Search

The management of schizophrenia necessitates a comprehensive treatment paradigm that considers individual patient nuances and the efficacy of lurasidone in addressing schizophrenia symptoms, particularly at elevated dosages. Numerous randomized trials have affirmed the efficacy of lurasidone across various dimensions of schizophrenia, demonstrating marked enhancements in positive, negative and cognitive symptoms compared to a placebo. In addition, lurasidone exhibits potential in ameliorating agitation amongst acutely ill patients, showcasing greater efficacy at higher doses. However, despite the favourable outcomes observed with higher lurasidone doses, routine clinical practice often opts for lower doses, potentially limiting its maximal therapeutic impact. Furthermore, lurasidone also shows efficacy in reducing post-psychotic depression in dual psychosis. Moreover, practical insights into lurasidone usage encompass swift dose escalation within a 1–5-day span and recommended combination strategies with other medications such as benzodiazepines for insomnia or agitation, beta-blockers for akathisia, and antihistamines or antimuscarinic drugs for patients transitioning rapidly from antipsychotics with substantial antihistamine and/or anticholinergic effects. Finally, a series of clinical cases is presented, highlighting benefits of lurasidone in terms of cognitive function, functional recovery and other therapeutic aspects for the management of schizophrenia.

3D printing has gained a spot within the industry during the last decade due to the advantages it presents regarding conventional manufacturing technologies. Nevertheless, the high processing time and the material waste due to the use of printing supports are still some of the main challenges that have to be addressed. In this research work, a simple strategy to minimize the processing time and the material waste is carried out through a two-stage processing method. Here, a flat specimen is obtained using a vat photopolymerization 3D printer, presenting a low curing degree. Then, the specimen is bent and subsequent post-curing treatments are performed to increase the cross-link density, thus fixing the desired shape. Furthermore, carbon nanotubes were used as nanoreinforcement for increasing the mechanical properties and exploiting their Joule heating capabilities for the thermal post-curing treatment, being way less energy-consuming (around 1W) than using a conventional oven (around 750 W). The results obtained with a proof-of-concept evinced the suitability of the proposed two-stage processing method to enhance the efficiency and sustainability of the 3D printing process. The printing time and the material waste were reduced by 94.3 % and 16.7 % on average, respectively, with regard to printing the part directly on its final desired shape, as well as showing a shape fixity ratio of around 98 %. Furthermore, an enhancement of the mechanical properties was obtained due to the reorientation of the printed layers during the two-stage processing.

Two different self-healing approaches are studied in this work to analyze the possible contribution of each of the self-healing mechanisms at different temperatures and the possible synergetic effects between them. Thermal and mechanical properties were differently affected by the addition of each of the thermoplastic polymers. This was caused by different phase separations induced during the curing reaction in terms of size and number of the thermoplastic phase domains dispersed within the epoxy matrix and due to the different amounts of thermoplastic polymer that remain solved in the matrix. When using the vitrimeric matrix, phase separation only occurred at the nanometer scale when utilizing poly(bisphenol-A-co-epichlorohydrin) (PBAE) as a thermoplastic agent or higher contents of polycaprolactone (PCL).Self-healing capabilities showed a strong dependence on the temperature used and the type of crack. Low temperatures allowed the thermoplastic phase to flow and fill partially the cracks with moderate levels of self-healing which were only available when phases were separated. Higher temperatures allowed dynamic bonds to induce material healing reaching very high efficiencies but, more importantly, a synergic effect was observed when material was removed from the cracks. In these cases, the flow of the thermoplastic phase filled better the crack and there was an enhanced cooperation between the two healing mechanisms. At higher self-healing temperatures, materials with nanometric size phase separation enabled greater self-healing efficiencies (above 90 %) due to the vitrimeric self-healing capability while the thermoplastic phase helped fill the gaps due to material removal.

Diglycidylether of vanillyl alcohol (DGEVA), in combination with mechanically recycled carbon fibers (RCFs), was used to make, via Radical-Induced Cationic Frontal Photopolymerization (RICFP), fully sustainable and bio-based conductive composites with good electrical conductivity and consequent Joule effect proprieties. Three different fiber lengths, using three different sieve sizes during the mechanical recycling process (0.2, 0.5, and 2.0 mm), were used in five different amounts (ranging from 1 to 25 phr). The samples were first characterized by dynamic mechanical thermal analysis (DMTA), followed byelectrical conductivity and Joule heating tests. More specifically, the mechanical properties of the composites increased when increasing fiber content. Furthermore, the composites obtained with the longest fibers showed the highest electrical conductivity, reaching a maximum of 11 S/m, due to their higher aspect ratio. In this context, the temperature reached by Joule effect was directly related to the electrical conductivity, and was able to reach an average and maximum temperatures of 80 °C and 120 °C, respectively, just by applying 6 V.

Graphene nanoplatelets (GNPs)/epoxy composites have been fabricated via gravity molding. The electrical and thermal properties of the composites have been studied with variable GNP type (C300, C500, and C750, whose surface areas are ~300, 500, and 750 m2/g, respectively), GNP loading (5, 10, 12, and 15 wt.%), and dispersion time via ultrasonication (0, 30, 60, and 120 min). By increasing the time of sonication of the GNP into the epoxy matrix, the electrical conductivity decreases, which is an effect of GNP fragmentation. The best results were observed with 10–12% loading and a higher surface area (C750), as they provide higher electrical conductivity, thereby preserving thermal conductivity. The influence of sonication over electrical conductivity was further analyzed via the study of the composite morphology by means of Raman spectroscopy and X-ray diffraction (XRD), providing information about the aspect ratio of GNPs. Moreover, electromagnetic shielding (EMI) has been studied up to 4 GHz. Composites with C750 and 120 min ultrasonication show the best performance in EMI shielding, influenced by their higher electrical conductivity.

Abstract Sarcomas constitute a heterogeneous group of rare and difficult-to-treat tumors that can affect people of all ages, representing one of the most common forms of cancer in childhood and adolescence. Little is known about the molecular entities involved in sarcomagenesis. Therefore, the identification of processes that lead to the development of the disease may uncover novel therapeutic opportunities. Here, we show that the MEK5/ERK5 signaling pathway plays a critical role in the pathogenesis of sarcomas. By developing a mouse model engineered to express a constitutively active form of MEK5, we demonstrate that the exclusive activation of the MEK5/ERK5 pathway can promote sarcomagenesis. Histopathological analyses identified these tumors as undifferentiated pleomorphic sarcomas. Bioinformatic studies revealed that sarcomas are the tumors in which ERK5 is most frequently amplified and overexpressed. Moreover, analysis of the impact of ERK5 protein expression on overall survival in patients diagnosed with different sarcoma types in our local hospital showed a 5-fold decrease in median survival in patients with elevated ERK5 expression compared with those with low expression. Pharmacological and genetic studies revealed that targeting the MEK5/ERK5 pathway drastically affects the proliferation of human sarcoma cells and tumor growth. Interestingly, sarcoma cells with knockout of ERK5 or MEK5 were unable to form tumors when engrafted into mice. Taken together, our results reveal a role of the MEK5/ERK5 pathway in sarcomagenesis and open a new scenario to be considered in the treatment of patients with sarcoma in which the ERK5 pathway is pathophysiologically involved.

The present study focuses on the multifunctional capabilities of carbon nanotube (CNT)-reinforced vitrimers. More specifically, the thermomechanical properties, the Joule effect heating capabilities, the electrical conductivity, the shape memory, and the chemical recycling capacity are explored as a function of the CNT content and the NH2/epoxy ratio. It is observed that the electrical conductivity increases with the CNT content due to a higher number of electrical pathways, while the effect of the NH2/epoxy ratio is not as prevalent. Moreover, the Tg of the material decreases when increasing the NH2/epoxy ratio due to the lower cross-link density, whereas the effect of the CNTs is more complex, in some cases promoting a steric hindrance. The results of Joule heating tests prove the suitability of the proposed materials for resistive heating, reaching average temperatures above 200 °C when applying 100 V for the most electrically conductive samples. Shape memory behavior shows an outstanding shape fixity ratio in every case (around 100%) and a higher shape recovery ratio (95% for the best-tested condition) when decreasing the NH2/epoxy ratio and increasing the CNT content, as both hinder the rearrangement of the dynamic bonds. Finally, the results of the recyclability tests show the ability to regain the nanoreinforcement for their further use. Therefore, from a multifunctional analysis, it can be stated that the proposed materials present promising properties for a wide range of applications, such as Anti-icing and De-icing Systems (ADIS), Joule heating devices for comfort or thermotherapy, or self-deployable structures, among others.

The Structural Health Monitoring (SHM) capabilities of a well-studied self-healing epoxy resin based on disulfide bonds, through the addition of carbon nanotubes (CNTs), are studied. Since these materials demonstrated, in recent works, a high dependency of the dynamic hardener content on the repair performance, this study aimed to analyze the effect of the vitrimeric chemistry on the electromechanical properties by studying different 2-aminophenyl disulfide (2-AFD) hardener and CNT contents. The electrical conductivity increases with both the CNT and AFD contents, in general. Moreover, an excess of AFD close to the stoichiometric ratio with a low CNT content improved the tensile strength by 45%, while higher AFD contents promoted its detriment by 41% due to a reduced crosslinking density. However, no significant difference in the mechanical properties was observed at a higher CNT content, regardless of the AFD ratio. The developed materials demonstrate a robust electromechanical response at quasi-static conditions. The sensitivity significantly increases at higher AFD ratios, from 0.69 to 2.22 for the 0.2 wt.%. CNT system, which is advantageous due to the enhanced repair performance of these vitrimeric materials with a higher hardener content. These results reveal the potential use of self-healing vitrimers as integrated SHM systems capable of detecting damages and self-repairing autonomously.

Background and purpose: MAPKs are among the most relevant signalling pathways involved in coordinating cell responses to different stimuli. This group includes p38MAPKs, constituted by 4 different proteins with a high sequence homology: MAPK14 (p38α), MAPK11 (p38β), MAPK12 (p38γ) and MAPK13 (p38δ). Despite their high similarity, each member shows unique expression patterns and even exclusive functions. Thus, analysing protein-specific functions of MAPK members is necessary to unequivocally uncover the roles of this signalling pathway. Here, we investigate the possible role of MAPK11 in the cell response to ionizing radiation (IR). Materials and methods: We developed MAPK11/14 knockdown through shRNA and CRISPR interference gene perturbation approaches and analysed the downstream effects on cell responses to ionizing radiation in A549, HCT-116 and MCF-7 cancer cell lines. Specifically, we assessed IR toxicity by clonogenic assays; DNA damage response activity by immunocytochemistry; apoptosis and cell cycle by flow cytometry (Annexin V and propidium iodide, respectively); DNA repair by comet assay; and senescence induction by both X-Gal staining and gene expression of senescence-associated genes by RT-qPCR. Results: Our findings demonstrate a critical role of MAPK11 in the cellular response to IR by controlling the associated senescent phenotype, and without observable effects on DNA damage response, apoptosis, cell cycle or DNA damage repair. Conclusion: Our results highlight MAPK11 as a novel mediator of the cellular response to ionizing radiation through the control exerted onto IR-associated senescence.

The pursuit of efficient, profitable, and ecofriendly materials has defined solar cell research from its inception to today. Some materials, such as copper nitride (Cu3N), show great promise for promoting sustainable solar technologies. This study employed reactive radio-frequency magnetron sputtering using a pure nitrogen environment to fabricate quality Cu3N thin films to evaluate how both temperature and gas working pressure affect their solar absorption capabilities. Several characterization techniques, including X-ray diffraction (XRD), Rutherford backscattering spectrometry (RBS), Raman spectroscopy, scanning electron microscopy (SEM), nanoindentation, and photothermal deflection spectroscopy (PDS), were used to determine the main properties of the thin films. The results indicated that, at room temperature, it is possible to obtain a material that is close to stoichiometric Cu3N material (Cu/N ratio ≈ 3) with (100) preferred orientation, which was lost as the substrate temperature increases, demonstrating a clear influence of this parameter on the film structure attributed to nitrogen re-emission at higher temperatures. Raman microscopy confirmed the formation of Cu-N bonds within the 628–637 cm−1 range. In addition, the temperature and the working pressure significantly also influence the film hardness and the grain size, affecting the elastic modulus. Finally, the optical properties revealed suitable properties at lower temperatures, including bandgap values, refractive index, and Urbach energy. These findings underscore the potential of Cu3N thin films in solar energy due to their advantageous properties and resilience against defects. This research paves the way for future advancements in efficient and sustainable solar technologies.

Disulfide containing vitrimers are being widely studied to get renewable, reprocessable and self-healable resins. The most of them are based on thermally cured epoxy resin. Herein, new thermoset systems based on typical acrylate monomers with photo-curing were synthesized with self-healing capabilities by introducing monomers with disulfide bonds. These disulfide groups are able to exchange upon heating, leading to a renewal of the crosslinks across the damaged surfaces. Different ratios of associative reversible exchange covalent bonds have been studied. The samples were evaluated in terms of thermal and mechanical properties. It was found that the glass transition temperature (Tg) is lower than that corresponding to typical acrylate thermosets, but mechanical properties are better. Increases in hardness of 2.4 times and in elastic modulus of 1.7 times with respect to the reference networks were achieved.Finally, the self-healing properties of the disulfide acrylates were demonstrated by monitoring the repair of a scratch upon heating. A new experimental test for quantifying the self-healing efficiency has been optimized, following the recovery of the surface crack by perfilometry. The composition optimization allows us to achieve repair percentages of 95% in shorter times.

Diglycidylether of vanillyl alcohol (DGEVA), in combination with mechanically recycled carbon fibers (RCFs), was used to make, via Radical-Induced Cationic Frontal Photopolymerization (RICFP), fully sustainable and bio-based conductive composites with good electrical conductivity and consequent Joule effect proprieties. Three different fiber lengths, using three different sieve sizes during the mechanical recycling process (0.2, 0.5, and 2.0 mm), were used in five different amounts (ranging from 1 to 25 phr). The samples were first characterized by dynamic mechanical thermal analysis (DMTA), followed byelectrical conductivity and Joule heating tests. More specifically, the mechanical properties of the composites increased when increasing fiber content. Furthermore, the composites obtained with the longest fibers showed the highest electrical conductivity, reaching a maximum of 11 S/m, due to their higher aspect ratio. In this context, the temperature reached by Joule effect was directly related to the electrical conductivity, and was able to reach an average and maximum temperatures of 80 °C and 120 °C, respectively, just by applying 6 V. [ABSTRACT FROM AUTHOR]

Sequential dual-cured epoxy composites, based on off-stoichiometric thiol–epoxy mixtures catalysed by 1-methylimidazole, have been developed by adding carbon nanotubes (CNT). The epoxy curing process initially consists in two thermally activated curing stages: a first thiol–epoxy reaction and later homopolymerization at a higher temperature. This system presents easy shaping/conforming and shape memory properties through thermo-mechanical treatments. Addition of the electrical CNT network into the epoxy matrix allows electrical switching, which increases its performance and in-situ applicability.The obtained results confirmed that CNTs catalyse the homopolymerization epoxy reaction, hindering the sequential curing process, due to the π–π anchoring of imidazole catalyser over the CNTs surface, enhanced by donor–acceptor interaction.Non-doped off-stoichiometric resins present relatively high thermal strength, with a glass transition temperature in the range of 73–109 °C, and high stiffness, with a storage modulus close to 2–3 GPa. They can be easily conformed at low temperature, 60 °C, before their second curing stage, showing a high shaping efficiency (around 90%) and full fixing efficiency (>98%).Nanocomposites with 0.2% CNT present efficient Joule heating, triggering the shape memory at low voltage,

The use of polymer and polymer-based composites has increased over the last decades [...]

Over the last 30 years, the study of the cellular response to ionizing radiation (IR) has increased exponentially. Among the various signaling pathways affected by IR, p38 MAPK has been shown to be activated both in vitro and in vivo, with involvement in key processes triggered by IR-mediated genotoxic insult, such as the cell cycle, apoptosis or senescence. However, we do not yet have a definitive clue about the role of p38 MAPK in terms of radioresistance/sensitivity and its potential use to improve current radiotherapy. In this review, we summarize the current knowledge on this family of MAPKs in response to IR as well as in different aspects related to radiotherapy, such as their role in the control of REDOX, fibrosis, and in the radiosensitizing effect of several compounds.

Self-healing materials have attracted great interest in recent years. Particularly, the use of thermoset/thermoplastics blends has emerged as a good option with relatively low activation temperatures and potential infinite healing cycles. Nevertheless, a methodical study of healing conditions and evaluation is still required for further industrial development. The effect of activation temperature and crack morphology in polycaprolactone (PCL)/epoxy blends are explored. For this purpose, PCL content was varied (5, 10, and 15 wt %) with contents lower than critical composition. Therefore, the morphology of all studied blends is the epoxy matrix with a separated PCL phase. In this sense, an increase in PCL content leads to a reduction in the Tg, due to the partial PCL miscibility, and the presence of larger PCL domains. It was observed that a higher temperature (150 °C) and PCL content led to a more efficient self-healing process because of both the lower viscosity of the melted PCL at higher temperatures and the presence of larger PCL reservoirs when increasing the PCL content. Crack morphology influence was studied by inducing cracks with different tools: a custom crack machine with a cutting blade, a scalpel, and a pin. The results show that the recovery was better when the cracks were smaller and shallower, that is, with the pin. In addition, the healing efficiency by means of both parameters, crack volume and depth change, showed more similar results in slimmer cracks, due to a lower crack width-to-depth ratio.

The influence of the average surface area of different graphene nanoplatelets (GNP) on the thermo-electrical behaviour, associated with Joule heating, and the attenuation of electromagnetic signals of epoxy composites has been studied, analysing the effect of the morphology obtained as a function of the dispersion time by ultrasonication and the GNP content added. Gravity moulding was used as the first stage in the scaling-up, oriented to the industrial manufacture of multilayer coatings, observing a preferential self-orientation of nanoparticles and, in several conditions, a self-stratification too. The increase of sonication time during the GNP dispersion provides a decrease in the electrical conductivity, due to the GNP fragmentation. Instead, the thermal conductivity is enhanced due to the higher homogeneous distribution of GNPs into the epoxy matrix. Finally, the lower surface area of GNPs reduces the thermal and electrical conductivity due to a greater separation between nanosheets. Regarding the study of the attenuation of electromagnetic waves, it has been discovered that in the frequency range from 100 Hz to 20 MHz, this attenuation is independent of the direction of analysis, the type of graphene, the sonication time, and the state of dispersion of the nano-reinforcement in the matrix. Furthermore, it has also been observed that the conservation of the constant shielding values for the three types of GNPs are in a range of average frequencies between 0.3 and 3 MHz.

The repair performance of the so-called self-healing polymer systems has been extensively studied in recent works. However, the characterization methodology carried out to analyze the repair performance of these materials has not been widely discussed. Herein, a study of the influence of the characterization parameters on the self-healing capabilities of a 2-Aminophenyl disulfide (AFD)/epoxy system via convective heating is carried out. Results show a decrease in the self-healing efficiency proportional to the damage depth. Finally, increasing the healing temperature and time does not significantly affect the repair performance, obtaining similar self-healing efficiency values (>>95%) in all cases.

The present work studies the electrical and electrothermal properties of CNT/GNP-doped nanocomposites for optimizing their anti-icing and de-icing capabilities. Here, a comparison between 3D-printed circuits and coatings based on these materials is carried out. In this regard, the higher electrical conductivity that is achieved by the specimens when increasing the nanoparticle content and the higher cross-sectional area of the coatings with regard to the 3D-printed circuits induces a higher heat generated by the Joule’s effect. Moreover, the successful de-icing test performed by the specimen with the highest self-heating capability, evinces that the studied nanocomposites are suitable for de-icing purposes.