bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Ilmenite Slag Using Laser-Induced Breakdown Spectroscopy
Authors: Gupta Avishek Kumar , Aula Matti , Negre Erwan , Viljanen Jan , Pauna Henri , Mäkelä Pasi , Toivonen Juha , Huttula Marko , Fabritius Timo
Published: September 2020

The feasibility of using laser-induced breakdown spectroscopy (LIBS) for the compositional analysis of ilmenite slag was explored. The slag was obtained from a pilot-scale ilmenite smelting furnace. The composition of major oxides TiO2, FeO, and MgO are determined by the calibrated LIBS method. LIBS measurements are done under normal atmosphere and temperature. A Q-switched Nd:YAG laser operating at 355 nm was used to create a plasma on an ilmenite slag sample. The characteristic lines based on the NIST database of Fe, Mg, and Ti can be identified on the normalized LIBS spectra for the slag samples. The spectral range chosen for the study is 370 to 390 nm. Calibration curves were plotted using the data collected from various industrial ilmenite samples of varying compositions of TiO2, FeO, and MgO. The univariate simple linear regression technique was used to do the analysis and the prediction accuracy was checked by the root mean square error (RMSE). To validate the application of LIBS, both qualitative and quantitative analysis is done and compared to the analytical ICP-OES results. The model predicts the magnesium content with the highest accuracy and gives good prediction for iron and titanium content. This study demonstrates the capability of using LIBS for the surface analysis of the ilmenite slag sample.
Factors Impacting σ- and π-Hole Regions as Revealed by the Electrostatic Potential and Its Source Function Reconstruction: The Case of 4,4′-Bipyridine Derivatives
Authors: Gatti Carlo , Dessì Alessandro , Dallocchio Roberto , Mamane Victor , Cossu Sergio , Weiss Robin , Pale Patrick , Aubert Emmanuel , Peluso Paola
Published: September 2020

Positive electrostatic potential (V) values are often associated with σ- and π-holes, regions of lower electron density which can interact with electron-rich sites to form noncovalent interactions. Factors impacting σ- and π-holes may thus be monitored in terms of the shape and values of the resulting V. Further precious insights into such factors are obtained through a rigorous decomposition of the V values in atomic or atomic group contributions, a task here achieved by extending the Bader–Gatti source function (SF) for the electron density to V. In this article, this general methodology is applied to a series of 4,4′-bipyridine derivatives containing atoms from Groups VI (S, Se) and VII (Cl, Br), and the pentafluorophenyl group acting as a π-hole. As these molecules are characterized by a certain degree of conformational freedom due to the possibility of rotation around the two C–Ch bonds, from two to four conformational motifs could be identified for each structure through conformational search. On this basis, the impact of chemical and conformational features on σ- and π-hole regions could be systematically evaluated by computing the V values on electron density isosurfaces (VS) and by comparing and dissecting in atomic/atomic group contributions the VS maxima (VS,max) values calculated for different molecular patterns. The results of this study confirm that both chemical and conformational features may seriously impact σ- and π-hole regions and provide a clear analysis and a rationale of why and how this influence is realized. Hence, the proposed methodology might offer precious clues for designing changes in the σ- and π-hole regions, aimed at affecting their potential involvement in noncovalent interactions in a desired way.
Dependence of the Optical Constant Parameters of p-Toluene Sulfonic Acid-Doped Polyaniline and Its Composites on Dispersion Solvents
Authors: Usman Fahad , Dennis John Ojur , Meriaudeau Fabrice , Ahmed Abdelaziz Yousif , Seong Khe Cheng , Fen Yap Wing , Sadrolhosseini Amir Reza , Abdulkadir Bashir Abubakar , Ayinla Ridwan Tobi , Daniyal Wan Mohd Ebtisyam Mustaqim Mohd , Omar Nur Alia Sheh , Tamam Nissren , Sulieman Abdelmoneim
Published: September 2020

The optical constants of Para-Toluene sulfonic acid-doped polyaniline (PANI), PANIchitosan composites, PANI-reduced graphene-oxide composites and a ternary composite comprising of PANI, chitosan and reduced graphene-oxide dispersed in diluted p-toluene sulfonic acid (PTSA) solution and N-Methyl-2-Pyrrolidone (NMP) solvent have been evaluated and compared. The optical constant values were extracted from the absorbance spectra of thin layers of the respective samples. The potential utilization of the materials as the active sensing materials of surface plasmon resonance biosensors has also been assessed in terms of the estimated value of the penetration depth through a dielectric medium. The results show a reasonable dependence of the optical constant parameters on the solvent type. Higher real part refractive index (n) and real part complex dielectric permittivity (ε’) values were observed for the samples prepared using PTSA solution, while higher optical conductivity values were observed for the NMP-based samples due to their relatively higher imaginary part refractive index (k) and imaginary part complex dielectric permittivity (ε″) values. In addition, NMP-based samples show improvement in terms of the penetration depth through a dielectric medium by around 9.5, 1.6, 4.4 and 2.9 times compared to PTSA-based samples for the PANI, PANI-chitosan, PANI-RGO and the ternary composites, respectively. Based on these, it is concluded that preparation of these materials using different dispersion solvents could produce materials of different optical properties. Thus, the variation of the dispersion solvent will allow the flexible utilization of the PANI and the composites for diverse applications.
Huisgen [3 + 2] Dipolar Cycloadditions of Phthalazinium Ylides to Activated Symmetric and Non-Symmetric Alkynes
Authors: Antoci Vasilichia , Moldoveanu Costel , Danac Ramona , Mangalagiu Violeta , Zbancioc Gheorghita
Published: September 2020

We present herein a straightforward and efficient pathway for the synthesis of pyrrolophthalazine cycloadducts via Huisgen [3 + 2] dipolar cycloaddition reactions of phthalazinium ylides to methyl propiolate or dimethyl acetylenedicarboxylate (DMAD). A thoroughly comparative study concerning the efficiency of synthesis, conventional thermal heating (TH) versus microwave (MW) and ultrasound (US) irradiation, has been performed. The cycloaddition reactions of phthalazinium ylides to methyl propiolate occur regiospecific, with a single regioisomer being obtained. Under conventional TH, the cycloaddition reaction of phthalazinium ylides with DMAD occurs to a mixture of inseparable partial and fully aromatized pyrrolophthalazine cycloadducts, while MW or US irradiation are leading only to fully aromatized compounds, with the reactions becoming selective. A feasible mechanism for formation of fully aromatized compounds is presented. Besides selectivity, it has to be noticed that the reaction setup under MW or US irradiation offer a number of other certain advantages: higher yields, decreasing of the amount of used solvent comparative with TH, decreasing of the reaction time from hours to minutes and decreasing of the consumed energy; consequently, these reactions could be considered environmentally friendly.
4-Hydroxy-7-Methoxycoumarin Inhibits Inflammation in LPS-activated RAW264.7 Macrophages by Suppressing NF-κB and MAPK Activation
Authors: Kang Jin Kyu , Hyun Chang-Gu
Published: September 2020

Coumarins are natural products with promising pharmacological activities owing to their anti-inflammatory, antioxidant, antiviral, anti-diabetic, and antimicrobial effects. Coumarins are present in many plants and microorganisms and have been widely used as complementary and alternative medicines. To date, the pharmacological efficacy of 4-hydroxy-7-methoxycoumarin (4H-7MTC) has not been reported yet. Therefore, in this study, we investigated the anti-inflammatory effects of 4H-7MTC in LPS-stimulated RAW264.7 cells as well as its mechanisms of action. Cells were treated with various concentrations of 4H-7MTC (0.3, 0.6, 0.9, and 1.2 mM) and 40 μM L-N6-(1-iminoethyl)-L-lysine (L-NIL) were used as controls. LPS-stimulated RAW264.7 cells showed that 4H-7MTC significantly reduced nitric oxide (NO) and prostaglandin E2 (PGE2) production without cytotoxic effects. In addition, 4H-7MTC strongly decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Furthermore, 4H-7MTC reduced the production of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. We also found that 4H-7MTC strongly exerted its anti-inflammatory actions by downregulating nuclear factor kappa B (NF-κB) activation by suppressing inhibitor of nuclear factor kappa B alpha (IκBα) degradation in macrophages. Moreover, 4H-7MTC decreased phosphorylation of extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase/stress-activated protein kinase (JNK), but not that of p38 MAPK. These results suggest that 4H-7MTC may be a good candidate for the treatment or prevention of inflammatory diseases such as dermatitis, psoriasis, and arthritis. Ultimately, this is the first report describing the effective anti-inflammatory activity of 4H-7MTC.
Synthesis, Characterization and Magnetic Hyperthermia of Monodispersed Cobalt Ferrite Nanoparticles for Cancer Therapeutics
Authors: Medina Mauricio A. , Oza Goldie , Ángeles-Pascual A. , González M. Marlene , Antaño-López R. , Vera A. , Leija L. , Reguera Edilso , Arriaga L. G. , Hernández Hernández José Manuel , Ramírez José Tapia
Published: September 2020

Magnetic nanoparticles such as cobalt ferrite are investigated under clinical hyperthermia conditions for the treatment of cancer. Cobalt ferrite nanoparticles (CFNPs) synthesized by the thermal decomposition method, using nonionic surfactant Triton-X100, possess hydrophilic polyethylene oxide chains acting as reducing agents for the cobalt and iron precursors. The monodispersed nanoparticles were of 10 nm size, as confirmed by high-resolution transmission electron microscopy (HR-TEM). The X-ray diffraction patterns of CFNPs prove the existence of cubic spinel cobalt ferrites. Cs-corrected scanning transmission electron microscopy–high-angle annular dark-field imaging (STEM–HAADF) of CFNPs confirmed their multi-twinned crystallinity due to the presence of atomic columns and defects in the nanostructure. Magnetic measurements proved that the CFNPs possess reduced remnant magnetization (MR/MS) (0.86), which justifies cubic anisotropy in the system. Microwave-based hyperthermia studies performed at 2.45 GHz under clinical conditions in physiological saline increased the temperature of the CFNP samples due to the transformation of radiation energy to heat. The specific absorption rate of CFNPs in physiological saline was 68.28 W/g. Furthermore, when triple-negative breast cancer cells (TNBC) in the presence of increasing CFNP concentration (5 mg/mL to 40 mg/mL) were exposed to microwaves, the cell cytotoxicity was enhanced compared to CFNPs alone.
New Real-Time PCRs to Differentiate Rickettsia spp. and Rickettsia conorii
Authors: Blanda Valeria , D’Agostino Rosalia , Giudice Elisabetta , Randazzo Kety , La Russa Francesco , Villari Sara , Vullo Stefano , Torina Alessandra
Published: September 2020

Rickettsia species are an important cause of emerging infectious diseases in people and animals, and rickettsiosis is one of the oldest known vector-borne diseases. Laboratory diagnosis of Rickettsia is complex and time-consuming. This study was aimed at developing two quantitative real-time PCRs targeting ompB and ompA genes for the detection, respectively, of Rickettsia spp. and R. conorii DNA. Primers were designed following an analysis of Rickettsia gene sequences. The assays were optimized using SYBR Green and TaqMan methods and tested for sensitivity and specificity. This study allowed the development of powerful diagnostic methods, able to detect and quantify Rickettsia spp. DNA and differentiate R. conorii species.
An Underestimated Factor: The Extent of Cross-Reactions Modifying APIs in Surface-Modified Liposomal Preparations Caused by Comprised Activated Lipids
Authors: Sauter Max , Burhenne Jürgen , Haefeli Walter E. , Uhl Philipp
Published: September 2020

Despite the nowadays available plentitude of strategies to selectively introduce functional surface modification of liposomes, in preclinical research this process is still primarily performed after liposomal preparation utilizing comprised activated phospholipids with functionalized head groups. However, because these activated lipids are present during the liposomal preparation process, they can cross-react with incorporated drugs, especially the particularly often utilized active esters and maleimide groups. Macromolecular drugs, being composed of amino acids, are particularly prone to such cross-reactions due to their often multiple reactive functionalities such as amino and disulfide groups. To demonstrate this impact on the formulation in liposomal surface modification, we assessed the extent of cross-reaction during the liposomal preparation of two activated phospholipids with typically used head group functionalized phospholipids, with the two peptide drugs vancomycin and insulin comprising disulfide and amino functionalities. Both drugs revealed a considerable fraction of covalent modification (estimated 2 to 12%) generated during the liposome preparation process with comprised activated lipids. Modification of the active pharmaceutical ingredients (APIs) was determined by high-resolution mass spectrometric analysis. These findings clearly demonstrate the non-negligibility of potential cross reactions using the post preparation liposomal surface modification strategy in preclinical research.
The Relative Content and Distribution of Absorbed Volatile Organic Compounds in Rats Administered Asari Radix et Rhizoma Are Different between Powder- and Decoction-Treated Groups
Authors: Liu Guang-Xue , Xu Feng , Shang Ming-Ying , Wang Xuan , Cai Shao-Qing
Published: September 2020

Asari Radix et Rhizoma (ARR) is an important traditional Chinese medicine. Volatile organic compounds (VOCs) are the main active constituents of ARR. Research on the metabolite profile of VOCs and the difference of absorbed constituents in vivo after an administration of ARR decoction and powder will be helpful to understand the pharmacological activity and safety of ARR. In this study, headspace solid-phase microextraction gas chromatography mass spectrometry (HS–SPME–GC–MS) was applied to profile the VOCs from ARR in rats in vivo. A total of 153 VOCs were tentatively identified; 101 were original constituents of ARR (98 in the powder-treated group and 43 in the decoction-treated group) and 15 were metabolites, and their metabolic reactions were mainly oxidation and reduction, with only two cases of methylation and esterification, and 37 unclassified compounds were identified only in the ARR-treated group. Of the 153 VOCs identified, 131 were reported in rats after oral administration of ARR for the first time, containing 79 original constituents, 15 metabolites, and 37 unclassified compounds. In the powder-treated group, methyleugenol, safrole, 3,5-dimethoxytoluene (3,5-DMT), 2,3,5-trimethoxytoluene (2,3,5-TMT), and 3,4,5-trimethoxytoluene (3,4,5-TMT) were the main absorbed constituents, the relative contents of which were significantly higher compared to the decoction-treated group, especially methyleugenol, safrole, and 3,5-DMT. In the decoction-treated group, 3,4,5-TMT, 2,3,5-TMT, kakuol, and eugenol were the main constituents with a higher content and wider distribution. The results of this study provide a reference for evaluating the efficacy and safety of ARR.
Hetiamacin E and F, New Amicoumacin Antibiotics from Bacillus subtilis PJS Using MS/MS-Based Molecular Networking
Authors: Wang Ting , Lu Qinpei , Sun Chenghang , Lukianov Dmitrii , Osterman Ilya Andreevich , Sergiev Petr Vladimirovich , Dontsova Olga Anatolievna , Hu Xinxin , You Xuefu , Liu Shaowei , Wu Gang
Published: September 2020

To combat escalating levels of antibiotic resistance, novel strategies are developed to address the everlasting demand for new antibiotics. This study aimed at investigating amicoumacin antibiotics from the desert-derived Bacillus subtilis PJS by using the modern MS/MS-based molecular networking approach. Two new amicoumacins, namely hetiamacin E (1) and hetiamacin F (2), were finally isolated. The planar structures were determined by analysis of extensive NMR spectroscopic and HR–ESI–MS data, and the absolute configurations were concluded by analysis of the CD spectrum. Hetiamacin E (1) showed strong antibacterial activities against methicillin-sensitive and resistant Staphylococcus epidermidis at 2–4 µg/mL, and methicillin-sensitive and resistant Staphylococcus aureus at 8–16 µg/mL. Hetiamacin F (2) exhibited moderate antibacterial activities against Staphylococcus sp. at 32 µg/mL. Both compounds were inhibitors of protein biosynthesis demonstrated by a double fluorescent protein reporter system.
Comparative Study of Growth Morphologies of Ga2O3 Nanowires on Different Substrates
Authors: Alhalaili Badriyah , Vidu Ruxandra , Mao Howard , Islam M. Saif
Published: September 2020

Gallium oxide (Ga2O3) is a new wide bandgap semiconductor with remarkable properties that offers strong potential for applications in power electronics, optoelectronics, and devices for extreme conditions. In this work, we explore the morphology of Ga2O3 nanostructures on different substrates and temperatures. We used silver catalysts to enhance the growth of Ga2O3 nanowires on substrates such as p-Si substrate doped with boron, 250 nm SiO2 on n-Si, 250 nm Si3N4 on p-Si, quartz, and n-Si substrates by using a thermal oxidation technique at high temperatures (~1000 °C) in the presence of liquid silver paste that served as a catalyst layer. We present the results of the morphological, structural, and elemental characterization of the Ga2O3 nanostructures. This work offers in-depth explanation of the dense, thin, and long Ga2O3 nanowire growth directly on the surfaces of various types of substrates using silver catalysts.
Use of Silica Based Materials as Modulators of the Lipase Catalyzed Hydrolysis of Fats under Simulated Duodenal Conditions
Authors: Muñoz-Pina Sara , Amorós Pedro , Haskouri Jamal El , Andrés Ana , Ros-Lis José V.
Published: September 2020

The effect of silica materials and their functionalization in the lipase catalyzed fat hydrolysis has been scarcely studied. Fifteen silica materials were prepared and their effect on the fat hydrolysis was measured, under simulated duodenal conditions, using the pH-stat method. The materials are composed of the combination of three supports (Stöber massive silica nanoparticles, Stöber mesoporous nanoparticles and UVM-7) and four surface functionalizations (methyl, trimethyl, propyl and octyl). In addition, the non-functionalized materials were tested. The functional groups were selected to offer a hydrophobic character to the material improving the interaction with the fat globules and the lipase. The materials are able to modulate the lipase activity and their effect depending on the support topology and the organic covering, being able to increase or reduce the fat hydrolysis. Depending of the material, relative fat hydrolysis rates of 75 to 140% in comparison with absence of the material were obtained. The results were analyzed by Partial Least Square Regression and suggest that the alkyl modified mesopores are able to improve the fat hydrolysis, by contrast the non-porous nanoparticles and the textural pores tend to induce inhibition. The effects are more pronounced for materials containing long alkyl chains and/or in absence of taurodeoxycholate.
Enhanced Activity of Hierarchical Nanostructural Birnessite-MnO2-Based Materials Deposited onto Nickel Foam for Efficient Supercapacitor Electrodes
Authors: Hung Shang-Chao , Chou Yi-Rong , Dong Cheng-Di , Tsai Kuang-Chung , Yang Wein-Duo
Published: September 2020

Hierarchical porous birnessite-MnO2-based nanostructure composite materials were prepared on a nickel foam substrate by a successive ionic layer adsorption and reaction method (SILAR). Following composition with reduced graphene oxide (rGO) and multiwall carbon nanotubes (MWCNTs), the as-obtained MnO2, MnO2/rGO and MnO2/rGO-MWCNT materials exhibited pore size distributions of 2–8 nm, 5–15 nm and 2–75 nm, respectively. For the MnO2/rGO-MWCNT material in particular, the addition of MWCNT and rGO enhanced the superb distribution of micropores, mesopores and macropores and greatly improved the electrochemical performance. The as-obtained MnO2/rGO-MWCNT/NF electrode showed a specific capacitance that reached as high as 416 F·g−1 at 1 A·g−1 in 1 M Na2SO4 aqueous electrolyte and also an excellent rate capability and high cycling stability, with a capacitance retention of 85.6% after 10,000 cycles. Electrochemical impedance spectroscopy (EIS) analyses showed a low resistance charge transfer resistance for the as-prepared MnO2/rGO-MWCNT/NF nanostructures. Therefore, MnO2/rGO-MWCNT/NF composites were successfully synthesized and displayed enhanced electrochemical performance as potential electrode materials for supercapacitors.
Sustainable Production of Hydrogen by Steam Reforming of Ethanol Using Cobalt Supported on Nanoporous Zeolitic Material
Authors: da Costa-Serra Javier Francisco , Navarro Maria Teresa , Rey Fernando , Chica Antonio
Published: September 2020

Cobalt catalysts supported on Y zeolite and mesoporized Y zeolite (Y-mod) have been studied in steam reforming of ethanol (SRE). Specifically, the effect of the mesoporosity and the acidity of the y zeolite as a support has been explored. Mesoporous were generated on Y zeolite by treatment with NH4F and the acidity was neutralized by Na incorporation. Four cobalt catalysts supported on Y zeolite have been prepared, two using Y zeolite without mesoporous (Co/Y, Co/Y-Na), and two using Y zeolite with mesoporous (Co/Y-mod and Co/Y-mod-Na). All catalysts showed a high activity, with ethanol conversion values close to 100%. The main differences were found in the distribution of the reaction products. Co/Y and Co/Y-mod catalysts showed high selectivity to ethylene and low hydrogen production, which was explained by their high acidity. On the contrary, neutralization of the acid sites could explain the higher hydrogen selectivity and the lower ethylene yields exhibited by the Co/Y-Na and Co/Y-mod-Na. In addition, the physicochemical characterization of these catalysts by XRD, BET surface area, temperature-programmed reduction (TPR), and TEM allowed to connect the presence of mesoporous with the formation of metallic cobalt particles with small size, high dispersion, and with high interaction with the zeolitic support, explaining the high reforming activity exhibited by the co/y-mod-Na sample as well as its higher hydrogen selectivity. It has been also observed that the formation of coke is affected by the presence of mesoporous and acidity. Both properties seem to have an opposite effect on the reforming catalyst, decreasing and increasing the coke deposition, respectively.
Protective Effect of Glycomacropeptide on Food Allergy with Gastrointestinal Manifestations in a Rat Model through Down-Regulation of Type 2 Immune Response
Authors: Reyes-Pavón Diana , Cervantes-García Daniel , Bermúdez-Humarán Luis G. , Córdova-Dávalos Laura Elena , Quintanar-Stephano Andrés , Jiménez Mariela , Salinas Eva
Published: September 2020

Glycomacropeptide (GMP) is a bioactive peptide derived from milk κ-casein with immune-modulatory and anti-inflammatory properties. Food allergy (FA) is an adverse immune reaction with a broad spectrum of manifestations. Allergen intake induces persistent intestinal inflammation and tissue damage. In this study, the anti-allergic activity of GMP was evaluated using a rat ovalbumin (OVA)-induced FA model with gastrointestinal manifestation. Rats were orally GMP treated from 3 days prior and during FA development. The severity of food anaphylaxis and diarrheal episodes, antibody production and histamine level were measured. Histopathological changes, inflammation and predominant cytokine profile at intestine were analyzed. Oral GMP intake decreased clinical signs and diarrhea severity induced by allergen, with a significant reduction in intestinal edema and expression level of IL-1β and TNF-α. Prophylaxis with GMP also diminished serum anti-OVA IgE and IgG1, and histamine levels. GMP treatment markedly decreased eosinophil infiltration, mast cell and goblet cell hyperplasia, total IgE expression in intestine, and prevented histological changes in villi, crypts and internal muscularis layer. The treatment effectively suppressed IL-5, IL-13 and GATA3 expression and skewed the intestinal cytokine profile toward type 1 and regulatory. These results suggest that GMP may protect against FA through down-regulating the type 2 inflammatory response.
Fatty Acid Reference Intervals in Red Blood Cells among Pregnant Women in Norway–Cross Sectional Data from the ‘Little in Norway’ Cohort
Authors: Araujo Pedro , Kjellevold Marian , Nerhus Ive , Dahl Lisbeth , Aakre Inger , Moe Vibeke , Smith Lars , Markhus Maria Wik
Published: September 2020

There is a growing interest in determining fatty acid reference intervals from pregnancy cohort, especially considering the lack of reference values for pregnant women in the literature and the generalized misconception of equating reference intervals for nonpregnant women as equivalent to pregnant women. Seafood and supplements are important dietary sources for the omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA), such as eicosapentaenoic acid (EPA, 20:5ω-3), docosapentaenoic acid (DPA, 22:55ω-3), and docosahexaenoic acid (DHA, 22:6ω-3). Sufficient intake of EPA and DHA is vital during pregnancy for the development of the fetus, as well as for maintaining adequate levels for the mother. This study describes the fatty acid status and suggests reference values and cut-offs for fatty acids in red blood cells (RBC) from pregnant women (n = 247). An electronic food frequency questionnaire (e-FFQ) mapped the dietary habits of the participants, and gas chromatography was used to determine the fatty acid levels in RBC. The association between e-FFQ variables and fatty acid concentrations was established using a principal component analysis (PCA). Twenty-nine-point-one percent (29.1%) of the participants reported eating seafood as dinner according to the Norwegian recommendations, and they added in their diet as well a high percentage (76.9%) intake of ω-3 supplements. The concentration levels of fatty acids in RBC were in agreement with those reported in similar populations from different countries. The reference interval 2.5/97.5 percentiles for EPA, DPA, DHA were 0.23/2.12, 0.56/2.80, 3.76/10.12 in relative concentration units (%), and 5.99/51.25, 11.08/61.97, 64.25/218.08 in absolute concentration units (µg/g), respectively. The number of participants and their selection from all over Norway vouch for the representativeness of the study and the validity of the proposed reference values, and therefore, the study may be a useful tool when studying associations between fatty acid status and health outcome in future studies. To the best of our knowledge, this is the first PCA study reporting a direct association between ω-3 LCPUFA and intake of seafood and ω-3 supplements in a pregnancy cohort.
Co-Administration of Propionate or Protocatechuic Acid Does Not Affect DHA-Specific Transcriptional Effects on Lipid Metabolism in Cultured Hepatic Cells
Authors: Danesi Francesca , Larsen Bjørk D. , Di Nunzio Mattia , Nielsen Ronni , de Biase Dario , Valli Veronica , Mandrup Susanne , Bordoni Alessandra
Published: September 2020

Long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) are collectively recognized triglyceride-lowering agents, and their preventive action is likely mediated by changes in gene expression. However, as most studies employ fish oil, which contains a mixture of n-3 LC-PUFAs, the docosahexaenoic acid (DHA)-specific transcriptional effects on lipid metabolism are still unclear. The aim of the present study was to further elucidate the DHA-induced transcriptional effects on lipid metabolism in the liver, and to investigate the effects of co-administration with other bioactive compounds having effects on lipid metabolism. To this purpose, HepG2 cells were treated for 6 or 24 h with DHA, the short-chain fatty acid propionate (PRO), and protocatechuic acid (PCA), the main human metabolite of cyanidin-glucosides. Following supplementation, we mapped the global transcriptional changes. PRO and PCA alone had a very slight effect on the transcriptome; on the contrary, supplementation of DHA highly repressed the steroid and fatty acid biosynthesis pathways, this transcriptional modulation being not affected by co-supplementation. Our results confirm that DHA effect on lipid metabolism are mediated at least in part by modulation of the expression of specific genes. PRO and PCA could contribute to counteracting dyslipidemia through other mechanisms.
Nutritional Risk Screening Tools for Older Adults with COVID-19: A Systematic Review
Authors: Silva David Franciole Oliveira , Lima Severina Carla Vieira Cunha , Sena-Evangelista Karine Cavalcanti Mauricio , Marchioni Dirce Maria , Cobucci Ricardo Ney , Andrade Fábia Barbosa de
Published: September 2020

Coronavirus disease 2019 (COVID-19) is associated with high risk of malnutrition, primarily in older people; assessing nutritional risk using appropriate screening tools is critical. This systematic review identified applicable tools and assessed their measurement properties. Literature was searched in the MEDLINE, Embase, and LILACS databases. Four studies conducted in China met the eligibility criteria. Sample sizes ranged from six to 182, and participants’ ages from 65 to 87 years. Seven nutritional screening and assessment tools were used: the Nutritional Risk Screening 2002 (NRS-2002), the Mini Nutritional Assessment (MNA), the MNA-short form (MNA-sf), the Malnutrition Universal Screening Tool (MUST), the Nutritional Risk Index (NRI), the Geriatric NRI (GNRI), and modified Nutrition Risk in the Critically ill (mNUTRIC) score. Nutritional risk was identified in 27.5% to 100% of participants. The NRS-2002, MNA, MNA-sf, NRI, and MUST demonstrated high sensitivity; the MUST had better specificity. The MNA and MUST demonstrated better criterion validity. The MNA-sf demonstrated better predictive validity for poor appetite and weight loss; the NRS-2002 demonstrated better predictive validity for prolonged hospitalization. mNUTRIC score demonstrated good predictive validity for hospital mortality. Most instruments demonstrate high sensitivity for identifying nutritional risk, but none are acknowledged as the best for nutritional screening in older adults with COVID-19.
The Effect of Glyceraldehyde-Derived Advanced Glycation End Products on β-Tubulin-Inhibited Neurite Outgrowth in SH-SY5Y Human Neuroblastoma Cells
Authors: Nasu Ryuto , Furukawa Ayako , Suzuki Keita , Takeuchi Masayoshi , Koriyama Yoshiki
Published: September 2020

Nutritional factors can affect the risk of developing neurological disorders and their rate of progression. In particular, abnormalities of carbohydrate metabolism in diabetes mellitus patients lead to an increased risk of neurological disorders such as Alzheimer’s disease (AD). In this study, we investigated the relationship between nervous system disorder and the pathogenesis of AD by exposing SH-SY5Y neuroblastoma cells to glyceraldehyde (GA). We previously reported that GA-derived toxic advanced glycation end products (toxic AGEs, TAGE) induce AD-like alterations including intracellular tau phosphorylation. However, the role of TAGE and their target molecules in the pathogenesis of AD remains unclear. In this study, we investigated the target protein for TAGE by performing two-dimensional immunoblot analysis with anti-TAGE antibody and mass spectrometry and identified β-tubulin as one of the targets. GA treatment induced TAGE-β-tubulin formation and abnormal aggregation of β-tubulin, and inhibited neurite outgrowth in SH-SY5Y cells. On the other hand, glucose-derived AGEs were also involved in developing AD. However, glucose did not make abnormal aggregation of β-tubulin and did not inhibit neurite outgrowth. Understanding the underlying mechanism of TAGE-β-tubulin formation by GA and its role in neurodegeneration may aid in the development of novel therapeutics and neuroprotection strategies.
Nurses and Doctors Heroes? A Risky Myth of the COVID19 Era
Authors: Bellieni Carlo V.
Published: September 2020

Recent newspapers reports have named health professionals as “heroes”. This is surprising, because in the last few decades, doctors and nurses have been taken into account by mass media only to describe cases of misconduct or of violence. This change was due to the coronavirus pandemic scenario that has produced fear in the population and the need for an alleged “savior”. This need for health professionals seen as heroes is also disclosed by the fact that even politicians have abdicated to their role in favor of the healthcare “experts” to whom important decisions on social life during this pandemic have been delegated, even those decisions that fall outside of the specific health field. This commentary is a claim to framing the job of caregivers in its correct role, neither angel nor devil, but allied to the suffering person, that the image of “heroes” risks to overshadow.
Retrospective Case-Control Study of 2017 G2P[4] Rotavirus Epidemic in Rural and Remote Australia
Authors: Middleton Bianca F. , Danchin Margie , Quinn Helen , Ralph Anna P. , Pingault Nevada , Jones Mark , Estcourt Marie , Snelling Tom
Published: September 2020

Background: A widespread G2P[4] rotavirus epidemic in rural and remote Australia provided an opportunity to evaluate the performance of Rotarix and RotaTeq rotavirus vaccines, ten years after their incorporation into Australia’s National Immunisation Program. Methods: We conducted a retrospective case-control analysis. Vaccine-eligible children with laboratory-confirmed rotavirus infection were identified from jurisdictional notifiable infectious disease databases and individually matched to controls from the national immunisation register, based on date of birth, Aboriginal status and location of residence. Results: 171 cases met the inclusion criteria; most were Aboriginal and/or Torres Strait Islander (80%) and the median age was 19 months. Of these cases, 65% and 25% were fully or partially vaccinated, compared to 71% and 21% of controls. Evidence that cases were less likely than controls to have received a rotavirus vaccine dose was weak, OR 0.79 (95% CI, 0.46–1.34). On pre-specified subgroup analysis, there was some evidence of protection among children <12 months (OR 0.48 [95% CI, 0.22–1.02]), and among fully vs. partially vaccinated children (OR 0.65 [95% CI, 0.42–1.01]). Conclusion: Despite the known effectiveness of rotavirus vaccination, a protective effect of either rotavirus vaccine during a G2P[4] outbreak in these settings among predominantly Aboriginal children was weak, highlighting the ongoing need for a more effective rotavirus vaccine and public health strategies to better protect Aboriginal children.
Activation of Gingival Fibroblasts by Bacterial Cyclic Dinucleotides and Lipopolysaccharide
Authors: Elmanfi Samira , Sintim Herman O. , Zhou Jie , Gürsoy Mervi , Könönen Eija , Gürsoy Ulvi K.
Published: September 2020

Human gingival fibroblasts (HGFs) recognize microbe-associated molecular patterns (MAMPs) and respond with inflammatory proteins. Simultaneous impacts of bacterial cyclic di-guanosine monophosphate (c-di-GMP), cyclic di-adenosine monophosphate (c-di-AMP), and lipopolysaccharide (LPS) on gingival keratinocytes have been previously demonstrated, but the effects of these MAMPs on other periodontal cell types, such as gingival fibroblasts, remain to be clarified. The present aim was to examine the independent and combined effects of these cyclic dinucleotides and LPS on interleukin (IL) and matrix metalloproteinase (MMP) response of HGFs. The cells were incubated with c-di-GMP and c-di-AMP, either in the presence or absence of Porphyromonas gingivalis LPS, for 2 h and 24 h. The levels of IL-8, -10, and -34, and MMP-1, -2, and -3 secreted were measured by the Luminex technique. LPS alone or together with cyclic dinucleotides elevated IL-8 levels. IL-10 levels were significantly increased in the presence of c-di-GMP and LPS after 2 h but disappeared after 24 h of incubation. Concurrent treatment of c-di-AMP and LPS elevated MMP-1 levels, whereas c-di-GMP with LPS suppressed MMP-2 levels but increased MMP-3 levels. To conclude, we produce evidence that cyclic dinucleotides interact with LPS-mediated early response of gingival fibroblasts, while late cellular response is mainly regulated by LPS.
Biofilm Growth Causes Damage to Silicone Voice Prostheses in Patients after Surgical Treatment of Locally Advanced Laryngeal Cancer
Authors: Spałek Jakub , Deptuła Piotr , Cieśluk Mateusz , Strzelecka Agnieszka , Łysik Dawid , Mystkowska Joanna , Daniluk Tamara , Król Grzegorz , Góźdź Stanisław , Bucki Robert , Durnaś Bonita , Okła Sławomir
Published: September 2020

Voice prosthesis implantation with the creation of a tracheoesophageal fistula is the gold standard procedure for voice rehabilitation in patients after a total laryngectomy. All patients implanted with a voice prosthesis (VP) have biofilms of fungi and bacteria grow on their surface. Biofilm colonization is one of the main reasons for VP degradation that can lead to VP dysfunction, which increases the high risk of pneumonia. In a 20-month evaluation period, 129 cases of prostheses after replacement procedures were investigated. Microbiological examination of the biofilms revealed that there were four of the most common fungi species (Candida spp.) and a large variety of bacterial species present. We studied the relationship between the time of proper function of Provox VP, the microorganism composition of the biofilm present on it, and the degradation level of the silicone material. Evaluation of the surface of the removed VP using an atomic force microscope (AFM) has demonstrated that biofilm growth might drastically change the silicone’s mechanical properties. Changes in silicone stiffness and thermal properties might contribute to the failure of VP function. Our data can serve in future studies for the development of methods to prevent or inhibit biofilm formation on the VP surface that would translate to an increase in their durability and safety.
FUT2 Secretor Status Influences Susceptibility to VP4 Strain-Specific Rotavirus Infections in South African Children
Authors: MacDonald Jaime , Groome Michelle J. , Mans Janet , Page Nicola
Published: September 2020

Gastroenteritis is a preventable cause of morbidity and mortality worldwide. Rotavirus vaccination has significantly reduced the disease burden, but the sub-optimal vaccine efficacy observed in low-income regions needs improvement. Rotavirus VP4 ‘spike’ proteins interact with FUT2-defined, human histo-blood group antigens on mucosal surfaces, potentially influencing strain circulation and the efficacy of P[8]-based rotavirus vaccines. Secretor status was investigated in 500 children <5 years-old hospitalised with diarrhoea, including 250 previously genotyped rotavirus-positive cases (P[8] = 124, P[4] = 86, and P[6] = 40), and 250 rotavirus-negative controls. Secretor status genotyping detected the globally prevalent G428A single nucleotide polymorphism (SNP) and was confirmed by Sanger sequencing in 10% of participants. The proportions of secretors in rotavirus-positive cases (74%) were significantly higher than in the rotavirus-negative controls (58%; p < 0.001). The rotavirus genotypes P[8] and P[4] were observed at significantly higher proportions in secretors (78%) than in non-secretors (22%), contrasting with P[6] genotypes with similar proportions amongst secretors (53%) and non-secretors (47%; p = 0.001). This suggests that rotavirus interacts with secretors and non-secretors in a VP4 strain-specific manner; thus, secretor status may partially influence rotavirus VP4 wild-type circulation and P[8] rotavirus vaccine efficacy. The study detected a mutation (rs1800025) ~50 bp downstream of the G428A SNP that would overestimate non-secretors in African populations when using the TaqMan® SNP Genotyping Assay.
Bayesian Analysis of Three Methods for Diagnosis of Cystic Echinococcosis in Sheep
Authors: Bonelli Piero , Loi Federica , Cancedda Maria Giovanna , Peruzzu Angela , Antuofermo Elisabetta , Pintore Elisabetta , Piseddu Toni , Garippa Giovanni , Masala Giovanna
Published: September 2020

Diagnosis of cystic echinococcosis (CE) in sheep is essentially based on necropsy findings. Clinical symptoms can be easily overlooked, while the use of immunological tests is still not recommended for an intra vitam diagnosis. This study assessed the performances of three post-mortem laboratory methods in the diagnosis of ovine CE. In the absence of a single and accurate test as a gold standard, the results of multiple analytical tests can be combined to estimate diagnostic performance based on a Bayesian statistical approach. For this purpose, livers (n = 77), and lungs (n = 79) were sampled from adult sheep and examined using gross pathology, histopathology and molecular analyses. Data from the three diagnostic methods were analyzed using a Bayesian latent class analysis model to evaluate their diagnostic accuracy in terms of sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). The gross pathology examination revealed excellent diagnostic capabilities in diagnosing ovine CE with an Se of 99.7 (96.7–99.8), Sp of 97.5 (90.3–99.8), PPV of 97.6 (90.5–100), and NPV of 99.7 (96.5–100). The experimental design used in this work could be implemented as a validation protocol in a quality assurance system.
A New Type of Chronic Wound Infection after Wisdom Tooth Extraction: A Diagnostic Approach with 16S-rRNA Gene Analysis, Next-Generation Sequencing, and Bioinformatics
Authors: Böttger Sebastian , Zechel-Gran Silke , Streckbein Philipp , Knitschke Michael , Hain Torsten , Weigel Markus , Wilbrand Jan-Falco , Domann Eugen , Howaldt Hans-Peter , Attia Sameh
Published: September 2020

Delayed-onset infections are rare postoperative complications of lower third molar extractions. This article presents a case of a chronic combined hard and soft tissue infection after the extraction of a third molar, where the causative organisms could only be elucidated by molecular methods. Experimental 16S-rRNA gene analysis with next-generation sequencing and bioinformatics was used to identify the bacterial spectrum of the infection. 16S-rRNA gene analysis delivered the microbiome of the abscessing inflammation while standard culture and laboratory examinations were all sterile. The microbiome showed a mixed bacterial infection with a dominance of Delftia and Alcanivorax (spp.) besides other bacteria of the normal oral flora. Using 16S-rRNA-gene analysis, next-generation sequencing, and bioinformatics, a new type of chronic wound infection after wisdom tooth extraction was found. The property of Delftia and Alcanivorax (spp.) as water-affine environmental bacteria raises suspicion of infection from contaminated water from a dental unit. Thus, osteotomies of teeth should only be done with sterile cooling water. The 16S-rRNA gene analysis should become a part of the routine diagnostics in medical microbiology.
Adipokinetic Hormones Enhance the Efficacy of the Entomopathogenic Fungus Isaria fumosorosea in Model and Pest Insects
Authors: Gautam Umesh Kumar , Hlávková Daniela , Shaik Haq Abdul , Karaca Ismail , Karaca Gürsel , Sezen Kazim , Kodrík Dalibor
Published: September 2020

Insect adipokinetic hormones (AKHs) are neuropeptides with a wide range of actions, including the control of insect energy metabolism. These hormones are also known to be involved in the insect defence system against toxins and pathogens. In this study, our aim was to demonstrate whether the application of external AKHs significantly enhances the efficacy of the entomopathogenic fungus Isaria fumosorosea in a model species (firebug Pyrrhocoris apterus) and pest species (Egyptian cotton leafworm Spodoptera littoralis and pea aphid Acyrthosiphon pisum). It was found that the co-application of Isaria with AKHs significantly enhanced insect mortality in comparison to the application of Isaria alone. The mode of action probably involves an increase in metabolism that is caused by AKHs (evidenced by the production of carbon dioxide), which accelerates the turnover of Isaria toxins produced into the infected insects. However, several species-specific differences probably exist. Intoxication by Isaria elicited the stimulation of Akh gene expression and synthesis of AKHs. Therefore, all interactions between Isaria and AKH actions as well as their impact on insect physiology from a theoretical and practical point of view need to be discussed further.
Papain-Like Proteases as Coronaviral Drug Targets: Current Inhibitors, Opportunities, and Limitations
Authors: Petushkova Anastasiia I. , Zamyatnin Andrey A.
Published: September 2020

Papain-like proteases (PLpro) of coronaviruses (CoVs) support viral reproduction and suppress the immune response of the host, which makes CoV PLpro perspective pharmaceutical targets. Their inhibition could both prevent viral replication and boost the immune system of the host, leading to the speedy recovery of the patient. Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third CoV outbreak in the last 20 years. Frequent mutations of the viral genome likely lead to the emergence of more CoVs. Inhibitors for CoV PLpro can be broad-spectrum and can diminish present and prevent future CoV outbreaks as PLpro from different CoVs have conservative structures. Several inhibitors have been developed to withstand SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). This review summarizes the structural features of CoV PLpro, the inhibitors that have been identified over the last 20 years, and the compounds that have the potential to become novel effective therapeutics against CoVs in the near future.
Defining a Regulatory Strategy for ATMP/Aerosol Delivery Device Combinations in the Treatment of Respiratory Disease
Authors: Woods Niamh , MacLoughlin Ronan
Published: September 2020

Advanced Therapeutic Medicinal Products (ATMP) are a heterogenous group of investigational medicinal products at the forefront of innovative therapies with direct applicability in respiratory diseases. ATMPs include, but are not limited to, stem cells, their secretome, or extracellular vesicles, and each have shown some potential when delivered topically within the lung. This review focuses on that subset of ATMPs. One key mode of delivery that has enabling potential in ATMP validation is aerosol-mediated delivery. The selection of the most appropriate aerosol generator technology is influenced by several key factors, including formulation, patient type, patient intervention, and healthcare economics. The aerosol-mediated delivery of ATMPs has shown promise for the treatment of both chronic and acute respiratory disease in pre-clinical and clinical trials; however, in order for these ATMP device combinations to translate from the bench through to commercialization, they must meet the requirements set out by the various global regulatory bodies. In this review, we detail the potential for ATMP utility in the lungs and propose the nebulization of ATMPs as a viable route of administration in certain circumstances. Further, we provide insight to the current regulatory guidance for nascent ATMP device combination product development within the EU and US.