bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulations on Simple Models of Connexin Hemichannels Indicate That Ca2+ Blocking Is Not a Pure Electrostatic Effect
Authors: Villanelo Felipe , Carrasco Jorge , Jensen-Flores Joaquin , Garate Jose Antonio , Perez-Acle Tomas
Published: May 2021

Connexin hemichannels allow the unspecific but regulated interchange of molecules from ions to second messenger and ATP, between the eukariotic cell and its extracellular space. The transport of ions and water through hemichannels is important for physiological functions and also in the progression of several pathological conditions. Extracellular Ca2+ concentration is one of the regulators that drives the channel to a closed state. However the relation between their functional and structural states is far for being totally understood. In this work, we modelled connexin hemichannels using simple systems based on a fixed array of carbon atoms and assess the Ca2+ regulation using molecular dynamics simulations. The two proposed mechanism described so far for calcium action were studied combined, e.g., an electrostatic effect and a pore stretching. Our results show that the addition of positive charge density inside the channel cannot stop the flow of potassium, chloride nor water. Only a pore stretching at the center of the pore can explain the channel blocking.
Machine Learning-Based Models for the Estimation of the Energy Consumption in Metal Forming Processes
Authors: Mirandola Irene , Berti Guido A. , Caracciolo Roberto , Lee Seungro , Kim Naksoo , Quagliato Luca
Published: May 2021

This research provides an insight on the performances of machine learning (ML)-based algorithms for the estimation of the energy consumption in metal forming processes and is applied to the radial-axial ring rolling process. To define the mutual influence between ring geometry, process settings, and ring rolling mill geometries with the resulting energy consumption, measured in terms of the force integral over the processing time (FIOT), FEM simulations have been implemented in the commercial SW Simufact Forming 15. A total of 380 finite element simulations with rings ranging from 650 mm < DF < 2000 mm have been implemented and constitute the bulk of the training and validation datasets. Both finite element simulation settings (input), as well as the FI (output), have been utilized for the training of eight machine learning models, implemented with Python scripts. The results allow defining that the Gradient Boosting (GB) method is the most reliable for the FIOT prediction in forming processes, being its maximum and average errors equal to 9.03% and 3.18%, respectively. The trained ML models have been also applied to own and literature experimental cases, showing a maximum and average error equal to 8.00% and 5.70%, respectively, thus proving once again its reliability.
A Comprehensive Study of Dynamic Recrystallization Behavior of Mg Alloy with 3 wt.% Bi Addition
Authors: Yu Hui , Liu Hao , Jiang Binan , Yu Wei , Kang Shaoming , Cheng Weili , Park Sunghyuk , Chen Dong , Yin Fuxing , Shin Kwangseon , Mu Jinyao , Cui Xiongwei , Li Jianghai
Published: May 2021

The effect of the addition of bismuth on the dynamic recrystallization (DRX) behavior of the matrix has been investigated by comparing coarse grain pure Mg with the addition of 3 wt.% Bi, using a uniaxial compression test in the temperature range of 473–623 K and the strain rate of 0.01–10 s−1. The constitutive equation, processing map, microstructure, and texture evolution of the Mg-3Bi alloy were systematically investigated. The results showed that the Bi addition could refine the grain size and accelerate the DRX process. The DRX kinetics is discussed in detail, accompanied by extensive characterization employing EBSD analysis. The DRX of the Mg-3Bi alloy depended on the deformation temperature rather than the strain rate. The {10–12} tensile twin appeared at 573 K/0.01–0.1 s−1, and discontinuous DRX (DDRX), continuous DRX (CDRX) as the main mechanism in the case of 573 K/0.01 s−1, while the dominant mechanism was DDRX when deformation temperature and strain rate increased. Particle-stimulated nucleation (PSN) was also involved in the DRX of this new RE-free Mg alloy.
MEROS Dust Quality of Different Plants and Its Potential Further Uses
Authors: Hledik Claudia , Goetz Martin , Ottner Franz , Fürhacker Maria
Published: May 2021

Sintering is a process of agglomeration of fine particles into porous sinters for blast furnaces. During the sintering process, high volumes of sinter plant gas containing high loads of dust, SO2 and NOX and toxic pollutants, such as heavy metals (e.g., Hg, Pb, Cr and Cd) and PCDD/F, are emitted. The objective of this study was to characterize dusts of different plants as the basis for suggestions of reutilization and treatment options. Dusts, eluates and residues were produced and DOC, T-N, ions and heavy metals were analyzed. The results show that dusts from different plants are very similar in terms of DOC, T-N, Mg, Ca and many heavy metals and only differ in criteria such as suspended solids and ions such as K, Na, Cl and SO4. Based on the high levels of alkalis and low levels of iron, direct recycling into the sinter or furnace process is not recommended. The dissolution of the soluble substances in water reduces the MEROS dust by 90% of the weight and extracts the alkalis. The remaining wastewater needs to be treated to reduce DOC, T-N and some heavy metals. The solid residues can be recycled into the sinter to reduce potential PCDD/F, which are attached to the activated carbon.
Effect of Gas Bubbling Filtration Treatment Conditions on Melt Quality of AlSiMgCu Alloy
Authors: Jang Ho-Sung , Kang Ho-Jung , Lee Gyu-Heun , Yoon Pil-Hwan , Park Jin-Young , Choi Yoon-Suk , Shin Sunmi
Published: May 2021

In this study, the optimal conditions of gas bubbling filtration (GBF) treatment for securing highly-clean molten Al-Si-Mg-Cu alloy were identified. The effects of GBF treatment time and stabilization time on the degree of molten metal cleanliness were examined by measuring melt quality parameters such as density index, bifilm index, porosity, and the amount of dissolved hydrogen [H]. A high melt quality was achieved when GBF treatment was performed on 10 kg melt for more than 10 min (i.e., 1 L gas/kg melt). However, as the stabilization holding time after GBF treatment increased to 10, 20, and 30 min, the melt quality degraded. GBF treatment for 30 min had a similar effect to treatment for 10 min, and the degree of deterioration of melt quality during the stabilization time was also similar. Considering the economics, 10 min GBF treatment and short holding time are required. Observations of the shape and volume of the largest pore suggested the cause of defect formation and confirmed that the volume of the largest pore can be used as an index of the melt quality.
The Improvement of Bonding Strength of W/Cu Joints via Nano-Treatment of the W Surface
Authors: Li Fei , Chen Yuanyuan , Chen Xin , Li Cai , Huang Yuan
Published: May 2021

W/Cu joining is key for the fabrication of plasma-facing compounds of fusion reactors. In this work, W and Cu are joined through three steps: (1) hydrothermal treatment and reduction annealing (i.e., nano-treatment), (2) Cu plating and annealing in a pure H2 atmosphere, and (3) W/Cu bonding at 980 °C for 3 h. After nano-treatment, nanosheets structure can be found on the W substrate surface. The tensile strength of the W/Cu joint prepared via nano-treatment reaches as high as approximately 93 MPa, which increases by about 60% compared with the one without nano-treatment. The microhardness curves exhibited continuous variations along the W/Cu interface. The TEM images show that the W/Cu interface is compact without any cracks or voids. This work may also be applied for enhancing bonding strength in other immiscible materials.
Radiation Effects in Amorphous Metallic Alloys as Revealed by Mössbauer Spectrometry: Part I. Neutron Irradiation
Authors: Miglierini Marcel B.
Published: May 2021

Iron-based amorphous metallic alloys (AMAs) of several compositions were exposed to neutron irradiation with fluences of up to 1019 n/cm2. These materials exhibit excellent magnetic properties which predetermine them for use in electronic devices operated also in radiation-exposed environments. Response of the studied AMAs to neutron irradiation is followed by Mössbauer spectrometry which probes the local microstructure. Neutron irradiation leads to rearrangement of constituent atoms, their clustering, and formation of stress centers. The observed modifications of topological short-range order result in changes of spectral parameters including average hyperfine magnetic field, ⟨B⟩, standard deviation of the distribution of hyperfine fields, and position of the net magnetic moment. After irradiation, especially differences in ⟨B⟩-values develop in two opposite directions. This apparent controversy can be explained by formation of specific atomic pairs with different exchange interactions, which depend on the composition of the samples. Part II of this paper will be devoted to radiation effects caused in Fe-based AMAs by ion irradiation.
Solidification Pattern of Si-Alloyed, Inoculated Ductile Cast Irons, Evaluated by Thermal Analysis
Authors: Stan Iuliana , Anca Denisa , Stan Stelian , Riposan Iulian
Published: May 2021

The solidification cooling curve itself as well as its first derivative, and related temperatures, reported to the calculated equilibrium temperatures in stable and metastable solidification systems, are used to predict the solidification characteristics of the cast iron. Silicon, as the most representative cast iron element, and inoculation, as graphitizing metallurgical treatment, have a major influence on the transition from the liquid to the solid state. Six experimental programs are performed, with Si content typically for non-alloyed (<3.0% Si), low (3.0–3.5% Si) and medium alloyed (4.5–5.5% Si) ductile cast irons, as Si-content increasing, and inoculation simultaneous effects. Silicon is an important influencing factor, but the base and minor elements also affect the equilibrium eutectic temperatures, much more in the Fe-C-Si-Xi stable system (15–20 °C) than in the metastable system (5–10 °C), comparing with their calculation based only on a Si effect (Fe-C-Si system). The highest positive effect of inoculation is visible in non-Si alloyed cast irons (2.5% Si): 9–15 °C for the eutectic reaction and 3 to 4 times increased at the end of solidification (37–47 °C). Increased Si content decreases inoculation power to 7–9 °C for low alloying grade (up to 3.5% Si), with the lowest contribution at more than 4.5% Si (0.3–2.0 °C). 2.5–3.5% Si ductile cast irons are more sensitive to high solidification undercooling, especially at the end of solidification (but with a higher efficiency of inoculation), compared to 4.5–5.5% Si ductile cast irons, at a lower undercooling level, and at lower inoculation contribution, as well.
Iron-Bound Lipocalin-2 Protects Renal Cell Carcinoma from Ferroptosis
Authors: Meier Julia K. , Schnetz Matthias , Beck Susanne , Schmid Tobias , Dominguez Monica , Kalinovic Sanela , Daiber Andreas , Brüne Bernhard , Jung Michaela
Published: May 2021

While the importance of the iron-load of lipocalin-2 (Lcn-2) in promoting tumor progression is widely appreciated, underlying molecular mechanisms largely remain elusive. Considering its role as an iron-transporter, we aimed at clarifying iron-loaded, holo-Lcn-2 (hLcn-2)-dependent signaling pathways in affecting renal cancer cell viability. Applying RNA sequencing analysis in renal CAKI1 tumor cells to explore highly upregulated molecular signatures in response to hLcn-2, we identified a cluster of genes (SLC7A11, GCLM, GLS), which are implicated in regulating ferroptosis. Indeed, hLcn-2-stimulated cells are protected from erastin-induced ferroptosis. We also noticed a rapid increase in reactive oxygen species (ROS) with subsequent activation of the antioxidant Nrf2 pathway. However, knocking down Nrf2 by siRNA was not sufficient to induce erastin-dependent ferroptotic cell death in hLcn-2-stimulated tumor cells. In contrast, preventing oxidative stress through N-acetyl-l-cysteine (NAC) supplementation was still able to induce erastin-dependent ferroptotic cell death in hLcn-2-stimulated tumor cells. Besides an oxidative stress response, we noticed activation of the integrated stress response (ISR), shown by enhanced phosphorylation of eIF-2α and induction of ATF4 after hLcn-2 addition. ATF4 knockdown as well as inhibition of the ISR sensitized hLcn-2-treated renal tumor cells to ferroptosis, thus linking the ISR to pro-tumor characteristics of hLcn-2. Our study provides mechanistic details to better understand tumor pro-survival pathways initiated by iron-loaded Lcn-2.
Room Temperature Direct Electron Beam Lithography in a Condensed Copper Carboxylate
Authors: Berger Luisa , Jurczyk Jakub , Madajska Katarzyna , Szymańska Iwona B. , Hoffmann Patrik , Utke Ivo
Published: May 2021

High-resolution metallic nanostructures can be fabricated with multistep processes, such as electron beam lithography or ice lithography. The gas-assisted direct-write technique known as focused electron beam induced deposition (FEBID) is more versatile than the other candidates. However, it suffers from low throughput. This work presents the combined approach of FEBID and the above-mentioned lithography techniques: direct electron beam lithography (D-EBL). A low-volatility copper precursor is locally condensed onto a room temperature substrate and acts as a positive tone resist. A focused electron beam then directly irradiates the desired patterns, leading to local molecule dissociation. By rinsing or sublimation, the non-irradiated precursor is removed, leaving copper-containing structures. Deposits were formed with drastically enhanced growth rates than FEBID, and their composition was found to be comparable to gas-assisted FEBID structures. The influence of electron scattering within the substrate as well as implementing a post-purification protocol were studied. The latter led to the agglomeration of high-purity copper crystals. We present this as a new approach to electron beam-induced fabrication of metallic nanostructures without the need for cryogenic or hot substrates. D-EBL promises fast and easy fabrication results.
A Microtester for Measuring the Reliability of Microdevices in Controlled Environmental Conditions
Authors: Li Yunjia , Dou Weitao , Zhou Chenyuan , Wang Xinyi , Yang Aijun , Zhang Yong , Qiao Dayong
Published: May 2021

A miniaturized reliability test system for microdevices with controlled environmental parameters is presented. The system is capable of measuring key electrical parameters of the microdevices while controlling the environmental conditions around the microdevices. The test system is compact and thus can be integrated with standard test equipment for microdevices. By using a feed-forward decoupling algorithm, the presented test system is capable of generating a temperature range of 0–120 °C and a humidity range of 20–90% RH (0–55 °C), within a small footprint and weight. The accuracy for temperature and humidity control is ±0.1 °C and ±1% RH (30 °C), respectively. The functionality of the proposed test system is verified by integrating it with a piezo shaker to test the environmental reliability of an electromagnetic vibration energy harvester. The proposed system can be used as a proof-of-technology platform for characterizing the performance of microdevices with controlled environmental parameters.
Carbon Monoxide Induced Metabolic Shift in the Carboxydotrophic Parageobacillus thermoglucosidasius DSM 6285
Authors: Aliyu Habibu , Kastner Ronnie , Maayer Pieter de , Neumann Anke
Published: May 2021

Parageobacillus thermoglucosidasius is known to catalyse the biological water gas shift (WGS) reaction, a pathway that serves as a source of alternative energy and carbon to a wide variety of bacteria. Despite increasing interest in this bacterium due to its ability to produce biological hydrogen through carbon monoxide (CO) oxidation, there are no data on the effect of toxic CO gas on its physiology. Due to its general requirement of O2, the organism is often grown aerobically to generate biomass. Here, we show that carbon monoxide (CO) induces metabolic changes linked to distortion of redox balance, evidenced by increased accumulation of organic acids such as acetate and lactate. This suggests that P. thermoglucosidasius survives by expressing several alternative pathways, including conversion of pyruvate to lactate, which balances reducing equivalents (oxidation of NADH to NAD+), and acetyl-CoA to acetate, which directly generates energy, while CO is binding terminal oxidases. The data also revealed clearly that P. thermoglucosidasius gained energy and grew during the WGS reaction. Combined, the data provide critical information essential for further development of the biotechnological potential of P. thermoglucosidasius.
Global Genomic Analysis of SARS-CoV-2 RNA Dependent RNA Polymerase Evolution and Antiviral Drug Resistance
Authors: Mari Alfredo , Roloff Tim , Stange Madlen , Søgaard Kirstine K. , Asllanaj Erblin , Tauriello Gerardo , Alexander Leila Tamara , Schweitzer Michael , Leuzinger Karoline , Gensch Alexander , Martinez Aurélien E. , Bielicki Julia , Pargger Hans , Siegemund Martin , Nickel Christian H. , Bingisser Roland , Osthoff Michael , Bassetti Stefano , Sendi Parham , Battegay Manuel , Marzolini Catia , Seth-Smith Helena M. B. , Schwede Torsten , Hirsch Hans H. , Egli Adrian
Published: May 2021

A variety of antiviral treatments for COVID-19 have been investigated, involving many repurposed drugs. Currently, the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8) has been targeted by numerous inhibitors, e.g., remdesivir, the only provisionally approved treatment to-date, although the clinical impact of these interventions remains inconclusive. However, the potential emergence of antiviral resistance poses a threat to the efficacy of any successful therapies on a wide scale. Here, we propose a framework to monitor the emergence of antiviral resistance, and as a proof of concept, we address the interaction between RdRp and remdesivir. We show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare in circulating lineages, and that those mutations, where present, do not destabilise RdRp. In more than 56,000 viral genomes from 105 countries from the first pandemic wave, we found negative selective pressure affecting nsp12 (Tajima’s D = −2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Potential escape mutations included known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations involved globally, in silico structural models found that they were unlikely to be associated with loss of stability in RdRp. No potential escape mutation was found in a local cohort of remdesivir treated patients. Collectively, these findings indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. We anticipate our framework to be the starting point of a larger effort for a global monitoring of drug resistance throughout the COVID-19 pandemic.
Comparison of Quantification Methods to Estimate Farm-Level Usage of Antimicrobials Other than in Medicated Feed in Dairy Farms from Québec, Canada
Authors: Lardé Hélène , Francoz David , Roy Jean-Philippe , Massé Jonathan , Archambault Marie , Paradis Marie-Ève , Dufour Simon
Published: May 2021

The objective of the study was to compare three quantification methods to a “garbage can audit” (reference method, REF) for monitoring antimicrobial usage (AMU) from products other than medicated feed over one year in 101 Québec dairy farms. Data were collected from veterinary invoices (VET method), from the “Amélioration de la Santé Animale au Québec” provincial program (GOV method), and from farm treatment records (FARM method). The AMU rate was reported in a number of Canadian Defined Course Doses for cattle (DCDbovCA) per 100 cow-years. Electronic veterinary sales data were obtained for all farms for VET and GOV methods. For the FARM method, a herd management software was used by 68% of producers whereas farm treatment records were handwritten for the others; records could not be retrieved in 4% of farms. Overall, agreement was almost perfect between REF and VET methods (concordance correlation coefficient (CCC) = 0.83), but moderate between REF and GOV (CCC = 0.44), and between REF and FARM (CCC = 0.51). Only a fair or slight agreement was obtained between any alternative method of quantification and REF for oral and intrauterine routes. The billing software used by most of Québec’s dairy veterinary practitioners seems promising in terms of surveillance and benchmarking of AMU in the province.
~25 Ma Ruby Mineralization in the Mogok Stone Tract, Myanmar: New Evidence from SIMS U–Pb Dating of Coexisting Titanite
Authors: Zhang Di , Guo Shun , Chen Yi , Li Qiuli , Ling Xiaoxiao , Liu Chuanzhou , Sein Kyaing
Published: May 2021

Ruby (red corundum) is one of the most prominent colored gemstones in the world. The highest-quality ruby (“pigeon blood” ruby) comes from marbles of the Mogok Stone Tract in central Myanmar. Although Mogok ruby has been exploited since the 6th century AD, the formation time of this gemstone is ambiguous and controversial. In this paper, we describe a mineralogical, geochemical, and geochronological study of ruby and titanite in ruby-bearing marbles obtained from an outcrop in the Mogok Stone Tract, central Myanmar. Petrographic observations have shown that titanite generally occurs in the marble matrix or occurs as inclusions in ruby. These two types of titanite exhibit identical chemical compositions. In situ secondary ion mass spectrometer (SIMS) U–Pb dating of the separated titanite from two representative samples of ruby-bearing marbles yielded lower intercept ages of 25.15 ± 0.24 Ma (MSWD = 0.26) and 25.06 ± 0.22 Ma (MSWD = 0.15), respectively. Because the closure temperature of the U–Pb system in titanite is close to the temperature of ruby growth, the obtained U–Pb ages (~25 Ma) are suggested to represent the timing of the studied ruby formation in Mogok. The acquired ages are in agreement with the timing of post-collisional extension in the Himalaya related to the migration of the eastern Himalayan syntaxis. Combining our dating results with previous geochronological data from the Mogok Stone Tract, we suggest that the formation of the studied ruby is most likely related to the high-temperature metamorphic event in the marbles during the India–Asia collision. Our study not only confirms that texturally constrained titanite could be a precise geochronometer to date the mineralization of different types of ruby, but also provides important geochronological information linking gemstone formation to the India–Asia collision.
Ultramafic Alkaline Rocks of Kepino Cluster, Arkhangelsk, Russia: Different Evolution of Kimberlite Melts in Sills and Pipes
Authors: Kargin Alexey Vladimirovich , Nosova Anna Andreevna , Sazonova Ludmila Vyacheslavovna , Tretyachenko Vladimir Vasilievich , Larionova Yulia Olegovna , Kovalchuk Elena Vladimirovna
Published: May 2021

To provide new insights into the evolution of kimberlitic magmas, we have undertaken a detailed petrographic and mineralogical investigation of highly evolved carbonate–phlogopite-bearing kimberlites of the Kepino cluster, Arkhangelsk kimberlite province, Russia. The Kepino kimberlites are represented by volcanoclastic breccias and massive macrocrystic units within pipes as well as coherent porphyritic kimberlites within sills. The volcanoclastic units from pipes are similar in petrography and mineral composition to archetypal (Group 1) kimberlite, whereas the sills represent evolved kimberlites that exhibit a wide variation in amounts of carbonate and phlogopite. The late-stage evolution of kimberlitic melts involves increasing oxygen fugacity and fluid-phase evolution (forming carbonate segregations by exsolution, etc.). These processes are accompanied by the transformation of primary Al- and Ti-bearing phlogopite toward tetraferriphlogopite and the transition of spinel compositions from magmatic chromite to magnesian ulvöspinel and titanomagnetite. Similar primary kimberlitic melts emplaced as sills and pipes may be transitional to carbonatite melts in the shallow crust. The kimberlitic pipes are characterised by low carbonate amounts that may reflect the fluid degassing process during an explosive emplacement of the pipes. The Kepino kimberlite age, determined as 397.3 ± 1.2 Ma, indicates two episodes of ultramafic alkaline magmatism in the Arkhangelsk province, the first producing non-economic evolved kimberlites of the Kepino cluster and the second producing economic-grade diamondiferous kimberlites.
Mechanical Performance of Concrete Exposed to Sewage—The Influence of Time and pH
Authors: Czajkowska Justyna , Malarski Maciej , Witkowska-Dobrev Joanna , Dohojda Marek , Nowak Piotr
Published: May 2021

Contact of concrete with aggressive factors, technological structures, reduces their durability through microstructural changes. This work presents the results of research on determining the influence of post grit chamber sewage and sewage from the active sludge chamber in three different environments, i.e., acidic, neutral, and alkaline, on the structure and compressive strength of concrete. Compressive strength tests were carried out after 11.5 months of concrete cubes being submerged in the solutions and compared. To complete the studies, the photos of the microstructure were done. This made it possible to accentuate the relationship between the microstructure and performance characteristics of concrete. The time of storing the cubes in both acidic environments (sewage from post grit chamber and active sludge chamber) has a negative influence on their compressive strength. The compressive strength of cubes decreases along with the time. Compressive strength of cubes increases with increasing pH of the environment.
Lead Recovery from Solid Residues of Copper Industry Using Triethylenetetramine Solution
Authors: Ciszewski Mateusz , Chmielarz Andrzej , Szołomicki Zbigniew , Drzazga Michał , Leszczyńska-Sejda Katarzyna
Published: May 2021

Industrial processing of mineral ores and concentrates generates large amounts of solid residues, which can be landfilled or further processed to recover selected elements depending on its economical profitability. Pressure leaching is a technology enabling high recovery of base metals like copper and zinc, transferring others like lead and iron to the solid residue. High temperature and pressure of such leaching leads to formation of sparingly soluble lead jarosite (plumbojarosite). The load of lead landfilled as solid residues resulting from such operation is so big that its recovery is perspective and crucial for waste-limiting technologies. This paper is devoted to lead extraction from pressure leaching residues using triethylenetetramine solution and then its precipitation as a commercial lead carbonate. The highest obtained recovery of lead was 91.3%. Additionally, presented technology allows to manage and recycle amine solution and reuse solid products. Produced pure lead carbonate can be directly added to smelting, not increasing temperature within the furnace.
Zebrafish and Flavonoids: Adjuvants against Obesity
Authors: Montalbano Giuseppe , Mhalhel Kamel , Briglia Marilena , Levanti Maria , Abbate Francesco , Guerrera Maria Cristina , D’Alessandro Enrico , Laurà Rosaria , Germanà Antonino
Published: May 2021

Obesity is a pathological condition, defined as an excessive accumulation of fat, primarily caused by an energy imbalance. The storage of excess energy in the form of triglycerides within the adipocyte leads to lipotoxicity and promotes the phenotypic switch in the M1/M2 macrophage. These changes induce the development of a chronic state of low-grade inflammation, subsequently generating obesity-related complications, commonly known as metabolic syndromes. Over the past decade, obesity has been studied in many animal models. However, due to its competitive aspects and unique characteristics, the use of zebrafish has begun to gain traction in experimental obesity research. To counteract obesity and its related comorbidities, several natural substances have been studied. One of those natural substances reported to have substantial biological effects on obesity are flavonoids. This review summarizes the results of studies that examined the effects of flavonoids on obesity and related diseases and the emergence of zebrafish as a model of diet-induced obesity.
In Vitro Antiviral Activity of α-Mangostin against Dengue Virus Serotype-2 (DENV-2)
Authors: Panda Kingshuk , Alagarasu Kalichamy , Patil Poonam , Agrawal Megha , More Ashwini , Kumar Naveen V. , Mainkar Prathama S. , Parashar Deepti , Cherian Sarah
Published: May 2021

Dengue virus (DENV), a member of the family Flaviviridae, is a threat for global health as it infects more than 100 million people yearly. Approved antiviral therapies or vaccines for the treatment or prevention of DENV infections are not available. In the present study, natural compounds were screened for their antiviral activity against DENV by in vitro cell line-based assay. α-Mangostin, a xanthanoid, was observed to exert antiviral activity against DENV-2 under pre-, co- and post-treatment testing conditions. The antiviral activity was determined by foci forming unit (FFU) assay, quantitative RT-PCR and cell-based immunofluorescence assay (IFA). A complete inhibition of DENV-2 was observed at 8 µM under the co-treatment condition. The possible inhibitory mechanism of α-Mangostin was also determined by docking studies. The molecular docking experiments indicate that α-Mangostin can interact with multiple DENV protein targets such as the NS5 methyltransferase, NS2B-NS3 protease and the glycoprotein E. The in vitro and in silico findings suggest that α-Mangostin possesses the ability to suppress DENV-2 production at different stages of its replication cycle and might act as a prophylactic/therapeutic agent against DENV-2.
Synergistic Interaction between 5-FU and an Analog of Sulforaphane—2-Oxohexyl Isothiocyanate—In an In Vitro Colon Cancer Model
Authors: Milczarek Małgorzata , Pogorzelska Anna , Wiktorska Katarzyna
Published: May 2021

Combination therapy is based on the beneficial effects of pharmacodynamic interaction (synergistic or additive) between combined drugs or substances. A considerable group of candidates for combined treatments are natural compounds (e.g., isothiocyanates) and their analogs, which are tested in combination with anticancer drugs. We tested the anticancer effect of the combined treatment of isothiocyanate 2-oxohexyl isothiocyanate and 5-fluorouracil in colon and prostate cancer cell lines. The type of interaction was described using the Chou-Talalay method. The cytostatic and cytotoxic activities of the most promising combined treatments were investigated. In conclusion, we showed that combined treatment with 5-fluorouracil and 2-oxohexyl isothiocyanate acted synergistically in colon cancer. This activity is dependent on the cytostatic properties of the tested compounds and leads to the intensification of their individual cytotoxic activity. The apoptotic process is considered to be the main mechanism of cytotoxicity in this combined treatment.
Preparation of Sorbents Containing Straetlingite Phase from Zeolitic By-Product and Their Performance for Ammonium Ion Removal
Authors: Mikelionienė Agnė , Vaičiukynienė Danutė , Kantautas Aras , Radzevičius Algirdas , Zarębska Katarzyna
Published: May 2021

In this study, straetlingite-based sorbents were used for NH4+ ion removal from a synthetic aqueous solution and from the wastewater of an open recirculation African catfish farming system. This study was performed using column experiments with four different filtration rates (2, 5, 10, and 15 mL/min). It was determined that breakthrough points and sorption capacity could be affected by several parameters such as flow rate and mineral composition of sorption materials. In the synthetic aqueous solution, NH4+ removal reached the highest sorption capacity, i.e., 0.341 mg/g with the S30 sorbent at a filtration rate of 10 mL/min and an initial concentration of 10 mg/L of NH4+ ions. It is important to emphasize that, in this case, the Ce/C0 ratio of 0.9 was not reached after 420 min of sorption. It was also determined that the NH4+ sorption capacity was influenced by phosphorus. In the wastewater, the NH4+ sorption capacity was almost seven times lower than that in the synthetic aqueous solution. However, it should be highlighted that the P sorption capacity reached 0.512 mg/g. According to these results, it can be concluded that straetlingite-based sorbents can be used for NH4+ ion removal from a synthetic aqueous solution, as well as for both NH4+ and P removal from industrial wastewater. In the wastewater, a significantly higher sorption capacity of the investigated sorbents was detected for P than for NH4+.
Structure–Activity Relationship Assessment of Sophorolipid Ester Derivatives against Model Bacteria Strains
Authors: Totsingan Filbert , Liu Fei , Gross Richard A.
Published: May 2021

Sophorolipids (SLs) are glycolipids that consist of a hydrophilic sophorose head group covalently linked to a hydrophobic fatty acid tail. They are produced by fermentation of non-pathogenic yeasts such as Candida Bombicola. The fermentation products predominantly consist of the diacetylated lactonic form that coexists with the open-chain acidic form. A systematic series of modified SLs were prepared by ring opening of natural lactonic SL with n-alkanols of varying chain length under alkaline conditions and lipase-selective acetylation of sophorose primary hydroxyl groups. The antimicrobial activity of modified SLs against Gram-positive human pathogens was a function of the n-alkanol length, as well as the degree of sophorose acetylation at the primary hydroxyl sites. Modified SLs were identified with promising antimicrobial activities against Gram-positive human pathogens with moderate selectivity (therapeutic index, TI = EC50/MICB. cereus = 6–33). SL-butyl ester exhibited the best antimicrobial activity (MIC = 12 μM) and selectivity (TI = 33) among all SLs tested. Kinetic studies revealed that SL-ester derivatives kill B. cereus in a time-dependent manner resulting in greater than a 3-log reduction in cell number within 1 h at 2×MIC. In contrast, lactonic SL required 3 h to achieve the same efficiency.
Antibacterial, Antifungal and Antibiofilm Activities of Silver Nanoparticles Supported by Crude Bioactive Metabolites of Bionanofactories Isolated from Lake Mariout
Authors: Eltarahony Marwa , Ibrahim Amany , El-shall Hadeel , Ibrahim Eman , Althobaiti Fayez , Fayad Eman
Published: May 2021

Lake Mariout is one of the polluted coastal marine ecosystems in Egypt which is considered to be a reservoir of serious effluents from different anthropogenic activities. Such selective pressure enforces indigenous microbial populations to acquire new advantageous themes. Thus, in this study, two Streptomyces strains were screened, from Lake Mariout’s sediment for bioreduction of 5 mM AgNO3. Both strains were identified molecularly; their biochemical and physiological characterization revealed their ability to secrete bioactive metabolites with antagonistic activity. The cultural and incubation conditions influencing AgNPs productivity were evaluated. Subsequently, the physicochemical properties of the biofabricated AgNPs were pursued. UV-Vis spectroscopy detected surface plasmon resonance at range 458–422 nm. XRD indicated crystalline, pure, face-centered cubic AgNPs; EDX demonstrated strong silver signal at 3.5 keV. Besides, FT-IR and TGA analysis unveiled self-stabilization and functionalization of AgNPs by bioorganic molecules. However, electron microscopy micrographs depicted numerous uniform spherical AgNPs (1.17–13.3 nm). Potent bactericidal and fungicide activity were recorded by zone of inhibition assay at 50 μg/mL. Further, the antibiofilm activity was exerted in a dose-dependent manner. Moreover, the conjugation of AgNPs with the crude bioactive metabolites of both bionanofactories ameliorated the antimicrobial potency, reflecting a synergistic efficiency versus examined pathogens (free-living and biofilm).
Geranyl Functionalized Materials for Site-Specific Co-Immobilization of Proteins
Authors: Brabcova Jana , Andreu Alicia , Aguilera David , Cabrera Zaida , de las Rivas Blanca , Muñoz Rosario , Palomo Jose M.
Published: May 2021

Different materials containing carboxylic groups have been functionalized with geranyl-amine molecules by using an EDC/NHS strategy. Chemical modification of the support was confirmed by XRD, UV-spectrophotometer, and FT-IR. This geranyl-functionalized material was successfully applied for four different strategies of site-selective immobilization of proteins at room temperature and aqueous media. A reversible hydrophobic immobilization of proteins (lipases, phosphoglucosidases, or tyrosinase) was performed in neutral pH in yields from 40 to >99%. An increase of the activity in the case of lipases was observed from a range of 2 to 4 times with respect to the initial activity in solution. When chemically or genetically functionalized cysteine enzymes were used, the covalent immobilization, via a selective thiol-alkene reaction, was observed in the presence of geranyl support at pH 8 in lipases in the presence of detergent (to avoid the previous hydrophobic interactions). Covalent attachment was confirmed with no release of protein after immobilization by incubation with hydrophobic molecules. In the case of a selenium-containing enzyme produced by the selenomethionine pathway, the selective immobilization was successfully yielded at acidic pH (pH 5) (89%) much better than at pH 8. In addition, when an azido-enzyme was produced by the azide–homoalanine pathway, the selective immobilization was successful at pH 6 and in the presence of CuI for the click chemistry reaction.
Design, Synthesis, and Evaluation of Dihydropyranopyrazole Derivatives as Novel PDE2 Inhibitors for the Treatment of Alzheimer’s Disease
Authors: Zhou Yan , Li Jinjian , Yuan Han , Su Rui , Huang Yue , Huang Yiyou , Li Zhe , Wu Yinuo , Luo Haibin , Zhang Chen , Huang Ling
Published: May 2021

Phosphodiesterase 2 (PDE2) has been regarded as a novel target for the treatment of Alzheimer’s disease (AD). In this study, we obtained (R)-LZ77 as a hit compound with moderate PDE2 inhibitory activity (IC50 = 261.3 nM) using a high-throughput virtual screening method based on molecular dynamics. Then, we designed and synthesized 28 dihydropyranopyrazole derivatives as PDE2 inhibitors. Among them, compound (+)-11h was the most potent PDE2 inhibitor, with an IC50 value of 41.5 nM. The molecular docking of PDE2-(+)-11h reveals that the 4-(trifluoromethyl)benzyl)oxyl side chain of the compound enters the H-pocket and forms strong hydrophobic interactions with L770/L809/F862, which improves inhibitory activity. The above results may provide insight for further structural optimization of highly potent PDE2 inhibitors and may lay the foundation for their use in the treatment of AD.
Antiplatelet Activity of Coumarins: In Vitro Assays on COX-1
Authors: Zaragozá Cristina , Zaragozá Francisco , Gayo-Abeleira Irene , Villaescusa Lucinda
Published: May 2021

Atherosclerotic cardiovascular disease is the leading cause of death in developed countries. Therefore, there is an increasing interest in developing new potent and safe antiplatelet agents. Coumarins are a family of polyphenolic compounds with several pharmacological activities, including platelet aggregation inhibition. However, their antiplatelet mechanism of action needs to be further elucidated. The aim of this study is to provide insight into the biochemical mechanisms involved in this activity, as well as to establish a structure–activity relationship for these compounds. With this purpose, the antiplatelet aggregation activities of coumarin, esculetin and esculin were determined in vitro in human whole blood and platelet-rich plasma, to set the potential interference with the arachidonic acid cascade. Here, the platelet COX activity was evaluated from 0.75 mM to 6.5 mM concentration by measuring the levels of metabolites derived from its activity (MDA and TXB2), together with colorimetric assays performed with the pure recombinant enzyme. Our results evidenced that the coumarin aglycones present the greatest antiplatelet activity at 5 mM and 6.5 mM on aggregometry experiments and inhibiting MDA levels.
Evaluation of Motor Coordination and Antidepressant Activities of Cinnamomum osmophloeum ct. Linalool Leaf Oil in Rodent Model
Authors: Chang Hui-Ting , Chang Mei-Ling , Chen Yen-Ting , Chang Shang-Tzen , Hsu Fu-Lan , Wu Chia-Chen , Ho Cheng-Kuen
Published: May 2021

Cinnamomum plants (Lauraceae) are a woody species native to South and Southeast Asia forests, and are widely used as food flavors and traditional medicines. This study aims to evaluate the chemical constituents of Cinnamomum osmophloeum ct. linalool leaf oil, and its antidepressant and motor coordination activities and the other behavioral evaluations in a rodent animal model. The major component of leaf oil is linalool, confirmed by GC-MS analysis. Leaf oil would not induce the extra body weight gain compared to the control mice at the examined doses after 6 weeks of oral administration. The present results provide the first evidence for motor coordination and antidepressant effects present in leaf oil. According to hypnotic, locomotor behavioral, and motor coordination evaluations, leaf oil would not cause side effects, including weight gain, drowsiness and a diminishment in the motor functions, at the examined doses. In summary, these results revealed C. osmophloeum ct. linalool leaf essential oil is of high potential as a therapeutic supplement for minor/medium depressive syndromes.
Influence of Gas Supply Changes on the Formation Process of Complex Mixed Gas Hydrates
Authors: Pan Mengdi , Schicks Judith M.
Published: May 2021

Natural gas hydrate occurrences contain predominantly methane; however, there are increasing reports of complex mixed gas hydrates and coexisting hydrate phases. Changes in the feed gas composition due to the preferred incorporation of certain components into the hydrate phase and an inadequate gas supply is often assumed to be the cause of coexisting hydrate phases. This could also be the case for the gas hydrate system in Qilian Mountain permafrost (QMP), which is mainly controlled by pores and fractures with complex gas compositions. This study is dedicated to the experimental investigations on the formation process of mixed gas hydrates based on the reservoir conditions in QMP. Hydrates were synthesized from water and a gas mixture under different gas supply conditions to study the effects on the hydrate formation process. In situ Raman spectroscopic measurements and microscopic observations were applied to record changes in both gas and hydrate phase over the whole formation process. The results demonstrated the effects of gas flow on the composition of the resulting hydrate phase, indicating a competitive enclathration of guest molecules into the hydrate lattice depending on their properties. Another observation was that despite significant changes in the gas composition, no coexisting hydrate phases were formed.
Effect of Saffron Extract on the Hepatotoxicity Induced by Copper Nanoparticles in Male Mice
Authors: Attia Azza A. , Ramdan Heba S. , Al-Eisa Rasha A. , Adle Fadle Bassant O. A. , El-Shenawy Nahla S.
Published: May 2021

Background: Nanotechnology application has widespread use in many products. Copper nanoparticles (CuNPs) are widely used in industrial applications. The present study was conducted to investigate the effect of the ethanolic saffron extract (ESE) as a natural antioxidant on the hepatotoxicity induced by CuNPs in male mice. Methods: The characterization of CuNPs was determined using ultraviolet–visible absorption spectroscopy, particle size analysis, zeta potential, Fourier-transform infrared spectroscopy, and electron microscope. The effect of saffron on the hepatotoxicity induced by CuNPs in mice was evaluated by evaluating the survival rate of the mice, oxidative stress, antioxidant capacity, DNA evaluation, as well as its effect on the histology and transmission electron microscope of the liver. Results: The results revealed that all parameters were affected in a dose-dependent manner by CuNPs. These effects have been improved when the treatment of CuNPs is combined with ethanolic saffron extract. Conclusions: We can conclude that saffron and its bioactive crocin portion can prevent CuNP-induced oxidative liver damage. This substance should be useful as a new pharmacological tool for oxidative stress prevention.
Aloe djiboutiensis: Antioxidant Activity, Molecular Networking-Based Approach and In Vivo Toxicity of This Endemic Species in Djibouti
Authors: Elmi Abdirahman , Mohamed Abdoul-Latif Fatouma , Spina Rosella , Dupire François , Philippot Stéphanie , Marie-France Champy , Jacobs Hugues , Laurain-Mattar Dominique
Published: May 2021

For the first time, the study of the antioxidant activity, the characterization of the phytoconstituants, and the evaluation of in vitro and in vivo toxicity of A. djiboutiensis leave and latex are performed. The antioxidant activity of both latex (ADL) and the methanolic extract of leaves (ADM) is determined using 1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) scavenging radical methods and ferric reducing/antioxidant power (FRAP) assay. The phytochemical study of latex is done using Liquid Chromatography-Mass Spectrometry (LC-MS/MS) and a molecular networking-based approach. The evaluation of in vivo toxicity is performed on mice by oral gavage with a suspension of ADL. Our results show that weak antioxidant activity of ADL and ADM in opposition to their high polyphenol, 83.01 mg and 46.4 mg expressed in gallic acid equivalent (GAE)/g of dry weight (DW), respectively, and flavonoid contents 13.12 mg and 4.25 mg expressed in quercetin equivalent (QE)/g dry weight (DW), respectively. Using the Global Natural Products Social Molecular Networking (GNPS) website, nine (9) anthraquinones derivatives, ten (10) chromones derivatives, two (2) flavonols/ chromones isomers are annotated in the molecular network. The treated mice do not display abnormalities in their general physical appearance and biochemistry parameters, compared to the controls. Only glucose and calcium levels are slightly higher in male treated mice compared to the vehicles.
Synthesis of the [11]Cyclacene Framework by Repetitive Diels–Alder Cycloadditions
Authors: Bauer John B. , Diab Fatima , Maichle-Mössmer Cäcilia , Schubert Hartmut , Bettinger Holger F.
Published: May 2021

The Diels–Alder cycloaddition between bisdienes and bisdienophile incorporating the 7-oxa-bicyclo[2.2.1]heptane unit are well known to show high diastereoselectivity that can be exploited for the synthesis of molecular belts. The related bisdiene 5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octene is a valuable building block for the synthesis of photoprecursors for acenes, but it has not been employed for the synthesis of molecular belts. The present work investigates by computational means the Diels–Alder reaction between these bisdiene building blocks with syn-1,4,5,8-tetrahydro-1,4:5,8-diepoxyanthracene, which shows that the diastereoselectivity of the Diels–Alder reaction of the etheno-bridged bisdiene is lower than that of the epoxy-bridged bisdiene. The reaction of the etheno-bridged bisdiene and syn-1,4,5,8-tetrahydro-1,4:5,8-diepoxyanthracene in 2:1 ratio yields two diastereomers that differ in the orientation of the oxa and etheno bridges based on NMR and X-ray crystallography. The all-syn diastereomer can be transformed into a molecular belt by inter- and intramolecular Diels–Alder reactions with a bifunctional building block. The molecular belt could function as a synthetic intermediate en route to a [11]cyclacene photoprecursor.