bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Laser Parameters on Processing of Biodegradable Magnesium Alloy WE43 via Selective Laser Melting Method
Authors: Suchy Jan , Horynová Miroslava , Klakurková Lenka , Palousek David , Koutny Daniel , Celko Ladislav
Published: June 2020

The global aim of the theme of magnesium alloy processing by the selective laser melting technology is to enable printing of replacements into the human body. By combining the advantages of WE43 magnesium alloy and additive manufacturing, it is possible to print support structures that have very similar properties to human bones. However, printing magnesium alloy parts is very difficult, and the printing strategies are still under development. Knowledge of weld deposit behaviour is needed to design a complex printing strategy and still missing. The main aim of the manuscript is the find a stable process window and identify the dependence of the weld deposit shape and properties on the laser power and scanning speed. The range of the tested parameters was 100–400 W and 100–800 mm/s for laser power and scanning speed. The profilometry and light microscopy were used to verify the continuity and shape evaluation. The microhardness and EDX analysis were used for the detailed view of the weld deposit. The manuscript specifies the weld deposit dimensions, their changes depending on laser power and scanning speed, and the continuity of the weld tracks. The stable weld deposits are made by the energy density of 5.5–12 J/mm2. Thin walls were also created by layering welds to determine the surface roughness scattering (Ra 35–60) for various settings of laser power and scanning speed.
Introduction of a New Surgical Method to Improve Bone Healing in a Large Bone Defect by Replacement of the Induced Membrane by a Human Decellularized Dermis Repopulated with Bone Marrow Mononuclear Cells in Rat
Authors: Leiblein Maximilian , Kolb Tobias , Christian Lion , Schröder Katrin , Yaman Ceyhan , Schaible Alexander , Marzi Ingo , Henrich Dirk , Janko Maren
Published: June 2020

The Masquelet technique for the treatment of large bone defects is a two-stage procedure based on an induced membrane. We eliminate the first surgical step by using a decellularized dermal skin graft (Epiflex®) populated with bone marrow mononuclear cells (BMC), as a replacement for the induced membrane. The aim of this study was to demonstrate the feasibility of this technology and provide evidence of equivalent bone healing in comparison to the induced membrane-technique. Therefore, 112 male Sprague–Dawley rats were allocated in six groups and received a 10 mm femoral defect. Defects were treated with either the induced membrane or decellularized dermis, with or without the addition of BMC. Defects were then filled with a scaffold (β-TCP), with or without BMC. After a healing time of eight weeks, femurs were taken for histological, radiological and biomechanical analysis. Defects treated with Epiflex® showed increased mineralization and bone formation predominantly in the transplanted dermis surrounding the defect. No significant decrease of biomechanical properties was found. Vascularization of the defect could be enhanced by addition of BMC. Considering the dramatic reduction of a patient’s burden by the reduced surgical stress and shortened time of treatment, this technique could have a great impact on clinical practice.
Erratum: Polozov, I., et al. Fabrication of Silicon Carbide Fiber-Reinforced Silicon Carbide Matrix Composites Using Binder Jetting Additive Manufacturing from Irregularly-Shaped and Spherical Powders. Materials 2020, 13, 1766
Authors: Polozov Igor , Razumov Nikolay , Masaylo Dmitriy , Silin Alexey , Lebedeva Yuliya , Popovich Anatoly
Published: June 2020

The authors wish to make the following correction to this paper [...]
A Further Improvement in the Room-Temperature Formability of Magnesium Alloy Sheets by Pre-Stretching
Authors: Masood Chaudry Umer , Hamad Kotiba , Kim Jung-Gu
Published: June 2020

Pre-stretching experiments were carried out on AZ31–0.5Ca magnesium alloy to alter the microstructure and texture for enhancing room-temperature formability. Compared to as-received alloy, the formability of a 5%-stretched sample was improved by 15%. This was attributed to enhanced strain hardening capability related to the weakening of basal texture and less homogeneous microstructure. In addition, in-grain misorientation axis analysis performed on the samples (as-received and stretched) also confirmed the higher activity of the non-basal slip systems in the 5%-stretched sample.
Effects of Process Parameters on the Thickness Uniformity in Two-Point Incremental Forming (TPIF) with a Positive Die for an Irregular Stepped Part
Authors: Ou Lu , An Zhiguo , Gao Zhengyuan , Zhou Shuqiang , Men Zhengxing
Published: June 2020

Incremental sheet forming (ISF) is a novel flexible forming technology with advantages, such as a low forming force, low-energy-consuming equipment, and good forming performance. The lack of available information about the formability of the two-point incremental forming (TPIF) process makes it limited for practical applications. Taking an irregular stepped part as the target part, the effects of process parameters on the thickness uniformity when using TPIF with a positive die for AA1060 aluminum alloy sheets were investigated. First, the set of optimal parameters regarding the diameter of the tool head, feed rate, and the step size were obtained through orthogonal experiments. Furthermore, the optimal parameter set of the number of forming passes, the direction of movement of the forming tool, and the forming angle was determined and the optimal forming result was numerically and experimentally verified. This demonstrated that the parameters affecting the thickness uniformity of the irregular stepped parts were, in descending order, the diameter of the forming tool, the feed rate, and the step size, with corresponding optimal values of 12 mm, 15,000 mm/min, and 0.4 mm, respectively. With an increase of the number of passes and a decrease of the forming angle between adjacent passes, and adopting an alternating clockwise and counterclockwise toolpath, the thickness uniformity of the formed parts was effectively improved.
Light-Mediated Toxicity of Porphyrin-Like Pigments from a Marine Polychaeta
Authors: D’Ambrosio Mariaelena , Santos Ana Catarina , Alejo-Armijo Alfonso , Parola A. Jorge , Costa Pedro M.
Published: June 2020

Porphyrins and derivatives form one of the most abundant classes of biochromes. They result from the breakdown of heme and have crucial physiological functions. Bilins are well-known representatives of this group that, besides significant antioxidant and anti-mutagenic properties, are also photosensitizers for photodynamic therapies. Recently, we demonstrated that the Polychaeta Eulalia viridis, common in the Portuguese rocky intertidal, holds a high variety of novel greenish and yellowish porphyrinoid pigments, stored as granules in the chromocytes of several organs. On the follow-up of this study, we chemically characterized pigment extracts from the worm’s skin and proboscis using HPLC and evaluated their light and dark toxicity in vivo and ex vivo using Daphnia and mussel gill tissue as models, respectively. The findings showed that the skin and proboscis have distinct patterns of hydrophilic or even amphiphilic porphyrinoids, with some substances in common. The combination of the two bioassays demonstrated that the extracts from the skin exert higher dark toxicity, whereas those from the proboscis rapidly exert light toxicity, then becoming exhausted. One particular yellow pigment that is highly abundant in the proboscis shows highly promising properties as a natural photosensitizer, revealing that porphyrinoids from marine invertebrates are important sources of these high-prized bioproducts.
Highly Oxygenated Constituents from a Marine Alga-Derived Fungus Aspergillus giganteus NTU967
Authors: Chen Jih-Jung , Wang Shih-Wei , Chiang Yin-Ru , Pang Ka-Lai , Kuo Yueh-Hsiung , Shih Tsai-Yen , Lee Tzong-Huei
Published: June 2020

Agar-based disc diffusion antimicrobial assay has shown that the ethyl acetate extract of the fermented broth of Aspergillus giganteus NTU967 isolated from Ulva lactuca exhibited significant antimicrobial activity in our preliminary screening of bioactive fungal strains. Therefore, column chromatography of the active principles from liquid- and solid–state fermented products of the fungal strain was carried out, and which had led to isolation of eleven compounds. Their structures were determined by spectral analysis to be seven new highly oxygenated polyketides, namely aspergilsmins A–G (1–7), along with previously reported patulin, deoxytryptoquivaline, tryptoquivaline and quinadoline B. Among these, aspergilsmin C (3) and patulin displayed promising anticancer activities against human hepatocellular carcinoma SK-Hep-1 cells and prostate cancer PC-3 cells with IC50 values between 2.7–7.3 μM. Furthermore, aspergilsmin C (3) and patulin exhibited significant anti-angiogenic functions by impeding cell growth and tube formation of human endothelial progenitor cells without any cytotoxicity.
The Determination of the Limit Load Solutions for the New Pipe-Ring Specimen Using Finite Element Modeling
Authors: Likeb Andrej , Gubeljak Nenad
Published: June 2020

To estimate the acceptable size of cracks and predict the loading limit of the pipeline or its resistance to the initiation and crack growth by following the structural integrity, the fracture toughness and limit load solutions are required. Standard fracture toughness testing of thin-walled pipelines is often difficult to perform in order to complete standard requirements. To find an alternative technique for the measurement of the fracture toughness of the already delivered pipeline segment, the new pipe-ring specimen has been proposed; however, the limit load solutions have not been investigated yet. The limit load depends on the geometry of the specimen and loading mode. The ligament yielding of pipe-ring specimens containing axial cracks through the thickness under combined loads was calculated by the finite element method. This paper provides limit load solutions of several different pipe-ring geometries containing two diametric symmetrical cracks with the same depth ratio in a range of 0.45 ≤ a/W ≤ 0.55. The limit load (LL) solutions calculated by numerical analysis are shown as a function of the full ring section’s size and the corresponding crack aspect ratio for determining the normalized load. These can potentially construct the failure assessment diagram to estimate the crack acceptance in a part of the pipe.
Enhancement of Versatile Extracellular Cellulolytic and Hemicellulolytic Enzyme Productions by Lactobacillus plantarum RI 11 Isolated from Malaysian Food Using Renewable Natural Polymers
Authors: Mohamad Zabidi Nursyafiqah A. , Foo Hooi Ling , Loh Teck Chwen , Mohamad Rosfarizan , Abdul Rahim Raha
Published: June 2020

Lactobacillus plantarum RI 11 was reported recently to be a potential lignocellulosic biomass degrader since it has the capability of producing versatile extracellular cellulolytic and hemicellulolytic enzymes. Thus, this study was conducted to evaluate further the effects of various renewable natural polymers on the growth and production of extracellular cellulolytic and hemicellulolytic enzymes by this novel isolate. Basal medium supplemented with molasses and yeast extract produced the highest cell biomass (log 10.51 CFU/mL) and extracellular endoglucanase (11.70 µg/min/mg), exoglucanase (9.99 µg/min/mg), β-glucosidase (10.43 nmol/min/mg), and mannanase (8.03 µg/min/mg), respectively. Subsequently, a statistical optimization approach was employed for the enhancement of cell biomass, and cellulolytic and hemicellulolytic enzyme productions. Basal medium that supplemented with glucose, molasses and soybean pulp (F5 medium) or with rice straw, yeast extract and soybean pulp (F6 medium) produced the highest cell population of log 11.76 CFU/mL, respectively. However, formulated F12 medium supplemented with glucose, molasses and palm kernel cake enhanced extracellular endoglucanase (4 folds), exoglucanase (2.6 folds) and mannanase (2.6 folds) specific activities significantly, indicating that the F12 medium could induce the highest production of extracellular cellulolytic and hemicellulolytic enzymes concomitantly. In conclusion, L. plantarum RI 11 is a promising and versatile bio-transformation agent for lignocellulolytic biomass.
Flavonoids and Stilbenoids of the Genera Dracaena and Sansevieria: Structures and Bioactivities
Authors: Thu Zaw Min , Myo Ko Ko , Aung Hnin Thanda , Armijos Chabaco , Vidari Giovanni
Published: June 2020

The genera Dracaena and Sansevieria (Asparagaceae, Nolinoideae) are still poorly resolved phylogenetically. Plants of these genera are commonly distributed in Africa, China, Southeast Asia, and America. Most of them are cultivated for ornamental and medicinal purposes and are used in various traditional medicines due to the wide range of ethnopharmacological properties. Extensive in vivo and in vitro tests have been carried out to prove the ethnopharmacological claims and other bioactivities. These investigations have been accompanied by the isolation and identification of hundreds of phytochemical constituents. The most characteristic metabolites are steroids, flavonoids, stilbenes, and saponins; many of them exhibit potent analgesic, anti-inflammatory, antimicrobial, antioxidant, antiproliferative, and cytotoxic activities. This review highlights the structures and bioactivities of flavonoids and stilbenoids isolated from Dracaena and Sansevieria.
Effect of Cultural Conditions on Protease Production by a Thermophilic Geobacillus thermoglucosidasius SKF4 Isolated from Sungai Klah Hot Spring Park, Malaysia
Authors: Suleiman Allison D. , Abdul Rahman Nor’Aini , Mohd Yusof Hidayat , Mohd Shariff Fairolniza , Yasid Nur Adeela
Published: June 2020

Major progress in the fields of agriculture, industry, and biotechnology over the years has influenced the quest for a potent microorganism with favorable properties to be used in scientific research and industry. This study intended to isolate a new thermophilic-protease-producing bacterium and evaluate its growth and protease production under cultural conditions. Protease producing bacteria were successfully isolated from Sungai Klah Hot Spring Park in Perak, Malaysia, and coded as SKF4; they were promising protease producers. Based on microscopic, morphological, and 16S rRNA gene analysis, isolate SKF4 was identified as Geobacillus thermoglucosidasius SKF4. The process of isolating SKF4 to grow and produce proteases under different cultural conditions, including temperature, pH, NaCl concentration, carbon and nitrogen sources, and incubation time, was explored. The optimum cultural conditions observed for growth and protease production were at 60 to 65 °C of temperature, pH 7 to 8, and under 1% NaCl concentration. Further, the use of casein and yeast extract as the nitrogen sources, and sucrose and fructose as the carbon sources enhanced the growth and protease production of isolate SKF4. Meanwhile, isolate SKF4 reached maximum growth and protease production at 24 h of incubation time. The results of this study revealed a new potent strain of thermophilic bacterium isolated from Sungai Klah Hot Spring Park in Perak, Malaysia for the first time. The high production of thermostable protease enzyme by G. thermoglucosidasius SKF4 highlighted the promising properties of this bacterium for industrial and biotechnological applications.
Chemical Profile and Biological Activity of Cherimoya (Annona cherimola Mill.) and Atemoya (Annona atemoya) Leaves
Authors: Mannino Giuseppe , Gentile Carla , Porcu Alessandra , Agliassa Chiara , Caradonna Fabio , Bertea Cinzia Margherita
Published: June 2020

Annona cherimola (Cherimoya) and Annona atemoya (Atemoya) are tropical plants known for their edible fruit. Scientific data suggest that their leaves, used in traditional medicine in the form of teas or infusions without evidence of toxicity, contain several bioactive compounds. However, only Annona muricata among all the Annona species is currently used in the nutraceutical field, and its dried leaves are marketed for tea preparation. In this work, we explored the nutraceutical potential of Atemoya and Cherimoya leaves, by evaluating their chemical profile and functional properties. Phytochemical analyses showed large amounts of phenolic compounds, in particular proanthocyanidins, and identified 18 compounds, either flavonoids or alkaloids. Concerning biological activity, we found antioxidative properties correlated with polyphenols, and antiproliferative activity against HeLa and HepG2 cell lines correlated with alkaloids. The obtained results demonstrate the potential use of Annona cherimola leaves for the preparation of dietary supplements aimed to promote the physiological redox balance. Moreover, the varietal comparison suggests that two commercial cultivars (Campas and White) and the local Torre 1, better suit this purpose. On the other hand, among the studied cultivars, Campas and Torre 1 are also the richest in alkaloids and, in consideration of the anti-proliferative properties of their extracts, dietary supplements based on these cultivars might also have chemo-preventive effects.
CASPT2 Potential Energy Curves for NO Dissociation in a Ruthenium Nitrosyl Complex
Authors: Talotta Francesco , González Leticia , Boggio-Pasqua Martial
Published: June 2020

Ruthenium nitrosyl complexes are fascinating photoactive compounds showing complex photoreactivity, such as N→O linkage photoisomerism and NO photorelease. This dual photochemical behavior has been the subject of many experimental studies in order to optimize these systems for applications as photoswitches or therapeutic agents for NO delivery. However, despite recent experimental and computational studies along this line, the underlying photochemical mechanisms still need to be elucidated for a more efficient design of these systems. Here, we present a theoretical contribution based on the calculations of excited-state potential energy profiles for NO dissociation in the prototype trans-[RuCl(NO)(py)4]2+ complex at the complete active space second-order perturbation theory (CASPT2). The results point to a sequential two-step photon absorption photorelease mechanism coupled to partial photoisomerization to a side-on intermediate, in agreement with previous density functional theory calculations.
Drug-Drug Interactions of Irinotecan, 5-Fluorouracil, Folinic Acid and Oxaliplatin and Its Activity in Colorectal Carcinoma Treatment
Authors: Zoetemelk Marloes , Ramzy George M. , Rausch Magdalena , Nowak-Sliwinska Patrycja
Published: June 2020

The combination of folinic acid, 5-fluorouracil, oxaliplatin and/or irinotecan (FOLFOXIRI) is the standard of care for metastatic colorectal cancer (CRC). This strategy inhibits tumor growth but provokes drug resistance and serious side effects. We aimed to improve FOLFOXIRI by optimization of the dosing and the sequence of drug administration. We employed an orthogonal array composite design and linear regression analysis to obtain cell line-specific drug combinations for four CRC cell lines (DLD1, SW620, HCT116, LS174T). Our results confirmed the synergy between folinic acid and 5-fluorouracil and additivity, or even antagonism, between the other drugs of the combination. The drug combination administered at clinical doses resulted in significantly higher antagonistic interactions compared to the low-dose optimized drug combination (ODC). We found that the concomitant administration of the optimized drug combination (ODC) was comparatively active to sequential administration. However, the administration of oxaliplatin or the active metabolite of irinotecan seemed to sensitize the cells to the combination of folinic acid and 5-fluorouracil. ODCs were similarly active in non-cancerous cells as compared to the clinically used doses, indicating a lack of reduction of side effects. Interestingly, ODCs were inactive in CRC cells chronically pretreated with FOLFOXIRI, suggesting the occurrence of resistance. We were unable to improve FOLFOXIRI in terms of efficacy or specificity. Improvement of CRC treatment should come from the optimization of targeted drugs and immunotherapy strategies.
Production and Semi-Automated Processing of 89Zr Using a Commercially Available TRASIS MiniAiO Module
Authors: Gaja Vijay , Cawthray Jacqueline , Geyer Clarence R. , Fonge Humphrey
Published: June 2020

The increased interest in 89Zr-labelled immunoPET imaging probes for use in preclinical and clinical studies has led to a rising demand for the isotope. The highly penetrating 511 and 909 keV photons emitted by 89Zr deliver an undesirably high radiation dose, which makes it difficult to produce large amounts manually. Additionally, there is a growing demand for Good Manufacturing Practices (GMP)-grade radionuclides for clinical applications. In this study, we have adopted the commercially available TRASIS mini AllinOne (miniAiO) automated synthesis unit to achieve efficient and reproducible batches of 89Zr. This automated module is used for the target dissolution and separation of 89Zr from the yttrium target material. The 89Zr is eluted with a very small volume of oxalic acid (1.5 mL) directly over the sterile filter into the final vial. Using this sophisticated automated purification method, we obtained satisfactory amount of 89Zr in high radionuclidic and radiochemical purities in excess of 99.99%. The specific activity of three production batches were calculated and was found to be in the range of 1351–2323 MBq/µmol. ICP-MS analysis of final solutions showed impurity levels always below 1 ppm.
Molecular Network-Guided Alkaloid Profiling of Aerial Parts of Papaver nudicaule L. Using LC-HRMS
Authors: Song Kwangho , Oh Jae-Hyeon , Lee Min Young , Lee Seok-Geun , Ha In Jin
Published: June 2020

Papaver nudicaule L. (Iceland poppy) is widely used for ornamental purposes. A previous study demonstrated the alleviation of lipopolysaccharide-induced inflammation mediated by P. nudicaule extract through nuclear factor-kappa B and signal transducer and activator of transcription 3 inactivation. As isoquinoline alkaloids are chemical markers and bioactive constituents of Papaver species, the present study investigated the alkaloid profile of aerial parts of five P. nudicaule cultivars with different flower colors and a P. rhoeas cropped for two years. A combination of liquid chromatography high-resolution mass spectrometry and molecular networking was used to cluster isoquinoline alkaloids in the species and highlight the possible metabolites. Aside from the 12 compounds, including rotundine, muramine, and allocryptopine, identified from Global Natural Products Social library and reported information, 46 structurally related metabolites were quantitatively investigated. Forty-two and 16 compounds were proposed for chemical profiles of P. nudicaule and P. rhoeas, respectively. Some species-specific metabolites showed similar fragmentation patterns. The alkaloid abundance of P. nudicaule differed depending on the flower color, and the possible chemical markers were proposed. These results show that molecular networking-guided dereplication allows investigation of unidentified metabolites. The derived chemical profile may facilitate evaluation of P. nudicaule quality for pharmacological applications.
Site-Selective Modification of a Porpholactone—Selective Synthesis of 12,13- and 17,18-Dihydroporpholactones
Authors: Cerqueira Ana F. R. , Snarskis Gustautas , Zurauskas Jonas , Guieu Samuel , Paz Filipe A. Almeida , Tomé Augusto C.
Published: June 2020

The reaction of meso-tetrakis(pentafluorophenyl)porpholactone with azomethine ylides and nitrones affords pyrrolidine-fused and isoxazolidine-fused dihydroporpholactones that display, respectively, isobacteriochlorin- and chlorin-type UV–Vis spectra. These reactions are site-selective, yielding, respectively, 17,18- or 12,13-dihydroporpholactones. The crystal and molecular features of pyrrolidine-fused and isoxazolidine-fused dihydroporpholactones were unveiled from single-crystal X-ray diffraction studies.
Targeting Oxidative Stress for Disease Prevention and Therapy: Where Do We Stand, and Where Do We Go from Here
Authors: Vassalle Cristina , Maltinti Maristella , Sabatino Laura
Published: June 2020

Oxidative stress (OxS) is one of the main processes related to aging and a common denominator of many different chronic/degenerative diseases (e.g., cardiovascular and neurodegenerative conditions and cancer). Thus, its potential modulation by supplementation/pharmacological therapy caused a lot of interest. However, these expectations have been mitigated by the obtainment of controversial results (beneficial, null, or adverse effects) following antioxidant interventions. Here, we discuss the current understanding of OxS assessment in health and disease, challenges and the potential of its evaluation in clinical practice, and available and future development for supplementation and pharmacologic strategies targeting OxS.
Corynanthean-Epicatechin Flavoalkaloids from Corynanthe pachyceras
Authors: Kouamé Tapé , Okpekon Aboua Timothée , Bony Nicaise F. , N’Tamon Amon Diane , Gallard Jean-François , Rharrabti Somia , Leblanc Karine , Mouray Elisabeth , Grellier Philippe , Champy Pierre , Beniddir Mehdi A. , Le Pogam Pierre
Published: June 2020

Epicatechocorynantheines A and B, and epicatechocorynantheidine were isolated from the stem bark of Corynanthe pachyceras. These molecules were pinpointed, and their isolation streamlined, by a molecular networking strategy. The structural elucidation was unambiguously accomplished from HRMS and 1D/2D NMR data. These compounds represent the first examples of corynanthean-type alkaloids tethered with a flavonoid. Epicatechocorynantheidine notably instigated two connections between the monoterpene indole alkaloid and the flavonoid, yielding an unprecedented octacyclic appendage. These flavoalkaloids exerted moderate antiplasmodial activities.
Cooperative Binding and Stepwise Encapsulation of Drug Molecules by Sulfonylcalixarene-Based Metal-Organic Supercontainers
Authors: Sheng Tian-Pu , Fan Xin-Xia , Zheng Guo-Zong , Dai Feng-Rong , Chen Zhong-Ning
Published: June 2020

The cooperative binding behavior of a face-directed octahedral metal-organic supercontainer featuring one endo cavity and six exo cavities was thoroughly examined in chloroform solution through ultraviolet-visible (UV-Vis) titration technique using two representative drug molecules as the guests. The titration curves and their nonlinear fit to Hill equation strongly suggest the efficient encapsulation of the guest molecules by the synthetic host, which exhibit interesting cooperative and stepwise binding behavior. Based on the control experiments using tetranuclear complex as a reference, it is clear that two equivalents of the guest molecules are initially encapsulated inside the endo cavity, followed by the trapping of six additional equivalents of the drug molecules through six exo cavities (1 eq. per exo cavity), and the remaining guests are entrapped by the external pockets. The results provide an in-depth understanding of the cooperative binding behavior of metal-organic supercontainers, which opens up new opportunities for designing synthetic receptors for truly biomimetic functional applications.
Bioengineering of Cytochrome P450 OleTJE: How Does Substrate Positioning Affect the Product Distributions?
Authors: Cantú Reinhard Fabián G. , Lin Yen-Ting , Stańczak Agnieszka , de Visser Sam P.
Published: June 2020

The cytochromes P450 are versatile enzymes found in all forms of life. Most P450s use dioxygen on a heme center to activate substrates, but one class of P450s utilizes hydrogen peroxide instead. Within the class of P450 peroxygenases, the P450 OleTJE isozyme binds fatty acid substrates and converts them into a range of products through the α-hydroxylation, β-hydroxylation and decarboxylation of the substrate. The latter produces hydrocarbon products and hence can be used as biofuels. The origin of these product distributions is unclear, and, as such, we decided to investigate substrate positioning in the active site and find out what the effect is on the chemoselectivity of the reaction. In this work we present a detailed computational study on the wild-type and engineered structures of P450 OleTJE using a combination of density functional theory and quantum mechanics/molecular mechanics methods. We initially explore the wild-type structure with a variety of methods and models and show that various substrate activation transition states are close in energy and hence small perturbations as through the protein may affect product distributions. We then engineered the protein by generating an in silico model of the double mutant Asn242Arg/Arg245Asn that moves the position of an active site Arg residue in the substrate-binding pocket that is known to form a salt-bridge with the substrate. The substrate activation by the iron(IV)-oxo heme cation radical species (Compound I) was again studied using quantum mechanics/molecular mechanics (QM/MM) methods. Dramatic differences in reactivity patterns, barrier heights and structure are seen, which shows the importance of correct substrate positioning in the protein and the effect of the second-coordination sphere on the selectivity and activity of enzymes.
Amount of Protein Required to Improve Muscle Mass in Older Adults
Authors: Kim Doyeon , Park Yongsoon
Published: June 2020

Increased protein intake has been suggested as an effective strategy to treat age-related loss of muscle mass and function, but the amount of protein required to improve muscle and function without exercise in older adults remains unclear. Thus, this secondary data analysis aimed to assess what amount of protein from habitual protein intake was positively associated with changes in muscle mass and gait speed in older women and men. Ninety-six community-dwelling older adults consumed 0.8, 1.2, or 1.5 g/kg/day of protein and maintained their usual physical activity for 12 weeks. Increased protein intake of >0.54 g/kg/day was positively associated with changes in appendicular skeletal muscle mass (ASM)/weight (B = 0.591, p = 0.026), ASM/body mass index (B = 0.615, p = 0.023), and ASM:fat ratio (B = 0.509, p = 0.030) in older men. However, change in protein intake was not associated with change in muscle mass in older women. Additionally, change in protein intake was not associated with change in gait speed in older women and men. The present study suggested that an increased absolute protein amount of >0.54 g/kg/day from habitual protein intake was positively associated with change in muscle mass in older men.
The Effect of Front-of-Pack Nutritional Labels and Back-of-Pack Tables on Dietary Quality
Authors: Rønnow Helene Normann
Published: June 2020

A healthy diet is important to prevent lifestyle diseases. Food labels have been proposed as a policy tool to improve the healthiness of food choices, as they provide information about nutritional content and health attributes which may otherwise have been unknown to the consumer. This study investigates the effect of food labels with different formats on dietary quality by using home-scan panel data and difference-in-difference methods to compare the change in dietary quality over time for households that start to use food labels with households that do not use labels. I find that the use of front-of-pack (FOP) nutritional labels increases overall dietary quality, which is driven by reduced intake of added sugar and increased intake of fiber. The use of back-of-pack (BOP) nutritional tables does not influence dietary quality. There is no additional benefit to overall dietary quality by using both labels. However, the results indicate that there could be a benefit of using both labels on certain nutrients. The results imply that additional policies are needed to supplement food labels in order to improve dietary quality.
Malnutrition as Key Predictor of Physical Frailty among Malaysian Older Adults
Authors: Norazman Camilla Wahida , Adznam Siti Nur’Asyura , Jamaluddin Rosita
Published: June 2020

Studies have been carried out on the association between frailty and malnutrition, but the similarities and divergence of the relationship remain debatable. This study aimed to explore the prevalence of malnutrition risk and frailty as well as the overlapping constructs. The associations that emerged were assessed independently of other risk factors. A total of 301 community-dwelling older adults with a mean age of 66.91 ± 5.59 years old were randomly recruited. Fried Criteria and Mini Nutritional Assessment-Short Form (MNA-SF) were used to assess frailty status and malnutrition, respectively. Other related nutritional assessments were assessed (body mass index (BMI), circumference measures, body fat % and skeletal muscle mass). The prevalence of frailty was 14.6% and prefrail was 59.7%; 29.6% were at risk of malnutrition, and 3.3% were malnourished. Malnutrition risk was significantly associated with a higher number of chronic diseases, BMI, circumference of mid-upper arm (MUAC), and calf, (CC)and skeletal muscle mass (SMM) and frailty, whereas frailty was significantly associated with higher number of chronic diseases, SMM and malnutrition. Frailty syndrome can be predicted with increasing age, body fat, lower skeletal muscle and malnutrition. Those who were frail were found to be five times more likely to be at risk of malnutrition. Results suggested that frailty and malnutrition shared considerable overlap, which emphasised the interrelated but discrete concepts. Therefore, the assessment of malnutrition is imperative and could be used as a practical implication in assessing frailty syndrome.
Understanding the Composition, Biosynthesis, Accumulation and Transport of Flavonoids in Crops for the Promotion of Crops as Healthy Sources of Flavonoids for Human Consumption
Authors: Ku Yee-Shan , Ng Ming-Sin , Cheng Sau-Shan , Lo Annie Wing-Yi , Xiao Zhixia , Shin Tai-Sun , Chung Gyuhwa , Lam Hon-Ming
Published: June 2020

Flavonoids are a class of polyphenolic compounds that naturally occur in plants. Sub-groups of flavonoids include flavone, flavonol, flavanone, flavanonol, anthocyanidin, flavanol and isoflavone. The various modifications on flavonoid molecules further increase the diversity of flavonoids. Certain crops are famous for being enriched in specific flavonoids. For example, anthocyanins, which give rise to a purplish color, are the characteristic compounds in berries; flavanols are enriched in teas; and isoflavones are uniquely found in several legumes. It is widely accepted that the antioxidative properties of flavonoids are beneficial for human health. In this review, we summarize the classification of the different sub-groups of flavonoids based on their molecular structures. The health benefits of flavonoids are addressed from the perspective of their molecular structures. The flavonoid biosynthesis pathways are compared among different crops to highlight the mechanisms that lead to the differential accumulation of different sub-groups of flavonoids. In addition, the mechanisms and genes involved in the transport and accumulation of flavonoids in crops are discussed. We hope the understanding of flavonoid accumulation in crops will guide the proper balance in their consumption to improve human health.
The Hepatotoxicity of Alantolactone and Germacrone: Their Influence on Cholesterol and Lipid Metabolism in Differentiated HepaRG Cells
Authors: Zárybnický Tomáš , Matoušková Petra , Skálová Lenka , Boušová Iva
Published: June 2020

The sesquiterpenes alantolactone (ATL) and germacrone (GER) are potential anticancer agents of natural origin. Their toxicity and biological activity have been evaluated using the differentiated HepaRG (dHepaRG) cells, a hepatocyte-like model. The half-maximal inhibitory concentrations of cell viability after 24-h treatment of dHepaRG cells are approximately 60 M for ATL and 250 M for GER. However, both sesquiterpenes induce reactive oxygen species (ROS) formation in non-toxic concentrations and significantly dysregulate the mRNA expression of several functional markers of mature hepatocytes. They similarly decrease the protein level of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) and their transcription target, intercellular adhesion molecule 1 (ICAM-1). Based on the results of a BATMAN-TCM analysis, the effects of sesquiterpenes on cholesterol and lipid metabolism were studied. Sesquiterpene-mediated dysregulation of both cholesterol and lipid metabolism was observed, during which these compounds influenced the protein expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and sterol regulatory element-binding protein 2 (SREBP-2), as well as the mRNA expression of HMGCR, CYP19A1, PLIN2, FASN, SCD, ACACB, and GPAM genes. In conclusion, the two sesquiterpenes caused ROS induction at non-toxic concentrations and alterations in cholesterol and lipid metabolism at slightly toxic and toxic concentrations, suggesting a risk of liver damage if administered to humans.
Clustering of Sedentary Behaviours, Physical Activity, and Energy-Dense Food Intake in Six-Year-Old Children: Associations with Family Socioeconomic Status
Authors: Yang-Huang Junwen , van Grieken Amy , Wang Lu , Jansen Wilma , Raat Hein
Published: June 2020

This study examined the clustering of lifestyle behaviours in children aged six years from a prospective cohort study in the Netherlands. Additionally, we analysed the associations between socioeconomic status and the lifestyle behaviour clusters that we identified. Data of 4059 children from the Generation R Study were analysed. Socioeconomic status was measured by maternal educational level and net household income. Lifestyle behaviours including screen time, physical activity, calorie-rich snack consumption and sugar-sweetened beverages consumption were measured via a parental questionnaire. Hierarchical and non-hierarchical cluster analyses were applied. The associations between socioeconomic status and lifestyle behaviour clusters were assessed using logistic regression models. Three lifestyle clusters were identified: “relatively healthy lifestyle” cluster (n = 1444), “high screen time and physically inactive” cluster (n = 1217), and “physically active, high snacks and sugary drinks” cluster (n = 1398). Children from high educated mothers or high-income households were more likely to be allocated to the “relatively healthy lifestyle” cluster, while children from low educated mothers or from low-income households were more likely to be allocated in the “high screen time and physically inactive” cluster. Intervention development and prevention strategies may use this information to further target programs promoting healthy behaviours of children and their families.
The Effect of a 2-Week Red Ginseng Supplementation on Food Efficiency and Energy Metabolism in Mice
Authors: Hwang Hyejung , Kim Jisu , Lim Kiwon
Published: June 2020

Red ginseng (RG) ingestion reportedly affects body weight, food intake, and fat accumulation reduction. It also induces changes in energy metabolism regulation and glycemic control. Previously, 2-week RG ingestion with endurance training was found to enhance fat oxidation during exercise. However, such effects on energy metabolism and the expression of mRNAs related to energy substrate utilization in resting mice (untrained mice) are still unclear. Here, we determined the effect of RG on energy metabolism and substrate utilization in untrained male mice. Twenty-four mice were separated into an RG group that received a daily dosage of 1 g/kg RG for 2 weeks, and a control (CON). Energy expenditure, blood and tissue glycogen levels, and expression of mRNAs related to energy substrate utilization in muscles were measured before and 2 weeks after treatment. Total food intake was significantly lower in the RG than in the CON group (p < 0.05), but final body weights did not differ. Carbohydrate and fat oxidation over 24 h did not change in either group. There were no significant differences in gastrocnemius GLUT4, MCT1, MCT4, FAT/CD36, and CPT1b mRNA levels between groups. Thus, the effects of RG ingested during rest differ from the effects of RG ingestion in combination with endurance exercise; administering RG to untrained mice for 2 weeks did not change body weight and energy metabolism. Therefore, future studies should consider examining the RG ingestion period and dosage for body weight control and improving energy metabolism.
Combination Therapy and Nanoparticulate Systems: Smart Approaches for the Effective Treatment of Breast Cancer
Authors: Gadag Shivaprasad , Sinha Shristi , Nayak Yogendra , Garg Sanjay , Nayak Usha Y.
Published: June 2020

Breast cancer has become one of the biggest concerns for oncologists in the past few decades because of its unpredictable etiopathology and nonavailability of personalized translational medicine. The number of women getting affected by breast cancer has increased dramatically, owing to lifestyle and environmental changes. Besides, the development of multidrug resistance has become a challenge in the therapeutic management of breast cancer. Studies reveal that the use of monotherapy is not effective in the management of breast cancer due to high toxicity and the development of resistance. Combination therapies, such as radiation therapy with adjuvant therapy, endocrine therapy with chemotherapy, and targeted therapy with immunotherapy, are found to be effective. Thus, multimodal and combination treatments, along with nanomedicine, have emerged as a promising strategy with minimum side effects and drug resistance. In this review, we emphasize the multimodal approaches and recent advancements in breast cancer treatment modalities, giving importance to the current data on clinical trials. The novel treatment approach by targeted therapy, according to type, such as luminal, HER2 positive, and triple-negative breast cancer, are discussed. Further, passive and active targeting technologies, including nanoparticles, bioconjugate systems, stimuli-responsive, and nucleic acid delivery systems, including siRNA and aptamer, are explained. The recent research exploring the role of nanomedicine in combination therapy and the possible use of artificial intelligence in breast cancer therapy is also discussed herein. The complexity and dynamism of disease changes require the constant upgrading of knowledge, and innovation is essential for future drug development for treating breast cancer.
Key-Protease Inhibition Regimens Promote Tumor Targeting of Neurotensin Radioligands
Authors: Kanellopoulos Panagiotis , Kaloudi Aikaterini , de Jong Marion , Krenning Eric P. , Nock Berthold A. , Maina Theodosia
Published: June 2020

Neurotensin subtype 1 receptors (NTS1R) represent attractive molecular targets for directing radiolabeled neurotensin (NT) analogs to tumor lesions for diagnostic and therapeutic purposes. This approach has been largely undermined by the rapid in vivo degradation of linear NT-based radioligands. Herein, we aim to increase the tumor targeting of three 99mTc-labeled NT analogs by the in-situ inhibition of two key proteases involved in their catabolism. DT1 ([N4-Gly7]NT(7-13)), DT5 ([N4-βAla7,Dab9]NT(7-13)), and DT6 ([N4-βAla7,Dab9,Tle12]]NT(7-13)) were labeled with 99mTc. Their profiles were investigated in NTS1R-positive colon adenocarcinoma WiDr cells and mice treated or not with the neprilysin (NEP)-inhibitor phosphoramidon (PA) and/or the angiotensin converting enzyme (ACE)-inhibitor lisinopril (Lis). Structural modifications led to the partial stabilization of 99mTc-DT6 in peripheral mice blood (55.1 ± 3.9% intact), whereas 99mTc-DT1 and 99mTc-DT5 were totally degraded within 5 min. Coinjection of PA and/or Lis significantly stabilized all three analogs, leading to a remarkable enhancement of tumor uptake for 99mTc-DT1 and 99mTc-DT5, but was less effective in the case of poorly internalizing 99mTc-DT6. In conclusion, NEP and/or ACE inhibition represents a powerful tool to improve tumor targeting and the overall pharmacokinetics of NT-based radioligands, and warrants further validation in the field of NTS1R-targeted tumor imaging and therapy.
Solution Blow Spinning of Polyvinylidene Fluoride Based Fibers for Energy Harvesting Applications: A Review
Authors: Atif Rasheed , Khaliq Jibran , Combrinck Madeleine , Hassanin Ahmed H. , Shehata Nader , Elnabawy Eman , Shyha Islam
Published: June 2020

Polyvinylidene fluoride (PVDF)-based piezoelectric materials (PEMs) have found extensive applications in energy harvesting which are being extended consistently to diverse fields requiring strenuous service conditions. Hence, there is a pressing need to mass produce PVDF-based PEMs with the highest possible energy harvesting ability under a given set of conditions. To achieve high yield and efficiency, solution blow spinning (SBS) technique is attracting a lot of interest due to its operational simplicity and high throughput. SBS is arguably still in its infancy when the objective is to mass produce high efficiency PVDF-based PEMs. Therefore, a deeper understanding of the critical parameters regarding design and processing of SBS is essential. The key objective of this review is to critically analyze the key aspects of SBS to produce high efficiency PVDF-based PEMs. As piezoelectric properties of neat PVDF are not intrinsically much significant, various additives are commonly incorporated to enhance its piezoelectricity. Therefore, PVDF-based copolymers and nanocomposites are also included in this review. We discuss both theoretical and experimental results regarding SBS process parameters such as solvents, dissolution methods, feed rate, viscosity, air pressure and velocity, and nozzle design. Morphological features and mechanical properties of PVDF-based nanofibers were also discussed and important applications have been presented. For completeness, key findings from electrospinning were also included. At the end, some insights are given to better direct the efforts in the field of PVDF-based PEMs using SBS technique.
Using Finite Element Approach for Crashworthiness Assessment of a Polymeric Auxetic Structure Subjected to the Axial Loading
Authors: Farokhi Nejad Ali , Alipour Roozbeh , Shokri Rad Mozafar , Yazid Yahya Mohd , Rahimian Koloor Seyed Saeid , Petrů Michal
Published: June 2020

Polyurethane foams are one of the most common auxetic structures regarding energy absorption enhancement. This present study evaluates the result reliability of two different numerical approaches, the H-method and the P-method, to obtain the best convergence solution. A polymeric re-entrant cell is created with a beam element and the results of the two different methods are compared. Additionally, the numerical results compare well with the analytical solution. The results show that there is a good agreement between converged FE models and the analytical solution. Regarding the computational cost, the P-method is more efficient for simulating the re-entrant structure subjected to axial loading. During the second part of this study, the re-entrant cell is used for generating a polymeric auxetic cellular tube. The mesh convergence study is performed on the cellular structures using the H- and P- methods. The cellular tube is subjected to tensional and compressive loading, the module of elasticity and Poisson’s ration to calculate different aspect ratios. A nonlinear analysis is performed to compare the dynamic response of a cellular tube versus a solid tube. The crashworthiness indicators are addressed and the results are compared with equivalent solid tubes. The results show that the auxetic cellular tubes have better responses against compressive loading. The primary outcome of this research is to assess a reliable FE approach for re-entrant structures under axial loading.