Introduction The impact of multi-domain preventive interventions on older adults, in particular on those with higher risk to develop Alzheimer's disease (AD), could be beneficial, as it may delay cognitive decline. However, the precise mechanism of such positive impact is not fully understood and may involve brain reserve and adaptability of brain functional connectivity (FC). Methods To determine the effect of multidomain interventions (involving physical activity, cognitive training, nutritional counseling alone or in combination with omega-3 fatty acid supplementation and vs. a placebo) on the brain, longitudinal FC changes were assessed after 36 months of intervention on 100 older adults (above 70 year-old) with subjective cognitive complaints. Results No global change in FC was detected after uni or multidomain preventive interventions. However, an effect of omega-3 fatty acid supplementation dependent on cognitive decline status was underlined for frontoparietal, salience, visual and sensorimotor networks FC. These findings were independent of the cortical thickness and vascular burden. Discussion These results emphasize the importance of patient stratification, based on risk factors, for preventive interventions.

Spinal cord injury (SCI) leads to persistent neurological deficits without available curative treatment. After SCI astrocytes within the lesion vicinity become reactive, these undergo major morphological, and molecular transformations. Previously, we reported that following SCI, over 10% of resident astrocytes surrounding the lesion spontaneously transdifferentiate towards a neuronal phenotype. Moreover, this conversion is associated with an increased expression of fibroblast growth factor receptor 4 (Fgfr4), a neural stem cell marker, in astrocytes. Here, we evaluate the therapeutic potential of gene therapy upon Fgfr4 over-expression in mature astrocytes following SCI in adult mice. We found that Fgfr4 over-expression in astrocytes immediately after SCI improves motor function recovery; however, it may display sexual dimorphism. Improved functional recovery is associated with a decrease in spinal cord lesion volume and reduced glial reactivity. Cell-specific transcriptomic profiling revealed concomitant downregulation of Notch signaling, and up-regulation of neurogenic pathways in converting astrocytes. Our findings suggest that gene therapy targeting Fgfr4 over-expression in astrocytes after injury is a feasible therapeutic approach to improve recovery following traumatism of the spinal cord. Moreover, we stress that a sex-dependent response to astrocytic modulation should be considered for the development of effective translational strategies in other neurological disorders.

Gold nanoparticles are widely used in sensing, notably in colorimetry-based methods, where a color change is associated to the Surface Plasmon Resonance peak shift due to a binding event or an environment modification in the vicinity of the nanoparticles. In this work, we explore the sensitivity of the Second Harmonic response from gold nanoparticles of two different diameters as this response stems principally from the nanoparticle surface at small sizes as opposed to the whole volume of the nanoparticle at larger sizes. The origin of this response is therefore different from that involved in the colorimetric response, the latter being of volume origin. Upon addition of Glycerol to an aqueous solution of nanoparticles, Surface Plasmon Resonance peak shifts are first observed but they cannot fully explain the Second Harmonic intensity changes recorded. Hence, in order to gain further insights into the origin of the changes observed in the experimental data, polarization-resolved Second Harmonic measurements are performed. A mechanism where first a modification of the first hyperpolarizability of the nanoparticles due to the presence of glycerol occurs followed by nanoparticle aggregation is then proposed. The potential alternative use of this nonlinear optical method of Second Harmonic scattering for sensing purposes is then discussed in light of a figure of merit proposed to describe the sensing sensitivity observed.

Biomechanical characterization of a fibrinogen–blood hydrogel for human dental pulp regeneration.

Spinal cord injury is a dramatic disease leading to severe motor, sensitive and autonomic impairments. After injury the axonal regeneration is partly inhibited by the glial scar, acting as a physical and chemical barrier. The scarring process involves microglia, astrocytes and extracellular matrix components, such as collagen, con- structing the fibrotic component of the scar. To investigate the role of collagen, we used a multimodal label-free imaging approach combining multiphoton and atomic force microscopy. The second harmonic generation signal exhibited by fibrillar collagen enabled to specifically monitor it as a biomarker of the lesion. An increase in collagen density and the formation of more tortuous fibers over time after injury are observed. Nano-mechanical investigations revealed a noticeable hardening of the injured area, correlated with collagen fibers' formation. These observations indicate the concomitance of important structural and mechanical modifications during the fibrotic scar evolution.

Random granular media may exhibit characteristics more often related to ordered media. In the present work, this feature is observed in the polarized Second Harmonic Generation (SHG) response from reduced iron-doped lithium niobate (LN:Fe) powders, an effect that is not expected due to multiple scattering. Besides, this subsisting order property of the powders can be further controlled using magnetic induction to tailor the SHG response. The samples where characterized employing X-Ray Diffraction (XRD) and confocal Raman Spectroscopy. Their SHG response both in the absence and the presence of an external static magnetic field was then studied as the fundamental beam focus was translated from air into the powder. The SHG intensity polarization state was then studied as a function of the linear polarization of the fundamental beam for different fundamental beam focus depths. These results demonstrate that the SHG properties from LN:Fe powders can be modified through post-thermal treatment in a reducing atmosphere in view of photonic applications.

Spinal cord injury (SCI) is a dramatic disease leading to severe motor, sensitive and autonomic impairments. After the injury, the axonal regeneration is partly inhibited by the glial scar, acting as a physical and chemical barrier[1]. The scarring process involves microglia, astrocytes, and extracellular matrix components, such as collagen, composing the fibrotic part of the scar[2]. To investigate the role of collagen and microglia, we used a multimodal label-free imaging approach combining multiphoton and atomic force microscopies. The second harmonic generation signal exhibited by fibrillar collagen-I enables specifically monitoring it as a biomarker of the lesion. An increase in collagen density and the formation of more curved fibers over time after SCI are observed. Whereas 2-photon excitation microscopy (2PEF) showed the appearance and activation of microglia over millimeters in length near the injured area. Nanomechanical investigations revealed a noticeable hardening of the injured area, correlated with collagen fibers’ development. Additionally, we observed that inhibition of microglial proliferation by oral administration of GW2580 decreased the collagen density at the injured area. These observations indicate the concomitance of relevant structural and mechanical modifications during the fibrotic scar evolution.