bluuebunny/crossref_metadata_2025 huggingface dataset:
Tunable Broadband Terahertz Waveband Absorbers Based on Fractal Technology of Graphene Metamaterial
Authors: Xie Tong , Chen Dingbo , Yang Huiping , Xu Yanhong , Zhang Zhenrong , Yang Junbo
Published: January 2021

In this paper, a metasurface Terahertz absorber based on the fractal technology of a graphene geometry resonator to realize ultra-wideband, ultrathin, adjustable double-layer cross-fractal formation is introduced. This paper proposes a dynamically tuned graphene absorbing material. The structure is composed of one- to four-level-fractal graphene pattern layers, MgF2 layers and metal reflective layers to form a two-sided mirror of an asymmetric Fabry–Perot cavity. To confine the terahertz electromagnetic wave, four different fractals are integrated into a supercell, and the coupling and superposition of adjacent resonant cavities form a broadband high-absorption absorber. Using finite element-based full-wave electromagnetic simulation software to simulate the response frequency of 0.4–2.0 THz, we found that the absorber achieves a broadband 1.26 THz range (absorption > 80%) and a relative bandwidth of 106.8%. By adjusting the Fermi energy, it can realize free switching and expand to wider broadband terahertz absorption, by adjusting the polarization angle (Φ) from 0 to 90° to prove that the structure is not sensitive to polarization, the absorber provides a 60° large angle of incidence, polarization for TE and TM the absorption pattern remains basically the same. Compared with the previous work, our proposed structure uses fractal technology to expand the bandwidth and provide dynamic adjustable characteristics with great degrees of freedom. The appearance of the fractal structure reduces the difficulty of actual processing.
Biological Activity of High-Purity β-1,3-1,6-Glucan Derived from the Black Yeast Aureobasidium pullulans: A Literature Review
Authors: Suzuki Toshio , Kusano Kisato , Kondo Nobuhiro , Nishikawa Kouji , Kuge Takao , Ohno Naohito
Published: January 2021

The black yeast Aureobasidium pullulans produces abundant soluble β-1,3-1,6-glucan—a functional food ingredient with known health benefits. For use as a food material, soluble β-1,3-1,6-glucan is produced via fermentation using sucrose as the carbon source. Various functionalities of β-1,3-1,6-glucan have been reported, including its immunomodulatory effect, particularly in the intestine. It also exhibits antitumor and antimetastatic effects, alleviates influenza and food allergies, and relieves stress. Moreover, it reduces the risk of lifestyle-related diseases by protecting the intestinal mucosa, reducing fat, lowering postprandial blood glucose, promoting bone health, and healing gastric ulcers. Furthermore, it induces heat shock protein 70. Clinical studies have reported the antiallergic and triglyceride-reducing effects of β-1,3-1,6-glucan, which are indicators of improvement in lifestyle-related diseases. The primary and higher-order structures of β-1,3-1,6-glucan have been elucidated. Specifically, it comprises a single highly-branched glucose residue with the β-1,6 bond (70% or more) on a backbone of glucose with 1,3-β bonds. β-Glucan shows a triple helical structure, and studies on its use as a drug delivery system have been actively conducted. β-Glucan in combination with anti-inflammatory substances or fullerenes can be used to target macrophages. Based on its health functionality, β-1,3-1,6-glucan is an interesting material as both food and medicine.
Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) and the Developing Immune System: A Narrative Review
Authors: Miles Elizabeth A. , Childs Caroline E. , Calder Philip C.
Published: January 2021

The immune system is complex: it involves many cell types and numerous chemical mediators. An immature immune response increases susceptibility to infection, whilst imbalances amongst immune components leading to loss of tolerance can result in immune-mediated diseases including food allergies. Babies are born with an immature immune response. The immune system develops in early life and breast feeding promotes immune maturation and protects against infections and may protect against allergies. The long-chain polyunsaturated fatty acids (LCPUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered to be important components of breast milk. AA, eicosapentaenoic acid (EPA) and DHA are also present in the membranes of cells of the immune system and act through multiple interacting mechanisms to influence immune function. The effects of AA and of mediators derived from AA are often different from the effects of the n-3 LCPUFAs (i.e., EPA and DHA) and of mediators derived from them. Studies of supplemental n-3 LCPUFAs in pregnant women show some effects on cord blood immune cells and their responses. These studies also demonstrate reduced sensitisation of infants to egg, reduced risk and severity of atopic dermatitis in the first year of life, and reduced persistent wheeze and asthma at ages 3 to 5 years, especially in children of mothers with low habitual intake of n-3 LCPUFAs. Immune markers in preterm and term infants fed formula with AA and DHA were similar to those in infants fed human milk, whereas those in infants fed formula without LCPUFAs were not. Infants who received formula plus LCPUFAs (both AA and DHA) showed a reduced risk of allergic disease and respiratory illness than infants who received standard formula. Studies in which infants received n-3 LCPUFAs report immune differences from controls that suggest better immune maturation and they show lower risk of allergic disease and respiratory illness over the first years of life. Taken together, these findings suggest that LCPUFAs play a role in immune development that is of clinical significance, particularly with regard to allergic sensitisation and allergic manifestations including wheeze and asthma.
Differential Effects of DHA- and EPA-Rich Oils on Sleep in Healthy Young Adults: A Randomized Controlled Trial
Authors: Patan Michael J. , Kennedy David O. , Husberg Cathrine , Hustvedt Svein Olaf , Calder Philip C. , Middleton Benita , Khan Julie , Forster Joanne , Jackson Philippa A.
Published: January 2021

Emerging evidence suggests that adequate intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs), which include docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), might be associated with better sleep quality. N-3 PUFAs, which must be acquired from dietary sources, are typically consumed at suboptimal levels in Western diets. Therefore, the current placebo-controlled, double-blind, randomized trial, investigated the effects of an oil rich in either DHA or EPA on sleep quality in healthy adults who habitually consumed low amounts of oily fish. Eighty-four participants aged 25–49 years completed the 26-week intervention trial. Compared to placebo, improvements in actigraphy sleep efficiency (p = 0.030) and latency (p = 0.026) were observed following the DHA-rich oil. However, these participants also reported feeling less energetic compared to the placebo (p = 0.041), and less rested (p = 0.017), and there was a trend towards feeling less ready to perform (p = 0.075) than those given EPA-rich oil. A trend towards improved sleep efficiency was identified in the EPA-rich group compared to placebo (p = 0.087), along with a significant decrease in both total time in bed (p = 0.032) and total sleep time (p = 0.019) compared to the DHA-rich oil. No significant effects of either treatment were identified for urinary excretion of the major melatonin metabolite 6-sulfatoxymelatonin. This study was the first to demonstrate some positive effects of dietary supplementation with n-3 PUFAs in healthy adult normal sleepers, and provides novel evidence showing the differential effects of n-3 PUFA supplements rich in either DHA or EPA. Further investigation into the mechanisms underpinning these observations including the effects of n-3 PUFAs on sleep architecture are required.
Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications
Authors: Checa-Ros Ana , Jeréz-Calero Antonio , Molina-Carballo Antonio , Campoy Cristina , Muñoz-Hoyos Antonio
Published: January 2021

Studies suggest that the bidirectional relationship existent between the gut microbiome (GM) and the central nervous system (CNS), or so-called the microbiome–gut–brain axis (MGBA), is involved in diverse neuropsychiatric diseases in children and adults. In pediatric age, most studies have focused on patients with autism. However, evidence of the role played by the MGBA in attention deficit/hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood, is still scanty and heterogeneous. This review aims to provide the current evidence on the functioning of the MGBA in pediatric patients with ADHD and the specific role of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in this interaction, as well as the potential of the GM as a therapeutic target for ADHD. We will explore: (1) the diverse communication pathways between the GM and the CNS; (2) changes in the GM composition in children and adolescents with ADHD and association with ADHD pathophysiology; (3) influence of the GM on the ω-3 PUFA imbalance characteristically found in ADHD; (4) interaction between the GM and circadian rhythm regulation, as sleep disorders are frequently comorbid with ADHD; (5) finally, we will evaluate the most recent studies on the use of probiotics in pediatric patients with ADHD.
Pathophysiological Basis for Nutraceutical Supplementation in Heart Failure: A Comprehensive Review
Authors: Mollace Vincenzo , Rosano Giuseppe M. C. , Anker Stefan D. , Coats Andrew J. S. , Seferovic Petar , Mollace Rocco , Tavernese Annamaria , Gliozzi Micaela , Musolino Vincenzo , Carresi Cristina , Maiuolo Jessica , Macrì Roberta , Bosco Francesca , Chiocchi Marcello , Romeo Francesco , Metra Marco , Volterrani Maurizio
Published: January 2021

There is evidence demonstrating that heart failure (HF) occurs in 1–2% of the global population and is often accompanied by comorbidities which contribute to increasing the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non-pharmacological approaches have led to a significant improvement in clinical outcomes in patients affected by HF, residual unmet needs remain, mostly related to the occurrence of poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to possibly contribute to protection of the failing myocardium, although their place in the treatment of HF requires further assessment, in order to find better therapeutic solutions. In this context, the Optimal Nutraceutical Supplementation in Heart Failure (ONUS-HF) working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease, in order to counteract selected pathways that are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring during the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, impaired cardiac stem cell mobilization and an imbalanced regulation of metalloproteinases. Moreover, we reviewed the potential of the nutraceutical supplementation of several natural products, such as coenzyme Q10 (CoQ10), a grape seed extract, Olea Europea L.-related antioxidants, a sodium–glucose cotransporter (SGLT2) inhibitor-rich apple extract and a bergamot polyphenolic fraction, in addition to their support in cardiomyocyte protection, in HF. Such an approach should contribute to optimising the use of nutraceuticals in HF, and the effect needs to be confirmed by means of more targeted clinical trials exploring the efficacy and safety of these compounds.
Association between Breakfast Skipping and Body Weight—A Systematic Review and Meta-Analysis of Observational Longitudinal Studies
Authors: Wicherski Julia , Schlesinger Sabrina , Fischer Florian
Published: January 2021

Globally, increasing rates of obesity are one of the most important health issues. The association between breakfast skipping and body weight is contradictory between cross-sectional and interventional studies. This systematic review and meta-analysis aims to summarize this association based on observational longitudinal studies. We included prospective studies on breakfast skipping and overweight/obesity or weight change in adults. The literature was searched until September 2020 in PubMed and Web of Science. Summary risk ratios (RRs) or β coefficients with a 95% confidence interval (CI), respectively, were estimated in pairwise meta-analyses by applying a random-effects model. In total, nine studies were included in the systematic review and three of them were included in the meta-analyses. The meta-analyses indicated an 11% increased RR for overweight/obesity when breakfast was skipped on ≥3 days per week compared to ≤2 days per week (95% CI: 1.04, 1.19, n = two studies). The meta-analysis on body mass index (BMI) change displayed no difference between breakfast skipping and eating (β = −0.02; 95% CI: −0.05, 0.01; n = two studies). This study provides minimal evidence that breakfast skipping might lead to weight gain and the onset of overweight and obesity.
Vitamin D Modulation of the Innate Immune Response to Paediatric Respiratory Pathogens Associated with Acute Lower Respiratory Infections
Authors: Bleakley Amy S. , Licciardi Paul V. , Binks Michael J.
Published: January 2021

Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs). Globally, the leading childhood respiratory pathogens are Streptococcus pneumoniae, respiratory syncytial virus and the influenza virus. There is a growing body of evidence describing the innate immunomodulatory properties of vitamin D during challenge with respiratory pathogens, but recent systematic and unbiased synthesis of data is lacking, and future research directions are unclear. We therefore conducted a systematic PubMed literature search using the terms “vitamin D” and “Streptococcus pneumoniae” or “Respiratory Syncytial Virus” or “Influenza”. A priori inclusion criteria restricted the review to in vitro studies investigating the effect of vitamin D metabolites on human innate immune cells (primary, differentiated or immortalised) in response to stimulation with the specified respiratory pathogens. Eleven studies met our criteria. Despite some heterogeneity across pathogens and innate cell types, vitamin D modulated pathogen recognition receptor (PRRs: Toll-like receptor 2 (TLR2), TLR4, TLR7 and nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)) expression; increased antimicrobial peptide expression (LL-37, human neutrophil peptide (HNP) 1-3 and β-defensin); modulated autophagosome production reducing apoptosis; and modulated production of inflammatory cytokines (Interleukin (IL) -1β, tumour necrosis factor-α (TNF-α), interferon-ɣ (IFN-ɣ), IL-12p70, IFN-β, Regulated on Activation, Normal T cell Expressed (RANTES), IL-10) and chemokines (IL-8 and C-X-C motif chemokine ligand 10 (CXCL10)). Differential modulation of PRRs and IL-1β was reported across immune cell types; however, this may be due to the experimental design. None of the studies specifically focused on immune responses in cells derived from children. In summary, vitamin D promotes a balanced immune response, potentially enhancing pathogen sensing and clearance and restricting pathogen induced inflammatory dysregulation. This is likely to be important in controlling both ALRIs and the immunopathology associated with poorer outcomes and progression to chronic lung diseases. Many unknowns remain and further investigation is required to clarify the nuances in vitamin D mediated immune responses by pathogen and immune cell type and to determine whether these in vitro findings translate into enhanced immunity and reduced ALRI in the paediatric clinical setting.
Protective Effects of Medicinal Plant Decoctions on Macrophages in the Context of Atherosclerosis
Authors: Checkouri Eloïse , Ramin-Mangata Stéphane , Diotel Nicolas , Viranaicken Wildriss , Marodon Claude , Reignier Franck , Robert-Da Silva Christine , Meilhac Olivier
Published: January 2021

Atherosclerosis is a hallmark of most cardiovascular diseases. The implication of macrophages in this pathology is widely documented, notably for their contribution to lipid accumulation within the arterial wall, associated with oxidative stress and inflammation processes. In order to prevent or limit the atherosclerosis damage, nutritional approaches and medicinal plant-based therapies need to be considered. In Reunion Island, medicinal plant-based beverages are traditionally used for their antioxidant, lipid-lowering and anti-inflammatory properties. The aim of our study was to assess the protective effects of eight medicinal plant decoctions in an in vitro model of RAW 264.7 murine macrophages exposed to pro-atherogenic conditions (oxidized low-density lipoproteins—ox-LDL—E. coli Lipopolysaccharides—LPS). The impact of polyphenol-rich medicinal plant decoctions on cell viability was evaluated by Neutral Red assay. Fluorescent ox-LDL uptake was assessed by flow cytometry and confocal microscopy. Activation of NF-κB was evaluated by quantification of secreted alkaline phosphatase in RAW-Blue™ macrophages. Our results show that medicinal plant decoctions limited the cytotoxicity induced by ox-LDL on macrophages. Flow cytometry analysis in macrophages demonstrated that medicinal plant decoctions from S. cumini and P. mauritianum decreased ox-LDL uptake and accumulation by more than 70%. In addition, medicinal plant decoctions also inhibited NF-κB pathway activation in the presence of pro-inflammatory concentrations of E. coli LPS. Our data suggest that medicinal plant decoctions exert protective effects on ox-LDL-induced cytotoxicity and limited macrophage lipid uptake. Moreover, herbal preparations displayed anti-inflammatory properties on macrophages that can be of interest for limiting the atherosclerotic process.
Consumption of Oleic Acid on the Preservation of Cognitive Functions in Japanese Elderly Individuals
Authors: Sakurai Keisuke , Shen Chutong , Shiraishi Izumi , Inamura Noriko , Hisatsune Tatsuhiro
Published: January 2021

We recruited 154 community-dwelling elderly individuals and conducted a cohort study to find out the nutrient intake that is suitable for maintaining cognitive function in Japanese elders. Cognitive function was evaluated by the two functional tests, the Montreal Cognitive Assessment (MoCA) and Wechsler Memory Scale-Delayed Recall (WMS-DR), and daily nutrient intake was estimated from a Brief-type Self-administered Diet History Questionnaire (BDHQ). By a multiple regression analysis, among the four major nutrients (protein, fat, carbohydrate and ash), we detected a significant correlation between the score of cognitive functions assessed by both MoCA and WMS-DR and daily consumption of fat (p = 0.0317 and p = 0.0111, respectively). Among categories of fatty acid, we found a significant correlation between the score of both MoCA and WMS-DR and consumption of monounsaturated fatty acid (MUFA) (p = 0.0157 and p = 0.0136, respectively). Finally, among MUFAs, we observed a significant correlation between the score of both MoCA and WMS-DR and consumption of oleic acid (p = 0.0405 and p = 0.0165, respectively). From these observations, we can propose that daily consumption of fat, especially in oleic acid, has a beneficial effect against cognitive decline in community-dwelling Japanese elderly individuals.
Effects of Early-Life Stress, Postnatal Diet Modulation and Long-Term Western-Style Diet on Peripheral and Central Inflammatory Markers
Authors: Ruigrok Silvie R. , Abbink Maralinde R. , Geertsema Jorine , Kuindersma Jesse E. , Stöberl Nina , van der Beek Eline M. , Lucassen Paul J. , Schipper Lidewij , Korosi Aniko
Published: January 2021

Early-life stress (ES) exposure increases the risk of developing obesity. Breastfeeding can markedly decrease this risk, and it is thought that the physical properties of the lipid droplets in human milk contribute to this benefit. A concept infant milk formula (IMF) has been developed that mimics these physical properties of human milk (Nuturis®, N-IMF). Previously, we have shown that N-IMF reduces, while ES increases, western-style diet (WSD)-induced fat accumulation in mice. Peripheral and central inflammation are considered to be important for obesity development. We therefore set out to test the effects of ES, Nuturis® and WSD on adipose tissue inflammatory gene expression and microglia in the arcuate nucleus of the hypothalamus. ES was induced in mice by limiting the nesting and bedding material from postnatal day (P) 2 to P9. Mice were fed a standard IMF (S-IMF) or N-IMF from P16 to P42, followed by a standard diet (STD) or WSD until P230. ES modulated adipose tissue inflammatory gene expression early in life, while N-IMF had lasting effects into adulthood. Centrally, ES led to a higher microglia density and more amoeboid microglia at P9. In adulthood, WSD increased the number of amoeboid microglia, and while ES exposure increased microglia coverage, Nuturis® reduced the numbers of amoeboid microglia upon the WSD challenge. These results highlight the impact of the early environment on central and peripheral inflammatory profiles, which may be key in the vulnerability to develop metabolic derangements later in life.
Higher Lipopolysaccharide Binding Protein and Chemerin Concentrations Were Associated with Metabolic Syndrome Features in Pediatric Subjects with Abdominal Obesity during a Lifestyle Intervention
Authors: Marti Amelia , Martínez Isabel , Ojeda-Rodríguez Ana , Azcona-Sanjulian María Cristina
Published: January 2021

Background: Elevated circulating plasma levels of both lipopolysaccharide-binding protein (LBP) and chemerin are reported in patients with obesity, but few studies are available on lifestyle intervention programs. We investigated the association of both LBP and chemerin plasma levels with metabolic syndrome (MetS) outcomes in a lifestyle intervention in children and adolescents with abdominal obesity Methods: Twenty-nine patients enrolled in a randomized controlled trial were selected. The lifestyle intervention with a 2-month intensive phase and a subsequent 10-month follow-up consisted of a moderate calorie-restricted diet, recommendations to increase physical activity levels, and nutritional education. Results: Weight loss was accompanied by a significant reduction in MetS prevalence (−43%; p = 0.009). Chemerin (p = 0.029) and LBP (p = 0.033) plasma levels were significantly reduced at 2 months and 12 months, respectively. At the end of intervention, MetS components were associated with both LBP (p = 0.017) and chemerin (p < 0.001) plasma levels. Conclusions: We describe for the first time a reduction in both LBP and chemerin plasma levels and its association with MetS risk factors after a lifestyle intervention program in children and adolescents with abdominal obesity. Therefore, LBP and chemerin plasma levels could be used as biomarkers for the progression of cardiovascular risk in pediatric populations.
Stunting Malnutrition Associated with Severe Tooth Decay in Cambodian Toddlers
Authors: Renggli Eva Peris , Turton Bathsheba , Sokal-Gutierrez Karen , Hondru Gabriela , Chher Tepirou , Hak Sithan , Poirot Etienne , Laillou Arnaud
Published: January 2021

Background: The persistently high prevalence of undernutrition in Cambodia, in particular stunting or chronic malnutrition, calls for innovative investigation into the risk factors that affect children’s growth during critical phases of development. Methods: Secondary data analysis was performed on a subgroup of children who were present at two time points within the Cambodian Health and Nutrition Monitoring Study (CAHENMS) and who were less than 24 months of age at the nominated baseline. Data consisted of parent interviews on sociodemographic characteristics and feeding practices, and clinical measures for anthropometric measures and dental status. Logistic regression modelling was used to examine the associations between severe dental caries (tooth decay)—as indicated by the Significant Caries Index—and the presence of new cases of stunting malnutrition at follow-up. Results: There were 1595 children who met the inclusion criteria and 1307 (81.9%) were followed after one year. At baseline, 14.4% of the children had severe dental caries, 25.6% presented with stunted growth. 17.6% of the children transitioned from healthy status to a low height-for-age over the observation period. Children with severe dental caries had nearly double the risk (OR = 1.8; CI 1.0–3.0) of making that transition. Conclusion: Severe caries experience was associated with poorer childhood growth and, as such, could be an underinvestigated contributor to stunting.
Assessment of Inorganic Phosphate Intake by the Measurement of the Phosphate/Urea Nitrogen Ratio in Urine
Authors: Pendón-Ruiz de Mier María Victoria , Vergara Noemí , Rodelo-Haad Cristian , López-Zamorano María Dolores , Membrives-González Cristina , López-Baltanás Rodrigo , Muñoz-Castañeda Juan Rafael , Caravaca Francisco , Martín-Malo Alejandro , Felsenfeld Arnold J. , De la Torre Eugenio J. , Soriano Sagrario , Santamaría Rafael , Rodríguez Mariano
Published: January 2021

In chronic kidney disease (CKD) patients, it would be desirable to reduce the intake of inorganic phosphate (P) rather than limit the intake of P contained in proteins. Urinary excretion of P should reflect intestinal absorption of P(inorganic plus protein-derived). The aim of the present study is to determine whether the ratio of urinary P to urinary urea nitrogen (P/UUN ratio) helps identify patients with a high intake of inorganic P.A cross-sectional study was performed in 71 patients affected by metabolic syndrome with CKD (stages 2–3) with normal serum P concentration. A 3-day dietary survey was performed to estimate the average daily amount and the source of P ingested. The daily intake of P was 1086.5 ± 361.3 mg/day; 64% contained in animal proteins, 22% in vegetable proteins, and 14% as inorganic P. The total amount of P ingested did not correlate with daily phosphaturia, but it did correlate with the P/UUN ratio (p < 0.018). Patients with the highest tertile of the P/UUN ratio >71.1 mg/g presented more abundant inorganic P intake (p < 0.038).The P/UUN ratio is suggested to be a marker of inorganic P intake. This finding might be useful in clinical practices to identify the source of dietary P and to make personalized dietary recommendations directed to reduce inorganic P intake.
Changes in the Splenic Melanomacrophage Centre Surface Area in Southern Bluefin Tuna (Thunnus maccoyii) Are Associated with Blood Fluke Infections
Authors: Nowak Barbara F. , Dang Mai , Webber Claire , Neumann Lukas , Bridle Andrew , Bermudez Roberto , Evans Daryl
Published: January 2021

Melanomacrophage centres (MMCs) are aggregates of macrophages accumulating various pigments. They have been proposed as an indicator of fish immune response. Blood flukes are common parasites in farmed fish. Two cohorts of wild Southern Bluefin Tuna (Thunnus maccoyi) were examined at transfer, before treatment against blood flukes (pre-treatment) and at harvest. MMCs were assessed in histological sections using image analysis, while Cardicola forsteri and Cardicola orientalis infection severity was determined using qPCR, count of adult flukes in heart flushes and count of eggs in gill filaments. Fish from both cohorts showed the same pattern in the changes in the surface area of MMCs. The surface area of splenic MMCs increased over the ranching duration and was positively correlated to the PCR determined copy numbers of Cardicola forsteri ITS2 rDNA in the gills of those fish. However, the infection with blood fluke was more variable, both between cohorts and individuals within the same cohort. Eggs of blood fluke were detected in renal MMCs using histology. Cardicola forsteri had a higher prevalence than Cardicola orientalis. This study contributes to our understanding of blood fluke infections in Southern Bluefin Tuna and their interactions with MMCs.
Hot-Melt Extruded Amorphous Solid Dispersion for Solubility, Stability, and Bioavailability Enhancement of Telmisartan
Authors: Giri Bhupendra Raj , Kwon Jaewook , Vo Anh Q. , Bhagurkar Ajinkya M. , Bandari Suresh , Kim Dong Wuk
Published: January 2021

Telmisartan (TEL, an antihypertensive drug) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its poor aqueous solubility. In this study, we enhanced the solubility, bioavailability, and stability of TEL through the fabrication of TEL-loaded pH-modulated solid dispersion (TEL pHM-SD) using hot-melt extrusion (HME) technology. We prepared different TEL pHM-SD formulations by varying the ratio of the drug (TEL, 10–60% w/w), the hydrophilic polymer (Soluplus®, 30–90% w/w), and pH-modifier (sodium carbonate, 0–10% w/w). More so, the tablets prepared from an optimized formulation (F8) showed a strikingly improved in vitro dissolution profile (~30-fold) compared to the free drug tablets. The conversion of crystalline TEL to its amorphous state is observed through solid-state characterizations. During the stability study, F8 tablets had a better stability profile compared to the commercial product with F8, showing higher drug content, low moisture content, and negligible physical changes. Moreover, compared to the TEL powder, in vivo pharmacokinetic studies in rats showed superior pharmacokinetic parameters, with maximum serum concentration (Cmax) and area under the drug concentration–time curve (AUC0–∞) of the TEL pHM-SD formulation increasing by 6.61- and 5.37-fold, respectively. Collectively, the results from the current study showed that the inclusion of a hydrophilic polymer, pH modulator, and the amorphization of crystalline drugs in solid dispersion prepared by HME can be an effective strategy to improve the solubility and bioavailability of hydrophobic drugs without compromising the drug’s physical stability.
Monosubstituted Acetophenone Thiosemicarbazones as Potent Inhibitors of Tyrosinase: Synthesis, Inhibitory Studies, and Molecular Docking
Authors: Hałdys Katarzyna , Goldeman Waldemar , Anger-Góra Natalia , Rossowska Joanna , Latajka Rafał
Published: January 2021

A set of 12 monosubstituted acetophenone thiosemicarbazone derivatives (TSCs) were synthesized and their inhibitory properties toward tyrosinase activity were tested. Moreover, their ability to inhibit melanogenesis in the B16F10 murine melanoma cell line was studied. In order to investigate the nature of interactions between the enzyme and the inhibitors, molecular docking to the active site was performed. TSCs 5, 6, 8, and 9 revealed a half maximal inhibitory concentration (IC50) below 1 µM. Compound 6 turned out to be the most potent tyrosinase inhibitor. All investigated compounds showed reversible inhibition of competitive or mixed type. The para-substituted TSCs had higher affinity for the enzyme as compared to their ortho- and meta-analogues. All investigated compounds inhibited melanin production in B16F10 cells at the micromolar level. Molecular docking showed that the sulfur atom of the thiourea moiety penetrates the active site and interacts with copper ions. The above outcomes might be helpful in the design of new tyrosinase inhibitors in the food and cosmetic industries.
The Impact of Lipid Handling and Phase Distribution on the Acoustic Behavior of Microbubbles
Authors: Langeveld Simone A.G. , Beekers Inés , Collado-Lara Gonzalo , van der Steen Antonius F. W. , de Jong Nico , Kooiman Klazina
Published: January 2021

Phospholipid-coated microbubbles are ultrasound contrast agents that can be employed for ultrasound molecular imaging and drug delivery. For safe and effective implementation, microbubbles must respond uniformly and predictably to ultrasound. Therefore, we investigated how lipid handling and phase distribution affected the variability in the acoustic behavior of microbubbles. Cholesterol was used to modify the lateral molecular packing of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-based microbubbles. To assess the effect of lipid handling, microbubbles were produced by a direct method, i.e., lipids directly dispersed in an aqueous medium or indirect method, i.e., lipids first dissolved in an organic solvent. The lipid phase and ligand distribution in the microbubble coating were investigated using confocal microscopy, and the acoustic response was recorded with the Brandaris 128 ultra-high-speed camera. In microbubbles with 12 mol% cholesterol, the lipids were miscible and all in the same phase, which resulted in more buckle formation, lower shell elasticity and higher shell viscosity. Indirect DSPC microbubbles had a more uniform response to ultrasound than direct DSPC and indirect DSPC-cholesterol microbubbles. The difference in lipid handling between direct and indirect DSPC microbubbles significantly affected the acoustic behavior. Indirect DSPC microbubbles are the most promising candidate for ultrasound molecular imaging and drug delivery applications.
Diagnosis of Glioma Molecular Markers by Terahertz Technologies
Authors: Cherkasova Olga , Peng Yan , Konnikova Maria , Kistenev Yuri , Shi Chenjun , Vrazhnov Denis , Shevelev Oleg , Zavjalov Evgeny , Kuznetsov Sergei , Shkurinov Alexander
Published: January 2021

This review considers glioma molecular markers in brain tissues and body fluids, shows the pathways of their formation, and describes traditional methods of analysis. The most important optical properties of glioma markers in the terahertz (THz) frequency range are also presented. New metamaterial-based technologies for molecular marker detection at THz frequencies are discussed. A variety of machine learning methods, which allow the marker detection sensitivity and differentiation of healthy and tumor tissues to be improved with the aid of THz tools, are considered. The actual results on the application of THz techniques in the intraoperative diagnosis of brain gliomas are shown. THz technologies’ potential in molecular marker detection and defining the boundaries of the glioma’s tissue is discussed.
Spiral Caustics of Vortex Beams
Authors: Soifer Viktor , Kharitonov Sergey , Khonina Svetlana , Strelkov Yurii , Porfirev Alexey
Published: January 2021

We discuss the nonparaxial focusing of laser light into a three-dimensional (3D) spiral distribution. For calculating the tangential and normal components of the electromagnetic field on a preset curved surface we propose an asymptotic method, using which we derive equations for calculating stationary points and asymptotic relations for the electromagnetic field components in the form of one-dimensional (1D) integrals over a radial component. The results obtained through the asymptotic approach and the direct calculation of the Kirchhoff integral are identical. For a particular case of focusing into a ring, an analytical relation for stationary points is derived. Based on the electromagnetic theory, we design and numerically model the performance of diffractive optical elements (DOEs) to generate field distributions shaped as two-dimensional (2D) and 3D light spirals with the variable angular momentum. We reveal that under certain conditions, there is an effect of splitting the longitudinal electromagnetic field component. Experimental results obtained with the use of a spatial light modulator are in good agreement with the modeling results.
Physiological and Molecular Traits Associated with Nitrogen Uptake under Limited Nitrogen in Soft Red Winter Wheat
Authors: Lamichhane Suman , Murata Chiaki , Griffey Carl A. , Thomason Wade E. , Fukao Takeshi
Published: January 2021

A sufficient nitrogen (N) supply is pivotal for high grain yield and desired grain protein content in wheat (Triticum aestivum L.). Elucidation of physiological and molecular mechanisms underlying nitrogen use efficiency (NUE) will enhance our ability to develop new N-saving varieties in wheat. In this study, we analyzed two soft red winter wheat genotypes, VA08MAS-369 and VA07W-415, with contrasting NUE under limited N. Our previous study demonstrated that higher NUE in VA08MAS-369 resulted from accelerated senescence and N remobilization in flag leaves at low N. The present study revealed that VA08MAS-369 also exhibited higher nitrogen uptake efficiency (NUpE) than VA07W-415 under limited N. VA08MAS-369 consistently maintained root growth parameters such as maximum root depth, total root diameter, total root surface area, and total root volume under N limitation, relative to VA07W-415. Our time-course N content analysis indicated that VA08MAS-369 absorbed N more abundantly than VA07W-415 after the anthesis stage at low N. More efficient N uptake in VA08MAS-369 was associated with the increased expression of genes encoding a two-component high-affinity nitrate transport system, including four NRT2s and three NAR2s, in roots at low N. Altogether, these results demonstrate that VA08MAS-369 can absorb N efficiently even under limited N due to maintained root development and increased function of N uptake. The ability of VA08MAS-369 in N remobilization and uptake suggests that this genotype could be a valuable genetic material for the improvement of NUE in soft red winter wheat.
Transcriptome Profiling of the Potato Exposed to French Marigold Essential Oil with a Special Emphasis on Leaf Starch Metabolism and Defense against Colorado Potato Beetle
Authors: Stupar Sofija , Dragićević Milan , Tešević Vele , Stanković-Jeremić Jovana , Maksimović Vuk , Ćosić Tatjana , Devrnja Nina , Tubić Ljiljana , Cingel Aleksandar , Vinterhalter Branka , Ninković Slavica , Savić Jelena
Published: January 2021

Flower strips of French Marigold are commonly used pest repellents in potato fields. However, the effect of French Marigold volatiles on potato metabolism, physiology and induced defense is unknown. Thus, a microarray transcriptome analysis was performed to study the effects of French Marigold essential oil (EO) on laboratory-grown potato. After 8 h of exposure to EO, with gas chromatography/mass spectrometry (GC/MS)-detected terpinolene and limonene as dominant compounds, 2796 transcripts were differentially expressed with fold change >2 compared to expression in controls. A slightly higher number of transcripts had suppressed expression (1493 down- vs. 1303 up-regulated). Since transcripts, annotated to different photosynthesis-related processes, were mostly down-regulated, we selected a set of 10 genes involved in the leaf starch metabolism pathway, and validated microarray patterns using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Except for decreased synthesis and induced decomposition of starch granule in leaves, 8 h long EO exposure slightly elevated the accumulation of sucrose compared to glucose and fructose in subjected potato plants. An in vitro feeding bioassay with Colorado potato beetle showed that EO-induced alternations on transcriptional level and in the sugars’ metabolism caused the enhancement of feeding behavior and overall development of the tested larvae. Results of comprehensive analysis of transcriptional responses in potato exposed to French Marigold EO provide a basis for further elucidation of molecular mechanisms underlying eco-physiological interactions in companion planting cropping systems.
Enhanced Abiotic Stress Tolerance of Vicia faba L. Plants Heterologously Expressing the PR10a Gene from Potato
Authors: Desouky Abeer F. , Ahmed Ahmed H. , Stützel Hartmut , Jacobsen Hans-Jörg , Pao Yi-Chen , Hanafy Moemen S.
Published: January 2021

Pathogenesis-related (PR) proteins are known to play relevant roles in plant defense against biotic and abiotic stresses. In the present study, we characterize the response of transgenic faba bean (Vicia faba L.) plants encoding a PR10a gene from potato (Solanum tuberosum L.) to salinity and drought. The transgene was under the mannopine synthetase (pMAS) promoter. PR10a-overexpressing faba bean plants showed better growth than the wild-type plants after 14 days of drought stress and 30 days of salt stress under hydroponic growth conditions. After removing the stress, the PR10a-plants returned to a normal state, while the wild-type plants could not be restored. Most importantly, there was no phenotypic difference between transgenic and non-transgenic faba bean plants under well-watered conditions. Evaluation of physiological parameters during salt stress showed lower Na+-content in the leaves of the transgenic plants, which would reduce the toxic effect. In addition, PR10a-plants were able to maintain vegetative growth and experienced fewer photosystem changes under both stresses and a lower level of osmotic stress injury under salt stress compared to wild-type plants. Taken together, our findings suggest that the PR10a gene from potato plays an important role in abiotic stress tolerance, probably by activation of stress-related physiological processes.
Leaf Monoterpene Emission Limits Photosynthetic Downregulation under Heat Stress in Field-Grown Grapevine
Authors: Bertamini Massimo , Faralli Michele , Varotto Claudio , Grando Maria Stella , Cappellin Luca
Published: January 2021

Rising temperature is among the most remarkably stressful phenomena induced by global climate changes with negative impacts on crop productivity and quality. It has been previously shown that volatiles belonging to the isoprenoid family can confer protection against abiotic stresses. In this work, two Vitis vinifera cv. ‘Chardonnay’ clones (SMA130 and INRA809) differing due to a mutation (S272P) of the DXS gene encoding for 1-deoxy-D-xylulose-5-phosphate (the first dedicated enzyme of the 2C-methyl-D-erythritol-4-phosphate (MEP) pathway) and involved in the regulation of isoprenoids biosynthesis were investigated in field trials and laboratory experiments. Leaf monoterpene emission, chlorophyll fluorescence and gas-exchange measurements were assessed over three seasons at different phenological stages and either carried out in in vivo or controlled conditions under contrasting temperatures. A significant (p < 0.001) increase in leaf monoterpene emission was observed in INRA809 when plants were experiencing high temperatures and over two experiments, while no differences were recorded for SMA130. Significant variation was observed for the rate of leaf CO2 assimilation under heat stress, with INRA809 maintaining higher photosynthetic rates and stomatal conductance values than SMA130 (p = 0.003) when leaf temperature increased above 30 °C. At the same time, the maximum photochemical quantum yield of PSII (Fv/Fm) was affected by heat stress in the non-emitting clone (SMA130), while the INRA809 showed a significant resilience of PSII under elevated temperature conditions. Consistent data were recorded between field seasons and temperature treatments in controlled environment conditions, suggesting a strong influence of monoterpene emission on heat tolerance under high temperatures. This work provides further insights on the photoprotective role of isoprenoids in heat-stressed Vitis vinifera, and additional studies should focus on unraveling the mechanisms underlying heat tolerance on the monoterpene-emitter grapevine clone.
Possible Role of Peroxynitrite in the Responses Induced by Fusicoccin in Plant Cultured Cells
Authors: Malerba Massimo , Cerana Raffaella
Published: January 2021

Fusicoccin (FC) is a well-known phytotoxin able to induce in Acer pseudoplatanus L. (sycamore) cultured cells, a set of responses similar to those induced by stress conditions. In this work, the possible involvement of peroxynitrite (ONOO−) in FC-induced stress responses was studied measuring both in the presence and in the absence of 2,6,8-trihydroxypurine (urate), a specific ONOO− scavenger: (1) cell death; (2) specific DNA fragmentation; (3) lipid peroxidation; (4) production of RNS and ROS; (5) activity of caspase-3-like proteases; and (6) release of cytochrome c from mitochondria, variations in the levels of molecular chaperones Hsp90 in the mitochondria and Hsp70 BiP in the endoplasmic reticulum (ER), and of regulatory 14-3-3 proteins in the cytosol. The obtained results indicate a role for ONOO− in the FC-induced responses. In particular, ONOO− seems involved in a PCD form showing apoptotic features such as specific DNA fragmentation, caspase-3-like protease activity, and cytochrome c release from mitochondria.
Cytotoxicity of Ficus Crocata Extract on Cervical Cancer Cells and Protective Effect against Hydrogen Peroxide-Induced Oxidative Stress in HaCaT Non-Tumor Cells
Authors: De la Cruz-Concepción Brenda , Espinoza-Rojo Mónica , Álvarez-Fitz Patricia , Illades-Aguiar Berenice , Acevedo-Quiroz Macdiel , Zacapala-Gómez Ana E. , Navarro-Tito Napoleón , Jiménez-Wences Hilda , Torres-Rojas Francisco I. , Mendoza-Catalán Miguel A.
Published: January 2021

Oxidative stress causes several chronic diseases including cancer. Some chemotherapeutic agents are not selective against tumor cells, causing oxidative stress in non-tumor cells. This study aimed to evaluate the cytotoxic effect of acetone extract of Ficus crocata(Miq.) Mart. ex Miq. (F. crocata) leaves (Ace-EFc) on cervical cancer cells, as well as its protective effect on hydrogen peroxide (H2O2)-induced lipoperoxidation and cytotoxicity in non-tumor HaCaT cells. Antioxidant activity was determined using the DPPH and ABTS radicals. Cell viability and lipoperoxidation were determined with MTT and 1-methyl-2-phenylindole assays, respectively. A model of H2O2-induced cytotoxicity and oxidative damage in HaCaT cells was established. HaCaT cells were exposed to the extract before or after exposure to H2O2, and oxidative damage and cell viability were evaluated. Ace-EFc inhibited the DPPH and ABTS radicals and showed a cytotoxic effect on SiHa and HeLa cells. Furthermore, the extract treatment had a protective effect on hydrogen peroxide-induced lipoperoxidation and cytotoxicity, avoiding the increase in MalonDiAldehyde (MDA) levels and the decrease in cell viability (p < 0.001). These results suggest that the metabolites of F. crocata leaves possess antioxidant and cytoprotective activity against oxidative damage. Thus, they could be useful for protecting cells from conditions that cause oxidative stress.
One-Dimensional Nanocomposites Based on Polypyrrole-Carbon Nanotubes and Their Thermoelectric Performance
Authors: Baghdadi Neazar , Zoromba M. Sh. , Abdel-Aziz M. H. , Al-Hossainy A. F. , Bassyouni M. , Salah Numan
Published: January 2021

Conducting polymers have attracted significant attention due to their easy fabrication, morphology modification, and their electrical properties. Amongst them, polypyrrole (PPy) has attractive thermoelectric (TE) properties. Engineering of this polymer in one-dimensional (1D) nanostructured form is found to enhance its TE performance. This was achieved in the present work by using multi-walled carbon nanotubes (MWCNTs) as a core template to direct the self-assembly of PPy and also to further enhance its TE performance. The growth of PPy on the sidewalls of MWCNTs was performed in an acidic medium based oxidative in situ polymerization. Various concentrations of MWCNTs within the range 1.1–14.6 wt.% were used to form the MWCNTs/PPy nanocomposites in 1D core-shell structures. The morphology and microstructure results of the produced nanocomposite samples showed that this MWCNTs were successfully coated by thick and thin layers of PPy. At low concentrations of MWCNTs, thick layers of PPy are formed. While at high concentrations thin layers are coated. The formed 1D nanocomposites have enhanced TE performance, particularly those containing higher contents of MWCNTs. The power factor and figure of merit values for the formed 1D nanocomposites recorded around 0.77 µV/mK2 and 1 × 10−3 at room temperature (RT), respectively. This enhancement was attributed to the perfect coating and good interaction between PPy and MWCNT through π–π stacking between the polymer chains and these nanotubes. These results might be useful for developing future TE materials and devices.