COXFA4L2 upregulation preserves residual cytochrome c oxidase activity in COXFA4-related Leigh-like encephalopathy
Nat Commun. 2026 May 30. doi: 10.1038/s41467-026-73455-9. Online ahead of print. ABSTRACT Primary mitochondrial diseases (PMDs) affect approximately 1 in 4300 individuals and cause early-onset neuromuscular and multisystem dysfunction with reduced lifespan. They result from pathogenic variants in mitochondrial or nuclear DNA that impair oxidative phosphorylation. Cytochrome c oxidase (COX; complex IV) deficiency is a […]
Systematic review and meta-analysis of humoral immunity proteins and mortality in sepsis
Crit Care. 2025 Dec 22. doi: 10.1186/s13054-025-05758-0. Online ahead of print. ABSTRACT PURPOSE: Humoral immunity proteins-immunoglobulins, complement proteins, and antimicrobial peptides-have key antimicrobial and immunomodulatory functions in sepsis. We hypothesised that their circulating levels are lower in non-survivors, potentially resulting in impaired bacterial clearance and persistent or recurrent infections. METHODS: We performed a systematic review […]
A fin-loop-like structure in GPX4 underlies neuroprotection from ferroptosis
Cell. 2025 Dec 4:S0092-8674(25)01310-8. doi: 10.1016/j.cell.2025.11.014. Online ahead of print. ABSTRACT Ferroptosis, driven by uncontrolled peroxidation of membrane phospholipids, is distinct from other cell death modalities because it lacks an initiating signal and is surveilled by endogenous antioxidant defenses. Glutathione peroxidase 4 (GPX4) is the guardian of ferroptosis, although its membrane-protective function remains poorly understood. […]
Sequencing Analysis Demonstrates That a Complex Genetic Architecture Contributes to Risk for Spina Bifida
Birth Defects Res. 2025 Oct;117(10):e2533. doi: 10.1002/bdr2.2533. ABSTRACT BACKGROUND: Spina bifida (SB), a common neural tube defects (NTDs), has a complex genetic architecture that remains incompletely understood. Although prior studies have identified rare, deleterious single nucleotide variants (SNVs) in SB, broader contributions to risk remain unclear. Here, we investigated shared genetic risk among 256 SB […]
Extrachromosomal DNA-Driven Oncogene Dosage Heterogeneity Promotes Rapid Adaptation to Therapy in MYCN-Amplified Cancers
Cancer Discov. 2025 Aug 7:OF1-OF24. doi: 10.1158/2159-8290.CD-24-1738. Online ahead of print. ABSTRACT Extrachromosomal DNA (ecDNA) amplification enhances intercellular oncogene dosage variability and accelerates tumor evolution by violating foundational principles of genetic inheritance through its asymmetric mitotic segregation. Spotlighting high-risk neuroblastoma, we demonstrate how ecDNA amplification undermines the clinical efficacy of current therapies in cancers with […]