bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hole Nucleation Method Combining BESO and Topological Sensitivity for Level Set Topology Optimization
Authors: Cao Shuangyuan , Wang Hanbin , Tong Jianbin , Sheng Zhongqi
Published: April 2021

As is known to all, the incapacity to nucleate holes automatically in the design domain is one of the main issues of the classical level set topology optimization method. To solve the issue of hole nucleation, this paper employs the bi-directional evolutionary structural optimization (BESO) method based on the material removal scheme and the frequently used topological sensitivity and proposes the combining BESO and topological sensitivity (CBT) method for level set topology optimization. This method can replace the existing hole nucleation method for level set topology optimization. First, the topological sensitivity is combined with BESO, and the BESO method based on topological sensitivity is proposed. Second, the method is integrated into level set topology optimization to solve the issue of hole nucleation. Two sensitivity thresholds are defined depending on the evolutionary volume ratio and boundary topological sensitivity, respectively, and the smaller one is used as the sensitivity threshold for hole nucleation. The material is removed from the design domain to nucleate holes based on this threshold. Three classical two-dimensional numerical examples are used to validate the proposed hole nucleation method.
Production of Nanocellulose by Enzymatic Treatment for Application in Polymer Composites
Authors: Zielińska Daria , Szentner Kinga , Waśkiewicz Agnieszka , Borysiak Sławomir
Published: April 2021

In the last few years, the scientific community around the world has devoted a lot of attention to the search for the best methods of obtaining nanocellulose. In this work, nanocellulose was obtained in enzymatic reactions with strictly defined dispersion and structural parameters in order to use it as a filler for polymers. The controlled enzymatic hydrolysis of the polysaccharide was carried out in the presence of cellulolytic enzymes from microscopic fungi—Trichoderma reesei and Aspergillus sp. It has been shown that the efficiency of bioconversion of cellulose material depends on the type of enzymes used. The use of a complex of cellulases obtained from a fungus of the genus Trichoderma turned out to be an effective method of obtaining cellulose of nanometric dimensions with a very low polydispersity. The effect of cellulose enzymatic reactions was assessed using the technique of high-performance liquid chromatography coupled with a refractometric detector, X-ray diffraction, dynamic light scattering and Fourier transform infrared spectroscopy. In the second stage, polypropylene composites with nanometric cellulose were obtained by extrusion and injection. It was found by means of X-ray diffraction, hot stage optical microscopy and differential scanning calorimetry that nanocellulose had a significant effect on the supermolecular structure, nucleation activity and the course of phase transitions of the obtained polymer nanocomposites. Moreover, the obtained nanocomposites are characterized by very good strength properties. This paper describes for the first time that the obtained cellulose nanofillers with defined parameters can be used for the production of polymer composites with a strictly defined polymorphic structure, which in turn may influence future decision making about obtaining materials with controllable properties, e.g., high flexibility, enabling the thermoforming process of packaging.
The Influence of Surface Preparation, Chewing Simulation, and Thermal Cycling on the Phase Composition of Dental Zirconia
Authors: Wertz Markus , Fuchs Florian , Hoelzig Hieronymus , Wertz Julia Maria , Kloess Gert , Hahnel Sebastian , Rosentritt Martin , Koenig Andreas
Published: April 2021

The effect of dental technical tools on the phase composition and roughness of 3/4/5 yttria-stabilized tetragonal zirconia polycrystalline (3y-/4y-/5y-TZP) for application in prosthetic dentistry was investigated. Additionally, the X-ray diffraction methods of Garvie-Nicholson and Rietveld were compared in a dental restoration context. Seven plates from two manufacturers, each fabricated from commercially available zirconia (3/4/5 mol%) for application as dental restorative material, were stressed by different dental technical tools used for grinding and polishing, as well as by chewing simulation and thermocycling. All specimens were examined via laser microscopy (surface roughness) and X-ray diffraction (DIN EN ISO 13356 and the Rietveld method). As a result, the monoclinic phase fraction was halved by grinding for the 3y-TZP and transformed entirely into one of the tetragonal phases by polishing/chewing for all specimens. The tetragonal phase t is preferred for an yttria content of 3 mol% and phase t″ for 5 mol%. Mechanical stress, such as polishing or grinding, does not trigger low-temperature degradation (LTD), but it fosters a phase transformation from monoclinic to tetragonal under certain conditions. This may increase the translucency and deteriorate the mechanical properties to some extent.
An Experimental Test Bench for Cable-Driven Transmission
Authors: Torres Charry Giovanni , Gómez Mendoza Juan Bernardo
Published: April 2021

Cable-driven transmissions are used widely in robotic applications. However, design variables and parameters of this kind of transmission remain under study, both analytically and experimentally. In this paper, an experimental test bench to evaluate the behavior of medium-low power pulley-cable transmissions is presented. The design of the test bench allows manipulating variables such as dimensions, external load, speed, and cable tension. The system consists mainly of a brushless direct current (DC) motor, two load cells to measure the mechanical reactive force in the motor, two dismountable pulleys, two drums, a perforated disk, and several masses that provide the load and the inertial load, and electronic modules to control the speed and position of the pulley. Special attention was paid to the calibration of the load cells, focused in compensating the effect of creep. Validation tests were carried out in order to evaluate the device design. Next, pilot experiments were performed to estimate the friction behavior in the transmission. Preliminary results suggest that the friction in the transmission is largely governed by the friction behavior of the bearings.
Miura-Reciprocal Transformation and Symmetries for the Spectral Problems of KdV and mKdV
Authors: Albares Paz , Estévez Pilar Garcia
Published: April 2021

We present reciprocal transformations for the spectral problems of Korteveg de Vries (KdV) and modified Korteveg de Vries (mKdV) equations. The resulting equations, RKdV (reciprocal KdV) and RmKdV (reciprocal mKdV), are connected through a transformation that combines both Miura and reciprocal transformations. Lax pairs for RKdV and RmKdV are straightforwardly obtained by means of the aforementioned reciprocal transformations. We have also identified the classical Lie symmetries for the Lax pairs of RKdV and RmKdV. Non-trivial similarity reductions are computed and they yield non-autonomous ordinary differential equations (ODEs), whose Lax pairs are obtained as a consequence of the reductions.
Dynamical Analysis and Optimal Control for a SEIR Model Based on Virus Mutation in WSNs
Authors: Liu Guiyun , Chen Jieyong , Liang Zhongwei , Peng Zhimin , Li Junqiang
Published: April 2021

With the rapid development of science and technology, the application of wireless sensor networks (WSNs) is more and more widely. It has been widely concerned by scholars. Viruses are one of the main threats to WSNs. In this paper, based on the principle of epidemic dynamics, we build a SEIR propagation model with the mutated virus in WSNs, where E nodes are infectious and cannot be repaired to S nodes or R nodes. Subsequently, the basic reproduction number R0, the local stability and global stability of the system are analyzed. The cost function and Hamiltonian function are constructed by taking the repair ratio of infected nodes and the repair ratio of mutated infected nodes as optimization control variables. Based on the Pontryagin maximum principle, an optimal control strategy is designed to effectively control the spread of the virus and minimize the total cost. The simulation results show that the model has a guiding significance to curb the spread of mutated virus in WSNs.
The Real Forms of the Fractional Supergroup SL(2,C)
Authors: Ucan Yasemen , Kosker Resat
Published: April 2021

The real forms of complex groups (or algebras) are important in physics and mathematics. The Lie group SL2,C is one of these important groups. There are real forms of the classical Lie group SL2,C and the quantum group SL2,C in the literature. Inspired by this, in our study, we obtain the real forms of the fractional supergroups shown with A3NSL2,C, for the non-trivial N = 1 and N = 2 cases, that is, the real forms of the fractional supergroups A31SL2,C and A32SL2,C.
Impact of Magnetic Field Environment on the EDM Performance of Al-SiC Metal Matrix Composite
Authors: Ablyaz Timur Rizovich , Bains Preetkanwal Singh , Sidhu Sarabjeet Singh , Muratov Karim Ravilevich , Shlykov Evgeny Sergeevich
Published: April 2021

In the present work, a hybrid magnetic field assisted powder mixed electrical discharge machining had been carried out on the Aluminum-Silicon Carbide (Al-SiC) metal matrix composite. The aim of the study was to obtain higher surface finish, and enhanced material removal rate. The dielectric mediums employed were plain EDM oil, SiCp mixed and graphite powder mixed EDM oil for flushing through the tube electrode. The magnetic field intensity, discharge current, T-on/off duration and type of dielectric were the control variables used for present investigation. From the results, it was observed that the machining variables for instance, discharge current, T-on/off duration and type of dielectric conditions remarkably affected the material removal rate, micro-hardness and surface roughness of the machined composite material. The MRR augmented considerably with an increase in the magnetic field intensity along with peak current. Subsequently, the composite with lesser vol.% of SiC particulates witnessed sharp rise in MRR in maximum magnetic field environment (0.66T). In addition, quality of the machined surface improved significantly in graphite powder mixed dielectric flushing condition with intermediate external magnetic field environment. Besides, an enhancement of micro-hardness was quantified as compared to base material due to the transfer of the material (SiCp) during powder mixed ED machining.
Bottom-Up (Cu, Ag, Au)/Al2O3/Bi2Te3 Assembled Thermoelectric Heterostructures
Authors: Wu Zhenhua , Zhang Shuai , Liu Zekun , Lu Cheng , Hu Zhiyu
Published: April 2021

The interface affects the transmission behavior of electrons and phonons, which in turn determines the performance of thermoelectric materials. In this paper, metals (Cu, Ag, Au)/Al2O3/Bi2Te3 heterostructures have been fabricated from bottom to up to optimize the thermoelectric power factor. The introducing metals can be alloyed with Bi2Te3 or form interstitials or dopants to adjust the carrier concentration and mobility. In addition, the metal-semiconductor interface as well as the metal-insulator-semiconductor interface constructed by the introduced metal and Al2O3 would further participate in the regulation of the carrier transport process. By adjusting the metal and oxide layer, it is possible to realize the simultaneous optimization of electric conductivity and Seebeck coefficient. This work will enable the optimal and novel design of heterostructures for thermoelectric materials with further improved performance.
Rethinking Manure Application: Increase in Multidrug-Resistant Enterococcus spp. in Agricultural Soil Following Chicken Litter Application
Authors: Fatoba Dorcas Oladayo , Abia Akebe Luther King , Amoako Daniel G. , Essack Sabiha Y.
Published: April 2021

The current study investigated the impact of chicken litter application on the abundance of multidrug-resistant Enterococcus spp. in agricultural soil. Soil samples were collected from five different strategic places on a sugarcane farm before and after manure application for four months. Chicken litter samples were also collected. Enterococci were enumerated using the Enterolert®/Quanti-Tray 2000® system and confirm and differentiated into species using real-time PCR. The antibiotic susceptibility profile of the isolates was determined using the disk diffusion method following the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The overall mean bacterial count was significantly higher (p < 0.05) in manure-amended soil (3.87 × 107 MPN/g) than unamended soil (2.89 × 107 MPN/g). Eight hundred and thirty-five enterococci (680 from soil and 155 from litter) were isolated, with E. casseliflavus being the most prevalent species (469; 56.2%) and E. gallinarum being the least (16; 1.2%). Approximately 56% of all the isolates were resistant to at least one antibiotic tested, with the highest resistance observed against tetracycline (33%) and the lowest against chloramphenicol (0.1%); 17% of E. faecium were resistant to quinupristin-dalfopristin. Additionally, 27.9% (130/466) of the isolates were multidrug-resistant, with litter-amended soil harbouring more multidrug-resistant (MDR) isolates (67.7%; 88/130) than unamended soil (10.0%; 13/130). All isolates were susceptible to tigecycline, linezolid and gentamicin. About 7% of the isolates had a multiple antimicrobial resistance index > 0.2, indicative of high antibiotic exposure. Although organic fertilizers are regarded as eco-friendly compared to chemical fertilizers for improving soil fertility, the application of untreated animal manure could promote the accumulation of antibiotics and their residues and antibiotic-resistant bacteria in the soil, creating an environmental reservoir of antimicrobial resistance, with potential human and environmental health risks.
Baicalein and Baicalin Inhibit SARS-CoV-2 RNA-Dependent-RNA Polymerase
Authors: Zandi Keivan , Musall Katie , Oo Adrian , Cao Dongdong , Liang Bo , Hassandarvish Pouya , Lan Shuiyun , Slack Ryan L. , Kirby Karen A. , Bassit Leda , Amblard Franck , Kim Baek , AbuBakar Sazaly , Sarafianos Stefan G. , Schinazi Raymond F.
Published: April 2021

Coronavirus Disease 2019 (COVID-19) is a deadly emerging infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Because SARS-CoV-2 is easily transmitted through the air and has a relatively long incubation time, COVID-19 has rapidly developed into a global pandemic. As there are no antiviral agents for the prevention and treatment of this severe pathogen except for remdesivir, development of antiviral therapies to treat infected individuals remains highly urgent. Here, we showed that baicalein and baicalin exhibited significant antiviral activity against SARS-CoV-2, the causative agent of COVID-19 through in vitro studies. Our data through cell-based and biochemical studies showed that both compounds act as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors directly and inhibit the activity of the SARS-CoV-2 RdRp, but baicalein was more potent. We also showed specific binding of baicalein to the SARS-CoV-2 RdRp, making it a potential candidate for further studies towards therapeutic development for COVID-19 as a selective non-nucleoside polymerase inhibitor.
Evaluating Transmission Paths for Three Different Bartonella spp. in Ixodes ricinus Ticks Using Artificial Feeding
Authors: Król Nina , Militzer Nina , Stöbe Elisa , Nijhof Ard M. , Pfeffer Martin , Kempf Volkhard A. J. , Obiegala Anna
Published: April 2021

Bartonellae are facultative intracellular alpha-proteobacteria often transmitted by arthropods. Ixodes ricinus is the most important vector for arthropod-borne pathogens in Europe. However, its vector competence for Bartonella spp. is still unclear. This study aimed to experimentally compare its vector competence for three Bartonella species: B. henselae, B. grahamii, and B. schoenbuchensis. A total of 1333 ticks (1021 nymphs and 312 adults) were separated into four groups, one for each pathogen and a negative control group. Ticks were fed artificially with bovine blood spiked with the respective Bartonella species. DNA was extracted from selected ticks to verify Bartonella-infection by PCR. DNA of Bartonella spp. was detected in 34% of nymphs and females after feeding. The best engorgement results were obtained by ticks fed with B. henselae-spiked blood (65.3%) and B. schoenbuchensis (61.6%). Significantly more nymphs fed on infected blood (37.3%) molted into adults compared to the control group (11.4%). Bartonella DNA was found in 22% of eggs laid by previously infected females and in 8.6% of adults molted from infected nymphs. The transovarial and transstadial transmission of bartonellae suggest that I. ricinus could be a potential vector for three bacteria.
Membrane-Supported Layered Coordination Polymer as an Advanced Sustainable Catalyst for Desulfurization
Authors: Mirante Fátima , Mendes Ricardo F. , Faria Rui G. , Cunha-Silva Luís , Paz Filipe A. Almeida , Balula Salete S.
Published: April 2021

The application of a catalytic membrane in the oxidative desulfurization of a multicomponent model diesel formed by most refractory sulfur compounds present in fuel is reported here for the first time. The catalytic membrane was prepared by the impregnation of the active lamellar [Gd(H4nmp)(H2O)2]Cl·2H2O (UAV-59) coordination polymer (CP) into a polymethyl methacrylate (PMMA, acrylic glass) supporting membrane. The use of the catalytic membrane in the liquid–liquid system instead of a powder catalyst arises as an enormous advantage associated with the facility of catalyst handling while avoiding catalyst mass loss. The optimization of various parameters allowed to achieve a near complete desulfurization after 3 h under sustainable conditions, i.e., using an aqueous H2O2 as oxidant and an ionic liquid as extraction solvent ([BMIM]PF6, 1:0.5 ratio diesel:[BMIM]PF6). The performance of the catalytic membrane and of the powdered UAV-59 catalyst was comparable, with the advantage that the former could be recycled successfully for a higher number of desulfurization cycles without the need of washing and drying procedures between reaction cycles, turning the catalytic membrane process more cost-efficient and suitable for future industrial application.
Inhibitory Effects of Erythrosine/Curcumin Derivatives/Nano-Titanium Dioxide-Mediated Photodynamic Therapy on Candida albicans
Authors: Kanpittaya Kasama , Teerakapong Aroon , Morales Noppawan Phumala , Hormdee Doosadee , Priprem Aroonsri , Weera-archakul Wilawan , Damrongrungruang Teerasak
Published: April 2021

This study focuses on the role of photosensitizers in photodynamic therapy. The photosensitizers were prepared in combinations of 110/220 µM erythrosine and/or 10/20 µM demethoxy/bisdemethoxy curcumin with/without 10% (w/w) nano-titanium dioxide. Irradiation was performed with a dental blue light in the 395–480 nm wavelength range, with a power density of 3200 mW/cm2 and yield of 72 J/cm2. The production of ROS and hydroxyl radical was investigated using an electron paramagnetic resonance spectrometer for each individual photosensitizer or in photosensitizer combinations. Subsequently, a PrestoBlue® toxicity test of the gingival fibroblast cells was performed at 6 and 24 h on the eight highest ROS-generating photosensitizers containing curcumin derivatives and erythrosine 220 µM. Finally, the antifungal ability of 22 test photosensitizers, Candida albicans (ATCC 10231), were cultured in biofilm form at 37 °C for 48 h, then the colonies were counted in colony-forming units (CFU/mL) via the drop plate technique, and then the log reduction was calculated. The results showed that at 48 h the test photosensitizers could simultaneously produce both ROS types. All test photosensitizers demonstrated no toxicity on the fibroblast cells. In total, 18 test photosensitizers were able to inhibit Candida albicans similarly to nystatin. Conclusively, 20 µM bisdemethoxy curcumin + 220 µM erythrosine + 10% (w/w) nano-titanium dioxide exerted the highest inhibitory effect on Candida albicans.
Sarracenia alata (Alph.Wood) Alph.Wood Microcuttings as a Source of Volatiles Potentially Responsible for Insects’ Respond
Authors: Łyczko Jacek , Twardowski Jacek Piotr , Skalny Bartłomiej , Galek Renata , Szumny Antoni , Gruss Iwona , Piesik Dariusz , Sendel Sebastian
Published: April 2021

Rare carnivorous plants representing the genus Sarracenia are perceived as very interesting to scientists involved in various fields of botany, ethnobotany, entomology, phytochemistry and others. Such high interest is caused mainly by the unique capacity of Sarracenia spp. to attract insects. Therefore, an attempt to develop a protocol for micropropagation of the Sarracenia alata (Alph.Wood) Alph.Wood, commonly named yellow trumpets, and to identify the specific chemical composition of volatile compounds of this plant in vitro and ex vivo was undertaken. Thus, the chemical volatile compounds excreted by the studied plant to attract insects were recognized with the application of the headspace solid-phase microextraction (HS-SPME) coupled with the GC-MS technique. As the major volatile compounds (Z)-3-hexen-1-ol (16.48% ± 0.31), (E)-3-hexen-1-ol acetate (19.99% ± 0.01) and β-caryophyllene (11.30% ± 0.27) were identified. Further, both the chemical assumed to be responsible for attracting insects, i.e., pyridine (3.10% ± 0.07), and whole plants were used in in vivo bioassays with two insect species, namely Drosophila hydei and Acyrthosiphon pisum. The obtained results bring a new perspective on the possibilities of cultivating rare carnivorous plants in vitro since they are regarded as a valuable source of bioactive volatile compounds, as including ones with repellent or attractant activity.
Structural Insights into the Host–Guest Complexation between β-Cyclodextrin and Bio-Conjugatable Adamantane Derivatives
Authors: Wang Jian-Wei , Yu Ka-Xi , Ji Xin-Yuan , Bai Hongzhen , Zhang Wen-Hua , Hu Xiurong , Tang Guping
Published: April 2021

Understanding the host–guest chemistry of α-/β-/γ- cyclodextrins (CDs) and a wide range of organic species are fundamentally attractive, and are finding broad contemporary applications toward developing efficient drug delivery systems. With the widely used β-CD as the host, we herein demonstrate that its inclusion behaviors toward an array of six simple and bio-conjugatable adamantane derivatives, namely, 1-adamantanol (adm-1-OH), 2-adamantanol (adm-2-OH), adamantan-1-amine (adm-1-NH2), 1-adamantanecarboxylic acid (adm-1-COOH), 1,3-adamantanedicarboxylic acid (adm-1,3-diCOOH), and 2-[3-(carboxymethyl)-1-adamantyl]acetic acid (adm-1,3-diCH2COOH), offer inclusion adducts with diverse adamantane-to-CD ratios and spatial guest locations. In all six cases, β-CD crystallizes as a pair supported by face-to-face hydrogen bonding between hydroxyl groups on C2 and C3 and their adjacent equivalents, giving rise to a truncated-cone-shaped cavity to accommodate one, two, or three adamantane derivatives. These inclusion complexes can be terminated as (adm-1-OH)2⊂CD2 (1, 2:2), (adm-2-OH)3⊂CD2 (2, 3:2), (adm-1-NH2)3⊂CD2 (3, 3:2), (adm-1-COOH)2⊂CD2 (4, 2:2), (adm-1,3-diCOOH)⊂CD2 (5, 1:2), and (adm-1,3-diCH2COOH)⊂CD2 (6, 1:2). This work may shed light on the design of nanomedicine with hierarchical structures, mediated by delicate cyclodextrin-based hosts and adamantane-appended drugs as the guests.
New Cocrystals of Antipsychotic Drug Aripiprazole: Decreasing the Dissolution through Cocrystallization
Authors: Liu Wenwen , Ma Ru , Liang Feifei , Duan Chenxin , Zhang Guisen , Chen Yin , Hao Chao
Published: April 2021

Cocrystallization is an important route to tuning the solubility in drugs development, including improving and reducing. Five cocrystals of aripiprazole (ARI) with resveratrol (RSV) and kaempferol (KAE), ARI-RSV, ARI2-RSV1·MeOH, ARI-KAE, ARI-KAE·EtOH, ARI-KAE·IPA, were synthesized and characterized. The single crystal of ARI2-RSV1·MeOH, ARI-KAE·EtOH, and ARI-KAE·IPA were analyzed by single crystal X-ray diffraction (SCXRD). The SCXRD showed multiple intermolecular interactions between API and the coformers, including hydrogen bond, halogen bond, and π-π interactions. Dissolution rate of the two nonsolvate ARI-RSV and ARI-KAE cocrystals were investigated through powder dissolution experiment in pH = 4.0 acetate buffer and pH = 6.8 phosphate buffer. The result showed that RSV could reduce the dissolution rate and solubility of ARI in both medium through cocrystallization. However, KAE improved the dissolution rate and solubility of ARI in pH = 4.0 medium, on the contrary, the two solubility indicators of ARI were both reduced for ARI-KAE cocrystal.
Multielemental Analysis of Bee Pollen, Propolis, and Royal Jelly Collected in West-Central Poland
Authors: Matuszewska Eliza , Klupczynska Agnieszka , Maciołek Krzysztof , Kokot Zenon J. , Matysiak Jan
Published: April 2021

Beehive products possess nutritional value and health-promoting properties and are recommended as so-called “superfoods”. However, because of their natural origin, they may contain relevant elemental contaminants. Therefore, to assess the quality of bee products, we examined concentrations of a broad range of 24 selected elements in propolis, bee pollen, and royal jelly. The quantitative analyses were performed with inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES) techniques. The results of our research indicate that bee products contain essential macronutrients (i.e., K, P, and S) and micronutrients (i.e., Zn and Fe) in concentrations depending on the products’ type. However, the presence of toxic heavy metals makes it necessary to test the quality of bee products before using them as dietary supplements. Bearing in mind that bee products are highly heterogenous and, depending on the environmental factors, differ in their elemental content, it is necessary to develop standards regulating the acceptable levels of inorganic pollutants. Furthermore, since bees and their products are considered to be an effective biomonitoring tool, our results may reflect the environment’s condition in west-central Poland, affecting the health and well-being of both humans and bees.
Efficient Red Thermally Activated Delayed Fluorescence Emitters Based on a Dibenzonitrile-Substituted Dipyrido[3,2-a:2′,3′-c]phenazine Acceptor
Authors: He Lin , Zeng Xuan , Ning Weimin , Ying Ao , Luo Yunbai , Gong Shaolong
Published: April 2021

How to construct efficient red-emitting thermally activated delayed fluorescence (TADF) materials is a challenging task in the field of organic light-emitting diodes (OLEDs). Herein, an electron acceptor moiety, 3,6-DCNB-DPPZ, with high rigidity and strong acceptor strength was designed by introducing two cyanobenzene groups into the 3,6-positions of a dipyrido[3,2-a:2′,3′-c]phenazine unit. A red-emitting compound, 3,6_R, has been designed and synthesized by combining the rigid acceptor unit with two triphenylamine donors. Due to high molecular rigidity and strong intramolecular charge transfer characteristic in donor–acceptor–donor skeleton, 3,6_R exhibited a red emission with a high photoluminescence quantum yield of 86% and distinct TADF nature with short delayed fluorescence lifetime of about 1 microsecond. Accordingly, the OLED using 3,6_R as the guest emitter gained a high external quantum efficiency of 12.0% in the red region with an electroluminescence peak of 619 nm and favorable Commission Internationale de l’Eclairage coordinates of (0.62, 0.38).
Design, Synthetic Strategies, and Therapeutic Applications of Heterofunctional Glycodendrimers
Authors: Mousavifar Leila , Roy René
Published: April 2021

Glycodendrimers have attracted considerable interest in the field of dendrimer sciences owing to their plethora of implications in biomedical applications. This is primarily due to the fact that cell surfaces expose a wide range of highly diversified glycan architectures varying by the nature of the sugars, their number, and their natural multiantennary structures. This particular situation has led to cancer cell metastasis, pathogen recognition and adhesion, and immune cell communications that are implicated in vaccine development. The diverse nature and complexity of multivalent carbohydrate–protein interactions have been the impetus toward the syntheses of glycodendrimers. Since their inception in 1993, chemical strategies toward glycodendrimers have constantly evolved into highly sophisticated methodologies. This review constitutes the first part of a series of papers dedicated to the design, synthesis, and biological applications of heterofunctional glycodendrimers. Herein, we highlight the most common synthetic approaches toward these complex molecular architectures and present modern applications in nanomolecular therapeutics and synthetic vaccines.
6,7,4′-Trihydroxyflavanone Mitigates Methamphetamine-Induced Neurotoxicity in SH-SY5y Cells via Nrf2/heme Oxyganase-1 and PI3K/Akt/mTOR Signaling Pathways
Authors: Lee Hyun-Su , Jeong Gil-Saeng
Published: April 2021

Methamphetamine (METH) is a synthetic psychostimulant drug that has detrimental effects on the health of its users. Although it has been investigated as a cause of neurodegenerative disease due to its neurotoxicity, whether small molecules derived from natural products attenuate these side effects remains elusive. 6,7,4′-trihydroxyflavanone (THF) is a flavanone family that possesses various pharmacological activities, including anti-rheumatic, anti-ischemic, anti-inflammatory, anti-osteoclastogenic, and protective effects against METH-induced deactivation of T cells. However, little is known about whether THF protects neuronal cells from METH-induced neurotoxicity. Here, we investigated the protective effects of THF on neurotoxicity induced by METH exposure by enhancing the Nrf2/HO-1 and PI3K/Akt/mTOR signaling pathways in SH-SY5y cells. Treatment with THF did not lead to cytotoxicity, but attenuated METH-induced neurotoxicity by modulating the expression of apoptosis-related proteins, METH-induced oxidative stress, and PI3K/Akt/mTOR phosphorylation in METH-exposed SH-SY5y cells. Moreover, we found THF induced Nrf2 nuclear translocation and HO-1 expression. An inhibitor assay confirmed that the induction of HO-1 by THF attenuates METH-induced neurotoxicity. Therefore, we suggest that THF preserves neuronal cells from METH-induced neurotoxicity by upregulating HO-1 expression through the Nrf2 and PI3K/Akt/mTOR signaling pathways. Thus, THF has therapeutic potential for use in the treatment of METH-addicts suffering from neurodegenerative diseases.
Computational NMR of Carbohydrates: Theoretical Background, Applications, and Perspectives
Authors: Krivdin Leonid B.
Published: April 2021

This review is written amid a marked progress in the calculation of NMR parameters of carbohydrates substantiated by a vast amount of experimental data coming from several laboratories worldwide. By no means are we trying to cover in the present compilation a huge amount of all available data. The main idea of the present review was only to outline general trends and perspectives in this dynamically developing area on the background of a marked progress in theoretical and computational NMR. Presented material is arranged in three basic sections: (1)—a brief theoretical introduction; (2)—applications and perspectives in computational NMR of monosaccharides; and (3)—calculation of NMR chemical shifts and spin-spin coupling constants of di- and polysaccharides.
Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans
Authors: Cumming Paul , Scheidegger Milan , Dornbierer Dario , Palner Mikael , Quednow Boris B. , Martin-Soelch Chantal
Published: April 2021

Hallucinogens are a loosely defined group of compounds including LSD, N,N-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with N1-([11C]-methyl)-2-bromo-LSD ([11C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [11C]-MBL specific binding was to serotonin 5-HT2A receptors. However, interactions at serotonin 5HT1A and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT2A/2C agonist N-(2[11CH3O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([11C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([15O]-water) or metabolism ([18F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research.
PyPLIF HIPPOS-Assisted Prediction of Molecular Determinants of Ligand Binding to Receptors
Authors: Istyastono Enade P. , Yuniarti Nunung , Prasasty Vivitri D. , Mungkasi Sudi
Published: April 2021

Identification of molecular determinants of receptor-ligand binding could significantly increase the quality of structure-based virtual screening protocols. In turn, drug design process, especially the fragment-based approaches, could benefit from the knowledge. Retrospective virtual screening campaigns by employing AutoDock Vina followed by protein-ligand interaction fingerprinting (PLIF) identification by using recently published PyPLIF HIPPOS were the main techniques used here. The ligands and decoys datasets from the enhanced version of the database of useful decoys (DUDE) targeting human G protein-coupled receptors (GPCRs) were employed in this research since the mutation data are available and could be used to retrospectively verify the prediction. The results show that the method presented in this article could pinpoint some retrospectively verified molecular determinants. The method is therefore suggested to be employed as a routine in drug design and discovery.
Toxin Removal and Inflammatory State Modulation during Online Hemodiafiltration Using Two Different Dialyzers (TRIAD2 Study)
Authors: Donati Gabriele , Cappuccilli Maria , Donadei Chiara , Righini Matteo , Scrivo Anna , Gasperoni Lorenzo , Zappulo Fulvia , La Manna Gaetano
Published: April 2021

Uremic toxins play a pathological role in atherosclerosis and represent an important risk factor in dialysis patients. Online hemodiafiltration (HDF) has been introduced to improve the clearance of middle- and large-molecular-weight solutes (>500 Da) and has been associated with reduced cardiovascular mortality compared to standard hemodialysis. This non-randomized, open-label observational study will explore the efficacy of two dialyzers currently used for online HDF, a polysulfone-based high-flux membrane, and a cellulose triacetate membrane, in hemodialysis patients with signs of middle-molecule intoxication or intradialytic hypotension. In particular, the two filters will be evaluated for their ability in uremic toxin removal and modulation of inflammatory status. Sixteen subjects in standard chronic bicarbonate hemodialysis requiring a switch to online HDF in view of their clinical status will be enrolled and divided into two treatment arms, according to the previous history of hypersensitivity to polysulfone/polyethersulfone dialysis filters and hypersensitivity to drugs or other allergens. Group A will consist of 16 patients without a previous history of hypersensitivity and will be treated with a polysulfone filter (Helixone FX100), and group B, also consisting of 16 patients, with a previous history of hypersensitivity and will be treated with asymmetric triacetate (ATA; SOLACEA 21-H) dialyzer. Each patient will be followed for a period of 24 months, with monthly assessments of circulating middle-weight toxins and protein-bound toxins, markers of inflammation and oxidative stress, lymphocyte subsets, activated lymphocytes, and monocytes, cell apoptosis, the accumulation of advanced glycation end-products (AGEs), variations in arterial stiffens measured by pulse wave velocity (PWV), and mortality rate. The in vitro effect on endothelial cells of uremic serum collected from patients treated with the two different dialyzers will also be investigated to examine the changes in angiogenesis, cell migration, differentiation, apoptosis and proliferative potential, and gene and protein expression profile. The expected results will be a better awareness of the different effects of polysulfone gold-standard membrane for online HDF and the new ATA membrane on the removal of uremic toxins removal and inflammation due to blood–membrane interaction.
Supporting User Onboarding in Automated Vehicles through Multimodal Augmented Reality Tutorials
Authors: Detjen Henrik , Degenhart Robert Niklas , Schneegass Stefan , Geisler Stefan
Published: April 2021

Misconceptions of vehicle automation functionalities lead to either non-use or dangerous misuse of assistant systems, harming the users’ experience by reducing potential comfort or compromise safety. Thus, users must understand how and when to use an assistant system. In a preliminary online survey, we examined the use, trust, and the perceived understanding of modern vehicle assistant systems. Despite remaining incomprehensibility (36–64%), experienced misunderstandings (up to 9%), and the need for training (around 30%), users reported high trust in the systems. In the following study with first-time users, we examine the effect of different User Onboarding approaches for an automated parking assistant system in a Tesla and compare the traditional text-based manual with a multimodal augmented reality (AR) smartphone application in means of user acceptance, UX, trust, understanding, and task performance. While the User Onboarding experience for both approaches shows high pragmatic quality, the hedonic quality was perceived significantly higher in AR. For the automated parking process, reported hedonic and pragmatic user experience, trust, automation understanding, and acceptance do not differ, yet the observed task performance was higher in the AR condition. Overall, AR might help motivate proper User Onboarding and better communicate how to operate the system for inexperienced users.
What Are the Pearls and Pitfalls of the Dietary Management for Chronic Diarrhoea?
Authors: O’Brien Leigh , Wall Catherine L. , Wilkinson Tim J. , Gearry Richard B.
Published: April 2021

Chronic diarrhoea affects up to 14% of adults, it impacts on quality of life and its cause can be variable. Patients with chronic diarrhoea are presented with a plethora of dietary recommendations, often sought from the internet or provided by those who are untrained or inexperienced. In this review, we summarise the possible causes of chronic diarrhoea that can be managed by diet, the symptom improvement and quality of life benefits but also the potential risks of such dietary treatments. Clinicians need to consider both the benefits and risks of dietary treatments before making dietary recommendations to manage chronic diarrhoea. The pivotal role that dietitians have in ensuring optimal symptom improvement without jeopardising nutritional and overall health is discussed.
Magnesium for Pain Treatment in 2021? State of the Art
Authors: Morel Véronique , Pickering Marie-Eva , Goubayon Jonathan , Djobo Marguérite , Macian Nicolas , Pickering Gisèle
Published: April 2021

Background: Magnesium (Mg) is commonly used in clinical practice for acute and chronic pain and has been reported to reduce pain intensity and analgesics consumption in a number of studies. Results are, however, contested. Objectives: This review aims to investigate randomised clinical trials (RCTs) on the effectiveness of Mg treatment on pain and analgesics consumption in situations including post-operative pain, migraine, renal pain, chronic pain, neuropathic pain and fibromyalgia. Results: The literature search identified 81 RCTs (n = 5447 patients) on Mg treatment in pain (50 RCTs in post-operative pain, 18 RCTs in migraine, 5 RCTs in renal pain, 6 RCTs in chronic/neuropathic pain, 2 RCTs in fibromyalgia). Conclusion: The level of evidence for the efficacy of Mg in reducing pain and analgesics consumption is globally modest and studies are not very numerous in chronic pain. A number of gaps have been identified in the literature that need to be addressed especially in methodology, rheumatic disease, and cancer. Additional clinical trials are needed to achieve a sufficient level of evidence and to better optimize the use of Mg for pain and pain comorbidities in order to improve the quality of life of patients who are in pain.
Using Oral Microbiota Data to Design a Short Sucrose Intake Index
Authors: Esberg Anders , Eriksson Linda , Hasslöf Pamela , Haworth Simon , Holgerson Pernilla Lif , Johansson Ingegerd
Published: April 2021

Excessive sucrose consumption is associated with numerous health problems, including dental caries, and is considered to play a critical role in shaping the human microbiota. Here, we aimed to confirm the association between sucrose exposure and oral microbiota profile, develop a short food-based index capturing variation among sucrose consumers and validate it against oral microbiota and dental caries in a derivation cohort with 16- to 79-year-old participants (n = 427). Intake and food preferences were recorded by questionnaires and saliva microbiota by 16S rDNA sequencing. Taxonomic similarities clustered participants into five clusters, where one stood out with highest sucrose intake and predicted sugar related metabolic pathways but lowest species diversity in the microbiota. Multivariate modelling of food intake and preferences revealed foods suitable for a sucrose index. This, similarly to sucrose intake, was related to bacterial pattern and caries status. The validity of the sucrose index was replicated in the population-based Gene-Lifestyle Interactions in Dental Endpoints (GLIDE, n = 105,520 Swedish adults) cohort. This suggested that the index captured clinically relevant variation in sucrose intake and that FFQ derived information may be suitable for screening of sucrose intake in the clinic and epidemiological studies, although adjustments to local consumption habits are needed.
Age-Related Changes in Zinc, Copper and Selenium Levels in the Human Prostate
Authors: Daragó Adam , Klimczak Michał , Stragierowicz Joanna , Jobczyk Mateusz , Kilanowicz Anna
Published: April 2021

Pathophysiological changes in the prostate gland—benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma (PCa)—are closely related to the age of men. In the prostate gland, zinc is of particular importance for its proper functioning, especially with regard to the effects of hormonal disorders. The aim of this study was to evaluate zinc, copper and selenium concentrations in different parts of the prostate gland in relation to age and the nature of pathological changes. Zinc and copper were determined by the AAS method and selenium by the spectrofluorometric method. The concentration of zinc in the central part of the prostate increases with age, and in patients over 36 years it is twice as high as in the peripheral part, where no increase in the level of this element was observed with the age of patients. The above data confirm a possible influence of zinc on the formation of PCa (located mostly in the peripheral part of the prostate, with low levels of zinc) and BPH in the central part where the levels of this element are the highest. The results apparently confirm the disturbed homeostasis of zinc and other essential elements in the etiology of BPH and PCa.
Mechanistic Modelling Identifies and Addresses the Risks of Empiric Concentration-Guided Sorafenib Dosing
Authors: Ruanglertboon Warit , Sorich Michael J. , Hopkins Ashley M. , Rowland Andrew
Published: April 2021

The primary objective of this study is to evaluate the capacity of concentration-guided sorafenib dosing protocols to increase the proportion of patients that achieve a sorafenib maximal concentration (Cmax) within the range 4.78 to 5.78 μg/mL. A full physiologically based pharmacokinetic model was built and validated using Simcyp® (version 19.1). The model was used to simulate sorafenib exposure in 1000 Sim-Cancer subjects over 14 days. The capacity of concentration-guided sorafenib dose adjustment, with/without model-informed dose selection (MIDS), to achieve a sorafenib Cmax within the range 4.78 to 5.78 μg/mL was evaluated in 500 Sim-Cancer subjects. A multivariable linear regression model incorporating hepatic cytochrome P450 (CYP) 3A4 abundance, albumin concentration, body mass index, body surface area, sex and weight provided robust prediction of steady-state sorafenib Cmax (R2 = 0.883; p < 0.001). These covariates identified subjects at risk of failing to achieve a sorafenib Cmax ≥ 4.78 μg/mL with 95.0% specificity and 95.2% sensitivity. Concentration-guided sorafenib dosing with MIDS achieved a sorafenib Cmax within the range 4.78 to 5.78 μg/mL for 38 of 52 patients who failed to achieve a Cmax ≥ 4.78 μg/mL with standard dosing. In a simulation setting, concentration-guided dosing with MIDS was the quickest and most effective approach to achieve a sorafenib Cmax within a designated range.