bluuebunny/crossref_metadata_2025 huggingface dataset:
Aquatic Environment Exposure and Toxicity of Engineered Nanomaterials Released from Nano-Enabled Products: Current Status and Data Needs
Authors: Moloi Mbuyiselwa Shadrack , Lehutso Raisibe Florence , Erasmus Mariana , Oberholster Paul Johan , Thwala Melusi
Published: October 2021

Rapid commercialisation of nano-enabled products (NEPs) elevates the potential environmental release of engineered nanomaterials (ENMs) along the product life cycle. The current review examined the state of the art literature on aquatic environment exposure and ecotoxicity of product released (PR) engineered nanomaterials (PR–ENMs). Additionally, the data obtained were applied to estimate the risk posed by PR–ENMs to various trophic levels of aquatic biota as a means of identifying priority NEPs cases that may require attention with regards to examining environmental implications. Overall, the PR–ENMs are predominantly associated with the matrix of the respective NEPs, a factor that often hinders proper isolation of nano-driven toxicity effects. Nevertheless, some studies have attributed the toxicity basis of observed adverse effects to a combination of the released ions, ENMs and other components of NEPs. Notwithstanding the limitation of current ecotoxicology data limitations, the risk estimated herein points to an elevated risk towards fish arising from fabrics’ PR–nAg, and the considerable potential effects from sunscreens’ PR–nZnO and PR–nTiO2 to algae, echinoderms, and crustaceans (PR–nZnO), whereas PR–nTiO2 poses no significant risk to echinoderms. Considering that the current data limitations will not be overcome immediately, we recommend the careful application of similar risk estimation to isolate/prioritise cases of NEPs for detailed characterisation of ENMs’ release and effects in aquatic environments.
Prenatal Exposure to Heavy Metals Affects Gestational Age by Altering DNA Methylation Patterns
Authors: Koh Eun Jung , Yu So Yeon , Kim Seung Hwan , Lee Ji Su , Hwang Seung Yong
Published: October 2021

Environmental exposure is known to have toxic effects. Maternal environmental exposure not only affects mothers but also their fetuses in utero, which may interrupt their early development. Preterm birth, one of the outcomes of prenatal exposure, is a significant factor in lifelong health risks. To understand the effects of prenatal exposome on preterm birth, we studied the association between maternal and prenatal heavy metal exposure and gestational age, using resources from the MOthers’ and Children’s Environmental Health (MOCEH) study in South Korea. Additionally, a methylation assay was performed to analyze epigenetic mediation using genomic DNA derived from the cord blood of 384 participants in the MOCEH study. The results suggest that maternal cadmium exposure is associated with a decrease in gestational age through an alteration in DNA methylation at a specific CpG site, cg21010642. The CpG site was annotated to a gene involved in early embryonic development. Therefore, irregular methylation patterns at this site may contribute to premature birth by mediating irregular biological mechanisms.
Electromagnetic Properties of Carbon Nanotube/BaFe12−xGaxO19/Epoxy Composites with Random and Oriented Filler Distributions
Authors: Yakovenko Olena S. , Matzui Lyudmila Yu. , Vovchenko Ludmila L. , Oliynyk Victor V. , Zagorodnii Volodymyr V. , Trukhanov Sergei V. , Trukhanov Alex V.
Published: October 2021

The microwave properties of epoxy composites filled with 30 wt.% of BaFe12–xGaxO19 (0.1 ≤ x ≤ 1.2) and with 1 wt.% of multi-walled carbon nanotubes (CNTs) were investigated in the frequency range 36–55 GHz. A sufficient increase in the microwave shielding efficiency was found for ternary 1 wt.%CNT/30 wt.% BaFe12–xGaxO19/epoxy composites compared with binary 1% CNT/epoxy and 30 wt.% BaFe12–xGaxO19/epoxy due to the complementary contributions of dielectric and magnetic losses. Thus, the addition of only 1 wt.% of CNTs along with 30 wt.% of barium hexaferrite into epoxy resin increased the frequency range where electromagnetic radiation is intensely attenuated. A correlation between the cation Ga3+ concentration in the BaFe12–xGaxO19 filler and amplitude–frequency characteristics of the natural ferromagnetic resonance (NFMR) in 1 wt.%CNT/30 wt.% BaFe12–xGaxO19/epoxy composites was determined. Higher values of the resonance frequency fres (51.8–52.4 GHz) and weaker dependence of fres on the Ga3+ concentration were observed compared with pressed polycrystalline BaFe12–xGaxO19 (fres = 49.6–50.4 GHz). An increase in the NFMR amplitude on the applied magnetic field for both random and aligned 1 wt.% CNT/30 wt.% BaFe12–xGaxO19/epoxy composites was found. The frequency of NFMR was approximately constant in the range of the applied magnetic field, H = 0–5 kOe, for the random 1 wt.% CNT/30 wt.% BaFe12–xGaxO19/epoxy composite, and it slightly increased for the aligned 1 wt.% CNT/30 wt.% BaFe12–xGaxO19/epoxy composite.
Smart Design of Mitochondria-Targeted and ROS-Responsive CPI-613 Delivery Nanoplatform for Bioenergetic Pancreatic Cancer Therapy
Authors: Zhang Yi-Mei , Xia Meng , Ao Rui , Gao Li-Xia , Tang Yan , Huang Jiu-Hong , Luo Ya-Fei , Chen Zhong-Zhu , Wang Bo-Chu , Huang Zheng
Published: October 2021

Mitochondria, as the powerhouse of most cells, are not only responsible for the generation of adenosine triphosphate (ATP) but also play a decisive role in the regulation of apoptotic cell death, especially of cancer cells. Safe potential delivery systems which can achieve organelle-targeted therapy are urgently required. In this study, for effective pancreatic cancer therapy, a novel mitochondria-targeted and ROS-triggered drug delivery nanoplatform was developed from the TPP-TK-CPI-613 (TTCI) prodrug, in which the ROS-cleave thioketal functions as a linker connecting mitochondrial targeting ligand TPP and anti-mitochondrial metabolism agent CPI-613. DSPE-PEG2000 was added as an assistant component to increase accumulation in the tumor via the EPR effect. This new nanoplatform showed effective mitochondrial targeting, ROS-cleaving capability, and robust therapeutic performances. With active mitochondrial targeting, the formulated nanoparticles (TTCI NPs) demonstrate much higher accumulation in mitochondria, facilitating the targeted delivery of CPI-613 to its acting site. The results of in vitro antitumor activity and cell apoptosis revealed that the IC50 values of TTCI NPs in three types of pancreatic cancer cells were around 20~30 µM, which was far lower than those of CPI-613 (200 µM); 50 µM TTCI NPs showed an increase in apoptosis of up to 97.3% in BxPC3 cells. Therefore, this mitochondria-targeted prodrug nanoparticle platform provides a potential strategy for developing safe, targeting and efficient drug delivery systems for pancreatic cancer therapy.
Dual-Spectral Plasmon-Induced Transparent Terahertz Metamaterial with Independently Tunable Amplitude and Frequency
Authors: Wu Tong , Wang Guan , Jia Yang , Shao Yabin , Chen Chen , Han Jing , Gao Yang , Gao Yachen
Published: October 2021

A bifunctional tunable metamaterial composed of pattern metal structure, graphene, and strontium titanate (STO) film is proposed and studied numerically and theoretically. The dual plasmon-induced transparency (PIT) window is obtained by coupling the bright state cut wire (CW) and two pairs of dark state dual symmetric semiring resonators (DSSRs) with different parameters. Correspondingly, slow light effect can also be realized. When shifting independently, the Fermi level of the graphene strips, the amplitudes of the two PIT transparency windows and slow light effect can be tuned, respectively. In addition, when independently tuning the temperature of the metamaterial, the frequency of the dual PIT windows and slow light effect can be tuned. The physical mechanism of the dual-PIT was analyzed theoretically by using a three-harmonic oscillator model. The results show that the regulation function of the PIT peak results from the change of the oscillation damping at the dark state DSSRs by tuning conductivity of graphene. Our design presents a new structure to realize the bifunctional optical switch and slow light.
Multi-Scale Photoacoustic Assessment of Wound Healing Using Chitosan–Graphene Oxide Hemostatic Sponge
Authors: Lin Xiangwei , Shen Yajing , Wang Lidai
Published: October 2021

Hemostasis is vital to save lives, reducing risks of organ failure and hemorrhagic shock. Exploring novel hemostatic materials and precise monitoring of the hemostatic status is of great importance for efficient hemostasis. We present the development of chitosan–graphene oxide-based hemostatic composite and multi-scale photoacoustic evaluation of the hemostatic performance. The hemostatic sponge can quickly and efficiently absorb the blood with its porous cavity and specific surficial property. We inspect the hemostatic performance via an in vitro blood absorption test and in vivo mouse bleeding injury experiments. Results show that the synthesized hemostatic sponge can not only absorb plasma in blood fast with its interior porous structure but also stimulate the interfacial reaction with erythrocytes and platelets. The superiority of multi-scale photoacoustic imaging for guiding, monitoring, and evaluating the hemostatic stages of sponges is demonstrated with high spatial resolution and great sensitivity at depths. Photoacoustic evaluation of a chitosan–graphene oxide-based hemostatic sponge has the potential to be transferred toward the clinical assessment of wound healing.
Synergistic Adsorption-Catalytic Sites TiN/Ta2O5 with Multidimensional Carbon Structure to Enable High-Performance Li-S Batteries
Authors: Wang Chong , Lu Jian-Hao , Wang Zi-Long , Wang An-Bang , Zhang Hao , Wang Wei-Kun , Jin Zhao-Qing , Fan Li-Zhen
Published: October 2021

Lithium-sulfur (Li-S) batteries are deemed to be one of the most optimal solutions for the next generation of high-energy-density and low-cost energy storage systems. However, the low volumetric energy density and short cycle life are a bottleneck for their commercial application. To achieve high energy density for lithium-sulfur batteries, the concept of synergistic adsorptive–catalytic sites is proposed. Base on this concept, the TiN@C/S/Ta2O5 sulfur electrode with about 90 wt% sulfur content is prepared. TiN contributes its high intrinsic electron conductivity to improve the redox reaction of polysulfides, while Ta2O5 provides strong adsorption capability toward lithium polysulfides (LiPSs). Moreover, the multidimensional carbon structure facilitates the infiltration of electrolytes and the motion of ions and electrons throughout the framework. As a result, the coin Li-S cells with TiN@C/S/Ta2O5 cathode exhibit superior cycle stability with a decent capacity retention of 56.1% over 300 cycles and low capacity fading rate of 0.192% per cycle at 0.5 C. Furthermore, the pouch cells at sulfur loading of 5.3 mg cm−2 deliver a high areal capacity of 5.8 mAh cm−2 at low electrolyte/sulfur ratio (E/S, 3.3 μL mg−1), implying a high sulfur utilization even under high sulfur loading and lean electrolyte operation.
Influence of Coating and Size of Magnetic Nanoparticles on Cellular Uptake for In Vitro MRI
Authors: Cortés-Llanos Belén , Ocampo Sandra M. , de la Cueva Leonor , Calvo Gabriel F. , Belmonte-Beitia Juan , Pérez Lucas , Salas Gorka , Ayuso-Sacido Ángel
Published: October 2021

Iron oxide nanoparticles (IONPs) are suitable materials for contrast enhancement in magnetic resonance imaging (MRI). Their potential clinical applications range from diagnosis to therapy and follow-up treatments. However, a deeper understanding of the interaction between IONPs, culture media and cells is necessary for expanding the application of this technology to different types of cancer therapies. To achieve new insights of these interactions, a set of IONPs were prepared with the same inorganic core and five distinct coatings, to study their aggregation and interactions in different physiological media, as well as their cell labelling efficiency. Then, a second set of IONPs, with six different core sizes and the same coating, were used to study how the core size affects cell labelling and MRI in vitro. Here, IONPs suspended in biological media experience a partial removal of the coating and adhesion of molecules. The FBS concentration alters the labelling of all types of IONPs and hydrodynamic sizes ≥ 300 nm provide the greatest labelling using the centrifugation-mediated internalization (CMI). The best contrast for MRI results requires a core size range between 12–14 nm coated with dimercaptosuccinic acid (DMSA) producing R2* values of 393.7 s−1 and 428.3 s−1, respectively. These findings will help to bring IONPs as negative contrast agents into clinical settings.
Direct and Indirect Genotoxicity of Graphene Family Nanomaterials on DNA—A Review
Authors: Wu Kangying , Zhou Qixing , Ouyang Shaohu
Published: October 2021

Graphene family nanomaterials (GFNs), including graphene, graphene oxide (GO), reduced graphene oxide (rGO), and graphene quantum dots (GQDs), have manifold potential applications, leading to the possibility of their release into environments and the exposure to humans and other organisms. However, the genotoxicity of GFNs on DNA remains largely unknown. In this review, we highlight the interactions between DNA and GFNs and summarize the mechanisms of genotoxicity induced by GFNs. Generally, the genotoxicity can be sub-classified into direct genotoxicity and indirect genotoxicity. The direct genotoxicity (e.g., direct physical nucleus and DNA damage) and indirect genotoxicity mechanisms (e.g., physical destruction, oxidative stress, epigenetic toxicity, and DNA replication) of GFNs were summarized in the manuscript, respectively. Moreover, the influences factors, such as physicochemical properties, exposure dose, and time, on the genotoxicity of GFNs are also briefly discussed. Given the important role of genotoxicity in GFNs exposure risk assessment, future research should be conducted on the following: (1) developing reliable testing methods; (2) elucidating the response mechanisms associated with genotoxicity in depth; and (3) enriching the evaluation database regarding the type of GFNs, applied dosages, and exposure times.
Effect of Nutritional Habits on the Glycemic Response to Different Carbohydrate Diet in Children with Type 1 Diabetes Mellitus
Authors: Lejk Agnieszka , Chrzanowski Jędrzej , Cieślak Adrianna , Fendler Wojciech , Myśliwiec Małgorzata
Published: October 2021

Unhealthy eating habits are associated with obesity, metabolic syndrome, and increased insulin resistance in young patients with type 1 diabetes mellitus (T1DM), and may impact the possible benefit from dietary interventions on glycaemic control. This study determines how nutritional patterns influence the quality of dietary intervention with a 30% or 50% carbohydrate diet in terms of glycaemic control measured with continuous glucose monitoring (CGM). Eating habits were obtained with a frequency-of-consumption questionnaire (FFQ-6) before the diet assessment. Altogether, we collected CGM and FFQ-6 data from 30 children (16 boys and 14 girls aged 10–17 years) with T1DM subjected to two consecutive 3-day nutritional plans. From these, 23 patients met the CGM data quality criteria for further analysis. Furthermore, high accuracy achieved in training (95.65%) and V-fold cross-validation (81.67%) suggest a significant impact of food habits in response to introduced nutritional changes. Patients who consumed more vegetables or grains (>4 times per day), more wheat products (>once per day), fewer fats (<1.5 times per day), and ranked fruit juice as the most common selection in the drinks category achieved glycaemic control more often after the introduction of a 30% carbohydrate diet, as opposed to those with different dietary patterns, whose glycaemic control was negatively impacted after switching to this diet. Additionally, the 50% carbohydrate diet was safe for all patients in the context of glycaemic control.
Disordered Eating among People with Schizophrenia Spectrum Disorders: A Systematic Review
Authors: Sankaranarayanan Anoop , Johnson Karthika , Mammen Sanop J. , Wilding Helen E. , Vasani Deepali , Murali Vijaya , Mitchison Deborah , Castle David J. , Hay Phillipa
Published: October 2021

Disordered eating, or abnormal eating behaviours that do not meet the criteria for an independent eating disorder, have been reported among people with schizophrenia. We aimed to systemati-cally review literature on disordered eating among people with schizophrenia spectrum disorder (SSD). Seven databases were systematically searched for studies that described the prevalence and correlates of disordered eating among patients with SSD from January 1984 to 15 February 2021. Qualitative analysis was performed using the National Institutes of Health scales. Of 5504 records identified, 31 studies involving 471,159 subjects were included in the systematic review. The ma-jority of studies (17) rated fair on qualitative analysis and included more men, and participants in their 30s and 40s, on antipsychotics. The commonest limitations include lack of sample size or power calculations, poor sample description, not using valid tools, or not adjusting for con-founders. The reported rates were 4.4% to 45% for binge eating, 16.1% to 64%, for food craving, 27% to 60.6% for food addiction, and 4% to 30% for night eating. Positive associations were re-ported for binge eating with antipsychotic use and female gender, between food craving and weight gain, between food addiction and increased dietary intake, and between disordered eating and female gender, mood and psychotic symptoms. Reported rates for disordered eating among people with SSD are higher than those in the general population. We will discuss the clinical, treatment and research implications of our findings.
Obsessed with Healthy Eating: A Systematic Review of Observational Studies Assessing Orthorexia Nervosa in Patients with Diabetes Mellitus
Authors: Grammatikopoulou Maria G. , Gkiouras Konstantinos , Polychronidou Georgia , Kaparounaki Chrysi , Gkouskou Kalliopi K. , Magkos Faidon , Donini Lorenzo Maria , Eliopoulos Aristides G. , Goulis Dimitrios G.
Published: October 2021

Orthorexia nervosa (ON) is an unspecified feeding or eating disorder (USFED) characterized by an exaggerated, unhealthy obsession with healthy eating. Τypical eating disorders (EDs) and USFEDs are common among patients with diabetes mellitus (DM), which complicates metabolic control and disease outcomes. The present systematic review summarizes the evidence on the prevalence of ON symptomatology among patients with DM. PubMed, Web of Science, Scopus, and grey literature were searched, and relevant observational studies were screened using the Rayyan software. The quality of the studies was assessed using the appraisal tool for cross-sectional studies (AXIS) and the Newcastle–Ottawa scale (NOS). Out of 4642 studies, 6 fulfilled the predefined criteria and were included in the qualitative synthesis. Most studies relied on the ORTO-15 or its adaptations to identify ON among patients with DM. No apparent sex or age differences exist regarding the prevalence of ON symptoms. None of the studies compared the prevalence of ON in patients with type 1 and type 2 DM. Most of the research was of average to good methodological quality. In conclusion, patients with DM often exhibit ON tendencies, although research is still limited regarding the etiology or mechanistic drivers behind ON and the characteristics of patients with a dual ON–DM diagnosis.
Trajectories and Determinants of Physical Activity during COVID-19 Pandemic: A Population-Based Study of Middle-Aged and Elderly Individuals in The Netherlands
Authors: Hofman Amy , Limpens Marlou A. M. , de Crom Tosca O. E. , Ikram Mohammad Arfan , Luik Annemarie I. , Voortman Trudy
Published: October 2021

Physical inactivity is a major public health problem, and there are concerns this might have increased during the COVID-19 pandemic. We aimed to identify distinct trajectories of physical activity over a 6-week period after the first restrictive measures and to explore determinants of these trajectories in a population-based cohort of middle-aged and elderly in the Netherlands (n = 5777). We observed that at least 59% of participants did not meet the World Health Organization recommendations for physical activity. Using latent class trajectory analyses over three time points, we identified five distinct trajectories, including four steady trajectories at different levels (very low, low, medium and high) and one increasing trajectory. Using multinomial logistic regression analyses, we observed that, compared to the ‘steadily high’ trajectory, participants in the ‘steadily very low’ trajectory were more often older, lower educated, reporting poorer physical health, more depressive symptoms, consuming a less healthy diet, smoking, and lower alcohol use, and were less often retired. A similar pattern of determinants was seen for those in the increasing trajectory, albeit with smaller effect sizes. Concluding, we observed low levels of physical activity that generally remained during the pandemic. The determinants we described can help identify groups that require additional preventive interventions.
Nutraceuticals and Cancer: Potential for Natural Polyphenols
Authors: Maiuolo Jessica , Gliozzi Micaela , Carresi Cristina , Musolino Vincenzo , Oppedisano Francesca , Scarano Federica , Nucera Saverio , Scicchitano Miriam , Bosco Francesca , Macri Roberta , Ruga Stefano , Cardamone Antonio , Coppoletta Annarita , Mollace Annachiara , Cognetti Francesco , Mollace Vincenzo
Published: October 2021

Cancer is one of the leading causes of death globally, associated with multifactorial pathophysiological components. In particular, genetic mutations, infection or inflammation, unhealthy eating habits, exposition to radiation, work stress, and/or intake of toxins have been found to contribute to the development and progression of cancer disease states. Early detection of cancer and proper treatment have been found to enhance the chances of survival and healing, but the side effects of anticancer drugs still produce detrimental responses that counteract the benefits of treatment in terms of hospitalization and survival. Recently, several natural bioactive compounds were found to possess anticancer properties, capable of killing transformed or cancerous cells without being toxic to their normal counterparts. This effect occurs when natural products are associated with conventional treatments, thereby suggesting that nutraceutical supplementation may contribute to successful anticancer therapy. This review aims to discuss the current literature on four natural bioactive extracts mostly characterized by a specific polyphenolic profile. In particular, several activities have been reported to contribute to nutraceutical support in anticancer treatment: (1) inhibition of cell proliferation, (2) antioxidant activity, and (3) anti-inflammatory activity. On the other hand, owing to their attenuation of the toxic effect of current anticancer therapies, natural antioxidants may contribute to improving the compliance of patients undergoing anticancer treatment. Thus, nutraceutical supplementation, along with current anticancer drug treatment, may be considered for better responses and compliance in patients with cancer. It should be noted, however, that when data from studies with bioactive plant preparations are discussed, it is appropriate to ensure that experiments have been conducted in accordance with accepted pharmacological research practices so as not to disclose information that is only partially correct.
Carbohydrate Taste Is Associated with Food Intake and Body Mass in Healthy Australian Adults
Authors: Costanzo Andrew , Settapramote Natwalinkhol , Utama-ang Niramon , Wanich Uracha , Lewin Simone , Keast Russell
Published: October 2021

Background: The taste of carbohydrates may drive their intake. Sensitivity to carbohydrate taste varies among individuals, thus, it is important to understand how differences in sensitivity influence eating behaviour and body mass. Objective: The aims of this study were to assess associations among carbohydrate taste sensitivity, habitual and acute food intake, and body mass; as well as assess the reliability of the carbohydrate detection threshold (DT) test within and across days. Methods: Carbohydrate DT was assessed six times across three sessions in 36 healthy adult participants (22 female) using a three-alternate forced choice methodology. Moreover, 24 h diet records were completed on the days prior to testing sessions, and food intake at a buffet lunch was collected following each session. Anthropometry was also measured. Linear mixed regression models were fitted. Results: The DT test required at least three measures within a given day for good reliability (ICC = 0.76), but a single measure had good reliability when compared at the same time across days (ICC = 0.54–0.86). Carbohydrate DT was associated with BMI (kg/m2: β = −0.38, p = 0.014), habitual carbohydrate intake (g: β = −41.8, p = 0.003) and energy intake (kJ: β = −1068, p = 0.019) from the 24-h diet records, as well as acute intake of a buffet lunch (food weight (g): β = −76.1, p = 0.008). Conclusions: This suggests that individuals who are more sensitive to carbohydrate are more likely to consume greater quantities of carbohydrates and energy, resulting in a greater body mass.
Could Vitamin D Be Effective in Prevention of Preeclampsia?
Authors: Poniedziałek-Czajkowska Elżbieta , Mierzyński Radzisław
Published: October 2021

Prevention of preeclampsia (PE) remains one of the most significant problems in perinatal medicine. Due to the possible unpredictable course of hypertension in pregnancy, primarily PE and the high complication rate for the mother and fetus/newborn, it is urgent to offer pregnant women in high-risk groups effective methods of preventing the PE development or delaying its appearance. In addition, due to the association of PE with an increased risk of developing cardiovascular diseases (CVD) in later life, effective preeclampsia prevention could also be important in reducing their incidence. Ideal PE prophylaxis should target the pathogenetic changes leading to the development of PE and be safe for the mother and fetus, inexpensive and freely available. Currently, the only recognized method of PE prevention recommended by many institutions around the world is the use of a small dose of acetylsalicylic acid in pregnant women with risk factors. Unfortunately, some cases of PE are diagnosed in women without recognized risk factors and in those in whom prophylaxis with acetylsalicylic acid is not adequate. Hence, new drugs which would target pathogenetic elements in the development of preeclampsia are studied. Vitamin D (Vit D) seems to be a promising agent due to its beneficial effect on placental implantation, the immune system, and angiogenic factors. Studies published so far emphasize the relationship of its deficiency with the development of PE, but the data on the benefits of its supplementation to reduce the risk of PE are inconclusive. In the light of current research, the key issue is determining the protective concentration of Vit D in a pregnant woman. The study aims to present the possibility of using Vit D to prevent PE, emphasizing its impact on the pathogenetic elements of preeclampsia development.
Provision and Supervision of Food and Protein Substitute in School for Children with PKU: Parent Experiences
Authors: Jones Hannah , Pinto Alex , Evans Sharon , Ford Suzanne , O’Driscoll Mike , Buckley Sharon , Ashmore Catherine , Daly Anne , MacDonald Anita
Published: October 2021

Children spend a substantial part of their childhood in school, so provision of dietary care and inclusion of children with phenylketonuria (PKU) in this setting is essential. There are no reports describing the dietary support children with PKU receive whilst at school. The aim of this cross-sectional study was to explore the experiences of the dietary management of children with PKU in schools across the UK. Data was collected using an online survey completed by parents/caregivers of children with PKU. Of 159 questionnaire responses, 92% (n = 146) of children attended state school, 6% (n = 10) private school and 2% (n = 3) other. Fourteen per cent (n = 21/154) were at nursery/preschool, 51% (n = 79/154) primary and 35% (n = 54/154) secondary school. Sixty-one per cent (n = 97/159) said their child did not have school meals, with some catering services refusing to provide suitable food and some parents distrusting the school meals service. Sixty-one per cent of children had an individual health care plan (IHCP) (n = 95/155). Children were commonly unsupervised at lunchtime (40%, n = 63/159), with snacks (46%, n = 71/155) and protein substitute (30%, n = 47/157), with significantly less supervision in secondary than primary school (p < 0.001). An IHCP was significantly associated with improved supervision of food and protein substitute administration (p < 0.01), and better communication between parents/caregivers and the school team (p < 0.05). Children commonly accessed non-permitted foods in school. Therefore, parents/caregivers described important issues concerning the school provision of low phenylalanine food and protein substitute. Every child should have an IHCP which details their dietary needs and how these will be met safely and discreetly. It is imperative that children with PKU are supported in school.
The Reactive Oxygen Species Singlet Oxygen, Hydroxy Radicals, and the Superoxide Radical Anion—Examples of Their Roles in Biology and Medicine
Authors: Edge Ruth , Truscott T. George
Published: October 2021

Reactive oxygen species comprise oxygen-based free radicals and non-radical species such as peroxynitrite and electronically excited (singlet) oxygen. These reactive species often have short lifetimes, and much of our understanding of their formation and reactivity in biological and especially medical environments has come from complimentary fast reaction methods involving pulsed lasers and high-energy radiation techniques. These and related methods, such as EPR, are discussed with particular reference to singlet oxygen, hydroxy radicals, the superoxide radical anion, and their roles in medical aspects, such as cancer, vision and skin disorders, and especially pro- and anti-oxidative processes.
Design and Microwave Synthesis of New (5Z) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5Z) 2-Amino-5-arylidene-1,3-thiazol-4(5H)-one as New Inhibitors of Protein Kinase DYRK1A
Authors: Bourahla Khadidja , Guihéneuf Solène , Limanton Emmanuelle , Paquin Ludovic , Le Guével Rémy , Charlier Thierry , Rahmouni Mustapha , Durieu Emilie , Lozach Olivier , Carreaux François , Meijer Laurent , Bazureau Jean-Pierre
Published: October 2021

Here, we report on the synthesis of libraries of new 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones 3 (twenty-two compounds) and new 2-amino-5-arylidene-1,3-thiazol-4(5H)-ones 5 (twenty-four compounds) with stereo controlled Z-geometry under microwave irradiation. The 46 designed final compounds were tested in order to determine their activity against four representative protein kinases (DYR1A, CK1, CDK5/p25, and GSK3α/β). Among these 1,3-thiazolidin-4-ones, the molecules (5Z) 5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one 3e (IC50 0.028 μM) and (5Z)-5-benzo[1,3]dioxol-5-ylmethylene-2-(pyridin-2-yl)amino-1,3-thiazol-4(5H)-one 5s (IC50 0.033 μM) were identified as lead compounds and as new nanomolar DYRK1A inhibitors. Some of these compounds in the two libraries have been also evaluated for their in vitro inhibition of cell proliferation (Huh7 D12, Caco2, MDA-MB 231, HCT 116, PC3, and NCI-H2 tumor cell lines). These results will enable us to use the 1,3-thiazolidin-4-one core as pharmacophores to develop potent treatment for neurological or oncological disorders in which DYRK1A is fully involved.
4-(Indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole Acylamines as Νovel Antimicrobial Agents: Synthesis, In Silico and In Vitro Evaluation
Authors: Simakov Sergei , Kartsev Victor , Petrou Anthi , Nicolaou Ioannis , Geronikaki Athina , Ivanov Marija , Kostic Marina , Glamočlija Jasmina , Soković Marina , Talea Despoina , Vizirianakis Ioannis S.
Published: October 2021

This manuscript deals with the synthesis and computational and experimental evaluation of the antimicrobial activity of twenty-nine 4-(indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole acylamines. An evaluation of antibacterial activity against Gram (+) and Gram (−) bacteria revealed that the MIC of indole derivatives is in the range of 0.06–1.88 mg/mL, while among fourteen methylindole derivatives, only six were active, with an MIC in the range of of 0.47–1.88 mg/mL. S. aureus appeared to be the most resistant strain, while S. Typhimurium was the most sensitive. Compound 5x was the most promising, with an MIC in the range of 0.06–0.12 mg/mL, followed by 5d and 5m. An evaluation of these three compounds against resistant strains, namely MRSA P. aeruginosa and E. coli, revealed that they were more potent against MRSA than ampicillin. Furthermore, compounds 5m and 5x were superior inhibitors of biofilm formation, compared to ampicillin and streptomycin, in terms Compounds 5d, 5m, and 5x interact with streptomycin in additive manner. The antifungal activity of some compounds exceeded or was equipotent to those of the reference antifungal agents bifonazole and ketoconazole. The most potent antifungal agent was found to be compound 5g. Drug likeness scores of compounds was in a range of −0.63 to 0.29, which is moderate to good. According to docking studies, E. coli MurB inhibition is probably responsible for the antibacterial activity of compounds, whereas CYP51 inhibition was implicated in antifungal activity. Compounds appeared to be non-toxic, according to the cytotoxicity assessment in MRC-5 cells.
A Rational Design of α-Helix-Shaped Peptides Employing the Hydrogen-Bond Surrogate Approach: A Modulation Strategy for Ras-RasGRF1 Interaction in Neuropsychiatric Disorders
Authors: Gulotta Maria Rita , Brambilla Riccardo , Perricone Ugo , Brancale Andrea
Published: October 2021

In the last two decades, abnormal Ras (rat sarcoma protein)–ERK (extracellular signal-regulated kinase) signalling in the brain has been involved in a variety of neuropsychiatric disorders, including drug addiction, certain forms of intellectual disability, and autism spectrum disorder. Modulation of membrane-receptor-mediated Ras activation has been proposed as a potential target mechanism to attenuate ERK signalling in the brain. Previously, we showed that a cell penetrating peptide, RB3, was able to inhibit downstream signalling by preventing RasGRF1 (Ras guanine nucleotide-releasing factor 1), a neuronal specific GDP/GTP exchange factor, to bind Ras proteins, both in brain slices and in vivo, with an IC50 value in the micromolar range. The aim of this work was to mutate and improve this peptide through computer-aided techniques to increase its inhibitory activity against RasGRF1. The designed peptides were built based on the RB3 peptide structure corresponding to the α-helix of RasGRF1 responsible for Ras binding. For this purpose, the hydrogen-bond surrogate (HBS) approach was exploited to maintain the helical conformation of the designed peptides. Finally, residue scanning, MD simulations, and MM-GBSA calculations were used to identify 18 most promising α-helix-shaped peptides that will be assayed to check their potential activity against Ras-RasGRF1 and prevent downstream molecular events implicated in brain disorders.
Model-Based Approach for Designing an Efficient Bioequivalence Study for Highly Variable Drugs
Authors: Song Eunjung , Lee Woojoo , Kim Bo-Hyung
Published: October 2021

The statistical procedures as outlined by the European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) guidelines for bioequivalence testing of highly variable drugs (HVDs) are complex. Additionally, the sample size is affected by clinical study designs or practical real-world problems, such as dropout rate or study budget. To overcome these difficulties, we propose a model-based approach for the selection of a study design with a sample size that satisfies the bioequivalence criteria using simulation studies based on a pharmacokinetic (PK) model. The designed approach was implemented using a simulation procedure considering some conventionally measured factors, such as geometric mean ratio and within-subject coefficient of variation, with various PK information important in determining bioequivalence. All simulation results were assessed according to the EMA and FDA guidelines. Furthermore, power calculations from simulation results were interpreted with regard to PK characteristics and compared among 2 × 2, 3 × 3, and 2 × 4 crossover designs to determine the efficient design considering appropriate sample size and duration of the clinical study. The proposed approach can be applied to bioequivalence studies of all drugs. However, the current study was targeted at HVDs, which are highly likely to require detailed decision making for sample size and study design.
Development of a Scalable Process of Film-Coated bi-Layer Tablet Containing Sustained-Release Metoprolol Succinate and Immediate-Release Amlodipine Besylate
Authors: Tuyen Nguyen Thi Linh , Nghiem Le Quan , Tuan Nguyen Duc , Le Phuoc Huu
Published: October 2021

The development of new drugs that combine active ingredients for the treatment hypertension is critically essential owing to its offering advantages for both patients and manufacturers. In this study, for the first time, detailed development of a scalable process of film-coated bi-layer tablets containing sustained-release metoprolol succinate and immediate-release amlodipine besylate in a batch size of 10,000 tablets is reported. The processing parameters of the manufacturing process during dry mixing-, drying-, dry mixing- completion stages were systematically investigated, and the evaluation of the film-coated bi-layer tablet properties was well established. The optimal preparation conditions for metoprolol succinate layer were 6 min- dry mixing with a high-speed mixer (120 rpm and 1400 rpm), 30-min drying with a fluid bed dryer, and 5-min- mixing completion at 25 rpm. For the preparation of amlodipine besylate layer, the optimal dry-mixing time using a cube mixer (25 rpm) was found to be 5 min. The average weight of metoprolol succinate layers and bi-layer tablets were controlled at 240–260 mg and 384–416 mg, respectively. Shewhart R chart and X¯ charts of all three sampling lots were satisfactory, confirming that the present scalable process was stable and successful. This study confirms that the manufacturing process is reproducible, robust; and it yields a consistent product that meets specifications.
Development of Lutein-Containing Eye Drops for the Treatment of Dry Eye Syndrome
Authors: Chen Yi-Zhou , Chen Zhi-Yu , Tang Yu-Jun , Tsai Cheng-Han , Chuang Yu-Lun , Hsieh Erh-Hsuan , Tucker Lachlan , Lin I-Chan , Tseng Ching-Li
Published: October 2021

Dry eye syndrome (DES) is a common ophthalmological disease that decreases tear secretion and causes dryness, photophobia, pain, severe corneal rupture, and even blindness. Ocular and lacrimal gland inflammation is one of the pathological mechanisms underlying DES. Therefore, effective suppression of inflammation is a crucial strategy for the treatment of DES. Lutein, commonly found in healthy foods, has anti-inflammatory effects in corneal or retina-related cells and may be a potential therapy for DES. The addition of lutein to artificial tears (AT) as an eye-drop formulation for DES treatment in a mouse model was studied in the present work. Polyvinyl alcohol (PVA) was used as a thickener to increase the viscosity of eye drops to prolong drug retention on the ocular surface. A WST-8 assay in human corneal epithelial cells (HCE-2) showed that a concentration of <5 μM lutein (L5) and <1% PVA (P1) maintained the cell viability at 80%. A real-time PCR showed that the inflamed human corneal epithelial cells (HCECs) cocultured with L5P1 had downregulated expression of inflammatory genes such as IL-1β, IL-6, and TNF-α. In a benzalkonium chloride- (BAC) induced DES mouse model, AT/L5P1 could repair damaged corneas, elevate tear secretion, increase the number of goblet cells, and inhibit the production of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, in the cornea. In conclusion, we demonstrate that lutein/PVA as eye drops could prolong the drug ocular retention time and effectively to decrease inflammation in DES mice. Therefore, lutein, obtained from eye drops, has a potential therapeutic role for DES.
Disposition of Cefquinome in Turkeys (Meleagris gallopavo) Following Intravenous and Intramuscular Administration
Authors: Elbadawy Mohamed , Soliman Ahmed , Abugomaa Amira , Alkhedaide Adel , Soliman Mohamed Mohamed , Aboubakr Mohamed
Published: October 2021

The bioavailability and pharmacokinetics in turkeys of cefquinome (CFQ), a broad-spectrum 4th-generation cephalosporin antibiotic, were explored after a single injection of 2 mg/kg body weight by intravenous (IV) and intramuscular (IM) routes. In a crossover design and 3-weeks washout interval, seven turkeys were assigned for this objective. Blood samples were collected prior to and at various time intervals following each administration. The concentration of CFQ in plasma was measured using HPLC with a UV detector set at 266 nm. For pharmacokinetic analysis, non-compartmental methods have been applied. Following IV administration, the elimination half-life (t1/2ʎz), distribution volume at steady state (Vdss), and total body clearance (Cltot) of CFQ were 1.55 h, 0.54 L/kg, and 0.32 L/h/kg, respectively. Following the IM administration, CFQ was speedily absorbed with an absorption half-life (t1/2ab) of 0.25 h, a maximum plasma concentration (Cmax) of 2.71 μg/mL, attained (Tmax) at 0.56 h. The bioavailability (F) and in vitro plasma protein binding of CFQ were 95.56% and 11.5%, respectively. Results indicated that CFQ was speedily absorbed with a considerable bioavailability after IM administration. In conclusion, CFQ has a favorable disposition in turkeys that can guide to estimate optimum dosage regimes and eventually lead to its usage to eradicate turkey’s susceptible bacterial infections.
Proximal Algorithms for Discrete-Level Phase-Shifting Mask Design with Application to Optogenetics
Authors: Ampeliotis Dimitris , Anastasiou Aggeliki , Politi Christina (Tanya) , Alexandropoulos Dimitris
Published: October 2021

This work studies the problem of designing computer-generated holograms using phase-shifting masks limited to represent only a small number of discrete phase levels. This problem has various applications, notably in the emerging field of optogenetics and lithography. A novel regularized cost function is proposed for the problem at hand that penalizes the unfeasible phase levels. Since the proposed cost function is non-smooth, we derive proper proximal gradient algorithms for its minimization. Simulation results, considering an optogenetics application, demonstrate that the proposed proximal gradient algorithm yields better performance as compared to other algorithms proposed in the literature.
Upcycling Biodegradable PVA/Starch Film to a Bacterial Biopigment and Biopolymer
Authors: Pantelic Brana , Ponjavic Marijana , Jankovic Vukasin , Aleksic Ivana , Stevanovic Sanja , Murray James , Fournet Margaret Brennan , Nikodinovic-Runic Jasmina
Published: October 2021

Meeting the challenge of circularity for plastics requires amenability to repurposing post-use, as equivalent or upcycled products. In a compelling advancement, complete circularity for a biodegradable polyvinyl alcohol/thermoplastic starch (PVA/TPS) food packaging film was demonstrated by bioconversion to high-market-value biopigments and polyhydroxybutyrate (PHB) polyesters. The PVA/TPS film mechanical properties (tensile strength (σu), 22.2 ± 4.3 MPa; strain at break (εu), 325 ± 73%; and Young’s modulus (E), 53–250 MPa) compared closely with low-density polyethylene (LDPE) grades used for food packaging. Strong solubility of the PVA/TPS film in water was a pertinent feature, facilitating suitability as a carbon source for bioprocessing and microbial degradation. Biodegradability of the film with greater than 50% weight loss occurred within 30 days of incubation at 37 °C in a model compost. Up to 22% of the PVA/TPS film substrate conversion to biomass was achieved using three bacterial strains, Ralstonia eutropha H16 (Cupriavidus necator ATCC 17699), Streptomyces sp. JS520, and Bacillus subtilis ATCC6633. For the first time, production of the valuable biopigment (undecylprodigiosin) by Streptomyces sp. JS520 of 5.3 mg/mL and the production of PHB biopolymer at 7.8% of cell dry weight by Ralstonia eutropha H16 from this substrate were reported. This low-energy, low-carbon post-use PVA/TPS film upcycling model approach to plastic circularity demonstrates marked progress in the quest for sustainable and circular plastic solutions.
Ferulic Acid as Building Block for the Lipase-Catalyzed Synthesis of Biobased Aromatic Polyesters
Authors: Bazin Alfred , Avérous Luc , Pollet Eric
Published: October 2021

Enzymatic synthesis of aromatic biobased polyesters is a recent and rapidly expanding research field. However, the direct lipase-catalyzed synthesis of polyesters from ferulic acid has not yet been reported. In this work, various ferulic-based monomers were considered for their capability to undergo CALB-catalyzed polymerization. After conversion into diesters of different lengths, the CALB-catalyzed polymerization of these monomers with 1,4-butanediol resulted in short oligomers with a DPn up to 5. Hydrogenation of the double bond resulted in monomers allowing obtaining polyesters of higher molar masses with DPn up to 58 and Mw up to 33,100 g·mol−1. These polyesters presented good thermal resistance up to 350 °C and Tg up to 7 °C. Reduction of the ferulic-based diesters into diols allowed preserving the double bond and synthesizing polyesters with a DPn up to 19 and Mw up to 15,500 g·mol−1 and higher Tg (up to 21 °C). Thus, this study has shown that the monomer hydrogenation strategy proved to be the most promising route to achieve ferulic-based polyester chains of high DPn. This study also demonstrates for the first time that ferulic-based diols allow the synthesis of high Tg polyesters. Therefore, this is an important first step toward the synthesis of competitive biobased aromatic polyesters by enzymatic catalysis.
RK4 and HAM Solutions of Eyring–Powell Fluid Coating Material with Temperature-Dependent-Viscosity Impact of Porous Matrix on Wire Coating Filled in Coating Die: Cylindrical Co-ordinates
Authors: Zeeshan  , Khan Waris , Khan Ilyas , Alshammari Nawa , Hamadneh Nawaf
Published: October 2021

In this work, we studied the impacts of transmitting light, nonlinear thermal, and micropolar fluid mechanics on a wire surface coating utilizing non-Newtonian viscoelastic flow. Models with temperature-dependent variable viscosity were used. The boundary layer equations governing the flow and heat transport processes were solved using the Runge–Kutta fourth order method. A distinguished constituent of this study was the use of a porous matrix that acted as an insulator to reduce heat loss. In this paper we discuss the effects of numerous development parameters, including β0, Q, m, Ω, Kp, and Br (non-Newtonian parameter, heat-producing parameter, viscosity parameter, variable viscosity parameter, porosity parameter, and Brinkman number, respectively). Furthermore, the effects of two other parameters, D and M, are also discussed as they relate to velocity and temperature distributions. We observed that the velocity profiles decreased with increasing values of Kp. Fluid velocity increased as the values of M, Br, N, and D increased, while it decreased when the values of Kp, Q and D increased. For increasing values of M, the temperature profile showed increasing behavior, while Br and Q showed decreasing behavior. Furthermore, the present work is validated by comparison with HAM and previously published work, with good results.