bluuebunny/crossref_metadata_2025 huggingface dataset:
An Update on Gene Therapy for Inherited Retinal Dystrophy: Experience in Leber Congenital Amaurosis Clinical Trials
Authors: Chiu Wei , Lin Ting-Yi , Chang Yun-Chia , Isahwan-Ahmad Mulyadi Lai Henkie , Lin Shen-Che , Ma Chun , Yarmishyn Aliaksandr A. , Lin Shiuan-Chen , Chang Kao-Jung , Chou Yu-Bai , Hsu Chih-Chien , Lin Tai-Chi , Chen Shih-Jen , Chien Yueh , Yang Yi-Ping , Hwang De-Kuang
Published: April 2021

Inherited retinal dystrophies (IRDs) are a group of rare eye diseases caused by gene mutations that result in the degradation of cone and rod photoreceptors or the retinal pigment epithelium. Retinal degradation progress is often irreversible, with clinical manifestations including color or night blindness, peripheral visual defects and subsequent vision loss. Thus, gene therapies that restore functional retinal proteins by either replenishing unmutated genes or truncating mutated genes are needed. Coincidentally, the eye’s accessibility and immune-privileged status along with major advances in gene identification and gene delivery systems heralded gene therapies for IRDs. Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for treating patients with confirmed biallelic RPE65 mutation-associated Leber Congenital Amaurosis (LCA) in 2017. This review includes current IRD gene therapy clinical trials and further summarizes preclinical studies and therapeutic strategies for LCA, including adeno-associated virus-based gene augmentation therapy, 11-cis-retinal replacement, RNA-based antisense oligonucleotide therapy and CRISPR-Cas9 gene-editing therapy. Understanding the gene therapy development for LCA may accelerate and predict the potential hurdles of future therapeutics translation. It may also serve as the template for the research and development of treatment for other IRDs.
Small-Molecule Inhibitors of the RNA M6A Demethylases FTO Potently Support the Survival of Dopamine Neurons
Authors: Selberg Simona , Yu Li-Ying , Bondarenko Olesja , Kankuri Esko , Seli Neinar , Kovaleva Vera , Herodes Koit , Saarma Mart , Karelson Mati
Published: April 2021

The fat mass and obesity-associated protein (FTO), an RNA N6-methyladenosine (m6A) demethylase, is an important regulator of central nervous system development, neuronal signaling and disease. We present here the target-tailored development and biological characterization of small-molecule inhibitors of FTO. The active compounds were identified using high-throughput molecular docking and molecular dynamics screening of the ZINC compound library. In FTO binding and activity-inhibition assays the two best inhibitors demonstrated Kd = 185 nM; IC50 = 1.46 µM (compound 2) and Kd = 337 nM; IC50 = 28.9 µM (compound 3). Importantly, the treatment of mouse midbrain dopaminergic neurons with the compounds promoted cellular survival and rescued them from growth factor deprivation induced apoptosis already at nanomolar concentrations. Moreover, both the best inhibitors demonstrated good blood-brain-barrier penetration in the model system, 31.7% and 30.8%, respectively. The FTO inhibitors demonstrated increased potency as compared to our recently developed ALKBH5 m6A demethylase inhibitors in protecting dopamine neurons. Inhibition of m6A RNA demethylation by small-molecule drugs, as presented here, has therapeutic potential and provides tools for the identification of disease-modifying m6A RNAs in neurogenesis and neuroregeneration. Further refinement of the lead compounds identified in this study can also lead to unprecedented breakthroughs in the treatment of neurodegenerative diseases.
NEIL1 and NEIL2 Are Recruited as Potential Backup for OGG1 upon OGG1 Depletion or Inhibition by TH5487
Authors: Hanna Bishoy M. F. , Michel Maurice , Helleday Thomas , Mortusewicz Oliver
Published: April 2021

DNA damage caused by reactive oxygen species may result in genetic mutations or cell death. Base excision repair (BER) is the major pathway that repairs DNA oxidative damage in order to maintain genomic integrity. In mammals, eleven DNA glycosylases have been reported to initiate BER, where each recognizes a few related DNA substrate lesions with some degree of overlapping specificity. 7,8-dihydro-8-oxoguanine (8-oxoG), one of the most abundant DNA oxidative lesions, is recognized and excised mainly by 8-oxoguanine DNA glycosylase 1 (OGG1). Further oxidation of 8-oxoG generates hydantoin lesions, which are recognized by NEIL glycosylases. Here, we demonstrate that NEIL1, and to a lesser extent NEIL2, can potentially function as backup BER enzymes for OGG1 upon pharmacological inhibition or depletion of OGG1. NEIL1 recruitment kinetics and chromatin binding after DNA damage induction increase in cells treated with OGG1 inhibitor TH5487 in a dose-dependent manner, whereas NEIL2 accumulation at DNA damage sites is prolonged following OGG1 inhibition. Furthermore, depletion of OGG1 results in increased retention of NEIL1 and NEIL2 at damaged chromatin. Importantly, oxidatively stressed NEIL1- or NEIL2-depleted cells show excessive genomic 8-oxoG lesions accumulation upon OGG1 inhibition, suggesting a prospective compensatory role for NEIL1 and NEIL2. Our study thus exemplifies possible backup mechanisms within the base excision repair pathway.
Simulated Microgravity Inhibits the Proliferation of Chang Liver Cells by Attenuation of the Major Cell Cycle Regulators and Cytoskeletal Proteins
Authors: Ho Chi Nguyen Quynh , Tran Minh Thi , Doan Chung Chinh , Hoang Son Nghia , Tran Diem Hong , Le Long Thanh
Published: April 2021

Simulated microgravity (SMG) induced the changes in cell proliferation and cytoskeleton organization, which plays an important factor in various cellular processes. The inhibition in cell cycle progression has been considered to be one of the main causes of proliferation inhibition in cells under SMG, but their mechanisms are still not fully understood. This study aimed to evaluate the effects of SMG on the proliferative ability and cytoskeleton changes of Chang Liver Cells (CCL-13). CCL-13 cells were induced SMG by 3D clinostat for 72 h, while the control group were treated in normal gravity at the same time. The results showed that SMG reduced CCL-13 cell proliferation by an increase in the number of CCL-13 cells in G0/G1 phase. This cell cycle phase arrest of CCL-13 cells was due to a downregulation of cell cycle-related proteins, such as cyclin A1 and A2, cyclin D1, and cyclin-dependent kinase 6 (Cdk6). SMG-exposed CCL-13 cells also exhibited a downregulation of α-tubulin 3 and β-actin which induced the cytoskeleton reorganization. These results suggested that the inhibited proliferation of SMG-exposed CCL-13 cells could be associate with the attenuation of major cell cycle regulators and main cytoskeletal proteins.
Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells
Authors: Fujisawa Satoshi , Komatsubara Motoshi , Tsukamoto-Yamauchi Naoko , Iwata Nahoko , Nada Takahiro , Wada Jun , Otsuka Fumio
Published: April 2021

Orexin is expressed mainly in the hypothalamus and is known to activate the hypothalamic–pituitary–adrenal (HPA) axis that is involved in various stress responses and its resilience. However, the effects of orexin on the endocrine function of pituitary corticotrope cells remain unclear. In this study, we investigated the roles of orexin A in pro-opiomelanocortin (POMC) transcription using mouse corticotrope AtT20 cells, focusing on the bone morphogenetic protein (BMP) system expressed in the pituitary. Regarding the receptors for orexin, type 2 (OXR2) rather than type 1 (OX1R) receptor mRNA was predominantly expressed in AtT20 cells. It was found that orexin A treatment enhanced POMC expression, induced by corticotropin-releasing hormone (CRH) stimulation through upregulation of CRH receptor type-1 (CRHR1). Orexin A had no direct effect on the POMC transcription suppressed by BMP-4 treatment, whereas it suppressed Smad1/5/9 phosphorylation and Id-1 mRNA expression induced by BMP-4. It was further revealed that orexin A had no significant effect on the expression levels of type I and II BMP receptors but upregulated inhibitory Smad6/7 mRNA and protein levels in AtT20 cells. The results demonstrated that orexin A upregulated CRHR signaling and downregulated BMP-Smad signaling, leading to an enhancement of POMC transcription by corticotrope cells.
Molecular Hydrogen as a Potential Clinically Applicable Radioprotective Agent
Authors: Hirano Shin-ichi , Ichikawa Yusuke , Sato Bunpei , Yamamoto Haru , Takefuji Yoshiyasu , Satoh Fumitake
Published: April 2021

Although ionizing radiation (radiation) is commonly used for medical diagnosis and cancer treatment, radiation-induced damages cannot be avoided. Such damages can be classified into direct and indirect damages, caused by the direct absorption of radiation energy into DNA and by free radicals, such as hydroxyl radicals (•OH), generated in the process of water radiolysis. More specifically, radiation damage concerns not only direct damages to DNA, but also secondary damages to non-DNA targets, because low-dose radiation damage is mainly caused by these indirect effects. Molecular hydrogen (H2) has the potential to be a radioprotective agent because it can selectively scavenge •OH, a reactive oxygen species with strong oxidizing power. Animal experiments and clinical trials have reported that H2 exhibits a highly safe radioprotective effect. This paper reviews previously reported radioprotective effects of H2 and discusses the mechanisms of H2, not only as an antioxidant, but also in intracellular responses including anti-inflammation, anti-apoptosis, and the regulation of gene expression. In doing so, we demonstrate the prospects of H2 as a novel and clinically applicable radioprotective agent.
Neurosurgical CSF Diversion in Idiopathic Intracranial Hypertension: A Narrative Review
Authors: Sunderland Geraint J. , Jenkinson Michael D. , Conroy Elizabeth J. , Gamble Carrol , Mallucci Conor L.
Published: April 2021

The prevalence of idiopathic intracranial hypertension (IIH), a complex disorder, is increasing globally in association with obesity. The IIH syndrome occurs as the result of elevated intracranial pressure, which can cause permanent visual impairment and loss if not adequately managed. CSF diversion via ventriculoperitoneal and lumboperitoneal shunts is a well-established strategy to protect vision in medically refractory cases. Success of CSF diversion is compromised by high rates of complication; including over-drainage, obstruction, and infection. This review outlines currently used techniques and technologies in the management of IIH. Neurosurgical CSF diversion is a vital component of the multidisciplinary management of IIH.
Editorial for the Special Issue on Nanomaterials in Health Care Diagnostics
Authors: Altintas Zeynep
Published: April 2021

The applications of nanomaterials in health care diagnostics have gained immense interest in recent years owing to their superior properties compared to traditional materials [...]
The Parameters Identification of High-Temperature Constitutive Model Based on Inverse Optimization Method and 3D Processing Map of Cr8 Alloy Steel
Authors: Chen Xuewen , Lian Tingting , Zhang Bo , Du Yuqing , Du Kexue , Liu Bingqi , Li Zhipeng , Tian Xuanhe , Jung Dong-Won
Published: April 2021

As a novel kind of cold roller steel, Cr8 alloy steel has the characteristics of high hardness, high wear resistance and good toughness, which can effectively prolong the service life of the roller that is an important part of the steel rolling mill. How to accurately define the constitutive model parameters of metal materials is the major problem, because it seriously affects the accuracy of numerical simulation results of the roller hot forming process. In the study of Cr8 alloy steel’s thermal deformation behavior of the present paper, the high temperature compression test was done on a Gleebel-1500D thermal/force simulation testing machine. A novel method of parameter identification was proposed based on inverse optimization. The Hansel–Spittel constitutive model was established by using the inverse optimization method. To carry out the verification on the accuracy of the established constitutive model, the predicted flow-stress of constitutive model was made a contrast to the experimental flow-stress, and the standard statistical parameters were also applied to further evaluation. The results showed a relatively high prediction accuracy of the Hansel–Spittel constitutive model based on the inverse optimization algorithm. Meanwhile, to obtain optimal parameters of Cr8 alloy steel in the thermal processing, 3D thermal processing maps concerning strain-rate, strain and temperature were built based on the dynamic material model. According to the 3D processing map, the most adequate thermal processing parameters of Cr8 alloy steel were obtianed as follows: strain 0.2–0.4, strain-rate 0.05–0.005 s−1, temperature 1100–1150 °C.
Synthesis and Characterization of a Nearly Single Bulk Ti2AlN MAX Phase Obtained from Ti/AlN Powder Mixture through Spark Plasma Sintering
Authors: Salvo Christopher , Chicardi Ernesto , Poyato Rosalía , García-Garrido Cristina , Jiménez José Antonio , López-Pernía Cristina , Tobosque Pablo , Mangalaraja Ramalinga Viswanathan
Published: April 2021

MAX phases are an advanced class of ceramics based on ternary carbides or nitrides that combine some of the ceramic and metallic properties, which make them potential candidate materials for many engineering applications under severe conditions. The present work reports the successful synthesis of nearly single bulk Ti2AlN MAX phase (>98% purity) through solid-state reaction and from a Ti and AlN powder mixture in a molar ratio of 2:1 as starting materials. The mixture of Ti and AlN powders was subjected to reactive spark plasma sintering (SPS) under 30 MPa at 1200 °C and 1300 °C for 10 min in a vacuum atmosphere. It was found that the massive formation of Al2O3 particles at the grain boundaries during sintering inhibits the development of the Ti2AlN MAX phase in the outer zone of the samples. The effect of sintering temperature on the microstructure and mechanical properties of the Ti2AlN MAX phase was investigated and discussed.
Water-Soluble Copper Ink for the Inkjet Fabrication of Flexible Electronic Components
Authors: Shabanov Nabi S. , Rabadanov Kamil Sh. , Suleymanov Sagim I. , Amirov Akhmed M. , Isaev Abdulgalim B. , Sobola Dinara S. , Murliev Eldar K. , Asvarova Gulnara A.
Published: April 2021

The aim of this work is preparation and investigation of copper conductive paths by printing with a different type of functional ink. The solutions based on copper-containing complex compounds were used as inks instead of dispersions of metal nanoparticles. Thermal characteristics of synthesized precursors were studied by thermogravimetry in an argon atmosphere. Based on the comparison of decomposition temperature, the dimethylamine complex of copper formate was found to be more suitable precursor for the formation of copper layers. Structure and performance of this compound was studied in detail by X-ray diffraction, test of wettability, printing on flexible substrate, and electrical measurements.
Thermal Conductivity of Ordered Porous Structures Coupling Gas and Solid Phases: A Molecular Dynamics Study
Authors: Niu Dong , Gao Hongtao
Published: April 2021

Heat transfer in a porous solid−gas mixture system is an important process for many industrial applications. Optimization design of heat insulation material is very important in many fields such as pipe insulation, thermal protection of spacecraft, and building insulation. Understanding the micro-mechanism of the solid−gas coupling effect is necessary for the design of insulation material. The prediction of thermal conductivity is difficult for some kinds of porous materials due to the coupling impact of solid and gas. In this study, the Grand Canonical Monte Carlo method (GCMC) and molecular dynamics simulation (MD) are used to investigate the thermal conductivity for the ordered porous structures of intersecting square rods. The effect of gas concentration (pressure) and solid−gas interaction on thermal conductivity is revealed. The simulation results show that for different framework structures the pressure effect on thermal conductivity presents an inconsistent mode which is different from previous studies. Under the same pressure, the thermal conductivity is barely changed for different interactions between gas and solid phases. This study provides the feasibility for the direct calculation of thermal conductivity for porous structures coupling gas and solid phases using molecular dynamics simulation. The heat transfer in porous structures containing gas could be understood on a fundamental level.
Effect of Fiber Content and Alignment on the Mechanical Properties of 3D Printing Cementitious Composites
Authors: Zhang Hao , Zhu Liming , Zhang Fan , Yang Mijia
Published: April 2021

This paper studies aligned glass fiber-reinforced composites for printing. To determine the influence of fiber content and alignment on the mechanical properties of this novel material, a large number of standard test specimens were prepared, which included samples fabricated by mold-casting, randomly dispersed fiber reinforced mixtures and aligned fiber cement composites containing 10 types of fiber volume ratios manufactured by nozzle sizes ranging of 24 and 10 mm (fiber length = 12 mm). Mechanical properties and failure modes of the specimens under compression and flexural tests were studied experimentally. The anisotropic behaviors of printed samples were analyzed by different loading directions. As a result, the compressive and flexural strength of printed samples showed obvious anisotropy. With the increase of fiber volume ratio, flexural strength of the fiber reinforced composite was elevated tremendously but its compression strength reduced slightly. Moreover, fiber alignment also had a significant influence on the mechanical properties of the fiber reinforced composite. The composite cement-based material with 1 vol.-% aligned fiber exhibited an excellent flexural strength of 9.38 MPa, which increased by 483% in comparison to that of the plain cement paste.
PROMETHEUS: A Copper-Based Polymetallic Catalyst for Automotive Applications. Part II: Catalytic Efficiency an Endurance as Compared with Original Catalysts
Authors: Yakoumis Iakovos , Polyzou Εkaterini , Moschovi Anastasia Maria
Published: April 2021

PROMETHEUS catalyst, a copper-based polymetallic nano-catalyst has been proven to be suitable for automotive emission control applications. This novel catalyst consists of copper, palladium and rhodium nanoparticles as active phases, impregnated on an inorganic oxide substrate, CeO2/ZrO2 (75%, 25%). The aim of PROMETHEUS catalyst’s development is the substitution of a significant amount (85%) of Platinum Group Metals (PGMs) with copper nanoparticles while, at the same time, presenting high catalytic efficiency with respect to the commercial catalysts. In this work, an extensive investigation of the catalytic activity of full scale PROMETHEUS fresh and aged catalyst deposited on ceramic cordierites is presented and discussed. The catalytic activity was tested on an Synthetic Gas Bench (SGB) towards the oxidation of CO and CH4 and the reduction of NO. The loading of the washcoat was 2 wt% (metal content) on Cu, Pd, Rh with the corresponding metal ratio at 21:7:1. The concentration of the full-scale monolithic catalysts to be 0.032% total PGM loading for meeting Euro III standard and 0.089% for meeting Euro IV to Euro VIb standards. The catalytic activity of all catalysts was tested both in rich-burn (λ = 0.99) and lean-burn conditions (λ = 1.03).
Study on the Compressive Strength of Alkali Activated Fly Ash and Slag under the Different Silicate Structure
Authors: Wang Zhipu , Rehemituli Rezeye , Zhang Xiaolei
Published: April 2021

Due to its high activation efficiency, waterglass has been widely used for alkali activations in geopolymer. In this study, the n(SiO2)/n(Na2O) (Ms) of waterglass was selected as the variable to investigate the role of the silicate structure on the mechanical properties of harden pastes. Ms was changed by the addition of NaOH to obtain the different silicate group, structure and experiments were performed by employing the liquid-sate 29Si nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and gel permeation chromatography (GPC) techniques. Furthermore, selected dissolution, scanning electron microscope (SEM-EDX), X-ray photoelectron spectroscopy (XPS) and FTIR experiments were used to measure the development of the amorphous gel and other materials with different curing condition. Results show that silicate structure of the waterglass was changed via the Si-ONa+ formation and the electric charge effect of Na+. Under the lower Ms waterglass, the Q0, Q1 and QC2 structure reverted to the main structure of the silicate group, which was kind of lower seize, molecule weight, linear or circular chain lower geopolymerization degree silicon structure. It would accelerate the geopolymerization speed of prepolymer formation. In addition, higher activity degree of Q0 and Q1 were useful to increase the formation amount of the gel structure with a low Si/Al ratio and size. Thus, silicate structure of waterglass controls the amorphous gel properties to adjust the compressive strength of alkali-activated materials.
The Design and Research of a New Hybrid Surface Plasmonic Waveguide Nanolaser
Authors: Liu Yahui , Li Fang , Xu Cheng , He Zhichong , Gao Jie , Zhou Yunpeng , Xu Litu
Published: April 2021

Using the hybrid plasmonic waveguide (HPW) principle as a basis, a new planar symmetric Ag-dielectric-SiO2 hybrid waveguide structure is designed and applied to nanolasers. First, the effects on the electric field distribution and the characteristic parameters of the waveguide structure of changes in the material, the nanometer radius, and the dielectric layer thickness were studied in detail using the finite element method with COMSOL Multiphysics software. The effects of two different dielectric materials on the HPW were studied. It was found that the waveguide performance could be improved effectively and the mode propagation loss was reduced when graphene was used as the dielectric, with the minimum effective propagation loss reaching 0.025. Second, the gain threshold and the quality factor of a nanolaser based on the proposed hybrid waveguide structure were analyzed. The results showed that the nanolaser has a lasing threshold of 1.76 μm−1 and a quality factor of 109 when using the graphene dielectric. A low-loss, low-threshold laser was realized, and the mode field was constrained by deep sub-wavelength light confinement. This structure has broad future application prospects in the integrated optics field and provides ideas for the development of subminiature photonic devices and high-density integrated circuits.
Tuned S-Scheme Cu2S_TiO2_WO3 Heterostructure Photocatalyst toward S-Metolachlor (S-MCh) Herbicide Removal
Authors: Enesca Alexandru , Isac Luminita
Published: April 2021

A dual S-scheme Cu2S_TiO2_WO3 heterostructure was constructed by sol–gel method using a two-step procedure. Due to the synthesis parameters and annealing treatment the heterostructure is characterized by sulfur deficit and oxygen excess allowing the passivation of oxygen vacancies. The photocatalytic activity was evaluated under UV and UV–Vis irradiation scenarios using S-MCh as reference pollutant. The heterostructure is composed on orthorhombic Cu2S, anatase TiO2 and monoclinic WO3 with crystallite sizes varying from 65.2 Å for Cu2S to 97.1 Å for WO3. The heterostructure exhibit a dense morphology with pellets and particle-like morphology closely combined in a relatively compact assembly. The surface elemental composition indicate that the heterostructure maintain a similar atomic ratio as established during the synthesis with a slight sulfur deficit due to the annealing treatments. The results indicate that the three-component heterostructure have higher photocatalytic efficiency (61%) comparing with two-component heterostructure or bare components. Moreover, Cu2S_TiO2_WO3 exhibit a superior constant rate (0.114 s−1) due to the high concentration of photogenerated charge carriers, efficient charge separation and migration.
Effect of Fibre Orientation on the Quasi-Static Axial Crushing Behaviour of Glass Fibre Reinforced Polyvinyl Chloride Composite Tubes
Authors: Khan Rahib A. , Mahdi Elsadig , Cabibihan John-John
Published: April 2021

In this study, glass fibre reinforced (GFRP) polyvinyl chloride (PVC) tubes were subjected to quasi-static axial compression tests to determine their crashworthiness performance. To this end, this study employed GFRP/PVC tubes with four different fibre orientations, 45°, 55°, 65° and 90°. A five-axis filament winding machine was used to fabricate the tubes. The results show that there was a considerable increase in all crashworthiness characteristics due to GFRP reinforcement. For the GFRP/PVC composite tubes of different fibre orientations, the load-bearing capacity, crush force efficiency and energy absorption capability generally improve with increasing fibre orientation. The GFRP/PVC 45° specimen was a notable exception as it exhibited the best specific energy absorption capacity and a crushing force efficiency that was only slightly less than for the GFRP/PVC 90° specimen.
Ultrashort Peptide Hydrogels Display Antimicrobial Activity and Enhance Angiogenic Growth Factor Release by Dental Pulp Stem/Stromal Cells
Authors: Afami Marina E. , El Karim Ikhlas , About Imad , Coulter Sophie M. , Laverty Garry , Lundy Fionnuala T.
Published: April 2021

Recent studies on peptide hydrogels have shown that ultrashort peptides (<8 amino acids) can self-assemble into hydrogels. Ultrashort peptides can be designed to incorporate antimicrobial motifs, such as positively charged lysine residues, so that the peptides have inherent antimicrobial characteristics. Antimicrobial hydrogels represent a step change in tissue engineering and merit further investigation, particularly in applications where microbial infection could compromise healing. Herein, we studied the biocompatibility of dental pulp stem/stromal cells (DPSCs) with an ultrashort peptide hydrogel, (naphthalene-2-ly)-acetyl-diphenylalanine-dilysine-OH (NapFFεKεK-OH), where the epsilon (ε) amino group forms part of the peptide bond rather than the standard amino grouping. We tested the antimicrobial properties of NapFFεKεK-OH in both solution and hydrogel form against Staphylococcus aureus, Enterococcus faecalis and Fusobacterium nucleatum and investigated the DPSC secretome in hydrogel culture. Our results showed NapFFεKεK-OH hydrogels were biocompatible with DPSCs. Peptides in solution form were efficacious against biofilms of S. aureus and E. faecalis, whereas hydrogels demonstrated antimicrobial activity against E. faecalis and F. nucleatum. Using an angiogenic array we showed that DPSCs encapsulated within NapFFεKεK-OH hydrogels produced an angiogenic secretome. These results suggest that NapFFεKεK-OH hydrogels have potential to serve as novel hydrogels in tissue engineering for cell-based pulp regeneration.
Thermal Transport and Thermoelectric Effect in Composites of Alumina and Graphene-Augmented Alumina Nanofibers
Authors: Saffar Shamshirgar Ali , Belmonte Manuel , Tewari Girish C. , Rojas Hernández Rocío E. , Seitsonen Jani , Ivanov Roman , Karppinen Maarit , Miranzo Pilar , Hussainova Irina
Published: April 2021

The remarkable tunability of 2D carbon structures combined with their non-toxicity renders them interesting candidates for thermoelectric applications. Despite some limitations related to their high thermal conductivity and low Seebeck coefficients, several other unique properties of the graphene-like structures could out-weight these weaknesses in some applications. In this study, hybrid structures of alumina ceramics and graphene encapsulated alumina nanofibers are processed by spark plasma sintering to exploit advantages of thermoelectric properties of graphene and high stiffness of alumina. The paper focuses on thermal and electronic transport properties of the systems with varying content of nanofillers (1–25 wt.%) and demonstrates an increase of the Seebeck coefficient and a reduction of the thermal conductivity with an increase in filler content. As a result, the highest thermoelectric figure of merit is achieved in a sample with 25 wt.% of the fillers corresponding to ~3 wt.% of graphene content. The graphene encapsulated nanofibrous fillers, thus, show promising potential for thermoelectric material designs by tuning their properties via carrier density modification and Fermi engineering through doping.
A Novel 4H-SiC MESFET with a Heavily Doped Region, a Lightly Doped Region and an Insulated Region
Authors: Jia Hujun , Dong Mengyu , Wang Xiaowei , Zhu Shunwei , Yang Yintang
Published: April 2021

A novel 4H-SiC MESFET was presented, and its direct current (DC), alternating current (AC) characteristics and power added efficiency (PAE) were studied. The novel structure improves the saturation current (Idsat) and transconductance (gm) by adding a heavily doped region, reduces the gate-source capacitance (Cgs) by adding a lightly doped region and improves the breakdown voltage (Vb) by embedding an insulated region (Si3N4). Compared to the double-recessed (DR) structure, the saturation current, the transconductance, the breakdown voltage, the maximum oscillation frequency (fmax), the maximum power added efficiency and the maximum theoretical output power density (Pmax) of the novel structure is increased by 24%, 21%, 9%, 11%, 14% and 34%, respectively. Therefore, the novel structure has excellent performance and has a broader application prospect than the double recessed structure.
A Separated Reset Waveform Design for Suppressing Oil Backflow in Active Matrix Electrowetting Displays
Authors: Liu Linwei , Bai Pengfei , Yi Zichuan , Zhou Guofu
Published: April 2021

The electrowetting display (EWD) is a kind of reflective paper-like display. Flicker and grayscale distortion are caused by oil backflow, which is one of the important factors restricting the wide application of EWDs. The charge embedding caused by the electric field force in the dielectric layer is the cause of oil backflow. To suppress oil backflow, a separated reset waveform based on the study of oil movement is proposed in this paper. The driving waveform is divided into two parts: a reset waveform and a grayscale waveform. The reset waveform generated by a reset circuit can be used to output various voltages. The grayscale waveform is set as a traditional PWM waveform. The reset waveform is composed of a charge-releasing stage and oil-moving back stage. Two phases are contained in the charge releasing stage. The overdriving voltage is used during the first phase to reverse the voltage of all pixels. The trapped charges can then be released from the dielectric layer during the second phase. A higher voltage is used during the oil-moving back stage to drive the oil faster in the pixel. By comparing the experimental data, the oil backflow time is extended 761 times by the reset waveform. The four grayscales can be maintained by the reset waveform after driving for 300 s.
Direct Writing of Cu Patterns on Polydimethylsiloxane Substrates Using Femtosecond Laser Pulse-Induced Reduction of Glyoxylic Acid Copper Complex
Authors: Ha Nam , Ohishi Tomoji , Mizoshiri Mizue
Published: April 2021

We investigate the direct writing properties of copper (Cu) patterns on glass and polydimethylsiloxane (PDMS) substrates using femtosecond laser pulse-induced thermochemical reduction of glyoxylic acid copper (GACu) complex. The films of the GACu complex coated on the substrates were irradiated by focused femtosecond laser pulses using a low numerical aperture of 0.45. Under the same conditions, such as laser scanning speed and pulse energy, the width of the line patterns fabricated on PDMS substrates was larger than that on glass substrates. X-ray diffraction peaks of the patterns on glass substrates corresponded to Cu without significant oxidation. By contrast, although Cu patterns were fabricated on PDMS substrates at a scanning speed of 10 mm/s and pulse energy of 0.49 nJ, Cu2O was also generated under overheating conditions at a scanning speed of 1 mm/s and pulse energy of 0.37 nJ. All the patterns exhibited electrical conductivity. The minimum resistivity of the patterns on PDMS substrates is 1.4 × 10−5 Ωm, which is 10 times higher than that on glass substrates, indicating that microcracks formed by thermal shrinkage of the substrates during the laser irradiation increase the resistivity. This direct Cu writing technique on soft materials is useful for fabricating flexible microdevices.
Design of Cell-Based Flotation Circuits under Uncertainty: A Techno-Economic Stochastic Optimization
Authors: Amini Seyed Hassan , Noble Aaron
Published: April 2021

The design of cell-based flotation circuits is often completed in two distinct phases, namely circuit structure identification and equipment sizing selection. While recent literature studies have begun to address the implications of stochastic analysis, industrial practice in flotation circuit design still strongly favors the use of deterministic metallurgical modeling approaches. Due to the complexity of the available mathematical models, most flotation circuit design techniques are constructed based on deterministic models. Neglecting the impact of various sources of uncertainty may result in the identification of circuit solutions that are only optimal in a narrow region of specific operating scenarios. One promising strategy to address this shortcoming is through the Sample Average Approximation (SAA) methodology, a stochastic approach to handling uncertainty that has been widely applied in other disciplines such as supply chain and facility location management problems. In this study, a techno-economic optimization algorithm was formulated to select the optimal size and number of flotation cells for a fixed circuit structure while considering potential uncertainty in several input parameter including feed grade, kinetic coefficients, and metal price. Initially, a sensitivity analysis was conducted to screen the uncertain parameters. After simplifying the optimization problem, the SAA approach was implemented to determine the equipment configuration (i.e., cell size and number) that maximizes the plant’s net present value while considering the range of potential input values due to parameter uncertainty. The SAA methodology was found to be useful in analyzing uncertainty in flotation kinetics; however, the approach did not provide a useful means to assess the influence of uncertainties in ore grade and metal price, as these values are not significant in determining equipment size but rather influence the optimal circuit structure, which was not considered in this study. Results from an application example indicate that the SAA approach produces optimal solutions not initially identified in a deterministic optimization, and these SAA solutions tend to provide greater robustness to uncertainty and variation in the flotation kinetics.
Editorial to the Special Issue “Food Bioactives: Chemical Challenges and Bio-Opportunities”
Authors: Pacifico Severina , Piccolella Simona
Published: April 2021

This Special Issue, entitled “Food Bioactives: Chemical Challenges and Bio-Opportunities”, was born with the aim of attracting contributions on analytical challenges in food bioactives’ chemistry and bioactivity, which form the basis of proper bio-opportunities [...]
Advanced Strategies for Tissue Engineering in Regenerative Medicine: A Biofabrication and Biopolymer Perspective
Authors: Lynch Courtney R. , Kondiah Pierre P. D. , Choonara Yahya E.
Published: April 2021

Tissue engineering is known to encompass multiple aspects of science, medicine and engineering. The development of systems which are able to promote the growth of new cells and tissue components are vital in the treatment of severe tissue injury and damage. This can be done through a variety of different biofabrication strategies including the use of hydrogels, 3D bioprinted scaffolds and nanotechnology. The incorporation of stem cells into these systems and the advantage of this is also discussed. Biopolymers, those which have a natural original, have been particularly advantageous in tissue engineering systems as they are often found within the extracellular matrix of the human body. The utilization of biopolymers has become increasing popular as they are biocompatible, biodegradable and do not illicit an immune response when placed into the body. Tissue engineering systems for use with the eye are also discussed. This is of particular interest as the eye is known as an immune privileged site resulting in an extremely limited ability for natural cell regeneration.
Zhang–Zhang Polynomials of Multiple Zigzag Chains Revisited: A Connection with the John–Sachs Theorem
Authors: Witek Henryk A.
Published: April 2021

Multiple zigzag chains Zm,n of length n and width m constitute an important class of regular graphene flakes of rectangular shape. The physical and chemical properties of these basic pericondensed benzenoids can be related to their various topological invariants, conveniently encoded as the coefficients of a combinatorial polynomial, usually referred to as the ZZ polynomial of multiple zigzag chains Zm,n. The current study reports a novel method for determination of these ZZ polynomials based on a hypothesized extension to John–Sachs theorem, used previously to enumerate Kekulé structures of various benzenoid hydrocarbons. We show that the ZZ polynomial of the Zm,n multiple zigzag chain can be conveniently expressed as a determinant of a Toeplitz (or almost Toeplitz) matrix of size m2×m2 consisting of simple hypergeometric polynomials. The presented analysis can be extended to generalized multiple zigzag chains Zkm,n, i.e., derivatives of Zm,n with a single attached polyacene chain of length k. All presented formulas are accompanied by formal proofs. The developed theoretical machinery is applied for predicting aromaticity distribution patterns in large and infinite multiple zigzag chains Zm,n and for computing the distribution of spin densities in biradical states of finite multiple zigzag chains Zm,n.
Inhibitory Effects of Cycloheterophyllin on Melanin Synthesis
Authors: Shim Joong-Hyun
Published: April 2021

This study was performed to clarify the inhibitory effects of cycloheterophyllin on melanin synthesis. In order to elucidate the inhibitory effects of cycloheterophyllin on the B16F10 cell line, cell viability, messenger ribonucleic acid (mRNA) expressions, tyrosinase activity assay, and melanin production assay were measured. The effects of cycloheterophyllin on tyrosinase-related protein 1 (TYRP1)/TYRP2/tyrosinase (TYR)/microphthalmia-associated transcription factor (MITF) mRNA expressions and melanin content were determined. Quantitative real-time RT-PCR showed that cycloheterophyllin decreased the mRNA expression level of TYRP1/TYRP2/TYR/MITF genes and melanin production contents than α-MSH-treated B16F10 cells. The tyrosinase activity assay revealed that cycloheterophyllin decreased the melanin production in the B16F10 cells. These data show that cycloheterophyllin increases the whitening effects in the B16F10 cells; thus, cycloheterophyllin is a potent ingredient for skin whitening. Thus, further research on the mechanism of action of cycloheterophyllin for the development of functional materials should be investigated.
Self-Associating Polymers Chitosan and Hyaluronan for Constructing Composite Membranes as Skin-Wound Dressings Carrying Therapeutics
Authors: Valachová Katarína , Šoltés Ladislav
Published: April 2021

Chitosan, industrially acquired by the alkaline N-deacetylation of chitin, belongs to β-N-acetyl-glucosamine polymers. Another β-polymer is hyaluronan. Chitosan, a biodegradable, non-toxic, bacteriostatic, and fungistatic biopolymer, has numerous applications in medicine. Hyaluronan, one of the major structural components of the extracellular matrix in vertebrate tissues, is broadly exploited in medicine as well. This review summarizes that these two biopolymers have a mutual impact on skin wound healing as skin wound dressings and carriers of remedies.
Development of Novel Potential Pleiotropic Compounds of Interest in Alzheimer’s Disease Treatment through Rigidification Strategy
Authors: Lecoutey Cédric , Legay Rémi , Davis Audrey , Sopková-de Oliveira Santos Jana , Dallemagne Patrick , Rochais Christophe
Published: April 2021

The development of Multi-Target Directed Ligand is of clear interest for the treatment of multifactorial pathology such as Alzheimer’s disease (AD). In this context, acetylcholinesterase (AChE) inhibitors have been modulated in order to generate novel pleiotropic compounds targeting a second protein of therapeutic interest in AD. Among them, donecopride was the first example of a dual acetylcholinesterase inhibitor and 5-HT4 receptor agonist. In order to explore the structural diversity around this preclinical candidate we have explored the preparation of novel constrained analogs through late-stage rigidification strategy. A series of phenylpyrazoles was prepared in a late-stage functionalization process and all compounds were evaluated in vitro towards AChE and 5-HTRs. A docking study was performed in order to better explain the observed SAR towards AChE, 5-HT4R and 5-HT6R and this study led to the description of novel ligand targeting both AChE and 5-HT6R.
The Health-Promoting Properties and Clinical Applications of Rice Bran Arabinoxylan Modified with Shiitake Mushroom Enzyme—A Narrative Review
Authors: Ooi Soo Liang , Pak Sok Cheon , Micalos Peter S. , Schupfer Emily , Lockley Catherine , Park Mi Houn , Hwang Sung-Joo
Published: April 2021

Rice bran arabinoxylan compound (RBAC) is derived from defatted rice bran hydrolyzed with Lentinus edodes mycelial enzyme. It has been marketed as a functional food and a nutraceutical with health-promoting properties. Some research has demonstrated this rice bran derivative to be a potent immunomodulator, which also possesses anti-inflammatory, antioxidant, and anti-angiogenic properties. To date, research on RBAC has predominantly focused on its immunomodulatory action and application as a complementary therapy for cancer. Nonetheless, the clinical applications of RBAC can extend beyond cancer therapy. This article is a narrative review of the research on the potential benefits of RBAC for cancer and other health conditions based on the available literature. RBAC research has shown it to be useful as a complementary treatment for cancer and human immunodeficiency virus infection. It can positively modulate serum glucose, lipid and protein metabolism in diabetic patients. Additionally, RBAC has been shown to ameliorate irritable bowel syndrome and protect against liver injury caused by hepatitis or nonalcoholic fatty liver disease. It can potentially ease symptoms in chronic fatigue syndrome and prevent the common cold. RBAC is safe to consume and has no known side effects at the typical dosage of 2–3 g/day. Nevertheless, further research in both basic studies and human clinical trials are required to investigate the clinical applications, mechanisms, and effects of RBAC.
Stereoselective Synthesis of Selenium-Containing Glycoconjugates via the Mitsunobu Reaction
Authors: Serpico Luigia , De Nisco Mauro , Cermola Flavio , Manfra Michele , Pedatella Silvana
Published: April 2021

A simple and efficient route for the synthesis of new glycoconjugates has been developed. The approach acts as a model for a mini-library of compounds with a deoxy-selenosugar core joined to a polyphenolic moiety with well-known antioxidant properties. An unexpected stereocontrol detected in the Mitsunobu key reaction led to the most attractive product showing a natural d-configuration. Thus, we were able to obtain the target molecules from the commercially available d-ribose via a shorter and convenient sequence of reactions.
Update on Calcium and Phosphorus Requirements of Preterm Infants and Recommendations for Enteral Mineral Intake
Authors: Mihatsch Walter , Thome Ulrich , Saenz de Pipaon Miguel
Published: April 2021

Background: With current Ca and P recommendations for enteral nutrition, preterm infants, especially VLBW, fail to achieve a bone mineral content (BMC) equivalent to term infants. During the first 3 years, most notably in light at term equivalent age (<−2 Z score) VLBW infants’ BMC does not catch up. In adults born preterm with VLBW or SGA, lower adult bone mass, lower peak bone mass, and higher frequency of osteopenia/osteoporosis have been found, implying an increased risk for future bone fractures. The aim of the present narrative review was to provide recommendation for enteral mineral intake for improving bone mineral accretion. Methods: Current preterm infant mineral recommendations together with fetal and preterm infant physiology of mineral accretion were reviewed to provide recommendations for improving bone mineral accretion. Results: Current Ca and P recommendations systematically underestimate the needs, especially for Ca. Conclusion: Higher enteral fortifier/formula mineral content or individual supplementation is required. Higher general mineral intake (especially Ca) will most likely improve bone mineralization in preterm infants and possibly the long-term bone health. However, the nephrocalcinosis risk may increase in infants with high Ca absorption. Therefore, individual additional enteral Ca and/or P supplementations are recommended to improve current fortifier/formula mineral intake.
Cyclodextrin-Assisted Extraction Method as a Green Alternative to Increase the Isoflavone Yield from Trifolium pratensis L. Extract
Authors: Kazlauskaite Jurga Andreja , Ivanauskas Liudas , Bernatoniene Jurga
Published: April 2021

Trifolium pratense L. is receiving increasing attention due to the isoflavones it contains, which have been studied for their benefits to human health. A common problem with isoflavone aglycones is a rather low water solubility and limited pharmaceutical applications. The use of excipients, such as cyclodextrins in the production of isoflavone rich extracts, could become one of the new strategies for the extraction of target compounds. The aim of this study was to evaluate an eco-friendly method using the effects of α-, β- and γ-cyclodextrins for isoflavone solubilization in plant extracts in comparison to a standard extract without excipients. Extractions of red clover were prepared using ultrasound-assisted combined with thermal hydrolysis and heat reflux. It was determined that cyclodextrins significantly increased the isoflavones aglycone yields. By increasing cyclodextrins in the extraction media from 1 to 5%, the daidzin concentration increased on average by 1.06 (α-cyclodextrins), 1.4 (β-cyclodextrins) and 1.25 (γ-cyclodextrins) times. Genistein concentration increased using α- and γ-cyclodextrins (1.28 and 1.12 times, α- and γ-cyclodextrins, respectively), but decreased using β-cyclodextrins. The results showed that the cyclodextrin-assisted extraction enhanced the yields of isoflavones from red clover, which suggests using cyclodextrins as a green alternative and a cost-effective method to increase its pharmaceutical application.