Shah, M. J. | bioRxiv Science

bioRxiv2026

Riboflavin-sensitized UVA collagen crosslinking produced a controllable, dose-dependent increase in the nanomechanical strength of ex vivo bovine dura mater

BackgroundDural defects, either from trauma, tumor resection, surgical approaches, genetics, or spontaneously represent a significant clinical challenge in neurosurgery. Given the established efficacy of riboflavin-sensitized ultraviolet-A (UVA) photo-crosslinking in ophthalmology, this study investigated its feasibility and dose-response characteristics as a novel strategy to biochemically augment the mechanical integrity and strength of ex-vivo bovine dura mater. MethodsForty bovine dura mater specimens were treated ex vivo using riboflavin concentrations of 2, 4, or 8 mM combined with UVA irradiation at 0.3 or 3 mW/cm{superscript 2}. PBS-treated specimens exposed to UVA served as controls. Atomic force microscopy nanoindentation was used to measure the local elastic modulus in matched regions before and after treatment, enabling paired assessment of treatment-induced mechanical changes while minimizing inter-sample variability. Post-treatment stiffness, fold-change from baseline, and riboflavin dose-response relationships were analyzed statistically. ResultsBaseline elastic moduli were equivalent across all groups (mean approximately 52 kPa, p=0.92). While UVA alone caused a modest approximately 2- to 3-fold stiffness increase, riboflavin-UVA treatment produced a dramatic, concentration-dependent effect. The highest treatment (8 mM RF, 3 mW/cm{superscript 2} UVA) increased the elastic modulus 150-fold, from approximately 53 kPa to approximately 8,000 kPa. Post-UV stiffness exhibited a strong linear relationship with riboflavin concentration (R{superscript 2} = 0.994), indicating a precisely titratable crosslinking effect. All treatment conditions were statistically distinguishable (p < 0.001). ConclusionRiboflavin-sensitized UVA crosslinking substantially increases the nanomechanical strength of ex vivo bovine dura mater in a controllable, dose-dependent manner. These findings establish a proof of concept for biochemical reinforcement of dural tissue that might be used clinically. As a next step evaluation using human dura, macroscopic biomechanical testing, penetration-depth analysis, and safety assessment is warranted.

bioengineering↗

bioRxiv2025

Iron-Associated Mesenchymal Plasticity and Tumor Invasion in Glioblastoma

Glioblastoma (GBM) recurrence is driven by tumor cells that infiltrate surrounding brain tissue and evade surgical and therapeutic eradication. Although dysregulated iron handling is a recognized feature of the necrotic and hemorrhagic GBM tumor core, its relationship to invasive tumor cell states remains incompletely defined. Here, we investigated how iron-associated microenvironments relate to transcriptional programs of invasion in human GBM. Using multi-regional single-nucleus RNA sequencing of human GBM specimens encompassing tumor core, invasive front, and infiltrated cortex, we found that malignant cells from the tumor core exhibit coordinated upregulation of iron uptake and storage pathways together with invasion-associated gene programs. At the single-cell level, iron metabolism and invasion signatures were strongly correlated, defining a distinct core-enriched malignant subpopulation with mesenchymal-like transcriptional identity, stress-adaptive features, and angiogenic signaling. These iron-high/invasion-high cells aligned with mesenchymal-and astrocyte-like GBM states and were associated with unfavorable patient survival. Despite elevated oxidative stress and ferroptosis-associated transcriptional pressure, this population concurrently expressed anti-apoptotic and anti-ferroptotic regulators, consistent with an iron-tolerant invasive state. To assess functional consequences of iron exposure, we modeled iron-rich conditions using non-cytotoxic particulate iron in patient-derived GBM cell lines and human organotypic cortical slice cultures. Iron exposure induced intracellular iron accumulation, oxidative stress responses, increased tumor cell motility in vitro, and enhanced invasion within intact human brain tissue. Collectively, these findings demonstrate that iron-rich tumor core niches are closely associated with mesenchymal plasticity and invasive behavior in GBM and support a role for iron-associated microenvironmental pressure in shaping invasive tumor cell states. Key PointsO_LITranscriptional profiling reveals that the GBM tumor core harbors malignant cells that strictly couple active iron metabolism with invasive programs. C_LIO_LIThis iron-accumulating, Mesenchymal-like subpopulation is distinctively characterized by angiogenesis and stress resistance. C_LIO_LIIron supplementation in vitro and human ex vivo models are sufficient to drive mesenchymal transition and significantly enhance tumor migration and tissue invasion. C_LI Importance of the StudyGlioblastoma (GBM) recurrence is driven by highly invasive tumor cells that evade resection and resist therapy. Yet the microenvironmental pressures that push GBM cells into an invasive, therapy-resistant state remain poorly defined. Although iron dysregulation has been implicated across cancers, its role as a microenvironmental determinant of GBM invasion has never been demonstrated in physiologically relevant human systems. By integrating multi-regional single-nucleus RNA sequencing with functional validation in patient-derived GBM lines and human organotypic cortical slice cultures, we uncover a core-enriched, iron-associated mesenchymal program that co-segregates with invasion, stress adaptation, and angiogenic signaling. We further show that physiologically relevant iron exposure is sufficient to induce mesenchymal transition, enhance motility, and accelerate tissue invasion within human cortical architecture. These findings position iron as a selective driver that links the hemorrhagic, necrotic GBM core to the emergence of invasive subpopulations that seed recurrence. The data identify iron handling and stress-response pathways as actionable therapeutic vulnerabilities, providing a foundation for strategies that target metabolic resilience and iron-dependent invasive states in GBM. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=157 SRC="FIGDIR/small/695920v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@141cc11org.highwire.dtl.DTLVardef@bcb055org.highwire.dtl.DTLVardef@1dcd332org.highwire.dtl.DTLVardef@ad7cad_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2021

Relationing of Labellum and Glossae Biomorphological characteristics of honeybee workers as breeding tool on honey collection potential of Apis mellifera L. honeybee colonies

This study focused on the correlation of honey collection Potential and the length and width of labellum and glossae in worker honey bees (Apis mellifera Ligustica). Sixty honeybee A. mellifera L. colonies were selected, among these 60 colonies, 3 worker bees were sampled from each colony total numbers of samples collected were 180 adult worker foraging bees. Fifteen colonies for each group were used to check the correlation of honey production with length of labellum, width of labellum, length of glossae and the width of glossae respectively. These worker bees were bought to the laboratory frozen, boiled, dissected and mounted on the slides. Measurements of the labellum length, labellum width, glossae length and glossae width were taken by the stereomicroscope with ocular micrometer at 0.8X magnification. Correlation values for the honey collectionand length and width of labellum and glossae were high and positive. These Results support the perception that worker bees with larger labellum and glossae have more ability for honey collection Potential. It is concluded that Biomorphological characters of labellum and glossae are significantly correlated with the honeycollection Potential in A. mellifera L.

zoology↗