Cross-Modal Imaging Reveals Nanoparticle Uptake Dynamics in Hematopoietic Bone Marrow during Inflammation.

Nanoparticles have been employed to elucidate the innate immune cell biology and trace cells accumulating at inflammation sites. Inflammation prompts innate immune cells, the initial responders, to undergo rapid turnover and replenishment within the hematopoietic bone marrow. Yet, we currently lack a precise understanding of how inflammation affects cellular nanoparticle uptake at the level of progenitors of innate immune cells in the hematopoietic marrow. To bridge this gap, we aimed to develop imaging tools to explore the uptake dynamics of fluorescently labeled cross-linked iron oxide nanoparticles in the bone marrow niche under varying degrees of inflammation. The inflammatory models included mice that received intramuscular lipopolysaccharide injections to induce moderate inflammation and streptozotocin-induced diabetic mice with additional intramuscular lipopolysaccharide injections to intensify inflammation. In vivo magnetic resonance imaging (MRI) and fluorescence imaging revealed an elevated level of nanoparticle uptake at the bone marrow as the levels of inflammation increased. The heightened uptake of nanoparticles within the inflamed marrow was attributed to enhanced permeability and retention with increased nanoparticle intake by hematopoietic progenitor cells. Moreover, intravital microscopy showed increased colocalization of nanoparticles within slowly patrolling monocytes in these inflamed hematopoietic marrow niches. Our discoveries unveil a previously unknown role of the inflamed hematopoietic marrow in enhanced storage and rapid deployment of nanoparticles, which can specifically target innate immune cells at their production site during inflammation. These insights underscore the critical function of the hematopoietic bone marrow in distributing iron nanoparticles to innate immune cells during inflammation. Our findings offer diagnostic and prognostic value, identifying the hematopoietic bone marrow as an imaging biomarker for early detection in inflammation imaging, advancing personalized clinical care.

Language First, Cognition Later: Different Trajectories of Subcomponents of the Future-Reading Network in Processing Narratives from Kindergarten to Adolescence.

Narrative comprehension is a linguistic ability that emerges early in life and has a critical role in language development, reading acquisition, and comprehension. According to the Simple View of Reading model, reading is acquired through word decoding and linguistic comprehension. Here, within and between networks, functional connectivity in several brain networks supporting both language and reading abilities was examined from prereading to proficient reading age in 32 healthy children, ages 5-18 years, scanned annually while listening to stories over 12 years. Functional connectivity changes within and between the networks were assessed and compared between the years using hierarchical linear regression and were related to reading abilities. At prereading age, the networks related to basic language processing accounted for 32.5% of the variation of reading ability at reading age (at 12-14 years) (R2 = 0.325, p = 0.05). At age 17, more complex cognitive networks were involved and accounted for 97.4% of the variation in reading ability (R2 = 0.974, p = 0.022). Overall, networks composing the future-reading network are highly involved in processing narratives along development; however, networks related to semantic, phonological, and syntactic processing predict reading ability earlier in life, and more complex networks predict reading proficiency later in life.