Spinal cord injury (SCI) remains a major clinical challenge, with limited therapeutic options for restoring lost neurological function. While efforts to mitigate secondary damage have improved early-phase management, achieving sustained neurorepair and functional recovery remains elusive. Advances in stem cell engineering and regenerative medicine have opened new avenues for targeted interventions, particularly through the transplantation of neural stem/progenitor cells (NSPCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs). However, patient-specific factors such as cellular senescence, genetic and epigenetic variability, injury microenvironment, and comorbidities influence the efficacy of stem cell therapies by affecting graft survival and differentiation. Overcoming these challenges necessitates cutting-edge technologies, including single-cell transcriptomics, CRISPR-mediated hypoimmunogenic engineering, and biomaterial-based delivery platforms, which enable personalized and precision-driven SCI repair. Leveraging these advancements may help stem cell therapies overcome translational barriers and establish clinically viable regenerative solutions. This review explores the intersection of patient-specific variability, bioengineering innovations, and transcriptomic-guided precision medicine to define the next frontier in SCI therapy.

Reactive oxygen species (ROS) are among the most severe types of cellular stressors with the ability to damage essential cellular biomolecules. Excess levels of ROS are correlated with multiple pathophysiological conditions including neurodegeneration, diabetes, atherosclerosis, and cancer. Failure to regulate the severely imbalanced levels of ROS can ultimately lead to cell death, highlighting the importance of investigating the molecular mechanisms involved in the detoxification procedures that counteract the effects of these compounds in living organisms. One of the most abundant forms of ROS is H ₂ O ₂ , mainly produced by the electron transport chain in the mitochondria. Numerous genes have been identified as essential to the process of cellular detoxification. Yeast YAP1 , which is homologous to mammalian AP‐1 type transcriptional factors, has a key role in oxidative detoxification by upregulating the expression of antioxidant genes in yeast. The current study reveals novel functions for COX5A and NPR3 in H ₂ O ₂ ‐induced stress by demonstrating that their deletions result in a sensitive phenotype. Our follow‐up investigations indicate that COX5A and NPR3 regulate the expression of YAP1 through an alternative mode of translation initiation. These novel gene functions expand our understanding of the regulation of gene expression and defense mechanism of yeast against oxidative stress.

The adult human spinal cord harbors diverse populations of neural stem/progenitor cells (NSPCs) essential for neuroregeneration and central nervous system repair. While induced pluripotent stem cell (iPSC)-derived NSPCs offer significant therapeutic potential, understanding their molecular and functional alignment with bona fide spinal cord NSPCs is crucial for developing autologous cell therapies that enhance spinal cord regeneration and minimize immune rejection. In this study, we present the first direct transcriptomic and functional comparison of syngeneic adult human NSPC populations, including bona fide spinal cord NSPCs and iPSC-derived NSPCs regionalized to the spinal cord (iPSC-SC) and forebrain (iPSC-Br). RNA sequencing analysis revealed distinct transcriptomic profiles and functional disparities among NSPC types. iPSC-Br NSPCs exhibited a close resemblance to bona fide spinal cord NSPCs, characterized by enriched expression of neurogenesis, axon guidance, synaptic signaling, and voltage-gated calcium channel activity pathways. Conversely, iPSC-SC NSPCs displayed significant heterogeneity, suboptimal regional specification, and elevated expression of neural crest and immune response-associated genes. Functional assays corroborated the transcriptomic findings, demonstrating superior neurogenic potential in iPSC-Br NSPCs. Additionally, we assessed donor-specific influences on NSPC behavior by analyzing gene expression and differentiation outcomes across syngeneic populations from multiple individuals. Donor-specific factors significantly modulated transcriptomic profiles, with notable variability in the alignment of iPSC-derived NSPCs to bona fide spinal cord NSPCs. Enrichment of pathways related to neurogenesis, axon guidance, and synaptic signaling varied across donors, highlighting the impact of genetic and epigenetic individuality on NSPC behavior.

Lithium chloride (LiCl) is a widely used and extensively researched drug for the treatment of bipolar disorder (BD). As a result, LiCl has been the subject of research studying its toxicity, mode of action, and downstream cellular responses. LiCl has been shown to influence cell signalling and signalling transduction pathways through protein kinase C and glycogen synthase kinase-3 in mammalian cells. LiCl's significant downstream effects on the translational pathway necessitate further investigation. In yeast, LiCl is found to lower the activity and alter the expression of PGM2, a gene encoding a sugar-metabolism phosphoglucomutase. When phosphoglucomutase activity is reduced in the presence of galactose, intermediates of galactose metabolism aggregate, causing cell sensitivity to LiCl. In this study, we identified that deleting the genes PEX11 and RIM20 increases yeast LiCl sensitivity. We further show that PEX11 and RIM20 regulate the expression of PGM2 mRNA at the translation level. The observed alteration of translation seems to target the structured 5′-untranslated region (5′-UTR) of the PGM2 mRNA.

Early warning scores for inpatient deterioration rely predominantly on contemporaneous vital signs and may not incorporate broader electronic health record (EHR) information. We developed and internally validated a multi-domain EHR machine-learning model using MIMIC-IV v3.1. A 6 hourly sliding-window framework generated 1,334,773 monitoring windows from 80,442 ICU-linked admissions. The composite outcome was ICU transfer, invasive mechanical ventilation, or in-hospital mortality within 24 h (prevalence 1.96%). XGBoost achieved an AUROC of 0.758 (patient-clustered 95% CI 0.753–0.763), compared with 0.568 for modified NEWS2, 0.549 for qSOFA, 0.539 for the Shock Index, and 0.533 for MEWS. Domain-level ablation identified vital signs as the dominant predictive domain, while multi-domain integration improved AUROC by 0.041 over a vitals-only model. At 90% sensitivity, the model generated 2.51 alerts per monitored patient-day with 2.8% positive predictive value. Collapsing contiguous alerts yielded 0.52 alert episodes per patient-day with 96.9% event-level sensitivity, although episode-level precision remained low at 5.1%. External validation and prospective operational evaluation are required before clinical use.

Spinal interneurons constitute the computational core of spinal circuitry, integrating excitatory and inhibitory inputs to generate the rhythmic patterns that drive locomotor, postural, and autonomic control. Their developmental logic, molecular diversity, and adaptive plasticity make them central determinants of functional recovery after spinal cord injury. Yet most regenerative strategies continue to emphasize cellular replacement rather than the restoration of the computational integrity of spinal networks. In this review, we reframe spinal repair as the reconstitution of circuit computation. We synthesize current insights into how embryonic patterning programs defined by SHH, Wnt, and BMP gradients, refined by Notch and retinoic acid signaling, and consolidated by axon guidance cues, establish interneuron diversity, connectivity, and network symmetry that together encode the logic of motor coordination. Spinal cord injury disrupts this developmental logic, fragmenting excitatory and inhibitory balance and desynchronizing rhythmic modules, while residual circuits retain latent capacity for resynchronization through plasticity and neuromodulation. Building upon this developmental and computational continuum, we propose the Patient Specific Interneuron Precision Model (PIPM), a closed loop framework that links patient specific biological states including progenitor competence, morphogen sensitivity, and metabolic tone to circuit level computation and recovery potential. By bridging molecular, physiological, and clinical insights, the PIPM establishes a systems logic that unifies biological competence with circuit recovery, positioning interneuron computation as the conceptual foundation for precision spinal cord regeneration.