Lighting the Path: Light Delivery Strategies to Activate Photoresponsive Biomaterials In Vivo

Photoresponsive biomaterials are experiencing a transition from in vitro models to in vivo demonstrations that point toward clinical translation. Dynamic hydrogels for cell encapsulation, light-responsive carriers for controlled drug delivery, and nanomaterials containing photosensitizers for photodynamic therapy are relevant examples. Nonetheless, the step to the clinic largely depends on their combination with technologies to bring light into the body. This review highlights the challenge of photoactivation in vivo, and presents strategies for light management that can be adopted for this purpose. The authors’ focus is on technologies that are materials-driven, particularly upconversion nanoparticles that assist in “direct path” light delivery through tissue, and optical waveguides that “clear the path” between external light source and in vivo target. The authors’ intention is to assist the photoresponsive biomaterials community transition toward medical technologies by presenting light delivery concepts that can be integrated with the photoresponsive targets. The authors also aim to stimulate further innovation in materials-based light delivery platforms by highlighting needs and opportunities for in vivo photoactivation of biomaterials.     

Extraction and characterization of hydroxyapatite-based materials from grey triggerfish skin and black scabbardfish bones

The conversion of food industry by-products to compounds with high added value is nowadays a significant topic, for social, environmental, and economic reasons. In this paper, calcium phosphate-based materials were obtained from black scabbardfish (Aphanopus carbo) bones and grey triggerfish (Balistes capriscus) skin, which are two of the most abundant fish by-products of Madeira Island. Different calcination temperatures between 400 and 1000°C were employed. Materials obtained from calcination of bones of black scabbard fish were composed by homogeneous mixtures of hydroxyapatite (Ca₁₀(PO4)₆(OH)₂, HAp) and β-tricalcium phosphate (β-Ca₃(PO₄)₂, β-TCP). Because of the high biocompatibility of HAp and the good resorbability of β-TCP, these natural biphasic materials could be very relevant in the field of biomaterials, as bone grafts. The ratio between HAp and β-TCP in the biphasic compound was dependent on the calcination temperature. Differently, the material obtained from skin of grey triggerfish contained HAp as the main phase, together with small amounts of other mineral phases, such as halite and rhenanite, which are known to enhance osteogenesis when used as bone substitutes. In both cases, the increase of calcination temperature led to an increase in the particles size with a consequent decrease in their specific surface area. These results demonstrate that from the fish by-products of the most consumed fishes in Madeira Island it is possible to obtain bioceramic materials with tunable composition and particle morphology, which could be promising materials for the biomedical field.     

Osteosarcoma Pathogenesis Leads the Way to New Target Treatments

Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.     

κ-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance

Several studies have reported that nicotine, the main bioactive component of tobacco, exerts a marked negative energy balance. Apart from its anorectic action, nicotine also modulates energy expenditure, by regulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. These effects are mainly controlled at the central level by modulation of hypothalamic neuropeptide systems and energy sensors, such as AMP-activated protein kinase (AMPK). In this study, we aimed to investigate the kappa opioid receptor (κOR)/dynorphin signaling in the modulation of nicotine’s effects on energy balance. We found that body weight loss after nicotine treatment is associated with a down-regulation of the κOR endogenous ligand dynorphin precursor and with a marked reduction in κOR signaling and the p70 S6 kinase/ribosomal protein S6 (S6K/rpS6) pathway in the lateral hypothalamic area (LHA). The inhibition of these pathways by nicotine was completely blunted in κOR deficient mice, after central pharmacological blockade of κOR, and in rodents where κOR was genetically knocked down specifically in the LHA. Moreover, κOR-mediated nicotine effects on body weight do not depend on orexin. These data unravel a new central regulatory pathway modulating nicotine’s effects on energy balance.     

Tailored-Made Polydopamine Nanoparticles to Induce Ferroptosis in Breast Cancer Cells in Combination with Chemotherapy

Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe³⁺ at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe³⁺ was adsorbed in PDA NPs at pH values close to which Fe(OH)₃ begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe³⁺. Otherwise, it was demonstrated that Fe³⁺ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca²⁺ content, and that when Fe³⁺ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe³⁺ and doxorubicin may constitute a good approach to target breast tumors.     

Structural Aspects of P2-Type Na0.67Mn0.6Ni0.2Li0.2O2 (MNL) Stabilization by Lithium Defects as a Cathode Material for Sodium-Ion Batteries

A known strategy for improving the properties of layered oxide electrodes in sodium-ion batteries is the partial substitution of transition metals by Li. Herein, the role of Li as a defect and its impact on sodium storage in P2-Na_0.67Mn_0.6Ni_0.2Li_0.2O₂ is discussed. In tandem with electrochemical studies, the electronic and atomic structure are studied using solid-state NMR, operando XRD, and density functional theory (DFT). For the as-synthesized material, Li is located in comparable amounts within the sodium and the transition metal oxide (TMO) layers. Desodiation leads to a redistribution of Li ions within the crystal lattice. During charging, Li ions from the Na layer first migrate to the TMO layer before reversing their course at low Na contents. There is little change in the lattice parameters during charging/discharging, indicating stabilization of the P2 structure. This leads to a solid-solution type storage mechanism (sloping voltage profile) and hence excellent cycle life with a capacity of 110 mAh g^-1 after 100 cycles. In contrast, the Li-free compositions Na_0.67Mn_0.6Ni_0.4O₂ and Na_0.67Mn_0.8Ni_0.2O₂ show phase transitions and a stair-case voltage profile. The capacity is found to originate from mainly Ni³⁺/Ni⁴⁺ and O^2-/O^2-δ redox processes by DFT, although a small contribution from Mn⁴⁺/Mn⁵⁺ to the capacity cannot be excluded.     

A practical assessment of risk-averse approaches in production lot-sizing problems

ABSTRACT

This paper presents an empirical assessment of four state-of-the-art risk-averse approaches to deal with the capacitated lot-sizing problem under stochastic demand. We analyse two mean-risk models based on the semideviation and on the conditional value-at-risk risk measures, and alternate first and second-order stochastic dominance approaches. The extensive computational experiments based on different instances characteristics and on a case-study suggest that CVaR exhibits a good trade-off between risk and performance, followed by the semideviation and first-order stochastic dominance approach. For all approaches, enforcing risk-aversion helps to reduce the cost-standard deviation substantially, which is usually accomplished via increasing production rates. Overall, we can say that very risk-averse decision-makers would be willing to pay an increased price to have a much less risky solution given by CVaR. In less risk-averse settings, though, semideviation and first-order stochastic dominance can be appealing alternatives to provide significantly more stable production planning costs with a marginal increase of the expected costs.     

ARP-P4: deep analysis of a hybrid SDN ARP-Path/P4Runtime switch

Telecommunication Systems - The Software-Defined Networking (SDN) architecture decouples the control plane from the data plane, but it does not explicitly state where the control should be located....     

Influence of the dispersion of Nanoclays on the cellular structure of foams based on polystyrene

In the present work blends of polystyrene (PS) with sepiolites have been produced using a melt extrusion process. The dispersion degree of the sepiolites in the PS has been analyzed by dynamic shear rheology and X-ray micro-computed tomography. Sepiolites treated with quaternary ammonium salts (O-QASEP) are better dispersed in the PS matrix than natural sepiolites (N-SEP) or sepiolites organo-modified with silane groups (O-SGSEP). A percolated network is obtained when using 6.0 wt% of O-QASEP, 8.0 wt% of N-SEP and 10.0 wt% of O-SGSEP. It has been shown that multiple extrusion processes have a negative effect on the polymer architecture. They produce a reduction in the length of the polymeric chains, and they do not lead to a better dispersion of the particles in the polymer matrix. Foams have been produced using a gas dissolution foaming process, where a strong effect of the dispersion degree on the cellular structure of the different foams was found. The effects on the cellular structure obtained by using different types of sepiolites, different contents of sepiolites and different extrusion conditions have been analyzed. The foams produced with the formulations containing O-QASEP present the lowest cell size and the most homogeneous cellular structures.