bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of a New SEN Design with an Inner Flow Divider
Authors: Gonzalez-Trejo Jesus , Gabbasov Ruslan , Miranda-Tello Jose Raul , Carvajal-Mariscal Ignacio , Cervantes-de-la-Torre Francisco , Sanchez-Silva Florencio , Real-Ramirez Cesar Augusto
Published: September 2021

To minimize the product imperfections due to slag entrapment and surface defects, the fluid flow pattern inside the mold must be symmetric, commonly named double-roll flow. Thus, the liquid steel must enter into the mold evenly distributed. The submerged entry nozzle (SEN) is crucial in product quality in vertical steel slab continuous casting machines because it distributes the molten steel from the tundish into the mold. This work evaluates the performance of a novel bifurcated nozzle design named “SEN with flow divider”. The symmetry at the outlet ports is obtained by imposing symmetry inside the SEN. The flow divider is a solid barrier attached at the SEN bottom inner wall, the height of which slightly surpasses the upper edges of the outlet ports. The performance analysis is done first using numerical simulations, where the Computational Fluid Dynamics (CFD) technique and the Smoothed Particle Hydrodynamics (SPH) approach are used. Then, experimental tests on a scaled model are also used to evaluate the SEN performance. Numerical and physical simulations showed that the flow divider considerably reduces the SEN outlet jets’ broadness and misalignment, producing compact, aligned, and symmetric jets. Therefore, the SEN design analyzed in this work is a promising alternative to improve process profitability.
Liver Impairment—The Potential Application of Volatile Organic Compounds in Hepatology
Authors: Stavropoulos Georgios , van Munster Kim , Ferrandino Giuseppe , Sauca Marius , Ponsioen Cyriel , van Schooten Frederik-Jan , Smolinska Agnieszka
Published: September 2021

Liver diseases are currently diagnosed through liver biopsy. Its invasiveness, costs, and relatively low diagnostic accuracy require new techniques to be sought. Analysis of volatile organic compounds (VOCs) in human bio-matrices has received a lot of attention. It is known that a musty odour characterises liver impairment, resulting in the elucidation of volatile chemicals in the breath and other body fluids such as urine and stool, which may serve as biomarkers of a disease. Aims: This study aims to review all the studies found in the literature regarding VOCs in liver diseases, and to summarise all the identified compounds that could be used as diagnostic or prognostic biomarkers. The literature search was conducted on ScienceDirect and PubMed, and each eligible publication was qualitatively assessed by two independent evaluators using the SANRA critical appraisal tool. Results: In the search, 58 publications were found, and 28 were kept for inclusion: 23 were about VOCs in the breath, one in the bile, three in urine, and one in faeces. Each publication was graded from zero to ten. A graphical summary of the metabolic pathways showcasing the known liver disease-related VOCs and suggestions on how VOC analysis on liver impairment could be applied in clinical practice are given.
Manipulation of Miniature and Microminiature Bodies on a Harmonically Oscillating Platform by Controlling Dry Friction
Authors: Kilikevičius Sigitas , Fedaravičius Algimantas , Daukantienė Virginija , Liutkauskienė Kristina , Paukštaitis Linas
Published: September 2021

Currently used nonprehensile manipulation systems that are based on vibrational techniques employ temporal (vibrational) asymmetry, spatial asymmetry, or force asymmetry to provide and control a directional motion of a body. This paper presents a novel method of nonprehensile manipulation of miniature and microminiature bodies on a harmonically oscillating platform by creating a frictional asymmetry through dynamic dry friction control. To theoretically verify the feasibility of the method and to determine the control parameters that define the motion characteristics, a mathematical model was developed, and modeling was carried out. Experimental setups for miniature and microminiature bodies were developed for nonprehensile manipulation by dry friction control, and manipulation experiments were carried out to experimentally verify the feasibility of the proposed method and theoretical findings. By revealing how characteristic control parameters influence the direction and velocity, the modeling results theoretically verified the feasibility of the proposed method. The experimental investigation verified that the proposed method is technically feasible and can be applied in practice, as well as confirmed the theoretical findings that the velocity and direction of the body can be controlled by changing the parameters of the function for dynamic dry friction control. The presented research enriches the classical theories of manipulation methods on vibrating plates and platforms, as well as the presented results, are relevant for industries dealing with feeding, assembling, or manipulation of miniature and microminiature bodies.
Design, Manufacture and Test of Piezoelectric Cantilever-Beam Energy Harvesters with Hollow Structures
Authors: Wang Baozhi , Zhang Chenggong , Lai Liyan , Dong Xuan , Li Yigui
Published: September 2021

This article presents a single-crystal piezoelectric energy harvester (PEH) with a trapezoidal hollow hole that can obtain high energy density at low frequency. Harvesters with a hollow structure were fabricated through a series of manufacturing processes such as thermocompression bonding, screen printing and laser cutting. Finite element analysis (FEA) and experimental results showed that using low modulus brass instead of stainless steel as the PEH substrate enhances the voltage output of the device, and the hollow design greatly increases the overall stress level and power density. In addition, the developed PEH with a trapezoidal hole obtained the best output performance; when the acceleration, resonance frequency and matched load resistance were 0.5 g, 56.3 Hz and 114 kΩ, respectively, the peak voltage was 17 V and the power density was 2.52 mW/cm3. Meanwhile, compared with the unhollowed device, the peak voltage and maximum power density of the proposed PEH were increased by 30.7% and 24.4%, respectively, and the resonance frequency was reduced by 7%. This study verified the feasibility of the optimized design through simulation and experimental comparison.
Distinct Roles of Tensile and Compressive Stresses in Graphitizing and Properties of Carbon Nanofibers
Authors: Liu Yujia , Lau Edmund , Mager Dario , Madou Marc , Ghazinejad Maziar
Published: September 2021

It is generally accepted that inducing molecular alignment in a polymer precursor via mechanical stresses influences its graphitization during pyrolysis. However, our understanding of how variations of the imposed mechanics can influence pyrolytic carbon microstructure and functionality is inadequate. Developing such insight is consequential for different aspects of carbon MEMS manufacturing and applicability, as pyrolytic carbons are the main building blocks of MEMS devices. Herein, we study the outcomes of contrasting routes of stress-induced graphitization by providing a comparative analysis of the effects of compressive stress versus standard tensile treatment of PAN-based carbon precursors. The results of different materials characterizations (including scanning electron microscopy, Raman and X-ray photoelectron spectroscopies, as well as high-resolution transmission electron microscopy) reveal that while subjecting precursor molecules to both types of mechanical stresses will induce graphitization in the resulting pyrolytic carbon, this effect is more pronounced in the case of compressive stress. We also evaluated the mechanical behavior of three carbon types, namely compression-induced (CIPC), tension-induced (TIPC), and untreated pyrolytic carbon (PC) by Dynamic Mechanical Analysis (DMA) of carbon samples in their as-synthesized mat format. Using DMA, the elastic modulus, ultimate tensile strength, and ductility of CIPC and TIPC films are determined and compared with untreated pyrolytic carbon. Both stress-induced carbons exhibit enhanced stiffness and strength properties over untreated carbons. The compression-induced films reveal remarkably larger mechanical enhancement with the elastic modulus 26 times higher and tensile strength 2.85 times higher for CIPC compared to untreated pyrolytic carbon. However, these improvements come at the expense of lowered ductility for compression-treated carbon, while tension-treated carbon does not show any loss of ductility. The results provided by this report point to the ways that the carbon MEMS industry can improve and revise the current standard strategies for manufacturing and implementing carbon-based micro-devices.
The Only Chemoreceptor Encoded by che Operon Affects the Chemotactic Response of Agrobacterium to Various Chemoeffectors
Authors: Ye Jingyang , Gao Miaomiao , Zhou Qingxuan , Wang Hao , Xu Nan , Guo Minliang
Published: September 2021

Chemoreceptor (also called methyl-accepting chemotaxis protein, MCP) is the leading signal protein in the chemotaxis signaling pathway. MCP senses and binds chemoeffectors, specifically, and transmits the sensed signal to downstream proteins of the chemotaxis signaling system. The genome of Agrobacterium fabrum (previously, tumefaciens) C58 predicts that a total of 20 genes can encode MCP, but only the MCP-encoding gene atu0514 is located inside the che operon. Hence, the identification of the exact function of atu0514-encoding chemoreceptor (here, named as MCP514) will be very important for us to understand more deeply the chemotaxis signal transduction mechanism of A. fabrum. The deletion of atu0514 significantly decreased the chemotactic migration of A. fabrum in a swim plate. The test of atu0514-deletion mutant (Δ514) chemotaxis toward single chemicals showed that the deficiency of MCP514 significantly weakened the chemotactic response of A. fabrum to four various chemicals, sucrose, valine, citric acid and acetosyringone (AS), but did not completely abolish the chemotactic response. MCP514 was localized at cell poles although it lacks a transmembrane (TM) region and is predicted to be a cytoplasmic chemoreceptor. The replacement of residue Phe328 showed that the helical structure in the hairpin subdomain of MCP514 is a direct determinant for the cellular localization of MCP514. Single respective replacements of key residues indicated that residues Asn336 and Val353 play a key role in maintaining the chemotactic function of MCP514.
Interrelationship between the Microbial Communities of the Root Canals and Periodontal Pockets in Combined Endodontic-Periodontal Diseases
Authors: Lopes Erica M. , Passini Maicon R. Z. , Kishi Luciano T. , Chen Tsute , Paster Bruce J. , Gomes Brenda P. F. A.
Published: September 2021

Periodontal and Endodontic diseases are biofilm-related diseases. The presence of microorganisms in root canals (RCs) and the complex microbiota of periodontal pockets (PPs) contribute to the development of endodontic-periodontal diseases. This study performed a systemic analysis using state-of-the-art sequence data to assess the microbial composition of infected RCs and PPs to further assess the microbiota and verify the possibility of cross-infection between these sites. The microbiomes of these combined diseases were examined with a focus on the V3-V4 hypervariable region of the 16S rRNA gene. The number of species in PP was higher than in RC, and there was a predominance of obligate anaerobes and gram-negative bacteria. In the RCs, the genera Enterococcus, Parvimonas, Stomatobaculum predominated, in contrast, the PPs revealed a predominance of Enterococcus, Parvimonas, Stomatobaculum, Peptostreptococcus and Mogibacterium. The RC and PP microbiome was not similar with regards to the sharing of OTUs for phyla and genera (8 and 67, respectively). The evaluation of molecular markers revealed a large number of markers for resistance to antibiotics of the carbapenem and beta-lactam type (broad spectrum). Another relevant finding of this study was the markers related to systemic diseases related to cardiac muscle and rheumatology, among others. In conclusion, the RC microbiota was less complex and diverse than PP. Interactions between microbial communities were present. The shared genus can signal communication between the endodontic and periodontal microbiomes.
Characterization of E. coli Isolates Producing Extended Spectrum Beta-Lactamase SHV-Variants from the Food Chain in Germany
Authors: Irrgang Alexandra , Zhao Ge , Juraschek Katharina , Kaesbohrer Annemarie , Hammerl Jens A.
Published: September 2021

Resistance of bacteria to 3rd generation cephalosporins mediated by beta-lactamases (ESBL, pAmpC) is a public health concern. In this study, 1517 phenotypically cephalosporin-resistant E. coli were screened for the presence of blaSHV genes. Respective genes were detected in 161 isolates. Majority (91%) were obtained from poultry production and meat. The SHV-12 beta-lactamase was the predominant variant (n = 155), while the remaining isolates exhibited SHV-2 (n = 4) or SHV-2a (n = 2). A subset of the isolates (n = 51) was further characterized by PCR, PFGE, or whole-genome sequencing and bioinformatics analysis. The SHV-12-producing isolates showed low phylogenetic relationships, and dissemination of the blaSHV-12 genes seemed to be mainly driven by horizontal gene transfer. In most of the isolates, blaSHV-12 was located on transferable IncX3 (~43 kb) or IncI1 (~100 kb) plasmids. On IncX3, blaSHV-12 was part of a Tn6 composite transposon located next to a Tn3 transposon, which harbored the fluoroquinolone resistance gene qnrS1. On IncI1 plasmids, blaSHV-12 was located on an incomplete class 1 integron as part of a Tn21 transposon. In conclusion, SHV-12 is widely distributed in German poultry production and spreads via horizontal gene transfer. Consumers are at risk by handling raw poultry meat and should take care in appropriate kitchen hygiene.
Relative Importance of Deterministic and Stochastic Processes on Soil Microbial Community Assembly in Temperate Grasslands
Authors: Liu Nana , Hu Huifeng , Ma Wenhong , Deng Ye , Wang Qinggang , Luo Ao , Meng Jiahui , Feng Xiaojuan , Wang Zhiheng
Published: September 2021

Changes in species composition across communities, i.e., β-diversity, is a central focus of ecology. Compared to macroorganisms, the β-diversity of soil microbes and its drivers are less studied. Whether the determinants of soil microbial β-diversity are consistent between soil depths and between abundant and rare microorganisms remains controversial. Here, using the 16S-rRNA of soil bacteria and archaea sampled at different soil depths (0–10 and 30–50 cm) from 32 sites along an aridity gradient of 1500 km in the temperate grasslands in northern China, we compared the effects of deterministic and stochastic processes on the taxonomic and phylogenetic β-diversity of soil microbes. Using variation partitioning and null models, we found that the taxonomic β-diversity of the overall bacterial communities was more strongly determined by deterministic processes in both soil layers (the explanatory power of environmental distance in topsoil: 25.4%; subsoil: 47.4%), while their phylogenetic counterpart was more strongly determined by stochastic processes (the explanatory power of spatial distance in topsoil: 42.1; subsoil 24.7%). However, in terms of abundance, both the taxonomic and phylogenetic β-diversity of the abundant bacteria in both soil layers was more strongly determined by deterministic processes, while those of rare bacteria were more strongly determined by stochastic processes. In comparison with bacteria, both the taxonomic and phylogenetic β-diversity of the overall abundant and rare archaea were strongly determined by deterministic processes. Among the variables representing deterministic processes, contemporary and historical climate and aboveground vegetation dominated the microbial β-diversity of the overall and abundant microbes of both domains in topsoils, but soil geochemistry dominated in subsoils. This study presents a comprehensive understanding on the β-diversity of soil microbial communities in the temperate grasslands in northern China. Our findings highlight the importance of soil depth, phylogenetic turnover, and species abundance in the assembly processes of soil microbial communities.
Gut Microbiota-Modulated Metabolomic Profiling Shapes the Etiology and Pathogenesis of Autoimmune Diseases
Authors: Tsai Yi-Wen , Dong Jia-Ling , Jian Yun-Jie , Fu Shin-Huei , Chien Ming-Wei , Liu Yu-Wen , Hsu Chao-Yuan , Sytwu Huey-Kang
Published: September 2021

Autoimmunity is a complex and multifaceted process that contributes to widespread functional decline that affects multiple organs and tissues. The pandemic of autoimmune diseases, which are a global health concern, augments in both the prevalence and incidence of autoimmune diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. The development of autoimmune diseases is phenotypically associated with gut microbiota-modulated features at the molecular and cellular levels. The etiology and pathogenesis of autoimmune diseases comprise the alterations of immune systems with the innate and adaptive immune cell infiltration into specific organs and the augmented production of proinflammatory cytokines stimulated by commensal microbiota. However, the relative importance and mechanistic interrelationships between the gut microbial community and the immune system during progression of autoimmune diseases are still not well understood. In this review, we describe studies on the profiling of gut microbial signatures for the modulation of immunological homeostasis in multiple inflammatory diseases, elucidate their critical roles in the etiology and pathogenesis of autoimmune diseases, and discuss the implications of these findings for these disorders. Targeting intestinal microbiome and its metabolomic associations with the phenotype of autoimmunity will enable the progress of developing new therapeutic strategies to counteract microorganism-related immune dysfunction in these autoimmune diseases.
Human Infections by Wohlfahrtiimonas chitiniclastica: A Mini-Review and the First Report of a Burn Wound Infection after Accidental Myiasis in Central Europe
Authors: Hladík Martin , Lipovy Bretislav , Kaloudova Yvona , Hanslianova Marketa , Vitkova Ivana , Deissova Tereza , Kempny Tomas , Svoboda Martin , Kala Zdenek , Brychta Pavel , Borilova Linhartova Petra
Published: September 2021

Wohlfahrtiimonas chitiniclastica are bacteria that cause rare infections, typically associated with the infestation of an open wound with fly larvae. Here, we present a unique case report of the first W. chitiniclastica isolation from a burn wound with accidental myiasis in a 63-year-old homeless man and a literature review focused on human infections caused by these bacteria. So far, 23 cases of infection with W. chitiniclastica have been reported; in 52% of these, larvae were found in the wound area. Most of these cases suffered from chronic non-healing wound infections but none of these were burn injuries. The overall fatality rate associated directly with W. chitiniclastica in these cases was 17%. Infections with parasitic larvae occur in moderate climates (especially in people living in poor conditions); therefore, an infection with rare bacteria associated with accidental myiasis, such as W. chitiniclastica, can be expected to become more common there. Thus, in view of the absence of recommendations regarding the treatment of patients with accidental myiasis and, therefore, the risk of infection with W. chitiniclastica or other rare pathogens, we provide a list of recommendations for the treatment of such patients. The importance of meticulous microbial surveillance using molecular biological methods to facilitate the detection of rare pathogens is emphasized.
Specific Changes in the Mammalian Gut Microbiome as a Biomarker for Oxytocin-Induced Behavioral Changes
Authors: Dangoor Itzhak , Stanić Dušanka , Reshef Leah , Pešić Vesna , Gophna Uri
Published: September 2021

Prolonged exposure to psychiatric pharmacological agents is often associated with marked gastrointestinal phenomena, including changes in food intake, bowel motility, gastric emptying, and transit time. Those changes are reflected in the gut microbiota composition of the patient and can, therefore, be objectively measured. This is in contrast to the standard psychiatric evaluation of patients, which includes symptoms that are subjectively assessed (i.e., mood, anxiety level, perception, thought disorders, etc.). The association between a drug’s effect on the microbiota and psychiatric symptoms may allow for quantifiable surrogate markers of treatment effectiveness. Changes in the levels of specific drug-sensitive bacterial species can, thus, potentially serve as biomarkers for the intake and effectiveness of psychiatric drugs. Here, we show substantial microbiota changes that were associated with oxytocin administration and the decreased anxiety/depression-like behaviors it conferred in a rat model of corticosterone-induced stress. Compared with oxytocin, citalopram produced more minor effects on the rats’ microbiota. Alterations in the gut microbiota may, therefore, reflect the consumption and effectiveness of some psychiatric drugs.
Petrochronology of Monazite-Bearing Garnet Micaschists as a Tool to Decipher the Metamorphic Evolution of the Alpine Basement
Authors: Schulz Bernhard
Published: September 2021

Garnet-bearing metapelites in the Helvetic and Austroalpine pre-Mesozoic polymetamorphic basement are characterised by pressure-temperature path segments reconstructed by microstructurally controlled geothermobarometry, and the Th-U-Pb monazite age distribution pattern revealed by the electron probe microanalyser (EPMA). In the Helvetic Aiguilles Rouges Massif and the Austroalpine Oetztal-Stubai basement to the NW an Ordovician-to-Silurian high temperature event preceded a pressure-dominated Carboniferous metamorphism. In the Austroalpine basement units to the south of the Tauern Window, the maximal pressures of the Carboniferous amphibolite-facies metamorphism range from 12 to 6 kbar. The decompressional P-T path segments signal a transition to low pressure conditions. A subsequent high pressure overprint is restricted to the Prijakt Subgroup unit in the Schobergruppe and documented by Cretaceous monazite crystallisation at 88 ± 6 Ma. In the Austroalpine Saualpe basement to the SE, a distinct early Permian metamorphism which started at low pressures of ~4 kbar/500 °C and reached maximal 6 kbar/600–650 °C predated the intrusion of Permian pegmatites. Permian monazite crystallised in line with the intrusion of pegmatites. Corona microstructures around the Permian monazites indicate retrogression previous to a Cretaceous high pressure metamorphism. That way, pressure-temperature-time paths resolve the spatial and temporal evolution in the polymetamorphic Alpine basement prior to the Tertiary collision.
Zr-Rich Eudialyte from the Lovozero Peralkaline Massif, Kola Peninsula, Russia
Authors: Panikorovskii Taras L. , Mikhailova Julia A. , Pakhomovsky Yakov A. , Bazai Ayya V. , Aksenov Sergey M. , Kalashnikov Andrey O. , Krivovichev Sergey V.
Published: September 2021

The Lovozero peralkaline massif (Kola Peninsula, Russia) has several deposits of Zr, Nb, Ta and rare earth elements (REE) associated with eudialyte-group minerals (EGM). Eudialyte from the Alluaiv Mt. often forms zonal grains with central parts enriched in Zr (more than 3 apfu) and marginal zones enriched in REEs. The detailed study of the chemical composition (294 microprobe analyses) of EGMs from the drill cores of the Mt. Alluaiv-Mt. Kedykvyrpakhk deposits reveal more than 70% Zr-enriched samples. Single-crystal X-ray diffraction (XRD) was performed separately for the Zr-rich (4.17 Zr apfu) core and the REE-rich (0.54 REE apfu) marginal zone. It was found that extra Zr incorporates into the octahedral M1A site, where it replaces Ca, leading to the symmetry lowering from R3¯m to R32. We demonstrated that the incorporation of extra Zr into EGMs makes the calculation of the eudialyte formula on the basis of Si + Al + Zr + Ti + Hf + Nb + Ta + W = 29 apfu inappropriate.
Valorisation of Partially Oxidized Tailings in a Cover System to Reclaim an Old Acid Generating Mine Site
Authors: Dublet-Adli Gabrielle , Pabst Thomas , Okkenhaug Gudny , Sætre Christian , Vårheim Anna , Tvedten Mari , Gelena Samuel , Smebye Andreas , Kvennås Marianne , Breedveld Gijs
Published: September 2021

The reclamation of acid-generating mine tailings typically involves building cover systems to limit interactions with water or oxygen. The choice of cover materials is critical to ensure long-term performance, and partly determines the environmental footprint of the reclamation strategy. The objective of this research was to evaluate if tailings pre-oxidized on-site could be used in cover systems. Column experiments were performed to assess the effectiveness of a cover with capillary barrier effects (CCBE), where the moisture retention layer (MRL) was made of pre-oxidized tailings with little to no remaining sulfides (LS tailings). The columns were submitted to regular wetting and drying cycles, and their hydrological and geochemical behaviour was monitored for 510 days. The LS tailings showed satisfying hydrological properties as an MRL and remained saturated throughout the test. The concentrations of Cu in the drainage decreased by more than two orders of magnitude compared to non-covered tailings. In addition, the pH increased by nearly one unit compared to the control column, and Fe and S concentrations decreased by around 50%. Despite these improvements, the leachate water remained acidic and contaminated, indicating that acid drainage continued to be generated despite a hydrologically efficient CCBE.
Microstructural Analysis of a Mylonitic Mantle Xenolith Sheared at Laboratory-like Strain Rates from the Edge of the Wyoming Craton
Authors: Boneh Yuval , Chin Emily J. , Hirth Greg
Published: September 2021

Combined observations from natural and experimental deformation microstructures are often used to constrain the rheological properties of the upper mantle. However, relating natural and experimental deformation processes typically requires orders of magnitude extrapolation in strain rate due to vastly different time scales between nature and the lab. We examined a sheared peridotite xenolith that was deformed under strain rates comparable to laboratory shearing time scales. Microstructure analysis using an optical microscope and electron backscatter diffraction (EBSD) was done to characterize the bulk crystallographic preferred orientation (CPO), intragrain misorientations, subgrain boundaries, and spatial distribution of grains. We found that the microstructure varied between monophase (olivine) and multiphase (i.e., olivine, pyroxene, and garnet) bands. Olivine grains in the monophase bands had stronger CPO, larger grain size, and higher internal misorientations compared with olivine grains in the multiphase bands. The bulk olivine CPO suggests a dominant (010)[100] and secondary activated (001)[100] that are consistent with the experimentally observed transition of the A to E-types. The bulk CPO and intragrain misorientations of olivine and orthopyroxene suggest that a coarser-grained initial fabric was deformed by dislocation creep coeval with the reduction of grain size due to dynamic recrystallization. Comparing the deformation mechanisms inferred from the microstructure with experimental flow laws indicates that the reduction of grain size in orthopyroxene promotes activation of diffusion creep and suggests a high activation volume for wet orthopyroxene dislocation creep.
The Effect of Betulin Diphosphate in Wound Dressings of Bacterial Cellulose-ZnO NPs on Platelet Aggregation and the Activity of Oxidoreductases Regulated by NAD(P)+/NAD(P)H-Balance in Burns on Rats
Authors: Melnikova Nina , Malygina Darina , Balakireva Alyona , Peretyagin Peter , Revin Vadim , Devyataeva Anna , Malafeeva Kseniya , Revin Viktor
Published: September 2021

The inhibition of platelet aggregation, and the activity of oxidoreductases and microhemocirculation in a burn wound on the treatment of burns with wound dressings based on bacterial nanocellulose (BC)-zinc oxide nanoparticles (ZnO NPs)-betulin diphosphate (BDP) were studied. The control of the treatment by BC-ZnO NPs-BDP on burned rats by the noninvasive DLF method showed an increase in perfusion and the respiratory component in wavelet spectra, characterizing an improvement in oxygen saturation in the wound. The study on the volunteers’ blood found the inhibition of ADP-induced platelet aggregation by 30–90%. Disaggregation depends on the dose under the action of the ionized form of BDP and ZnO NPs-BDP in a phosphate buffer; it was reversible and had two waves. It was shown on rats that the specific activity of LDHreverse and LDHdirect (control-intact animals) on day 21 of treatment increased by 11–38% and 23%, respectively. The LDHreverse/LDHdirect ratio increased at BC-ZnO NPs-BDP treatment, which characterizes efficient NAD+ regeneration. AlDH activity increased significantly in the first 10 days by 70–170%, reflecting the effectiveness of the enzyme and NAD+ in utilizing toxic aldehydes at this stage of burn disease. The activities of GR and G6PDH using NADP(H) were increased with BC-ZnO NPs-BDP treatment.
The Effect of Different Ester Chain Modifications of Two Guaianolides for Inhibition of Colorectal Cancer Cell Growth
Authors: Al Aaraj Lamis , Hayar Berthe , Jaber Zaynab , Saad Walid , Saliba Najat A. , Darwiche Nadine , Ghaddar Tarek
Published: September 2021

Several sesquiterpene lactones (STLs) have been tested as lead drugs in cancer clinical trials. Salograviolide-A (Sal-A) and salograviolide-B (Sal-B) are two STLs that have been isolated from Centaurea ainetensis, an indigenous medicinal plant of the Middle Eastern region. The parent compounds Sal-A and Sal-B were modified and successfully prepared into eight novel guaianolide-type STLs (compounds 1–8) bearing ester groups of different geometries. Sal-A, Sal-B, and compounds 1–8 were tested against a human colorectal cancer cell line model with differing p53 status; HCT116 with wild-type p53 and HCT116 p53−/− null for p53, and the normal-like human colon mucosa cells with wild-type p53, NCM460. IC50 values indicated that derivatization of Sal-A and Sal-B resulted in potentiation of HCT116 cell growth inhibition by 97% and 66%, respectively. The effects of the different molecules on cancer cell growth were independent of p53 status. Interestingly, the derivatization of Sal-A and Sal-B molecules enhanced their anti-growth properties versus 5-Fluorouracil (5-FU), which is the drug of choice in colorectal cancer. Structure-activity analysis revealed that the enhanced molecule potencies were mainly attributed to the position and number of the hydroxy groups, the lipophilicity, and the superiority of ester groups over hydroxy substituents in terms of their branching and chain lengths. The favorable cytotoxicity and selectivity of the potent molecules, to cancer cells versus their normal counterparts, pointed them out as promising leads for anti-cancer drug design.
In Situ Water Quantification in Natural Deep Eutectic Solvents Using Portable Raman Spectroscopy
Authors: Elderderi Suha , Wils Laura , Leman-Loubière Charlotte , Byrne Hugh J. , Chourpa Igor , Enguehard-Gueiffier Cécile , Munnier Emilie , Elbashir Abdalla A. , Boudesocque-Delaye Leslie , Bonnier Franck
Published: September 2021

Raman spectroscopy is a label-free, non-destructive, non-invasive analytical tool that provides insight into the molecular composition of samples with minimum or no sample preparation. The increased availability of commercial portable Raman devices presents a potentially easy and convenient analytical solution for day-to-day analysis in laboratories and production lines. However, their performance for highly specific and sensitive analysis applications has not been extensively evaluated. This study performs a direct comparison of such a commercially available, portable Raman system, with a research grade Raman microscope system for the analysis of water content of Natural Deep Eutectic Solvents (NADES). NADES are renewable, biodegradable and easily tunable “green” solvents, outcompeting existing organic solvents for applications in extraction from biomass, biocatalysis, and nanoparticle synthesis. Water content in NADES is, however, a critical parameter, affecting their properties, optimal use and extraction efficiency. In the present study, portable Raman spectroscopy coupled with Partial Least Squares Regression (PLSR) is investigated for rapid determination of water content in NADES samples in situ, i.e., directly in glassware. Three NADES systems, namely Betaine Glycerol (BG), Choline Chloride Glycerol (CCG) and Glucose Glycerol (GG), containing a range of water concentrations between 0% (w/w) and 28.5% (w/w), were studied. The results are directly compared with previously published studies of the same systems, using a research grade Raman microscope. PLSR results demonstrate the reliability of the analysis, surrendering R2 values above 0.99. Root Mean Square Errors Prediction (RMSEP) of 0.6805%, 0.9859% and 1.2907% w/w were found for respectively unknown CCG, BG and GG samples using the portable device compared to 0.4715%, 0.3437% and 0.7409% w/w previously obtained by analysis in quartz cuvettes with a Raman confocal microscope. Despite the relatively higher values of RMSEP observed, the comparison of the percentage of relative errors in the predicted concentration highlights that, overall, the portable device delivers accuracy below 5%. Ultimately, it has been demonstrated that portable Raman spectroscopy enables accurate quantification of water in NADES directly through glass vials without the requirement for sample withdrawal. Such compact instruments provide solvent and consumable free analysis for rapid analysis directly in laboratories and for non-expert users. Portable Raman is a promising approach for high throughput monitoring of water content in NADES that can support the development of new analytical protocols in the field of green chemistry in research and development laboratories but also in the industry as a routine quality control tool.
Exploring the Role of L10 Loop in New Delhi Metallo-β-lactamase (NDM-1): Kinetic and Dynamic Studies
Authors: Piccirilli Alessandra , Criscuolo Emanuele , Brisdelli Fabrizia , Mercuri Paola Sandra , Cherubini Sabrina , De Sciscio Maria Laura , Maccarrone Mauro , Galleni Moreno , Amicosante Gianfranco , Perilli Mariagrazia
Published: September 2021

Four NDM-1 mutants (L218T, L221T, L269H and L221T/Y229W) were generated in order to investigate the role of leucines positioned in L10 loop. A detailed kinetic analysis stated that these amino acid substitutions modified the hydrolytic profile of NDM-1 against some β-lactams. Significant reduction of kcat values of L218T and L221T for carbapenems, cefazolin, cefoxitin and cefepime was observed. The stability of the NDM-1 and its mutants was explored by thermofluor assay in real-time PCR. The determination of TmB and TmD demonstrated that NDM-1 and L218T were the most stable enzymes. Molecular dynamic studies were performed to justify the differences observed in the kinetic behavior of the mutants. In particular, L218T fluctuated more than NDM-1 in L10, whereas L221T would seem to cause a drift between residues 75 and 125. L221T/Y229W double mutant exhibited a decrease in the flexibility with respect to L221T, explaining enzyme activity improvement towards some β-lactams. Distances between Zn1-Zn2 and Zn1-OH- or Zn2-OH- remained unaffected in all systems analysed. Significant changes were found between Zn1/Zn2 and first sphere coordination residues.
Bioactive Electrospun Fibers of Poly(ε-Caprolactone) Incorporating α-Tocopherol for Food Packaging Applications
Authors: Dumitriu Raluca P. , Stoleru Elena , Mitchell Geoffrey R. , Vasile Cornelia , Brebu Mihai
Published: September 2021

Antioxidant activity is an important feature for food contact materials such as packaging, aiming to preserve freshness and retard food spoilage. Common bioactive agents are highly susceptible to various forms of degradation; therefore, protection is required to maintain functionality and bioavailability. Poly(ε-caprolactone) (PCL), a biodegradable GRAS labeled polymer, was used in this study for encapsulation of α-tocopherol antioxidant, a major component of vitamin E, in the form of electrospun fibers. Rheological properties of the fiber forming solutions, which determine the electrospinning behavior, were correlated with the properties of electrospun fibers, e.g., morphology and surface properties. Interactions through hydrogen bonds were evidenced between the two components. These have strong effect on structuration of macromolecular chains, especially at low α-tocopherol amounts, decreasing viscosity and elastic modulus. Intra-molecular interactions in PCL strengthen at high α-tocopherol amounts due to decreased solvation, allowing good structural recovery after cease of mechanical stress. Morphologically homogeneous electrospun fibers were obtained, with ~6 μm average diameter. The obtained fibers were highly hydrophobic, with fast release in 95% ethanol as alternative simulant for fatty foods. This induced good in vitro antioxidant activity and significant in vivo reduction of microbial growth on cheese, as determined by respirometry. Therefore, the electrospun fibers from PCL entrapping α-tocopherol as bioactive agent showed potential use in food packaging materials.
Berberine Inhibits Dengue Virus through Dual Mechanisms
Authors: Ratanakomol Thippayawan , Roytrakul Sittiruk , Wikan Nitwara , Smith Duncan R.
Published: September 2021

Mosquito transmitted viruses, particularly those of the genus Flavivirus, are a significant healthcare burden worldwide, especially in tropical and sub-tropical areas. However, effective medicines for these viral infections remains lacking. Berberine (BBR) is an alkaloid found in some plants used in traditional medicines in Southeast Asia and elsewhere, and BBR has been shown to possess anti-viral activities. During a screen for potential application to mosquito transmitted viruses, BBR was shown to have virucidal activity against dengue virus (DENV; IC50 42.87 µM) as well as against Zika virus (IC50 11.42 µM) and chikungunya virus (IC50 14.21 µM). BBR was shown to have cellular effects that lead to an increase in cellular DENV E protein without a concomitant effect on DENV nonstructural proteins, suggesting an effect on viral particle formation or egress. While BBR was shown to have an effect of ERK1/2 activation this did not result in defects in viral egress mechanisms. The primary effect of BBR on viral production was likely to be through BBR acting through AMPK activation and disruption of lipid metabolism. Combined these results suggest that BBR has a dual effect on DENV infection, and BBR may have the potential for development as an anti-DENV antiviral.
PTP1B Inhibitory Secondary Metabolites from an Antarctic Fungal Strain Acremonium sp. SF-7394
Authors: Kim Hye Jin , Li Xiao-Jun , Kim Dong-Cheol , Kim Tai Kyoung , Sohn Jae Hak , Kwon Haeun , Lee Dongho , Kim Youn-Chul , Yim Joung Han , Oh Hyuncheol
Published: September 2021

Chemical investigation of the Antarctic lichen-derived fungal strain Acremonium sp. SF-7394 yielded a new amphilectane-type diterpene, acrepseudoterin (1), and a new acorane-type sesquiterpene glycoside, isocordycepoloside A (2). In addition, three known fungal metabolites, (−)-ternatin (3), [D-Leu]-ternatin (4), and pseurotin A (5), were isolated from the EtOAc extract of the fungal strain. Their structures were mainly elucidated by analyzing their NMR and MS data. The absolute configuration of 1 was proposed by electronic circular dichroism calculations, and the absolute configuration of the sugar unit in 2 was determined by a chemical method. The inhibitory effects of the isolated compounds on protein tyrosine phosphatase 1B (PTP1B) were evaluated by enzymatic assays; results indicated that acrepseudoterin (1) and [D-Leu]-ternatin (4) dose-dependently inhibited the enzyme activity with IC50 values of 22.8 ± 1.1 μM and 14.8 ± 0.3 μM, respectively. Moreover, compound 1 was identified as a competitive inhibitor of PTP1B.
Participation of the Cholinergic System in the Development of Polycystic Ovary Syndrome
Authors: Linares Rosa , Acuña Xóchitl N. , Rosas Gabriela , Vieyra Elizabeth , Ramírez Deyra A. , Chaparro Andrea , Espinoza Julieta A. , Domínguez Roberto , Morales-Ledesma Leticia
Published: September 2021

In rats with polycystic ovary syndrome (PCOS) induced by injection of estradiol valerate (EV), unilateral or bilateral section of the vagus nerve restores ovulatory function in 75% of animals, suggesting that the vagus nerve participates in the development of PCOS. Since the vagus nerve is a mixed nerve through which mainly cholinergic-type information passes, the objective of the present study was to analyze whether acetylcholine (ACh) is involved in the development of PCOS. Ten-day-old rats were injected with 2.0 mg EV, and at 60 days of age, they were microinjected on the day of diestrus in the bursa of the left or right ovary with 100 or 700 mg/kg of ovarian weight atropine, a blocker of muscarinic receptors, and sacrificed for histopathological examination after the surgery. Animals with PCOS microinjected with 100 mg of atropine showed a lack of ovulation, lower serum concentrations of progesterone and testosterone, and cysts. Histology of the ovaries of animals microinjected with 700 mg of atropine showed corpus luteum and follicles at different stages of development, which was accompanied by a lower concentration of progesterone and testosterone. These results allow us to suggest that in animals with PCOS, ACh, which passes through parasympathetic innervation, is an important component in the persistence and development of the pathophysiology.
Analysis of Molar Substitution of Hydroxybutyl Group by Zeisel Reaction in Starch Ethers
Authors: Man Xiao-Lei , Peng Wei-Kang , Chen Jun , Liu Xue-Li
Published: September 2021

A new etherified starch, δ-hydroxybutyl starch (δ-HBS), was prepared by utilising 4-chlorobutan-1-ol as the etherifying reagent. The method of Zeisel gas chromatography for the determination of the molar substitution was described. This technique offers a simple and rapid method for quantitative analysis with reproducible results. Meanwhile, the mechanism of the Zeisel reaction was also investigated.
The Influence of Propolis on Dental Plaque Reduction and the Correlation between Dental Plaque and Severity of COVID-19 Complications—A Literature Review
Authors: Kurek-Górecka Anna , Walczyńska-Dragon Karolina , Felitti Rafael , Nitecka-Buchta Aleksandra , Baron Stefan , Olczyk Paweł
Published: September 2021

Current studies suggest that cariogenic bacteria in dental plaque influence the severity of COVID-19 complications since the oral cavity is a reservoir for respiratory pathogens potentially responsible for the development of hospital-acquired pneumonia. This article focuses on the association between dental plaque and COVID-19 concerning the influence of altered oral biofilm on the risk of increased severity of SARS-CoV-2 infection. Moreover, it concentrates on the usefulness of propolis, with its apitherapeutic antibacterial properties, for treating oral bacterial infections co-occurring with SARS-CoV-2 infection. A review of the literature on PubMed, Cochrane Library and Medline between 2000 and 2021 revealed 56 published articles indicating that a link between dental plaque and COVID-19 complications was probable. Furthermore, they indicated that propolis may minimize COVID-19 severity by reducing dental plaque accumulation. The possibility that improved oral health could reduce the risk of COVID-19 complications should be of interest to scientists.
Detection of Heavy Metals in Water Using Graphene Oxide Quantum Dots: An Experimental and Theoretical Study
Authors: Gontrani Lorenzo , Pulci Olivia , Carbone Marilena , Pizzoferrato Roberto , Prosposito Paolo
Published: September 2021

In this work, we investigate by ab initio calculations and optical experiments the sensitivity of graphene quantum dots in their use as devices to measure the presence, and concentration, of heavy metals in water. We demonstrate that the quenching or enhancement in the optical response (absorption, emission) depends on the metallic ion considered. In particular, two cases of opposite behaviour are considered in detail: Cd2+, where we observe an increase in the emission optical response for increasing concentration, and Pb2+ whose emission spectra, vice versa, are quenched along the concentration rise. The experimental trends reported comply nicely with the different hydration patterns suggested by the models that are also capable of reproducing the minor quenching/enhancing effects observed in other ions. We envisage that quantum dots of graphene may be routinely used as cheap detectors to measure the degree of poisoning ions in water.
Conjugation of Aminoadamantane and γ-Carboline Pharmacophores Gives Rise to Unexpected Properties of Multifunctional Ligands
Authors: Bachurin Sergey O. , Makhaeva Galina F. , Shevtsova Elena F. , Aksinenko Alexey Yu. , Grigoriev Vladimir V. , Shevtsov Pavel N. , Goreva Tatiana V. , Epishina Tatiana A. , Kovaleva Nadezhda V. , Pushkareva Elena A. , Boltneva Natalia P. , Lushchekina Sofya V. , Gabrelyan Alexey V. , Zamoyski Vladimir L. , Dubova Lyudmila G. , Rudakova Elena V. , Fisenko Vladimir P. , Bovina Elena V. , Richardson Rudy J.
Published: September 2021

A new series of conjugates of aminoadamantane and γ-carboline, which are basic scaffolds of the known neuroactive agents, memantine and dimebon (Latrepirdine) was synthesized and characterized. Conjugates act simultaneously on several biological structures and processes involved in the pathogenesis of Alzheimer’s disease and some other neurodegenerative disorders. In particular, these compounds inhibit enzymes of the cholinesterase family, exhibiting higher inhibitory activity against butyrylcholinesterase (BChE), but having almost no effect on the activity of carboxylesterase (anti-target). The compounds serve as NMDA-subtype glutamate receptor ligands, show mitoprotective properties by preventing opening of the mitochondrial permeability transition (MPT) pore, and act as microtubule stabilizers, stimulating the polymerization of tubulin and microtubule-associated proteins. Structure–activity relationships were studied, with particular attention to the effect of the spacer on biological activity. The synthesized conjugates showed new properties compared to their prototypes (memantine and dimebon), including the ability to bind to the ifenprodil-binding site of the NMDA receptor and to occupy the peripheral anionic site of acetylcholinesterase (AChE), which indicates that these compounds can act as blockers of AChE-induced β-amyloid aggregation. These new attributes of the conjugates represent improvements to the pharmacological profiles of the separate components by conferring the potential to act as neuroprotectants and cognition enhancers with a multifunctional mode of action.