Biology subjects

Ridolfo, A.

Publications and source records attributed to Ridolfo, A..

4 recordsLinked to original sources

bioRxiv2026

Individual-level metabolic connectivity captures cortical morphology and their coupling strengthens with age

PurposeCerebral glucose metabolism and cortical morphology are known to undergo significant changes across the lifespan, yet their network-level coordination remains poorly understood. This study aimed to investigate whether individual-level metabolic connectivity (MC) reflects underlying inter-areal morphometric similarity, and to determine how this metabolic-morphometric coupling evolves across the adult lifespan. MethodsDynamic [18F]FDG-PET and structural MRI data were acquired from 67 healthy adults (age range: 38-86 years). Individual MC networks were estimated based on the similarity between regional time-activity curves. Corresponding structural similarity networks were generated using the morphometric inverse divergence (MIND) framework, which integrates multiple vertex-wise features of cortical morphology. The correspondence between metabolic and structural networks was quantified at both global and local scales using Spearman correlations. General linear models were employed to assess age-related effects on MC-MIND similarity. ResultsMC demonstrated a robust positive association with cortical morphometric similarity ({rho} = 0.32, p < 0.0001), an association that persisted after distance correction and was replicated at the individual level. Regional coupling followed a topographic gradient, peaking in heteromodal association cortices and reaching its minimum in paralimbic areas. Crucially, morphology-metabolism alignment systematically strengthened with age at the global level ({beta} = 0.59, p < 0.001). Local age-related increases were spatially heterogeneous, predominantly affecting visual, dorsal parietal, and premotor cortices alongside adjacent multimodal regions. ConclusionIndividual-level MC captures the morphometric organisation of the brain. The age-related increase in morphology-metabolism coupling indicates that metabolic coordination becomes progressively more aligned with cortical architecture, consistent with reduced neuroenergetic flexibility in the ageing brain.

neuroscience↗

bioRxiv2026

Comparative Effects of Hypoxic vs. Normoxic Mesenchymal Stem Cell-Derived Extracellular Vesicles on Tissue Repair Following Volumetric Muscle Loss (VML)

Volumetric muscle loss (VML) is an irreversible muscle injury that results in chronic functional impairment. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) can facilitate tissue repair through immunomodulatory, angiogenic, and anti-fibrotic effects. However, their low yield and poor on-site retention limit their therapeutic efficacy. Hypoxia can boost MSC metabolism, proliferation, and EV production. Hypoxic (3% O2) preconditioning of MSCs increased the yield of EVs (30-300 nm) by 1.5-fold but decreased the expression of characteristic EV markers (i.e., CD81, ICAM, and FLOT1). Fibrin hydrogels promote skeletal muscle regeneration and can sequester EVs via integrins or electrostatic interactions. We hypothesized that encapsulating EVs in fibrin hydrogels would further enhance regeneration and prolong the retention of EVs at the VML injury site. VML was created by removing [~]20% of the gastrocnemius-soleus muscles mass in mice using a 3 mm biopsy punch. EVs (4.48x1010 particles/mL) derived from MSCs cultured under hypoxic (Hypo-EV) or normoxic (Norm-EV) conditions were encapsulated within fibrin hydrogels and implanted at the VML injury site. Fibrin hydrogels containing PBS (PFG) were used as controls. On day 14 post-injury, Norm-EV treatment resulted in increased muscle mass, angiogenesis, and myofiber regeneration relative to the Hypo-EV group. Both the Norm-EV and Hypo-EV treatment groups reduced macrophage infiltration at the injury site compared to the PFG. These findings highlight that while both Norm-EV and Hypo-EV exhibit immunomodulatory effects, they differ in their regenerative potential. We speculate that hypoxic conditions could have caused MSCs to prioritize survival over repair-promoting activities, thereby producing EVs with less pro-regenerative signals. The increased quantity of EVs in response to hypoxia doesnt compensate for their diminished regenerative potential, highlighting the importance of quality over quantity when considering EVs for therapeutic applications. Graphical AbstractJain et al., Comparative Effects of Hypoxic vs. Normoxic Mesenchymal Stem Cell-Derived Extracellular Vesicles on Tissue Repair Following Volumetric Muscle Loss (VML) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=186 SRC="FIGDIR/small/697216v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@79a1feorg.highwire.dtl.DTLVardef@17a5f41org.highwire.dtl.DTLVardef@103c2e8org.highwire.dtl.DTLVardef@1f13e13_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

BIOSPONGES EMBEDDED WITH GDNF ENHANCE NEUROMUSCULAR RECOVERY FOLLOWING VOLUMETRIC MUSCLE LOSS

Skeletal muscle cannot regenerate after volumetric muscle loss (VML), a traumatic injury defined as the loss of > 20% of a muscles mass. VML directly reduces the number of myofibers and causes axonal degeneration of nerves, resulting in reduced muscle function and impaired neuromuscular junctions (NMJs). Biosponge (BSG) scaffolds, composed of gelatin, collagen, and laminin-111, have been shown to improve muscle mass, cross-sectional area, and myofiber number following VML. However, improvements in NMJ quantity were not observed. Glial cell line-derived neurotrophic factor (GDNF) is a growth factor that enhances motor unit survival and neurite outgrowth. In this work, BSG scaffolds were electrostatically coupled with GDNF via gelatin nanoparticles (GNPs) to support myofiber regeneration and preserve NMJs post-VML in a rodent model. In vitro determination of release kinetics revealed an initial burst release of surface bound GDNF with almost an equivalent amount of electrostatically bound GDNF retained within the BSG post 1 week of incubation at 37{degrees}C in phosphate buffered saline (PBS). To create the VML injury in male Lewis rats (10-12 weeks old), [~]20% of the muscle mass was removed from the tibialis anterior (TA) muscle of both hindlimbs. Relative to BSG+GNP alone, treatment with BSG+GNP+GDNF showed a significant increase ([~]25%) in peak isometric torque at 6 weeks post-injury. Qualitative and quantitative histological analysis of NMJs revealed an enhanced overlap between pre- and post-synaptic structures in the BSG+GNP+GDNF group. Additionally, the incorporation of GDNF slowed BSG remodeling and degradation. Overall, these results suggest that the BSG-mediated delivery of GDNF is an effective strategy for mitigating NMJ loss and enhancing muscle recovery following VML. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=96 SRC="FIGDIR/small/693478v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1719d84org.highwire.dtl.DTLVardef@1c6bceorg.highwire.dtl.DTLVardef@1e9a9a5org.highwire.dtl.DTLVardef@180ad57_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical Abstract Tadiwala et al., 2025 Biosponges embedded with GDNF promote neuromuscular recovery following volumetric muscle loss.

bioengineering↗

bioRxiv2025

Glucose Metabolism echoes Long-Range Temporal Correlations in the Human Brain

Intrinsic brain activity is characterized by pervasive long-range temporal correlations. While these scale-invariant dynamics are a fundamental hallmark of brain function, their implications for individual-level metabolic regulation remain poorly understood. Here, we address this gap by integrating resting-state functional Magnetic Resonance Imaging (fMRI) and dynamic [18F]FDG Positron Emission Tomography (PET) data acquired from the same cohort of participants. We uncover a systematic relationship between long-range temporal correlations, quantified via the Hurst exponent, and glucose metabolism. Our findings reveal that persistent temporal dependencies impose a measurable metabolic cost, with brains exhibiting higher long-range temporal correlations incurring greater energetic demands. Beyond glucose metabolism, we also show that these dynamics are likely supported by continuous biosynthetic processes, such as protein synthesis, which are critical for neural circuit maintenance and remodeling. Overall, our results suggest that a significant fraction of the brains so-called "Dark Energy" is actively spent to power spontaneous long-range temporal correlations.

neuroscience↗