bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Laser Shock Peening Parameters on Residual Stresses and Corrosion Fatigue of AA5083
Authors: Kaufman Jan , Špirit Zbyněk , Vasudevan Vijay Krishnaswami , Steiner Matthew Alan , Mannava Seetha Ramaiah , Brajer Jan , Pína Ladislav , Mocek Tomáš
Published: October 2021

Aluminium alloy 5083 was subjected to Laser Shock Peening both with (LSP) and without protective coating (LPwC) at multiple pulse densities. A second LPwC treatment was conducted fully submersed under water, in addition to the standard laminar water flow condition. The results show that compressive residual stresses were generated in all cases, although their character varied depending on the peening strategy and method of confinement. In all cases, higher pulse density lead to an increase in compressive stresses with a saturation point of −325 MPa at 1089 p/cm2 for the LPwC treatments. Corrosion fatigue testing of sensitized samples then showed 59% and 69% improvement in fatigue strength after the LSP and LPwC treatments, respectively.
The Recovery of Cu, Co, Zn, and Mn from a Complex Oxide Ore Using an Enhanced Reduction Leaching
Authors: Seo Sangyun , Han Kyu Sung , Lee Sung Il , Kim Myong Jun
Published: October 2021

The processing of Cu, Co, and Zn at the Boleo project in Mexico involves two-stage (oxidation–reduction) leaching to extract a total of 85–88% Cu in 4 h. The first stage is an oxidation leaching using sulphuric acid (120 kg/tonne ore) at an Eh of 900 mV for 2 h. Then, the reduction stage takes place in 2 h with SO2 gas sparging for Mn and Co extraction at an Eh of 350–370 mV. The final extraction rates of metal values are 92% of Mn, 80% of Co, and 60% of Co, respectively, after 4 h of leaching at 70 °C. However, the same metal recoveries were obtained within 2 h using an equal amount of sulphuric acid and the addition of 25 kg of SO2 per tonne of ore in a single stage leaching in this research. In this case, the Fe extracted from the ore as Fe2+/Fe3+ is believed to have acted as an electrochemical couple contiguously leaching the Cu sulphide and Mn oxides, which also increased the Cu recovery as the Cu mineralised mostly intergrowths in these mineral structure matrices. A significant improvement was made in which the leaching time was halved to 2 h compared to 4 h in the previous plant design and current operation, involving the two-stage oxidation–reduction leaching.
Interfacial Behavior and Shear Strength of Al-25Si-4Cu-1Mg Joints by Transient Liquid Phase Bonding with Cu as Interlayer
Authors: Qi Kai , Xu Guo , Wang Fengjiang
Published: October 2021

Spray-formed hypereutectic Al-Si-Cu-Mg alloy is the candidate for automotive and aerospace industries due to its superior wear resistance, lower thermal expansion coefficient and density, and higher thermal conductivity. This paper aims to investigate the bonding properties of hypereutectic Al-25Si-4Cu-1Mg alloys using the transient liquid phase (TLP) method with Cu as an interlayer. To obtain the suitable bonding parameters, the interfacial microstructure and shear strength of Al-25Si-4Cu-1Mg joints were investigated with the effect of different bonding temperatures and holding times. The results showed that TLP bonding between Al-Si-Mg-Cu alloy was mainly realized by large amounts of Al2Cu intermetallic compounds (IMCs), primary Si and α-Al phases. With the brazing temperature increasing, the width of the brazing seam gradually increased, and the voids began to be produced. With the holding time increasing, θ-Al2Cu phases approached into the base metal and Si particles in the brazing seam were obviously coarsened. With the formation of θ-Al2Cu phases into the base metal, more Si particles were segregated at the interface between brazing seam and base metal, and the shear test confirmed that it was the weakest bonding location. Finally, the effect of bonding parameters on the joint strength indicated that the joint brazed at 540 °C for 7.5 min presented the best shear performance with the shear strength reaching 75 MPa because the size of Si particles in the brazing seam was closest to the size of Si particles in base metal under this parameter.
Growth and Drug Interaction Monitoring of NIH 3T3 Cells by Image Analysis and Capacitive Biosensor
Authors: Lee Gayoung , Jeong Jaehun , Kim Yeeun , Kang Dahyun , Shin Sooyong , Lee Jongwon , Jeon Sung Ho , Jang Moongyu
Published: October 2021

Capacitive biosensors are manufactured on glass slides using the semiconductor process to monitor cell growth and cell–drug interactions in real time. Capacitance signals are continuously monitored for each 10 min interval during a 48 h period, with the variations of frequency from 1 kHz to 1 MHz. The capacitance values showed a gradual increase with the increase in NIH 3T3 cell numbers. After 48 h of growth, 6.67 μg/mL puromycin is injected for the monitoring of the cell–drug interaction. The capacitance values rapidly increased during a period of about 10 h, reflecting the rapid increase in the cell numbers. In this study, we monitored the state of cells and the cell–drug interactions using the developed capacitive biosensor. Additionally, we monitored the state of cell behavior using a JuLiTM Br&FL microscope. The monitoring of cell state by means of a capacitive biosensor is more sensitive than confluence measuring using a JuLiTM Br&FL microscope image. The developed capacitive biosensor could be applied in a wide range of bio-medical areas; for example, non-destructive real-time cell growth and cell–drug interaction monitoring.
Environmental Drivers and Potential Distribution of Schistosoma mansoni Endemic Areas in Ethiopia
Authors: Ponpetch Keerati , Erko Berhanu , Bekana Teshome , Kebede Tadesse , Tian Di , Yang Yang , Liang Song
Published: October 2021

In Ethiopia, human schistosomiasis is caused by two species of schistosome, Schistosoma mansoni and S. haematobium, with the former being dominant in the country, causing infections of more than 5 million people and more than 37 million at risk of infection. What is more, new transmission foci for S. mansoni have been reported over the past years in the country, raising concerns over the potential impacts of environmental changes (e.g., climate change) on the disease spread. Knowledge on the distribution of schistosomiasis endemic areas and associated drivers is much needed for surveillance and control programs in the country. Here we report a study that aims to examine environmental determinants underlying the distribution and suitability of S. mansoni endemic areas at the national scale of Ethiopia. The study identified that, among five physical environmental factors examined, soil property, elevation, and climatic factors (e.g., precipitation and temperature) are key factors associated with the distribution of S. mansoni endemic areas. The model predicted that the suitable areas for schistosomiasis transmission are largely distributed in northern, central, and western parts of the country, suggesting a potentially wide distribution of S. mansoni endemic areas. The findings of this study are potentially instrumental to inform public health surveillance, intervention, and future research on schistosomiasis in Ethiopia. The modeling approaches employed in this study may be extended to other schistosomiasis endemic regions and to other vector-borne diseases.
SARS-CoV-2 Evolution among Oncological Population: In-Depth Virological Analysis of a Clinical Cohort
Authors: Laubscher Florian , Cordey Samuel , Friedlaender Alex , Schweblin Cecilia , Noetzlin Sarah , Simand Pierre-François , Bordry Natacha , De Sousa Filipe , Pigny Fiona , Baggio Stephanie , Getaz Laurent , Dietrich Pierre-Yves , Kaiser Laurent , Vu Diem-Lan
Published: October 2021

Background: Oncological patients have a higher risk of prolonged SARS-CoV-2 shedding, which, in turn, can lead to evolutionary mutations and emergence of novel viral variants. The aim of this study was to analyze biological samples of a cohort of oncological patients by deep sequencing to detect any significant viral mutations. Methods: High-throughput sequencing was performed on selected samples from a SARS-CoV-2-positive oncological patient cohort. Analysis of variants and minority variants was performed using a validated bioinformatics pipeline. Results: Among 54 oncological patients, we analyzed 12 samples of 6 patients, either serial nasopharyngeal swab samples or samples from the upper and lower respiratory tracts, by high-throughput sequencing. We identified amino acid changes D614G and P4715L as well as mutations at nucleotide positions 241 and 3037 in all samples. There were no other significant mutations, but we observed intra-host evolution in some minority variants, mainly in the ORF1ab gene. There was no significant mutation identified in the spike region and no minority variants common to several hosts. Conclusions: There was no major and rapid evolution of viral strains in this oncological patient cohort, but there was minority variant evolution, reflecting a dynamic pattern of quasi-species replication.
Staphylococcus aureus Transcriptome Data and Metabolic Modelling Investigate the Interplay of Ser/Thr Kinase PknB, Its Phosphatase Stp, the glmR/yvcK Regulon and the cdaA Operon for Metabolic Adaptation
Authors: Liang Chunguang , Rios-Miguel Ana B. , Jarick Marcel , Neurgaonkar Priya , Girard Myriam , François Patrice , Schrenzel Jacques , Ibrahim Eslam S. , Ohlsen Knut , Dandekar Thomas
Published: October 2021

Serine/threonine kinase PknB and its corresponding phosphatase Stp are important regulators of many cell functions in the pathogen S. aureus. Genome-scale gene expression data of S. aureus strain NewHG (sigB+) elucidated their effect on physiological functions. Moreover, metabolic modelling from these data inferred metabolic adaptations. We compared wild-type to deletion strains lacking pknB, stp or both. Ser/Thr phosphorylation of target proteins by PknB switched amino acid catabolism off and gluconeogenesis on to provide the cell with sufficient components. We revealed a significant impact of PknB and Stp on peptidoglycan, nucleotide and aromatic amino acid synthesis, as well as catabolism involving aspartate transaminase. Moreover, pyrimidine synthesis was dramatically impaired by stp deletion but only slightly by functional loss of PknB. In double knockouts, higher activity concerned genes involved in peptidoglycan, purine and aromatic amino acid synthesis from glucose but lower activity of pyrimidine synthesis from glucose compared to the wild type. A second transcriptome dataset from S. aureus NCTC 8325 (sigB−) validated the predictions. For this metabolic adaptation, PknB was found to interact with CdaA and the yvcK/glmR regulon. The involved GlmR structure and the GlmS riboswitch were modelled. Furthermore, PknB phosphorylation lowered the expression of many virulence factors, and the study shed light on S. aureus infection processes.
Preliminary Risk Assessment of Dam Failure at the Location of the Cukaru Peki Deposit, Bor (Serbia)
Authors: Nišić Dragana
Published: October 2021

Industrial waste landfills, as evidenced by frequent accidents occurring in recent years, are regarded as one of the most hazardous facilities in the world. For the adequate management of a landfill, risk assessments of dam failures should be performed before operations begin. This paper deals with the preliminary risk assessment used for the tailings and pyrite concentrate storage facilities, as well as the drainage waters reservoir, which are currently at the development and construction stage in the Cukaru Peki deposit located in eastern Serbia. The research was conducted to establish the facts and level of risk at an early stage to allow for timely prevention of potential accidents and bring operational practice in line with design requirements. The annual failure probability was estimated using a semi-empirical method, based on the dam stability factor. While, the framework proposed by the New Zealand Society on Large Dams was applied to assess the consequences of potential failures. The risk was assessed as a function of accident probability and the severity of possible consequences, and a 7 × 7 risk matrix was applied for analysis and evaluation. The level of dam failure risk at the location of the Cukaru Peki deposit was preliminarily assessed as moderate and conditionally tolerable, based on a low estimated probability of accident and a significant severity of consequences. Once the operation of these facilities starts risk assessments should be regularly updated, in order to maintain this level, and in accordance with the current situation, the modelling of specific accident scenarios should be included.
Study on Magnetite Ore Crushing Assisted by Microwave Irradiation
Authors: Hao Jiawang , Li Qingwen , Qiao Lan
Published: October 2021

High energy consumption in ore crushing brings great challenges to the mining industry. Microwave irradiation provides a promising solution for rock breaking. However, there is currently a lack of detailed understanding of the microwave parameters regarding magnetite ore. The purpose of this study is to fully understand the potential value of microwave irradiation applied in auxiliary crushing of magnetite ore. It is typically found that increasing power reduces the mechanical properties of ore, increasing energy utilization, and crushing degree, more than extending time. Based on wave impedance, this reveals the dependence of energy utilization on thermal damage. Increasing irradiation power, time and cooling rate will cause more transgranular cracks and cleavage tears in the crushed ore. Based on the separate microwave response of several minerals, the microwave-damage mechanism of magnetite ore is further demonstrated.
A FORTRAN Program to Model Magnetic Gradient Tensor at High Susceptibility Using Contraction Integral Equation Method
Authors: Chen Longwei , Ouyang Fang
Published: October 2021

The magnetic gradient tensor provides a powerful tool for detecting magnetic bodies because of its ability to emphasize detailed features of the magnetic anomalies. To interpret field measurements obtained by magnetic gradiometry, the forward calculation of magnetic gradient fields is always necessary. In this paper, we present a contraction integral equation method to simulate the gradient fields produced by 3-D magnetic bodies of arbitrary shapes and high susceptibilities. The method employs rectangular prisms to approximate the source region with the assumption that the magnetization in each element is homogeneous. The gradient fields are first solved in the Fourier domain and then transformed into the spatial domain by 2-D Gauss-FFT. This calculation is performed iteratively until the required accuracy is reached. The convergence of the iterative procedure is ensured by a contraction operator. To facilitate application, we introduce a FORTRAN program to implement the algorithm. This program is intended for users who show interests in 3D magnetic modeling at high susceptibility. The performance of the program, including its computational accuracy, efficiency and convergence behavior, is tested by several models. Numerical results show that the code is computationally accurate and efficient, and performs well at a wide range of magnetic susceptibilities from 0 SI to 1000 SI. This work, therefore, provides a significant tool for 3D forward modeling of magnetic gradient fields at high susceptibility.
The Development History and Latest Progress of Deep-Sea Polymetallic Nodule Mining Technology
Authors: Kang Yajuan , Liu Shaojun
Published: October 2021

Deep-sea polymetallic nodules are a mineral resource with potential for commercial development. Due to the unique deep-sea environment in which they are found, specialized technology and equipment are required for their extraction. In this paper, firstly, the development of deep-sea polymetallic nodule mining technology is classified into three stages, and its characteristics are summarized. Moreover, the results from research into deep-sea polymetallic nodule mining technology are analyzed, including proposals for mining systems, research into key technologies, basic scientific problems, and proof of technical feasibility from sea tests. Secondly, the testing of the collector prototype and the environmental impact assessment study of Global Sea Mineral Resources NV, as well as the progress of the deep-sea polymetallic nodule mining test project in China, are introduced. On this basis, the opportunities and challenges brought by the fast-growing demand for electric vehicles to the development of deep-sea polymetallic mining technology is analyzed, and a possible technical scheme for a mining system and the trends in its development towards high reliability and high standards of environmental protection according to the requirements of commercial exploitation are explored. This provides a reference for the research and development of high-efficiency technology and equipment for the mining of deep-sea polymetallic nodules.
Determination of Potentially Harmful Element (PHE) Distribution in Water Bodies in Krugersdorp, a Mining City in the West Rand, Gauteng Province, South Africa
Authors: Shapi Michael , Jordaan Maryam Amra , Mbambo Andile Truelove , Davies Theophilus Clavell , Chirenje Emmanuel , Dube Mpumelelo
Published: October 2021

The town of Krugersdorp in South Africa is the locus of an important wildlife game reserve, the Krugersdorp Game Reserve (KGR), which is juxtaposed by the (<1000 m) down-gradient of the large-scale gold mining outfits of Mintails Mogale Gold (MMG) and Rand Uranium (RU). The aim of the study was to determine the concentration levels of potentially harmful elements (PHEs) that have accumulated due to post-mining activities in the local water bodies in Krugersdorp and to use these data as a prerequisite and basis for formulation of the most appropriate remediation measures. Thirty water samples were collected and analysed in situ for: water temperature, pH, dissolved oxygen (mgl−1), dissolved oxygen (%), total dissolved solids (TDS), oxidation/reduction potential (ORP), and electrical conductivity (EC). This was later followed by laboratory analyses of aliquots of the water samples by ICP-MS for twelve PHEs whose concentration ranges were: As (0.70–32.20), Ag (0.16–105.00), Al (1.00–41.00), Co (0.07–6.16), Cr (1.60–5.00), Cu (0.80–8.00), Fe (23.00–117.00), Mn (0.14–12 255.00), Ni (0.20–7.00), Pb (0.80–6.30), V (1.90–55.20), and Zn (2.20–783.00). Areas of the town where excessive concentration levels of these elements have negatively impacted the health of its wildlife population and surrounding ecosystems are identified, and credible mitigation measures proffered.
Excellent Bipolar Resistive Switching Characteristics of Bi4Ti3O12 Thin Films Prepared via Sol-Gel Process
Authors: Zhou He-Chun , Jiang Yan-Ping , Tang Xin-Gui , Liu Qiu-Xiang , Li Wen-Hua , Tang Zhen-Hua
Published: October 2021

Herein, Bi4Ti3O12 (BIT) ferroelectric thin films were fabricated into Au/BIT/LaNiO3/Si structures to demonstrate their memristor properties. Repeatable and stable bipolar resistive switching (RS) characteristics of the device are first reported in this work. The switching ratio of the device annealed in air reached approximately 102 at 0.1 and −0.1 V. The RS performance was not significantly degraded after 100 consecutive cycles of testing. We also explored the factors affecting the RS behavior of the device. By investigating the RS characteristics of the devices annealed in O2, and in combination with XPS analysis, we found that the RS properties were closely related to the presence of oxygen vacancies. The devices annealed in air exhibited a markedly improved RS effect over those annealed in O2. According to the slope fitting, the conduction mechanism of the device was the ohmic conduction and space charge limited current (SCLC). This study is the first to successfully apply BIT ferroelectric films to the RS layers of memristors. Additionally, a theory of conductive filaments is proposed to adequately explain the relationship between RS behavior and oxygen vacancies, providing meaningful inspiration for designing high-quality resistive random access memory devices.
Statistically Representative Metrology of Nanoparticles via Unsupervised Machine Learning of TEM Images
Authors: Wen Haotian , Luna-Romera José María , Riquelme José C. , Dwyer Christian , Chang Shery L. Y.
Published: October 2021

The morphology of nanoparticles governs their properties for a range of important applications. Thus, the ability to statistically correlate this key particle performance parameter is paramount in achieving accurate control of nanoparticle properties. Among several effective techniques for morphological characterization of nanoparticles, transmission electron microscopy (TEM) can provide a direct, accurate characterization of the details of nanoparticle structures and morphology at atomic resolution. However, manually analyzing a large number of TEM images is laborious. In this work, we demonstrate an efficient, robust and highly automated unsupervised machine learning method for the metrology of nanoparticle systems based on TEM images. Our method not only can achieve statistically significant analysis, but it is also robust against variable image quality, imaging modalities, and particle dispersions. The ability to efficiently gain statistically significant particle metrology is critical in advancing precise particle synthesis and accurate property control.
Localized Energy Band Bending in ZnO Nanorods Decorated with Au Nanoparticles
Authors: Bruno Luca , Strano Vincenzina , Scuderi Mario , Franzò Giorgia , Priolo Francesco , Mirabella Salvo
Published: October 2021

Surface decoration by means of metal nanostructures is an effective way to locally modify the electronic properties of materials. The decoration of ZnO nanorods by means of Au nanoparticles was experimentally investigated and modelled in terms of energy band bending. ZnO nanorods were synthesized by chemical bath deposition. Decoration with Au nanoparticles was achieved by immersion in a colloidal solution obtained through the modified Turkevich method. The surface of ZnO nanorods was quantitatively investigated by Scanning Electron Microscopy, Transmission Electron Microscopy and Rutherford Backscattering Spectrometry. The Photoluminescence and Cathodoluminescence of bare and decorated ZnO nanorods were investigated, as well as the band bending through Mott–Schottky electrochemical analyses. Decoration with Au nanoparticles induced a 10 times reduction in free electrons below the surface of ZnO, together with a decrease in UV luminescence and an increase in visible-UV intensity ratio. The effect of decoration was modelled with a nano-Schottky junction at ZnO surface below the Au nanoparticle with a Multiphysics approach. An extensive electric field with a specific halo effect formed beneath the metal–semiconductor interface. ZnO nanorod decoration with Au nanoparticles was shown to be a versatile method to tailor the electronic properties at the semiconductor surface.
Choice Architecture Cueing to Healthier Dietary Choices and Physical Activity at the Workplace: Implementation and Feasibility Evaluation
Authors: Rantala Eeva , Vanhatalo Saara , Tilles-Tirkkonen Tanja , Kanerva Markus , Hansen Pelle Guldborg , Kolehmainen Marjukka , Männikkö Reija , Lindström Jaana , Pihlajamäki Jussi , Poutanen Kaisa , Karhunen Leila , Absetz Pilvikki
Published: October 2021

Redesigning choice environments appears a promising approach to encourage healthier eating and physical activity, but little evidence exists of the feasibility of this approach in real-world settings. The aim of this paper is to portray the implementation and feasibility assessment of a 12-month mixed-methods intervention study, StopDia at Work, targeting the environment of 53 diverse worksites. The intervention was conducted within a type 2 diabetes prevention study, StopDia. We assessed feasibility through the fidelity, facilitators and barriers, and maintenance of implementation, building on implementer interviews (n = 61 informants) and observations of the worksites at six (t1) and twelve months (t2). We analysed quantitative data with Kruskall–Wallis and Mann–Whitney U tests and qualitative data with content analysis. Intervention sites altogether implemented 23 various choice architectural strategies (median 3, range 0–14 strategies/site), employing 21 behaviour change mechanisms. Quantitative analysis found implementation was successful in 66%, imperfect in 25%, and failed in 9% of evaluated cases. These ratings were independent of the ease of implementation of applied strategies and reminders that implementers received. Researchers’ assistance in intervention launch (p = 0.02) and direct contact to intervention sites (p < 0.001) predicted higher fidelity at t1, but not at t2. Qualitative content analysis identified facilitators and barriers related to the organisation, intervention, worksite environment, implementer, and user. Contributors of successful implementation included apt implementers, sufficient implementer training, careful planning, integration into worksite values and activities, and management support. After the study, 49% of the worksites intended to maintain the implementation in some form. Overall, the choice architecture approach seems suitable for workplace health promotion, but a range of practicalities warrant consideration while designing real-world implementation.
Prebiotic Galactooligosaccharide Supplementation in Adults with Ulcerative Colitis: Exploring the Impact on Peripheral Blood Gene Expression, Gut Microbiota, and Clinical Symptoms
Authors: Wilson Bridgette , Eyice Özge , Koumoutsos Ioannis , Lomer Miranda C. , Irving Peter M. , Lindsay James O. , Whelan Kevin
Published: October 2021

Prebiotics may promote immune homeostasis and reduce sub-clinical inflammation in humans. This study investigated the effect of prebiotic galactooligosaccharide (GOS) supplementation in colonic inflammation. Seventeen patients with active ulcerative colitis (UC) consumed 2.8 g/d GOS for 6 weeks. At baseline and 6 weeks, gene expression (microarray), fecal calprotectin (ELISA), microbiota (16S rRNA), short-chain fatty acids (SCFAs; gas-liquid chromatography), and clinical outcomes (simple clinical colitis activity index (SCCAI), gastrointestinal symptom rating scale (GSRS), and Bristol stool form scale (BSFS)) were measured. Following prebiotics, clinical scores (SCCAI), fecal calprotectin, SCFAs, and pH were unchanged. Five genes were upregulated and two downregulated. Normal stool proportion (BSFS) increased (49% vs. 70%, p = 0.024), and the incidence (46% vs. 23%, p = 0.016) and severity (0.7 vs. 0.5, p = 0.048) of loose stool (GSRS), along with urgency (SCCAI) scores (1.0 vs. 0.5, p = 0.011), were reduced. In patients with a baseline SCCAI ≤2, prebiotics increased the relative abundance of Bifidobacterium from 1.65% (1.97) to 3.99% (5.37) (p = 0.046) and Christensenellaceae from 0.13% (0.33) to 0.31% (0.76) (p = 0.043). Prebiotics did not lower clinical scores or inflammation but normalized stools. Bifidobacterium and Christensenellaceae proportions only increased in patients with less active diseases, indicating that the prebiotic effect may depend on disease activity. A controlled study is required to validate these observations.
Dietary Phytoestrogens Ameliorate Hydrochloric Acid-Induced Chronic Lung Injury and Pulmonary Fibrosis in Mice
Authors: Solopov Pavel , Colunga Biancatelli Ruben Manuel Luciano , Dimitropoulou Christiana , Catravas John D.
Published: October 2021

We previously reported that female mice exhibit protection against chemically induced pulmonary fibrosis and suggested a potential role of estrogen. Phytoestrogens act, at least in part, via stimulation of estrogen receptors; furthermore, compared to residents of Western countries, residents of East Asian countries consume higher amounts of phytoestrogens and exhibit lower rates of pulmonary fibrosis. Therefore, we tested the hypothesis that dietary phytoestrogens ameliorate the severity of experimentally induced pulmonary fibrosis. Male mice placed on either regular soybean diet or phytoestrogen-free diet were instilled with 0.1 N HCl to provoke pulmonary fibrosis. Thirty days later, lung mechanics were measured as indices of lung function and bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed for biomarkers of fibrosis. Mice on phytoestrogen-free diet demonstrated increased mortality and stronger signs of chronic lung injury and pulmonary fibrosis, as reflected in the expression of collagen, extracellular matrix deposition, histology, and lung mechanics, compared to mice on regular diet. We conclude that dietary phytoestrogens play an important role in the pathogenesis of pulmonary fibrosis and suggest that phytoestrogens (e.g., genistein) may be useful as part of a therapeutic regimen against hydrochloric acid-induced lung fibrosis and chronic lung dysfunction.
Mother’s Milk Microbiome Shaping Fecal and Skin Microbiota in Infants with Food Allergy and Atopic Dermatitis: A Pilot Analysis
Authors: Gołębiewski Marcin , Łoś-Rycharska Ewa , Sikora Marcin , Grzybowski Tomasz , Gorzkiewicz Marta , Krogulska Aneta
Published: October 2021

The child microbiome, including gut and skin communities, is shaped by a multitude of factors, and breastfeeding is one of the most essential. Food allergy (FA) and atopic dermatitis (AD) are among the most common diseases in pediatrics, with the prevalence of each up to 6% and 20%, respectively. Therefore, we aimed at finding differences between the fecal and skin microbiomes of FA and AD patients in the context of breastfeeding, by means of the Illumina sequencing of 16S rRNA gene fragment libraries amplified from the total DNA isolated from samples collected from allergic and healthy infants. We also analyzed milk samples from the mothers of the examined children and searched for patterns of incidence suggesting milk influence on an infant’s allergy status. Here we show that a mother’s milk influences her child’s fecal and skin microbiomes and identify Acinetobacter as the taxon whose abundance is correlated with milk and child-derived samples. We demonstrate that breastfeeding makes allergic children's fecal and skin communities more similar to those of healthy infants than in the case of formula-feeding. We also identify signature taxa that might be important in maintaining health or allergy development.
Untargeted Metabolomic Analysis of Human Milk from Mothers of Preterm Infants
Authors: Nolan Lila S. , Lewis Angela N. , Gong Qingqing , Sollome James J. , DeWitt Olivia N. , Williams Robert D. , Good Misty
Published: October 2021

The application of metabolomics in neonatology offers an approach to investigate the complex relationship between nutrition and infant health. Characterization of the metabolome of human milk enables an investigation into nutrients that affect the neonatal metabolism and identification of dietary interventions for infants at risk of diseases such as necrotizing enterocolitis (NEC). In this study, we aimed to identify differences in the metabolome of breast milk of 48 mothers with preterm infants with NEC and non-NEC healthy controls. A minimum significant difference was observed in the human milk metabolome between the mothers of infants with NEC and mothers of healthy control infants. However, significant differences in the metabolome related to fatty acid metabolism, oligosaccharides, amino sugars, amino acids, vitamins and oxidative stress-related metabolites were observed when comparing milk from mothers with control infants of ≤1.0 kg birth weight and >1.5 kg birth weight. Understanding the functional biological features of mothers’ milk that may modulate infant health is important in the future of tailored nutrition and care of the preterm newborn.
Emergence and Characterization of a Novel Reassortant Canine Influenza Virus Isolated from Cats
Authors: Zhao Jin , He Wanting , Lu Meng , He Haijian , Lai Alexander
Published: October 2021

Cats are susceptible to a wide range of influenza A viruses (IAV). Furthermore, cats can serve as an intermediate host, and transfer avian influenza virus (AIV) H7N2 to a veterinarian. In this report, a novel reassortant influenza virus, designated A/feline/Jiangsu/HWT/2017 (H3N2), and abbreviated as FIV-HWT-2017, was isolated from nasal swab of a symptomatic cat in Jiangsu province, China. Sequence analysis indicated that, whilst the other seven genes were most similar to the avian-origin canine influenza viruses (CIV H3N2) isolated in China, the NS gene was more closely related to the circulating human influenza virus (H3N2) in the region. Therefore, FIV-HWT-2017 is a reassortant virus. In addition, some mutations were identified, and they were similar to a distinctive CIV H3N2 clade. Whether these cats were infected with the reassortant virus was unknown, however, this random isolation of a reassortant virus indicated that domestic or stray cats were “mixing vessel” for IAV cannot be ruled out. An enhanced surveillance for novel influenza virus should include pet and stray cats.
Pioglitazone Is a Mild Carrier-Dependent Uncoupler of Oxidative Phosphorylation and a Modulator of Mitochondrial Permeability Transition
Authors: Kharechkina Ekaterina S. , Nikiforova Anna B. , Belosludtsev Konstantin N. , Rokitskaya Tatyana I. , Antonenko Yuri N. , Kruglov Alexey G.
Published: October 2021

Pioglitazone (PIO) is an insulin-sensitizing antidiabetic drug, which normalizes glucose and lipid metabolism but may provoke heart and liver failure and chronic kidney diseases. Both therapeutic and adverse effects of PIO can be accomplished through mitochondrial targets. Here, we explored the capability of PIO to modulate the mitochondrial membrane potential (ΔΨm) and the permeability transition pore (mPTP) opening in different models in vitro. ΔΨm was measured using tetraphenylphosphonium and the fluorescent dye rhodamine 123. The coupling of oxidative phosphorylation was estimated polarographically. The transport of ions and solutes across membranes was registered by potentiometric and spectral techniques. We found that PIO decreased ΔΨm in isolated mitochondria and intact thymocytes and the efficiency of ADP phosphorylation, particularly after the addition of Ca2+. The presence of the cytosolic fraction mitigated mitochondrial depolarization but made it sustained. Carboxyatractyloside diminished the PIO-dependent depolarization. PIO activated proton transport in deenergized mitochondria but not in artificial phospholipid vesicles. PIO had no effect on K+ and Ca2+ inward transport but drastically decreased the mitochondrial Ca2+-retention capacity and protective effects of adenine nucleotides against mPTP opening. Thus, PIO is a mild, partly ATP/ADP-translocase-dependent, uncoupler and a modulator of ATP production and mPTP sensitivity to Ca2+ and adenine nucleotides. These properties contribute to both therapeutic and adverse effects of PIO.
A Novel Three-Polysaccharide Blend In Situ Gelling Powder for Wound Healing Applications
Authors: Amante Chiara , Esposito Tiziana , Del Gaudio Pasquale , Di Sarno Veronica , Porta Amalia , Tosco Alessandra , Russo Paola , Nicolais Luigi , Aquino Rita P.
Published: October 2021

In this paper, alginate/pectin and alginate/pectin/chitosan blend particles, in the form of an in situ forming hydrogel, intended for wound repair applications, have been successfully developed. Particles have been used to encapsulate doxycycline in order to control the delivery of the drug, enhance its antimicrobial properties, and the ability to inhibit host matrix metalloproteinases. The presence of chitosan in the particles strongly influenced their size, morphology, and fluid uptake properties, as well as drug encapsulation efficiency and release, due to both chemical interactions between the polymers in the blend and interactions with the drug demonstrated by FTIR studies. In vitro antimicrobial studies highlighted an increase in antibacterial activity related to the chitosan amount in the powders. Moreover, in situ gelling powders are able to induce a higher release of IL-8 from the human keratinocytes that could stimulate the wound healing process in difficult-healing. Interestingly, doxycycline-loaded particles are able to increase drug activity against MMPs, with good activity against MMP-9 even at 0.5 μg/mL over 72 h. Such results suggest that such powders rich in chitosan could be a promising dressing for exudating wounds.
Development and Validation of a Questionnaire to Measure Medication Adherence to Direct-Acting Agents in Patients with Hepatitis C
Authors: Turcu-Stiolica Adina , Doica Irina Paula , Ungureanu Bogdan Silviu , Rogoveanu Ion , Florescu Dan Nicolae , Subtirelu Mihaela-Simona , Gheonea Dan Ionut
Published: October 2021

This study aims to develop a new self-report tool (HCV-AD) measuring adherence factors, intentional or unintentional, during Hepatitis C Virus (HCV) treatment with direct-acting antivirals (DAA) aiming to achieve high efficacy, otherwise resulting in drug resistance and treatment failure. Two phases were conducted: in the first phase, items were generated based on an extensive literature review, and, in the second phase, a prospective cohort study was conducted using HCV patients from Gastroenterology Department from University County Hospital of Craiova, Romania (n = 222), to evaluate the validity and reliability of the questionnaire. A number of 19 items were generated following a systematic review and through expert opinion. The internal consistency reliability was evaluated using Cronbach’s alpha. The construct validity was assessed using correlations with two other instruments: visual analog scale (VAS) and medication possession ratio (MPR). The final questionnaire (HCV-AD10) was derived through exploratory factor analysis, with 82% of total variance explained. This instrument appeared as a reliable and valid measure for medication adherence, with Cronbach’s alpha (0.867) and significant high positive correlations between adherence scores calculated with HCV-AD10 and VAS (ρ = 0.61, p < 0.001) or with HCV-AD10 and MPR (ρ = 0.75, p < 0.001). This research would make a worthwhile contribution to HCV management.
Development of a 3D-Printed Dosing Platform to Aid in Zolpidem Withdrawal Therapy
Authors: Henry Silke , De Vadder Lien , Decorte Milan , Francia Susanna , Van Steenkiste Magali , Saevels Jan , Vanhoorne Valérie , Vervaet Chris
Published: October 2021

The long-term use of benzodiazepine receptor agonists (BZRAs) is associated with multiple side effects, such as increased sedation, hangover or an elevated risk of dependency and abuse. Unfortunately, the long-term use of BZRAs is reaching worrying intake rates, and therefore, the need for action is high. It was demonstrated already that the overall willingness of patients for deprescription increased when a slow dose reduction scheme with the possibility for dose increase, if needed, is employed. The current study aims to develop a flexible dosing platform of zolpidem hemitartrate (ZHT) to facilitate such withdrawal therapy. As this is the first report on the extrusion and 3D printing of ZHT, its thermal behaviour and sensitivity towards photolytic degradation was characterised. It was shown that ZHT possesses multiple polymorphs and was especially prone to oxidative photolysis. Next, a variety of immediate release polymers (Eudragit EPO, Kollidon VA64, Kollidon 12PF and Soluplus) were blended and extruded with Polyox WSR N10 to investigate their feedability and printability by mechanical and rheological analysis. The addition of PEO was shown to enable printing of these brittle pharmaceutical polymers, although the processing temperature was deemed critical to avoid surface defects on the resulting filaments. An EPO(70)PEO(30) system was selected based on its suitable mechanical properties and low hygroscopicity favoring ZHT stability. The matrix was blended with 1% or 10% API. The effect of certain printing parameters (caplet size, nozzle diameter, % overlap) on dissolution behaviour and caplet weight/dimensions/quality was assessed. A flexible dosing platform capable of delivering <1 mg and up to 10 mg of ZHT was created. Either caplet modification (incorporation of channels) or disintegrant addition (Primojel, Explotab, Ac-Di-Sol, Primellose and Polyplasdone-XL) failed to achieve an immediate release profile. This study provides the first report of a 3D-printed flexible dosing platform containing ZHT to aid in withdrawal therapy.
Posterior Segment Ophthalmic Drug Delivery: Role of Muco-Adhesion with a Special Focus on Chitosan
Authors: Burhan Ayah Mohammad , Klahan Butsabarat , Cummins Wayne , Andrés-Guerrero Vanessa , Byrne Mark E. , O’Reilly Niall J. , Chauhan Anuj , Fitzhenry Laurence , Hughes Helen
Published: October 2021

Posterior segment eye diseases (PSEDs) including age macular degeneration (AMD) and diabetic retinopathy (DR) are amongst the major causes of irreversible blindness worldwide. Due to the numerous barriers encountered, highly invasive intravitreal (IVT) injections represent the primary route to deliver drugs to the posterior eye tissues. Thus, the potential of a more patient friendly topical route has been widely investigated. Mucoadhesive formulations can decrease precorneal clearance while prolonging precorneal residence. Thus, they are expected to enhance the chances of adherence to corneal and conjunctival surfaces and as such, enable increased delivery to the posterior eye segment. Among the mucoadhesive polymers available, chitosan is the most widely explored due to its outstanding mucoadhesive characteristics. In this review, the major PSEDs, their treatments, barriers to topical delivery, and routes of topical drug absorption to the posterior eye are presented. To enable the successful design of mucoadhesive ophthalmic drug delivery systems (DDSs), an overview of mucoadhesion, its theory, characterization, and considerations for ocular mucoadhesion is given. Furthermore, chitosan-based DDs that have been explored to promote topical drug delivery to the posterior eye segment are reviewed. Finally, challenges of successful preclinical to clinical translation of these DDSs for posterior eye drug delivery are discussed.
Chemical and Enantioselective Analysis of the Essential Oils from Different Morphological Structures of Ocotea quixos (Lam.) Kosterm
Authors: Gilardoni Gianluca , Montalván Mayra , Vélez Marjorie , Malagón Omar
Published: October 2021

The traditional Ecuadorian spice Ishpingo, characterized by a strong cinnamon-like aroma, is constituted by the dry cupules of Amazonian species Ocotea quixos. Nevertheless, bark and leaves also present aromatic properties and are sometimes used as substitutes. In the present study, the essential oils, distilled from these morphological structures, are comparatively analyzed for their chemical and enantiomeric compositions. A total of 88 components were identified with 2 orthogonal GC columns, whereas 79, corresponding to more than 94%, were also quantified with at least 1 column. Major compounds were (E)-methyl cinnamate in cupules (35.9–34.2%), (E)-cinnamaldehyde in bark (44.7–47.0%), and (E)-cinnamyl acetate (46.0–50.4%) in leaves. For what concerns the enantioselective analysis, 10 chiral terpenes and terpenoids were detected, of which 6 were present as enantiomeric pairs in at least 1 essential oil, the others being enantiomerically pure. Both quantitative and enantioselective analyses were submitted to Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA), where their results confirmed significative difference among the three products.
Known and New Emerging Viruses Infecting Blueberry
Authors: Saad Norsazilawati , Olmstead James W. , Jones Jeffrey B. , Varsani Arvind , Harmon Philip F.
Published: October 2021

Blueberry (Vaccinium spp.) plants are exposed to existing and emerging viruses as a result of expanding acreage of blueberry plantations across the world, primarily in North America. Since blueberry is cultivated in areas where there are wild Vaccinium spp., there is increasing risk of virus movement between wild and cultivated blueberries. This is theoretically possible because viruses can spread from commercial cultivars to native species and vice versa causing the spread of existing and new viruses. The occurrence of these viruses in blueberry can be devastating to the industry considering the cost for cultivation and production of this perennial crop. However, the advent of high-throughput sequencing and bioinformatic sequence analysis have allowed for rapid identification of known and novel viruses in any crop including blueberry, thus facilitating proper intervention in response to serious viral diseases. In this paper, we aim to focus on the current status of known and novel viruses emerging in blueberry worldwide, which may impact the blueberry industry.
Metabolic Perturbation and Synthetic Biology Strategies for Plant Terpenoid Production—An Updated Overview
Authors: Mani Vimalraj , Park Soyoung , Kim Jin A , Lee Soo In , Lee Kijong
Published: October 2021

Terpenoids represent one of the high-value groups of specialized metabolites with vast structural diversity. They exhibit versatile human benefits and have been successfully exploited in several sectors of day-to-day life applications, including cosmetics, foods, and pharmaceuticals. Historically, the potential use of terpenoids is challenging, and highly hampered by their bioavailability in their natural sources. Significant progress has been made in recent years to overcome such challenges by advancing the heterologous production platforms of hosts and metabolic engineering technologies. Herein, we summarize the latest developments associated with analytical platforms, metabolic engineering, and synthetic biology, with a focus on two terpenoid classes: monoterpenoids and sesquiterpenoids. Accumulated data showed that subcellular localization of both the precursor pool and the introduced enzymes were the crucial factors for increasing the production of targeted terpenoids in plants. We believe this timely review provides a glimpse of current state-of-the-art techniques/methodologies related to terpenoid engineering that would facilitate further improvements in terpenoids research.
Light Spectrum Differentially Affects the Yield and Phytochemical Content of Microgreen Vegetables in a Plant Factory
Authors: Bantis Filippos
Published: October 2021

Light quality exerts considerable effects on crop development and phytochemical content. Moreover, crops grown as microgreens are ideal for plant factories with artificial lighting, since they contain greater amounts of bioactive compounds compared to fully-grown plants. The aim of the present study was to evaluate the effect of broad-spectra light with different red/blue ratios on the yield, morphology, and phytochemical content of seven microgreens. Mustard, radish, green basil, red amaranth, garlic chives, borage, and pea shoots were grown in a vertical farming system under three light sources emitting red/blue ratios of about 2, 5, and 9 units (RB2, RB5, and RB9, respectively). Mustard exhibited the most profound color responses. The yield was enhanced in three microgreens under RB9 and in garlic under RB2. Both the hypocotyl length and the leaf and cotyledon area were significantly enhanced by increasing the red light in three microgreens each. Total soluble solids (Brix) were reduced in 4 microgreens under RB2. The total phenolic content and antioxidant capacity were reduced under RB2 in 6 and 5 microgreens, respectively. The chlorophylls were variably affected but total the carotenoid content was reduced in RB9 in three microgreens. Overall, light wavelength differentially affected the microgreens’ quality, while small interplays in spectral bands enhanced their phytochemical content.