Genetic factors and symptom dimensions associated with antidepressant treatment outcomes: clues for new potential therapeutic targets?

Treatment response and resistance in major depressive disorder (MDD) show a significant genetic component, but previous studies had limited power also due to MDD heterogeneity. This literature review focuses on the genetic factors associated with treatment outcomes in MDD, exploring their overlap with those associated with clinically relevant symptom dimensions. We searched PubMed for: (1) genome-wide association studies (GWASs) or whole exome sequencing studies (WESs) that investigated efficacy outcomes in MDD; (2) studies examining the association between MDD treatment outcomes and specific depressive symptom dimensions; and (3) GWASs of the identified symptom dimensions. We identified 13 GWASs and one WES of treatment outcomes in MDD, reporting several significant loci, genes, and gene sets involved in gene expression, immune system regulation, synaptic transmission and plasticity, neurogenesis and differentiation. Nine symptom dimensions were associated with poor treatment outcomes and studied by previous GWASs (anxiety, neuroticism, anhedonia, cognitive functioning, melancholia, suicide attempt, psychosis, sleep, sociability). Four genes were associated with both treatment outcomes and these symptom dimensions: CGREF1 (anxiety); MCHR1 (neuroticism); FTO and NRXN3 (sleep). Other overlapping signals were found when considering genes suggestively associated with treatment outcomes. Genetic studies of treatment outcomes showed convergence at the level of biological processes, despite no replication at gene or variant level. The genetic signals overlapping with symptom dimensions of interest may point to shared biological mechanisms and potential targets for new treatments tailored to the individual patient's clinical profile.

Reinforcing Efficiency of Recycled Carbon Fiber PLA Filament Suitable for Additive Manufacturing.

The use of 3D printing technology for manufacturing new products based on sustainable materials enables one to take advantage of secondary raw materials derived from recycling. This work investigates the structural performances of 3D printing composite filaments based on polylactic acid (PLA), as a matrix, reinforced by recycled carbon fiber (rCF). Carbon fibers were recovered from industrial scraps by a patented thermal process and used to produce thermoplastic composite filaments for additive manufacturing without any additional treatment and additives. The influence of the recovered carbon fiber (rCF) content on the thermal properties, mechanical properties and microstructure of the composites was studied in the range of 3-20 wt%. The recorded TGA curves exhibited a one-stage weight loss within the temperature range 290-380 °C for all samples and the residual rCF content was in good agreement with the theoretical fiber loading. The Young modulus of the extruded filaments strongly increased below a critical content (5 wt%), while at higher content the improvement was reduced. An increase in the storage modulus of 54% compared to neat PLA 3D printed sample resulted in a printed specimen with a higher rCF content. SEM images highlighted a strong rCF prevailing alignment in the direction of the extrusion flow, creating almost unidirectional reinforcement inside the filament. These findings suggest that homogeneous composite filaments reinforced with well-dispersed recycled CF without additional chemical modification and additives are suitable materials for additive manufacturing. The effect of rCF topological distribution within the material on the mechanical performances has been discussed, highlighting that the isolated fibers could efficiently transfer loads with respect to the percolated 3D network and have been correlated with the microstructure.

Thermally Mendable Self-Healing Epoxy Coating for Corrosion Protection in Marine Environments.

Polymeric coatings represent a well-established protection system that provides a barrier between a metallic substrate and the environment. The development of a smart organic coating for the protection of metallic structures in marine and offshore applications is a challenge. In the present study, we investigated the use of self-healing epoxy as an organic coating suitable for metallic substrates. The self-healing epoxy was obtained by mixing Diels-Alder (D-A) adducts with a commercial diglycidyl ether of bisphenol-A (DGEBA) monomer. The resin recovery feature was assessed through morphological observation, spectroscopic analysis, and mechanical and nanoindentation tests. Barrier properties and anti-corrosion performance were evaluated through electrochemical impedance spectroscopy (EIS). The film on a metallic substrate was scratched and subsequently repaired using proper thermal treatment. The morphological and structural analysis confirmed that the coating restored its pristine properties. In the EIS analysis, the repaired coating exhibited diffusive properties similar to the pristine material, with a diffusivity coefficient of 1.6 × 10-6 cm2/s (undamaged system 3.1 × 10-6 cm2/s), confirming the restoration of the polymeric structure. These results reveal that a good morphological and mechanical recovery was achieved, suggesting very promising applications in the field of corrosion-resistant protective coatings and adhesives.

An Investigation of the Healing Efficiency of Epoxy Vitrimer Composites Based on Zn2+ Catalyst.

The need to recycle carbon-fibre-reinforced composite polymers (CFRP) has grown significantly to reduce the environmental impact generated by their production. To meet this need, thermoreversible epoxy matrices have been developed in recent years. This study investigates the performance of an epoxy vitrimer made by introducing a metal catalyst (Zn2+) and its carbon fibre composites, focusing on the healing capability of the system. The dynamic crosslinking networks endow vitrimers with interesting rheological behaviour; the capability of the formulated resin (AV-5) has been assessed by creep tests. The analysis showed increased molecular mobility above a topology freezing temperature (Tv). However, the reinforcement phase inhibits the flow capability, reducing the flow. The fracture behaviour of CFRP made with the vitrimeric resin has been investigated by Mode I and Mode II tests and compared with the conventional system. The repairability of the vitrimeric CFRP has been investigated by attempting to recover the delaminated samples, which yielded unsatisfactory results. Moreover, the healing efficiency of the modified epoxy composites has been assessed using the vitrimer as an adhesive layer. The joints were able to recover about 84% of the lap shear strength of the pristine system.

Influence of Catalyst Content and Epoxy/Carboxylate Ratio on Isothermal Creep of Epoxy Vitrimers.

In the present work, a commercial epoxy based on epoxy anhydride and tertiary amine was modified by a metallic catalyst (Zn2+) to induce vitrimeric behavior by promoting the transesterification reaction. The effect of two different epoxy/acid ratios (1 and 0.6) at two different zinc acetate amounts (Zn(Ac)2) on the thermomechanical and viscoelastic performances of the epoxy vitrimers were investigated. Creep experiments showed an increase in molecular mobility above the critical "Vitrimeric" temperature (Tv) of 170 °C proportionally to the amount of Zn(Ac)2. A procedure based on Burger's model was set up to investigate the effect of catalyst content on the vitrimer ability to flow as the effect of the dynamic exchange reaction. The analysis showed that in the case of a balanced epoxy/acid formulation, the amount of catalyst needed for promoting molecular mobility is 5%. This system showed a value of elastic modulus and dynamic viscosity at 170 °C of 9.50 MPa and 2.23 GPas, respectively. The material was easily thermoformed in compression molding, paving the way for the recyclability and weldability of the thermoset system.

Insights on Shear Transfer Efficiency in "Brick-and-Mortar" Composites Made of 2D Carbon Nanoparticles.

Achieving high mechanical performances in nanocomposites reinforced with lamellar fillers has been a great challenge in the last decade. Many efforts have been made to fabricate synthetic materials whose properties resemble those of the reinforcement. To achieve this, special architectures have been considered mimicking existing materials, such as nacre. However, achieving the desired performances is challenging since the mechanical response of the material is influenced by many factors, such as the filler content, the matrix molecular mobility and the compatibility between the two phases. Most importantly, the properties of a macroscopic bulk material strongly depend on the interaction at atomic levels and on their synergetic effect. In particular, the formation of highly-ordered brick-and-mortar structures depends on the interaction forces between the two phases. Consequently, poor mechanical performances of the material are associated with interface issues and low stress transfer from the matrix to the nanoparticles. Therefore, improvement of the interface at the chemical level enhances the mechanical response of the material. The purpose of this review is to give insight into the stress transfer mechanism in high filler content composites reinforced with 2D carbon nanoparticles and to describe the parameters that influence the efficiency of stress transfer and the strategies to improve it.

Effect of microneedles shape on skin penetration and transdermal drug administration.

Microneedle (MN) patches are highly efficient and versatile tools for transdermal drug administration, in particular for pain-free, self-medication and rapid local applications. Diffraction ultraviolet (UV) light lithography offers an advanced method in fabricating poly(ethylene glycol)-based MNs with different shapes, by changing both the UV-light exposure time and photomask design. The exposure time interval is limited at obtaining conical structures with aspect ratio < 1:3, otherwise MNs exhibit reduced fracture load and poor indentation ability, not suitable for practical application. Therefore, this work is focused on a systematic analysis of the MN's base shapes effects on the structural characteristics, skin penetration and drug delivery. Analyzing four different base shapes (circle, triangle, square and star), it has been found that the number of vertices in the polygon base heavily affects these properties. The star-like MNs reveal the most efficient skin penetration ability (equal to 40 % of -their length), due to the edges action on the skin during the perforation. Furthermore, the quantification of the drug delivered by the MNs through ex-vivo porcine skin shows that the amounts of small molecules released over 24 h by star-like MNs coated by local anesthetic (Lidocaine) and an anti-inflammatory (Diclofenac epolamine) drugs are 1.5× and 2× higher than the circular-MNs, respectively.