Adoptive cell therapy has been revolutionized by chimeric antigen receptor (CAR)-based immunotherapy, but its applications are still mainly limited to T and natural killer (NK) cells. The FDA-approved seven CAR-T products in less than ten years, demonstrating the high capacity of this approach. However, given the limitations of CAR-T cell therapy, such as low tumor infiltration and clinical efficacy in solid tumors, there has been significant interest in recent years to engineer other immune cell types, including neutrophils, with CARs because they provide special advantages for cancer therapy, such as rapid infiltration into tumor sites, strong cytotoxic functions, and the ability to modify the tumor microenvironment (TME). However, the main barriers to the practical translation of CAR-neutrophils are their short lifespan, restricted ex vivo proliferation, and inherent resistance to genetic alterations, which calls for the availability of an infinite source for the ongoing supply of CAR-neutrophil therapy. These obstacles may be overcome by developments in induced pluripotent stem cell (iPSC) technology, which offers a consistent, renewable, and genetically changeable source of CAR-neutrophils (CAR-Neuts). The goal of this study is to present a comprehensive analysis of the state, gaps, and potential future directions of this recently developed topic.
Soil salinity significantly limits wheat productivity by impairing key processes such as photosynthesis, ion homeostasis, and antioxidant defense mechanisms. This study evaluated the effectiveness of foliar-applied chitosan selenium nanoparticles in improving wheat performance under saline conditions, using two contrasting cultivars: the salt-tolerant LU 26 S and the salt-sensitive NIAB 6. Plants were treated with different concentrations of chitosan selenium nanoparticles (10, 20, 30, and 40 mg L− 1). The optimal dosage was found to be 20 mg L− 1 for LU 26 S and 30 mg L− 1 for NIAB 6. In LU 26 S, 20 mg L− 1 increased grain yield per pot from 25.99 g to 29.10 g, while in NIAB 6, 30 mg L− 1 increased the yield from 20.67 g to 25.10 g. Foliar application enhanced several physiological parameters, including canopy persistence, biomass accumulation, and the remobilization of dry matter to the grains. In LU 26 S, 20 mg L− 1 increased transpiration rate by 35.60
The hippocampus, essential for learning, memory, and affective regulation, is increasingly recognized as vulnerable to systemic and remote insults. Spinal cord injury (SCI), traditionally viewed as a motor-sensory disorder, can trigger widespread neurobiological changes that extend beyond the lesion site and affect distant brain regions, particularly the hippocampus. SCI-induced systemic inflammation, oxidative stress, HPA axis dysregulation, autonomic dysfunction, chronic pain, and disrupted neuroimmune signaling collectively contribute to hippocampal pathology. Preclinical studies reveal a biphasic glial response characterized by early astrocytic and microglial activation followed by chronic pro-inflammatory polarization, sustained cytokine release, and loss of inhibitory checkpoints. Convergent mechanisms, including ER stress, chemokine signaling, cell-cycle re-entry, and α-synuclein accumulation, exacerbate neuronal loss and impair adult neurogenesis. Structural and functional consequences include persistent silent glutamatergic synapses enriched in NR2B-containing NMDA receptors, dendritic atrophy, mitochondrial dysfunction, and reductions in theta and gamma oscillations, all of which are associated with impaired synaptic plasticity and apoptosis. Behaviorally, experimental models consistently demonstrate spatial and recognition memory deficits, together with depression- and anxiety-like phenotypes. Translation to humans remains variable. While structural MRI studies often fail to demonstrate overt hippocampal atrophy, proton MR spectroscopy has revealed reduced hippocampal Glx levels associated with impaired memory performance. Together, these findings position SCI-induced hippocampal dysfunction as a multidimensional process involving neuroinflammation, oxidative stress, impaired neurogenesis, synaptic remodeling, and network disruption. These alterations may substantially contribute to the cognitive, emotional, and memory-related sequelae observed after SCI and identify the hippocampus as an important but often overlooked therapeutic target.
Small extracellular vesicles (sEVs) have rapidly emerged as versatile mediators of intercellular communication with significant potential to transform the diagnosis and treatment of neurodegenerative diseases (NDDs). Increasing evidence shows that sEVs not only participate in the propagation of pathogenic proteins but also serve as accessible, CNS-informative carriers of molecular signatures that reflect neuronal, glial, and systemic disease processes. This dual role positions sEVs at the intersection of biomarker discovery and therapeutic innovation. In the diagnostic domain, advances in immunoaffinity capture, single-vesicle analysis, and multi-omics profiling have enabled increasingly precise characterization of neuron-, astrocyte-, and microglia-derived sEVs, revealing candidate markers for Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and related disorders. However, translation remains limited by methodological heterogeneity, a lack of large-scale validation, and the need for standardized pre-analytical and analytical pipelines aligned with the ISEV/MISEV guidelines. On the therapeutic front, native and engineered sEVs, particularly those derived from mesenchymal and neural stem cells, demonstrate promising neuroprotective effects, including the modulation of neuroinflammation; the enhancement of synaptic resilience; and the delivery of antioxidant, anti-amyloid, or gene-modifying cargo across the blood-brain barrier. Scalable GMP manufacturing, cargo-loading strategies, targeting specificity, and long-term safety remain key challenges for clinical translation. This narrative review synthesizes current advances in sEV-based biomarkers and therapeutics, outlines technological and regulatory barriers, and proposes a translational roadmap spanning mechanistic discovery, platform standardization, and integration into precision-medicine frameworks. Collectively, emerging data position sEVs as powerful tools capable of reshaping the diagnostic and therapeutic landscape of NDDs, provided that coordinated multidisciplinary efforts address the remaining gaps in validation, scalability, and regulatory readiness.
Cousinia (Asteraceae: Cardueae) represents one of the most species-rich genera within the Irano-Turanian floristic region, yet interspecific relationships remain incompletely resolved. Here, nine chloroplast genomes from species endemic to the Pamir-Alay mountain system were newly sequenced and analyzed in combination with previously published complete chloroplast (cp) genome sequences and nuclear ribosomal DNA (nrDNA) data. The assembled cp genomes were highly uniform in size (approximately 152 kb), displayed the quadripartite organization of angiosperm chloroplasts, and possessed a GC content of 37.7%. Gene composition was largely conserved, with 131 annotated genes identified in most taxa. Examination of synonymous codon usage across 16 cp genomes revealed a consistent bias toward A/T-ending codons. Sliding-window analysis demonstrated generally low nucleotide diversity (Pi = 0-0.00918), although several divergence hotspots were detected, primarily within the large and small single-copy regions. Eleven categories of simple sequence repeats were identified, with A/T-rich mononucleotide motifs predominating. Phylogenetic reconstruction based on cp genomes data did not consistently recover morphologically defined sections as monophyletic, whereas the nrDNA dataset provided improved resolution of sectional delimitations. Comparative analysis of anther appendage morphology recognized nine structural groups and showed partial congruence with molecular evidence. Together, these findings highlight incongruence between chloroplast and nuclear signals and indicate that certain infrageneric classifications within Cousinia warrant re-evaluation.
