bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Thermal Debinding Conditions on the Sintered Density of Low-Pressure Powder Injection Molded Iron Parts
Authors: Tafti Atefeh A. , Demers Vincent , Majdi Seyed Mohammad , Vachon Guillem , Brailovski Vladimir
Published: February 2021

Low-pressure powder injection molding (LPIM) is a cost-effective technology for producing intricate small metal parts at high, medium, and low production volumes in applications which, to date, have involved ceramics or spherical metal powders. Since the use of irregular metal powders represents a promising way to reduce overall production costs, this study aims to investigate the potential of manufacturing powder injection molded parts from irregular commercial iron powders using the LPIM approach. To this end, a low viscosity feedstock was injected into a rectangular mold cavity, thermally wick-debound using three different pre-sintering temperatures, and finally sintered using an identical sintering cycle. During debinding, an increase in pre-sintering temperature from 600 to 850 °C decreased the number of fine particles. This decreased the sintered density from 6.2 to 5.1 g/cm3, increased the average pore size from 9 to 14 μm, and decreased pore circularity from 67 to 59%.
Additive Manufacturing of Titanium with Different Surface Structures for Adhesive Bonding and Thermal Direct Joining with Fiber-Reinforced Polyether-Ether-Ketone (PEEK) for Lightweight Design Applications
Authors: Moritz Juliane , Götze Philipp , Schiefer Tom , Stepien Lukas , Klotzbach Annett , Standfuß Jens , López Elena , Brückner Frank , Leyens Christoph
Published: February 2021

Hybrid joints consisting of metals and fiber-reinforced polymer composites exhibit highly desirable properties for many lightweight design applications. This study investigates the potential of additively manufactured surface structures for enhancing the bond strength of such joints in comparison to face milled and laser structured surfaces. Titanium samples with different surface structures (as-built surface, groove-, and pin-shaped structures) were manufactured via electron beam melting and joined to carbon fiber-reinforced polyether-ether-ketone (PEEK) via adhesive bonding and thermal direct joining, respectively. Bond strength was evaluated by tensile shear testing. Samples were exposed to salt spray testing for 1000 h for studying bond stability under harsh environmental conditions. The initial tensile shear strengths of the additively manufactured samples were competitive to or in some cases even exceeded the values achieved with laser surface structuring for both investigated joining methods. The most promising results were found for pin-shaped surface structures. However, the hybrid joints with additively manufactured structures tended to be more susceptible to degradation during salt spray exposure. It is concluded that additively manufactured structures can be a viable alternative to laser surface structuring for both adhesive bonding and thermal direct joining of metal-polymer hybrid joints, thus opening up new potentials in lightweight design.
The Effect of Wire Feeding Speed on Solidification Cracking of CMT Welding for Al-Si Alloys
Authors: Huang Lei , Chen Xizhang , Konovalov Sergey , Siddiquee Arshad Noor , Lu Gang , Pan Xiaoming
Published: February 2021

In this work, a welding solidification crack sensitivity test platform was established to study the effect of wire feeding speed (WFS) on solidification crack sensitivity during cold metal transfer (CMT) welding for AA6061 aluminum alloy. The test results show that as the WFS increased from 4 m/min to 5.5 m/min, the sensitivity of the solidification cracks also increased. With a further increase in the value of the WFS, the crack sensitivity decreased and eventually ceased to exist. A new perspective of the microstructure and crack propagation mechanics model was applied to understand the effect of WFS on solidification cracks. With the use of scanning electron microscopy (SEM) and a high-speed camera, it was found that as the WFS increased from 4 m/min to 5.5 m/min, the microstructure of the grain size changed from bigger to smaller, and the stability of the crystal microstructure was reduced. The crack propagation mechanics model was changed, which promotes crack propagation, increasing by 233%. When the WFS continued to increase beyond 5.5 m/min, the size of the crystal structure changed from small to big, the stability of the crystal microstructure was increased, the crack generation was suppressed, and the cracking rate was significantly reduced.
Effects of Silicon and Heat-Treatment on Microstructure and Mechanical Properties of Biomedical Ti-39Nb-6Zr Alloy
Authors: Jang Ji-Hoon , Lee Dong-Geun
Published: February 2021

The cytotoxic tissue reactions of alloying elements (Al, V) of Ti-6Al-4V have been reported, whereas the Ti-39Nb-6Zr (TNZ40) alloy developed by adding β-phase stabilizing elements is known to have no cytotoxicity and exhibits excellent biocompatibility. In addition, there is a slight modulus difference between the TNZ40 alloy and human bones as the elastic modulus of the TNZ40 alloy is very low. This can inhibit detrimental effects such as osteoblast loss due to a stress-shielding effect. In this study, various Si contents were added and heat treatment under various conditions was performed to control the microstructure and mechanical properties of the TNZ40 alloy. In the β-type titanium alloy, the ω phase is commonly observed by quenching from the solution-treatment or aging-treatment temperature. These ω precipitates can typically increase the elastic modulus, hardness, and embrittlement of the β-type titanium alloy, which are important to control this phase. The correlation between Si content and precipitation and the effects of solution treatment and aging condition on the mechanical properties such as tensile strength, and hardness, were analyzed.
Validation of Candidate Phospholipid Biomarkers of Chronic Kidney Disease in Hyperglycemic Individuals and Their Organ-Specific Exploration in Leptin Receptor-Deficient db/db Mouse
Authors: Huang Jialing , Covic Marcela , Huth Cornelia , Rommel Martina , Adam Jonathan , Zukunft Sven , Prehn Cornelia , Wang Li , Nano Jana , Scheerer Markus F. , Neschen Susanne , Kastenmüller Gabi , Gieger Christian , Laxy Michael , Schliess Freimut , Adamski Jerzy , Suhre Karsten , de Angelis Martin Hrabe , Peters Annette , Wang-Sattler Rui
Published: February 2021

Biological exploration of early biomarkers for chronic kidney disease (CKD) in (pre)diabetic individuals is crucial for personalized management of diabetes. Here, we evaluated two candidate biomarkers of incident CKD (sphingomyelin (SM) C18:1 and phosphatidylcholine diacyl (PC aa) C38:0) concerning kidney function in hyperglycemic participants of the Cooperative Health Research in the Region of Augsburg (KORA) cohort, and in two biofluids and six organs of leptin receptor-deficient (db/db) mice and wild type controls. Higher serum concentrations of SM C18:1 and PC aa C38:0 in hyperglycemic individuals were found to be associated with lower estimated glomerular filtration rate (eGFR) and higher odds of CKD. In db/db mice, both metabolites had a significantly lower concentration in urine and adipose tissue, but higher in the lungs. Additionally, db/db mice had significantly higher SM C18:1 levels in plasma and liver, and PC aa C38:0 in adrenal glands. This cross-sectional human study confirms that SM C18:1 and PC aa C38:0 associate with kidney dysfunction in pre(diabetic) individuals, and the animal study suggests a potential implication of liver, lungs, adrenal glands, and visceral fat in their systemic regulation. Our results support further validation of the two phospholipids as early biomarkers of renal disease in patients with (pre)diabetes.
A Study of Blood Fatty Acids Profile in Hyperlipidemic and Normolipidemic Subjects in Association with Common PNPLA3 and ABCB1 Polymorphisms
Authors: Mouskeftara Thomai , Goulas Antonis , Ioannidou Despoina , Ntenti Charikleia , Agapakis Dimitris , Assimopoulou Andreana , Gika Helen
Published: February 2021

Adiponutrin (patatin-like phospholipase domain-containing 3; PNPLA3), encoded in humans by the PNPLA3 gene, is a protein associated with lipid droplet and endoplasmic reticulum membranes, where it is apparently involved in fatty acid redistribution between triglycerides and phospholipids. A common polymorphism of PNPLA3 (I148M, rs738409), linked to increased PNPLA3 presence on lipid droplets, is a strong genetic determinant of non-alcoholic fatty liver disease (NAFLD) and of its progression. P-glycoprotein (Pgp, MDR1—multidrug resistance protein 1, ABCB1—ATP-binding cassette sub-family B member 1), encoded by the ABCB1 gene, is another membrane protein implicated in lipid homeostasis and steatosis. In the past, common ABCB1 polymorphisms have been associated with the distribution of serum lipids but not with fatty acids (FA) profiles. Similarly, data on the effect of PNPLA3 I148M polymorphism on blood FAs are scarce. In this study, a gas chromatography-flame ionization detection (GC-FID) method was optimized, allowing us to analyze twenty FAs (C14: 0, C15: 0, C15: 1, C16: 0, C16: 1, C17: 0, C17: 1, C18: 0, C18: 1cis, C18: 2cis, C20: 0, C20: 1n9, C20: 2, C20: 3n6, C20: 4n6, C20: 5, C23: 0, C24: 0, C24: 1 and C22: 6) in whole blood, based on the indirect determination of the fatty acids methyl esters (FAMES), in 62 hyperlipidemic patients and 42 normolipidemic controls. FA concentrations were then compared between the different genotypes of the rs738409 and rs2032582 (ABCB1 G2677T) polymorphisms, within and between the hyperlipidemic and normolipidemic groups. The rs738409 polymorphism appears to exert a significant effect on the distribution of blood fatty acids, in a lipidemic and fatty acid saturation state-depending manner. The effect of rs2032582 was less pronounced, but the polymorphism did appear to affect the relative distribution of blood fatty acids between hyperlipidemic patients and normolipidemic controls.
Optical Monitoring of the Production Quality of Si-Nanoribbon Chips Intended for the Detection of ASD-Associated Oligonucleotides
Authors: Malsagova Kristina A. , Pleshakova Tatyana O. , Popov Vladimir P. , Kupriyanov Igor N. , Galiullin Rafael A. , Kozlov Andrey F. , Shumov Ivan D. , Kaysheva Anna L. , Tikhonenko Fedor V. , Archakov Alexander I. , Ivanov Yuri D.
Published: February 2021

Gas-phase etching and optical lithography were employed for the fabrication of a silicon nanoribbon chip (Si-NR chip). The quality of the so-fabricated silicon nanoribbons (Si-NRs) was monitored by optical Raman scattering spectroscopy. It was demonstrated that the structures of the Si-NRs were virtually defect-free, meaning they could be used for highly sensitive detection of biological macromolecules. The Si-NR chips were then used for the highly sensitive nanoelectronics detection of DNA oligonucleotides (oDNAs), which represent synthetic analogs of 106a-5p microRNA (miR-106a-5p), associated with the development of autism spectrum disorders in children. The specificity of the analysis was attained by the sensitization of the Si-NR chip sur-face by covalent immobilization of oDNA probes, whose nucleotide sequence was complementary to the known sequence of miR-106a-5p. The use of the Si-NR chip was demonstrated to al-low for the rapid label-free real-time detection of oDNA at ultra-low (~10−17 M) concentrations.
Generation and Dynamics of Janus Droplets in Shear-Thinning Fluid Flow in a Double Y-Type Microchannel
Authors: Bai Fan , Zhang Hongna , Li Xiaobin , Li Fengchen , Joo Sang Woo
Published: February 2021

Droplets composed of two different materials, or Janus droplets, have diverse applications, including microfluidic digital laboratory systems, DNA chips, and self-assembly systems. A three-dimensional computational study of Janus droplet formation in a double Y-type microfluidic device filled with a shear-thinning fluid is performed by using the multiphaseInterDyMFoam solver of the OpenFOAM, based on a finite-volume method. The bi-phase volume-of-fluid method is adopted to track the interface with an adaptive dynamic mesh refinement for moving interfaces. The formation of Janus droplets in the shear-thinning fluid is characterized in five different states of tubbing, jetting, intermediate, dripping and unstable dripping in a multiphase microsystem under various flow conditions. The formation mechanism of Janus droplets is understood by analyzing the influencing factors, including the flow rates of the continuous phase and of the dispersed phase, surface tension, and non-Newtonian rheological parameters. Studies have found that the formation of the Janus droplets and their sizes are related to the flow rate at the inlet under low capillary numbers. The rheological parameters of shear-thinning fluid have a significant impact on the size of Janus droplets and their formation mechanism. As the apparent viscosity increases, the frequency of Janus droplet formation increases, while the droplet volume decreases. Compared with Newtonian fluid, the Janus droplet is more readily generated in shear-thinning fluid due to the interlay of diminishing viscous force, surface tension, and pressure drop.
Design and Locomotion Study of Stick-Slip Piezoelectric Actuator Using Two-Stage Flexible Hinge Structure
Authors: Li Zheng , Su Zhirong , Zhao Liang , Han Haitao , Guo Zhanyu , Zhao Yuyang , Sun Hexu
Published: February 2021

A novel piezoelectric actuator using a two-stage flexure hinge structure is proposed in this paper, which is used in a compact and high-precision electromechanical field. The two-stage flexure hinge structure is used to provide horizontal thrust and vertical clamping force to the driving feet, which solves the problems of unstable clamping force and insufficient load capacity in traditional stick-slip piezoelectric actuators. Firstly, the main structure of the driver and the working process under the triangular wave excitation voltage are briefly introduced. Secondly, after many simulation tests, the structure of the actuator is optimized and the stability of the structure in providing clamping force is verified. Finally, through the research of the operating performance, when the amplitude is 150 V and the frequency is 3.25 kHz as the excitation source, the maximum speed can reach 338 mm/s and can bear about 3 kg load. It can be seen from the analysis that the two-stage flexure hinge structure can improve the displacement trajectory.
Exploring the Chemical Space of Macro- and Micro-Algae Using Comparative Metabolomics
Authors: Hughes Alison H. , Magot Florent , Tawfike Ahmed F. , Rad-Menéndez Cecilia , Thomas Naomi , Young Louise C. , Stucchi Laura , Carettoni Daniele , Stanley Michele S. , Edrada-Ebel RuAngelie , Duncan Katherine R.
Published: February 2021

With more than 156,000 described species, eukaryotic algae (both macro- and micro-algae) are a rich source of biological diversity, however their chemical diversity remains largely unexplored. Specialised metabolites with promising biological activities have been widely reported for seaweeds, and more recently extracts from microalgae have exhibited activity in anticancer, antimicrobial, and antioxidant screens. However, we are still missing critical information on the distinction of chemical profiles between macro- and microalgae, as well as the chemical space these metabolites cover. This study has used an untargeted comparative metabolomics approach to explore the chemical diversity of seven seaweeds and 36 microalgal strains. A total of 1390 liquid chromatography-mass spectrometry (LC-MS) features were detected, representing small organic algal metabolites, with no overlap between the seaweeds and microalgae. An in-depth analysis of four Dunaliella tertiolecta strains shows that environmental factors may play a larger role than phylogeny when classifying their metabolomic profiles.
Diversity of Leptogium (Collemataceae, Ascomycota) in East African Montane Ecosystems
Authors: Kaasalainen Ulla , Tuovinen Veera , Kirika Paul M. , Mollel Neduvoto P. , Hemp Andreas , Rikkinen Jouko
Published: February 2021

Tropical mountains and especially their forests are hot spots of biodiversity threatened by human population pressure and climate change. The diversity of lichens in tropical Africa is especially poorly known. Here we use the mtSSU and nuITS molecular markers together with morphology and ecology to assess Leptogium (Peltigerales, Ascomycota) diversity in the tropical mountains of Taita Hills and Mt. Kasigau in Kenya and Mt. Kilimanjaro in Tanzania. The sampled habitats cover a wide range of ecosystems from savanna to alpine heath vegetation and from relatively natural forests to agricultural environments and plantation forests. We demonstrate that Leptogium diversity in Africa is much higher than previously known and provide preliminary data on over 70 putative species, including nine established species previously known from the area and over 60 phylogenetically, morphologically, and/or ecologically defined Operational Taxonomic Units (OTUs). Many traditional species concepts are shown to represent morphotypes comprised of several taxa. Many of the species were only found from specific ecosystems and/or restricted habitats and are thus threatened by ongoing habitat fragmentation and degradation of the natural environment. Our results emphasize the importance of molecular markers in species inventories of highly diverse organism groups and geographical areas.
Interaction between Dickeya dianthicola and Pectobacterium parmentieri in Potato Infection under Field Conditions
Authors: Ge Tongling , Ekbataniamiri Fatemeh , Johnson Steven B. , Larkin Robert P. , Hao Jianjun
Published: February 2021

Dickeya and Pectobacterium spp. both cause blackleg and soft rot of potato, which can be a yield-reducing factor to potato production. The purpose of this study was to examine the interaction between these two bacterial genera causing potato infection, and subsequent disease development and yield responses under field conditions. Analysis of 883 potato samples collected in Northeastern USA using polymerase chain reaction determined that Dickeya dianthicola and P. parmentieri were found in 38.1% and 53.3% of all samples, respectively, and that 20.6% of samples contained both D. dianthicola and P. parmentieri. To further investigate the relationship between the two bacterial species and their interaction, field trials were established. Potato seed pieces of “Russet Burbank”, “Lamoka”, and “Atlantic” were inoculated with bacterial suspension of D. dianthicola at 107 colony-forming unite (CFU)/mL using a vacuum infiltration method, air dried, and then planted in the field. Two-year results showed that there was a high correlation (p < 0.01) between yield loss and percent of inoculated seed pieces. In a secondary field trial conducted in 2018 and 2019, seed pieces of potato “Shepody”, “Lamoka” and “Atlantic” were inoculated with D. dianthicola, P. parmentieri, or mixture of both species, and then planted. In 2019, disease severity index, as measured by the most sensitive variety “Lamoka”, was 16.2 with D. dianthicola inoculation, 10.4 with P. parmentieri, 25.4 with inoculation with both bacteria. Two-year data had a similar trend. Thus, D. dianthicola was more virulent than P. parmentieri, but the co-inoculation of the two species resulted in increased disease severity compared to single-species inoculation with either pathogen.
Impact of Ceftiofur Administration in Steers on the Prevalence and Antimicrobial Resistance of Campylobacter spp.
Authors: Fan Sicun , Foster Derek , Miller William G. , Osborne Jason , Kathariou Sophia
Published: February 2021

Bacterial resistance to ceftiofur raises health concerns due to ceftiofur’s extensive veterinary usage and structural similarity with the human antibiotic ceftriaxone. Ceftiofur crystalline-free acid (CCFA) and ceftiofur hydrochloride (CHCL) are ceftiofur types used therapeutically in cattle, but their potential impacts on Campylobacter prevalence and antimicrobial resistance remain unclear. In this study two groups of steers were each treated with CCFA or CHCL. In vivo active drug concentrations were measured and fecal samples were analyzed for Campylobacter for up to 42 days post-treatment. Following administration, the colonic concentration of ceftiofur initially increased then dropped to pre-treatment levels by day 8. The estimated prevalence of Campylobacter spp. was significantly (p = 0.0009) higher during the first week after CCFA treatment than after CHCL treatment (81.3% vs. 45.2%). Campylobacter jejuni predominated overall, with other Campylobacter spp. mainly identified in the first week after CCFA treatment. No treatment impacts were noted on ceftiofur minimum inhibitory concentration (MIC) for C. jejuni (10–20 μg/mL). More C. jejuni genotypes were detected in CCFA-treated than CHCL-treated steers. These findings suggest that ceftiofur did not significantly impact Campylobacter prevalence or ceftiofur MIC. However, CHCL may be preferable due to the lower likelihood of temporary increases in Campylobacter prevalence.
Leishmanicidal Activity of Betulin Derivatives in Leishmania amazonensis; Effect on Plasma and Mitochondrial Membrane Potential, and Macrophage Nitric Oxide and Superoxide Production
Authors: Alcazar Wilmer , Alakurtti Sami , Padrón-Nieves Maritza , Tuononen Maija Liisa , Rodríguez Noris , Yli-Kauhaluoma Jari , Ponte-Sucre Alicia
Published: February 2021

Herein, we evaluated in vitro the anti-leishmanial activity of betulin derivatives in Venezuelan isolates of Leishmania amazonensis, isolated from patients with therapeutic failure. Methods: We analyzed promastigote in vitro susceptibility as well as the cytotoxicity and selectivity of the evaluated compounds. Additionally, the activity of selected compounds was determined in intracellular amastigotes. Finally, to gain hints on their potential mechanism of action, the effect of the most promising compounds on plasma and mitochondrial membrane potential, and nitric oxide and superoxide production by infected macrophages was determined. Results: From the tested 28 compounds, those numbered 18 and 22 were chosen for additional studies. Both 18 and 22 were active (GI50 ≤ 2 µM, cytotoxic CC50 > 45 µM, SI > 20) for the reference strain LTB0016 and for patient isolates. The results suggest that 18 significantly depolarized the plasma membrane potential (p < 0.05) and the mitochondrial membrane potential (p < 0.05) when compared to untreated cells. Although neither 18 nor 22 induced nitric oxide production in infected macrophages, 18 induced superoxide production in infected macrophages. Conclusion: Our results suggest that due to their efficacy and selectivity against intracellular parasites and the potential mechanisms underlying their leishmanicidal effect, the compounds 18 and 22 could be used as tools for designing new chemotherapies against leishmaniasis.
Cross-Feeding of a Toxic Metabolite in a Synthetic Lignocellulose-Degrading Microbial Community
Authors: Lee Jessica A. , Baugh Alyssa C. , Shevalier Nicholas J. , Strand Brandi , Stolyar Sergey , Marx Christopher J.
Published: February 2021

The recalcitrance of complex organic polymers such as lignocellulose is one of the major obstacles to sustainable energy production from plant biomass, and the generation of toxic intermediates can negatively impact the efficiency of microbial lignocellulose degradation. Here, we describe the development of a model microbial consortium for studying lignocellulose degradation, with the specific goal of mitigating the production of the toxin formaldehyde during the breakdown of methoxylated aromatic compounds. Included are Pseudomonas putida, a lignin degrader; Cellulomonas fimi, a cellulose degrader; and sometimes Yarrowia lipolytica, an oleaginous yeast. Unique to our system is the inclusion of Methylorubrum extorquens, a methylotroph capable of using formaldehyde for growth. We developed a defined minimal “Model Lignocellulose” growth medium for reproducible coculture experiments. We demonstrated that the formaldehyde produced by P. putida growing on vanillic acid can exceed the minimum inhibitory concentration for C. fimi, and, furthermore, that the presence of M. extorquens lowers those concentrations. We also uncovered unexpected ecological dynamics, including resource competition, and interspecies differences in growth requirements and toxin sensitivities. Finally, we introduced the possibility for a mutualistic interaction between C. fimi and M. extorquens through metabolite exchange. This study lays the foundation to enable future work incorporating metabolomic analysis and modeling, genetic engineering, and laboratory evolution, on a model system that is appropriate both for fundamental eco-evolutionary studies and for the optimization of efficiency and yield in microbially-mediated biomass transformation.
The Kynurenine Pathway is Differentially Activated in Children with Lyme Disease and Tick-Borne Encephalitis
Authors: Wickström Ronny , Fowler Åsa , Goiny Michel , Millischer Vincent , Ygberg Sofia , Schwieler Lilly
Published: February 2021

In children, tick-borne encephalitis and neuroborreliosis are common infections affecting the central nervous system. As inflammatory pathways including cytokine expression are activated in these children and appear to be of importance for outcome, we hypothesized that induction of the kynurenine pathway may be part of the pathophysiological mechanism. Inflammatory biomarkers were analyzed in cerebrospinal fluid from 22 children with tick-borne encephalitis (TBE), 34 children with neuroborreliosis (NB) and 6 children with no central nervous system infection. Cerebrospinal fluid levels of kynurenine and kynurenic acid were increased in children with neuroborreliosis compared to the comparison group. A correlation was seen between expression of several cerebrospinal fluid cytokines and levels of kynurenine and kynurenic acid in children with neuroborreliosis but not in children with tick-borne encephalitis. These findings demonstrate a strong induction of the kynurenine pathway in children with neuroborreliosis which differs from that seen in children with tick-borne encephalitis. The importance of brain kynurenic acid (KYNA) in both immune modulation and neurotransmission raises the possibility that abnormal levels of the compound in neuroborreliosis might be of importance for the pathophysiology of the disease. Drugs targeting the enzymes of this pathway may open the venue for novel therapeutic interventions.
Full-Length Genome and Partial Viral Genes Phylogenetic and Geographical Analysis of Dengue Serotype 3 Isolates
Authors: Amir Muhammad , Hussain Abrar , Asif Muhammad , Ahmed Sagheer , Alam Hina , Moga Marius Alexandru , Cocuz Maria Elena , Marceanu Luigi , Blidaru Alexandru
Published: February 2021

Dengue fever is among the most common vector-borne diseases. Dengue virus (DENV), responsible for dengue fever as well as dengue hemorrhagic fever, belongs to the genus flavivirus and family Flaviviridae. Flaviviruses infect various vertebrate species and arthropods and are also responsible for diseases in birds, wild animals, and primates. DENV consists of a single-stranded, positive-sense RNA genome ~11 kb in size. Complete genome and partial gene sequences of geographically distinct DENV-3 strains were retrieved from the GenBank database. The evolutionary divergence of the 33 whole-genome and individual gene sequences of the nucleotides and amino acids of DENV-3 strains were generated with the maximum likelihood (ML) and Bayesian phylogenetic study (BEAST) methods using the MEGA 7 software. The genome size varied from 10,484 to 10,724 nucleotides among the strains with distinct geographical backgrounds belonging to Central America, South-Central Asia, and Eastern Asia. A phylogenetic analysis of the nucleotide and amino acid sequences of these DENV-3 isolates revealed extensive differences in the topologies due to PrM/M, NS1, NS2B, and NS3 genes. These results suggest substantial variation in the evolutionary pathways of the studied genes and genomes.
Natural and Anthropogenic Origin of Metals in Lacustrine Sediments; Assessment and Consequences—A Case Study of Wigry Lake (Poland)
Authors: Kostka Anna , Leśniak Andrzej
Published: February 2021

The contamination of aquatic sediments by metals is a worldwide phenomenon and its assessment is a fairly complex issue, as numerous factors affect the distribution of particular contaminants in the environment, as well as their bioavailability. Wigry Lake, as the object of this study, is almost a perfect water body for such considerations. It has been well investigated and densely sampled (up to 459 sediment samples). The quantities of seven metals were determined using the atomic absorption spectrometry (AAS) or inductively coupled plasma (ICP)-MS methods, following previous extraction in a microwave oven. The levels of concentration of the examined elements were as follows (min–max (mg·kg−1)): Cd—0.003–3.060; Cr—0.20–22.61; Cu—0.02–59.70; Fe—80–32,857; Mn—18–1698; Pb—7.0–107.5; Zn—3.1–632.1. Significant differences were also registered in terms of particular metal concentrations in different sediment types found at the lake bottom. Five different geochemical backgrounds and sediment quality guidelines implemented in the study enabled a very scrupulous contamination assessment of the lake sediments’ condition, as well as the evaluation of the natural and anthropogenic contribution to the enrichment of examined sediments in metals. Although Wigry Lake is situated in a pristine region, it is still subject to anthropopressure, which seems to be the lowest in respect to Cr and Mn, while the highest in the case of Pb. The chemoecological state of the lake was ultimately assessed as good. The study highlighted the necessity of an integrated approach to the assessment of contamination or pollution in the course of an environmental research.
Unraveling Sources and Climate Conditions Prevailing during the Deposition of Neoproterozoic Evaporites Using Coupled Chemistry and Boron Isotope Compositions (δ11B): The Example of the Salt Range, Punjab, Pakistan
Authors: Hussain Syed Asim , Han Feng-Qing , Ma Zhe , Hussain Amjad , Mughal Muhammad Saleem , Han Jibin , Alhassan Abdullah , Widory David
Published: February 2021

In this study, the ion concentrations (K+, Na+, Ca2+, Mg2+, Cl−, SO42−, Br−, NO3−, and B3+) and boron isotope compositions (δ11B) of 34 halite and brines samples from the Neoproterozoic Salt Range Formation, Punjab, Pakistan were studied. Relation among B3+ vs. Mg2+, B3+ vs. SO42−, δ11B vs. B3+, and δ11B vs K+ were observed, they indicated that these elements originate from multiple sources and the end members were identified as seawater, B desorption from clays, and meteoric precipitation. Halite samples of the area under study displayed a Na-HCO3-type to Ca-Cl type sedimentary basin of deposition, on δ11B vs. 1/B plot. Molar ratios of B/Cl vs. δ11B revealed the addition of B in some of the studied samples from desorption of clay minerals. This type of diagenetic desorption of B from clays is the consequence of a stress driven mechanism, generated in the proximity of a decollement zone. Results confirm that the number of B stable isotopes that fractionate between the brine and the halite is low. The halite δ11B from the Salt Range Formation vary from +2.1 to +24.4‰, compared to +17.3 to +26.1‰ in the salt pool brines, and suggest that boron isotope compositions are controlled by the δ11B of the B sources. The positive relationship between the boron content and the corresponding δ11B indicates a higher salinity and drier paleoclimate conditions during the formation process, associated with a high evaporation rate in the Late Neoproterozoic time. Presence of elevated δ11B in the present study, demonstrate compatibility with other marine basins of the world, arising the need for further investigations to better characterize the 11B-enriching processes.
Influence of Two Mass Variables on Inertia Cone Crusher Performance and Optimization of Dynamic Balance
Authors: Cheng Jiayuan , Ren Tingzhi , Zhang Zilong , Jin Xin , Liu Dawei
Published: February 2021

Inertia cone crushers are widely used in complex ore mineral processing. The two mass variables (fixed cone mass and moving cone mass) affect the dynamic performance of the inertia cone crusher. Particularly the operative crushing force of the moving cone and the amplitude of the fixed cone are affected, and thus the energy consumption of the crusher. In this paper, the process of crushing steel slag is taken as a specific research object, to analyze the influence of two mass variables on the inertia cone crusher performance. A real-time dynamic model based on the multi-body dynamic (MBD) and the discrete element method (DEM) is established. Furthermore, the influence of the fixed cone mass and moving cone mass on the operative crushing force, amplitude and average power draw are explored by the design of simulation experiments. The predictive regression models of inertia cone crusher performance are obtained using response surface methodology (RSM). After increasing the fixed cone mass, the optimized amplitude, average power and moving cone mass are decreased by 37.1%, 33.1% and 10%, respectively, compared to without the adjustment. Finally, a more effective dynamic balancing mechanism of inertia cone crusher is achieved, which can utilize the kinetic energy of a balancer, and minimize the mass of the fixed and moving cone. The fixed cone mass and moving cone mass of a balancing crusher are decreased by 78.9% and 22.8%, respectively, compared to without the balancing mechanism.
Editorial for Special Issue “Leaching of Rare Earth Elements from Various Sources”
Authors: Han Kenneth N.
Published: February 2021

Rare earth elements (REEs) have become an important group of metals used in many high-tech industries, including high-strength magnets, plasma TVs, various military applications, and clean and efficient green energy industries [...]
A Multi-Objective Approach for Drug Repurposing in Preeclampsia
Authors: Tejera Eduardo , Pérez-Castillo Yunierkis , Chamorro Andrea , Cabrera-Andrade Alejandro , Sanchez Maria Eugenia
Published: February 2021

Preeclampsia is a hypertensive disorder that occurs during pregnancy. It is a complex disease with unknown pathogenesis and the leading cause of fetal and maternal mortality during pregnancy. Using all drugs currently under clinical trial for preeclampsia, we extracted all their possible targets from the DrugBank and ChEMBL databases and labeled them as “targets”. The proteins labeled as “off-targets” were extracted in the same way but while taking all antihypertensive drugs which are inhibitors of ACE and/or angiotensin receptor antagonist as query molecules. Classification models were obtained for each of the 55 total proteins (45 targets and 10 off-targets) using the TPOT pipeline optimization tool. The average accuracy of the models in predicting the external dataset for targets and off-targets was 0.830 and 0.850, respectively. The combinations of models maximizing their virtual screening performance were explored by combining the desirability function and genetic algorithms. The virtual screening performance metrics for the best model were: the Boltzmann-Enhanced Discrimination of ROC (BEDROC)α=160.9 = 0.258, the Enrichment Factor (EF)1% = 31.55 and the Area Under the Accumulation Curve (AUAC) = 0.831. The most relevant targets for preeclampsia were: AR, VDR, SLC6A2, NOS3 and CHRM4, while ABCG2, ERBB2, CES1 and REN led to the most relevant off-targets. A virtual screening of the DrugBank database identified estradiol, estriol, vitamins E and D, lynestrenol, mifrepristone, simvastatin, ambroxol, and some antibiotics and antiparasitics as drugs with potential application in the treatment of preeclampsia.
Injectable Capsaicin for the Management of Pain Due to Osteoarthritis
Authors: Campbell James N. , Stevens Randall , Hanson Peter , Connolly James , Meske Diana S. , Chung Man-Kyo , Lascelles Benedict Duncan X.
Published: February 2021

Capsaicin is a potent agonist of the TRPV1 channel, a transduction channel that is highly expressed in nociceptive fibers (pain fibers) throughout the peripheral nervous system. Given the importance of TRPV1 as one of several transduction channels in nociceptive fibers, much research has been focused on the potential therapeutic benefits of using TRPV1 antagonists for the management of pain. However, an antagonist has two limitations. First, an antagonist in principle generally only affects one receptor. Secondly, most antagonists must have an ongoing presence on the receptor to have an effect. Capsaicin overcomes both liabilities by disrupting peripheral terminals of nociceptive fibers that express TRPV1, and thereby affects all of the potential means of activating that pain fiber (not just TRPV1 function). This disruptive effect is dependent on the dose and can occur within minutes. Thus, unlike a typical receptor antagonist, continued bioavailability at the level of the receptor is not necessary. By disrupting the entire terminal of the TRPV1-expressing nociceptive fiber, capsaicin blocks all the activation mechanisms within that fiber, and not just TRPV1 function. Topical capsaicin, an FDA approved treatment for neuropathic pain, addresses pain from abnormal nociceptor activity in the superficial layers of the skin. Effects after a single administration are evident over a period of weeks to months, but in time are fully reversible. This review focuses on the rationale for using capsaicin by injection for painful conditions such as osteoarthritis (OA) and provides an update on studies completed to date.
Mealworm Oil (MWO) Enhances Wound Healing Potential through the Activation of Fibroblast and Endothelial Cells
Authors: Kim Joung-Hee , Kim Eun-Yeong , Chung Kyu Jin , Lee Jung-Hee , Choi Hee-Jung , Chung Tae-Wook , Kim Keuk-Jun
Published: February 2021

Mealworm and mealworm oil (MWO) have been reported to affect antioxidant, anti-coagulation, anti-adipogenic and anti-inflammatory activities. However, the function of MWO in wound healing is still unclear. In this study, we found that MWO induced the migration of fibroblast cells and mRNA expressions of wound healing factors such as alpha-smooth muscle actin (α-SMA), collagen-1 (COL-1) and vascular endothelial growth factor (VEGF) in fibroblast cells. The tube formation and migration of endothelial cells were promoted through the activation of VEGF/VEGF receptor-2 (VEGFR-2)-mediated downstream signals including AKT, extracellular signal-regulated kinase (ERK) and p38 by MWO-stimulated fibroblasts for angiogenesis. Moreover, we confirmed that MWO promoted skin wound repair by collagen synthesis, re-epithelialization and angiogenesis in an in vivo excisional wound model. These results demonstrate that MWO might have potential as a therapeutic agent for the treatment of skin wounds.
Synthesis and Anti-Hepatocarcinoma Effect of Amino Acid Derivatives of Pyxinol and Ocotillol
Authors: Zhang Ying , Yu Hui , Fu Shuzheng , Tan Luying , Liu Junli , Zhou Baisong , Li Le , Liu Yunhe , Wang Caixia , Li Pingya , Liu Jinping
Published: February 2021

Aiming at seeking an effective anti-hepatocarcinoma drug with low toxicity, a total of 24 amino acid derivatives (20 new along with 4 known derivatives) of two active ocotillol-type sapogenins (pyxinol and ocotillol) were synthesized. Both in vitro and in vivo anti-hepatocarcinoma effects of derivatives were evaluated. At first, the HepG2 human cancer cell was employed to evaluate the anti-cancer activity. Most of the derivatives showed obvious enhanced activity compared with pyxinol or ocotillol. Among them, compound 2e displayed the most excellent activity with an IC50 value of 11.26 ± 0.43 µM. Next, H22 hepatoma-bearing mice were used to further evaluate the anti-liver cancer activity of compound 2e. It was revealed that the growth of H22 transplanted tumor was significantly inhibited when treated with compound 2e or compound 2e combined with cyclophosphamide (CTX) (p < 0.05, p < 0.01), and the inhibition rates of tumor growth were 35.32% and 55.30%, respectively. More importantly, compound 2e caused limited damage to liver and kidney in contrast with CTX causing significant toxicity. Finally, the latent mechanism of compound 2e was explored by serum and liver metabolomics based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) technology. A total of 21 potential metabolites involved in 8 pathways were identified. These results suggest that compound 2e is a promising agent for anti-hepato-carcinoma, and that it also could be used in combination with CTX to increase efficiency and to reduce toxicity.
Transcriptome Changes Reveal the Molecular Mechanisms of Humic Acid-Induced Salt Stress Tolerance in Arabidopsis
Authors: Cha Joon-Yung , Kang Sang-Ho , Ji Myung Geun , Shin Gyeong-Im , Jeong Song Yi , Ahn Gyeongik , Kim Min Gab , Jeon Jong-Rok , Kim Woe-Yeon
Published: February 2021

Humic acid (HA) is a principal component of humic substances, which make up the complex organic matter that broadly exists in soil environments. HA promotes plant development as well as stress tolerance, however the precise molecular mechanism for these is little known. Here we conducted transcriptome analysis to elucidate the molecular mechanisms by which HA enhances salt stress tolerance. Gene Ontology Enrichment Analysis pointed to the involvement of diverse abiotic stress-related genes encoding HEAT-SHOCK PROTEINs and redox proteins, which were up-regulated by HA regardless of salt stress. Genes related to biotic stress and secondary metabolic process were mainly down-regulated by HA. In addition, HA up-regulated genes encoding transcription factors (TFs) involved in plant development as well as abiotic stress tolerance, and down-regulated TF genes involved in secondary metabolic processes. Our transcriptome information provided here provides molecular evidences and improves our understanding of how HA confers tolerance to salinity stress in plants.
Novel Biphenyl Amines Inhibit Oestrogen Receptor (ER)-α in ER-Positive Mammary Carcinoma Cells
Authors: Basappa Basappa , Chumadathil Pookunoth Baburajeev , Shinduvalli Kempasiddegowda Mamatha , Knchugarakoppal Subbegowda Rangappa , Lobie Peter E. , Pandey Vijay
Published: February 2021

Herein, the activity of adamantanyl-tethered-biphenyl amines (ATBAs) as oestrogen receptor alpha (ERα) modulating ligands is reported. Using an ERα competitor assay it was demonstrated that ATBA compound 3-(adamantan-1-yl)-4-methoxy-N-(4-(trifluoromethyl) phenyl) aniline (AMTA) exhibited an inhibitory concentration 50% (IC50) value of 62.84 nM and demonstrated better binding affinity compared to tamoxifen (IC50 = 79.48 nM). Treatment of ERα positive (ER+) mammary carcinoma (MC) cells (Michigan Cancer Foundation-7 (MCF7)) with AMTA significantly decreased cell viability at an IC50 value of 6.4 μM. AMTA treatment of MC cell-generated three-dimensional (3D) spheroids resulted in significantly decreased cell viability. AMTA demonstrated a superior inhibitory effect compared to tamoxifen-treated MC cell spheroids. Subsequently, by use of an oestrogen response element (ERE) luciferase reporter construct, it was demonstrated that AMTA treatment significantly deceased ERE transcriptional activity in MC cells. Concordantly, AMTA treatment of MC cells also significantly decreased protein levels of oestrogen-regulated CCND1 in a dose-dependent manner. In silico molecular docking analysis suggested that AMTA compounds interact with the ligand-binding domain of ERα compared to the co-crystal ligand, 5-(4-hydroxyphenoxy)-6-(3-hydroxyphenyl)-7- methylnaphthalen-2-ol. Therefore, an analogue of AMTA may provide a structural basis to develop a newer class of ERα partial agonists.
Ethanol Extract of Amomum tsao-ko Ameliorates Ovariectomy-Induced Trabecular Loss and Fat Accumulation
Authors: Shim Ki-Shuk , Hwang Youn-Hwan , Jang Seon-A , Kim Taesoo , Ha Hyunil
Published: February 2021

In Asia, Amomum tsao-ko has long been used as a spice or seasoning in food to stimulate digestion. In the present study, we evaluated the effects of ethanol extract of Amomum tsao-ko (EEAT) on menopausal osteoporosis and obesity. After the administration of EEAT in ovariectomy (OVX) mice models for five weeks, microcomputed tomography and a histological analysis were performed to assess, respectively, the trabecular structure and the fat accumulation in adipose, liver, and bone tissues. We also examined the effects of EEAT on a bone marrow macrophage model of osteoclastogenesis by in vitro stimulation from the receptor activator of nuclear factor-kappa Β ligand (RANKL) through real-time PCR and Western blot analysis. In addition, ultrahigh performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) with authentic standards was applied to characterize the phytochemical profiling of EEAT. We found that EEAT significantly decreased OVX-induced body weight gain and fat accumulation, significantly prevented OVX-induced deterioration of bone mineral density and microstructure of trabecular tissues, and significantly inhibited osteoclast differentiation by downregulating NF-κB/Fos/NFATc1 signaling in osteoclasts. Furthermore, UHPLC–MS/MS identified eight beneficial phytochemicals in EEAT. Collectively, these results suggest that EEAT might be an effective nutraceutical candidate to attenuate menopausal osteoporosis by inhibiting osteoclastogenesis and to prevent obesity by suppressing fat accumulation.
Recent Advances in Nanotechnology for the Treatment of Melanoma
Authors: Cassano Roberta , Cuconato Massimo , Calviello Gabriella , Serini Simona , Trombino Sonia
Published: February 2021

Melanoma is one of the most aggressive forms of skin cancer, with few possibilities for therapeutic approaches, due to its multi-drug resistance and, consequently, low survival rate for patients. Conventional therapies for treatment melanoma include radiotherapy, chemotherapy, targeted therapy, and immunotherapy, which have various side effects. For this reason, in recent years, pharmaceutical and biomedical research has focused on new sito-specific alternative therapeutic strategies. In this regard, nanotechnology offers numerous benefits which could improve the life expectancy of melanoma patients with very low adverse effects. This review aims to examine the latest advances in nanotechnology as an innovative strategy for treating melanoma. In particular, the use of different types of nanoparticles, such as vesicles, polymers, metal-based, carbon nanotubes, dendrimers, solid lipid, microneedles, and their combination with immunotherapies and vaccines will be discussed.
Prospects and Challenges of Microwave-Combined Technology for Biodiesel and Biolubricant Production through a Transesterification: A Review
Authors: Mohamad Aziz Nur Atiqah , Yunus Robiah , Kania Dina , Abd Hamid Hamidah
Published: February 2021

Biodiesels and biolubricants are synthetic esters produced mainly via a transesterification of other esters from bio-based resources, such as plant-based oils or animal fats. Microwave heating has been used to enhance transesterification reaction by converting an electrical energy into a radiation, becoming part of the internal energy acquired by reactant molecules. This method leads to major energy savings and reduces the reaction time by at least 60% compared to a conventional heating via conduction and convection. However, the application of microwave heating technology alone still suffers from non-homogeneous electromagnetic field distribution, thermally unstable rising temperatures, and insufficient depth of microwave penetration, which reduces the mass transfer efficiency. The strategy of integrating multiple technologies for biodiesel and biolubricant production has gained a great deal of interest in applied chemistry. This review presents an advanced transesterification process that combines microwave heating with other technologies, namely an acoustic cavitation, a vacuum, ionic solvent, and a supercritical/subcritical approach to solve the limitations of the stand-alone microwave-assisted transesterification. The combined technologies allow for the improvement in the overall product yield and energy efficiency. This review provides insights into the broader prospects of microwave heating in the production of bio-based products.