spinal cord injury remains unclear. Here, we generated conditional endogenous neural stem cell-specific Rictor knockout mice using the Cre-loxP system. Although the endogenous neural stem cell-specific Rictor knockout mice displayed normal baseline spinal cord morphology and function, they exhibited impaired functional recovery after spinal cord injury compared with wild-type controls. This deficit correlated with elevated inflammatory responses and the increased susceptibility of endogenous neural stem cells to necroptosis. Mechanistically, lentiviral-mediated Rictor knockdown in neural stem cells in vitro impaired lysosomal function, leading to heightened sensitivity to tumor necrosis factor-alpha- and lipopolysaccharide-induced necroptosis. Collectively, these findings indicate that Rictor/mTORC2 signaling protects endogenous neural stem cells against receptor-interacting protein kinase 1-mediated necroptosis following spinal cord injury. Consequently, the modulation of intrinsic Rictor activity represents a potential therapeutic strategy to enhance endogenous neural stem cell survival and functional recovery post-spinal cord injury.

Objective: To evaluate the utility of synovial iron quantification using Magnetic resonance imaging (MRI) in assessing structural joint damage in the knee of patients with rheumatoid arthritis (RA). Methods: This cross-sectional study employed a two-stage design. In the initial comparative stage, 6 patients with RA and 5 patients with osteoarthritis (OA) were recruited to compare synovial R2* values, a metric derived from iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) MRI sequences representing synovial iron content. Following this, the RA cohort was expanded to a total of 51 patients to investigate the association between R2* values and clinical parameters, including disease activity and bone erosion. Synovial fluid iron levels were measured with an Iron Assay Kit and synovial iron deposits were semi-quantified via Prussian blue staining. Associations between R2* and clinical and laboratory parameters, including inflammatory factors and joint damage indices, were analyzed using Spearman’s rank correlation. Univariate and multivariate ordered logistic regression models were employed to identify factors associated with bone erosion severity. An R2*-based nomogram was developed and validated using receiver operating characteristic (ROC) analysis and calibration curves. Results: Synovial R2* values were significantly higher in RA patients than those with osteoarthritis (53.66 S⁻¹ vs. 31.38 S⁻¹, p < 0.05), consistent with Prussian blue staining results. While synovial R2* values showed no significant correlation with systemic iron metabolic markers, inflammatory indicators, or the Disease Activity Score 28, they were positively correlated with bone erosion severity (ρ = 0.500, p < 0.001) and negatively associated with the joint space width (ρ = −0.307, p < 0.05). Multivariate analysis identified R2* as an independent indicator linked to bone erosion extent (OR = 2358.336, p < 0.001). The R2*-based nomogram demonstrated good discriminative performance. (AUC = 0.83). Conclusions: The R2* value derived from IDEAL-IQ MRI is a reliable tool for quantifying synovial iron and may represent a promising non-invasive imaging biomarker reflecting bone erosion in RA patients.