bluuebunny/crossref_metadata_2025 huggingface dataset:
The Meso-Structural Characteristics of Crack Generation and Propagation during Rock Fracturing
Authors: Zhang Yanbo , Gao Guangyu , Yan Shaohong , Yao Xulong , Liu Xiangxin , Liang Peng , Xu Yuedong
Published: January 2022

Meso-structure is an important factor affecting the characteristics of rock fracture. To determine the factors influencing the internal meso-structural characteristics upon the crack generation and extension, rock samples were tested under uniaxial cyclic loading and unloading and examined using computed tomography (CT) scanning. CT scanning was used to visualize and investigate the entire process of fracture source generation and its development in three dimensions, and finally the location information of the fracture source was determined. The mineral composition and structure along the fracture path inside the specimen were studied by using a polarizing microscope, and the evolution of fracture propagation around mineral particles was revealed based on its mineralogical characteristics. Results indicate that based on the fracture source around different rock meso-structure types, the initial fracture source can also be divided into different types, namely, the primary porosity type, the micro-crack type, and the mineral grain type. The strength characteristics of mineral grains can determine whether the crack extends around the gravel or through it. The hard grains at the crack-tip promote the transformation of tensile stress to shear stress, which lead to the change in the direction of crack extension and bifurcation. The spatial shape of the cracks after rock fracture is related to the initial distribution of minerals and is more complicated in areas where minerals are concentrated. The crack extension around gravel particles also generates a mode of failure, affecting large grains with gravel spalling from the matrix. The findings provide a study basis for identifying the potentially dangerous areas and provide early warning for the safety of underground engineering construction operations.
Crystal Structure Prediction and Lattice Dynamical Calculations for the Rare Platinum-Group Mineral Zaccariniite (RhNiAs)
Authors: Ibáñez-Insa Jordi
Published: January 2022

The crystal structures of newly found minerals are routinely determined using single-crystal techniques. However, many rare minerals usually form micrometer-sized aggregates that are difficult to study with conventional structural methods. This is the case for numerous platinum-group minerals (PGMs) such as, for instance, zaccariniite (RhNiAs), the crystal structure of which was first obtained by studying synthetic samples. The aim of the present work is to explore the usefulness of USPEX, a powerful crystal structure prediction method, as an alternative means of determining the crystal structure of minerals such as zaccariniite, with a relatively simple crystal structure and chemical formula. We show that fixed composition USPEX searches with a variable number of formula units, using the ideal formula of the mineral as the only starting point, successfully predict the tetragonal structure of a mineral. Density functional theory (DFT) calculations can then be performed in order to more tightly relax the structure of the mineral and calculate different fundamental properties, such as the frequency of zone-center Raman-active phonons, or even their pressure behavior. These theoretical data can be subsequently compared to experimental results, which, in the case of newly found minerals, would allow one to confirm the correctness of the crystal structure predicted by the USPEX code.
Geochemical, Isotopic and Petrological Constraints on the Origin and Evolution of the Recent Silicic Magmatism of the Greater Caucasus
Authors: Shcherbakov Vasily , Bindeman Ilya , Gazeev Viktor
Published: January 2022

Significant volumes of rhyolites and granites of the Pliocene-Pleistocene age are exposed in the collision zone of the Greater Caucasus, Russia. The volcanic history of the region includes ignimbrites and lavas associated with the Chegem caldera (2.9 Ma) and Elbrus volcano (1.98 and 0.7 Ma) and rhyolitic necks and granites in Tyrnyauz (1.98 Ma). They are characterized by a similar bulk and mineral composition and close ratios of incompatible elements, which indicates their related origin. The 1.98 Ma Elbrus ignimbrites, compared to the 2.9 Ma Chegem ignimbrites, have elevated concentrations of both compatible (Cr, Sr, Ca, Ni) and incompatible elements (Cs, Rb, U). We argue that the Elbrus ignimbrites were produced from magma geochemically similar to Chegem rhyolites through fractionation crystallization coupled with the assimilation of crustal material. The 1.98 Ma Eldjuta granites of Tyrnyauz and early ignimbrites of the Elbrus region (1.98 Ma) are temporally coeval, similar mineralogically, and have comparable major and trace element composition, which indicates that the Elbrus ignimbrites probably erupted from the area of modern Tyrnyauz; the Eldjurta granite could represent a plutonic reservoir that fed this eruption. Late ignimbrites of Elbrus (0.7 Ma) and subsequent lavas demonstrate progressively more mafic mineral assemblage and bulk rock composition in comparison with rhyolites. This indicates their origin in response to the mixing of rhyolites with magmas of a more basic composition at the late stage of magma system development. The composition of these basic magmas may be close to the basaltic trachyandesite, the flows exposed along the periphery of the Elbrus volcano. All studied young volcanic rocks of the Greater Caucasus are characterized by depletion in HSFE and enrichment in LILE, Li, and Pb, which emphasizes the close relationship of young silicic magmatism with magmas of suprasubduction geochemical affinity. An important geochemical feature is the enrichment of U up to 8 ppm and Th up to 35 ppm. The trace element composition of the rocks indicates that the original rhyolitic magma of Chegem ignimbrites caldera was formed at >80%–90% fractionation of calc-alkaline arc basalts with increased alkalinity. This observation, in addition to published data for isotopic composition (O-Hf-Sr) of the same units, shows that the crustal isotopic signatures of silicic volcanics may arise due to the subduction-induced fertilization of peridotites producing parental basaltic magmas before a delamination episode reactivated the melting of the former mantle and the lower crust.
Enhancement of the Detection Performance of Paper-Based Analytical Devices by Nanomaterials
Authors: Pang Renzhu , Zhu Qunyan , Wei Jia , Meng Xianying , Wang Zhenxin
Published: January 2022

Paper-based analytical devices (PADs), including lateral flow assays (LFAs), dipstick assays and microfluidic PADs (μPADs), have a great impact on the healthcare realm and environmental monitoring. This is especially evident in developing countries because PADs-based point-of-care testing (POCT) enables to rapidly determine various (bio)chemical analytes in a miniaturized, cost-effective and user-friendly manner. Low sensitivity and poor specificity are the main bottlenecks associated with PADs, which limit the entry of PADs into the real-life applications. The application of nanomaterials in PADs is showing great improvement in their detection performance in terms of sensitivity, selectivity and accuracy since the nanomaterials have unique physicochemical properties. In this review, the research progress on the nanomaterial-based PADs is summarized by highlighting representative recent publications. We mainly focus on the detection principles, the sensing mechanisms of how they work and applications in disease diagnosis, environmental monitoring and food safety management. In addition, the limitations and challenges associated with the development of nanomaterial-based PADs are discussed, and further directions in this research field are proposed.
Targeting Colorectal Cancer Cells with a Functionalised Calix[4]arene Receptor: Biophysical Studies
Authors: Danil de Namor Angela F , Al Hakawati Nawal , Farhat Sami Y
Published: January 2022

Colorectal cancer (CRC) is a disease which is causing a high degree of mortality around the world. The present study reports the antiproliferative impact of the thioacetamide calix[4]arene, CAII receptor on a highly differentiated Caco-2 cell line. This statement is corroborated by the MTT assay results which revealed a reduction in the cell viability with an IC50 value of 19.02 ± 0.04 µM. Microscopic results indicated that at the starting amount of 10 µM of CAII, a decrease in cells confluency can already be observed in addition to changes in cells morphology. Cell metabolic pathway changes were also investigated. 1H NMR findings showed downregulation in lactate, pyruvate, phosphocholine, lipids, and hydroxybutyrate with the upregulation of succinate, indicating a decline in the cells proliferation. Some biochemical alterations in the cells as a result of the CAII treatment were found by Raman spectroscopy.
Recent Advances in Visible-Light-Mediated Amide Synthesis
Authors: Lu Bin , Xiao Wen-Jing , Chen Jia-Rong
Published: January 2022

Visible-light photoredox catalysis has attracted tremendous interest within the synthetic community. As such, the activation mode potentially provides a more sustainable and efficient platform for the activation of organic molecules, enabling the invention of many controlled radical-involved reactions under mild conditions. In this context, amide synthesis via the strategy of photoredox catalysis has received growing interest due to the ubiquitous presence of this structural motif in numerous natural products, pharmaceuticals and functionalized materials. Employing this strategy, a wide variety of amides can be prepared effectively from halides, arenes and even alkanes under irradiation of visible light. These methods provide a robust alternative to well-established strategies for amide synthesis that involve condensation between a carboxylic acid and amine mediated by a stoichiometric activating agent. In this review, the representative progresses made on the synthesis of amides through visible light-mediated radical reactions are summarized.
Optimization of Bioactive Phenolics Extraction and Cosmeceutical Activity of Eco-Friendly Polypropylene-Glycol–Lactic-Acid-Based Extracts of Olive Leaf
Authors: Marijan Marijan , Mitar Anamarija , Jakupović Lejsa , Prlić Kardum Jasna , Zovko Končić Marijana
Published: January 2022

Olive leaf is a rich source of phenolic compounds with numerous activities related to skin health and appearance. In this study, a green extraction method was developed using eco-friendly solvents: polypropylene glycol (PPG), lactic acid (LA), and water. The optimal extraction conditions were established, including solvent, extraction time, technique (magnetic stirrer vs. ultrasound-assisted extraction), and herbal material/solvent ratio. The composition of the solvent mixture was optimized using a mixture design. The content of phenolic compounds, including oleuropein and verbascoside, was determined using high-performance liquid chromatography (HPLC) and spectrophotometric methods. Using different extraction conditions, three extracts were prepared and their phytochemical compositions and antioxidant and skin-related bioactivities were investigated. The extracts were excellent inhibitors of elastase, collagenase, tyrosinase, and lipoxygenase. The best activity was shown by the extract richest in phenolics and prepared using magnetic-stirrer-assisted extraction for 20 min, with 0.8 g of herbal material extracted in 10 mL of PPG/LA/water mixture (28.6/63.6/7.8, w/w/w), closely followed by the extract prepared using the same extraction conditions but with 0.42 g of herbal material. The investigated PPG/LA/water mixtures contributed to the overall enzyme-inhibitory activity of the extracts. The prepared extracts were appropriate for direct use in cosmetic products, thus saving the time and energy consumption necessary for the evaporation of conventional solvents.
Novel Molecular Targets of Antidepressants
Authors: Jarończyk Małgorzata , Walory Jarosław
Published: January 2022

Antidepressants target a variety of proteins in the central nervous system (CNS), the most important belonging to the family of G-protein coupled receptors and the family of neurotransmitter transporters. The increasing number of crystallographic structures of these proteins have significantly contributed to the knowledge of their mechanism of action, as well as to the design of new drugs. Several computational approaches such as molecular docking, molecular dynamics, and virtual screening are useful for elucidating the mechanism of drug action and are important for drug design. This review is a survey of molecular targets for antidepressants in the CNS and computer based strategies to discover novel compounds with antidepressant activity.
Microwave-Assisted Desulfation of the Hemolytic Saponins Extracted from Holothuria scabra Viscera
Authors: Savarino Philippe , Colson Emmanuel , Caulier Guillaume , Eeckhaut Igor , Flammang Patrick , Gerbaux Pascal
Published: January 2022

Saponins are plant and marine animal specific metabolites that are commonly considered as molecular vectors for chemical defenses against unicellular and pluricellular organisms. Their toxicity is attributed to their membranolytic properties. Modifying the molecular structures of saponins by quantitative and selective chemical reactions is increasingly considered to tune the biological properties of these molecules (i) to prepare congeners with specific activities for biomedical applications and (ii) to afford experimental data related to their structure–activity relationship. In the present study, we focused on the sulfated saponins contained in the viscera of Holothuria scabra, a sea cucumber present in the Indian Ocean and abundantly consumed on the Asian food market. Using mass spectrometry, we first qualitatively and quantitatively assessed the saponin content within the viscera of H. scabra. We detected 26 sulfated saponins presenting 5 different elemental compositions. Microwave activation under alkaline conditions in aqueous solutions was developed and optimized to quantitatively and specifically induce the desulfation of the natural saponins, by a specific loss of H2SO4. By comparing the hemolytic activities of the natural and desulfated extracts, we clearly identified the sulfate function as highly responsible for the saponin toxicity.
Surfactant-Free Monodispersed Pd Nanoparticles Template for Core-Shell Pd@PdPt Nanoparticles as Electrocatalyst towards Methanol Oxidation Reaction (MOR)
Authors: Zheng Fulin , Kwong Tsz-Lung , Yung Ka-Fu
Published: January 2022

An eco-friendly two-step synthetic method for synthesizing Pd@PdPt/CNTs nanoparticles was introduced and studied for the methanol oxidation reaction. The Pd@PdPt alloy core-shell structure was synthesized by preparing a surfactant-free monodispersed Pd/CNTs precursor through the hydrolysis of tetrachloropalladate (II) ion ([PdCl4]2−) in the presence of carbon nanotubes (CNTs) and the subsequent hydrogen reduction and followed by a galvanic replacement reaction. This method opens up an eco-friendly, practical, and straightforward route for synthesizing monometallic or bimetallic nanoparticles with a clean surfactant-free electrocatalytic surface. It is quite promising for large-scale preparation. The Pd@PdPt/CNTs electrocatalyst demonstrated a high specific mass activity for methanol oxidation (400.2 mAmgPt−1) and excellent stability towards direct methanol oxidation compared to its monometallic counterparts.
Sustainable and Printable Nanocellulose-Based Ionogels as Gel Polymer Electrolytes for Supercapacitors
Authors: González-Gil Rosa M. , Borràs Mateu , Chbani Aiman , Abitbol Tiffany , Fall Andreas , Aulin Christian , Aucher Christophe , Martínez-Crespiera Sandra
Published: January 2022

A new gel polymer electrolyte (GPE) based supercapacitor with an ionic conductivity up to 0.32–0.94 mS cm−2 has been synthesized from a mixture of an ionic liquid (IL) with nanocellulose (NC). The new NC-ionogel was prepared by combining the IL 1-ethyl-3-methylimidazolium dimethyl phosphate (EMIMP) with carboxymethylated cellulose nanofibers (CNFc) at different ratios (CNFc ratio from 1 to 4). The addition of CNFc improved the ionogel properties to become easily printable onto the electrode surface. The new GPE based supercapacitor cell showed good electrochemical performance with specific capacitance of 160 F g−1 and an equivalent series resistance (ESR) of 10.2 Ω cm−2 at a current density of 1 mA cm−2. The accessibility to the full capacitance of the device is demonstrated after the addition of CNFc in EMIMP compared to the pristine EMIMP (99 F g−1 and 14.7 Ω cm−2).
Nanodelivery Strategies for Skin Diseases with Barrier Impairment: Focusing on Ceramides and Glucocorticoids
Authors: Almeida Cíntia , Filipe Patrícia , Rosado Catarina , Pereira-Leite Catarina
Published: January 2022

The human epidermis has a characteristic lipidic composition in the stratum corneum, where ceramides play a crucial role in the skin barrier homeostasis and in water-holding capacity. Several skin diseases, such as atopic dermatitis and psoriasis, exhibit a dysfunction in the lipid barrier with altered ceramide levels and increased loss of transepidermal water. Glucocorticoids are normally employed in the therapeutical management of these pathologies. However, they have shown a poor safety profile and reduced treatment efficiency. The main objective of this review is to, within the framework of the limitations of the currently available therapeutical approaches, establish the relevance of nanocarriers as a safe and efficient delivery strategy for glucocorticoids and ceramides in the topical treatment of skin disorders with barrier impairment.
Abstracts of the Fourth Brainstorming Research Assembly for Young Neuroscientists (BraYn), Italy, 20–22 October 2021
Authors: Ferrara Giovanni
Published: January 2022

On behalf of the BraYn Association, we are pleased to present the Abstracts of the Fourth Brainstorming Research Assembly for Young Neuroscientists, which was held from 20–22 October 2021. We congratulate all the presenters on their research work and contribution.
Hydroethanolic Extract of Prunus domestica L.: Metabolite Profiling and In Vitro Modulation of Molecular Mechanisms Associated to Cardiometabolic Diseases
Authors: Ullah Hammad , Sommella Eduardo , Santarcangelo Cristina , D’Avino Danilo , Rossi Antonietta , Dacrema Marco , Minno Alessandro Di , Di Matteo Giacomo , Mannina Luisa , Campiglia Pietro , Magni Paolo , Daglia Maria
Published: January 2022

High consumption of fruit and vegetables has an inverse association with cardiometabolic risk factors. This study aimed to chemically characterize the hydroethanolic extract of P. domestica subsp. syriaca fruit pulp and evaluate its inhibitory activity against metabolic enzymes and production of proinflammatory mediators. Ultra-high-performance liquid chromatography high-resolution mass spectrometry(UHPLC-HRMS) analysis showed the presence of hydroxycinnamic acids, flavanols, and glycoside flavonols, while nuclear magnetic resonance(NMR) analysis showed, among saccharides, an abundant presence of glucose. P. domestica fruit extract inhibited α-amylase, α-glucosidase, pancreatic lipase, and HMG CoA reductase enzyme activities, with IC50 values of 7.01 mg/mL, 6.4 mg/mL, 6.0 mg/mL, and 2.5 mg/mL, respectively. P. domestica fruit extract inhibited lipopolysaccharide-induced production of nitrite, interleukin-1 β and PGE2 in activated J774 macrophages. The findings of the present study indicate that P. domestica fruit extracts positively modulate in vitro a series of molecular mechanisms involved in the pathophysiology of cardiometabolic diseases. Further research is necessary to better characterize these properties and their potential application for human health.
The Impact of Probiotics, Prebiotics, and Synbiotics during Pregnancy or Lactation on the Intestinal Microbiota of Children Born by Cesarean Section: A Systematic Review
Authors: Martín-Peláez Sandra , Cano-Ibáñez Naomi , Pinto-Gallardo Miguel , Amezcua-Prieto Carmen
Published: January 2022

The gut microbiota is a key factor in the correct development of the gastrointestinal immune system. Studies have found differences between the gut microbiota of newborns delivered by cesarean section compared to those vaginally delivered. Our objective was to evaluate the effect of ingestion of probiotics, prebiotics, or synbiotics during pregnancy and/or lactation on the development of the gut microbiota of the C-section newborns. We selected experimental studies in online databases from their inception to October 2021. Of the 83 records screened, 12 met the inclusion criteria. The probiotics used belonged to the genera Lactobacillus, Bifidobacterium, Propionibacterium, and Streptococcus, or a combination of those, with dosages varying between 2 × 106 and 9 × 1011 CFU per day, and were consumed during pregnancy and/or lactation. Probiotic strains were combined with galacto-oligosaccharides, fructo-oligosaccharides, or bovine milk-derived oligosaccharides in the synbiotic formulas. Probiotic, prebiotic, and synbiotic interventions led to beneficial gut microbiota in cesarean-delivered newborns, closer to that in vaginally delivered newborns, especially regarding Bifidobacterium colonization. This effect was more evident in breastfed infants. The studies indicate that this beneficial effect is achieved when the interventions begin soon after birth, especially the restoration of bifidobacterial population. Changes in the infant microbial ecosystem due to the interventions seem to continue after the end of the intervention in most of the studies. More interventional studies are needed to elucidate the optimal synbiotic combinations and the most effective strains and doses for achieving the optimal gut microbiota colonization of C-section newborns.
The Role of Diet in Prognosis among Cancer Survivors: A Systematic Review and Meta-Analysis of Dietary Patterns and Diet Interventions
Authors: Castro-Espin Carlota , Agudo Antonio
Published: January 2022

Cancer survival continues to improve in high-income countries, partly explained by advances in screening and treatment. Previous studies have mainly examined the relationship between individual dietary components and cancer prognosis in tumours with good therapeutic response (breast, colon and prostate cancers). The aim of this review is to assess qualitatively (and quantitatively where appropriate) the associations of dietary patterns and cancer prognosis from published prospective cohort studies, as well as the effect of diet interventions by means of randomised controlled trials (RCT). A systematic search was conducted in PubMed, and a total of 35 prospective cohort studies and 14 RCT published between 2011 and 2021 were selected. Better overall diet quality was associated with improved survival among breast and colorectal cancer survivors; adherence to the Mediterranean diet was associated to lower risk of mortality in colorectal and prostate cancer survivors. A meta-analysis using a random-effects model showed that higher versus lower diet quality was associated with a 23% reduction in overall mortality in breast cancer survivors. There was evidence that dietary interventions, generally combined with physical activity, improved overall quality of life, though most studies were in breast cancer survivors. Further cohort and intervention studies in other cancers are needed to make more specific recommendations.
Associations of Nutritional Behavior and Gut Microbiota with the Risk of COVID-19 in Healthy Young Adults in Poland
Authors: Jagielski Paweł , Łuszczki Edyta , Wnęk Dominika , Micek Agnieszka , Bolesławska Izabela , Piórecka Beata , Kawalec Paweł
Published: January 2022

The numerous consequences of the coronavirus disease 2019 (COVID-19) pandemic in healthy young people and the lack of clarity as to the long-term disease outcomes have spurred the search for risk factors for SARS-CoV-2 infection. We aimed to evaluate the associations of nutritional behaviors, gut microbiota, and physical activity with the risk of COVID-19 in healthy young nonobese people. Data on body composition, anthropometric measurements, physical activity, dietary intake, and gut microbiota were obtained from 95 adults (mean age, 34.66 ± 5.76 years). A balanced diet rich in vegetables and fruit, including nuts, wholegrain cereal products, and legumes, covers the need for vitamins and minerals. Such a diet can be an effective measure to reduce the risk of COVID-19 in nonobese healthy physically active young people with normal immune function. People with balanced diet and an average daily consumption of >500 g of vegetables and fruit and >10 g of nuts had an 86% lower risk of COVID-19 compared with those whose diet was not balanced and who consumed lower amounts of these products. It is well documented that proper nutrition, physical activity, and maintenance of normal weight facilitate good health by ensuring optimal immune function. The beneficial effects of these interventions should be strongly emphasized during the COVID-19 pandemic.
Olive Mill Wastewater Inhibits Growth and Proliferation of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro by Down-Regulating the Akt/mTOR-Signaling Pathway
Authors: Rutz Jochen , Maxeiner Sebastian , Juengel Eva , Chun Felix K.-H. , Tsaur Igor , Blaheta Roman A.
Published: January 2022

Bladder cancer patients whose tumors develop resistance to cisplatin-based chemotherapy often turn to natural, plant-derived products. Beneficial effects have been particularly ascribed to polyphenols, although their therapeutic relevance when resistance has developed is not clear. The present study evaluated the anti-tumor potential of polyphenol-rich olive mill wastewater (OMWW) on chemo-sensitive and cisplatin- and gemcitabine-resistant T24, RT112, and TCCSUP bladder cancer cells in vitro. The cells were treated with different dilutions of OMWW, and tumor growth and clone formation were evaluated. Possible mechanisms of action were investigated by evaluating cell cycle phases and cell cycle-regulating proteins. OMWW profoundly inhibited the growth and proliferation of chemo-sensitive as well as gemcitabine- and cisplatin-resistant bladder cancer cells. Depending on the cell line and on gemcitabine- or cisplatin-resistance, OMWW induced cell cycle arrest at different phases. These differing phase arrests were accompanied by differing alterations in the CDK-cyclin axis. Considerable suppression of the Akt-mTOR pathway by OMWW was observed in all three cell lines. Since OMWW blocks the cell cycle through the manipulation of the cyclin-CDK axis and the deactivation of Akt-mTOR signaling, OMWW could become relevant in supporting bladder cancer therapy.
Receptor Mediated Effects of Advanced Glycation End Products (AGEs) on Innate and Adaptative Immunity: Relevance for Food Allergy
Authors: Briceno Noriega Daniela , Zenker Hannah E. , Croes Cresci-Anne , Ewaz Arifa , Ruinemans-Koerts Janneke , Savelkoul Huub F. J. , van Neerven R. J. Joost , Teodorowicz Malgorzata
Published: January 2022

As of late, evidence has been emerging that the Maillard reaction (MR, also referred to as glycation) affects the structure and function of food proteins. MR induces the conformational and chemical modification of food proteins, not only on the level of IgG/IgE recognition, but also by increasing the interaction and recognition of these modified proteins by antigen-presenting cells (APCs). This affects their biological properties, including digestibility, bioavailability, immunogenicity, and ultimately their allergenicity. APCs possess various receptors that recognize glycation structures, which include receptor for advanced glycation end products (RAGE), scavenger receptors (SRs), galectin-3 and CD36. Through these receptors, glycation structures may influence the recognition, uptake and antigen-processing of food allergens by dendritic cells (DCs) and monocytes. This may lead to enhanced cytokine production and maturation of DCs, and may also induce adaptive immune responses to the antigens/allergens as a result of antigen uptake, processing and presentation to T cells. Here, we aim to review the current literature on the immunogenicity of AGEs originating from food (exogenous or dietary AGEs) in relation to AGEs that are formed within the body (endogenous AGEs), their interactions with receptors present on immune cells, and their effects on the activation of the innate as well as the adaptive immune system. Finally, we review the clinical relevance of AGEs in food allergies.
Effectiveness of Nutritional Strategies on Improving the Quality of Diet of Children from 6 to 12 Years Old: A Systematic Review
Authors: Andueza Naroa , Navas-Carretero Santiago , Cuervo Marta
Published: January 2022

Dietary habits, that are formed during childhood and consolidated in adulthood, are known to influence the development of future chronic diseases such as metabolic syndrome or type 2 diabetes. The aim of this review was to evaluate the effectiveness of nutritional interventions carried out in recent years focused on improving the quality of the diet of the child population. A systematic search of the PubMed and Scopus databases was performed from January 2011 until September 2021. A total of 910 articles were identified and screened based on their title, abstract and full text. Finally, 12 articles were included in the current systematic review. Of those, in six studies the intervention was based on the provision of healthy meals and in the other six studies the intervention focused on modifying the school environment. Six of the studies selected included other components in their intervention such as nutritional education sessions, physical activity and/or families. A wide variety of methods were used for diet assessments, from direct method to questionnaires. The results suggest that interventions that modify the school environment or provide different meals or snacks may be effective in improving children’s dietary patterns, both in the short and long term. Further research is necessary to evaluate the real effectiveness of strategies with multidisciplinary approach (nutritional sessions, physical activity and family’s involvement).
Attacking the Intruder at the Gate: Prospects of Mucosal Anti SARS-CoV-2 Vaccines
Authors: Karczmarzyk Kacper , Kęsik-Brodacka Małgorzata
Published: January 2022

The sudden outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic in December 2019 caused crises and health emergencies worldwide. The rapid spread of the virus created an urgent need for the development of an effective vaccine and mass immunization to achieve herd immunity. Efforts of scientific teams at universities and pharmaceutical companies around the world allowed for the development of various types of preparations and made it possible to start the vaccination process. However, it appears that the developed vaccines are not effective enough and do not guarantee long-lasting immunity, especially for new variants of SARS-CoV-2. Considering this problem, it is promising to focus on developing a Coronavirus Disease 2019 (COVID-19) mucosal vaccine. Such a preparation applied directly to the mucous membranes of the upper respiratory tract might provide an immune barrier at the primary point of virus entry into the human body while inducing systemic immunity. A number of such preparations against SARS-CoV-2 are already in various phases of preclinical and clinical trials, and several of them are very close to being accepted for general use, constituting a milestone toward pandemic containment.
The Role of Glucosinolates from Cruciferous Vegetables (Brassicaceae) in Gastrointestinal Cancers: From Prevention to Therapeutics
Authors: Melim Catarina , Lauro Maria R. , Pires Isabel M. , Oliveira Paulo J. , Cabral Célia
Published: January 2022

The gastrointestinal (GI) tract is composed of rapidly renewing cells, which increase the likelihood of cancer. Colorectal cancer is one of the most frequently diagnosed GI cancers and currently stands in second place regarding cancer-related mortality. Unfortunately, the treatment of GI is limited, and few developments have occurred in the field over the years. With this in mind, new therapeutic strategies involving biologically active phytocompounds are being evaluated as anti-cancer agents. Vegetables such as broccoli, brussels sprouts, cabbage, cauliflower, and radish, all belonging to the Brassicaceae family, are high in dietary fibre, minerals, vitamins, carotenoids, polyphenols, and glucosinolates. The latter compound is a secondary metabolite characteristic of this family and, when biologically active, has demonstrated anti-cancer properties. This article reviews the literature regarding the potential of Cruciferous vegetables in the prevention and/or treatment of GI cancers and the relevance of appropriate compound formulations for improving the stability and bioaccessibility of the major Cruciferous compounds, with a particular focus on glucosinolates.
Time-Prolonged Release of Tumor-Targeted Protein–MMAE Nanoconjugates from Implantable Hybrid Materials
Authors: Serna Naroa , Falgàs Aïda , García-León Annabel , Unzueta Ugutz , Núñez Yáiza , Sánchez-Chardi Alejandro , Martínez-Torró Carlos , Mangues Ramón , Vazquez Esther , Casanova Isolda , Villaverde Antonio
Published: January 2022

The sustained release of small, tumor-targeted cytotoxic drugs is an unmet need in cancer therapies, which usually rely on punctual administration regimens of non-targeted drugs. Here, we have developed a novel concept of protein–drug nanoconjugates, which are packaged as slow-releasing chemically hybrid depots and sustain a prolonged secretion of the therapeutic agent. For this, we covalently attached hydrophobic molecules (including the antitumoral drug Monomethyl Auristatin E) to a protein targeting a tumoral cell surface marker abundant in several human neoplasias, namely the cytokine receptor CXCR4. By this, a controlled aggregation of the complex is achieved, resulting in mechanically stable protein–drug microparticles. These materials, which are mimetics of bacterial inclusion bodies and of mammalian secretory granules, allow the slow leakage of fully functional conjugates at the nanoscale, both in vitro and in vivo. Upon subcutaneous administration in a mouse model of human CXCR4+ lymphoma, the protein–drug depots release nanoconjugates for at least 10 days, which accumulate in the tumor with a potent antitumoral effect. The modification of scaffold cell-targeted proteins by hydrophobic drug conjugation is then shown as a novel transversal platform for the design of slow releasing protein–drug depots, with potential application in a broad spectrum of clinical settings.
Swallowability of Minitablets among Children Aged 6–23 Months: An Exploratory, Randomized Crossover Study
Authors: Mitsui Nao , Hida Noriko , Kamiya Taro , Yamazaki Taigi , Miyazaki Kazuki , Saito Kiyomi , Saito Jumpei , Yamatani Akimasa , Ishikawa Yoichi , Nakamura Hidefumi , Nakamura Akihiro , Harada Tsutomu
Published: January 2022

Minitablets have garnered interest as a new paediatric formulation that is easier to swallow than liquid formulations. In Japan, besides the latter, fine granules are frequently used for children. We examined the swallowability of multiple drug-free minitablets and compared it with that of fine granules and liquid formulations in 40 children of two age groups (n = 20 each, aged 6–11 and 12–23 months). We compared the percentage of children who could swallow minitablets without chewing with that of children who could swallow fine granules or liquid formulations without leftover. The children who visited the paediatric department of Showa University Hospital were enrolled. Their caregivers were allowed to choose the administration method. In total, 37 out of 40 caregivers dispersed the fine granules in water. Significantly more children (80%, 95% CI: 56–94%) aged 6–11 months could swallow the minitablets than those who could swallow all the dispersed fine granules and liquid formulations (22%, 95% CI: 6–47% and 35%, 95% CI: 15–59%, respectively). No significant differences were observed in children aged 12–23 months. Hence, minitablets may be easier to swallow than dispersed fine granules and liquid formulations in children aged 6–11 months.
Resveratrol Encapsulation and Release from Pristine and Functionalized Mesoporous Silica Carriers
Authors: Ioniţă Simona , Lincu Daniel , Mitran Raul-Augustin , Ziko Laila , Sedky Nada K. , Deaconu Mihaela , Brezoiu Ana-Maria , Matei Cristian , Berger Daniela
Published: January 2022

Resveratrol, a naturally occurring polyphenol, has attracted significant attention due to its antioxidant, cardioprotective and anticancer potential. However, its low aqueous solubility limits resveratrol bioavailability and use. In this work, different mesoporous silica matrices were used to encapsulate the polyphenol and to increase its dissolution rate. Pristine MCM-41, MCM-48, SBA-15, SBA-16, FDU-12 and MCF silica were obtained. The influence of SBA-15 functionalized with aminopropyl, isocyanate, phenyl, mercaptopropyl, and propionic acid moieties on resveratrol loading and release profiles was also assessed. The cytotoxic effects were evaluated for mesoporous carriers and resveratrol-loaded samples against human lung cancer (A549), breast cancer (MDA-MB-231) and human skin fibroblast (HSF) cell lines. The effect on apoptosis and cell cycle were assayed for selected resveratrol-loaded carriers. The polyphenol molecules are encapsulated only inside the mesopores, mostly in amorphous state. All materials containing either pristine or functionalized silica carriers increased polyphenol dissolution rate. The influence of the physico-chemical properties of the mesoporous carriers and resveratrol–loaded supports on the kinetic parameters was identified. Resv@SBA-15-SH and Resv@SBA-15-NCO samples exhibited the highest anticancer effect against A549 cells (IC50 values were 26.06 and 36.5 µg/mL, respectively) and against MDA-MB-231 (IC50 values were 35.56 and 19.30 µg/mL, respectively), which highlights their potential use against cancer.
Formulation, Preparation, Characterization, and Evaluation of Dicarboxylic Ionic Liquid Donepezil Transdermal Patches
Authors: Dinh Linh , Lee Soohun , Abuzar Sharif Md , Park Heejun , Hwang Sung-Joo
Published: January 2022

Donepezil (DPZ) is generally administered orally to treat Alzheimer’s disease (AD). However, oral administration can cause gastrointestinal side effects. Therefore, to enhance compliance, a new way to deliver DPZ from transdermal patch was developed. Ionic bonds were created by dissolving dicarboxylic acid and DPZ in ethanol, resulting in a stable ionic liquid (IL) state. The synthesized ILs were characterized by differential scanning calorimetry, optical microscope, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The DPZ ILs were then transformed to a suitable drug-in-adhesive patch for transdermal delivery of DPZ. The novel DPZ ILs patch inhibits crystallization of the IL, indicating coherent design. Moreover, DPZ ILs and DPZ IL patch formulations performed excellent skin permeability compared to that of the DPZ free-base patch in both in vitro and ex vivo skin permeability studies.
Skin Regenerative Potential of Cupuaçu Seed Extract (Theobroma grandiflorum), a Native Fruit from the Amazon: Development of a Topical Formulation Based on Chitosan-Coated Nanocapsules
Authors: Barbalho Geisa Nascimento , Matos Breno Noronha , da Silva Brito Gabriel Ferreira , da Cunha Miranda Thamires , Alencar-Silva Thuany , Sodré Fernando Fabriz , Gelfuso Guilherme Martins , Cunha-Filho Marcilio , Carvalho Juliana Lott , da Silva Joyce Kelly do Rosário , Gratieri Taís
Published: January 2022

Scarless skin regeneration is a challenge in regenerative medicine. Herein, we explore the regenerative potential of a Cupuaçu seed extract (Theobroma grandiflorum) to develop an innovative skin regeneration formulation based on chitosan-coated nanocapsules. Cupuaçu seed extract significantly stimulated cell proliferation and migration. A reparative gene expression profile could be verified following extract treatment, which included high levels of MKI67, a cellular proliferation marker, and extracellular matrix genes, such as ELN and HAS2, which code for elastin and hyaluronic acid synthase 2. Formulations with Cupuaçu seed extract successfully entrapped into nanocapsules (EE% > 94%) were developed. Uncoated or coated nanocapsules with low-molecular-weight chitosan presented unimodal size distribution with hydrodynamic diameters of 278.3 ± 5.0 nm (PDI = 0.18 ± 0.02) and 337.2 ± 2.1 nm (PDI = 0.27 ± 0.01), respectively. Both nanosystems were physically stable for at least 120 days and showed to be non-irritating to reconstructed human epidermis. Chitosan coating promoted active penetration into undamaged skin areas, which were still covered by the stratum corneum. In conclusion, the present study demonstrated for the first time the biotechnological potential of the frequently discarded Cupuaçu seed as a valuable pharmaceutical ingredient to be used in regenerative skin products.
Tablet Disintegration and Dispersion under In Vivo-like Hydrodynamic Conditions
Authors: Lenz Jan , Fuest Frederik , Finke Jan Henrik , Bunjes Heike , Kwade Arno , Juhnke Michael
Published: January 2022

Disintegration and dispersion are functional properties of tablets relevant for the desired API release. The standard disintegration test (SDT) described in different pharmacopoeias provides only limited information on these complex processes. It is considered not to be comparable to the biorelevant conditions due to the frequent occurrence of high hydrodynamic forces, among other reasons. In this study, 3D tomographic laser-induced fluorescence imaging (3D Tomo-LIF) is applied to analyse tablet disintegration and dispersion. Disintegration time (DT) and time-resolved particle size distribution in close proximity to the tablet are determined in a continuously operated flow channel, adjustable to very low fluid velocities. A case study on tablets of different porosity, which are composed of pharmaceutical polymers labelled with a fluorescent dye, a filler, and disintegrants, is presented to demonstrate the functionality and precision of the novel method. DT results from 3D Tomo-LIF are compared with results from the SDT, confirming the analytical limitations of the pharmacopoeial disintegration test. Results from the 3D Tomo-LIF method proved a strong impact of fluid velocity on disintegration and dispersion. Generally, shorter DTs were determined when cross-linked sodium carboxymethly cellulose (NaCMCXL) was used as disintegrant compared to polyvinyl polypyrrolidone (PVPP). Tablets containing Kollidon VA64 were found to disintegrate by surface erosion. The novel method provides an in-depth understanding of the functional behaviour of the tablet material, composition and structural properties under in vivo-like hydrodynamic forces regarding disintegration and the temporal progress of dispersion. We consider the 3D Tomo-LIF in vitro method to be of improved biorelevance in terms of hydrodynamic conditions in the human stomach.
Assessment of Genetic Parameters and Gene Action Associated with Heterosis for Enhancing Yield Characters in Novel Hybrid Rice Parental Lines
Authors: Gaballah Mahmoud M. , Attia Kotb A. , Ghoneim Adel M. , Khan Naeem , EL-Ezz Aziz F. , Yang Baochang , Xiao Langtao , Ibrahim Eid I. , Al-Doss Abdullah A.
Published: January 2022

The technology of hybrid rice utilizing heterosis is an essential requirement for achieving food security. The current study was aimed at assessing the genetic parameters and the gene actions of 15 yield-component traits associated with heterosis, in 9 new parental lines of hybrid rice and their generated hybrids. Five cytoplasmic male sterile (CMS) lines were crossed with four restorer (R) lines using twenty generated line × tester designation hybrid combinations. The results revealed that all the traits were controlled by additive and non-additive gene actions. However, the additive variance was the main component of the total genotypic variance. Assessment of the general combining ability (GCA) detected the best combiners among the genotypes. The hybrid combinations that expressed the highest-positive specific combining ability (SCA) for grain-yield were detected. The correlation between the GCA and SCA was evaluated. The hybrid crosses with high-positive heterosis, due to having a better parent for grain yield, were detected. The principal component analysis (PCA) recorded the first four principal axis displayed Eigenvalues >1 and existing variation cumulative of 83.92% in the genotypes for yield component characteristics. Three-dimensional plots corresponding to the studied traits illustrated that the genotypes Guang8A × Giza181, Quan-9311A × Giza179, II-32A × Giza181, and II-32A × Giza179 are classified as possessing superior grain yield.
Effective Stiffness of Fused Deposition Modeling Infill Lattice Patterns Made of PLA-Wood Material
Authors: Cuan-Urquizo Enrique , Álvarez-Trejo Alberto , Robles Gil Andrés , Tejada-Ortigoza Viridiana , Camposeco-Negrete Carmita , Uribe-Lam Esmeralda , Treviño-Quintanilla Cecilia D.
Published: January 2022

Fused deposition modeling (FDM) uses lattice arrangements, known as infill, within the fabricated part. The mechanical properties of parts fabricated via FDM are dependent on these infill patterns, which make their study of great relevance. One of the advantages of FDM is the wide range of materials that can be employed using this technology. Among these, polylactic acid (PLA)-wood has been recently gaining attention as it has become commercially available. In this work, the stiffness of two different lattice structures fabricated from PLA-wood material using FDM are studied: hexagonal and star. Rectangular samples with four different infill densities made of PLA-wood material were fabricated via FDM. Samples were subjected to 3-point bending to characterize the effective stiffness and their sensitivity to shear deformation. Lattice beams proved to be more sensitive to shear deformations, as including the contribution of shear in the apparent stiffness of these arrangements leads to more accurate results. This was evaluated by comparing the effective Young’s modulus characterized from 3-point bending using equations with and without shear inclusion. A longer separation between supports yielded closer results between both models (~41% for the longest separation tested). The effective stiffness as a function of the infill density of both topologies showed similar trends. However, the maximum difference obtained at low densities was the hexagonal topology that was ~60% stiffer, while the lowest difference was obtained at higher densities (star topology being stiffer by ~20%). Results for stiffness of PLA-wood samples were scattered. This was attributed to the defects at the lattice element level inherent to the material employed in this study, confirmed via micro-characterization.