New Hybrid Nanomaterial Based on Self-Assembly of Cyclodextrins and Cobalt Prussian Blue Analogue Nanocubes

Supramolecular self-assembly has been demonstrated to be a useful approach to developing new functional nanomaterials. In this work, we used a cobalt Prussian blue analogue (PBA, Co₃[Co(CN)₆]₂) compound and a β-cyclodextrin (CD) macrocycle to develop a novel host-guest PBA-CD nanomaterial. The preparation of the functional magnetic material involved the self-assembly of CD molecules onto a PBA surface by a co-precipitation method. According to transmission electronic microscopy results, PBA-CD exhibited a polydisperse structure composed of 3D nanocubes with a mean edge length of 85 nm, which became shorter after CD incorporation. The supramolecular arrangement and structural, crystalline and thermal properties of the hybrid material were studied in detail by vibrational and electronic spectroscopies and X-ray diffraction. The cyclic voltammogram of the hybrid material in a 0.1 mol·L⁻¹ NaCl supporting electrolyte exhibited a quasi-reversible redox process, attributed to Co²⁺/Co³⁺ conversion, with an E_1/2 value of 0.46 V (vs. SCE), with higher reversibility observed for the system in the presence of CD. The standard rate constants for PBA and PBA-CD were determined to be 0.07 and 0.13 s⁻¹, respectively, which suggests that the interaction between the nanocubes and CD at the supramolecular level improves electron transfer. We expect that the properties observed for the hybrid material make it a potential candidate for (bio)sensing designs with a desirable capability for drug delivery.     

A New HPLC-MS Method for Measuring Maslinic Acid and Oleanolic Acid in HT29 and HepG2 Human Cancer Cells

Maslinic acid (MA) and oleanolic acid (OA), the main triterpenic acids present in olive, have important properties for health and disease prevention. MA selectively inhibits cell proliferation of the HT29 human colon-cancer cell line by inducing selective apoptosis. For measuring the MA and OA concentration inside the cell and in the culture medium, a new HPLC-MS procedure has been developed. With this method, a determination of the amount of MA and OA incorporated into HT29 and HepG2 human cancer-cell lines incubated with different concentrations of MA corresponding to 50% growth inhibitory concentration (IC₅₀), IC_50/2, IC_50/4, and IC_50/8 has been made. The results demonstrate that this method is appropriate for determining the MA and OA concentration in different types of cultured cells and reveals the specific dynamics of entry of MA into HT29 and HepG2 cells.     

Base Modification Strategies to Modulate Immune Stimulation by an siRNA

Immune stimulation triggered by siRNAs is one of the major challenges in the development of safe RNAi‐based therapeutics. Within an immunostimulatory siRNA sequence, this hurdle is commonly addressed by using ribose modifications (e.g., 2′‐OMe or 2′‐F), which results in decreased cytokine production. However, as immune stimulation by siRNAs is a sequence‐dependent phenomenon, recognition of the nucleobases by the trigger receptor(s) is also likely. Here, we use the recently published crystal structures of Toll‐like receptor 8 (TLR8) bound to small‐molecule agonists to generate computational models for ribonucleotide binding by this immune receptor. Our modeling suggested that modification of either the Watson–Crick or Hoogsteen face of adenosine would disrupt nucleotide/TLR8 interactions. We employed chemical synthesis to alter either the Watson–Crick or Hoogsteen face of adenosine and evaluated the effect of these modifications in an siRNA guide strand by measuring the immunostimulatory and RNA interference properties. For the siRNA guide strand tested, we found that modifying the Watson–Crick face is generally more effective at blocking TNFα production in human peripheral blood mononuclear cells (PBMCs) than modification at the Hoogsteen edge. We also observed that modifications near the 5′‐end were more effective at blocking cytokine production than those placed at the 3′‐end. This work advances our understanding of how chemical modifications can be used to optimize siRNA performance.     

The Fuzzy Project Scheduling Problem with Minimal Generalized Precedence Relations

In scheduling, estimations are affected by the imprecision of limited information on future events, and the reduction in the number and level of detail of activities. Overlapping of processes and activities requires the study of their continuity, along with analysis of the risks associated with imprecision. In this line, this article proposes a fuzzy heuristic model for the Project Scheduling Problem with flows and minimal feeding, time and work Generalized Precedence Relations with a realistic approach to overlapping, in which the continuity of processes and activities is allowed in a discretionary way. This fuzzy algorithm handles the balance of process flows, and computes the optimal fragmentation of tasks, avoiding the interruption of the critical path and reverse criticality. The goodness of this approach is tested on several problems found in the literature; furthermore, an example of a 15‐story building was used to compare the better performance of the algorithm implemented in Visual Basic for Applications (Excel) over that same example input in Primavera© P6 Professional V8.2.0, using five different scenarios.     

Friction stir welding of duplex stainless steels

Duplex stainless steels are successful in a variety of applications such as the food industry, petrochemicals and plants for desalination of seawater, where high corrosion resistance and high mechanical strength are required. However, the beneficial microstructure may change during fusion welding steps, and it can compromise the performance of these materials. Friction stir welding is a solid-state process avoiding typical problems concerning solidification such as solidification cracks, liquation and segregation of alloying elements. Superduplex stainless steels can avoid unbalanced proportions of ferrite and austenite, formation of secondary deleterious phases and grain growth of ferrite in the heat-affected zone. Consolidated friction stir welded joints with full penetration 6 mm thick were obtained for UNS S32101 and S32205 duplex and S32750 and S32760 superduplex stainless steels. The friction stir welds were submitted to tensile tests indicating an improvement of strength in welded joints, showing increased yield and tensile strength for all studied cases. Regarding the microstructural characterization, an outstanding grain refinement was observed in the welded joint, achieving grain sizes as small as 1 μm. This refinement was associated with the combination of microstructural restoration mechanisms in the dual-phase microstructure promoted by severe deformation associated with a high temperature during the welding process.     

Rapid Generation of Biologically Relevant Hydrogels Containing Long‐Range Chemical Gradients

Many biological processes are regulated by gradients of bioactive chemicals. Thus, the generation of materials with embedded chemical gradients may be beneficial for understanding biological phenomena and generating tissue‐mimetic constructs. Here a simple and versatile method to rapidly generate materials containing centimeter‐long gradients of chemical properties in a microfluidic channel is described. The formation of a chemical gradient is initiated by a passive‐pump‐induced forward flow and further developed during an evaporation‐induced backward flow. The gradient is spatially controlled by the backward flow time and the hydrogel material containing the gradient is synthesized via photopolymerization. Gradients of a cell‐adhesion ligand, Arg‐Gly‐Asp‐Ser (RGDS), are incorporated in poly(ethylene glycol)‐diacrylate (PEG‐DA) hydrogels to test the response of endothelial cells. The cells attach and spread along the hydrogel material in a manner consistent with the RGDS‐gradient profile. A hydrogel containing a PEG‐DA concentration gradient and constant RGDS concentration is also shown. The morphology of cells cultured on such hydrogel changes from round in the lower PEG‐DA concentration regions to well‐spread in the higher PEG‐DA concentration regions. This approach is expected to be a valuable tool to investigate the cell–material interactions in a simple and high‐throughput manner and to design graded biomimetic materials for tissue engineering applications.