bluuebunny/crossref_metadata_2025 huggingface dataset:
Tepotinib Inhibits Several Drug Efflux Transporters and Biotransformation Enzymes: The Role in Drug-Drug Interactions and Targeting Cytostatic Resistance In Vitro and Ex Vivo
Authors: Vagiannis Dimitrios , Budagaga Youssif , Morell Anselm , Zhang Yu , Novotná Eva , Skarka Adam , Kammerer Sarah , Küpper Jan-Heiner , Hanke Ivo , Rozkoš Tomáš , Hofman Jakub
Published: November 2021

Tepotinib is a novel tyrosine kinase inhibitor recently approved for the treatment of non-small cell lung cancer (NSCLC). In this study, we evaluated the tepotinib’s potential to perpetrate pharmacokinetic drug interactions and modulate multidrug resistance (MDR). Accumulation studies showed that tepotinib potently inhibits ABCB1 and ABCG2 efflux transporters, which was confirmed by molecular docking. In addition, tepotinib inhibited several recombinant cytochrome P450 (CYP) isoforms with varying potency. In subsequent drug combination experiments, tepotinib synergistically reversed daunorubicin and mitoxantrone resistance in cells with ABCB1 and ABCG2 overexpression, respectively. Remarkably, MDR-modulatory properties were confirmed in ex vivo explants derived from NSCLC patients. Furthermore, we demonstrated that anticancer effect of tepotinib is not influenced by the presence of ABC transporters associated with MDR, although monolayer transport assays designated it as ABCB1 substrate. Finally, tested drug was observed to have negligible effect on the expression of clinically relevant drug efflux transporters and CYP enzymes. In conclusion, our findings provide complex overview on the tepotinib’s drug interaction profile and suggest a promising novel therapeutic strategy for future clinical investigations.
Experimental Study of a Tilt Single Slope Solar Still Integrated with Aluminum Condensate Plate
Authors: Alwan Naseer T. , Majeed Milia H. , Shcheklein Sergey E. , Ali Obed M. , PraveenKumar Seepana
Published: November 2021

The low freshwater productivity of a conventional solar still is considered a challenge for researchers due to the high temperature of the glass cover or basin water depth. In current work, a newly designed solar still was suggested according to the climatic conditions of Yekaterinburg/Russia, which included an enhanced condensation and evaporation process by spraying a thin water film on a hot absorber plate and then passing the generated water vapor by free convection over the aluminum plate (low temperature). The distillation system under study was tested during July 2020 and 29 July was chosen as a typical day from 08:00 a.m. to 8:00 p.m. The results showed that the largest amount of water vapor condenses on the aluminum plate (about 46%), and the rest condenses on the glass cover. This means that the aluminum plate effectively improved productivity due to the flow of humid air naturally (free convection) on the aluminum plate (its surface temperature was lower than that of the glass cover). The cost analytical calculations showed that the cost of producing one liter of distilled water from the suggested solar still was 0.063$.
Current Concepts in Humeral Component Design for Anatomic and Reverse Shoulder Arthroplasty
Authors: Sanchez-Sotelo Joaquin
Published: November 2021

The history of humeral component design has evolved from prostheses with relatively long stems and limited anatomic head options to a contemporary platform with short stems and stemless implants with shared instrumentation and the ability to provide optimal shoulder reconstruction for both anatomic and reverse configurations. Contemporary humeral components aim to preserve the bone, but they are potentially subject to malalignment. Modern components are expected to favorably load the humerus and minimize adverse bone reactions. Although there will likely continue to be further refinements in humeral component design, the next frontiers in primary shoulder arthroplasty will revolve around designing an optimal plan, including adequate soft tissue tension and providing computer-assisted tools for the accurate execution of the preoperative plan in the operating room.
Session Rating of Perceived Exertion (sRPE) Load and Training Impulse Are Strongly Correlated to GPS-Derived Measures of External Load in NCAA Division I Women’s Soccer Athletes
Authors: Askow Andrew T. , Lobato Alexa L. , Arndts Daniel J. , Jennings Will , Kreutzer Andreas , Erickson Jacob L. , Esposito Phil E. , Oliver Jonathan M. , Foster Carl , Jagim Andrew R.
Published: November 2021

Purpose: The purpose of this study was to determine whether session rating of perceived exertion-derived training load (sRPE-TL) correlates with GPS-derived measures of external load in National Collegiate Athletics Association (NCAA) Division I female soccer athletes. Methods: Twenty-one NCAA Division 1 collegiate women’s soccer athletes (11 starters, 10 non-starters; 65.1 ± 7.2 kg, 168.4 ± 7.9 cm, 20.3 ± 1.5 yrs) volunteered to take part in this study. Data for this study were collected over the course of 16 weeks during the 2018 NCAA women’s soccer season. External load and heart rate (HR) data were collected during each training session and match during the season. At least 30 min after the end of an activity (e.g., match or practice), athletes were prompted to complete a questionnaire reporting their perceived exertion for the session. sRPE-TL was calculated at the end of the season by multiplying perceived exertion by the respective session duration. Results: sRPE-TL was very strongly correlated with total distance, distance covered in velocity zones 1–3, the number of accelerations in zones 4 and 5, total PlayerLoad™, and PlayerLoad™. For internal load, sRPE-TL correlated very strongly (0.70 ≤ |r| < 0.90) with Edward’s and Bannister’s TRIMP and strongly (0.50 ≤ |r| < 0.70) with duration spent in in heart rate zones 5 and 6 (80–90% and 90–100% max HR, respectively) while correlations with maximum HR (bpm), mean HR (bpm), and mean HR (%) and sRPE-TL were moderate (0.30 ≤ |r| < 0.50). Conclusions: In NCAA Division I women soccer, sRPE-TL is strongly associated with external measures of workload. These relationships were stronger during match play, with acceleration load and total distance exhibiting the strongest relationship with sRPE-TL.
Evaluation of the Post-Training Hypotensor Effect in Paralympic and Conventional Powerlifting
Authors: Aidar Felipe J. , Paz Ângelo de Almeida , Gama Dihogo de Matos , de Souza Raphael Fabricio , Vieira Souza Lúcio Marques , Santos Jymmys Lopes dos , Almeida-Neto Paulo Francisco , Marçal Anderson Carlos , Neves Eduardo Borba , Moreira Osvaldo Costa , Garrido Nuno Domingos , Cabral Breno Guilherme Araújo Tinôco , Clemente Filipe Manuel , Reis Victor Machado , Nikolaidis Pantelis Theo , Knechtle Beat
Published: November 2021

High blood pressure (HBP) has been associated with several complications and causes of death. The objective of the study was to analyze the hemodynamic responses in Paralympic bench press powerlifting (PP) and conventional powerlifting (CP) before and after training and up to 60 minutes (min) after training. Ten PP and 10 CP athletes performed five sets of five repetition maximal bench press exercises, and we evaluated systolic, diastolic, and mean blood pressure (SBP, DBP, and MBP, respectively), heart rate (HR), heart pressure product (HPP), and myocardial oxygen volume (MVO2). The SBP increased after training (p < 0.001), and there were differences in the post training and 30, 40, and 60 min later (p = 0.021), between 10 and 40 min after training (p = 0.031, η2p = 0.570), and between CP and PP (p =0.028, η2p = 0.570). In the MBP, there were differences between before and after (p = 0.016) and 40 min later (p = 0.040, η2p = 0.309). In the HR, there was a difference between before and after, and 5 and 10 min later (p = 0.002), and between after and 10, 20, 30, 40, 50, and 60 min later (p < 0.001, η2p = 0.767). In HPP and MVO2, there were differences between before and after (p = 0.006), and between after and 5, 10, 20, 30, 40, 50, and 60 min later (p < 0.001, η2p = 0.816). In CP and PP, there is no risk of hemodynamic overload to athletes, considering the results of the HPP, and training promotes a moderate hypotensive effect, with blood pressure adaptation after and 60 min after exercise.
Mechanical Properties and Failure Mechanisms of Refill Friction Stir Spot Welds
Authors: Lakshmi Balasubramaniam Guruvignesh , Boldsaikhan Enkhsaikhan , Joseph Rosario Gratias Fernandez , Ravichandran Saravana Prabu , Fukada Shintaro , Fujimoto Mitsuo , Kamimuki Kenichi
Published: November 2021

Refill friction stir spot welding (RFSSW) is an innovative solid-state welding technology for aluminum structures. The presented study aimed to evaluate the mechanical properties of refill spot welds and their failure mechanisms with the use of industrial test standards. The mechanical properties of refill spot welds were compared with those of rivet joints with comparable joint sizes. Static load tests indicated that RFSSW coupons demonstrate higher ultimate shear strengths but slightly lower ultimate tension strengths than those of rivet coupons. Fatigue test results indicated that both RFSSW coupons and rivet coupons demonstrate comparable performances during low-load-level fatigue lap shear tests but RFSSW coupons outperform rivet coupons during high-load-level fatigue lap shear tests. The failure mechanisms of refill spot welds were characterized in terms of external loading, parent metal properties, and weld properties. Refill spot weld failures included parent metal tensile failures, nugget pullouts, and interfacial failures. A refill spot weld may demonstrate one or a combination of these mechanical failures. Although the mechanical tests of refill spot welds demonstrated promising results with predictable failure mechanisms, the metallurgical evolution involved in RFSSW remains a subject to study.
Rheological and Technological Aspects in Designing the Properties of Shear Thickening Fluids
Authors: Żurowski Radosław , Falkowski Paweł , Zygmuntowicz Justyna , Szafran Mikołaj
Published: November 2021

This work focuses on shear thickening fluids (STFs) as ceramic–polymer composites with outstanding protective properties. The investigation aims to determine the influence of raw material parameters on the functional properties of STFs. The following analyses were used to characterize both the raw materials and the STFs: scanning electron microscopy, dynamic light scattering, matrix-assisted laser desorption/ionization time-of-flight, chemical sorption analysis, rheological analysis, and kinetic energy dissipation tests. It was confirmed that the morphology of the solid particles plays a key role in designing the rheological and protective properties of STFs. In the case of irregular silica, shear thickening properties can be obtained from a solid content of 12.5 vol.%. For spherical silica, the limit for achieving shear thickening behavior is 40 vol.%. The viscosity curve analysis allowed for the introduction of a new parameter defining the functional properties of STFs: the technological critical shear rate. The ability of STFs to dissipate kinetic energy was determined using a unique device that allows pure fluids to be tested without prior encapsulation. Because of this, it was possible to observe even slight differences in the protective properties between different STFs, which has not been possible so far. During tests with an energy of 50 J, the dissipation factor was over 96%.
Mechanical Behavior Modelling and Filler Geometry Effect of Glass Filler Reinforced Starch-Epoxy Hybrid Matrix Composites
Authors: Kontaxis Lykourgos C. , Kozaniti Foteini K. , Papanicolaou George C.
Published: November 2021

The aim of the present study is to investigate the inclusion geometry and concentration effect on the quasi-static properties of a starch-epoxy hybrid matrix composite. The composites investigated consisted of a starch-epoxy hybrid matrix reinforced with four different glass inclusions such as 3 mm long chopped strands, 0.2 mm long short glass fibers, glass beads (120 μm in diameter) and glass bubbles (65 μm in diameter) at different concentrations. The flexural modulus and the strength of all materials tested were determined using three-point bending tests. The Property Prediction Model (PPM) was applied to predict the experimental findings. The model predicted remarkably well the mechanical behavior of all the materials manufactured and tested. The maximum value of the flexural modulus in the case of the 3 mm long chopped strands was found to be 75% greater than the modulus of the hybrid matrix. Furthermore, adding glass beads in the hybrid matrix led to a simultaneous increase in both the flexural modulus and the strength.
Batch Reactor vs. Microreactor System for Efficient AuNP Deposition on Activated Carbon Fibers
Authors: Luty-Błocho Magdalena , Wojnicki Marek , Tokarski Tomasz , Hessel Volker , Fitzner Krzysztof
Published: November 2021

The process of noble metals ions recovery and the removal small fraction of nanoparticles from waste solution is an urgent topic not only from the economic but also ecology point of view. In this paper, the use of activated carbon fibers (ACF) as a “trap” for gold nanoparticles obtained by a chemical reduction method is described. The synthesized nanoparticles were stabilized either electrostatically or electrosterically and then deposited on carbon fibers or activated carbon fibers. Moreover, the deposition of metal on fibers was carried out in a batch reactor and a microreactor system. It is shown, that process carried out in the microreactor system is more efficient (95%) as compared to the batch reactor and allows for effective gold nanoparticles removal from the solution. Moreover, for similar conditions, the adsorption time of the AuNPs on ACF is shortened from 11 days for the process carried out in the batch reactor to 2.5 min in the microreactor system.
Fly Ash as an Eco-Friendly Filler for Rigid Polyurethane Foams Modification
Authors: Kuźnia Monika , Magiera Anna , Zygmunt-Kowalska Beata , Kaczorek-Chrobak Katarzyna , Pielichowska Kinga , Szatkowski Piotr , Benko Aleksandra , Ziąbka Magdalena , Jerzak Wojciech
Published: November 2021

There is currently a growing demand for more effective thermal insulation materials with the best performance properties. This research paper presents the investigation results on the influence of two types of filler on the structure and properties of rigid polyurethane foam composites. Fly ash as a product of coal combustion in power plants and microspheres of 5, 10, 15, and 20 wt.%, were used as rigid polyurethane foams modifiers. The results of thermal analysis, mechanical properties testing, and cellular structure investigation performed for polyurethane composites show that the addition of fly ash, up to 10 wt.%, significantly improved the majority of the tested parameters. The use of up to 20 wt.% of microspheres improves the mechanical and thermal properties and thermal stability of rigid polyurethane foams.
Fabrication and Characterization of New Functional Graded Material Based on Ti, Ta, and Zr by Powder Metallurgy Method
Authors: Matuła Izabela , Dercz Grzegorz , Sowa Maciej , Barylski Adrian , Duda Piotr
Published: November 2021

In view of the aging population and various diseases worldwide, the demand for implants has been rapidly increasing. Despite the efforts of doctors, engineers, and medical companies, the fabrication of and procedures associated with implants have not yet been perfected. Therefore, a high percentage of premature implantations has been observed. The main problem with metal implants is the mechanical mismatch between human bone and the implant material. Zirconium/titanium-based materials with graded porosity and composition were prepared by powder metallurgy. The whole samples are comprised of three zones, with a radial gradient in the phase composition, microstructure, and pore structure. The samples were prepared by a three-step powder metallurgy method. The microstructure and properties were observed to change gradually with the distance from the center of the sample. The x-ray diffraction analysis and microstructure observation confirmed the formation of diffusive connections between the particular areas. Additionally, the mechanical properties of the obtained materials were checked, with respect to the distance from the center of the sample. An analysis of the corrosion properties of the obtained materials was also carried out.
Predicting the Cochlear Dead Regions Using a Machine Learning-Based Approach with Oversampling Techniques
Authors: Chang Young-Soo , Park Hee-Sung , Moon Il-Joon
Published: November 2021

Background and Objectives: Determining the presence or absence of cochlear dead regions (DRs) is essential in clinical practice. This study proposes a machine learning (ML)-based model that applies oversampling techniques for predicting DRs in patients. Materials and Methods: We used recursive partitioning and regression for classification tree (CT) and logistic regression (LR) as prediction models. To overcome the imbalanced nature of the dataset, oversampling techniques to duplicate examples in the minority class or to synthesize new examples from existing examples in the minority class were adopted, namely the synthetic minority oversampling technique (SMOTE). Results: The accuracy results of the 10-fold cross-validation of the LR and CT with the original data were 0.82 (±0.02) and 0.93 (±0.01), respectively. The accuracy results of the 10-fold cross-validation of the LR and CT with the oversampled data were 0.66 (±0.02) and 0.86 (±0.01), respectively. Conclusions: This study is the first to adopt the SMOTE method to assess the role of oversampling methods on audiological datasets and to develop an ML-based model. Considering that the SMOTE method did not improve the model’s performance, a more flexible model or more clinical features may be needed.
Structural Change of TiAl Alloy under Uniaxial Tension and Compression in the <001> Direction: A Molecular Dynamics Study
Authors: Arifin Rizal , Astuti Fahmi , Baqiya Malik Anjelh , Winardi Yoyok , Wicaksono Yoga Arob , Darminto  , Selamat Ali
Published: November 2021

TiAl alloys can be used in aircraft and high-performance vehicle engines owing to their structural stability at high temperatures and their light weight. Although many studies have focused on developing this alloy material, there is still a lack of information about the changes in the structure of TiAl alloys under tensile and compressive loading. Therefore, we performed molecular dynamics simulations of the tensile and compressive loading of TiAl alloys in the <001> direction at temperatures of 10 and 300 K. From our simulation results, we found that the tensile and compressive strengths of TiAl alloys are significantly affected by temperature. It was found that TiAl alloys can withstand greater compression loading than tensile loading. This is due to the change in the crystal structure of TiAl alloys after being deformed to a strain of 0.4 by compressive loading, according to the analysis of structural changes under loading conditions. From the radial distribution analysis results, there was a change in the orientation of the face-centered cubic-like structure as it reached the maximum compressive stress compared to the initial structure.
Plasma Spheroidisation of Irregular Ti6Al4V Powder for Powder Bed Fusion
Authors: Nkhasi Nthateng , du Preez Willie , Bissett Hertzog
Published: November 2021

Metal powders suitable for use in powder bed additive manufacturing processes should ideally be spherical, dense, chemically pure and of a specified particle size distribution. Ti6Al4V is commonly used in the aerospace, medical and automotive industries due to its high strength-to-weight ratio and excellent corrosion resistance properties. Interstitial impurities in titanium alloys have an impact upon mechanical properties, particularly oxygen, nitrogen, hydrogen and carbon. The plasma spheroidisation process can be used to spheroidise metal powder consisting of irregularly shaped particles. In this study, the plasma spheroidisation of metal powder was performed on Ti6Al4V powder consisting of irregularly shaped particles. The properties of the powder relevant for powder bed fusion that were determined included the particle size distribution, morphology, particle porosity and chemical composition. Conclusions were drawn regarding the viability of using this process to produce powder suitable for additive manufacturing.
Rapid Alloy Surface Engineering through Closed-Vessel Reagent Pyrolysis
Authors: Illing Cyprian , Ren Zhe , Agaponova Anna , Heuer Arthur , Ernst Frank
Published: November 2021

For rapid surface engineering of Cr-containing alloys by low-temperature nitrocarburization, we introduce a process based on pyrolysis of solid reagents, e.g., urea, performed in an evacuated closed vessel. Upon heating to temperatures high enough for rapid diffusion of interstitial solute, but low enough to avoid second-phase precipitation, the reagent is pyrolyzed to a gas atmosphere containing molecules that (i) activate the alloy surface by stripping away the passivating Cr2O3-rich surface film (diffusion barrier) and (ii) rapidly infuse carbon and nitrogen into the alloy. We demonstrate quantitatively that this method can generate a subsurface zone with concentrated carbon and nitrogen comparable to what can be accomplished by established (e.g., gas-phase- or plasma-based) methods, but with significantly reduced processing time. As another important difference to established gas-phase processing, the interaction of gas molecules with the alloy surface can have auto-catalytic effects by altering the gas composition in a way that accelerates solute infusion by providing a high activity of HNCO. The new method lends itself to rapid experimentation with a minimum of laboratory equipment.
Measuring Salinity and Density of Seawater Samples with Different Salt Compositions and Suspended Materials
Authors: Grekov Aleksandr N. , Grekov Nikolay A. , Sychov Evgeniy N.
Published: November 2021

Determining the solute mass amount in seawater using in situ measurements in seas and oceans is currently an unresolved problem. To solve it, it is necessary to develop both new methods and instruments for measurements. The authors of this article analyzed methods for the indirect measurement of salinity and density using parameters that can be measured in situ, including relative electrical conductivity, speed of sound, temperature, and hydrostatic pressure. The authors propose an electric conductivity sensor design that allows for the obtainment of data on solid suspensions along with measuring the impedance of electrodes under various the alternating current frequencies. The authors analyzed the joint measurement technique using the Conductivity-Temperature-Depth (CTD) and Sound Velocity Profiler (SVP) devices in a marine testing area. Based on the results of joint measurements, the authors present tests of water samples of various salt compositions for the presence of solid suspensions.
Organic Phase Change Materials for Thermal Energy Storage: Influence of Molecular Structure on Properties
Authors: Kahwaji Samer , White Mary Anne
Published: November 2021

Materials that change phase (e.g., via melting) can store thermal energy with energy densities comparable to batteries. Phase change materials will play an increasing role in reduction of greenhouse gas emissions, by scavenging thermal energy for later use. Therefore, it is useful to have summaries of phase change properties over a wide range of materials. In the present work, we review the relationship between molecular structure and trends in relevant phase change properties (melting temperature, and gravimetric enthalpy of fusion) for about 200 organic compounds from several chemical families, namely alkanes (paraffins), fatty acids, fatty alcohols, esters, diamines, dinitriles, diols, dioic acids, and diamides. We also review availability and cost, chemical compatibility, and thermal and chemical stabilities, to provide practical information for PCM selection. Compounds with even chain alkyl lengths generally give higher melting temperatures, store more thermal energy per unit mass due to more efficient packing, and are of lower cost than the comparable compounds with odd alkyl chains.
Polyamines Upregulate Cephalosporin C Production and Expression of β-Lactam Biosynthetic Genes in High-Yielding Acremonium chrysogenum Strain
Authors: Zhgun Alexander A. , Eldarov Mikhail A.
Published: November 2021

The high-yielding production of pharmaceutically significant secondary metabolites in filamentous fungi is obtained by random mutagenesis; such changes may be associated with shifts in the metabolism of polyamines. We have previously shown that, in the Acremonium chrysogenum cephalosporin C high-yielding strain (HY), the content of endogenous polyamines increased by four- to five-fold. Other studies have shown that the addition of exogenous polyamines can increase the production of target secondary metabolites in highly active fungal producers, in particular, increase the biosynthesis of β-lactams in the Penicillium chrysogenum Wis 54–1255 strain, an improved producer of penicillin G. In the current study, we demonstrate that the introduction of exogenous polyamines, such as spermidine or 1,3-diaminopropane, to A. chrysogenum wild-type (WT) and HY strains, leads to an increase in colony germination and morphological changes in a complete agar medium. The addition of 5 mM polyamines during fermentation increases the production of cephalosporin C in the A. chrysogenum HY strain by 15–20% and upregulates genes belonging to the beta-lactam biosynthetic cluster. The data obtained indicate the intersection of the metabolisms of polyamines and beta-lactams in A. chrysogenum and are important for the construction of improved producers of secondary metabolites in filamentous fungi.
Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy
Authors: Lachowicz Joanna Izabela , Lecca Luigi Isaia , Meloni Federico , Campagna Marcello
Published: November 2021

An increasing number of pathologies correlates with both toxic and essential metal ions dyshomeostasis. Next to known genetic disorders (e.g., Wilson’s Disease and β-Thalassemia) other pathological states such as neurodegeneration and diabetes are characterized by an imbalance of essential metal ions. Metal ions can enter the human body from the surrounding environment in the form of free metal ions or metal-nanoparticles, and successively translocate to different tissues, where they are accumulated and develop distinct pathologies. There are no characteristic symptoms of metal intoxication, and the exact diagnosis is still difficult. In this review, we present metal-related pathologies with the most common onsets, biomarkers of metal intoxication, and proper techniques of metal qualitative and quantitative analysis. We discuss the possible role of drugs with metal-chelating ability in metal dyshomeostasis, and present recent advances in therapies of metal-related diseases.
Interaction of Carrier Protein with Potential Metallic Drug Candidate N-Glycoside ‘GATPT’: Validation by Multi-Spectroscopic and Molecular Docking Approaches
Authors: Parveen Sabiha , Ali Mohd. Sajid , Al-Lohedan Hamad A. , Tabassum Sartaj
Published: November 2021

Lysozyme is often used as a model protein to study interaction with drug molecules and to understand biological processes which help in illuminating the therapeutic effectiveness of the drug. In the present work, in vitro interaction studies of 1-{(2-hydroxyethyl)amino}-2-amino-1,2-dideoxy-d-glucose triphenyl tin (IV) (GATPT) complex with lysozyme were carried out by employing various biophysical methods such as absorption, fluorescence, and circular dichroism (CD) spectroscopies. The experimental results revealed efficient binding affinity of GATPT with lysozyme with intrinsic binding (Kb) and binding constant (K) values in the order of 105 M−1. The number of binding sites and thermodynamic parameters ΔG, ΔH, and ΔS at four different temperatures were also calculated and the interaction of GATPT with lysozyme was found to be enthalpy and entropy driven. The CD spectra revealed alterations in the population of α–helical content within the secondary structure of lysozyme in presence of GATPT complex. The morphological analysis of the complex with lysozyme and lysozyme-DNA condensates was carried out by employing confocal and SEM studies. Furthermore, the molecular docking studies confirmed the interaction of GATPT within the larger hydrophobic pocket of the lysozyme via several non-covalent interactions.
Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[e][1,4]oxazepin-2(3H)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro
Authors: Josa-Culleré Laia , Cogswell Thomas , Georgiou Irene , Jay-Smith Morgan , Jackson Thomas , Bataille Carole , Davies Stephen , Vyas Paresh , Milne Thomas , Wynne Graham , Russell Angela
Published: November 2021

Acute myeloid leukemia (AML) is the most aggressive type of blood cancer, and there is a continued need for new treatments that are well tolerated and improve long-term survival rates in patients. Induction of differentiation has emerged as a promising alternative to conventional cytotoxic chemotherapy, but known agents lack efficacy in genetically distinct patient populations. Previously, we established a phenotypic screen to identify small molecules that could stimulate differentiation in a range of AML cell lines. Utilising this strategy, a 1,5-dihydrobenzo[e][1,4]oxazepin-2(3H)-one hit compound was identified. Herein, we report the hit validation in vitro, structure-activity relationship (SAR) studies and the pharmacokinetic profiles for selected compounds.
Modern Methods for the Sustainable Synthesis of Metalloporphyrins
Authors: Gomes Carla , Peixoto Mariana , Pineiro Marta
Published: November 2021

Metalloporphyrins are involved in many and diverse applications that require the preparation of these compounds in an efficient manner, which nowadays, also involves taking into consideration sustainability issues. In this context, we use ball milling mechanochemistry and sonochemistry for the rational development of synthetic strategies for the sustainable preparation of metalloporphyrins. Zinc, copper, cobalt and palladium complexes of hydrophobic porphyrins were obtained in high yields and under mechanical action with a moderate excess of the metal salt, without any solvent or additive. Sonochemistry prove to be a good alternative for the preparation of metal complexes of water-soluble porphyrins in good yields and short reaction times. Both strategies have good sustainability scores, close to the ideal values, which is useful in comparing and helping to choose the more adequate method.
Facile Synthesis of Peptide-Conjugated Gold Nanoclusters with Different Lengths
Authors: Ma Qun , Liu Lichao , Yang Zeyue , Zheng Peng
Published: November 2021

The synthesis of ultra-small gold nanoclusters (Au NCs) with sizes down to 2 nm has received increasing interest due to their unique optical and electronic properties. Like many peptide-coated gold nanospheres synthesized before, modified gold nanoclusters with peptide conjugation are potentially significant in biomedical and catalytic fields. Here, we explore whether such small-sized gold nanoclusters can be conjugated with peptides also and characterize them using atomic force microscopy. Using a long and flexible elastin-like polypeptide (ELP)20 as the conjugated peptide, (ELP)20-Au NCs was successfully synthesized via a one-pot synthesis method. The unique optical and electronic properties of gold nanoclusters are still preserved, while a much larger size was obtained as expected due to the peptide conjugation. In addition, a short and rigid peptide (EAAAK)3 was conjugated to the gold nanoclusters. Their Yong’s modulus was characterized using atomic force microscopy (AFM). Moreover, the coated peptide on the nanoclusters was pulled using AFM-based single molecule-force spectroscopy (SMFS), showing expected properties as one of the first force spectroscopy experiments on peptide-coated nanoclusters. Our results pave the way for further modification of nanoclusters based on the conjugated peptides and show a new method to characterize these materials using AFM-SMFS.
Analytical Calculations of Scattering Amplitude of Surface Plasmon Polaritons Excited by a Spherical Nanoantenna
Authors: Dyshlyuk Anton V. , Proskurin Alexey , Bogdanov Andrey A. , Vitrik Oleg B.
Published: November 2021

Since surface plasmon polaritons (SPPs) are surface waves, they cannot be excited by an incident plane wave, because free-space photons do not possess a sufficient in-plane momentum. Phase matching between the incident light and SPP can be achieved using a high-refractive-index prism, grating, or nanoantennas. In this work, we found an expression for the amplitude of SPP excited by an arbitrary 3D current distribution placed near a metal interface. The developed method is based on the well-known technique used in waveguide theory that enables finding the amplitudes of waveguide modes excited by the external currents. It reduces the SPP excitation problem to the summation of the set of emitters. As a particular example, we considered a spherical dipole nanoantenna on a metal substrate illuminated by a normally incident plane wave. The analytical calculations were in good agreement with the full-wave numerical simulations.
Ga2O3(Sn) Oxides for High-Temperature Gas Sensors
Authors: Vorobyeva Nataliya , Rumyantseva Marina , Platonov Vadim , Filatova Darya , Chizhov Artem , Marikutsa Artem , Bozhev Ivan , Gaskov Alexander
Published: November 2021

Gallium(III) oxide is a promising functional wide-gap semiconductor for high temperature gas sensors of the resistive type. Doping of Ga2O3 with tin improves material conductivity and leads to the complicated influence on phase content, microstructure, adsorption sites, donor centers and, as a result, gas sensor properties. In this work, Ga2O3 and Ga2O3(Sn) samples with tin content of 0–13 at.% prepared by aqueous co-precipitation method were investigated by X-ray diffraction, nitrogen adsorption isotherms, X-ray photoelectron spectroscopy, infrared spectroscopy and probe molecule techniques. The introduction of tin leads to a decrease in the average crystallite size, increase in the temperature of β-Ga2O3 formation. The sensor responses of all Ga2O3(Sn) samples to CO and NH3 have non-monotonous character depending on Sn content due to the following factors: the formation of donor centers and the change of free electron concentration, increase in reactive chemisorbed oxygen ions concentration, formation of metastable Ga2O3 phases and segregation of SnO2 on the surface of Ga2O3(Sn) grains.
Synthesis and Enhanced Light Photocatalytic Activity of Modulating Band BiOBrXI1−X Nanosheets
Authors: Zhang Bingke , Fu Shengwen , Wang Dongbo , Jiao Shujie , Zeng Zhi , Zhang Xiangyu , Xu Zhikun , Liu Yaxin , Zhao Chenchen , Pan Jingwen , Liu Donghao , Wang Jinzhong
Published: November 2021

The photocatalysis technique has been proven to be a promising method to solve environmental pollution in situations of energy shortage, and has been intensively investigated in the field of pollutant degradation. In this work, a band structure-controlled solid solution of BiOBrXI1−X (x = 0.00, 0.05, 0.10, 0.15, 0.20, 1.00) with highly efficient light-driven photocatalytic activities was successfully synthesized via simple solvothermal methods. The phase composition, crystal structure, morphology, internal molecular vibration, optical properties, and energy band structure were characterized and analyzed by XRD, SEM, HRTEM, XPS, Raman, and UV Vis DRS. To evaluate the photocatalytic activity of BiOBrXI1−X, rhodamine B was selected as an organic pollutant. In particular, BiOBr0.15I0.85 displayed significantly enhanced photocatalytic activity by virtue of modulating the energy band position, optimizing redox potentials, and accelerating carrier separation. Moreover, the enhancement mechanism was elucidated on the basis of band structure engineering, which provides ideas for the design of highly active photocatalysts for practical application in the fields of environmental issues and energy conservation.
Advances in Non-Coding RNA Sequencing
Authors: Micheel Julia , Safrastyan Aram , Wollny Damian
Published: November 2021

Non-coding RNAs (ncRNAs) comprise a set of abundant and functionally diverse RNA molecules. Since the discovery of the first ncRNA in the 1960s, ncRNAs have been shown to be involved in nearly all steps of the central dogma of molecular biology. In recent years, the pace of discovery of novel ncRNAs and their cellular roles has been greatly accelerated by high-throughput sequencing. Advances in sequencing technology, library preparation protocols as well as computational biology helped to greatly expand our knowledge of which ncRNAs exist throughout the kingdoms of life. Moreover, RNA sequencing revealed crucial roles of many ncRNAs in human health and disease. In this review, we discuss the most recent methodological advancements in the rapidly evolving field of high-throughput sequencing and how it has greatly expanded our understanding of ncRNA biology across a large number of different organisms.
Oral Squamous Cell Carcinoma Mimicking Medication-Related Osteonecrosis of the Jaws (MRONJ): A Case Series
Authors: Mauceri Rodolfo , Toro Corrado , Panzarella Vera , Iurato Carbone Martina , Rodolico Vito , Campisi Giuseppina
Published: November 2021

(1) Background: Medication-related osteonecrosis of the jaw (MRONJ) is a potential adverse drug reaction of antiresorptive and/or antiangiogenic treatment. MRONJ is mostly diagnosed by anamnestic data, clinical examination and radiological findings, with signs and symptoms often unspecific. On the other hand, oral squamous cell carcinoma (OSCC) is characteristic for its pleomorphic appearance (e.g., ulcer, mucous dehiscence, non-healing post-extractive socket). We report three cases where OSCC mimicked MRONJ lesions. (2) Patients: Three patients undergoing amino-bisphosphonate treatment for osteoporosis presented with areas of intraorally exposed jawbone and unspecific radiological signs compatible with MRONJ. Due to the clinical suspicious of malignant lesion, incisional biopsy for histological examination was also performed. (3) Results: Histological examination of the tissue specimen revealed the presence of OSCC. All patients underwent cancer treatment. (4) Conclusions: Several signs and symptoms of OSCC may simulate, in patients with a history of anti-resorptive, MRONJ; for these reasons, it is important to perform histologic analysis when clinicians are facing a suspicious malignant lesion.
Experimental Evaluation of 65Zn Decorporation Kinetics Following Rapid and Delayed Zn-DTPA Interventions in Rats. Biphasic Compartmental and Square-Root Law Mathematical Modeling
Authors: Voicu Victor , Jiquidi Marilena , Mircioiu Constantin , Sandulovici Roxana , Nicolescu Adrian
Published: November 2021

The decorporation kinetics of internal radionuclide contamination is a long-term treatment raising modeling, planning, and managing problems, especially in the case of late intervention when the radiotoxic penetrated the deep compartments. The decorporation effectiveness of the highly radiotoxic 65ZnCl2 by Zn-DTPA (dosed at 3.32 mg and 5 mg/0.25 mL/100 g body weight) was investigated in Wistar male rats over a ten-day period under various treatments (i.e., as a single dose before contamination; as a single dose before and 24 h after contamination; and as daily administrations for five consecutive days starting on day 12 after contamination). The radioactivity was measured using the whole-body counting method. Mono- and bi-compartmental decorporation kinetics models proved applicable in the case of a rapid intervention. It was found that a diffusion model of the radionuclide from tissues to blood better describes the decorporation kinetics after more than ten days post treatment, and the process has been mathematically modeled as a diffusion from an infinite reservoir to a semi-finite medium. The mathematical solution led to a square-root law for describing the 65Zn decorporation. This law predicts a slower release than exponential or multiexponential equations, and could better explain the very long persistence of radionuclides in the living body. Splitting data and modeling in two steps allows a better understanding, description and prediction of the evolution of contamination, a separate approach to the treatment schemes of acute and chronic contamination.
Therapeutic Stomatocytes with Aggregation Induced Emission for Intracellular Delivery
Authors: Shao Jingxin , Cao Shoupeng , Wu Hanglong , Abdelmohsen Loai K. E. A. , van Hest Jan C. M.
Published: November 2021

Bowl-shaped biodegradable polymersomes, or stomatocytes, have much potential as drug delivery systems, due to their intriguing properties, such as controllable size, programmable morphology, and versatile cargo encapsulation capability. In this contribution, we developed well-defined therapeutically active stomatocytes with aggregation-induced emission (AIE) features by self-assembly of biodegradable amphiphilic block copolymers, comprising poly(ethylene glycol) (PEG) and AIEgenic poly(trimethylene carbonate) (PTMC) moieties. The presence of the AIEgens endowed the as-prepared stomatocytes with intrinsic fluorescence, which was employed for imaging of cellular uptake of the particles. It simultaneously enabled the photo-mediated generation of reactive oxygen species (ROS) for photodynamic therapy. The potential of the therapeutic stomatocytes as cargo carriers was demonstrated by loading enzymes (catalase and glucose oxidase) in the nanocavity, followed by a cross-linking reaction to achieve stable encapsulation. This provided the particles with a robust motile function, which further strengthened their therapeutic effect. With these unique features, enzyme-loaded AIEgenic stomatocytes are an attractive platform to be exploited in the field of nanomedicine.
Optimization of Printing Parameters for Digital Light Processing 3D Printing of Hollow Microneedle Arrays
Authors: Mathew Essyrose , Pitzanti Giulia , Gomes dos Santos Ana L. , Lamprou Dimitrios A.
Published: November 2021

3D printing is an emerging technology aiming towards personalized drug delivery, among many other applications. Microneedles (MN) are a viable method for transdermal drug delivery that is becoming more popular for delivery through the skin. However, there is a need for a faster fabrication process with potential for easily exploring different geometries of MNs. In the current study, a digital light processing (DLP) method of 3D printing for fabrication of hollow MN arrays using commercial UV curable resin was proposed. Print quality was optimised by assessing the effect of print angle on needle geometries. Mechanical testing of MN arrays was conducted using a texture analyser. Angled prints were found to produce prints with geometries closer to the CAD designs. Curing times were found to affect the mechanical strength of MNs, with arrays not breaking when subjected to 300 N of force but were bent. Overall, DLP process produced hollow MNs with good mechanical strength and depicts a viable, quick, and efficient method for the fabrication of hollow MN arrays.
Broad Spectrum Antiviral Properties of Cardiotonic Steroids Used as Potential Therapeutics for Emerging Coronavirus Infections
Authors: Jin Young-Hee , Jeon Sangeun , Lee Jihye , Kim Seungtaek , Jang Min Seong , Park Chul Min , Song Jong Hwan , Kim Hyoung Rae , Kwon Sunoh
Published: November 2021

Cardiotonic steroids are steroid-like natural compounds known to inhibit Na+/K+-ATPase pumps. To develop a broad-spectrum antiviral drug against the emerging coronavirus infection, this study assessed the antiviral properties of these compounds. The activity of seven types of cardiotonic steroids against the MERS-CoV, SARS-CoV, and SARS-CoV-2 coronavirus varieties was analyzed using immunofluorescence antiviral assay in virus-infected cells. Bufalin, cinobufagin, and telocinobufagin showed high anti-MERS-CoV activities (IC50, 0.017~0.027 μM); bufalin showed the most potent anti-SARS-CoV and SARS-CoV-2 activity (IC50, 0.016~0.019 μM); cinobufotalin and resibufogenin showed comparatively low anti-coronavirus activity (IC50, 0.231~1.612 μM). Differentially expressed genes in Calu3 cells treated with cinobufagin, telocinobufagin, or bufalin, which had high antiviral activity during MERS-CoV infection were analyzed using QuantSeq 3′ mRNA-Seq analysis and data showed similar gene expression patterns. Furthermore, the intraperitoneal administration of 10 mg/kg/day bufalin, cinobufagin, or digitoxin induced 100% death after 1, 2, and 4 days in 5-day repeated dose toxicity studies and it indicated that bufalin had the strongest toxicity. Pharmacokinetic studies suggested that telocinobufagin, which had high anti-coronavirus activity and low toxicity, had better microsomal stability, lower CYP inhibition, and better oral bioavailability than cinobufagin. Therefore, telocinobufagin might be the most promising cardiotonic steroid as a therapeutic for emerging coronavirus infections, including COVID-19.
New Compounds with Bioisosteric Replacement of Classic Choline Kinase Inhibitors Show Potent Antiplasmodial Activity
Authors: Aguilar-Troyano Francisco José , Torretta Archimede , Rubbini Gianluca , Fasiolo Alberto , Luque-Navarro Pilar María , Carrasco-Jimenez María Paz , Pérez-Moreno Guiomar , Bosch-Navarrete Cristina , González-Pacanowska Dolores , Parisini Emilio , Lopez-Cara Luisa Carlota
Published: November 2021

In the fight against Malaria, new strategies need to be developed to avoid resistance of the parasite to pharmaceutics and other prevention barriers. Recently, a Host Directed Therapy approach based on the suppression of the starting materials uptake from the host by the parasite has provided excellent results. In this article, we propose the synthesis of bioisosteric compounds that are capable of inhibiting Plasmodium falciparum Choline Kinase and therefore to reduce choline uptake, which is essential for the development of the parasite. Of the 41 bioisosteric compounds reported herein, none showed any influence of the linker on the antimalarial and enzyme inhibitory activity, whereas an effect of the type of cationic heads used could be observed. SARs determined that the thienopyrimidine substituted in 4 by a pyrrolidine is the best scaffold, independently of the chosen linker. The decrease in lipophilicity seems to improve the antimalarial activity but to cause an opposite effect on the inhibition of the enzyme. While potent compounds with similar good inhibitory values have been related to the proposed mechanism of action, some of them still show discrepancies and further studies are needed to determine their specific molecular target.