bluuebunny/crossref_metadata_2025 huggingface dataset:
Formulation and Nanotechnology-Based Approaches for Solubility and Bioavailability Enhancement of Zerumbone
Authors: Kesharwani Siddharth S. , Bhat G. Jayarama
Published: October 2020

About 40–70% of drug molecules in the clinical development pipeline suffer from one of either low aqueous solubility, poor absorption, or extremely low bioavailability. Approximately 75% of the world population relies on traditional therapies and therefore there has been a growing interest in the utilization of natural compounds. Zerumbone is one such natural compound, classified as a sesquiterpenoid that is extracted from the essential volatile oils of rhizomes from Zingiber zerumbet. It possesses strong antitumor, antioxidant, antimicrobial, and anti-inflammatory activity. However, despite promising preclinical studies demonstrating the therapeutic utility of zerumbone, its clinical development has been limited due to its low aqueous solubility, poor absorption, or associated low bioavailability. Multiple reviews demonstrating the pharmacological effects of zerumbone for various diseases have been published. However, to our knowledge, no review demonstrates the various formulation strategies developed to overcome the biopharmaceutical challenges of zerumbone. The purpose of this review is to provide a comprehensive perspective on zerumbone as a molecule for formulation development. A section related to pharmacokinetics, toxicity, and patents of zerumbone is included. This review provides the importance of developing novel formulations of zerumbone to overcome its biopharmaceutical challenges thereby advance its potential in the treatment of various diseases.
A Volumetric Heat Source Model for Thermal Modeling of Additive Manufacturing of Metals
Authors: Yang Yabin , Zhou Xin
Published: October 2020

In additive manufacturing of metallic materials, an accurate description of the thermal histories of the built part is important for further analysis of the distortions and residual stresses, which is a big issue for additively manufactured metal products. In the present paper, a computationally volumetric heat source model based on a semianalytical thermal modeling approach is proposed. The proposed model is applied to model the thermal response during a selective laser melting (SLM) process. The interaction between the laser and the material is described using a moving volumetric heat source. High computational efficiency can be achieved with considerable accuracy. Several case studies are conducted to examine the accuracy of the proposed model. By comparing with the experimentally measured melt-pool dimensions, it is found that the error between the predictions obtained by the proposed model and the experimental results can be controlled to less than 10%. High computational efficiency can also be achieved for the proposed model. It is shown that for simulating the thermal process of scanning a single layer with the dimension of 2 mm × 2 mm, the calculation can be finished in around 110 s.
Effect of Deformation on Precipitation and the Microstructure Evolution during Multistep Thermomechanical Processing of Al-Zn-Mg-Cu Alloy
Authors: Zuo Jinrong , Hou Longgang , Shu Xuedao , Peng Wenfei , Yin Anmin , Zhang Jishan
Published: October 2020

In order to obtain fine grained structure efficiently, a new multi-step rolling process (MSR: pre-deformation + intermediate annealing + hot deformation) was applied in Al-Zn-Mg-Cu plates. Conventional hot rolling (CHR) was also carried out as a contrast experiment. The evolution of microstructures and improvement of mechanical properties were analyzed by optical microscope, scanning electron microscope, transmission electron microscope, X-ray diffractometer, and tensile tests. The results show that the MSR process can obtain finer longitudinal grain size and better mechanical properties than CHR, which can be explained as follows: spheroidization of precipitates wrapped by high density dislocations could be promoted by increased pre-deformation; numerous ordered substructures were formed during short-period intermediate annealing at high temperature; in the subsequent hot rolling process, the retained spherical precipitates pinned dislocations and boundaries. With the increase of accumulated strain, low angle grain boundaries gradually transformed into high angle grain boundaries, leading to grain refinement. With the increased pre-deformation (MSR1 20 + 60%, MSR2 40 + 40%, MSR3 60 + 20%), the effect of grain refinement and plasticity improvement gradually weakened. The optimum thermomechanical process (MSR1 solid solution + pre-deformation (300 °C/20%) + intermediate annealing (430 °C/5 min) + hot deformation (400 °C/60%)) was obtained, which can increase elongation by ~25% compared with the CHR process, while maintaining similar high strength for reduced longitudinal grain size.
Multi-Targeted Metabolic Profiling of Carotenoids, Phenolic Compounds and Primary Metabolites in Goji (Lycium spp.) Berry and Tomato (Solanum lycopersicum) Reveals Inter and Intra Genus Biomarkers
Authors: Dumont Doriane , Danielato Giorgia , Chastellier Annie , Hibrand Saint Oyant Laurence , Fanciullino Anne-Laure , Lugan Raphaël
Published: October 2020

Metabolic profile is a key component of fruit quality, which is a challenge to study due to great compound diversity, especially in species with high nutritional value. This study presents optimized analytical methods for metabolic profiling in the fruits of three Solanaceae species: Lycium barbarum, Lycium chinense and Solanumlycopersicum. It includes the most important chemical classes involved in nutrition and taste, i.e., carotenoids, phenolic compounds and primary compounds. Emphasis has been placed on the systematic achievement of good extraction yields, sample stability, and high response linearity using common LC-ESI-TQ-MS and GC-EI-MS apparatuses. A set of 13 carotenoids, 46 phenolic compounds and 67 primary compounds were profiled in fruit samples. Chemometrics revealed metabolic markers discriminating Lycium and Solanum fruits but also Lycium barbarum and Lycium chinense fruits and the effect of the crop environment. Typical tomato markers were found to be lycopene, carotene, glutamate and GABA, while lycibarbarphenylpropanoids and zeaxanthin esters characterized goji (Lycium spp.) fruits. Among the compounds discriminating the Lycium species, reported here for the first time to our knowledge, chlorogenic acids, asparagine and quinic acid were more abundant in Lycium chinense, whereas Lycium barbarum accumulated more lycibarbarphenylpropanoids A-B, coumaric acid, fructose and glucose.
Cryptosporidium parvum Subverts Antimicrobial Activity of CRAMP by Reducing Its Expression in Neonatal Mice
Authors: Guesdon William , Pezier Tiffany , Menard Sandrine , Nicolosi Alessandra , Le Vern Yves , Silvestre Anne , Diana Julien , Laurent Fabrice , Lacroix-Lamandé Sonia
Published: October 2020

Cryptosporidium parvum causes diarrhea in infants under 5 years, in immunosuppressed individuals or in young ruminants. This parasite infects the apical side of ileal epithelial cells where it develops itself and induces inflammation. Antimicrobial peptides (AMPs) are part of the innate immune response, playing a major role in the control of the acute phase of C. parvum infection in neonates. Intestinal AMP production in neonates is characterized by high expressions of Cathelicidin Related Antimicrobial Peptide (CRAMP), the unique cathelicidin in mice known to fight bacterial infections. In this study, we investigated the role of CRAMP during cryptosporidiosis in neonates. We demonstrated that sporozoites are sensitive to CRAMP antimicrobial activity. However, during C. parvum infection the intestinal expression of CRAMP was significantly and selectively reduced, while other AMPs were upregulated. Moreover, despite high CRAMP expression in the intestine of neonates at homeostasis, the depletion of CRAMP did not worsen C. parvum infection. This result might be explained by the rapid downregulation of CRAMP induced by infection. However, the exogenous administration of CRAMP dampened the parasite burden in neonates. Taken together these results suggest that C. parvum impairs the production of CRAMP to subvert the host response, and highlight exogenous cathelicidin supplements as a potential treatment strategy.
The Mobile Colistin Resistance Gene, mcr-1.1, Is Carried on IncX4 Plasmids in Multidrug Resistant E. coli Isolated from Rainbow Trout Aquaculture
Authors: Hassan Jouman , Eddine Razan Zein , Mann David , Li Shaoting , Deng Xiangyu , Saoud Imad P. , Kassem Issmat I.
Published: October 2020

Colistin, a last resort antibiotic, is important for controlling infections with carbapenem-resistant Enterobacteriaceae. The recent emergence of mobile-colistin-resistance (mcr) genes has threatened the effectiveness of colistin. Aquaculture is hypothesized to be a major contributor to the evolution and dissemination of mcr. However, data on mcr in aquaculture are limited. Here, the occurrence of mcr-1 was assessed in Rainbow Trout in Lebanon, a country with developing antimicrobial stewardship and an established use of colistin for medical and farming purposes. mcr-1 was detected in 5 Escherichia coli isolated from fish guts. The isolates were classified as multidrug-resistant and their colistin minimum inhibitory concentration ranged between 16 and 32 μg/mL. Whole genome sequencing analysis showed that mcr-1 was carried on transmissible IncX4 plasmids and that the isolates harbored more than 14 antibiotic resistance genes. The isolates belonged to ST48 and ST101, which have been associated with mcr and can occur in humans and fish. The mcr-1-positive E. coli persisted in 6-day biofilms, but there was a potential fitness cost. Given the status of infrastructure in Lebanon, there is a high potential for the dissemination of mcr via aquatic environments. Urgent actions are needed to control mcr and to enhance antimicrobial stewardship in Lebanon.
Multinucleated Giant Cell Formation as a Portal to Chronic Bacterial Infections
Authors: Stockton Jacob L. , Torres Alfredo G.
Published: October 2020

This review provides a snapshot of chronic bacterial infections through the lens of Burkholderia pseudomallei and detailing its ability to establish multi-nucleated giant cells (MNGC) within the host, potentially leading to the formation of pyogranulomatous lesions. We explore the role of MNGC in melioidosis disease progression and pathology by comparing the similarities and differences of melioidosis to tuberculosis, outline the concerted events in pathogenesis that lead to MNGC formation, discuss the factors that influence MNGC formation, and consider how they fit into clinical findings reported in chronic cases. Finally, we speculate about future models and techniques that can be used to delineate the mechanisms of MNGC formation and function.
Prevention of Clostridium difficile Infection and Associated Diarrhea: An Unsolved Problem
Authors: Principi Nicola , Gnocchi Margherita , Gagliardi Martina , Argentiero Alberto , Neglia Cosimo , Esposito Susanna
Published: October 2020

For many years, it has been known that Clostridium difficile (CD) is the primary cause of health-care-associated infectious diarrhea, afflicting approximately 1% of hospitalized patients. CD may be simply carried or lead to a mild disease, but in a relevant number of patients, it can cause a very severe, potentially fatal, disease. In this narrative review, the present possibilities of CD infection (CDI) prevention will be discussed. Interventions usually recommended for infection control and prevention can be effective in reducing CDI incidence. However, in order to overcome limitations of these measures and reduce the risk of new CDI episodes, novel strategies have been developed. As most of the cases of CDI follow antibiotic use, attempts to rationalize antibiotic prescriptions have been implemented. Moreover, to reconstitute normal gut microbiota composition and suppress CD colonization in patients given antimicrobial drugs, administration of probiotics has been suggested. Finally, active and passive immunization has been studied. Vaccines containing inactivated CD toxins or components of CD spores have been studied. Passive immunization with monoclonal antibodies against CD toxins or the administration of hyperimmune whey derived from colostrum or breast milk from immunized cows has been tried. However, most advanced methods have significant limitations as they cannot prevent colonization and development of primary CDI. Only the availability of vaccines able to face these problems can allow a resolutive approach to the total burden due to this pathogen.
Longer Ubiquinone Side Chains Contribute to Enhanced Farnesol Resistance in Yeasts
Authors: Pathirana Ruvini U. , Boone Cory , Nickerson Kenneth W.
Published: October 2020

Ubiquinones (UQ) are intrinsic lipid components of many membranes. Besides their role in electron-transfer reactions there is evidence for them acting as free radical scavengers, yet their other roles in biological systems have received little study. The dimorphic fungal pathogen Candida albicans secretes farnesol as both a virulence factor and a quorum-sensing molecule. Thus, we were intrigued by the presence of UQ9 isoprenologue in farnesol-producing Candida species while other members of this genera harbor UQ7 as their major electron carrier. We examined the effect of UQ side chain length in Saccharomyces cerevisiae and C. albicans with a view towards identifying the mechanisms by which C. albicans protects itself from the high levels of farnesol it secretes, levels that are toxic to many other fungi including S. cerevisiae. In this study, we identify UQ9 as the major UQ isoprenoid in C. albicans, regardless of growth conditions or cell morphology. A S. cerevisiae model yeast engineered to make UQ9 instead of UQ6 was 4–5 times more resistant to exogenous farnesol than the parent yeast and this resistance was accompanied by greatly reduced reactive oxygen species (ROS) production. The resistance provided by UQ9 is specific for farnesol in that it does not increase resistance to high salt (1M NaCl) or other oxidants (5 mM H2O2 or 1 mM menadione). Additionally, the protection provided by UQ9 appears to be structural rather than transcriptional; UQ9 does not alter key transcriptional responses to farnesol stress. Here, we propose a model in which the longer UQ side chains are more firmly embedded in the mitochondrial membrane making them harder to pry out, so that in the presence of farnesol they remain functional without producing excess ROS. C. albicans and Candida dubliniensis evolved to use UQ9 rather than UQ7 as in other Candida species or UQ6 as in S. cerevisiae. This adaptive mechanism highlights the significance of UQ side chains in farnesol production and resistance quite apart from being an electron carrier in the respiratory chain.
More than Pneumonia: Distinctive Features of SARS-Cov-2 Infection. From Autopsy Findings to Clinical Implications: A Systematic Review
Authors: D’Errico Stefano , Zanon Martina , Montanaro Martina , Radaelli Davide , Sessa Francesco , Di Mizio Giulio , Montana Angelo , Corrao Salvatore , Salerno Monica , Pomara Cristoforo
Published: October 2020

Despite safety recommendations for the management of corpses with COVID-19 infection and the high number of deaths worldwide, the post-mortem investigation rate is extremely low as well as the scientific contributions describing the pathological features. The first results of post-mortem investigations provided interesting findings and contributed to promoting unexplored therapeutic approaches and new frontiers of research. A systematic review is provided with the aim of summarizing all autopsy studies up to February 2020 in which a complete post-mortem investigation in patients with COVID-19 disease was performed, focusing on histopathological features. We included case reports, case series, retrospective and prospective studies, letters to the editor, and reviews. A total of 28 studies fulfilled the inclusion criteria, producing a pooled dataset of 407 full autopsies. Analyzing the medical history data, only 12 subjects had died without any comorbidities (for 15 cases the data were not available). The post-mortem investigation highlighted that acute respiratory distress syndrome (ARDS) and multiple organ failure represent the main clinical features of COVID-19 disease, often leading to pulmonary thromboembolism and superimposed bronchopneumonia. The discussed data showed a strict relationship among the inflammatory processes, diffuse alveolar, and endothelial damage. In light of these results, the full autopsy can be considered as the gold standard to investigate unknown infections or pathogens resulting in death.
Anti-neoplastic Potential of Flavonoids and Polysaccharide Phytochemicals in Glioblastoma
Authors: Atiq Ayesha , Parhar Ishwar
Published: October 2020

Clinically, gliomas are classified into four grades, with grade IV glioblastoma multiforme being the most malignant and deadly, which accounts for 50% of all gliomas. Characteristically, glioblastoma involves the aggressive proliferation of cells and invasion of normal brain tissue, outcomes as poor patient prognosis. With the current standard therapy of glioblastoma; surgical resection and radiotherapy followed by adjuvant chemotherapy with temozolomide, it remains fatal, because of the development of drug resistance, tumor recurrence, and metastasis. Therefore, the need for the effective therapeutic option for glioblastoma remains elusive. Previous studies have demonstrated the chemopreventive role of naturally occurring pharmacological agents through preventing or reversing the initiation phase of carcinogenesis or arresting the cancer progression phase. In this review, we discuss the role of natural phytochemicals in the amelioration of glioblastoma, with the aim to improve therapeutic outcomes, and minimize the adverse side effects to improve patient’s prognosis and enhancing their quality of life.
Synthesis of Oxide Iron Nanoparticles Using Laser Ablation for Possible Hyperthermia Applications
Authors: Rivera-Chaverra María J. , Restrepo-Parra Elisabeth , Acosta-Medina Carlos D. , Mello Alexandre. , Ospina Rogelio.
Published: October 2020

In this work, iron oxide nanoparticles produced using the laser ablation technique were studied in order to determine the characteristics of these nanoparticles as a function of the laser energy for the possible application in magnetic hyperthermia. Nanoparticles were obtained by varying the power of the laser considering values of 90, 173, 279 and 370 mJ. The morphology of these nanoparticles was determined using the dynamic light scattering (DLS) and scattering transmission electron microscopy (STEM) techniques, confirming that the size of the particles was in the order of nanometers. A great influence of the laser power on the particle size was also observed, caused by the competition between the energy and the temperature. The composition was determined by X-ray diffraction and Raman spectroscopy, showing the presence of magnetite, maghemite and hematite. The hyperthermia measurements showed that the temperature rise of the iron oxide nanoparticles was not greatly influenced by the energy change, the heating capacity of magnetic NPs is quantified by the specific absorption rate (SAR), that tends to decrease with increasing energy, which indicates a dependence of these values on the nanoparticles concentration.
Experimental Studies on the Dynamic Memcapacitance Modulation of the ReO3@ReS2 Composite Material-Based Diode
Authors: Borowiec Joanna , Liu Mengren , Liang Weizheng , Kreouzis Theo , Bevan Adrian J. , He Yi , Ma Yao , Gillin William P.
Published: October 2020

In this study, both memcapacitive and memristive characteristics in the composite material based on the rhenium disulfide (ReS2) rich in rhenium (VI) oxide (ReO3) surface overlayer (ReO3@ReS2) and in the indium tin oxide (ITO)/ReO3@ReS2/aluminum (Al) device configuration is presented. Comprehensive experimental analysis of the ReO3@ReS2 material properties’ dependence on the memcapacitor electrical characteristics was carried out by standard as well as frequency-dependent current–voltage, capacitance–voltage, and conductance–voltage studies. Furthermore, determination of the charge carrier conduction model, charge carrier mobility, density of the trap states, density of the available charge carrier, free-carrier concentration, effective density of states in the conduction band, activation energy of the carrier transport, as well as ion hopping was successfully conducted for the ReO3@ReS2 based on the experimental data. The ITO/ReO3@ReS2/Al charge carrier conduction was found to rely on the mixed electronic–ionic processes, involving electrochemical metallization and lattice oxygen atoms migration in response to the externally modulated electric field strength. The chemical potential generated by the electronic–ionic ITO/ReO3@ReS2/Al resistive memory cell non-equlibrium processes leads to the occurrence of the nanobattery effect. This finding supports the possibility of a nonvolatile memory cell with a new operation principle based on the potential read function.
Stress and Refractive Index Control of SiO2 Thin Films for Suspended Waveguides
Authors: Wostbrock Neal , Busani Tito
Published: October 2020

Film stress and refractive index play an important role in the fabrication of suspended waveguides. SiO2 waveguides were successfully fabricated on multiple substrates including Si, Ge, and Al2O3 wafers; the waveguides were deposited using inductively coupled plasma chemical vapor deposition at 100 °C. The precursor gases were SiH4 and N2O at 1:3 and 1:9 ratios with variable flow rates. The occurrence of intrinsic stress was validated through the fabrication of suspended SiO2 bridges, where the curvature of the bridge corresponded to measured intrinsic stress, which measured less than 1 µm thick and up to 50 µm in length. The flow rates allow film stress tunability between 50 and −65 MPa, where a negative number indicates a compressive state of the SiO2. We also found that the gas ratios have a slight influence on the refractive index in the UV and visible range but do not affect the stress in the SiO2 bridges. To test if this method can be used to produce multi-layer devices, three layers of SiO2 bridges with air cladding between each bridge were fabricated on a silicon substrate. We concluded that a combination of low temperature deposition (100 °C) and photoresist as the sacrificial layer allows for versatile SiO2 bridge fabrication that is substrate and refractive index independent, providing a framework for future tunable waveguide fabrication.
Recent Advances in Nanostructured Transition Metal Carbide- and Nitride-Based Cathode Electrocatalysts for Li–O2 Batteries (LOBs): A Brief Review
Authors: Karuppasamy K. , Prasanna K. , Jothi Vasanth Rajendiran , Vikraman Dhanasekaran , Hussain Sajjad , Hwang Jung-Hoon , Kim Hyun-Seok
Published: October 2020

A large volume of research on lithium–oxygen (Li–O2) batteries (LOBs) has been conducted in the recent decades, inspired by their high energy density and power density. However, these future generation energy-storage devices are still subject to technical limitations, including a squat round-trip efficiency and a deprived rate-capability, due to the slow-moving electrochemical kinetics of both the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) over the surface of the cathode catalyst. Because the electrochemistry of LOBs is rather complex, only a limited range of cathode catalysts has been employed in the past. To understand the catalytic mechanisms involved and improve overall cell performance, the development of new cathode electrocatalysts with enhanced round-trip efficiency is extremely important. In this context, transition metal carbides and nitrides (TMCs and TMNs, respectively) have been explored as potential catalysts to overcome the slow kinetics of electrochemical reactions. To provide an accessible and up-to-date summary for the research community, the present paper reviews the recent advancements of TMCs and TMNs and its applications as active electrocatalysts for LOBs. In particular, significant studies on the rational design of catalysts and the properties of TMC/TMN in LOBs are discussed, and the prospects and challenges facing the continued development of TMC/TMN electrocatalysts and strategies for attaining higher OER/ORR activity in LOBs are presented.
Preparation of Fe3+ Doped High-Ordered TiO2 Nanotubes Arrays with Visible Photocatalytic Activities
Authors: Zhang Jin , Yang Chen , Li Shijie , Xi Yingxue , Cai Changlong , Liu Weiguo , Golosov Dmitriy , Zavadski Sergry , Melnikov Siarhei
Published: October 2020

In this paper, the Fe3+ doped rutile phase TiO2 nanotubes arrays (NTAs) were prepared in a low temperature water-assistant crystallization method. It is noteworthy that the Fe3+ doping hardly hinders either the crystallization of rutile TiO2 NTAs or the highly-ordered nanotubular morphologies. Moreover, Fe3+ did not form other compound impurities, which indicated that Fe3+ substitute Ti4+ into the lattice of TiO2. With the introduction of Fe3+, the light absorption range of TiO2 NTAs extends from the ultraviolet band to the visible light range. Photocatalytic testing results indicate that Fe3+ doped TiO2 NTAs can effectively improve the degradation rate of methyl orange aqueous solution in visible light, and the TiO2 NTAs with 0.2 mol/L Fe3+ doping exhibits the highest photocatalytic degradation efficiency.
Bonding of Gold Nanoclusters on Graphene with and without Point Defects
Authors: Pavloudis Theodoros , Kioseoglou Joseph , Palmer Richard E.
Published: October 2020

Hybrid nanostructures of size-selected nanoparticles (NPs) and 2D materials exhibit striking physical and chemical properties and are attractive for many technology applications. A major issue for the performance of these applications is device stability. In this work, we investigate the bonding of cuboctahedral, decahedral and icosahedral Au NPs comprising 561 atoms on graphene sheets via 103-atom scale ab initio spin-polarized calculations. Two distinct cases we considered: (i) the Au NPs sit with their (111) facets on graphene and (ii) the NPs are oriented with a vertex on graphene. In both cases, we compare the binding energies with and without a graphene vacancy under the NP. We find that in all cases, the presence of the graphene vacancy enhances the bonding of the NPs. Significantly, in the vertex-on-graphene case, the binding energy is considerably increased by several eVs and becomes similar to the (111) facet-on-graphene case. The strain in the NPs is found to be minimal and the displacement of the carbon atoms in the immediate neighborhood of the vacancy is on the 0.1 Å scale. The work suggests the creation of stable NP-graphene systems for a variety of electronic, chemical and photonic applications.
Structural and Optical Properties of Self-Catalyzed Axially Heterostructured GaPN/GaP Nanowires Embedded into a Flexible Silicone Membrane
Authors: Koval Olga Yu. , Fedorov Vladimir V. , Bolshakov Alexey D. , Fedina Sergey V. , Kochetkov Fedor M. , Neplokh Vladimir , Sapunov Georgiy A. , Dvoretckaia Liliia N. , Kirilenko Demid A. , Shtrom Igor V. , Islamova Regina M. , Cirlin George E. , Tchernycheva Maria , Serov Alexey Yu. , Mukhin Ivan S.
Published: October 2020

Controlled growth of heterostructured nanowires and mechanisms of their formation have been actively studied during the last decades due to perspectives of their implementation. Here, we report on the self-catalyzed growth of axially heterostructured GaPN/GaP nanowires on Si(111) by plasma-assisted molecular beam epitaxy. Nanowire composition and structural properties were examined by means of Raman microspectroscopy and transmission electron microscopy. To study the optical properties of the synthesized nanoheterostructures, the nanowire array was embedded into the silicone rubber membrane and further released from the growth substrate. The reported approach allows us to study the nanowire optical properties avoiding the response from the parasitically grown island layer. Photoluminescence and Raman studies reveal different nitrogen content in nanowires and parasitic island layer. The effect is discussed in terms of the difference in vapor solid and vapor liquid solid growth mechanisms. Photoluminescence studies at low temperature (5K) demonstrate the transition to the quasi-direct gap in the nanowires typical for diluted nitrides with low N-content. The bright room temperature photoluminescent response demonstrates the potential application of nanowire/polymer matrix in flexible optoelectronic devices.
Effects of Euglena gracilis Intake on Mood and Autonomic Activity under Mental Workload, and Subjective Sleep Quality: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Nakashima Ayaka , Yasuda Kosuke , Murata Ako , Suzuki Kengo , Miura Naoki
Published: October 2020

While the human body maintains homeostasis by altering the balance in the autonomic nervous, endocrine, and immune systems, a prolonged imbalance in these systems can result in physical and mental symptoms, including a decline in sleep quality and work efficiency. Euglenagracilis (Euglena) is a single-celled microalga with the properties of both plants and animals and contains abundant nutrients, such as vitamins, minerals, amino acids, and fatty acids, which have various beneficial health effects. This study evaluated the effects of Euglena intake on the mood states and stress coping under mental workload tasks, and subjective sleep quality. We assigned men and women aged 20 to 64 years to Euglena and placebo intake groups, and measured indices related to the autonomic nervous system, psychological states, and sleep quality together with the application of workload stress before food intake, and 4, 8, and 12 weeks after commencing intake. Euglena intake regulated the autonomic nervous system under a workload and improved psychological parameters and sleep conditions. These results indicate that the consumption of Euglena may regulate the balance of the autonomic nervous system during stress and may have a favorable effect on psychological status and sleep quality.
A Novel Bead-Based Immunoassay for the Measurement of Heat Shock Proteins 27 and 70
Authors: Njemini Rose , Verhaeghen Katrijn , Mets Tony , Weets Ilse , Bautmans Ivan
Published: October 2020

Heat shock proteins (HSPs) play an essential role in protecting proteins from denaturation and are implicated in diverse pathophysiological conditions like cardiovascular diseases, cancer, infections, and neurodegenerative diseases. Scientific evidence indicates that if HSP expression falls below a certain level, cells become sensitive to oxidative damage that accelerates protein aggregation diseases. On the other hand, persistently enhanced levels of HSP can lead to inflammatory and oncogenic changes. To date, although techniques for measuring HSPs exist, these assays are limited for use in specific sample types or are time consuming. Therefore, in the present study, we developed a single-molecule assay digital ELISA technology (Single Molecule Array—SIMOA) for the measurement of HSPs, which is time effective and can be adapted to measure multiple analytes simultaneously from a single sample. This technique combines two distinct HSP-specific antibodies that recognize different epitopes on the HSP molecule. A recombinant human HSP protein was used as the standard material. The assay performance characteristics were evaluated by repeated testing of samples spiked with HSP peptide at different levels. The limit of detection was 0.16 and 2 ng/mL for HSP27 and HSP70, respectively. The inter- and intra-assay coefficients of variation were less than 20% in all tested conditions for both HSPs. The HSP levels assayed after serial dilution of samples portrayed dilutional linearity (on average 109%, R2 = 0.998, p < 0.001, for HSP27 and 93%, R2 = 0.994, p < 0.001, for HSP70). A high linear response was also demonstrated with admixtures of plasma exhibiting relatively very low and high levels of HSP70 (R2 = 0.982, p < 0.001). Analyte spike recovery varied between 57% and 95%. Moreover, the relative HSP values obtained using Western blotting correlated significantly with HSP values obtained with the newly developed SIMOA assay (r = 0.815, p < 0.001 and r = 0.895, p < 0.001 for HSP70 and HSP27, respectively), indicating that our method is reliable. In conclusion, the assay demonstrates analytical performance for the accurate assessment of HSPs in various sample types and offers the advantage of a huge range of dilution linearity, indicating that samples with HSP concentration highly above the calibration range can be diluted into range without affecting the precision of the assay.
Listeria monocytogenes Infection of Bat Pipistrellus nathusii Epithelial cells Depends on the Invasion Factors InlA and InlB
Authors: Povolyaeva Olga , Chalenko Yaroslava , Kalinin Egor , Kolbasova Olga , Pivova Elena , Kolbasov Denis , Yurkov Sergey , Ermolaeva Svetlana
Published: October 2020

L. monocytogenes is a widespread facultative intracellular pathogen. The range of natural hosts that supporting L. monocytogenes persistence in the environment has not been fully established yet. In this study, we were interested in the potential of L. monocytogenes to infect cells of bats, which are being increasingly recognized as a reservoir for microorganisms that are pathogenic to humans and domestic animals. A stable epithelial cell line was developed from the kidneys of Pipistrellus nathusii, a small bat widely distributed across Europe. The wild-type L. monocytogenes strain EGDe infected this cell line with an invasion efficiency of 0.0078 ± 0.0009%. Once it entered bat cells, L. monocytogenes doubled within about 70 min. When L. monocytogenes lacked either of the major invasion factors, InlA and InlB, invasion efficiency decreased by a factor of 10 and 25 respectively (p < 0.000001). The obtained results suggest that bat epithelial cells are susceptible to L. monocytogenes infection and that L. monocytogenes invasion of bat cells depends on the major invasion factors InlA and InlB. These results constitute the first report on in vitro studies of L. monocytogenes infection in bats.
Regulation of the MIE Locus During HCMV Latency and Reactivation
Authors: Dooley Abigail L. , O’Connor Christine M.
Published: October 2020

Human cytomegalovirus (HCMV) is a ubiquitous herpesviral pathogen that results in life-long infection. HCMV maintains a latent or quiescent infection in hematopoietic cells, which is broadly defined by transcriptional silencing and the absence of de novo virion production. However, upon cell differentiation coupled with immune dysfunction, the virus can reactivate, which leads to lytic replication in a variety of cell and tissue types. One of the mechanisms controlling the balance between latency and reactivation/lytic replication is the regulation of the major immediate-early (MIE) locus. This enhancer/promoter region is complex, and it is regulated by chromatinization and associated factors, as well as a variety of transcription factors. Herein, we discuss these factors and how they influence the MIE locus, which ultimately impacts the phase of HCMV infection.
Chronic Viral Hepatitis in a Cohort of Inflammatory Bowel Disease Patients from Southern Italy: A Case-Control Study
Authors: Losurdo Giuseppe , Iannone Andrea , Contaldo Antonella , Barone Michele , Ierardi Enzo , Di Leo Alfredo , Principi Mariabeatrice
Published: October 2020

We performed an epidemiologic study to assess the prevalence of chronic viral hepatitis in inflammatory bowel disease (IBD) and to detect their possible relationships. Methods: It was a single centre cohort cross-sectional study, during October 2016 and October 2017. Consecutive IBD adult patients and a control group of non-IBD subjects were recruited. All patients underwent laboratory investigations to detect chronic hepatitis B (HBV) and C (HCV) infection. Parameters of liver function, elastography and IBD features were collected. Univariate analysis was performed by Student’s t or chi-square test. Multivariate analysis was performed by binomial logistic regression and odds ratios (ORs) were calculated. We enrolled 807 IBD patients and 189 controls. Thirty-five (4.3%) had chronic viral hepatitis: 28 HCV (3.4%, versus 5.3% in controls, p = 0.24) and 7 HBV (0.9% versus 0.5% in controls, p = 0.64). More men were observed in the IBD–hepatitis group (71.2% versus 58.2%, p < 0.001). Patients with IBD and chronic viral hepatitis had a higher mean age and showed a higher frequency of diabetes, hypertension and wider waist circumference. They suffered more frequently from ulcerative colitis. Liver stiffness was greater in subjects with IBD and chronic viral hepatitis (7.0 ± 4.4 versus 5.0 ± 1.2 KPa; p < 0.001). At multivariate analysis, only old age directly correlated with viral hepatitis risk (OR = 1.05, 95%CI 1.02–1.08, p < 0.001). In conclusion, the prevalence of HBV/HCV in IBD is low in our region. Age may be the only independent factor of viral hepatitis–IBD association. Finally, this study firstly measured liver stiffness in a large scale, showing higher values in subjects with both diseases.
Research on Integrated Management for Cattle Fever Ticks and Bovine Babesiosis in the United States and Mexico: Current Status and Opportunities for Binational Coordination
Authors: Esteve-Gasent Maria D. , Rodríguez-Vivas Roger I. , Medina Raúl F. , Ellis Dee , Schwartz Andy , Cortés Garcia Baltazar , Hunt Carrie , Tietjen Mackenzie , Bonilla Denise , Thomas Don , Logan Linda L. , Hasel Hallie , Alvarez Martínez Jesús A. , Hernández-Escareño Jesús J. , Mosqueda Gualito Juan , Alonso Díaz Miguel A. , Rosario-Cruz Rodrigo , Soberanes Céspedes Noé , Merino Charrez Octavio , Howard Tami , Chávez Niño Victoria M. , Pérez de León Adalberto A.
Published: October 2020

Bovine babesiosis is a reportable transboundary animal disease caused by Babesia bovis and Babesiabigemina in the Americas where these apicomplexan protozoa are transmitted by the invasive cattle fever ticks Rhipicephalus (Boophilus) microplus and Rhipicephalus(Boophilus) annulatus. In countries like Mexico where cattle fever ticks remain endemic, bovine babesiosis is detrimental to cattle health and results in a significant economic cost to the livestock industry. These cattle disease vectors continue to threaten the U.S. cattle industry despite their elimination through efforts of the Cattle Fever Tick Eradication Program. Mexico and the U.S. share a common interest in managing cattle fever ticks through their economically important binational cattle trade. Here, we report the outcomes of a meeting where stakeholders from Mexico and the U.S. representing the livestock and pharmaceutical industry, regulatory agencies, and research institutions gathered to discuss research and knowledge gaps requiring attention to advance progressive management strategies for bovine babesiosis and cattle fever ticks. Research recommendations and other actionable activities reflect commitment among meeting participants to seize opportunities for collaborative efforts. Addressing these research gaps is expected to yield scientific knowledge benefitting the interdependent livestock industries of Mexico and the U.S. through its translation into enhanced biosecurity against the economic and animal health impacts of bovine babesiosis and cattle fever ticks.
Recombinant Myxoma Virus-Derived Immune Modulator M-T7 Accelerates Cutaneous Wound Healing and Improves Tissue Remodeling
Authors: Yaron Jordan R. , Zhang Liqiang , Guo Qiuyun , Awo Enkidia A. , Burgin Michelle , Schutz Lauren N. , Zhang Nathan , Kilbourne Jacquelyn , Daggett-Vondras Juliane , Lowe Kenneth M. , Lucas Alexandra R.
Published: October 2020

Complex dermal wounds represent major medical and financial burdens, especially in the context of comorbidities such as diabetes, infection and advanced age. New approaches to accelerate and improve, or “fine tune” the healing process, so as to improve the quality of cutaneous wound healing and management, are the focus of intense investigation. Here, we investigate the topical application of a recombinant immune modulating protein which inhibits the interactions of chemokines with glycosaminoglycans, reducing damaging or excess inflammation responses in a splinted full-thickness excisional wound model in mice. M-T7 is a 37 kDa-secreted, virus-derived glycoprotein that has demonstrated therapeutic efficacy in numerous animal models of inflammatory immunopathology. Topical treatment with recombinant M-T7 significantly accelerated wound healing when compared to saline treatment alone. Healed wounds exhibited properties of improved tissue remodeling, as determined by collagen maturation. M-T7 treatment accelerated the rate of peri-wound angiogenesis in the healing wounds with increased levels of TNF, VEGF and CD31. The immune cell response after M-T7 treatment was associated with a retention of CCL2 levels, and increased abundances of arginase-1-expressing M2 macrophages and CD4 T cells. Thus, topical treatment with recombinant M-T7 promotes a pro-resolution environment in healing wounds, and has potential as a novel treatment approach for cutaneous tissue repair.
Impact of Glycosylation and Species Origin on the Uptake and Permeation of IgGs through the Nasal Airway Mucosa
Authors: Ladel Simone , Maigler Frank , Flamm Johannes , Schlossbauer Patrick , Handl Alina , Hermann Rebecca , Herzog Helena , Hummel Thomas , Mizaikoff Boris , Schindowski Katharina
Published: October 2020

Although we have recently reported the involvement of neonatal Fc receptor (FcRn) in intranasal transport, the transport mechanisms are far from being elucidated. Ex vivo porcine olfactory tissue, primary cells from porcine olfactory epithelium (OEPC) and the human cell line RPMI 2650 were used to evaluate the permeation of porcine and human IgG antibodies through the nasal mucosa. IgGs were used in their wild type and deglycosylated form to investigate the impact of glycosylation. Further, the expression of FcRn and Fc-gamma receptor (FCGR) and their interaction with IgG were analyzed. Comparable permeation rates for human and porcine IgG were observed in OEPC, which display the highest expression of FcRn. Only traces of porcine IgGs could be recovered at the basolateral compartment in ex vivo olfactory tissue, while human IgGs reached far higher levels. Deglycosylated human IgG showed significantly higher permeation in comparison to the wild type in RPMI 2650 and OEPC, but insignificantly elevated in the ex vivo model. An immunoprecipitation with porcine primary cells and tissue identified FCGR2 as a potential interaction partner in the nasal mucosa. Glycosylation sensitive receptors appear to be involved in the uptake, transport, but also degradation of therapeutic IgGs in the airway epithelial layer.
Comparison of Downstream Processing of Nanocrystalline Solid Dispersion and Nanosuspension of Diclofenac Acid to Develop Solid Oral Dosage Form
Authors: Jadhav Sanika , Kaur Amanpreet , Bansal Arvind Kumar
Published: October 2020

The conventional “top-down”, “bottom-up” and “combination” approaches of generating drug nanocrystals produce a “nanosuspension” (NS). It requires significant downstream processing for drying the liquid by suitable means followed by its granulation to develop an oral solid dosage form (OSD). In this paper, we used a novel, spray drying-based NanoCrySP technology for the generation of drug nanocrystals in the form of nanocrystalline solid dispersion (NCSD). We hypothesized that the NCSD would require minimal downstream processing since the nanocrystals are obtained in powder form during spray drying. We further compared downstream processing of NS and NCSD of diclofenac acid (DCF) prepared by wet media milling and NanoCrySP technology, respectively. The NS and NCSD were characterized for crystallinity, crystal size, assay and dissolution. The NCSD was physically mixed with 0.3% Aerosil® 200, 1.76% croscarmellose sodium (CCS) and 0.4% sodium stearyl fumarate (SSF) and filled into size 0 hard gelatin capsules. The NS was first wet granulated using Pearlitol® SD 200 (G1 granules) and Celphere® 203 (G2 granules) in a fluidized bed processor, and the resulting granules were mixed using the same extra granular excipients as NCSD and filled into capsules. A discriminatory dissolution method was developed to monitor changes in dissolution behavior due to crystal growth during processing. Cost analysis and comparison of process efficiency was performed using an innovation radar tool. The NS and NCSD were successfully fabricated with a crystal size of 363 ± 21.87 and 361.61 ± 11.78, respectively. In comparison to NCSD-based capsules (65.13%), the G1 and G2 granules showed crystal growth and decrease in dissolution to 52.68% and 48.37%, respectively, in 120 min. The overall cost for downstream processing of NCSD was up to 80% lower than that of NS. An innovation radar tool also concluded that the one-step NanoCrySP technology was more efficient and required less downstream processing than the two-step wet media milling approach for conversion of nanocrystals to OSD.
Characterization of Absorption Losses and Transient Thermo-Optic Effects in a High-Power Laser System
Authors: Gorajek Lukasz , Gontar Przemyslaw , Jabczynski Jan , Firak Jozef , Stefaniak Marek , Dabrowski Miroslaw , Orzanowski Tomasz , Trzaskawka Piotr , Sosnowski Tomasz , Firmanty Krzysztof , Miczuga Marcin , Barela Jaroslaw , Kopczynski Krzysztof
Published: October 2020

(1) Background: The modeling, characterization, and mitigation of transient lasers, thermal stress, and thermo-optic effects (TOEs) occurring inside high energy lasers have become hot research topics in laser physics over the past few decades. The physical sources of TOEs are the un-avoidable residual absorption and scattering in the volume and on the surface of passive and active laser elements. Therefore, it is necessary to characterize and mitigate these effects in real laser systems under high-power operations. (2) Methods: The laboratory setup comprised a 10-kW continuous wave laser source with a changeable beam diameter, and dynamic registration of the transient temperature profiles was applied using an infrared camera. Modeling using COMSOL Multiphysics enabled matching of the surface and volume absorption coefficients to the experimental data of the temperature profiles. The beam quality was estimated from the known optical path differences (OPDs) occurring within the examined sample. (3) Results: The absorption loss coefficients of dielectric coatings were determined for the evaluation of several coating technologies. Additionally, OPDs for typical transmissive and reflective elements were determined. (4) Conclusions: The idea of dynamic self-compensation of transient TOEs using a tailored design of the considered transmissive and reflecting elements is proposed.