bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic Effect of Mandarin Peels and Hesperidin with Sodium Nitrite against Some Food Pathogen Microbes
Authors: Attia Gouda H. , Marrez Diaa A. , Mohammed Mona A. , Albarqi Hassan A. , Ibrahim Ammar M. , Raey Mohamed A. El
Published: May 2021

Food preservatives such as NaNO2, which are widely used in human food products, undoubtedly affect, to some extent, human organs and health. For this reason, there is a need to reduce the hazards of these chemical preservatives, by replacing them with safe natural bio-preservatives, or adding them to synthetic ones, which provides synergistic and additive effects. The Citrus genus provides a rich source of such bio-preservatives, in addition to the availability of the genus and the low price of citrus fruit crops. In this study, we identify the most abundant flavonoids in citrus fruits (hesperidin) from the polar extract of mandarin peels (agro-waste) by using spectroscopic techniques, as well as limonene from the non-polar portion using GC techniques. Then, we explore the synergistic and additive effects of hesperidin from total mandarin extract with widely used NaNO2 to create a chemical preservative in food products. The results are promising and show a significant synergistic and additive activity. The combination of mandarin peel extract with NaNO2 had synergistic antibacterial activity against B. cereus, Staph. aureus, E. coli, and P. aeruginosa, while hesperidin showed a synergistic effect against B. cereus and P. aeruginosa and an additive effect against Staph. aureus and E. coli. These results refer to the ability of reducing the concentration of NaNO2 and replacing it with a safe natural bio-preservative such as hesperidin from total mandarin extract. Moreover, this led to gaining benefits from their biological and nutritive values.
Cytoprotective Potential of Aged Garlic Extract (AGE) and Its Active Constituent, S-allyl-l-cysteine, in Presence of Carvedilol during Isoproterenol-Induced Myocardial Disturbance and Metabolic Derangements in Rats
Authors: Asdaq Syed Mohammed Basheeruddin , Challa Obulesu , Alamri Abdulhakeem S. , Alsanie Walaa F. , Alhomrani Majid , Almutiri Abdulrahman Hadi , Alshammari Majed Sadun
Published: May 2021

This study was conducted to determine the potential interaction of aged garlic extract (AGE) with carvedilol (CAR), as well as to investigate the role of S-allyl-l-cysteine (SAC), an active constituent of AGE, in rats with isoproterenol (ISO)-induced myocardial dysfunction. At the end of three weeks of treatment with AGE (2 and 5 mL/kg) or SAC (13.1 and 32.76 mg/kg), either alone or along with CAR (10 mg/kg) in the respective groups of animals, ISO was administered subcutaneously to induce myocardial damage. Myocardial infarction (MI) diagnostic predictor enzymes, lactate dehydrogenase (LDH) and creatinine kinase (CK-MB), were measured in both serum and heart tissue homogenates (HTH). Superoxide dismutase (SOD), catalase, and thiobarbituric acid reactive species (TBARS) were estimated in HTH. When compared with other groups, the combined therapy of high doses of AGE and SAC given alone or together with CAR caused a significant decrease in serum LDH and CK-MB activities. Further, significant rise in the LDH and CK-MB activities in HTH was noticed in the combined groups of AGE and SAC with CAR. It was also observed that both doses of AGE and SAC significantly increased endogenous antioxidants in HTH. Furthermore, histopathological observations corroborated the biochemical findings. The cytoprotective potential of SAC and AGE were dose-dependent, and SAC was more potent than AGE. The protection offered by aged garlic may be attributed to SAC. Overall, the results indicated that a high dose of AGE and its constituent SAC, when combined with carvedilol, has a synergistic effect in preventing morphological and physiological changes in the myocardium during ISO-induced myocardial damage.
Identification of SARS-CoV-2 Receptor Binding Inhibitors by In Vitro Screening of Drug Libraries
Authors: David Alon Ben , Diamant Eran , Dor Eyal , Barnea Ada , Natan Niva , Levin Lilach , Chapman Shira , Mimran Lilach Cherry , Epstein Eyal , Zichel Ran , Torgeman Amram
Published: May 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) global pandemic. The first step of viral infection is cell attachment, which is mediated by the binding of the SARS-CoV-2 receptor binding domain (RBD), part of the virus spike protein, to human angiotensin-converting enzyme 2 (ACE2). Therefore, drug repurposing to discover RBD-ACE2 binding inhibitors may provide a rapid and safe approach for COVID-19 therapy. Here, we describe the development of an in vitro RBD-ACE2 binding assay and its application to identify inhibitors of the interaction of the SARS-CoV-2 RBD to ACE2 by the high-throughput screening of two compound libraries (LOPAC®1280 and DiscoveryProbeTM). Three compounds, heparin sodium, aurintricarboxylic acid (ATA), and ellagic acid, were found to exert an effective binding inhibition, with IC50 values ranging from 0.6 to 5.5 µg/mL. A plaque reduction assay in Vero E6 cells infected with a SARS-CoV-2 surrogate virus confirmed the inhibition efficacy of heparin sodium and ATA. Molecular docking analysis located potential binding sites of these compounds in the RBD. In light of these findings, the screening system described herein can be applied to other drug libraries to discover potent SARS-CoV-2 inhibitors.
Photoactive Thin-Film Structures of Curcumin, TiO2 and ZnO
Authors: Philip Anish , Ghiyasi Ramin , Karppinen Maarit
Published: May 2021

Curcumin is known as a biologically active compound and a possible antimicrobial agent. Here, we combine it with TiO2 and ZnO semiconductors, known for their photocatalytic properties, with an eye towards synergistic photo-harvesting and/or antimicrobial effects. We deposit different nanoscale multi-layer structures of curcumin, TiO2 and ZnO, by combining the solution-based spin-coating (S-C) technique and the gas-phase atomic layer deposition (ALD) and molecular layer deposition (MLD) thin-film techniques. As one of the highlights, we demonstrate for these multi-layer structures a red-shift in the absorbance maximum and an expansion of the absorbance edge as far as the longest visible wavelength region, which activates them for the visible light harvesting. The novel fabrication approaches introduced here should be compatible with, e.g., textile substrates, opening up new horizons for novel applications such as new types of protective masks with thin conformal antimicrobial coatings.
Protective Effects of Thymoquinone, an Active Compound of Nigella sativa, on Rats with Benzo(a)pyrene-Induced Lung Injury through Regulation of Oxidative Stress and Inflammation
Authors: Alzohairy Mohammad A. , Khan Amjad Ali , Alsahli Mohammed A. , Almatroodi Saleh A. , Rahmani Arshad Husain
Published: May 2021

Benzopyrene [B(a)P] is a well-recognized environmental carcinogen, which promotes oxidative stress, inflammation, and other metabolic complications. In the current study, the therapeutic effects of thymoquinone (TQ) against B(a)P-induced lung injury in experimental rats were examined. B(a)P used at 50 mg/kg b.w. induced lung injury that was investigated via the evaluation of lipid profile, inflammatory markers, nitric oxide (NO), and malondialdehyde (MDA) levels. B(a)P also led to a decrease in superoxide dismutase (SOD) (34.3 vs. 58.5 U/mg protein), glutathione peroxidase (GPx) (42.4 vs. 72.8 U/mg protein), catalase (CAT) (21.2 vs. 30.5 U/mg protein), and total antioxidant capacity compared to normal animals. Treatment with TQ, used at 50 mg/kg b.w., led to a significant reduction in triglycerides (TG) (196.2 vs. 233.7 mg/dL), total cholesterol (TC) (107.2 vs. 129.3 mg/dL), and inflammatory markers and increased the antioxidant enzyme level in comparison with the group that was administered B(a)P only (p < 0.05). B(a)P administration led to the thickening of lung epithelium, increased inflammatory cell infiltration, damaged lung tissue architecture, and led to accumulation of collagen fibres as studied through haematoxylin and eosin (H&E), Sirius red, and Masson’s trichrome staining. Moreover, the recognition of apoptotic nuclei and expression pattern of NF-κB were evaluated through the TUNEL assay and immunohistochemistry, respectively. The histopathological changes were found to be considerably low in the TQ-treated animal group. The TUNEL-positive cells increased significantly in the B(a)P-induced group, whereas the TQ-treated group showed a decreased apoptosis rate. Significantly high cytoplasmic expression of NF-κB in the B(a)P-induced group was seen, and this expression was prominently reduced in the TQ-treated group. Our results suggest that TQ can be used in the protection against benzopyrene-caused lung injury.
Copper-Catalyzed Synthesis of Axially Chiral Biaryls with Diaryliodonium Salts as Arylation Reagents
Authors: Zhang Ji-Wei , Xiang Shao-Hua , Li Shaoyu , Tan Bin
Published: May 2021

NOBIN and BINAM derivatives harboring biaryl frameworks are recognized as a class of important atropisomers with versatile applications. Here, we present an efficient synthetic route to access such compounds through copper-catalyzed domino arylation of N-arylhydroxylamines or N-arylhydrazines with diaryliodonium salts and [3,3]-sigmatropic rearrangement. This reaction features mild conditions, good substrate compatibility, and excellent efficiency. The practicality of this protocol was further extended by the synthesis of biaryl amino alcohols.
Fish and Shellfish-Derived Anti-Inflammatory Protein Products: Properties and Mechanisms
Authors: Kemp David C. , Kwon Jung Yeon
Published: May 2021

The interest in utilizing food-derived compounds therapeutically has been rising. With the growing prevalence of systematic chronic inflammation (SCI), efforts to find treatments that do not result in the side effects of current anti-inflammatory drugs are underway. Bioactive peptides (BAPs) are a particularly promising class of compounds for the treatment of SCI, and the abundance of high-quality seafood processing byproducts (SPB) makes it a favorable material to derive anti-inflammatory BAPs. Recent research into the structural properties of anti-inflammatory BAPs has found a few key tendencies including they tend to be short and of low molecular weight (LMW), have an overall positive charge, contain hydrophobic amino acids (AAs), and be rich in radical scavenging AAs. SPB-derived anti-inflammatory BAPs have been observed to work via inhibition of the NF-κB and MAPK pathways by disrupting the phosphorylation of IκBα and one or more kinases (ERK, JNK, and p38), respectively. Radical scavenging capacity has also been shown to play a significant role in the efficacy of SPB-derived anti-inflammatory BAPs. To determine if SPB-derived BAPs can serve as an effective treatment for SCI it will be important to understand their properties and mechanisms of action, and this review highlights such findings in recent research.
Shoot Multiplication and Callus Induction of Labisia pumila var. alata as Influenced by Different Plant Growth Regulators Treatments and Its Polyphenolic Activities Compared with the Wild Plant
Authors: Najhah Mat Yunus , Jaafar Hawa Z. E. , Nakasha Jaafar Juju , Hakiman Mansor
Published: May 2021

This study aims to investigate whether the in vitro-cultured L. pumila var. alata has higher antioxidant activity than its wild plant. An 8-week-old L. pumila var. alata nodal segment and leaf explants were cultured onto Murashige and Skoog (MS) medium supplemented with various cytokinins (zeatin, kinetin, and 6-benzylaminopurine (BAP)) for shoot multiplication and auxins (2,4-dichlorophenoxyacetic acid (2,4-D) and picloram) for callus induction, respectively. The results showed that 2 mg/L zeatin produced the optimal results for shoot and leaf development, and 0.5 mg/L 2,4-D produced the highest callus induction results (60%). After this, 0.5 mg/L 2,4-D was combined with 0.25 mg/L cytokinins and supplemented to the MS medium. The optimal results for callus induction (100%) with yellowish to greenish and compact texture were obtained using 0.5 mg/L 2,4-D combined with 0.25 mg/L zeatin. Leaves obtained from in vitro plantlets and wild plants as well as callus were extracted and analyzed for their antioxidant activities (DPPH and FRAP methods) and polyphenolic properties (total flavonoid and total phenolic content). When compared with leaf extracts of in vitro plantlets and wild plants of L. pumila var. alata, the callus extract displayed significantly higher antioxidant activities and total phenolic and flavonoid content. Hence, callus culture potentially can be adapted for antioxidant and polyphenolic production to satisfy pharmaceutical and nutraceutical needs while conserving wild L. pumila var. alata.
Carrier Blocking Layer Materials and Application in Organic Photodetectors
Authors: Li Yi , Chen Hu , Zhang Jianhua
Published: May 2021

As a promising candidate for next-generation photodetectors, organic photodetectors (OPDs) have gained increasing interest as they offer cost-effective fabrication methods using solution processes and a tunable spectral response range, making them particularly attractive for large area image sensors on lightweight flexible substrates. Carrier blocking layers engineering is very important to the high performance of OPDs that can select a certain charge carriers (holes or electrons) to be collected and suppress another carrier. Carrier blocking layers of OPDs play a critical role in reducing dark current, boosting their efficiency and long-time stability. This Review summarizes various materials for carrier blocking layers and some of the latest progress in OPDs. This provides the reader with guidelines to improve the OPD performance via carrier blocking layers engineering.
Emergence and Evolution of Crystallization in TiO2 Thin Films: A Structural and Morphological Study
Authors: Durante Ofelia , Di Giorgio Cinzia , Granata Veronica , Neilson Joshua , Fittipaldi Rosalba , Vecchione Antonio , Carapella Giovanni , Chiadini Francesco , DeSalvo Riccardo , Dinelli Franco , Fiumara Vincenzo , Pierro Vincenzo , Pinto Innocenzo M. , Principe Maria , Bobba Fabrizio
Published: May 2021

Among all transition metal oxides, titanium dioxide (TiO2) is one of the most intensively investigated materials due to its large range of applications, both in the amorphous and crystalline forms. We have produced amorphous TiO2 thin films by means of room temperature ion-plasma assisted e-beam deposition, and we have heat-treated the samples to study the onset of crystallization. Herein, we have detailed the earliest stage and the evolution of crystallization, as a function of both the annealing temperature, in the range 250–1000 °C, and the TiO2 thickness, varying between 5 and 200 nm. We have explored the structural and morphological properties of the as grown and heat-treated samples with Atomic Force Microscopy, Scanning Electron Microscopy, X-ray Diffractometry, and Raman spectroscopy. We have observed an increasing crystallization onset temperature as the film thickness is reduced, as well as remarkable differences in the crystallization evolution, depending on the film thickness. Moreover, we have shown a strong cross-talking among the complementary techniques used displaying that also surface imaging can provide distinctive information on material crystallization. Finally, we have also explored the phonon lifetime as a function of the TiO2 thickness and annealing temperature, both ultimately affecting the degree of crystallinity.
Funneling Spontaneous Emission into Waveguides via Epsilon-Near-Zero Metamaterials
Authors: Channab M. , Pirri C. , Angelini A.
Published: May 2021

In this work, we discuss the use of epsilon-near-zero (ENZ) metamaterials to efficiently couple light radiated by a dipolar source to an in-plane waveguide. We exploit both enhanced and directional emission provided by ENZ metamaterials to optimize the injection of light into the waveguide by tuning the metal fill factor. We show that a net increase in intensity injected into the waveguide with respect to the total power radiated by the isolated dipole can be achieved in experimentally feasible conditions. We think the proposed system may open up new opportunities for several optical applications and integrated technologies, especially for those limited by outcoupling efficiency and emission rate.
Hybrid Materials Based on Multi-Walled Carbon Nanotubes and Nanoparticles with Antimicrobial Properties
Authors: David Madalina Elena , Ion Rodica-Mariana , Grigorescu Ramona Marina , Iancu Lorena , Holban Alina Maria , Nicoara Adrian Ionut , Alexandrescu Elvira , Somoghi Raluca , Ganciarov Mihaela , Vasilievici Gabriel , Gheboianu Anca Irina
Published: May 2021

In this study, multi-walled carbon nanotubes (MWCNTs) were decorated with different types of nanoparticles (NPs) in order to obtain hybrid materials with improved antimicrobial activity. Structural and morphological analysis, such as Fourier transformed infrared spectroscopy, Raman spectroscopy, X-ray diffraction, transmission electron microscopy, environmental scanning electron microscopy/energy-dispersive X-ray spectroscopy and the Brunauer–Emmett–Teller technique were used in order to investigate the decoration of the nanotubes with NPs. Analysis of the decorated nanotubes showed a narrow size distribution of NPs, 7–13 nm for the nanotubes decorated with zinc oxide (ZnO) NPs, 15–33 nm for the nanotubes decorated with silver (Ag) NPs and 20–35 nm for the nanotubes decorated with hydroxyapatite (HAp) NPs, respectively. The dispersion in water of the obtained nanomaterials was improved for all the decorated MWCNTs, as revealed by the relative absorbance variation in time of the water-dispersed nanomaterials. The obtained nanomaterials showed a good antimicrobial activity; however, the presence of the NPs on the surface of MWCNTs improved the nanocomposites’ activity. The presence of ZnO and Ag nanoparticles enhanced the antimicrobial properties of the material, in clinically relevant microbial strains. Our data proves that such composite nanomaterials are efficient antimicrobial agents, suitable for the therapy of severe infection and biofilms.
Carbothermal Synthesis of Ni/Fe Bimetallic Nanoparticles Embedded into Graphitized Carbon for Efficient Removal of Chlorophenol
Authors: Zhuang Min , Shi Wen , Wang Hui , Cui Liqiang , Quan Guixiang , Yan Jinlong
Published: May 2021

The reactivity of nanoscale zero-valent iron is limited by surface passivation and particle agglomeration. Here, Ni/Fe bimetallic nanoparticles embedded into graphitized carbon (NiFe@GC) were prepared from Ni/Fe bimetallic complex through a carbothermal reduction treatment. The Ni/Fe nanoparticles were uniformly distributed in the GC matrix with controllable particle sizes, and NiFe@GC exhibited a larger specific surface area than unsupported nanoscale zero-valent iron/nickel (FeNi NPs). The XRD results revealed that Ni/Fe bimetallic nanoparticles embedded into graphitized carbon were protected from oxidization. The NiFe@GC performed excellently in 2,4,6-trichlorophenol (TCP) removal from an aqueous solution. The removal efficiency of TCP for NiFe@GC-50 was more than twice that of FeNi nanoparticles, and the removal efficiency of TCP increased from 78.5% to 94.1% when the Ni/Fe molar ratio increased from 0 to 50%. The removal efficiency of TCP by NiFe@GC-50 can maintain 76.8% after 10 days of aging, much higher than that of FeNi NPs (29.6%). The higher performance of NiFe@GC should be ascribed to the significant synergistic effect of the combination of NiFe bimetallic nanoparticles and GC. In the presence of Ni, atomic H* generated by zero-valent iron corrosion can accelerate TCP removal. The GC coated on the surface of Ni/Fe bimetallic nanoparticles can protect them from oxidation and deactivation.
Fabrication, Microstructure and Colloidal Stability of Humic Acids Loaded Fe3O4/APTES Nanosorbents for Environmental Applications
Authors: Bondarenko Lyubov , Illés Erzsébet , Tombácz Etelka , Dzhardimalieva Gulzhian , Golubeva Nina , Tushavina Olga , Adachi Yasuhisa , Kydralieva Kamila
Published: May 2021

Nowadays, numerous researches are being performed to formulate nontoxic multifunctional magnetic materials possessing both high colloidal stability and magnetization, but there is a demand in the prediction of chemical and colloidal stability in water solutions. Herein, a series of silica-coated magnetite nanoparticles (MNPs) has been synthesized via the sol-gel method with and without establishing an inert atmosphere, and then it was tested in terms of humic acids (HA) loading applied as a multifunctional coating agent. The influence of ambient conditions on the microstructure, colloidal stability and HA loading of different silica-coated MNPs has been established. The XRD patterns show that the content of stoichiometric Fe3O4 decreases from 78.8% to 42.4% at inert and ambient atmosphere synthesis, respectively. The most striking observation was the shift of the MNPs isoelectric point from pH ~7 to 3, with an increasing HA reaching up to the reversal of the zeta potential sign as it was covered completely by HA molecules. The zeta potential data of MNPs can be used to predict the loading capacity for HA polyanions. The data help to understand the way for materials’ development with the complexation ability of humic acids and with the insolubility of silica gel to pave the way to develop a novel, efficient and magnetically separable adsorbent for contaminant removal.
Using Wearable Cameras to Assess Foods and Beverages Omitted in 24 Hour Dietary Recalls and a Text Entry Food Record App
Authors: Chan Virginia , Davies Alyse , Wellard-Cole Lyndal , Lu Silvia , Ng Hoi , Tsoi Lok , Tiscia Anjali , Signal Louise , Rangan Anna , Gemming Luke , Allman-Farinelli Margaret
Published: May 2021

Technology-enhanced methods of dietary assessment may still face common limitations of self-report. This study aimed to assess foods and beverages omitted when both a 24 h recall and a smartphone app were used to assess dietary intake compared with camera images. For three consecutive days, young adults (18–30 years) wore an Autographer camera that took point-of-view images every 30 seconds. Over the same period, participants reported their diet in the app and completed daily 24 h recalls. Camera images were reviewed for food and beverages, then matched to the items reported in the 24 h recall and app. ANOVA (with post hoc analysis using Tukey Honest Significant Difference) and paired t-test were conducted. Discretionary snacks were frequently omitted by both methods (p < 0.001). Water was omitted more frequently in the app than in the camera images (p < 0.001) and 24 h recall (p < 0.001). Dairy and alternatives (p = 0.001), sugar-based products (p = 0.007), savoury sauces and condiments (p < 0.001), fats and oils (p < 0.001) and alcohol (p = 0.002) were more frequently omitted in the app than in the 24 h recall. The use of traditional self-report methods of assessing diet remains problematic even with the addition of technology and finding new objective methods that are not intrusive and are of low burden to participants remains a challenge.
Short- and Branched-Chain Fatty Acids as Fecal Markers for Microbiota Activity in Vegans and Omnivores
Authors: Trefflich Iris , Dietrich Stefan , Braune Annett , Abraham Klaus , Weikert Cornelia
Published: May 2021

A vegan diet could impact microbiota composition and bacterial metabolites like short-chain (SCFA) and branched-chain fatty acids (BCFA). The aim of this study was to compare the concentrations of SCFA, BCFA, ammonia, and fecal pH between vegans and omnivores. In this cross-sectional study (vegans n = 36; omnivores n = 36), microbiota composition, fecal SCFA, BCFA, and ammonia concentrations and pH were analyzed in complete stool samples. A random forest regression (RFR) was used to identify bacteria predicting SCFA/BCFA concentrations in vegans and omnivores. No significant differences in SCFA and BCFA concentrations were observed between vegans and omnivores. Fecal pH (p = 0.005) and ammonia concentration (p = 0.01) were significantly lower in vegans than in omnivores, while fiber intake was higher (p < 0.0001). Shannon diversity was higher in omnivores compared to vegans on species level (p = 0.04) only. In vegans, a cluster of Faecalibacterium prausnitzii, Prevotella copri, Dialister spp., and Eubacterium spp. was predictive for SCFA and BCFA concentrations. In omnivores, Bacteroides spp., Clostridium spp., Ruminococcus spp., and Prevotella copri were predictive. Though SCFA and BCFA did not differ between vegans and omnivores, the results of the RFR suggest that bacterial functionality may be adapted to varying nutrient availability in these diets.
Anthropometric Dimensions and Bone Quality in International Male Beach Handball Players: Junior vs. Senior Comparison
Authors: Martínez-Rodríguez Alejandro , Sánchez-Sánchez Javier , Vicente-Martínez Manuel , Martínez-Olcina María , Miralles-Amorós Laura , Sánchez-Sáez Juan Antonio
Published: May 2021

Background: Beach handball is a recent team sport characterized by defensive and offensive actions on a sand surface. Scientific evidence has shown that body composition is fundamental in sports performance. The main objective of this study was to know the body composition, anthropometric characteristics, and bone mineral density of elite beach handball players. Furthermore, another purpose was to analyze the differences between categories (junior and senior) and playing position. Methods: A descriptive, cross-sectional study of 36 male players (18 juniors and 18 seniors) of the Spanish National Beach Handball Team was conducted. Full profile anthropometry and calcaneal ultrasound measurements were used. Results: Significant differences between categories (p < 0.05) were found in: height, body mass, arm span, BMI, muscle mass, fat mass, bone mass, skinfolds, and body perimeters. The somatotype changes depending on the playing position. Bone mineral density of the players was adequate. No significant differences were found by playing position. Conclusions: Senior players had a better body composition due to the presence of less fat mass than junior players. This study provides reference values of elite junior and senior beach handball players and by playing positions. This data is useful for the identification of talents and players who should be trained to improve their body composition.
Adequate Urinary Iodine Concentration among Infants in the Inland Area of Norway
Authors: Bakken Kjersti Sletten , Aarsland Tonje Eiane , Groufh-Jacobsen Synne , Solvik Beate Stokke , Gjengedal Elin Lovise Folven , Henjum Sigrun , Strand Tor Arne
Published: May 2021

Considering the importance of iodine to support optimal growth and neurological development of the brain and central nervous system, this study aimed to assess and evaluate iodine status in Norwegian infants. We collected data on dietary intake of iodine, iodine knowledge in mothers, and assessed iodine concentration in mother’s breast milk and in infant’s urine in a cross-sectional study at two public healthcare clinics in the inland area of Norway. In the 130 mother–infant pairs, the estimated infant 24-h median iodine intake was 50 (IQR 31, 78) µg/day. The median infant urinary iodine concentration (UIC) was 146 (IQR 93, 250) µg/L and within the recommended median defined by the World Health Organization for this age group. Weaned infants had a higher UIC [210 (IQR 130, 330) µg/L] than exclusively breastfed infants [130 (IQR 78, 210) µg/L] and partially breastfed infants [135 (IQR 89, 250) µg/L], which suggest that the dietary data obtained in this study did not capture the accurate iodine intake of the included infants. The iodine status of infants in the inland area of Norway seemed adequate. Weaned infants had higher UIC compared to breastfed infants, suggesting early access and consumption of other sources of iodine in addition to breast milk.
Obesity and Circulating Levels of Vitamin D before and after Weight Loss Induced by a Very Low-Calorie Ketogenic Diet
Authors: Buscemi Silvio , Buscemi Carola , Corleo Davide , De Pergola Giovanni , Caldarella Rosalia , Meli Francesco , Randazzo Cristiana , Milazzo Salvatore , Barile Anna Maria , Rosafio Giuseppe , Settipani Valentina , Gurrera Sabina , Borzì Antonio Maria , Ciaccio Marcello
Published: May 2021

Background: Vitamin D plays a pivotal role in calcium and phosphorus metabolism, also influencing bone tissue. Several studies have reported that vitamin D blood levels were significantly lower in people with obesity, probably due to its uptake by the adipose tissue. Clinical studies that investigated the changes of circulating levels of vitamin D following weight loss reported controversial data. A very low-calorie ketogenic diet is acknowledged as a reliable treatment to achieve a rapid weight loss. Therefore, we investigated the effect of weight loss, consequent to a very low-calorie ketogenic diet, on vitamin D blood concentrations. Methods: A cohort of 31 people with obesity underwent a very low-calorie ketogenic diet for 10–12 weeks. The serum concentrations of vitamin D, parathormone, calcium and phosphorous were measured before and after weight loss; they were compared to a control group of 20 non-obese, non-diabetic, age- and gender-matched persons. Results: Patients with obesity had a higher habitual intake of vitamin D than the control group (p < 0.05). However, the vitamin D blood levels of the obese group were significantly lower than those of the control group (p < 0.005) and they increased after weight loss (p < 0.001). At baseline, vitamin D blood concentrations of the persons with obesity were significantly correlated with both fat mass–kg (r = −0.40; p < 0.05) and body mass index (r = −0.47; p < 0.01). Following very low-calorie ketogenic diet, the change in vitamin D serum concentrations was correlated only with the change in fat mass–kg (r = −0.43; p < 0.01). Conclusion: This study confirmed that patients with obesity have lower vitamin D levels that normalize after significant weight loss, supporting the hypothesis that vitamin D is stored in the adipose tissue and released following weight loss.
Novice Nurses’ Experiences Caring for Acutely Ill Patients during a Pandemic
Authors: Naylor Heather , Hadenfeldt Cynthia , Timmons Patricia
Published: May 2021

The Coronavirus pandemic erupted in 2020 and new graduate registered nurses (RNs) found themselves caring for those with devastating illness as they were transitioning into nursing practice. The purpose of this study was to describe the experience of novice nurses working in acute care settings during a pandemic. This qualitative phenomenological study of novice nurses working in facilities providing acute care for COVID-19 patients was conducted in Phoenix, Arizona, USA. Purposive sampling identified 13 participants for interviews. Data were analyzed using thematic analysis. Eight themes emerged: Dealing with death, Which personal protective equipment (PPE) will keep us safe?, Caring for high acuity patients with limited training, Difficulties working short-staffed, Everything is not okay, Support from the healthcare team, Nursing school preparation for a pandemic, I would still choose nursing. Novice nurses felt challenged by the experience and were at times overwhelmed and struggling to cope. Support from peers and coping skills learned during nursing school helped them continue to work during a critical time. Data from this study suggest that some participants may have been experiencing symptoms of anxiety, depression, or post-traumatic stress disorder, and findings provide foundational insights for nursing education and psychological interventions to support the nursing workforce.
Comparative Assessment of In-House Real-Time PCRs Targeting Enteric Disease-Associated Microsporidia in Human Stool Samples
Authors: Tanida Konstantin , Hahn Andreas , Eberhardt Kirsten Alexandra , Tannich Egbert , Landt Olfert , Kann Simone , Feldt Torsten , Sarfo Fred Stephen , Di Cristanziano Veronica , Frickmann Hagen , Loderstädt Ulrike
Published: May 2021

Microsporidiosis is an infection predominantly occurring in immunosuppressed patients and infrequently also in travelers. This study was performed to comparatively evaluate the diagnostic accuracy of real-time PCR assays targeting microsporidia with etiological relevance in the stool of human patients in a latent class analysis-based test comparison without a reference standard with perfect accuracy. Thereby, two one-tube real-time PCR assays and two two-tube real-time PCR assays targeting Enterocytozoon bieneusi and Encephalocytozoon spp. were included in the assessment with reference stool material (20), stool samples from Ghanaian HIV-positive patients (903), and from travelers, migrants and Colombian indigenous people (416). Sensitivity of the assays ranged from 60.4% to 97.4% and specificity from 99.1% to 100% with substantial agreement according to Cohen’s kappa of 79.6%. Microsporidia DNA was detected in the reference material and the stool of the HIV patients but not in the stool of the travelers, migrants, and the Colombian indigenous people. Accuracy-adjusted prevalence was 5.8% (n = 78) for the study population as a whole. In conclusion, reliable detection of enteric disease-associated microsporidia in stool samples by real-time PCR could be demonstrated, but sensitivity between the compared microsporidia-specific real-time PCR assays varied.
Regulation of AMPK Activity by CRBN Is Independent of the Thalidomide-CRL4CRBN Protein Degradation Axis
Authors: Yang Seung-Joo , Jeon Seungje , Baek Jeong Won , Lee Kwang Min , Park Chul-Seung
Published: May 2021

Cereblon (CRBN), a primary target of immune-modulatory imide drugs (IMiDs), functions as a substrate receptor in the CUL4-RBX1-DDB1-CRBN (known as CRL4CRBN) E3 ubiquitin ligase complex. Binding of IMiDs to CRBN redirects the CRL4CRBN E3 ubiquitin ligase to recruit or displace its substrates. Interaction between CRBN and the AMPK α subunit leads to CRL4CRBN-dependent degradation of the γ subunit and inhibits AMPK activity. However, the effect of thalidomide on the function of CRBN as a negative regulator of AMPK through interaction with the α subunit remains unclear. Here, we show that thalidomide does not affect AMPK activation or the binding affinity between CRBN and the AMPK α subunit. Thalidomide had no effect on AMPK activity independent of CRBN expression. The N-terminal region and C-terminal tail of CRBN, which is distinct from the IMiD binding site, were critical for interaction with the AMPK α subunit. The present results suggest that CRL4CRBN negatively regulates AMPK through a pathway independent from the CRBN-IMiD binding region.
Biomedical Text Link Prediction for Drug Discovery: A Case Study with COVID-19
Authors: McCoy Kevin , Gudapati Sateesh , He Lawrence , Horlander Elaina , Kartchner David , Kulkarni Soham , Mehra Nidhi , Prakash Jayant , Thenot Helena , Vanga Sri Vivek , Wagner Abigail , White Brandon , Mitchell Cassie S.
Published: May 2021

Link prediction in artificial intelligence is used to identify missing links or derive future relationships that can occur in complex networks. A link prediction model was developed using the complex heterogeneous biomedical knowledge graph, SemNet, to predict missing links in biomedical literature for drug discovery. A web application visualized knowledge graph embeddings and link prediction results using TransE, CompleX, and RotatE based methods. The link prediction model achieved up to 0.44 hits@10 on the entity prediction tasks. The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, served as a case study to demonstrate the efficacy of link prediction modeling for drug discovery. The link prediction algorithm guided identification and ranking of repurposed drug candidates for SARS-CoV-2 primarily by text mining biomedical literature from previous coronaviruses, including SARS and middle east respiratory syndrome (MERS). Repurposed drugs included potential primary SARS-CoV-2 treatment, adjunctive therapies, or therapeutics to treat side effects. The link prediction accuracy for nodes ranked highly for SARS coronavirus was 0.875 as calculated by human in the loop validation on existing COVID-19 specific data sets. Drug classes predicted as highly ranked include anti-inflammatory, nucleoside analogs, protease inhibitors, antimalarials, envelope proteins, and glycoproteins. Examples of highly ranked predicted links to SARS-CoV-2: human leukocyte interferon, recombinant interferon-gamma, cyclosporine, antiviral therapy, zidovudine, chloroquine, vaccination, methotrexate, artemisinin, alkaloids, glycyrrhizic acid, quinine, flavonoids, amprenavir, suramin, complement system proteins, fluoroquinolones, bone marrow transplantation, albuterol, ciprofloxacin, quinolone antibacterial agents, and hydroxymethylglutaryl-CoA reductase inhibitors. Approximately 40% of identified drugs were not previously connected to SARS, such as edetic acid or biotin. In summary, link prediction can effectively suggest repurposed drugs for emergent diseases.
Synthesis of Novel, Dual-Targeting 68Ga-NODAGA-LacN-E[c(RGDfK)]2 Glycopeptide as a PET Imaging Agent for Cancer Diagnosis
Authors: Gyuricza Barbara , Szabó Judit , Arató Viktória , Szücs Dániel , Vágner Adrienn , Szikra Dezső , Fekete Anikó
Published: May 2021

Radiolabeled peptides possessing an Arg-Gly-Asp (RGD) motif are widely used radiopharmaceuticals for PET imaging of tumor angiogenesis due to their high affinity and selectivity to αvβ3 integrin. This receptor is overexpressed in tumor and tumor endothelial cells in the case of numerous cancer cell lines, therefore, it is an excellent biomarker for cancer diagnosis. The galectin-3 protein is also highly expressed in tumor cells and N-acetyllactosamine is a well-established ligand of this receptor. We have developed a synthetic method to prepare a lactosamine-containing radiotracer, namely 68Ga-NODAGA-LacN-E[c(RGDfK)]2, for cancer diagnosis. First, a lactosamine derivative with azido-propyl aglycone was synthetized. Then, NODAGA-NHS was attached to the amino group of this lactosamine derivative. The obtained compound was conjugated to an E[c(RGDfK)]2 peptide with a strain-promoted click reaction. We have accomplished the radiolabeling of the synthetized NODAGA-LacN-E[c(RGDfK)]2 precursor with a positron-emitting 68Ga isotope (radiochemical yield of >95%). The purification of the labeled compound with solid-phase extraction resulted in a radiochemical purity of >99%. Subsequently, the octanol–water partition coefficient (log P) of the labeled complex was determined to be −2.58. In addition, the in vitro stability of 68Ga-NODAGA-LacN-E[c(RGDfK)]2 was investigated and it was found that it was stable under the examined conditions.
Identification and Relative Quantification of hFSH Glycoforms in Women’s Sera via MS–PRM-Based Approach
Authors: Melchiorre Chiara , Chhuon Cerina , Jung Vincent , Lipecka Joanna , Di Rella Francesca , Conforti Alessandro , Amoresano Angela , Carpentieri Andrea , Guerrera Ida Chiara
Published: May 2021

Follicle-stimulating hormone (FSH) is a glycohormone synthesized by adenohypophysis, and it stimulates ovulation in women and spermatogenesis in men by binding to its receptor (FSHR). FSHR is involved in several mechanisms to transduce intracellular signals in response to the FSH stimulus. Exogenous FSH is currently used in the clinic for ovarian hyperstimulation during in vitro fertilization in women, and for treatment of infertility caused by gonadotropin deficiency in men. The glycosylation of FSH strongly affects the binding affinity to its receptor, hence significantly influencing the biological activity of the hormone. Therefore, the accurate measurement and characterization of serum hFSH glycoforms will contribute to elucidating the complex mechanism of action by which different glycoforms elicit distinct biological activity. Nowadays ELISA is the official method with which to monitor serum hFSH, but the test is unable to distinguish between the different FSH glycovariants and is therefore unsuitable to study the biological activity of this hormone. This study presents a preliminary alternative strategy for identifying and quantifying serum hFSH glycoforms based on immunopurification assay and mass spectrometry (MS), and parallel reaction monitoring (PRM) analysis. In this study, we provide an MS–PRM data acquisition method for hFSH glycopeptides identification with high specificity and their quantification by extracting the chromatographic traces of selected fragments of glycopeptides. Once set up for all its features, the proposed method could be transferred to the clinic to improve fertility treatments and follow-ups in men and women.
Optimized Loading of Idarubicin in CalliSpheres® Drug-Eluting Beads and Characterization of Release Profiles and Morphological Properties
Authors: Lu Enhao , Shao Guoliang , Ma Jingqin , He Yiwei , Gong Yuanchuan , Yan Zhiping , Sha Xianyi
Published: May 2021

This study aimed to investigate the idarubicin loading method, compatible stability with contrast agent, release profiles, and morphological properties of 50–150, 100–300, and 300–500 μm CalliSpheres®. The amounts of idarubicin added, loading medium, loading condition, and drug concentration were investigated as factors influencing drug loading efficiency. The drug loading rate was negatively correlated with the amount drug added and diameter of CalliSpheres® and positively correlated with the drug concentration. Compared to loading in purified water and incubation at room temperature, 5% glucose, heating, and ultrasound could accelerate drug loading. The idarubicin loading efficiency was above 95% after 10 min for all three CalliSpheres® with the optimized method of adding 20 mg of idarubicin at a concentration of 2 mg/mL and incubating at room temperature. The drug leak rate was under 1% within 8 h after mixing with iopamidol. Drug release tests indicated the sustained-release performance of CalliSpheres®, and the time to reach 75% of the release plateau level was 8, 26, and 51 min for 50–150, 100–300, and 300–500 μm CalliSpheres®, respectively. After idarubicin loading, the diameters increased by 12%, 36%, and 38% for 50–150, 100–300, and 300–500 μm CalliSpheres®, respectively, and the surface of CalliSpheres® was observed to become smoother than that before drug loading. All three CalliSpheres® presented satisfactory loading efficiency with the optimized method, as well as proper compatible stability and sustained release performance. Among them, 100–300 μm CalliSpheres® are recommended.
Solid Form and Phase Transformation Properties of Fexofenadine Hydrochloride during Wet Granulation Process
Authors: Li Suye , Wu Hengqian , Zhao Yanna , Zhang Ruiyan , Wang Zhengping , Han Jun
Published: May 2021

The quality control of drug products during manufacturing processes is important, particularly the presence of different polymorphic forms in active pharmaceutical ingredients (APIs) during production, which could affect the performance of the formulated products. The objective of this study was to investigate the phase transformation of fexofenadine hydrochloride (FXD) and its influence on the quality and performance of the drug. Water addition was key controlling factor for the polymorphic conversion from Form I to Form II (hydrate) during the wet granulation process of FXD. Water-induced phase transformation of FXD was studied and quantified with XRD and thermal analysis. When FXD was mixed with water, it rapidly converted to Form II, while the conversion is retarded when FXD is formulated with excipients. In addition, the conversion was totally inhibited when the water content was <15% w/w. The relationship between phase transformation and water content was studied at the small scale, and it was also applicable for the scale-up during wet granulation. The effect of phase transition on the FXD tablet performance was investigated by evaluating granule characterization and dissolution behavior. It was shown that, during the transition, the dissolved FXD acted as a binder to improve the properties of granules, such as density and flowability. However, if the water was over added, it can lead to the incomplete release of the FXD during dissolution. In order to balance the quality attributes and the dissolution of granules, the phase transition of FXD and the water amount added should be controlled during wet granulation.
Biomaterials for the Prevention of Oral Candidiasis Development
Authors: Gheorghe Dan Cristian , Niculescu Adelina-Gabriela , Bîrcă Alexandra Cătălina , Grumezescu Alexandru Mihai
Published: May 2021

Thousands of microorganisms coexist within the human microbiota. However, certain conditions can predispose the organism to the overgrowth of specific pathogens that further lead to opportunistic infections. One of the most common such imbalances in the normal oral flora is the excessive growth of Candida spp., which produces oral candidiasis. In immunocompromised individuals, this fungal infection can reach the systemic level and become life-threatening. Hence, prompt and efficient treatment must be administered. Traditional antifungal agents, such as polyenes, azoles, and echinocandins, may often result in severe adverse effects, regardless of the administration form. Therefore, novel treatments have to be developed and implemented in clinical practice. In this regard, the present paper focuses on the newest therapeutic options against oral Candida infections, reviewing compounds and biomaterials with inherent antifungal properties, improved materials for dental prostheses and denture adhesives, drug delivery systems, and combined approaches towards developing the optimum treatment.
Sulfur Deprivation Modulates Salicylic Acid Responses via Nonexpressor of Pathogenesis-Related Gene 1 in Arabidopsis thaliana
Authors: Criollo-Arteaga Steven , Moya-Jimenez Sofia , Jimenez-Meza Martin , Gonzalez-Vera Victor , Gordon-Nunez Jessica , Llerena-Llerena Sol , Ramirez-Villacis Dario X. , van ‘t Hof Pieter , Leon-Reyes Antonio
Published: May 2021

Mineral nutrients are essential for plant growth and reproduction, yet only a few studies connect the nutritional status to plant innate immunity. The backbone of plant defense response is mainly controlled by two major hormones: salicylic acid (SA) and jasmonic acid (JA). This study investigated changes in the macronutrient concentration (deficiency/excess of nitrogen, phosphorus, potassium, magnesium, and sulfur) on the expression of PR1, a well-characterized marker in the SA-pathway, and PDF1.2 and LOX2 for the JA-pathway, analyzing plants carrying the promoter of each gene fused to GUS as a reporter. After histochemical GUS assays, we determined that PR1 gene was strongly activated in response to sulfur (S) deficiency. Using RT-PCR, we observed that the induction of PR1 depended on the function of Non-expressor of Pathogenesis-Related gene 1 (NPR1) and SA accumulation, as PR1 was not expressed in npr1-1 mutant and NahG plants under S-deprived conditions. Plants treated with different S-concentrations showed that total S-deprivation was required to induce SA-mediated defense responses. Additionally, bioassays revealed that S-deprived plants, induced resistance to the hemibiotrophic pathogen Pseudomonas syringae pv. DC3000 and increase susceptibility to the necrotrophic Botrytis cinerea. In conclusion, we observed a relationship between S and SA/JA-dependent defense mechanisms in Arabidopsis.