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This review offers a critical survey of the published studies concerning nano-enhanced phase change materials to be applied in energy harvesting and conversion. Also, the main thermophysical characteristics of nano-enhanced phase change materials are discussed in detail. In addition, we carried out an analysis of the thermophysical properties of these types of materials as well as of some specific characteristics like the phase change duration and the phase change temperature. Moreover, the fundamental improving techniques for the phase change materials for solar thermal applications are described in detail, including the use of nano-enhanced phase change materials, foam skeleton-reinforced phase change materials, phase change materials with extended surfaces, and the inclusion of high-thermal-conductivity nanoparticles in nano-enhanced phase change materials, among others. Those improvement techniques can increase the thermal conductivity of the systems by up to 100%. Furthermore, it is also reported that the exploration of phase change materials enhances the overall efficiency of solar thermal energy storage systems and photovoltaic-nano-enhanced phase change materials systems. Finally, the main limitations and guidelines for future research in the field of nano-enhanced phase change materials are summarized.
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Three-dimensional (3D) in vitro models, such as organ-on-a-chip platforms, are an emerging and effective technology that allows the replication of the function of tissues and organs, bridging the gap amid the conventional models based on planar cell cultures or animals and the complex human system. Hence, they have been increasingly used for biomedical research, such as drug discovery and personalized healthcare. A promising strategy for their fabrication is 3D printing, a layer-by-layer fabrication process that allows the construction of complex 3D structures. In contrast, 3D bioprinting, an evolving biofabrication method, focuses on the accurate deposition of hydrogel bioinks loaded with cells to construct tissue-engineered structures. The purpose of the present work is to conduct a systematic review (SR) of the published literature, according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, providing a source of information on the evolution of organ-on-a-chip platforms obtained resorting to 3D printing and bioprinting techniques. In the literature search, PubMed, Scopus, and ScienceDirect databases were used, and two authors independently performed the search, study selection, and data extraction. The goal of this SR is to highlight the importance and advantages of using 3D printing techniques in obtaining organ-on-a-chip platforms, and also to identify potential gaps and future perspectives in this research field. Additionally, challenges in integrating sensors in organs-on-chip platforms are briefly investigated and discussed.
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Bioimpressão , Dispositivos Lab-On-A-Chip , Animais , Humanos , Hidrogéis , Impressão Tridimensional , Engenharia TecidualRESUMO
Heat shock protein 90 (HSP90) stabilizes many client proteins, including the BCR-ABL1 oncoprotein. BCR-ABL1 is the hallmark of chronic myeloid leukemia (CML) in which treatment-free remission (TFR) is limited, with clinical and economic consequences. Thus, there is an urgent need for novel therapeutics that synergize with current treatment approaches. Several inhibitors targeting the N-terminal domain of HSP90 are under investigation, but side effects such as induction of the heat shock response (HSR) and toxicity have so far precluded their US Food and Drug Administration approval. We have developed a novel inhibitor (aminoxyrone [AX]) of HSP90 function by targeting HSP90 dimerization via the C-terminal domain. This was achieved by structure-based molecular design, chemical synthesis, and functional preclinical in vitro and in vivo validation using CML cell lines and patient-derived CML cells. AX is a promising potential candidate that induces apoptosis in the leukemic stem cell fraction (CD34+CD38-) as well as the leukemic bulk (CD34+CD38+) of primary CML and in tyrosine kinase inhibitor (TKI)-resistant cells. Furthermore, BCR-ABL1 oncoprotein and related pro-oncogenic cellular responses are downregulated, and targeting the HSP90 C terminus by AX does not induce the HSR in vitro and in vivo. We also probed the potential of AX in other therapy-refractory leukemias. Therefore, AX is the first peptidomimetic C-terminal HSP90 inhibitor with the potential to increase TFR in TKI-sensitive and refractory CML patients and also offers a novel therapeutic option for patients with other types of therapy-refractory leukemia because of its low toxicity profile and lack of HSR.
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Antineoplásicos/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/química , Resposta ao Choque Térmico/efeitos dos fármacos , Mesilato de Imatinib/farmacologia , Domínios e Motivos de Interação entre Proteínas , Inibidores de Proteínas Quinases/farmacologia , Multimerização Proteica , Animais , Antineoplásicos/química , Sítios de Ligação , Biomarcadores Tumorais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/química , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Mesilato de Imatinib/química , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Camundongos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/química , Multimerização Proteica/efeitos dos fármacos , Análise Espectral , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Ovarian cancer is the fifth leading cause of cancer deaths. Chemoresistance, particularly against platinum compounds, contributes to a poor prognosis. Histone deacetylase inhibitors (HDACi) and heat shock protein 90 inhibitors (HSP90i) are known to modulate pathways involved in chemoresistance. This study investigated the effects of HDACi (panobinostat, LMK235) and HSP90i (luminespib, HSP990) on the potency of cisplatin in ovarian cancer cell lines (A2780, CaOV3, OVCAR3 and cisplatin-resistant sub-clones). Preincubation with HDACi increased the cytotoxic potency of HSP90i, whereas preincubation with HSP90i had no effect. Preincubation with HSP90i or HDACi 48h prior to cisplatin enhanced the cisplatin potency significantly in all cell lines via apoptosis induction and affected the expression of apoptosis-relevant genes and proteins. For CaOV3CisR and A2780CisR, a preincubation with HDACi for 48-72 h led to complete reversal of cisplatin resistance. Furthermore, permanent presence of HDACi in sub-cytotoxic concentrations prevented the development of cisplatin resistance in A2780. However, triple combinations of HDACi, HSP90i and cisplatin were not superior to dual combinations. Overall, priming with HDACi sensitizes ovarian cancer cells to treatment with HSP90i or cisplatin and has an influence on the development of cisplatin resistance, both of which may contribute to an improved ovarian cancer treatment.
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Inibidores de Histona Desacetilases/farmacologia , Neoplasias Ovarianas/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Carcinoma Epitelial do Ovário/metabolismo , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Inibidores de Histona Desacetilases/metabolismo , Humanos , Isoxazóis/farmacologia , Panobinostat/farmacologia , Piridonas/farmacologia , Pirimidinas/farmacologia , Resorcinóis/farmacologiaRESUMO
α-Aminoxy peptides are peptidomimetic foldamers with high proteolytic and conformational stability. To gain an improved synthetic access to α-aminoxy oligopeptides we used a straightforward combination of solution- and solid-phase-supported methods and obtained oligomers that showed a remarkable anticancer activity against a panel of cancer cell lines. We solved the first X-ray crystal structure of an α-aminoxy peptide with multiple turns around the helical axis. The crystal structure revealed a right-handed 28 -helical conformation with precisely two residues per turn and a helical pitch of 5.8â Å. By 2Dâ ROESY experiments, molecular dynamics simulations, and CD spectroscopy we were able to identify the 28 -helix as the predominant conformation in organic solvents. In aqueous solution, the α-aminoxy peptides exist in the 28 -helical conformation at acidic pH, but exhibit remarkable changes in the secondary structure with increasing pH. The most cytotoxic α-aminoxy peptides have an increased propensity to take up a 28 -helical conformation in the presence of a model membrane. This indicates a correlation between the 28 -helical conformation and the membranolytic activity observed in mode of action studies, thereby providing novel insights in the folding properties and the biological activity of α-aminoxy peptides.
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Oligopeptídeos/química , Oligopeptídeos/síntese química , Solventes/química , Modelos Moleculares , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Estrutura Secundária de ProteínaRESUMO
This overview intends to provide a comprehensive assessment of the novel fluids and the current techniques for surface modification for pool boiling enhancement. The surface modification at macro-, micro-, and nanoscales is assessed concerning the underlying fluid routing and capability to eliminate the incipient boiling hysteresis and ameliorate the pool boiling heat-transfer ability, particularly when employed together with self-rewetting fluids and nanofluids with enriched thermophysical properties. Considering the nanofluids, it is viable to take the profit of their high thermal conductivity and their specific heat simultaneously and to produce a film of deposited nanoparticles onto the heating surface, which possesses enhanced surface roughness and an increased density of nucleation sites. Whilst the diverse improvement scales are found to achieve distinct levels of success regarding the nucleate boiling heat-transfer capability enhancement, it is also shown that the micro-nanoscale boiling surface features are susceptible to blockage, leading to the degradation of the improvement with time. Furthermore, topics relating to the heat transfer thermal behavior, ease of manufacture, cost-effectiveness, reliability, and durability are reviewed whenever available and challenges and recommendations for further research are highlighted.
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This review attempts to provide a comprehensive assessment of recent methodologies, structures, and devices for pool boiling heat transfer enhancement. Several enhancement approaches relating to the underlying fluid route and the capability to eliminate incipient boiling hysteresis, augment the nucleate boiling heat transfer coefficient, and improve the critical heat flux are assessed. Hence, this study addresses the most relevant issues related to active and passive enhancement techniques and compound enhancement schemes. Passive heat transfer enhancement techniques encompass multiscale surface modification of the heating surface, such as modification with nanoparticles, tunnels, grooves, porous coatings, and enhanced nanostructured surfaces. Also, there are already studies on the employment of a wide range of passive enhancement techniques, like displaced enhancement, swirl flow aids, and bi-thermally conductive surfaces. Moreover, the combined usage of two or more enhancement techniques, commonly known as compound enhancement approaches, is also addressed in this survey. Additionally, the present work highlights the existing scarcity of sufficiently large available databases for a given enhancement methodology regarding the influencing factors derived from the implementation of innovative thermal management systems for temperature-sensitive electronic and power devices, for instance, material, morphology, relative positioning and orientation of the boiling surface, and nucleate boiling heat transfer enhancement pattern and scale. Such scarcity means the available findings are not totally accurate and suitable for the design and implementation of new thermal management systems. The analysis of more than 100 studies in this field shows that all such improvement methodologies aim to enhance the nucleate boiling heat transfer parameters of the critical heat flux and nucleate heat transfer coefficient in pool boiling scenarios. Finally, diverse challenges and prospects for further studies are also pointed out, aimed at developing important in-depth knowledge of the underlying enhancement mechanisms of such techniques.
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It is widely known by the scientific community that the suspended nanoparticles of nanofluids can enhance the thermophysical properties of base fluids and maximize pool-boiling heat transfer. However, the nanoparticles may undergo extended boiling times and deposit onto the heating surfaces under pool-boiling conditions, thus altering their intrinsic characteristics such as wettability and roughness over time. The present study reviews the fundamental mechanisms and characteristics of nanoparticle deposition, and its impact on surface roughness and wettability, density of vaporized core points, and thermal resistance, among other factors. Moreover, the effect of the nanoparticle layer in long-term thermal boiling performance parameters such as the heat transfer coefficient and critical heat flux is also discussed. This work attempts to highlight, in a comprehensive manner, the pros and cons of nanoparticle deposition after extended pool-boiling periods, leading the scientific community toward further investigation studies of pool-boiling heat-transfer enhancement using nanofluids. This review also attempts to clarify the inconsistent results of studies on heat transfer parameters using nanofluids.
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Fluids containing colloidal suspensions of nanometer-sized particles (nanofluids) have been extensively investigated in recent decades with promising results. Driven by the increase in the thermal conductivity of these new thermofluids, this topic has been growing in order to improve the thermal capacity of a series of applications in the thermal area. However, when it comes to measure nanofluids (NFs) thermal conductivity, experimental results need to be carefully analyzed. Hence, in this review work, the main traditional and new techniques used to measure thermal conductivity of the NFs are presented and analyzed. Moreover, the fundamental parameters that affect the measurements of the NFs' thermal conductivity, such as, temperature, concentration, preparation of NFs, characteristics and thermophysical properties of nanoparticles, are also discussed. In this review, the experimental methods are compared with the theoretical methods and, also, a comparison between experimental methods are made. Finally, it is expected that this review will provide a guidance to researchers interested in implementing and developing the most appropriate experimental protocol, with the aim of increasing the level of reliability of the equipment used to measure the NFs thermal conductivity.
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The development of cancer models that rectify the simplicity of monolayer or static cell cultures physiologic microenvironment and, at the same time, replicate the human system more accurately than animal models has been a challenge in biomedical research. Organ-on-a-chip (OoC) devices are a solution that has been explored over the last decade. The combination of microfluidics and cell culture allows the design of a dynamic microenvironment suitable for the evaluation of treatments' efficacy and effects, closer to the response observed in patients. This systematic review sums the studies from the last decade, where OoC with cancer cell cultures were used for drug screening assays. The studies were selected from three databases and analyzed following the research guidelines for systematic reviews proposed by PRISMA. In the selected studies, several types of cancer cells were evaluated, and the majority of treatments tested were standard chemotherapeutic drugs. Some studies reported higher drug resistance of the cultures on the OoC devices than on 2D cultures, which indicates the better resemblance to in vivo conditions of the former. Several studies also included the replication of the microvasculature or the combination of different cell cultures. The presence of vasculature can influence positively or negatively the drug efficacy since it contributes to a greater diffusion of the drug and also oxygen and nutrients. Co-cultures with liver cells contributed to the evaluation of the systemic toxicity of some drugs metabolites. Nevertheless, few studies used patient cells for the drug screening assays.
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This study addresses the combination of customized surface modification with the use of nanofluids, to infer on its potential to enhance pool-boiling heat transfer. Hydrophilic surfaces patterned with superhydrophobic regions were developed and used as surface interfaces with different nanofluids (water with gold, silver, aluminum and alumina nanoparticles), in order to evaluate the effect of the nature and concentration of the nanoparticles in bubble dynamics and consequently in heat transfer processes. The main qualitative and quantitative analysis was based on extensive post-processing of synchronized high-speed and thermographic images. To study the nucleation of a single bubble in pool boiling condition, a numerical model was also implemented. The results show an evident benefit of using biphilic patterns with well-established distances between the superhydrophobic regions. This can be observed in the resulting plot of the dissipated heat flux for a biphilic pattern with seven superhydrophobic spots, δ = 1/d and an imposed heat flux of 2132 w/m2. In this case, the dissipated heat flux is almost constant (except in the instant t* ≈ 0.9 when it reaches a peak of 2400 W/m2), whilst when using only a single superhydrophobic spot, where the heat flux dissipation reaches the maximum shortly after the detachment of the bubble, dropping continuously until a new necking phase starts. The biphilic patterns also allow a controlled bubble coalescence, which promotes fluid convection at the hydrophilic spacing between the superhydrophobic regions, which clearly contributes to cool down the surface. This effect is noticeable in the case of employing the Ag 1 wt% nanofluid, with an imposed heat flux of 2132 W/m2, where the coalescence of the drops promotes a surface cooling, identified by a temperature drop of 0.7 °C in the hydrophilic areas. Those areas have an average temperature of 101.8 °C, whilst the average temperature of the superhydrophobic spots at coalescence time is of 102.9 °C. For low concentrations as the ones used in this work, the effect of the nanofluids was observed to play a minor role. This can be observed on the slight discrepancy of the heat dissipation decay that occurred in the necking stage of the bubbles for nanofluids with the same kind of nanoparticles and different concentration. For the Au 0.1 wt% nanofluid, a heat dissipation decay of 350 W/m2 was reported, whilst for the Au 0.5 wt% nanofluid, the same decay was only of 280 W/m2. The results of the numerical model concerning velocity fields indicated a sudden acceleration at the bubble detachment, as can be qualitatively analyzed in the thermographic images obtained in this work. Additionally, the temperature fields of the analyzed region present the same tendency as the experimental results.