Glioblastoma Stem Cells—Useful Tools in the Battle against Cancer

Glioblastoma stem cells (GSCs) are cells with a self-renewal ability and capacity to initiate tumors upon serial transplantation that have been linked to tumor cell heterogeneity. Most standard treatments fail to completely eradicate GSCs, causing the recurrence of the disease. GSCs could represent one reason for the low efficacy of cancer therapy and for the short relapse time. Nonetheless, experimental data suggest that the presence of therapy-resistant GSCs could explain tumor recurrence. Therefore, to effectively target GSCs, a comprehensive understanding of their biology and the survival and developing mechanisms during treatment is mandatory. This review provides an overview of the molecular features, microenvironment, detection, and targeting strategies of GSCs, an essential information required for an efficient therapy. Despite the outstanding results in oncology, researchers are still developing novel strategies, of which one could be targeting the GSCs present in the hypoxic regions and invasive edge of the glioblastoma.     

Comparative Antimicrobial Activity of Silver Nanoparticles Obtained by Wet Chemical Reduction and Solvothermal Methods

The synthesis of nanoparticles from noble metals has received high attention from researchers due to their unique properties and their wide range of applications. Silver nanoparticles (AgNPs), in particular, show a remarkable inhibitory effect against microorganisms and viruses. Various methods have been developed to obtain AgNPs, however the stability of such nanostructures over time is still challenging. Researchers attempt to obtain particular shapes and sizes in order to tailor AgNPs properties for specific areas, such as biochemistry, biology, agriculture, electronics, medicine, and industry. The aim of this study was to design AgNPs with improved antimicrobial characteristics and stability. Two different wet chemical routes were considered: synthesis being performed (i) reduction method at room temperatures and (ii) solvothermal method at high temperature. Here, we show that the antimicrobial properties of the obtained AgNPs, are influenced by their synthesis route, which impact on the size and shape of the structures. This work analyses and compares the antimicrobial properties of the obtained AgNPs, based on their structure, sizes and morphologies which are influenced, in turn, not only by the type or quantities of precursors used but also by the temperature of the reaction. Generally, AgNPs obtained by solvothermal, at raised temperature, registered better antimicrobial activity as compared to NPs obtained by reduction method at room temperature.     

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body’s own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016–2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.     

Bioavailability Improvement Strategies for Icariin and Its Derivates: A Review

In recent years, there has been considerable interest in icariin (ICA) and its derivates, icariside II (ICS) and icaritin (ICT), due to their wide range of potential applications in preventing cancer, cardiovascular disease, osteoporosis, delaying the effects of Alzheimer’s disease, treating erectile dysfunction, etc. However, their poor water solubility and membrane permeability, resulting in low bioavailability, dampens their potential beneficial effects. In this regard, several strategies have been developed, such as pharmaceutical technologies, structural transformations, and absorption enhancers. All these strategies manage to improve the bioavailability of the above-mentioned flavonoids, thus increasing their concentration in the desired places. This paper focuses on gathering the latest knowledge on strategies to improve bioavailability for enhancing the efficacy of icariin, icariside II, and icaritin. We conclude that there is an opportunity for many further improvements in this field. To the best of our knowledge, no such review articles scoping the bioavailability improvement of icariin and its derivates have been published to date. Therefore, this paper can be a good starting point for all those who want to deepen their understanding of the field.     

A Spin Resonance Investigation of Magnetism and Dynamics in the Charge-transfer Salts β"-(BEDT-TTF)4[(H3O)M(C2O4)3]S

We report a spin resonance study of the family of quasi-two-dimensional organic (super)conductors β”-(BEDT-TTF)₄[(H₃O)M(C₂O₄)₃]S, where M is a 3d transition metal ion and S is a host solvent molecule. The spin systems for M = Cr³⁺ (S = 3/2) and M = Fe³⁺ (S = 5/2) are investigated by means of both resonant and field modulation techniques in the frequency range between 50 and 313 GHz. The role of the different solvent molecules in determining the degree of spin-orbit coupling and the local symmetry at the metal ion site is established. The low temperature behaviour of intensities, positions and widths of the resonant lines shows significant modifications of the spin-orbit coupling, and of the inter-and intra-ionic spin-spin inter actions. Despite the onset of a weak antiferromagnetic internal field at low temperature, the ultimate narrowing of the lines suggests spin-lattice interactions may still be the dominant relaxation process. Diamagnetic screening in the mixed state of the superconducting samples for fields parallel to the quasi-two-dimensional layers induces additional lineshifts only below B = 2.5T and T = 4K, determining the threshold of full field penetration within the anion layers.     

Focused ion beam-shaped microtools for ultra-precision machining of cylindrical components

Focused ion beam (FIB) sputtering is used to shape a variety of cutting tools with dimensions in the 15–100 μm range and cutting edge radii of curvature of 40 nm. The shape of each microtool is controlled to a pre-specified geometry that includes rake and relief features. We demonstrate tools having rectangular, triangular, and other complex-shaped face designs. A double-triangle tip on one tool is unique and demonstrates the versatility of the fabrication process. The FIB technique allows observation of the tool during fabrication, and, thus, reproducible features are generated with sub-micron precision. Tools are made from tungsten carbide, high-speed tool steel, and single crystal diamond. Application of FIB-shaped tools in ultra-precision microgrooving tests shows that the cross-section of a machined groove is an excellent replication of the microtool face. Microgrooves on 40–150 μm pitch are cut into 3 mm diameter polymer rods, for groove arc lengths greater than 12 cm. The surface finish of machined features is also reported; groove roughness (R_a) is typically less than 0.2 μm. Ultra-precision machining of cylindrical substrates is extended to make bound metal microcoils having feature sizes of 20–40 μm.     

Optical Chemical Barcoding Based on Polarization Controlled Plasmonic Nanopixels

Plasmonic devices offer the possibility of passively detecting changes in local chemistry that opens up a wide range of applications from molecular sensing to monitoring water quality. Conventional plasmonics have previously shown great promise as nanoscale chemical sensors through detection of small variations in the local refractive index (RI). The motivation behind using plasmonics for these applications includes the fact that detection is entirely passive and the devices themselves can be readily miniaturized. Previously, a lack of any control over the output of these devices, has fundamentally limited their application to chemicals which produce clearly identifiable resonances within the range of detection. Here it is demonstrated that microfluidic devices, incorporating polarization‐controlled plasmonic nanopixels, allow the device response to be tuned to the particular analyte of interest, anywhere within the visible spectrum. This dramatically increases the effective dynamic range and allows local variations in RI to be perceived directly as color changes by the human eye. Active control over the output of the device also enables clear differentiation between a number of different analytes, paving the way for plasmonics to be used for a wide range of real‐world chemical sensing applications.     

Improved Speech Synthesis Using Fuzzy Methods

The paper presents theoretical support for and describes the use of a fuzzy paradigm in implementing a TTS system for the Romanian language, employing a rule-based formant synthesizer. In the framework of classic TTS systems, we propose a new approach in order to improve formant trace computation, aiming at increasing synthetic speech perceptual quality. A fuzzy system is proposed for solving the problem of the phonemes that are prone to multi-definitions in rule-based speech synthesis. In the introductory section, we briefly present the background of the problem and our previous results in speech synthesis. In the second section, we deal with the problem of the context-dependent phonemes at the letter-to-sound module level of our TTS system. Then, we discuss the case of the phoneme /l/ and the solution adopted to define it for different contexts. A fuzzy system is associated with each parameter (denoted F1 and F2) to implement the results of the complete analysis of the phoneme /l/ behavior. The knowledge used in implementing the fuzzy module is acquired by natural speech analysis. In the third section, we exemplify the computation of the synthesis parameters F1 and F2 of the phoneme /l/ in the context of the two syllable sequences. The parameter values are contrasted with those obtained from the spectrogram analysis of the natural speech sequences. The last section presents the main conclusions and further research objectives.     

Output‐based H2 optimal controllers for a class of discrete‐time stochastic linear systems with periodic coefficients

The aim of the paper is to present a design procedure of the optimal controller minimizing the H₂‐type norm of discrete‐time stochastic linear systems with periodic coefficients simultaneously affected by a nonhomogeneous but periodic Markov chain and state and control multiplicative white noise perturbations. Firstly, two H₂‐type norms for the linear stochastic systems under consideration were introduced. These H₂‐type norms may be viewed as measures of the effect of the additive white noise perturbations on the regulated output of the considered system. Before deriving of the state space representation of the optimal controller, some useful formulae of the two H₂‐type norms were obtained. These formulae are expressed in terms of periodic solutions of some suitable linear equations and are derived in the absence of some additional assumptions regarding the Markov chain other than the periodicity of the sequence of the transition probability matrices. Further, it is shown that the optimal H₂ controller depends on the stabilizing solutions of some specific systems of coupled Riccati equations, which generalize the well‐known control and filtering equations from linear time invariant case. For the readers convenience, the paper presents iterative numerical algorithms for the computations of the stabilizing solutions of these Riccati type systems. The theoretical developments are illustrated by numerical examples. Copyright © 2014 John Wiley & Sons, Ltd.