Significant enhancement of ferromagnetism above room temperature in epitaxial 2D van der Waals ferromagnet FeGeTe/BiTe heterostructures.

Two-dimensional (2D) van der Waals (vdW) ferromagnetic metals FeGeTe with = 3-5 have raised significant interest in the scientific community. FeGeTe shows prospects for spintronic applications since the Curie temperature has been reported near or higher than 300 K. In the present work, epitaxial FeGeTe (FGT) heterostructures were grown by Molecular Beam Epitaxy (MBE) on insulating crystalline substrates.

The Inhibitory Properties of a Novel, Selective LMTK3 Kinase Inhibitor.

Recently, the oncogenic role of lemur tyrosine kinase 3 (LMTK3) has been well established in different tumor types, highlighting it as a viable therapeutic target. In the present study, using in vitro and cell-based assays coupled with biophysical analyses, we identify a highly selective small molecule LMTK3 inhibitor, namely C36. Biochemical/biophysical and cellular studies revealed that C36 displays a high in vitro selectivity profile and provides notable therapeutic effect when tested in the National Cancer Institute (NCI)-60 cancer cell line panel.

Molecular profile and clinical features of patients with gliomas using a broad targeted next generation-sequencing panel.

Gliomas are the most common malignant primary brain tumors characterized by poor prognosis. The genotyping of tumors using next generation sequencing (NGS) platforms enables the identification of genetic alterations that constitute diagnostic, prognostic and predictive biomarkers. The present study investigated the molecular profile of 32 tumor samples from 32 patients with high-grade gliomas by implementing a broad 80-gene targeted NGS panel while reporting their clinicopathological characteristics and outcomes.

A quantum walks assisted algorithm for peptide and protein folding prediction.

Proteins are considered as the working force of cells. Their functionality is determined by their spatial form. In 1973 Anfinsen proposed that the spatial form is determined by the sequence of amino acids in the protein backbone.

Phosphinic Peptides as Tool Compounds for the Study of Pharmacologically Relevant Zn-Metalloproteases.

Phosphinic peptides constitute an important class of bioactive compounds that have found a wide range of applications in the field of biology and pharmacology of Zn-metalloproteases, the largest family of proteases in humans. They are designed to mimic the structure of natural substrates during their proteolysis, thus acting as mechanism-based, transition state analogue inhibitors. A combination of electrostatic interactions between the phosphinic acid group and the Zn cation as well as optimal noncovalent enzyme-ligand interactions can result in both high binding affinity for the desired target and selectivity against other proteases.

The κ-opioid receptor-induced autophagy is implicated in stress-driven synaptic alterations.

Recent evidence has shown that G protein-coupled receptors (GPCRs) are direct sensors of the autophagic machinery and opioid receptors regulate neuronal plasticity and neurotransmission with an as yet unclarified mechanism. Using and experimental approaches, this study aims to clarify the potential role of autophagy and κ-opioid receptor (κ-OR) signaling in synaptic alterations. We hereby demonstrate that the selective κ-OR agonist U50,488H, induces autophagy in a time-and dose-dependent manner in Neuro-2A cells stably expressing the human κ-OR by upregulating microtubule-associated protein Light Chain 3-II (LC3-II), Beclin 1 and Autophagy Related Gene 5 (ATG5).

Modelling the biodistribution of inhaled gold nanoparticles in rats with interspecies extrapolation to humans.

The increasing intentional and non-intentional exposure to nanoparticles (NPs) has raised the interest concerning their fate and biodistribution in the body of animals and humans after inhalation. In this context, Physiologically Based (pharmaco)Kinetic (PBK) modelling has emerged as an in silico approach that simulates the biodistribution kinetics of NPs in the body using mathematical equations. Due to restrictions in data availability, such models are first developed for rats or mice.

Design, synthesis and biological evaluation of new 3,4-dihydroquinoxalin-2(1)-one derivatives as soluble guanylyl cyclase (sGC) activators.

Herein, we present the structure-based design, synthesis and biological evaluation of novel mono- and di-carboxylic 3,4-dihydroquinoxalin-2(1)-one derivatives as potential heme-independent activators of soluble guanylate cyclase (sGC). Docking calculations of several known sGC agonists by utilizing both a homology model of human sGC Η-ΝΟΧ domain and a recent cryo-EM structure of the same domain guided the structural optimization of various designed compounds. Among these, mono- and di-carboxylic 3,4-dihydroquinoxalin-2(1)-one derivatives arose as promising candidate sGC activators.

Controlling thermal expansion and phase transitions in CaSrMnO by Sr-content.

Perovskite oxides of the general formula ABO, with A and B being metal cations, present themselves in various crystal structures that originate from a distorted ideal cubic perovskite. Understanding how composition, temperature, atmosphere and reduction extent of these non-stoichiometric redox materials induce structural changes on an atomic, as well as macroscopic, level is crucial to transfer newly developed materials to industrial scale applications in the redox-based energy conversion sector. Herein, CaSrMnO ( ∈ [0,0.

Structure revision and chemical synthesis of ligandrol's main bishydroxylated long-term metabolic marker.

Although the main bishydroxylated long-term metabolite of the WADA-banned anabolic agent ligandrol (LGD-4033) is an important metabolic marker, it is not readily available in sufficient quantities to facilitate the development and validation of related analytical protocols or sensors. A chemically more robust structure was postulated as an alternative to the one previously established. The NMR spectra of the synthesized material and its LC-HRMS comparison with a relevant metabolic sample support the proposed structural revision.

Metal Complexes as Antifungals? From a Crowd-Sourced Compound Library to the First Experiments.

There are currently fewer than 10 antifungal drugs in clinical development, but new fungal strains that are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents.

Peptide inhibitors of angiotensin-I converting enzyme based on angiotensin (1-7) with selectivity for the C-terminal domain.

The renin-angiotensin system (RAS) is a key regulator of human arterial pressure. Several of its effects are modulated by angiotensin II, an octapeptide originating from the action of angiotensin-I converting enzyme (ACE) on the decapeptide angiotensin-I. ACE possess two active sites (nACE and cACE) that have their own kinetic and substrate specificities.

Biological Response of Human Cancer Cells to Ionizing Radiation in Combination with Gold Nanoparticles.

In the context of improving radiation therapy, high-atomic number (Z) metallic nanoparticles and, more importantly, gold-based nanostructures are developed as radiation enhancers/radiosensitizers. Due to the diversity of cell lines, nanoparticles, as well as radiation types or doses, the resulting biological effects may differ and remain obscure. In this multiparameter study, we aim to shed light on these effects and investigate them further by employing X-irradiation and three human cancer cell lines (PC3, A549, and U2OS cells) treated by multiple techniques.

Fast and Accurate Determination of Minute Ochratoxin A Levels in Cereal Flours and Wine with the Label-Free White Light Reflectance Spectroscopy Biosensing Platform.

Ochratoxin A (OTA) is one of the most toxic naturally encountered contaminants and is found in a variety of foods and beverages, including cereals and wine. Driven by the strict regulations regarding the maximum allowable OTA concentration in foodstuff and the necessity for on-site determination, the development of fast and sensitive methods for the OTA determination in cereal flours and wine samples, based on white light reflectance spectroscopy, is presented. The method relied on appropriately engineered silicon chips, on top of which an OTA-protein conjugate was immobilized.

Graphene-Based Composites with Silver Nanowires for Electronic Applications.

Graphene/metal nanocomposites have shown a strong potential for use in electronic applications. In particular, the combination of silver nanowires (AgNWs) with graphene derivatives leads to the formation of an efficient conductive network, thus improving the electrical properties of a composite. This work focused on developing highly conductive hydrophilic hybrids of simultaneously functionalized and reduced graphene oxide (-rGO) and AgNWs in different weight ratios by following two different synthetic routes: (a) the physical mixture of -rGO and AgNWs, and (b) the in situ reduction of GO in the presence of AgNWs.

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers.

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation.

Protein Crystals Nucleated and Grown by Means of Porous Materials Display Improved X-ray Diffraction Quality.

Well-diffracting protein crystals are indispensable for X-ray diffraction analysis, which is still the most powerful method for structure-function studies of biomolecules. A promising approach to growing such crystals is the use of porous nucleation-inducing materials. However, while protein crystal nucleation in pores has been thoroughly considered, little attention has been paid to the subsequent growth of crystals.

A Riboswitch-Driven Era of New Antibacterials.

Riboswitches are structured non-coding RNAs found in the 5' UTR of important genes for bacterial metabolism, virulence and survival. Upon the binding of specific ligands that can vary from simple ions to complex molecules such as nucleotides and tRNAs, riboswitches change their local and global mRNA conformations to affect downstream transcription or translation. Due to their dynamic nature and central regulatory role in bacterial metabolism, riboswitches have been exploited as novel RNA-based targets for the development of new generation antibacterials that can overcome drug-resistance problems.

Leaching from a 3D-printed aligner resin.

Aim: To quantitatively assess the degree of conversion and the water-leaching targeted compound from 3D-printed aligners.

Materials And Methods: 3D-printed aligners were made of photopolymerized resin (Tera Harz TC85A). The molecular structure and degree of conversion of the set resin were investigated by ATR-FTIR spectroscopy (n = 5).

Functional characterization of putative ecdysone transporters in lepidopteran pests.

The insect steroid hormone ecdysone plays a critical role in insect development. Several recent studies have shown that ecdysone enters cells through Organic Anion Transporting Polypeptides (OATPs) in insects such as flies and mosquitoes. However, the conservation of this mechanism across other arthropods and the role of this transporter in canonical ecdysone pathways are less well studied.

Modeling of clearance, retention, and translocation of inhaled gold nanoparticles in rats.

The increasing exposure to gold nanoparticles (AuNPs), due to their wide range of applications, has led to the need for thorough understanding of their biodistribution, following exposure. The objective of this paper is to develop a PBK model in order to study the clearance, retention and translocation of inhaled gold nanoparticles in rats, providing a basis for the understanding of the absorption, distribution, metabolism and elimination (ADME) mechanisms of AuNPs in various organs. A rat PBK computational model was developed, connected to a detailed respiratory model, including the olfactory, tracheobronchial, and alveolar regions.

Investigation of prognostic biomarkers in patients with urothelial carcinoma treated with platinum-based regimens.

Background: Bladder cancer (BC) is a heterogeneous malignancy with dismal outcome.

Patients And Methods: Mutations in genes, altered or linked to platinum sensitivity in BC, were examined in 66 patients' tumors along with tumor infiltrating lymphocytes (TILs) density and MMR, PD-L1 and CD8 protein expression, as well as basal and luminal subtypes, defined by protein expression of markers, including CK5/6 and GATA3 or CK20, respectively.

Results: 41 tumors harbored mutations, mainly in TP53 (38%), ARID1A (17%) and the DNA damage response and repair (DDR) genes ERCC2 (17%) and BRCA2 (15%).