bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal and Technological Shifts of the WHO Priority Multi-Resistant Pathogens in Municipal Wastewater Treatment Plant and Its Receiving Surface Water: A Case Study
Authors: Jałowiecki Łukasz , Hubeny Jakub , Harnisz Monika , Płaza Grażyna
Published: December 2021

The present study was focused on the identification of multi-resistant bacteria from the WHO priority pathogens list in the samples taken from different stages of the full-scale municipal wastewater treatment plant and receiving water. Additionally, the seasonal variations of the selected multi-resistant pathogens were analyzed in the samples. In order to the aim of the study, the metagenomic DNA from the collected samples was isolated and sequenced. The samples were collected in three campaigns (spring, summer, autumn). Metagenomic DNA was isolated by the commercial kits, according to the manufacturer’s instruction. Illumina sequencing system was employed, and the R program was used to metagenomic analysis. It was found that the wastewater samples and receiving water contained the multi-resistant bacteria from the WHO priority pathogens list. The seasonal and technological variations affected the distribution of the pathogens in the wastewater. No effect of the effluent on the pathogens in the receiving water was observed. The results indicated that antibiotic-resistant “priority pathogens” from the WHO list are there in the waste- and receiving water. Technological process and seasons effected their distribution in the environment. Metagenomic analysis can be used as sufficient tool in microbiological and human health risk assessment.
Weather Factors Associated with Reduced Risk of Dengue Transmission in an Urbanized Tropical City
Authors: Gui Hao , Gwee Sylvia , Koh Jiayun , Pang Junxiong
Published: December 2021

This study assessed the impact of weather factors, including novel predictors—pollutant standards index (PSI) and wind speed—on dengue incidence in Singapore between 2012 and 2019. Autoregressive integrated moving average (ARIMA) model was fitted to explore the autocorrelation in time series and quasi-Poisson model with a distributed lag non-linear term (DLNM) was set up to assess any non-linear association between climatic factors and dengue incidence. In DLNM, a PSI level of up to 111 was positively associated with dengue incidence; incidence reduced as PSI level increased to 160. A slight rainfall increase of up to 7 mm per week gave rise to higher dengue risk. On the contrary, heavier rainfall was protective against dengue. An increase in mean temperature under around 28.0 °C corresponded with increased dengue cases whereas the association became negative beyond 28.0 °C; the minimum temperature was significantly positively associated with dengue incidence at around 23–25 °C, and the relationship reversed when temperature exceed 27 °C. An overall positive association, albeit insignificant, was observed between maximum temperature and dengue incidence. Wind speed was associated with decreasing relative risk (RR). Beyond prevailing conclusions on temperature, this study observed that extremely poor air quality, high wind speed, minimum temperature ≥27 °C, and rainfall volume beyond 12 mm per week reduced the risk of dengue transmission in an urbanized tropical environment.
A Novel Antibacterial Component and the Mechanisms of an Amaranthus tricolor Leaf Ethyl Acetate Extract against Acidovorax avenae subsp. citrulli
Authors: Zhang Ya , Gao Ke , Wang Chong , Liu Shuangqing
Published: December 2021

The aim of the present investigation was to determine the active ingredients in Amaranthus tricolor L. leaves and develop a biological pesticide. Organic solvent extraction, column chromatography, liquid chromatography, ODS-C18 reverse elution, Sephadex LH-20 gel filtration, H spectrum, and C spectrum were used to isolate the pure product for an assessment of the agricultural activity and bacteriostatic mechanisms. The results showed that the activity of the crude extract following carbon powder filtration was 1.63-fold that of the non-filtered extract. Further isolation was performed to obtain two pure products, namely, hydroxybenzoic acid (HBA) and benzo[b]furan-2-carboxaldehyde (BFC), and their molecular formulas and molecular weights were C7H6O3 and 138.12, and C9H6O2 and 146.12, respectively. Our study is the first to determine that HBA has bacteriostatic activity (MIC 125 μg/mL) and is also the first to isolate BFC from A. tricolor. The ultrastructure observation results showed that HBA caused the bacteria to become shriveled, distorted, and deformed, as well as exhibit uneven surfaces. After HBA treatment, 70 differentially expressed metabolites were detected in the bacteria, of which 9 were downregulated and 61 were upregulated. The differentially expressed metabolites were mainly strigolactones, organic acids and derivatives, fatty acids, benzene and substituted benzene derivatives, amino acids and associated metabolites, and alcohols and amines. Among all of the downregulated differentially expressed metabolites, MEDP1280 was the most critical, as it participates in many physiological and biochemical processes. The enrichment analysis showed that the differentially expressed metabolites mainly participate in tyrosine metabolism, biosynthesis of amino acids, cysteine and methionine metabolism, and arginine and proline metabolism. Additionally, HBA was found to disrupt cell membrane permeability and integrity, causing the leakage of substances and apoptosis. The physiological and biochemical test results showed that HBA could increase the pyruvate levels in bacteria but could decrease the activities of respiratory enzymes (malate dehydrogenase (MDH) and NADH oxidase) and antioxidant enzymes (superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX)). Inverse molecular docking was used to study the binding between HBA and respiratory and antioxidant enzymes. The results showed that HBA could bind to MDH, NADH oxidase, SOD, and GSH-PX, suggesting that these enzymes may be the effector targets of HBA. Conclusion: The optimal active ingredient in A. tricolor that can inhibit Acidovorax avenae subsp. citrulli was identified as HBA. HBA mainly disrupts the cell membrane, damages the metabolic system, and inhibits respiration and antioxidant enzyme activity to control bacterial growth. These results provide a reference for the further development of biological pesticides.
Modulation by 17,20S(OH)2pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic Sclerosis
Authors: Brown Lobbins Monica L. , Slominski Andrzej T. , Hasty Karen A. , Zhang Sicheng , Miller Duane D. , Li Wei , Kim Tae-Kang , Janjetovic Zorica , Tuckey Robert C. , Scott Imara-Safi O. , Myers Linda K. , Postlethwaite Arnold E.
Published: December 2021

We previously demonstrated that the non-calcemic pregnacalciferol (pD) analog 17,20S (OH)2pD suppressed TGF-β1-induced type I collagen production in cultured normal human dermal fibroblasts. In the present studies, we examined fibroblasts cultured from the lesional skin of patients with systemic sclerosis (scleroderma (SSc)) and assessed the effects of 17,20S(OH)2pD on fibrosis-related mediators. Dermal fibroblast lines were established from skin biopsies from patients with SSc and healthy controls. Fibroblasts were cultured with either 17,20S(OH)2pD or 1,25(OH)2D3 (positive control) with/without TGF-β1 stimulation and extracted for protein and/or mRNA for collagen synthesis and mediators of fibrosis (MMP-1, TIMP-1, PAI-1, BMP-7, PGES, GLI1, and GLI2). 1 7,20S(OH)2pD (similar to 1,25(OH)2D3) significantly suppressed net total collagen production in TGF-β1-stimulated normal donor fibroblast cultures and in cultures of SSc dermal fibroblasts. 17,20S(OH)2pD (similar to 1,25(OH)2D3) also increased MMP-1, BMP-7, and PGES and decreased TIMP-1 and PAI1 expression in SSc fibroblasts. Although 17,20S(OH)2pD had no effect on Gli1 or Gli2 in SSc fibroblasts, it increased Gli2 expression when cultured with TGF-β1 in normal fibroblasts. These studies demonstrated that 17,20S(OH)2pD modulates mediators of fibrosis to favor the reduction of fibrosis and may offer new noncalcemic secosteroidal therapeutic approaches for treating SSc and fibrosis.
Identification of Unique Key miRNAs, TFs, and mRNAs in Virulent MTB Infection Macrophages by Network Analysis
Authors: Zhu Tingting , Liu Han , Su Li , Dawood Ali , Hu Changmin , Chen Xi , Chen Huanchun , Chen Yingyu , Guo Aizhen
Published: December 2021

Although Mycobacterium tuberculosis (MTB) has existed for thousands of years, its immune escape mechanism remains obscure. Increasing evidence signifies that microRNAs (miRNAs) play pivotal roles in the progression of tuberculosis (TB). RNA sequencing was used to sequence miRNAs in human acute monocytic leukemia cells (THP-1) infected by the virulent MTB-1458 strain and the avirulent vaccine strain Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Sets of differentially expressed miRNAs (DE-miRNAs) between MTB-1458/BCG-infected groups and uninfected groups were identified, among which 18 were differentially expressed only in the MTB-1458-infected THP-1 group. Then, 13 transcription factors (TFs) and 81 target genes of these 18 DE-miRNAs were matched. Gene Ontology classification as well as Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the candidate targets were predominantly involved in apoptotic-associated and interferon-γ-mediated signaling pathways. A TF-miRNA-mRNA interaction network was constructed to analyze the relationships among these 18 DE-miRNAs and their targets and TFs, as well as display the hub miRNAs, TFs, and target genes. Considering the degrees from network analysis and the reported functions, this study focused on the BHLHE40-miR-378d-BHLHE40 regulation axis and confirmed that BHLHE40 was a target of miR-378d. This cross-talk among DE-miRNAs, mRNAs, and TFs might be an important feature in TB, and the findings merited further study and provided new insights into immune defense and evasion underlying host-pathogen interactions.
Physical Activity and Diet Quality: Effects on Cardiovascular Morbidity in Women with Turner Syndrome—Results from an Online Patient Survey
Authors: Arnold Leonie , Bacova Martina , Dalla-Pozza Robert , Haas Nikolaus Alexander , Oberhoffer Felix Sebastian
Published: December 2021

Turner syndrome (TS) is a rare chromosomal disease with increased cardiovascular morbidity and mortality. The aim of this study was to investigate the influence of physical activity and diet quality on cardiovascular morbidity in German TS women. An anonymous online questionnaire was established. The questionnaire was based on the 2020 WHO recommendations on physical activity and sedentary behaviour and included the 14-Item Mediterranean Diet Assessment Tool. In addition, TS patients were asked about existing cardiovascular conditions. In total, 83 TS women were included in the final analysis. The achievement of <600 Metabolic Equivalent-minutes per week for recreational activities was significantly associated with the presence of arterial hypertension (p = 0.006). High adherence to the Mediterranean diet was achieved by only 20.5% of TS subjects and tended to be inversely associated with the presence of lipid metabolism disorders (p = 0.063). Only 37.3% of TS participants received nutritional counselling. Given the increased cardiovascular risk, specific counselling for lifestyle optimisation may play an important role in the management of TS. Further studies are required to evaluate the effects of regular aerobic physical training and different nutritional programs on cardiovascular morbidity in TS.
Finite Element Modelling Approach for Progressive Crushing of Composite Tubular Absorbers in LS-DYNA: Review and Findings
Authors: Rabiee Ali , Ghasemnejad Hessam
Published: December 2021

Robust finite element models are utilised for their ability to predict simple to complex mechanical behaviour under certain conditions at a very low cost compared to experimental studies, as this reduces the need for physical prototypes while allowing for the optimisation of components. In this paper, various parameters in finite element techniques were reviewed to simulate the crushing behaviour of glass/epoxy tubes with different material models, mesh sizes, failure trigger mechanisms, element formulation, contact definitions, single and various numbers of shells and delamination modelling. Six different modelling approaches, namely, a single-layer approach and a multi-layer approach, were employed with 2, 3, 4, 6, and 12 shells. In experimental studies, 12 plies were used to fabricate a 3 mm wall thickness GFRP specimen, and the numerical results were compared with experimental data. This was achieved by carefully calibrating the values of certain parameters used in defining the above parameters to predict the behaviour and energy absorption response of the finite element model against initial failure peak load (stiffness) and the mean crushing force. In each case, the results were compared with each other, including experimental and computational costs. The decision was made from an engineering point of view, which means compromising accuracy for computational efficiency. The aim is to develop an FEM that can predict energy absorption capability with a higher level of accuracy, around 5% error, than the experimental studies.
Dynamic Response of Rock-like Materials Based on SHPB Pulse Waveform Characteristics
Authors: Sun Bi , Chen Rui , Ping Yang , Zhu Zhende , Wu Nan , He Yanxin
Published: December 2021

Rock-like brittle materials under dynamic load will show more complex dynamic mechanical properties than those under static load. The relationship between pulse waveform characteristics and strain rate effect and inertia effect is rarely discussed in the split-Hopkinson pressure bar (SHPB) numerical simulation research. In response to this problem, this paper discusses the effects of different pulse types and pulse waveforms on the incident waveform and dynamic response characteristics of specimens based on particle flow code (PFC). The research identifies a critical interval of rock dynamic strength, where the dynamic strength of the specimen is independent of the strain rate but increases with the amplitude of the incident stress wave. When the critical interval is exceeded, the dynamic strength is determined by the strain rate and strain rate gradient. The strain rate of the specimen is only related to the slope of the incident stress wave and is independent of its amplitude. It is also determined that the inertia effect cannot be eliminated in the SHPB. The slope of the velocity pulse waveform determines the strain rate of the specimen, the slope of the force pulse waveform determines the strain rate gradient of the specimen, and the upper bottom time determines the strain rate of the specimen. It provides a reference for SHPB numerical simulation. A dynamic strength prediction model of rock-like materials is then proposed, which considers the effects of strain rate and strain rate gradient.
Photocatalytic Degradation of Cefixime Trihydrate by Bismuth Ferrite Nanoparticles
Authors: Nazir Ammara , Latif Shoomaila , Adil Syed Farooq , Kuniyil Mufsir , Imran Muhammad , Hatshan Mohammad Rafe , Kanwal Farah , Shaik Baji
Published: December 2021

The present work was carried out to synthesize bismuth ferrite (BFO) nanoparticles by combustion synthesis, and to evaluate the photocatalytic activity of synthesized bismuth ferrite nanoparticles against cefixime trihydrate. BFO nanoparticles were successfully synthesized using bismuth (III) nitrate and iron (III) nitrate by a combustion synthesis method employing different types of fuels such as maltose, succinic acid, cinnamic acid, and lactose. The effects of the different types of fuels on the morphology and size of the bismuth ferrite nanoparticles were investigated. Characterization of the as-obtained bismuth ferrite nanoparticles was carried out by different techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-Dispersive Spectroscopy (EDS), N2-sorption analysis, Fourier-transform infrared spectroscopy (FT-IR), and ultraviolet-visible (UV–vis) spectroscopy. Photoluminescence studies were also carried out for the various bismuth ferrite nanoparticles obtained. Degradation of cefixime trihydrate was investigated under sunlight to evaluate the photocatalytic properties of the bismuth ferrite nanoparticles, and it was found that the bismuth ferrite nanoparticles followed first-order degradation kinetics in solar irradiation in the degradation of antibiotic, cefixime trihydrate.
Photoconductivity of Thin Films Obtained from a New Type of Polyindole
Authors: Salikhov Renat B. , Mustafin Akhat G. , Mullagaliev Ilnur N. , Salikhov Timur R. , Andriianova Anastasiia N. , Latypova Lyaysan R. , Sharafullin Ildus F.
Published: December 2021

The optoelectronic properties of a new poly(2-ethyl-3-methylindole) (MPIn) are discussed in this paper. The absorption and photoluminescence spectra were studied. The electronic spectrum of MPIn showed a single absorption maximum at 269 nm that is characteristic of the entire series of polyindoles. The fluorescence spectra show that the emission peaks of the test sample are centered around 520 nm. The photoconductivity of thin film samples of MPIn polyindole was studied by measuring the current-voltage characteristics under ultraviolet radiation with a wavelength of 350 nm. Samples of phototransistors were obtained, where thin films of MPIn polyindole were used as a transport layer, and their characteristics were measured and analyzed. The value of the quantum efficiency and the values of the mobility of charge carriers in thin polyindole films were estimated.
Hyaluronic Acid-Silver Nanocomposites and Their Biomedical Applications: A Review
Authors: Dulińska-Litewka Joanna , Dykas Kacper , Felkle Dominik , Karnas Karolina , Khachatryan Gohar , Karewicz Anna
Published: December 2021

For the last years scientific community has witnessed a rapid development of novel types of biomaterials, which properties made them applicable in numerous fields of medicine. Although nanosilver, well-known for its antimicrobial, anti-angiogenic, anti-inflammatory and anticancer activities, as well as hyaluronic acid, a natural polysaccharide playing a vital role in the modulation of tissue repair, signal transduction, angiogenesis, cell motility and cancer metastasis, are both thoroughly described in the literature, their complexes are still a novel topic. In this review we introduce the most recent research about the synthesis, properties, and potential applications of HA-nanosilver composites. We also make an attempt to explain the variety of mechanisms involved in their action. Finally, we present biocompatible and biodegradable complexes with bactericidal activity and low cytotoxicity, which properties suggest their suitability for the prophylaxis and therapy of chronic wounds, as well as analgetic therapies, anticancer strategies and the detection of chemical substances and malignant cells. Cited studies reveal that the usage of hyaluronic acid-silver nanocomposites appears to be efficient and safe in clinical practice.
Effects of Different Air Particle Abrasion Protocols on the Biaxial Flexural Strength and Fractography of High/Ultra-Translucent Zirconia
Authors: AlMutairi Reem , AlNahedh Hend , Maawadh Ahmed , Elhejazi Ahmed
Published: December 2021

In this study, the biaxial flexural strength (BFS) and fractography of high/ultra-translucent monolithic zirconia ceramics subjected to different mechanical surface pretreatments were evaluated. A total of 108 disc-shaped samples (12 mm diameter, 1.2 mm thickness) of three zirconia materials (5Y-ZP KATANA Zirconia UTML (ML), 3Y-TZP DD Bio ZX2 (DB), and 5Y-ZP DD cube X2 (DC)) were used. The BFS was investigated after subjecting the samples to surface treatment using air abrasion particles of two types (aluminum oxide or glass microbeads). The data were analyzed using two-way analysis of variance, followed by Scheffe’s post hoc test for multiple comparisons. The mean ± standard deviation BFS for DB was highest after treatment with 50 µm Al2O3 (1626.05 ± 31.9 MPa), with lower values being observed following treatment with 50 µm glass microbeads (1399.53 ± 24.2 MPa) and in the control sample (1198.51 ± 21.1 MPa). The mean ± standard deviation (SD) BFSs for DC and ML were the highest in the control groups. Surface air abrasion with 50 µm Al2O3 particles and 2 bar pressure is recommended for 3Y-TZP translucent zirconia, while no abrasion of 5Y-ZP translucent zirconia ceramic.
Deep-Learning Based Estimation of Dielectrophoretic Force
Authors: Ajala Sunday , Jalajamony Harikrishnan , Fernandez Renny
Published: December 2021

The ability to accurately quantify dielectrophoretic (DEP) force is critical in the development of high-efficiency microfluidic systems. This is the first reported work that combines a textile electrode-based DEP sensing system with deep learning in order to estimate the DEP forces invoked on microparticles. We demonstrate how our deep learning model can process micrographs of pearl chains of polystyrene (PS) microbeads to estimate the DEP forces experienced. Numerous images obtained from our experiments at varying input voltages were preprocessed and used to train three deep convolutional neural networks, namely AlexNet, MobileNetV2, and VGG19. The performances of all the models was tested for their validation accuracies. Models were also tested with adversarial images to evaluate performance in terms of classification accuracy and resilience as a result of noise, image blur, and contrast changes. The results indicated that our method is robust under unfavorable real-world settings, demonstrating that it can be used for the direct estimation of dielectrophoretic force in point-of-care settings.
A Near-Infrared CMOS Silicon Avalanche Photodetector with Ultra-Low Temperature Coefficient of Breakdown Voltage
Authors: Liu Daoqun , Li Tingting , Tang Bo , Zhang Peng , Wang Wenwu , Liu Manwen , Li Zhihua
Published: December 2021

Silicon avalanche photodetector (APD) plays a very important role in near-infrared light detection due to its linear controllable gain and attractive manufacturing cost. In this paper, a silicon APD with punch-through structure is designed and fabricated by standard 0.5 μm complementary metal oxide semiconductor (CMOS) technology. The proposed structure eliminates the requirements for wafer-thinning and the double-side metallization process by most commercial Si APD products. The fabricated device shows very low level dark current of several tens Picoamperes and ultra-high multiplication gain of ~4600 at near-infrared wavelength. The ultra-low extracted temperature coefficient of the breakdown voltage is 0.077 V/K. The high performance provides a promising solution for near-infrared weak light detection.
Advances in Medical Wearable Biosensors: Design, Fabrication and Materials Strategies in Healthcare Monitoring
Authors: Pillai Sangeeth , Upadhyay Akshaya , Sayson Darren , Nguyen Bich Hong , Tran Simon D.
Published: December 2021

In the past decade, wearable biosensors have radically changed our outlook on contemporary medical healthcare monitoring systems. These smart, multiplexed devices allow us to quantify dynamic biological signals in real time through highly sensitive, miniaturized sensing platforms, thereby decentralizing the concept of regular clinical check-ups and diagnosis towards more versatile, remote, and personalized healthcare monitoring. This paradigm shift in healthcare delivery can be attributed to the development of nanomaterials and improvements made to non-invasive biosignal detection systems alongside integrated approaches for multifaceted data acquisition and interpretation. The discovery of new biomarkers and the use of bioaffinity recognition elements like aptamers and peptide arrays combined with the use of newly developed, flexible, and conductive materials that interact with skin surfaces has led to the widespread application of biosensors in the biomedical field. This review focuses on the recent advances made in wearable technology for remote healthcare monitoring. It classifies their development and application in terms of electrochemical, mechanical, and optical modes of transduction and type of material used and discusses the shortcomings accompanying their large-scale fabrication and commercialization. A brief note on the most widely used materials and their improvements in wearable sensor development is outlined along with instructions for the future of medical wearables.
Nrf2 Regulation by Curcumin: Molecular Aspects for Therapeutic Prospects
Authors: Shahcheraghi Seyed Hossein , Salemi Fateme , Peirovi Niloufar , Ayatollahi Jamshid , Alam Waqas , Khan Haroon , Saso Luciano
Published: December 2021

Nuclear factor erythroid 2 p45-related factor (2Nrf2) is an essential leucine zipper protein (bZIP) that is primarily located in the cytoplasm under physiological conditions. Nrf2 principally modulates endogenous defense in response to oxidative stress in the brain.In this regard, Nrf2 translocates into the nucleus and heterodimerizes with the tiny Maf or Jun proteins. It then attaches to certain DNA locations in the nucleus, such as electrophile response elements (EpRE) or antioxidant response elements (ARE), to start the transcription of cytoprotective genes. Many neoplasms have been shown to have over activated Nrf2, strongly suggesting that it is responsible for tumors with a poor prognosis. Exactly like curcumin, Zinc–curcumin Zn (II)–curc compound has been shown to induce Nrf2 activation. In the cancer cell lines analyzed, Zinc–curcumin Zn (II)–curc compound can also display anticancer effects via diverse molecular mechanisms, including markedly increasing heme oxygenase-1 (HO-1) p62/SQSTM1 and the Nrf2 protein levels along with its targets. It also strikingly decreases the levels of Nrf2 inhibitor, Kelch-like ECH-associated protein 1 (Keap1) protein.As a result, the crosstalk between p62/SQSTM1 and Nrf2 could be used to improve cancer patient response to treatments. The interconnected anti-inflammatory and antioxidative properties of curcumin resulted from its modulatory effects on Nrf2 signaling pathway have been shown to improve insulin resistance. Curcumin exerts its anti-inflammatory impact through suppressing metabolic reactions and proteins such as Keap1 that provoke inflammation and oxidation. A rational amount of curcumin-activated antioxidant Nrf2 HO-1 and Nrf2-Keap1 pathways and upregulated the modifier subunit of glutamate-cysteine ligase involved in the production of the intracellular antioxidant glutathione. Enhanced expression of glutamate-cysteine ligase, a modifier subunit (GLCM), inhibited transcription of glutamate-cysteine ligase, a catalytic subunit (GCLC). A variety of in vivo, in vitro and clinical studies has been done so far to confirm the protective role of curcumin via Nrf2 regulation. This manuscript is designed to provide a comprehensive review on the molecular aspects of curcumin and its derivatives/analogs via regulation of Nrf2 regulation.
Oligochitosan Synthesized by Cunninghamella elegans, a Fungus from Caatinga (The Brazilian Savanna) Is a Better Antioxidant than Animal Chitosan
Authors: Paiva Weslley Souza , de Souza Neto Francisco Ernesto , Queiroz Moacir Fernandes , Batista Lucas Alighieri Neves Costa , Rocha Hugo Alexandre Oliveira , de Lima Batista Anabelle Camarotti
Published: December 2021

Animal chitosan (Chit-A) is gaining more acceptance in daily activities. It is used in a range of products from food supplements for weight loss to even raw materials for producing nanoparticles and hydrogel drug carriers; however, it has low antioxidant activity. Fungal oligochitosan (OChit-F) was identified as a potential substitute for Chit-A. Cunninghamella elegans is a fungus found in the Brazilian savanna (Caatinga) that produces OligoChit-F, which is a relatively poorly studied compound. In this study, 4 kDa OChit-F with a 76% deacetylation degree was extracted from C. elegans. OChit-F showed antioxidant activity similar to that of Chit-A in only one in vitro test (copper chelation) but exhibited higher activity than that of Chit-A in three other tests (reducing power, hydroxyl radical scavenging, and iron chelation). These results indicate that OChit-F is a better antioxidant than Chit-A. In addition, Chit-A significantly increased the formation of calcium oxalate crystals in vitro, particularly those of the monohydrate (COM) type; however, OChit-F had no effect on this process in vitro. In summary, OChit-F had higher antioxidant activity than Chit-A and did not induce the formation of CaOx crystals. Thus, OChit-F can be used as a Chit-A substitute in applications affected by oxidative stress.
Evaluation of Virtual Screening Strategies for the Identification of γ-Secretase Inhibitors and Modulators
Authors: Ioppolo Alicia , Eccles Melissa , Groth David , Verdile Giuseppe , Agostino Mark
Published: December 2021

γ-Secretase is an intramembrane aspartyl protease that is important in regulating normal cell physiology via cleavage of over 100 transmembrane proteins, including Amyloid Precursor Protein (APP) and Notch family receptors. However, aberrant proteolysis of substrates has implications in the progression of disease pathologies, including Alzheimer’s disease (AD), cancers, and skin disorders. While several γ-secretase inhibitors have been identified, there has been toxicity observed in clinical trials associated with non-selective enzyme inhibition. To address this, γ-secretase modulators have been identified and pursued as more selective agents. Recent structural evidence has provided an insight into how γ-secretase inhibitors and modulators are recognized by γ-secretase, providing a platform for rational drug design targeting this protease. In this study, docking- and pharmacophore-based screening approaches were evaluated for their ability to identify, from libraries of known inhibitors and modulators with decoys with similar physicochemical properties, γ-secretase inhibitors and modulators. Using these libraries, we defined strategies for identifying both γ-secretase inhibitors and modulators incorporating an initial pharmacophore-based screen followed by a docking-based screen, with each strategy employing distinct γ-secretase structures. Furthermore, known γ-secretase inhibitors and modulators were able to be identified from an external set of bioactive molecules following application of the derived screening strategies. The approaches described herein will inform the discovery of novel small molecules targeting γ-secretase.
Effect of Spontaneous and Water-Based Passivation on Components and Parameters of Ti6Al4V (ELI Grade) Surface Tension and Its Wettability by an Aqueous Solution of Sucrose Ester Surfactants
Authors: Krawczyk Joanna , Gallardo-Moreno Amparo María , González-Martín María Luisa
Published: December 2021

Solid wettability is especially important for biomaterials and implants in the context of microbial adhesion to their surfaces. This adhesion can be inhibited by changes in biomaterial surface roughness and/or its hydrophilic–hydrophobic balance. The surface hydrophilic–hydrophobic balance can be changed by the specifics of the surface treatment (proper conditions of surface preparation) or adsorption of different substances. From the practical point of view, in systems that include biomaterials and implants, the adsorption of compounds characterized by bacteriostatic or bactericidal properties is especially desirable. Substances that are able to change the surface properties of a given solid as a result of their adsorption and possess at least bacteriostatic properties include sucrose ester surfactants. Thus, in our studies the analysis of a specific surface treatment effect (proper passivation conditions) on a biomaterial alloy’s (Ti6Al4V ELI, Grade 23) properties was performed based on measurements of the contact angles of water, formamide and diiodomethane. In addition, the changes in the studied solid surface’s properties resulting from the sucrose monodecanoate (SMD) and sucrose monolaurate (SML) molecules’ adsorption at the solid–water interface were also analyzed. For the analysis, the values of the contact angles of aqueous solutions of SMD and SML were measured at 293 K, and the surface tensions of the aqueous solutions of studied surfactants measured earlier were tested. From the above-mentioned tests, it was found that water environment significantly influences the components and parameters of Ti6Al4V ELI’s surface tension. It also occurred that the addition of both SMD and SML to water (separately) caused a drop in the water contact angle on Ti6Al4V ELI’s surface. However, the sucrose monolaurate surfactant is characterized by a slightly better tendency towards adsorption at the solid–water interface in the studied system compared to sucrose monodecanoate. Additionally, based on the components and parameters of Ti6Al4V ELI’s surface tension calculated from the proper values of components and parameters of model liquids, it was possible to predict the wettability of Ti6Al4V ELI using the aqueous solutions of SMD and SML at various concentrations in the solution.
Ochratoxin A and 2′R-Ochratoxin A in Selected Foodstuffs and Dietary Risk Assessment
Authors: Zapaśnik Agnieszka , Bryła Marcin , Waśkiewicz Agnieszka , Ksieniewicz-Woźniak Edyta , Podolska Grażyna
Published: December 2021

The aim of this study was to estimate the contamination of grain coffee, roasted coffee, instant coffee, and cocoa purchased in local markets with ochratoxin A (OTA) and its isomerization product 2′R-ochratoxin A (2′R-OTA), and to assess risk of dietary exposure to the mycotoxins. OTA and 2′R-OTA content was determined using the HPLC chromatography with immunoaffinity columns dedicated to OTA. OTA levels found in all the tested samples were below the maximum limits specified in the European Commission Regulation EC 1881/2006. Average OTA concentrations calculated for positive samples of grain coffee/roasted coffee/instant coffee/cocoa were 0.94/0.79/3.00/0.95 µg/kg, with the concentration ranges: 0.57–1.97/0.44–2.29/0.40–5.15/0.48–1.97 µg/kg, respectively. Average 2′R-OTA concentrations calculated for positive samples of roasted coffee/instant coffee were 0.90/1.48 µg/kg, with concentration ranges: 0.40–1.26/1.00–2.12 µg/kg, respectively. In turn, diastereomer was not found in any of the tested cocoa samples. Daily intake of both mycotoxins with coffee/cocoa would be below the TDI value even if the consumed coffee/cocoa were contaminated with OTA/2′R-OTA at the highest levels found in this study. Up to now only a few papers on both OTA and 2′R-OTA in roasted food products are available in the literature, and this is the first study in Poland.
Influence of Hydrogen Peroxide on Disinfection and Soil Removal during Low-Temperature Household Laundry
Authors: Tavčer Petra Forte , Brenčič Katja , Fink Rok , Tomšič Brigita
Published: December 2021

In the Water, Energy and Waste Directive, the European Commission provides for the use of household washing programmes with lower temperatures (30–40 °C) and lower water consumption. However, low washing temperatures and the absence of oxidising agents in the liquid detergents, and their reduced content in powder detergents, allow biofilm formation in washing machines and the development of an unpleasant odour, while the washed laundry can become a carrier of pathogenic bacteria, posing a risk to human health. The aim of the study was to determine whether the addition of hydrogen peroxide (HP) to liquid detergents in low-temperature household washing allows disinfection of the laundry without affecting the properties of the washed textiles even after several consecutive washes. Fabrics of different colours and of different raw material compositions were repeatedly washed in a household washing machine using a liquid detergent with the addition of 3% stabilised HP solution in the main wash, prewash or rinse. The results of the antimicrobial activity, soil removal activity, colour change and tensile strength confirmed the excellent disinfection activity of the 3% HP, but only if added in the main wash. Its presence did not discolour nor affect the tensile strength of the laundry, thus maintaining its overall appearance.
The Role of Household Structure and Composition in Influencing Complementary Feeding Practices in Ethiopia
Authors: Irenso Asnake Ararsa , Chamberlain Dan , Zheng Miaobing , Campbell Karen J. , Laws Rachel
Published: December 2021

While the household in which a child grows up is considered a critical environment that influences nutrition outcomes, there is little research examining the influence of household composition and structure on complementary feeding practices. This study examined the influence of household structure and composition on complementary feeding practices, using the Ethiopian Demographic and Health Survey (EDHS), 2000 to 2016. The composition variables were calculated from the attributes of household members (alters) and the structure variables from their kinship status. A multilevel mixed-effects regression model, specifying survey rounds as the random effect, was used to examine the association between household structure/composition and the Minimum Meal Frequency (MMF) and Minimum Dietary Diversity (MDD). The average Marginal Effects (MEs) were calculated to facilitate practical interpretation. Children of caregivers with a higher number of alters (degree), unique number of kinship category (effect size), closely related (constraint), and mixed-age alters (age diversity) seemed to increase the probability of meeting the MDD. Degree and effective size decreased the probability of meeting MMF, while constraint increased it. Overall, this study revealed some associations between household structure and composition and complementary feeding practices. Hence, complementary feeding interventions could be adapted to account for the household structure and composition variations.
Association of Habitual Dietary Intake with Liver Iron—A Population-Based Imaging Study
Authors: Filler Jule , von Krüchten Ricarda , Wawro Nina , Maier Lisa , Lorbeer Roberto , Nattenmüller Johanna , Thorand Barbara , Bamberg Fabian , Peters Annette , Schlett Christopher L. , Linseisen Jakob , Rospleszcz Susanne
Published: December 2021

Iron-related disorders of the liver can result in serious health conditions, such as liver cirrhosis. Evidence on the role of modifiable lifestyle factors like nutrition in liver iron storage is lacking. Thus, we aimed to assess the association of habitual diet with liver iron content (LIC). We investigated 303 participants from the population-based KORA-MRI study who underwent whole-body magnetic resonance imaging (MRI). Dietary habits were evaluated using repeated 24 h food lists and a food frequency questionnaire. Sex-stratified multiple linear regression models were applied to quantify the association between nutrition variables of interest and LIC, adjusting for liver fat content (LFC), energy intake, and age. Mean age of participants was 56.4 ± 9.0 years and 44.2% were female. Mean LIC was 1.23 ± 0.12 mg/g dry weight, with higher values in men than in women (1.26 ± 0.13 and 1.20 ± 0.10 mg/g, p < 0.001). Alcohol intake was positively associated with LIC (men: β = 1.94; women: β = 4.98, p-values < 0.03). Significant negative associations with LIC were found for fiber (β = −5.61, p < 0.001) and potassium (β = −0.058, p = 0.034) for female participants only. Furthermore, LIC was highly correlated with liver fat content in both sexes. Our findings suggests that there are sex-specific associations of habitual dietary intake and LIC. Alcohol, fiber, and potassium may play a considerable role in liver iron metabolism.
A Synbiotic Formulation Comprising Bacillus subtilis DSM 32315 and L-Alanyl-L-Glutamine Improves Intestinal Butyrate Levels and Lipid Metabolism in Healthy Humans
Authors: tom Dieck Heike , Schön Christiane , Wagner Tanja , Pankoke Helga , Fluegel Monika , Speckmann Bodo
Published: December 2021

The gut microbiota is a crucial modulator of health effects elicited by food components, with SCFA (short chain fatty acids), especially butyrate, acting as important mediators thereof. We therefore developed a nutritional synbiotic composition targeted at shifting microbiome composition and activity towards butyrate production. An intestinal screening model was applied to identify probiotic Bacillus strains plus various amino acids and peptides with suitable effects on microbial butyrate producers and levels. A pilot study was performed to test if the synbiotic formulation could improve fecal butyrate levels in healthy humans. A combination of Bacillus subtilis DSM (Number of German Collection of Microorganisms and Cell Cultures) 32315 plus L-alanyl-L-glutamine resulted in distinctly increased levels of butyrate and butyrate-producing taxa (Clostridium group XIVa, e.g., Faecalibacterium prausnitzii), both in vitro and in humans. Moreover, circulating lipid parameters (LDL-, and total cholesterol and LDL/HDL cholesterol ratio) were significantly decreased and further metabolic effects such as glucose-modulation were observed. Fasting levels of PYY (Peptide YY) and GLP-1 (Glucagon-like Peptide 1) were significantly reduced. In conclusion, our study indicates that this synbiotic composition may provide an effective and safe tool for stimulation of intestinal butyrate production with effects on e.g., lipid and glucose homeostasis. Further investigations in larger cohorts are warranted to confirm and expand these findings.
Exercise Training Combined with Calanus Oil Supplementation Improves the Central Cardiodynamic Function in Older Women
Authors: Štěpán Marek , Daďová Klára , Matouš Miloš , Krauzová Eva , Sontáková Lenka , Koc Michal , Larsen Terje , Kuda Ondrej , Štich Vladimír , Rossmeislová Lenka , Šiklová Michaela
Published: December 2021

The aim of this study was to investigate the possible beneficial effects of exercise training (ET) with omega-3/Calanus oil supplementation on cardiorespiratory and adiposity parameters in elderly women. Fifty-five women (BMI: 19–37 kg/m2, 62–80 years old) were recruited and randomly assigned to the 4 month intervention with ET and omega-3 supplementation (Calanus oil, ET-Calanus) or ET and the placebo (sunflower oil; ET-Placebo). The body composition was determined by dual-energy X-ray absorptiometry (DXA), and cardiorespiratory parameters were measured using spiroergometry and PhysioFlow hemodynamic testing. Both interventions resulted in an increased lean mass whereas the fat mass was reduced in the leg and trunk as well as the android and gynoid regions. The content of trunk fat (in percent of the total fat) was lower and the content of the leg fat was higher in the ET-Calanus group compared with the ET-Placebo. Although both interventions resulted in similar improvements in cardiorespiratory fitness (VO2max), it was explained by an increased peripheral oxygen extraction (a-vO2diff) alone in the ET-Placebo group whereas increased values of both a-vO2diff and maximal cardiac output (COmax) were observed in the ET-Calanus group. Changes in COmax were associated with changes in systemic vascular resistance, circulating free fatty acids, and the omega-3 index. In conclusion, Calanus oil supplementation during a 4 month ET intervention in elderly women improved the cardiorespiratory function, which was due to combined central and peripheral cardiodynamic mechanisms.
Formation of Self-Assembled Liquid Crystalline Nanoparticles and Absorption Enhancement of Ω-3s by Phospholipids and Oleic Acids
Authors: Jeon Sang-Won , Jin Han-Sol , Park Young-Joon
Published: December 2021

This study aimed to optimize and evaluate self-assembled liquid crystalline nanoparticles (SALCs) prepared from phospholipids and oleic acid for enhancing the absorption of Ω-3s. We explored the structure and optimal formulation of SALCs, which are composed of Ω-3 ethyl ester (Ω-3 EE), phospholipids, and oleic acid, using a ternary diagram and evaluated the improvement in Ω-3 dissolution, permeation, and oral bioavailability. The in vitro dissolution and pharmacokinetics of Ω-3 SALCs were compared with those of Omacor soft capsules (as the reference). The shape of the liquid crystal was determined according to the composition of phospholipids, oleic acids, and Ω-3s and was found to be in cubic, lamellar, and hexagonal forms. The dissolution rates of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) obtained from Ω-3 SALCs were 1.7 to 2.3-fold higher than those of the Omacor soft capsules. Furthermore, a pharmacokinetic study in male beagle dogs revealed that Ω-3 SALCs increased the oral bioavailability of Ω-3 EE by 2.5-fold for EPA and 3.1-fold for DHA compared with the reference. We found an optimal formulation that spontaneously forms liquid crystal-based nanoparticles, improving the bioavailability of EPA and DHA, not found in the existing literature. Our findings offer insight into the impact of nanoparticle phase on the oral delivery of oil-soluble drugs and provide a novel Ω-3 EE formulation that improves the bioavailability of EPA and DHA.
Development and Optimization of Acriflavine-Loaded Polycaprolactone Nanoparticles Using Box–Behnken Design for Burn Wound Healing Applications
Authors: Nawaz Touseef , Iqbal Muhammad , Khan Barkat Ali , Nawaz Asif , Hussain Talib , Hosny Khaled M. , Abualsunun Walaa A. , Rizg Waleed Y.
Published: December 2021

Nanoparticles are used increasingly for the treatment of different disorders, including burn wounds of the skin, due to their important role in wound healing. In this study, acriflavine-loaded poly (ε-caprolactone) nanoparticles (ACR-PCL-NPs) were prepared using a double-emulsion solvent evaporation method. All the formulations were prepared and optimized by using a Box–Behnken design. Formulations were evaluated for the effect of independent variables, i.e., poly (ε-caprolactone) (PCL) amount (X1), stirring speed of external phase (X2), and polyvinyl alcohol (PVA) concentration (X3), on the formulation-dependent variables (particle size, polydispersity index (PDI), and encapsulation efficiency) of ACR-PCL-NPs. The zeta potential, PDI, particle size, and encapsulation efficiency of optimized ACR-PCL-NPs were found to be −3.98 ± 1.58 mV, 0.270 ± 0.19, 469.2 ± 5.6 nm, and 71.9 ± 5.32%, respectively. The independent variables were found to be in excellent correlation with the dependent variables. The release of acriflavine from optimized ACR-PCL-NPs was in biphasic style with the initial burst release, followed by a slow release for up to 24 h of the in vitro study. Morphological studies of optimized ACR-PCL-NPs revealed the smooth surfaces and spherical shapes of the particles. Thermal and FTIR analyses revealed the drug–polymer compatibility of ACR-PCL-NPs. The drug-treated group showed significant re-epithelialization, as compared to the controlled group.
Cyclic Methacrylate Tetrahydropyrimidinones: Synthesis, Properties, (Co)Polymerization
Authors: Gerasin Victor A. , Zhurina Marina V. , Kleshcheva Natalia A. , Sivov Nikolai A. , Mendeleev Dmitry I.
Published: December 2021

During radical polymerization of novel biocidal methacrylate guanidine monomers, a cyclic byproduct was discovered and identified as 2-imino-5-methyltetrahydropyrimidin-4(1H)-one (THP). Its methacrylate salt (MTHP) was synthesized and characterized via 1H and 13C NMR and pyrolysis chromatography. Synthesis conditions of both THP and MTHP were optimized to high yields, and both MTHP homopolymerization (in aqua) and copolymerization with diallyldimethylammonium chloride (in aqua in salt form) were successfully carried out with middle to high yields, providing a promising platform for potential tailored biocide polymers.