bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances on the Amaryllidacea Alkaloids Collected in South Africa, Andean South America and the Mediterranean Basin
Authors: Evidente Antonio
Published: May 2023

The alkaloids are one of the most represented family of natural occurring biological active compounds. Amaryllidaceae are also very well known for their beautiful flower and are thus used as ornamental plants in historic and public gardens. The Amaryllidacea alkaloids constitute an important group that is subdivided into different subfamilies with different carbon skeletons. They are well known from ancient times for their long application in folk medicine, and in particular, Narcissus poeticus L. was known to Hippocrates of Cos (ca. B.C. 460–370), who treated uterine tumors with a formulate prepared from narcissus oil. To date, more than 600 alkaloids of 15 chemical groups exhibiting various biological activities have been isolated from the Amaryllidaceae plants. This plant genus is diffused in regions of Southern Africa, Andean South America and the Mediterranean basin. Thus, this review describes the chemical and biological activity of the alkaloids collected in these regions in the last two decades as weel those of isocarbostyls isolated from Amaryllidaceae in the same regions and same period.
New Random Aromatic/Aliphatic Copolymers of 2,5-Furandicarboxylic and Camphoric Acids with Tunable Mechanical Properties and Exceptional Gas Barrier Capability for Sustainable Mono-Layered Food Packaging
Authors: Guidotti Giulia , Soccio Michelina , Gazzano Massimo , Siracusa Valentina , Lotti Nadia
Published: May 2023

High molecular weight, fully biobased random copolymers of 2,5-furandicarboxylic acid (2,5-FDCA) containing different amounts of (1R, 3S)-(+)-Camphoric Acid (CA) have been successfully synthesized by two-stage melt polycondensation and compression molding in the form of films. The synthesized copolyesters have been first subjected to molecular characterization by nuclear magnetic resonance spectroscopy and gel-permeation chromatography. Afterward, the samples have been characterized from a thermal and structural point of view by means of differential scanning calorimetry, thermogravimetric analysis, and wide-angle X-ray scattering, respectively. Mechanical and barrier properties to oxygen and carbon dioxide were also tested. The results obtained revealed that chemical modification permitted a modulation of the abovementioned properties depending on the amount of camphoric co-units present in the copolymers. The outstanding functional properties promoted by camphor moieties addition could be associated with improved interchain interactions (π-π ring stacking and hydrogen bonds).
Comparison of Identification and Quantification of Polyphenolic Compounds in Skins and Seeds of Four Grape Varieties
Authors: Chengolova Zlatina , Ivanov Yavor , Godjevargova Tzonka
Published: May 2023

The aim of this study was to identify and quantify polyphenolic compounds in skin extracts from four Bulgarian grape varieties and compare them to those of seed extracts. The values of total phenolic contents, flavonoids, anthocyanins, procyanidins and an ascorbic acid in grape skin extracts were determined. The antioxidant capacities of skin extracts were evaluated using four different methods. The total phenolic content of skin extracts was 2–3 times lower than those of seed extracts. The significant difference between total parameter values of individual grape varieties were also found. According to the total phenolic content and antioxidant capacity of skin extracts, the different grape varieties were arranged in the following order: Marselan ≥ Pinot Noir ˃ Cabernet Sauvignon ˃ Tamyanka. The individual compounds in the grape skin extracts were determined using RP-HPLC and compared with those of the seed extracts. The determined composition of skin extracts was significantly different from the seed extracts’ composition. Quantitative evaluation of the procyanidins and catechins in the skins was carried out. A correlation between phenolic contents, individual compounds and antioxidant capacity of different extracts was found. The studied grape extracts have a potential to be applied as natural antioxidants in the pharmaceutical and food industries.
UPLC-QE-Orbitrap-Based Cell Metabolomics and Network Pharmacology to Reveal the Mechanism of N-Benzylhexadecanamide Isolated from Maca (Lepidium meyenii Walp.) against Testicular Dysfunction
Authors: Zhang Kai-Yue , Li Chun-Nan , Zhang Nan-Xi , Gao Xiao-Chen , Shen Jia-Ming , Cheng Duan-Duan , Wang Yue-Long , Zhang Hui , Lv Jing-Wei , Sun Jia-Ming
Published: May 2023

Testicular dysfunction (TDF) is characterized by testosterone deficiency and is caused by oxidative stress injury in Leydig cells. A natural fatty amide named N-benzylhexadecanamide (NBH), derived from cruciferous maca, has been shown to promote testosterone production. Our study aims to reveal the anti-TDF effect of NBH and explore its potential mechanism in vitro. This study examined the effects of H2O2 on cell viability and testosterone levels in mouse Leydig cells (TM3) under oxidative stress. In addition, cell metabolomics analysis based on UPLC-Q-Exactive-MS/MS showed that NBH was mainly involved in arginine biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, the TCA cycle and other metabolic pathways by affecting 23 differential metabolites, including arginine and phenylalanine. Furthermore, we also performed network pharmacological analysis to observe the key protein targets in NBH treatment. The results showed that its role was to up-regulate ALOX5, down-regulate CYP1A2, and play a role in promoting testicular activity by participating in the steroid hormone biosynthesis pathway. In summary, our study not only provides new insights into the biochemical mechanisms of natural compounds in the treatment of TDF, but also provides a research strategy that integrates cell metabolomics and network pharmacology in order to promote the screening of new drugs for the treatment of TDF.
Novel Adsorbent Material from Plinia cauliflora for Removal of Cationic Dye from Aqueous Solution
Authors: Janner Natalia Nara , Tholozan Luana Vaz , Maron Guilherme Kurz , Carreno Neftali Lenin Villarreal , Valério Filho Alaor , da Rosa Gabriela Silveira
Published: May 2023

The food industry is responsible for the generation of large amounts of organic residues, which can lead to negative environmental and economic impacts when incorrectly disposed of. The jaboticaba peel is an example of organic waste, widely used in industry due to its organoleptic characteristcs. In this study, residues collected during the extraction of bioactive compounds from jaboticaba bark (JB) were chemically activated with H3PO4 and NaOH and used to develop a low-cost adsorbent material for the removal of the cationic dye methylene blue (MB). For all adsorbents, the batch tests were carried out with the adsorbent dosage of 0.5 g L−1 and neutral pH, previously determined by 22 factorial design. In the kinetics tests, JB and JB-NaOH presented a fast adsorption rate, reaching equilibrium in 30 min. For JB-H3PO4, the equilibrium was reached in 60 min. JB equilibrium data were best represented by the Langmuir model and JB-NaOH and JB-H3PO4 data by the Freundlich model. The maximum adsorption capacities from JB, JB-NaOH, and JB-H3PO4 were 305.81 mg g−1, 241.10 mg g−1, and 122.72 mg g−1, respectively. The results indicate that chemical activations promoted an increase in the volume of large pores but interacted with functional groups responsible for MB adsorption. Therefore, JB has the highest adsorption capacity, thus presenting as a low-cost and sustainable alternative to add value to the product, and it also contributes to water decontamination studies, resulting in a zero-waste approach.
Synthesis of Aminoalkyl Sclareolide Derivatives and Antifungal Activity Studies
Authors: Li Ziyi , Gao Hua , Mei Haibo , Wu Guangwei , Soloshonok Vadim A. , Han Jianlin
Published: May 2023

Sclareolide was developed as an efficient C-nucleophilic reagent for an asymmetric Mannich addition reaction with a series of N-tert-butylsulfinyl aldimines. The Mannich reaction was carried out under mild conditions, affording the corresponding aminoalkyl sclareolide derivatives with up to 98% yield and 98:2:0:0 diastereoselectivity. Furthermore, the reaction could be performed on a gram scale without any reduction in yield and diastereoselectivity. Additionally, deprotection of the obtained Mannich addition products to give the target sclareolide derivatives bearing a free N-H group was demonstrated. In addition, target compounds 4–6 were subjected to an antifungal assay in vitro, which showed considerable antifungal activity against forest pathogenic fungi.
Phonon-Assisted Tunneling through Quantum Dot Systems Connected to Majorana Bound States
Authors: Máthé Levente , Kovács-Krausz Zoltán , Botiz Ioan , Grosu Ioan , El Anouz Khadija , El Allati Abderrahim , Zârbo Liviu P.
Published: May 2023

We theoretically analyze phonon-assisted tunneling transport in a quantum dot side connected to a Majorana bound state in a topological superconducting nanowire. We investigate the behavior of the current through the dot, for a range of experimentally relevant parameters, in the presence of one long-wave optical phonon mode. We consider the current-gate voltage, the current-bias voltage and the current-dot–Majorana coupling characteristics under the influence of the electron–phonon coupling. In the absence of electron–phonon interaction, the Majorana bound states suppress the current when the gate voltage matches the Fermi level, but the increase in the bias voltage counteracts this effect. In the presence of electron–phonon coupling, the current behaves similarly as a function of the renormalized gate voltage. As an added feature at large bias voltages, it presents a dip or a plateau, depending on the size of the dot–Majorana coupling. Lastly, we show that the currents are most sensitive to, and depend non-trivially on the parameters of the Majorana circuit element, in the regime of low temperatures combined with low voltages. Our results provide insights into the complex physics of quantum dot devices used to probe Majorana bound states.
Effect of Biosynthesized Silver Nanoparticles on the Growth of the Green Microalga Haematococcus pluvialis and Astaxanthin Synthesis
Authors: Venckus Petras , Endriukaitytė Ieva , Čekuolytė Kotryna , Gudiukaitė Renata , Pakalniškis Andrius , Lastauskienė Eglė
Published: May 2023

Silver nanoparticles (AgNPs) are widely known for their antimicrobial activity in various systems from microorganisms to cell cultures. However, the data on their effects on microalgae are very limited. Unicellular green algae Haematococcus pluvialis is known for its ability to accumulate large amounts of astaxanthin under stress conditions. Therefore, it can be used as a suitable model system to test the influence of AgNPs on stress induction in unicellular algae, with visible phenotypic effects, such as astaxanthin synthesis and cell morphology. This study tested different AgNP concentrations (0–8 mg/L) effects on different growth stages (red and green) of H. pluvialis culture. Effects on cell morphology, culture productivity, and astaxanthin synthesis were evaluated. Data showed that the addition of high concentrations of AgNPs to the growing culture had a significant negative impact on culture productivity. Green-stage (HpG) cultures productivity was reduced by up to 85% by increasing AgNPs concentration to 8 mg/L while the impact on red-stage (HpR) culture was lower. Astaxanthin concentration measurements showed that AgNPs do not have any effect on astaxanthin concentration in HpG culture and caused decreased astaxanthin production rate in HpR culture. HpG culture astaxanthin concentration stayed constant at ~0.43% dry weight, while HpR culture astaxanthin concentration was significantly reduced from 1.89% to 0.60% dry weight by increasing AgNP concentration. AgNPs in the media lead to significant changes in cell morphology in both HpG and HpR cultures. Cell deformations and disrupted cytokinesis, as well as AgNPs and induced sexual reproduction, were observed.
All-Atom Molecular Dynamics Simulations of the Temperature Response of Poly(glycidyl ether)s with Oligooxyethylene Side Chains Terminated with Alkyl Groups
Authors: Terada Erika , Isono Takuya , Satoh Toshifumi , Yamamoto Takuya , Kakuchi Toyoji , Sato Shinichiro
Published: May 2023

Recently, experimental investigations of a class of temperature-responsive polymers tethered to oligooxyethylene side chains terminated with alkyl groups have been conducted. In this study, aqueous solutions of poly(glycidyl ether)s (PGE) with varying numbers of oxyethylene units, poly(methyl(oligooxyethylene)n glycidyl ether) (poly(Me(EO)nGE)), and poly(ethyl(oligooxyethylene)n glycidyl ether) (poly(Et(EO)nGE) (n = 0, 1, and 2) were investigated by all-atom molecular dynamics simulations, focusing on the thermal responses of their chain extensions, the recombination of intrapolymer and polymer–water hydrogen bonds, and water-solvation shells around the alkyl groups. No clear relationship was established between the phase-transition temperature and the polymer-chain extensions unlike the case for the coil–globule transition of poly(N-isopropylacrylamide). However, the temperature response of the first water-solvation shell around the alkyl group exhibited a notable correlation with the phase-transition temperature. In addition, the temperature at which the hydrophobic hydration shell strength around the terminal alkyl group equals the bulk water density (TCRP) was slightly lower than the cloud point temperature (TCLP) for the methyl-terminated poly(Me(EO)nGE) and slightly higher for the ethyl-terminated poly(Et(EO)nGE). It was concluded that the polymer-chain fluctuation affects the relationship between TCRP and TCLP.
Depression Severity Is Different in Dysosmic Patients Who Have Experienced Traumatic Brain Injury Compared with Those Who Have Not
Authors: Sabiniewicz Agnieszka , Lindner Kyri-Kristin , Haehner Antje , Hummel Thomas
Published: May 2023

Traumatic brain injury (TBI) in humans can result in olfactory, cognitive, and affective changes. Surprisingly, research on the consequences of TBI often did not control for olfactory function in the investigated groups. Consequently, the affective or cognitive differences might be misleading as related rather to different olfactory performance than to a TBI experience. Hence, our study aimed to investigate whether TBI occurrence would lead to altered affective and cognitive functioning in two groups of dysosmic patients, one with TBI experience and one without. In total, 51 patients with TBI experience and 50 controls with varied causes of olfactory loss were thoroughly examined in terms of olfactory, cognitive, and affective performance. Student t-tests demonstrated that the only significant difference between the groups appeared in the depression severity, with TBI patients being more depressed (t = 2.3, p = 0.011, Cohen’s d = −0.47). Regression analyses further showed that TBI experience was significantly associated with depression severity (R2 = 0.05, F [1, 96] = 5.5, p = 0.021, beta = 1.4). In conclusion, the present study showed that TBI experience is linked to depression, which is more pronounced compared to individuals with olfactory loss without TBI.
Gut Microbial Metabolite Butyrate and Its Therapeutic Role in Inflammatory Bowel Disease: A Literature Review
Authors: Recharla Neeraja , Geesala Ramasatyaveni , Shi Xuan-Zheng
Published: May 2023

Background and objective: Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic inflammatory disorder characterized by aberrant immune responses and compromised barrier function in the gastrointestinal tract. IBD is associated with altered gut microbiota and their metabolites in the colon. Butyrate, a gut microbial metabolite, plays a crucial role in regulating immune function, epithelial barrier function, and intestinal homeostasis. In this review, we aim to present an overview of butyrate synthesis and metabolism and the mechanism of action of butyrate in maintaining intestinal homeostasis and to discuss the therapeutic implications of butyrate in IBD. Methods: We searched the literature up to March 2023 through PubMed, Web of Science, and other sources using search terms such as butyrate, inflammation, IBD, Crohn’s disease, and ulcerative colitis. Clinical studies in patients and preclinical studies in rodent models of IBD were included in the summary of the therapeutic implications of butyrate. Results: Research in the last two decades has shown the beneficial effects of butyrate on gut immune function and epithelial barrier function. Most of the preclinical and clinical studies have shown the positive effect of butyrate oral supplements in reducing inflammation and maintaining remission in colitis animal models and IBD patients. However, butyrate enema showed mixed effects. Butyrogenic diets, including germinated barley foodstuff and oat bran, are found to increase fecal butyrate concentrations and reduce the disease activity index in both animal models and IBD patients. Conclusions: The current literature suggests that butyrate is a potential add-on therapy to reduce inflammation and maintain IBD remission. Further clinical studies are needed to determine if butyrate administration alone is an effective therapeutic treatment for IBD.
Protein and Immune Component Content of Donor Human Milk in Japan: Variation with Gestational and Postpartum Age
Authors: Tanaka Miori , Date Midori , Miura Kumiko , Ito Mizuho , Mizuno Noriko , Mizuno Katsumi
Published: May 2023

Donor human milk (DHM) is the second-best nutrition for preterm infants when their own mother’s milk is unavailable. The nutrient content of human milk is influenced by various factors, including gestational and postpartum age, but there are no data regarding DHM composition in Japan. The aim of this study was to determine the protein and immune component content of DHM in Japan and to elucidate the effects of gestational and postpartum age on nutrient composition. From September 2021 to May 2022, 134 DHM samples were collected from 92 mothers of preterm and term infants. Protein concentrations in preterm DHM (n = 41) and term DHM (n = 93) were analyzed using a Miris Human Milk Analyzer. The concentrations of secretory immunoglobulin A (sIgA) and lactoferrin, major immune components, were measured using enzyme-linked immunosorbent assays. Preterm DHM exhibited higher protein content than term DHM (1.2 g/dL and 1.0 g/dL, respectively, p < 0.001), whereas sIgA content was higher in term DHM than in preterm DHM (110 μg/mL and 68.4 μg/mL, respectively, p < 0.001). Gestational age was negatively correlated with protein levels and positively correlated with sIgA and lactoferrin levels. Furthermore, a negative correlation was found between postpartum week and protein, sIgA, and lactoferrin concentrations. Our data suggest that gestational and postpartum age affects protein, sIgA, and lactoferrin concentrations in DHM. These results indicate the importance of nutritional analysis for the appropriate use of DHM in preterm infants.
Assessment of Nutritional Status and Its Influence on Ovarian Reserve: A Systematic Review
Authors: Prieto-Huecas Laura , Piera-Jordán Clara Ángela , Serrano De La Cruz-Delgado Verónica , Zaragoza-Martí Ana , García-Velert María Belén , Tordera-Terrades Cristina , Sánchez-Sansegundo Miriam , Martín-Manchado Laura
Published: May 2023

Background: Nowadays, there is a growing interest in the relationship among lifestyle, reproductive health, and fertility. Recent investigations highlight the influence of environmental and lifestyle factors such as stress, diet, and nutritional status on reproductive health. The aim of this review was to determine the influence of nutritional status on ovarian reserve in order to improve the reproductive health of women of childbearing age. Methods: A systematic literature review was carried out following the PRISMA method. The quality of the studies was assessed using the Cochrane Collaboration Risk of Bias tool. Data were extracted, and the results were summarized into two blocks: according to the technique used to assess ovarian reserve and nutritional status; according to the results found in the relationship between ovarian reserve and nutritional status. Results: A total of 22 articles involving 5929 women were included. In 12 of the included articles (54.5%), a relationship between nutritional status and ovarian reserve was demonstrated. In seven publications (31.8%), the increased body mass index (BMI) led to a decrease in ovarian reserve, two of them (0.9%) in patients with polycystic ovary syndrome, showing a decrease only if BMI > 25. In two articles (0.9%), there was a negative relationship between ovarian reserve and waist-to-hip ratio, and in one (0.45%), a positive relationship was shown between ovarian reserve and testosterone levels, the latter being related to body mass index. In five articles (22.7%), body mass index was used as a confounder and was negatively related to ovarian reserve, and in another four (18%), no correlation was found. Conclusions: Ovarian reserve appears to be influenced by nutritional status. A high body mass index has a negative impact on the ovary, decreasing antral follicle count and anti-Müllerian hormone. Oocyte quality is compromised, increasing the rate of reproductive problems and the demand for assisted reproductive techniques. Further studies are needed to understand which dietary factors have the greatest effect on ovarian reserve in order to promote reproductive health.
Advances in Nutrition: Opportunities and Challenges in 2022
Authors: Pérez-Cano Francisco J.
Published: May 2023

Many aspects of how food and diet can improve individual health, performance, and wellbeing remain to be discovered [...]
Antioxidant Nutraceutical Strategies in the Prevention of Oxidative Stress Related Eye Diseases
Authors: Rodella Umberto , Honisch Claudia , Gatto Claudio , Ruzza Paolo , D’Amato Tóthová Jana
Published: May 2023

This review aims to discuss the delicate balance between the physiological production of reactive oxygen species and the role of antioxidant nutraceutical molecules in managing radicals in the complex anatomical structure of the eye. Many molecules and enzymes with reducing and antioxidant potential are present in different parts of the eye. Some of these, such as glutathione, N-acetylcysteine, α-lipoic acid, coenzyme Q10, and enzymatic antioxidants, are endogenously produced by the body. Others, such as plant-derived polyphenols and carotenoids, vitamins B2, C, and E, zinc and selenium, and omega-3 polyunsaturated fatty acids, must be obtained through the diet and are considered essential nutrients. When the equilibrium between the production of reactive oxygen species and their scavenging is disrupted, radical generation overwhelms the endogenous antioxidant arsenal, leading to oxidative stress-related eye disorders and aging. Therefore, the roles of antioxidants contained in dietary supplements in preventing oxidative stress-based ocular dysfunctions are also discussed. However, the results of studies investigating the efficacy of antioxidant supplementation have been mixed or inconclusive, indicating a need for future research to highlight the potential of antioxidant molecules and to develop new preventive nutritional strategies.
Generic Workflow to Predict Medicine Concentrations in Human Milk Using Physiologically-Based Pharmacokinetic (PBPK) Modelling—A Contribution from the ConcePTION Project
Authors: Nauwelaerts Nina , Macente Julia , Deferm Neel , Bonan Rodolfo Hernandes , Huang Miao-Chan , Van Neste Martje , Bibi David , Badee Justine , Martins Frederico S. , Smits Anne , Allegaert Karel , Bouillon Thomas , Annaert Pieter
Published: May 2023

Women commonly take medication during lactation. Currently, there is little information about the exposure-related safety of maternal medicines for breastfed infants. The aim was to explore the performance of a generic physiologically-based pharmacokinetic (PBPK) model to predict concentrations in human milk for ten physiochemically diverse medicines. First, PBPK models were developed for “non-lactating” adult individuals in PK-Sim/MoBi v9.1 (Open Systems Pharmacology). The PBPK models predicted the area-under-the-curve (AUC) and maximum concentrations (Cmax) in plasma within a two-fold error. Next, the PBPK models were extended to include lactation physiology. Plasma and human milk concentrations were simulated for a three-months postpartum population, and the corresponding AUC-based milk-to-plasma (M/P) ratios and relative infant doses were calculated. The lactation PBPK models resulted in reasonable predictions for eight medicines, while an overprediction of human milk concentrations and M/P ratios (>2-fold) was observed for two medicines. From a safety perspective, none of the models resulted in underpredictions of observed human milk concentrations. The present effort resulted in a generic workflow to predict medicine concentrations in human milk. This generic PBPK model represents an important step towards an evidence-based safety assessment of maternal medication during lactation, applicable in an early drug development stage.
Investigation of N-Acetyltransferase 2-Mediated Drug Interactions of Amifampridine: In Vitro and In Vivo Evidence of Drug Interactions with Acetaminophen
Authors: Park Yeo-Dim , Chae Yoon-Jee , Maeng Han-Joo
Published: May 2023

Amifampridine is a drug used for the treatment of Lambert–Eaton myasthenic syndrome (LEMS) and was approved by the Food and Drug Administration (FDA) of the United States (US) in 2018. It is mainly metabolized by N-acetyltransferase 2 (NAT2); however, investigations of NAT2-mediated drug interactions with amifampridine have rarely been reported. In this study, we investigated the effects of acetaminophen, a NAT2 inhibitor, on the pharmacokinetics of amifampridine using in vitro and in vivo systems. Acetaminophen strongly inhibits the formation of 3-N-acetylamifmapridine from amifampridine in the rat liver S9 fraction in a mixed inhibitory manner. When rats were pretreated with acetaminophen (100 mg/kg), the systemic exposure to amifampridine significantly increased and the ratio of the area under the plasma concentration–time curve for 3-N-acetylamifampridine to amifampridine (AUCm/AUCp) decreased, likely due to the inhibition of NAT2 by acetaminophen. The urinary excretion and the amount of amifampridine distributed to the tissues also increased after acetaminophen administration, whereas the renal clearance and tissue partition coefficient (Kp) values in most tissues remained unchanged. Collectively, co-administration of acetaminophen with amifampridine may lead to relevant drug interactions; thus, care should be taken during co-administration.
Nano Differential Scanning Fluorimetry as a Rapid Stability Assessment Tool in the Nanoformulation of Proteins
Authors: Lisina Sofia , Inam Wali , Huhtala Mikko , Howaili Fadak , Zhang Hongbo , Rosenholm Jessica M.
Published: May 2023

The development and production of innovative protein-based therapeutics is a complex and challenging avenue. External conditions such as buffers, solvents, pH, salts, polymers, surfactants, and nanoparticles may affect the stability and integrity of proteins during formulation. In this study, poly (ethylene imine) (PEI) functionalized mesoporous silica nanoparticles (MSNs) were used as a carrier for the model protein bovine serum albumin (BSA). To protect the protein inside MSNs after loading, polymeric encapsulation with poly (sodium 4-styrenesulfonate) (NaPSS) was used to seal the pores. Nano differential scanning fluorimetry (NanoDSF) was used to assess protein thermal stability during the formulation process. The MSN-PEI carrier matrix or conditions used did not destabilize the protein during loading, but the coating polymer NaPSS was incompatible with the NanoDSF technique due to autofluorescence. Thus, another pH-responsive polymer, spermine-modified acetylated dextran (SpAcDEX), was applied as a second coating after NaPSS. It possessed low autofluorescence and was successfully evaluated with the NanoDSF method. Circular dichroism (CD) spectroscopy was used to determine protein integrity in the case of interfering polymers such as NaPSS. Despite this limitation, NanoDSF was found to be a feasible and rapid tool to monitor protein stability during all steps needed to create a viable nanocarrier system for protein delivery.
Hybrid Membranes of the Ureasil-Polyether Containing Glucose for Future Application in Bone Regeneration
Authors: da Silva Camila Garcia , Monteiro João Rodrigues , Oshiro-Júnior João Augusto , Chiavacci Leila Aparecida
Published: May 2023

The application of mesenchymal stem cells (MSC) in bone tissue regeneration can have unpredictable results due to the low survival of cells in the process since the lack of oxygen and nutrients promotes metabolic stress. Therefore, in this work, polymeric membranes formed by organic–inorganic hybrid materials called ureasil-polyether for modified glucose release were developed in order to overcome the problems posed by a of lack of this nutrient. Thus, membranes formed by polymeric blend of polypropylene oxide (PPO4000) and polyethylene oxide (PEO500) with 6% glucose incorporation were developed. Physical–chemical characterization techniques were performed, as well as tests that evaluated thermal properties, bioactivity, swelling, and release in SBF solution. The results of the swelling test showed an increase in membrane mass correlated with an increase in the concentration of ureasil-PEO500 in the polymeric blends. The membranes showed adequate resistance when subjected to the application of a high compression force (15 N). X-ray diffraction (XRD) evidenced peaks corresponding to orthorhombic crystalline organization, but the absence of glucose-related peaks showed characteristics of the amorphous regions of hybrid materials, likely due to solubilization. Thermogravimetry (TG) and differential scanning calorimetry (DSC) analyses showed that the thermal events attributed to glucose and hybrid materials were similar to that seen in the literature, however when glucose was incorporated into the PEO500, an increase in rigidity occurs. In PPO400, and in the blends of both materials, there was a slight decrease in Tg values. The smaller contact angle for the ureasil-PEO500 membrane revealed the more hydrophilic character of the material compared to other membranes. The membranes showed bioactivity and hemocompatibility in vitro. The in vitro release test revealed that it is possible to control the release rate of glucose and the kinetic analysis revealed a release mechanism characteristic of anomalous transport kinetics. Thus, we can conclude that ureasil-polyether membranes have great potential to be used as a glucose release system, and their future application has the potential to optimize the bone regeneration process.
A Single Infusion of Polyethylene Glycol-Coated Superparamagnetic Magnetite Nanoparticles Alters Differently the Expressions of Genes Involved in Iron Metabolism in the Liver and Heart of Rats
Authors: Kluknavsky Michal , Micurova Andrea , Skratek Martin , Balis Peter , Okuliarova Monika , Manka Jan , Bernatova Iveta
Published: May 2023

This study investigated genotype- and tissue-related differences in the biodistribution of superparamagnetic magnetite (Fe3O4) nanoparticles (IONs) into the heart and liver of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats after a single i.v. infusion of polyethylene glycol-coated IONs (~30 nm, 1mg Fe/kg) 100 min post-infusion. The effects of IONs on the expression of selected genes involved in the regulation of iron metabolism, including Nos, Sod and Gpx4, and their possible regulation by nuclear factor (erythroid-derived 2)-like 2 (NRF2, encoded by Nfe2l2) and iron-regulatory protein (encoded by Irp1) were investigated. In addition, superoxide and nitric oxide (NO) production were determined. Results showed reduced ION incorporations into tissues of SHR compared to WKY and in the hearts compared to the livers. IONs reduced plasma corticosterone levels and NO production in the livers of SHR. Elevated superoxide production was found only in ION-treated WKY. Results also showed differences in the regulation of iron metabolism on the gene level in the heart and liver. In the hearts, gene expressions of Nos2, Nos3, Sod1, Sod2, Fpn, Tf, Dmt1 and Fth1 correlated with Irp1 but not with Nfe2l2, suggesting that their expression is regulated by mainly iron content. In the livers, expressions of Nos2, Nos3, Sod2, Gpx4, and Dmt1 correlated with Nfe2l2 but not with Irp1, suggesting a predominant effect of oxidative stress and/or NO.
Thermoreversible Gels Based on Chitosan Copolymers as “Intelligent” Drug Delivery System with Prolonged Action for Intramuscular Injection
Authors: Zlotnikov Igor D. , Malashkeevich Stanislav M. , Belogurova Natalia G. , Kudryashova Elena V.
Published: May 2023

Thermosensitive gels based on copolymers (PEG–chitosan, chitosan–polyethylenimine, chitosan–arginine and glycol–chitosan–spermine) are presented as promising polycations for the formation of DNA polyplexes and the potential for the development of drugs with prolonged release (up to 30 days). Being in liquid form at room temperature, such compounds can be injected into muscle tissue with rapid gel formation at human body temperature. An intramuscular depot is formed with a therapeutic agent that provides a gradual release of the drug, such as an antibacterial or cytostatic. The physico-chemical parameters of the formation of polyplexes between polycationic polymers of various compositions and molecular architecture and DNA were studied via FTIR, UV-vis and fluorescence spectroscopy using the dyes rhodamine 6G (R6G) and acridine orange (AO). The competitive displacement of AO from AO-DNA complexes showed that, with a ratio of N/P = 1, most of the DNA is bound to a polycation. During the formation of polyplexes, the DNA charge is neutralized by a polycation, which is reflected in electrophoretic immobility. The cationic polymers described in this work at a concentration of 1–4% are capable of forming gels, and the thermoreversible property is most characteristic of pegylated chitosan. BSA, as a model anionic molecule, is released by half in 5 days from the Chit5-PEG5 gel; full release is achieved in 18–20 days. At the same time, in 5 days, the gel is destroyed up to 30%, and in 20 days, by 90% (release of chitosan particles). For the first time, flow cytometry was used to study DNA polyplexes, which showed the existence of fluorescent particles in a much larger number in combination with free DNA. Thus, functional stimulus-sensitive polymers are potentially applicable for the creation of prolonged therapeutic formulations for gene delivery systems, which were obtained. The revealed regularities appear to be a platform for the design of polyplexes with controllable stability, in particular, fulfilling the requirements imposed for gene delivery vehicles.
The Effect of Intracellular Tacrolimus Exposure on Calcineurin Inhibition in Immediate- and Extended-Release Tacrolimus Formulations
Authors: Fontova Pere , van Merendonk Lisanne N. , Vidal-Alabró Anna , Rigo-Bonnin Raül , Cerezo Gema , van Oevelen Stefaan , Bestard Oriol , Melilli Edoardo , Montero Nuria , Coloma Ana , Manonelles Anna , Torras Joan , Cruzado Josep M. , Grinyó Josep M. , Colom Helena , Lloberas Nuria
Published: May 2023

Despite intensive monitoring of whole blood tacrolimus concentrations, acute rejection after kidney transplantation occurs during tacrolimus therapy. Intracellular tacrolimus concentrations could better reflect exposure at the site of action and its pharmacodynamics (PD). Intracellular pharmacokinetic (PK) profile following different tacrolimus formulations (immediate-release (TAC-IR) and extended-release (TAC-LCP)) remains unclear. Therefore, the aim was to study intracellular tacrolimus PK of TAC-IR and TAC-LCP and its correlation with whole blood (WhB) PK and PD. A post-hoc analysis of a prospective, open-label, crossover investigator-driven clinical trial (NCT02961608) was performed. Intracellular and WhB tacrolimus 24 h time-concentration curves were measured in 23 stable kidney transplant recipients. PD analysis was evaluated measuring calcineurin activity (CNA) and simultaneous intracellular PK/PD modelling analysis was conducted. Higher dose-adjusted pre-dose intracellular concentrations (C0 and C24) and total exposure (AUC0–24) values were found for TAC-LCP than TAC-IR. Lower intracellular peak concentration (Cmax) was found after TAC-LCP. Correlations between C0, C24 and AUC0–24 were observed within both formulations. Intracellular kinetics seems to be limited by WhB disposition, in turn, limited by tacrolimus release/absorption processes from both formulations. The faster intracellular elimination after TAC-IR was translated into a more rapid recovery of CNA. An Emax model relating % inhibition and intracellular concentrations, including both formulations, showed an IC50, a concentration to achieve 50% CNA inhibition, of 43.9 pg/million cells.
Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles
Authors: Leng Qixin , Imtiyaz Zuha , Woodle Martin C. , Mixson A. James
Published: May 2023

With less than one percent of systemically injected nanoparticles accumulating in tumors, several novel approaches have been spurred to direct and release the therapy in or near tumors. One such approach depends on the acidic pH of the extracellular matrix and endosomes of the tumor. With an average pH of 6.8, the extracellular tumor matrix provides a gradient for pH-responsive particles to accumulate, enabling greater specificity. Upon uptake by tumor cells, nanoparticles are further exposed to lower pHs, reaching a pH of 5 in late endosomes. Based on these two acidic environments in the tumor, various pH-dependent targeting strategies have been employed to release chemotherapy or the combination of chemotherapy and nucleic acids from macromolecules such as the keratin protein or polymeric nanoparticles. We will review these release strategies, including pH-sensitive linkages between the carrier and hydrophobic chemotherapy agent, the protonation and disruption of polymeric nanoparticles, an amalgam of these first two approaches, and the release of polymers shielding drug-loaded nanoparticles. While several pH-sensitive strategies have demonstrated marked antitumor efficacy in preclinical trials, many studies are early in their development with several obstacles that may limit their clinical use.
Design, Preparation, and Physicochemical Characterisation of Alginate-Based Honey-Loaded Topical Formulations
Authors: Hossain Md Lokman , Lim Lee Yong , Hammer Katherine , Hettiarachchi Dhanushka , Locher Cornelia
Published: May 2023

Honey has widespread use as a nutritional supplement and flavouring agent. Its diverse bioactivities, including antioxidant, antimicrobial, antidiabetic, anti-inflammatory, and anticancer properties, have also made it an aspirant natural product for therapeutic applications. Honey is highly viscous and very sticky, and its acceptance as a medicinal product will require formulation into products that are not only effective but also convenient for consumers to use. This study presents the design, preparation, and physicochemical characterisation of three types of alginate-based topical formulations incorporating a honey. The honeys applied were from Western Australia, comprising a Jarrah honey, two types of Manuka honeys, and a Coastal Peppermint honey. A New Zealand Manuka honey served as comparator honey. The three formulations were a pre-gel solution consisting of 2–3% (w/v) sodium alginate solution with 70% (w/v) honey, as well as a wet sheet and a dry sheet. The latter two formulations were obtained by further processing the respective pre-gel solutions. Physical properties of the different honey-loaded pre-gel solutions (i.e., pH, colour profile, moisture content, spreadability, and viscosity), wet sheets (i.e., dimension, morphology, and tensile strength) and dry sheets (i.e., dimension, morphology, tensile strength, and swelling index) were determined. High-Performance Thin-Layer Chromatography was applied to analyse selected non-sugar honey constituents to assess the impacts of formulation on the honey chemical composition. This study demonstrates that, irrespective of the honey type utilised, the developed manufacturing techniques yielded topical formulations with high honey content while preserving the integrity of the honey constituents. A storage stability study was conducted on formulations containing the WA Jarrah or Manuka 2 honey. The samples, appropriately packaged and stored over 6 months at 5, 30, and 40 °C, were shown to retain all physical characteristics with no loss of integrity of the monitored honey constituents.
Ultracompact Integrated Mode-Order Converter and Reciprocal Optical Diode with Etched Subwavelength Structures
Authors: Zhu Danfeng , Deng Dingnan , Chen Junbo , Qiu Shaobin , Li Jing , Ye Han
Published: May 2023

Three ultracompact integrated photonic devices are proposed, assisted by etched structures. A mode-order converter (MOC) is achieved with a footprint of 0.85 × 1.4 μm2, which exhibits high performances with insertion loss (IL) below 0.34 dB and mode purity (MP) above 90% within 100 nm waveband. Moreover, a mode blocking filter (MBF) is proposed based on a subwavelength grating with a footprint of 0.8 × 4.12 μm2, which allows the propagation of TM0 mode but blocks the TM1 mode with a remarkably high extinction ratio of 31.6 dB at the wavelength of 1550 nm. Finally, a compact reciprocal optical diode (ROD) is presented by cascading the abovementioned MOC and MBF with a footprint of 0.85 × 5.9 μm2. This ROD enables one-way transmissions for both TM0 mode and TM1 mode with contrast ratios of 19.74 dB and 32.04 dB, respectively. The design methodology paves a new way for mode manipulation in integrated multimode photonic circuits.
An Opto-Electro-Thermal Model for Black-Silicon Assisted Photovoltaic Cells in Thermophotovoltaic Applications
Authors: Chai Jasman Y.-H. , Wong Basil T. , Sunarso Jaka
Published: May 2023

Black silicon (b-Si)-assisted photovoltaic cells have textured b-Si surfaces, which have excellent light-trapping properties. There has been a limited amount of work performed on the theoretical modelling of b-Si photovoltaic cells, and hence, in this work, a coupled optical-electrical-thermal model has been proposed for the simulation of b-Si photovoltaic cells. In particular, the thermal aspects in b-Si photovoltaic cells have not been discussed in the literature. In the proposed model, the finite-difference time-domain (FDTD) method was used to study the optical response of the b-Si photovoltaic cell. Semiconductor equations were used for the electrical modelling of the cell. For the thermal model, the Energy Balance Transport Model was used. The developed model was used to simulate b-Si photovoltaic cells under thermophotovoltaic sources. The impacts of heat generation on the electrical performance of thermophotovoltaic cells are discussed. Simulation results from this study showed that black silicon layer improved efficiency and power output in thermophotovoltaic cells compared to thermophotovoltaic cells with no surface texture. In addition, heat generation due to Joule heating and electron thermalization in b-Si-assisted thermophotovoltaic cells reduced the open-circuit voltage and electrical performance.
Development of Taper-in-Taper-Based Optical Fiber Sensors for Chemical and Biological Sensing
Authors: Liu Fei , Zhang Wen , Lang Xianzheng , Liu Xuecheng , Singh Ragini , Li Guoru , Xie Yiyan , Zhang Bingyuan , Kumar Santosh
Published: May 2023

This paper presents the development of taper-in-taper fiber (TITF)–optical fiber-based sensors for chemical and biological detection. TITF structure is a fiber structure formed by fabricating a taper again on the taper region of the traditional taper fiber. The experimental results show that the TITF structure has a lower transmitted intensity than the common taper fiber structure. It is demonstrated that the structure of TITF is more conducive to evanescent waves, thereby making it more sensitive to changes in the refractive index (RI) of the external environment. To confirm this, measurements of ethanol solutions with different water contents are taken using the TITF structure to showcase the chemical sensing, thus verifying its sensitivity to RI changes in the external environment. The sensor can measure ethanol solutions from 0 to 100% with a sensitivity of 4.06 a.u./%. Thereafter, the TITF sensor is modified with ZnO-NPs to enhance its sensitivity for biological sensing (creatinine detection). The transmitted intensity of different concentrations of creatinine solution (0–2000 μM) is measured using the proposed sensor. The sensor showed good linearity and a high sensitivity of 0.11 a.u./μM for creatinine solution. Therefore, it is demonstrated that the TITF sensor with ZnO-NPs can be used for effective biological sensing.
EUV/VUV Spectroscopy for the Study of Carbon Impurity Transport in Hydrogen and Deuterium Plasmas in the Edge Stochastic Magnetic Field Layer of Large Helical Device
Authors: Oishi Tetsutarou , Morita Shigeru , Kobayashi Masahiro , Kawamura Gakushi , Kawamoto Yasuko , Kawate Tomoko , Masuzaki Suguru , Suzuki Chihiro , Goto Motoshi
Published: May 2023

The ergodic layer in the Large Helical Device (LHD) consists of stochastic magnetic fields exhibiting a three-dimensional structure that is intrinsically formed by helical coils. Spectroscopic diagnostics was employed in the extreme ultraviolet (EUV) and vacuum ultraviolet (VUV) wavelength ranges to investigate emission lines of carbon impurities in both hydrogen (H) and deuterium (D) plasmas, aiming to elucidate the impact of distinct bulk ions on impurity generation and transport in the edge plasmas of the LHD. The emission intensity of carbon CIII, CIV, CV, and CVI lines is significantly higher in the D plasma compared to the H plasma, indicating a greater sputtering rate of carbon materials in the D plasma, resulting in a higher quantity of carbon impurities originating from the divertor plates. A Doppler profile measurement of the second order of CIV line emission (1548.20 × 2 Å) was attempted using a 3 m normal-incidence VUV spectrometer in the edge plasma at a horizontally elongated plasma position. The flow velocity reaches its maximum value close to the outermost region of the ergodic layer, and the observed flow direction aligns with the friction force in the parallel momentum balance. The flow velocity increases with the electron density in H plasmas, suggesting that the friction force becomes more dominant in the force balance at higher density regimes. This leads to an increase in the impurity flow, which can contribute to the impurity screening. In contrast, the flow velocity in the D plasma is smaller than that in the H plasma. The difference in flow values between D and H plasmas, when the friction force term dominates in the momentum balance, could be attributed to the mass dependence of the thermal velocity of the bulk ions.