bluuebunny/crossref_metadata_2025 huggingface dataset:
Free-Living Amoebae in Soil Samples from Santiago Island, Cape Verde
Authors: Sousa-Ramos Djeniffer , Reyes-Batlle María , Bellini Natália K. , Rodríguez-Expósito Rubén L. , Piñero José E. , Lorenzo-Morales Jacob
Published: July 2021

Free-Living Amoebae (FLA) are widely distributed protozoa, which contain some groups considered as pathogenic microorganisms. These members are able to produce several opportunistic diseases including epithelial disorders, such as keratitis and fatal encephalitis. Even though they have been reported in numerous sources, such as soils, dust and water, there is no legislation related to the presence of these protozoa in soil-related environments worldwide. Therefore, there are no established prevention or disinfection protocols to advise the population regarding FLA infections or eliminate these microorganisms from human-related environments to date. Acanthamoeba spp. are the most common FLA isolated in soil samples, which is also the most common genera found in clinical cases. Thus, the aim of the present study was to evaluate the presence of potentially pathogenic FLA in human-related soil samples of Santiago Island, Cabo Verde. A total of 26 soil samples were seeded in non-nutrient agar plates (2%), incubated at 26 °C, and monitored daily to evaluate the presence of FLA. DNA was extracted from those plates on which there was suspected FLA growth, and PCR amplification of the 18S rRNA gene was carried out. A total of 17 from the 26 analysed samples were positive for FLA, where Acanthamoeba is the most abundant isolated genus (14/17; 82.4%), with the T4 genotype being the most common (13/14; 92.9%), followed by the T5 genotype, A. lenticulata (1/14; 7.1%). Moreover, Vermamoeba vermiformis, Stenamoeba dejonckheerei and Vannella pentlandi were isolated in three other samples. To the best of our knowledge, this is the first report of FLA presence in Cape Verde and the first report of V. vermiformis in beach sand worldwide.
Mineral Inactivation of Zinc in Polluted Soil—Sustainability of Zeolite, Bentonite and Blends
Authors: Diatta Jean , Andrzejewska Agnieszka , Grzebisz Witold , Drobek Leszek , Karolewski Zbigniew
Published: July 2021

The study outlines a novel and traceable procedure for inactivating zinc polluted soil (an Anthrosols) adjacent to a former zinc (Zn) ore mine “Orzel Biały” in Bytom (Poland), where the total content of Zn amounted to 3988.0 mg kg−1. This pollution level initiated an inactivation process involving two natural mineral sorbents, i.e., zeolite (Z) and bentonite (B), as well as their five blends (ZeoBen) expressed as ZB: (1) ZB15/85, (2) ZB30/70, (3) ZB50/50, (4) ZB70/30 and (5) ZB85/15. Next, phosphorus (P) as triple superphosphate (TSP, 46% P2O5) was added to individual ZB at rates: 0.25%, 0.5%, 1.0% and 2.0%. All sorbents were added to the Zn polluted soil at 0%, 0.25%, 0.5%, 1.0% and 2.0% (dry weight basis). Treatments (1.0 kg of Zn-polluted soil with ZB sorbents) were aged for 115 days. Data revealed that ZB85/15 with prevailing zeolite caused a Znact inactivation of 66–71%, while zeolite induced 54% and 47% for bentonite. Reactive zinc (Znreac) decreased much more (20%) when zeolite was incorporated at the rate 2.5 g·kg−1 soil, and bentonite was (10%) at the same rate. The application of the sorbent ZB50/50 enriched with triple superphosphate (TSP) raised the stabilization degree for both Zn fractions. The efficiency was significant at the TSP rate of 2.0% of the sorbent and at least the sorbent +TSP of 10 g·kg−1 soil. The cation exchange capacity (CEC) of about 2 cmol(+)·kg−1 controlled the activity −0.50 mmol·dm−3 of either γZnreac or γZnact, hence a very low zinc ionic activity. The use of mineral blends with higher sharing of zeolite is promising for remediating metal-polluted lands in the case of zinc.
The Balance between Hydrogen Bonds, Halogen Bonds, and Chalcogen Bonds in the Crystal Structures of a Series of 1,3,4-Chalcogenadiazoles
Authors: De Silva Viraj , Averkiev Boris B. , Sinha Abhijeet S. , Aakeröy Christer B.
Published: July 2021

In order to explore how specific atom-to-atom replacements change the electrostatic potentials on 1,3,4-chalcogenadiazole derivatives, and to deliberately alter the balance between intermolecular interactions, four target molecules were synthesized and characterized. DFT calculations indicated that the atom-to-atom substitution of Br with I, and S with Se enhanced the σ-hole potentials, thus increasing the structure directing ability of halogen bonds and chalcogen bonds as compared to intermolecular hydrogen bonding. The delicate balance between these intermolecular forces was further underlined by the formation of two polymorphs of 5-(4-iodophenyl)-1,3,4-thiadiazol-2-amine; Form I displayed all three interactions while Form II only showed hydrogen and chalcogen bonding. The results emphasize that the deliberate alterations of the electrostatic potential on polarizable atoms can cause specific and deliberate changes to the main synthons and subsequent assemblies in the structures of this family of compounds.
Ellagitannin Digestion in Moth Larvae and a New Dimeric Ellagitannin from the Leaves of Platycarya strobilacea
Authors: Takayoshi Juri , Huang Yong-Lin , Matsuo Yosuke , Saito Yoshinori , Li Dian-Peng , Tanaka Takashi
Published: July 2021

Ellagitannins (ETs) are plant polyphenols with various health benefits. Recent studies have indicated that the biological activities of ETs are attributable to their degradation products, including ellagic acid and its gut microflora metabolites, such as urolithins. Insect tea produced in the Guangxi region, China, is made from the frass of moth larvae that feed on the ET-rich leaves of Platycarya strobilacea. Chromatographic separation of the Guangxi insect tea showed that the major phenolic constituents are ellagic acid, brevifolin carboxylic acid, gallic acid, brevifolin, and polymeric polyphenols. Chemical investigation of the feed of the larvae, the fresh leaves of P. strobilacea, showed that the major polyphenols are ETs including pedunculagin, casuarictin, strictinin, and a new ET named platycaryanin E. The new ET was confirmed as a dimer of strictinin having a tergalloyl group. The insect tea and the leaves of P. strobilacea contained polymeric polyphenols, both of which were shown to be composed of ETs and proanthocyanidins by acid hydrolysis and thiol degradation. This study clarified that Guangxi insect tea contains ET metabolites produced in the digestive tract of moth larvae, and the metabolites probably have higher bioavailabilities than the original large-molecular ETs of the leaves of P. strobilacea.
Chemical Characteristics of Croatian Traditional Istarski pršut (PDO) Produced from Two Different Pig Genotypes
Authors: Krvavica Marina , Lasić Dario , Kljusurić Jasenka Gajdoš , Đugum Jelena , Janović Špiro , Milovac Srđan , Bošnir Jasna
Published: July 2021

Chemical characteristics of raw and processed Istarski pršut (PDO) produced from two different pig genotypes were studied with special emphasis on amino and fatty acid composition and factors of lipid stability. Raw hams of Large White (LW)xLandrace (L), and (LWxL)xDuroc (D) pig genotypes were used in the study (20 hams of each genotype). All left raw hams from each carcass were processed in accordance with the PDO specification of Istarski pršut, and other half (the right ones) of LWxL)xD genotype were used for analyses of raw hams (fresh muscles). Istarski pršut was evaluated on the basis of the chemical parameters of the raw and matured lean ham. The process of dry curing significantly influenced the chemical properties of Istarski pršut. Despite the higher content of intramuscular fat and polyunsaturated fatty acids, the fat of (LWxL)xD ham was much more resistant to hydrolysis and oxidation, suggesting that fatty acid profile and other factors, also play a significant role. Significant differences between pig genotypes in the amino acid and fatty acid profiles were found. The analyzed Istarski pršut may be distinguished by prints of multivariate chemometric statistical analysis, based on their amino acid and fatty acid compositions.
High Hole Concentration and Diffusion Suppression of Heavily Mg-Doped p-GaN for Application in Enhanced-Mode GaN HEMT
Authors: Dai Jin-Ji , Mai Thi Thu , Wu Ssu-Kuan , Peng Jing-Rong , Liu Cheng-Wei , Wen Hua-Chiang , Chou Wu-Ching , Ho Han-Chieh , Wang Wei-Fan
Published: July 2021

The effect of Mg doping on the electrical and optical properties of the p-GaN/AlGaN structures on a Si substrate grown by metal organic chemical vapor deposition was investigated. The Hall measurement showed that the activation efficiency of the sample with a 450 sccm Cp2Mg flow rate reached a maximum value of 2.22%. No reversion of the hole concentration was observed due to the existence of stress in the designed sample structures. This is attributed to the higher Mg-to-Ga incorporation rate resulting from the restriction of self-compensation under compressive strain. In addition, by using an AlN interlayer (IL) at the interface of p-GaN/AlGaN, the activation rate can be further improved after the doping concentration reaches saturation, and the diffusion of Mg atoms can also be effectively suppressed. A high hole concentration of about 1.3 × 1018 cm−3 can be achieved in the p-GaN/AlN-IL/AlGaN structure.
Ultrathin Silicon Nanowires for Optical and Electrical Nitrogen Dioxide Detection
Authors: Morganti Dario , Leonardi Antonio Alessio , Lo Faro Maria José , Leonardi Gianluca , Salvato Gabriele , Fazio Barbara , Musumeci Paolo , Livreri Patrizia , Conoci Sabrina , Neri Giovanni , Irrera Alessia
Published: July 2021

The ever-stronger attention paid to enhancing safety in the workplace has led to novel sensor development and improvement. Despite the technological progress, nanostructured sensors are not being commercially transferred due to expensive and non-microelectronic compatible materials and processing approaches. In this paper, the realization of a cost-effective sensor based on ultrathin silicon nanowires (Si NWs) for the detection of nitrogen dioxide (NO2) is reported. A modification of the metal-assisted chemical etching method allows light-emitting silicon nanowires to be obtained through a fast, low-cost, and industrially compatible approach. NO2 is a well-known dangerous gas that, even with a small concentration of 3 ppm, represents a serious hazard for human health. We exploit the particular optical and electrical properties of these Si NWs to reveal low NO2 concentrations through their photoluminescence (PL) and resistance variations reaching 2 ppm of NO2. Indeed, these Si NWs offer a fast response and reversibility with both electrical and optical transductions. Despite the macro contacts affecting the electrical transduction, the sensing performances are of high interest for further developments. These promising performances coupled with the scalable Si NW synthesis could unfold opportunities for smaller sized and better performing sensors reaching the market for environmental monitoring.
Emergence of Nontrivial Spin Textures in Frustrated Van Der Waals Ferromagnets
Authors: Ukpong Aniekan Magnus
Published: July 2021

In this work, first principles ground state calculations are combined with the dynamic evolution of a classical spin Hamiltonian to study the metamagnetic transitions associated with the field dependence of magnetic properties in frustrated van der Waals ferromagnets. Dynamically stabilized spin textures are obtained relative to the direction of spin quantization as stochastic solutions of the Landau–Lifshitz–Gilbert–Slonczewski equation under the flow of the spin current. By explicitly considering the spin signatures that arise from geometrical frustrations at interfaces, we may observe the emergence of a magnetic skyrmion spin texture and characterize the formation under competing internal fields. The analysis of coercivity and magnetic hysteresis reveals a dynamic switch from a soft to hard magnetic configuration when considering the spin Hall effect on the skyrmion. It is found that heavy metals in capped multilayer heterostructure stacks host field-tunable spiral skyrmions that could serve as unique channels for carrier transport. The results are discussed to show the possibility of using dynamically switchable magnetic bits to read and write data without the need for a spin transfer torque. These results offer insight to the spin transport signatures that dynamically arise from metamagnetic transitions in spintronic devices.
Current Developments in Native Nanometric Discoidal Membrane Bilayer Formed by Amphipathic Polymers
Authors: Esmaili Mansoore , Eldeeb Mohamed A. , Moosavi-Movahedi Ali Akbar
Published: July 2021

Unlike cytosolic proteins, membrane proteins (MPs) are embedded within the plasma membrane and the lipid bilayer of intracellular organelles. MPs serve in various cellular processes and account for over 65% of the current drug targets. The development of membrane mimetic systems such as bicelles, short synthetic polymers or amphipols, and membrane scaffold proteins (MSP)-based nanodiscs has facilitated the accommodation of synthetic lipids to stabilize MPs, yet the preparation of these membrane mimetics remains detergent-dependent. Bio-inspired synthetic polymers present an invaluable tool for excision and liberation of superstructures of MPs and their surrounding annular lipid bilayer in the nanometric discoidal assemblies. In this article, we discuss the significance of self-assembling process in design of biomimetic systems, review development of multiple series of amphipathic polymers and the significance of these polymeric “belts” in biomedical research in particular in unraveling the structures, dynamics and functions of several high-value membrane protein targets.
The Role of Diet in Bone and Mineral Metabolism and Secondary Hyperparathyroidism
Authors: Bargagli Matteo , Arena Maria , Naticchia Alessandro , Gambaro Giovanni , Mazzaferro Sandro , Fuster Daniel , Ferraro Pietro Manuel
Published: July 2021

Bone disorders are a common complication of chronic kidney disease (CKD), obesity and gut malabsorption. Secondary hyperparathyroidism (SHPT) is defined as an appropriate increase in parathyroid hormone (PTH) secretion, driven by either reduced serum calcium or increased phosphate concentrations, due to an underlying condition. The available evidence on the effects of dietary advice on secondary hyperparathyroidism confirms the benefit of a diet characterized by decreased phosphate intake, avoiding low calcium and vitamin D consumption (recommended intakes 1000–1200 mg/day and 400–800 UI/day, respectively). In addition, low protein intake in CKD patients is associated with a better control of SHPT risk factors, although its strength in avoiding hyperphosphatemia and the resulting outcomes are debated, mostly for dialyzed patients. Ultimately, a consensus on the effect of dietary acid loads in the prevention of SHPT is still lacking. In conclusion, a reasonable approach for reducing the risk for secondary hyperparathyroidism is to individualize dietary manipulation based on existing risk factors and concomitant medical conditions. More studies are needed to evaluate long-term outcomes of a balanced diet on the management and prevention of secondary hyperparathyroidism in at-risk patients at.
Menu Engineering and Dietary Behavior Impact on Young Adults’ Kilocalorie Choice
Authors: Bergman Christine , Tian Yuan , Moreo Andrew , Raab Carola
Published: July 2021

The obesity pandemic is associated with increased consumption of restaurant food. Labeling of menus is an intervention used to provide consumers with kilocalorie (calorie) information in hopes of them making healthier food choices. This study evaluated the relationship between young adults’ calorie choices on restaurant menus and menu design, dietary behaviors, and demographic characteristics. A 3 (fast-casual restaurants) × 4 (menu-designs based on menu engineering theories) between-subjects (n = 480, 18–24-year olds) experimental design was used. The relationship between the participants’ calorie choices (high versus low) and menu design, stage of change, gender, race, educational level and weight status was evaluated using logistic regression. All independent variables had at least one category that had greater odds (CI 95% ± 5%) of subjects choosing a lower calorie entree, except education level and race/ethnic group. Normal weight and overweight subjects had greater odds of choosing lower calorie entrees than those that were obese. In addition, subjects that had started to control their calorie intake for less than six months or had sustained this change for at least six months, had greater odds of choosing lower calorie entrees compared to others. Including a green symbol and calories on fast casual restaurant menus may influence some young adults to choose lower calorie entrees.
Directional Dark Matter Searches with CYGNO
Authors: Amaro Fernando Domingues , Baracchini Elisabetta , Benussi Luigi , Bianco Stefano , Capoccia Cesidio , Caponero Michele , Cavoto Gianluca , Cortez André , Costa Igor Abritta , Dané Emiliano , Dho Giorgio , Di Marco Emanuele , D’Imperio Giulia , Di Giambattista Flaminia , Gregorio Robert R. M. , Iacoangeli Francesco , Lima Júnior Herman Pessoa , Silva Lopes Júnior Amaro da , Maccarrone Giovanni , Mano Rui Daniel Passos , Marafini Michela , Mazzitelli Giovanni , McLean Alasdair G. , Messina Andrea , Bernardes Monteiro Cristina Maria , Nobrega Rafael Antunes , Pains Igor Fonseca , Paoletti Emiliano , Passamonti Luciano , Pelosi Sandro , Petrucci Fabrizio , Piacentini Stefano , Piccolo Davide , Pierluigi Daniele , Pinci Davide , Prajapati Atul , Renga Francesco , Cruz Roque Rita Joana da , Rosatelli Filippo , Russo Andrea , Santos Joaquim Marques Ferreira dos , Saviano Giovanna , Spooner Neil , Tesauro Roberto , Tomassini Sandro , Torelli Samuele
Published: July 2021

The CYGNO project aims at developing a high resolution Time Projection Chamber with optical readout for directional dark matter searches and solar neutrino spectroscopy. Peculiar CYGNO’s features are the 3D tracking capability provided by the combination of photomultipliers and scientific CMOS camera signals, combined with a helium-fluorine-based gas mixture at atmospheric pressure amplified by gas electron multipliers structures. In this paper, the performances achieved with CYGNO prototypes and the prospects for the upcoming underground installation at Laboratori Nazionali del Gran Sasso of a 50-L detector in fall 2021 will be discussed, together with the plans for a 1-m3 experiment. The synergy with the ERC consolidator, grant project INITIUM, aimed at realising negative ion drift operation within the CYGNO 3D optical approach, will be further illustrated.
Transferrins Reduce Replication of Chlamydia suis in McCoy Cells
Authors: De Puysseleyr Leentje , De Puysseleyr Kristien , Rybarczyk Joanna , Vander Donck Paulien , De Vos Winnok H. , Vanrompay Daisy
Published: July 2021

Chlamydia suis (C. suis) resides in the intestines of pigs and tetracycline-resistant strains are emerging worldwide. Intestinal infections are often subclinical. However, the gut is regarded as a C. suis reservoir and clinical infections have been associated with enteritis, conjunctivitis, pneumonia and reproductive failure. C. suis was found in boar semen and venereal transmission occurred. We studied the anti-Chlamydia suis activity of ovotransferrin (ovoTF) and bovine lactoferrin (bLF). Pre-incubation of C. suis with bLF or ovoTF had no significant effect on overall chlamydia replication (mean fluorescence area) in McCoy cells. The addition of ovoTF to the culture medium had no effect on bacterial replication, but the addition of 0.5 or 5 mg/mL of bLF significantly reduced the inclusion size by 17% and 15% respectively. Egg components are used for cryopreservation of boar semen. When inoculating an ovoTF-containing and Chlamydia suis-spiked semen sample in McCoy cells, a significant reduction in inclusion number (by 7%) and overall replication (by 11%) was observed. Thus, we showed that transferrins possess anti-chlamydial activity. Moreover, ovoTF addition to semen extenders might reduce C. suis venereal transmission. Further research is needed to unravel the mechanisms behind the observations and to enhance the effect of transferrins on C. suis.
Evaluation for Potential Drug–Drug Interaction of MT921 Using In Vitro Studies and Physiologically–Based Pharmacokinetic Models
Authors: Ryu Hyo-jeong , Moon Hyun-ki , Lee Junho , Yang Gi-hyeok , Yang Sung-yoon , Yun Hwi-yeol , Chae Jung-woo , Kang Won-ho
Published: July 2021

MT921 is a new injectable drug developed by Medytox Inc. to reduce submental fat. Cholic acid is the active pharmaceutical ingredient, a primary bile acid biosynthesized from cholesterol, endogenously produced by liver in humans and other mammals. Although individuals treated with MT921 could be administered with multiple medications, such as those for hypertension, diabetes, and hyperlipidemia, the pharmacokinetic drug–drug interaction (DDI) has not been investigated yet. Therefore, we studied in vitro against drug-metabolizing enzymes and transporters. Moreover, we predicted the potential DDI between MT921 and drugs for chronic diseases using physiologically-based pharmacokinetic (PBPK) modeling and simulation. The magnitude of DDI was found to be negligible in in vitro inhibition and induction of cytochrome P450s and UDP-glucuronosyltransferases. Organic anion transporting polypeptide (OATP)1B3, organic anion transporter (OAT)3, Na+-taurocholate cotransporting polypeptide (NTCP), and apical sodium-dependent bile acid transporter (ASBT) are mainly involved in MT921 transport. Based on the result of in vitro experiments, the PBPK model of MT921 was developed and evaluated by clinical data. Furthermore, the PBPK model of amlodipine was developed and evaluated. PBPK DDI simulation results indicated that the pharmacokinetics of MT921 was not affected by the perpetrator drugs. In conclusion, MT921 could be administered without a DDI risk based on in vitro study and related in silico simulation. Further clinical studies are needed to validate this finding.
Water-in-Oil Nano-Emulsions Prepared by Spontaneous Emulsification: New Insights on the Formulation Process
Authors: Akram Salman , Anton Nicolas , Omran Ziad , Vandamme Thierry
Published: July 2021

Nano-emulsions consist of stable suspensions of nano-scaled droplets that have huge loading capacities and are formulated with safe compounds. For these reasons, a large number of studies have described the potential uses of nano-emulsions, focusing on various aspects such as formulation processes, loading capabilities, and surface modifications. These studies typically concern direct nano-emulsions (i.e., oil-in-water), whereas studies on reverse nano-emulsions (i.e., water-in-oil) remain anecdotal. However, reverse nano-emulsion technology is very promising (e.g., as an alternative to liposome technology) for the development of drug delivery systems that encapsulate hydrophilic compounds within double droplets. The spontaneous emulsification process has the added advantages of optimization of the energetic yield, potential for industrial scale-up, improved loading capabilities, and preservation of fragile compounds targeted for encapsulation. In this study, we propose a detailed investigation of the processes and formulation parameters involved in the spontaneous nano-emulsification that produces water-in-oil nano-emulsions. The following details were addressed: (i) the order of mixing of the different compounds (method A and method B), (ii) mixing rates, (iii) amount of surfactants, (iv) type and mixture of surfactants, (v) amount of dispersed phase, and (vi) influence of the nature of the oil. The results emphasized the effects of the formulation parameters (e.g., the volume fraction of the dispersed phase, nature or concentration of surfactant, or nature of the oil) on the nature and properties of the nano-emulsions formed.
In Vitro Metabolism Study of Seongsanamide A in Human Liver Microsomes Using Non-Targeted Metabolomics and Feature-Based Molecular Networking
Authors: Wu Zhexue , Kim Geum Jin , Park So-Young , Shon Jong Cheol , Liu Kwang-Hyeon , Choi Hyukjae
Published: July 2021

Seongsanamide A is a bicyclic peptide with an isodityrosine residue discovered in Bacillus safensis KCTC 12796BP which exhibits anti-allergic activity in vitro and in vivo without significant cytotoxicity. The purpose of this study was to elucidate the in vitro metabolic pathway and potential for drug interactions of seongsanamide A in human liver microsomes using non-targeted metabolomics and feature-based molecular networking (FBMN) techniques. We identified four metabolites, and their structures were elucidated by interpretation of high-resolution tandem mass spectra. The primary metabolic pathway associated with seongsanamide A metabolism was hydroxylation and oxidative hydrolysis. A reaction phenotyping study was also performed using recombinant cytochrome P450 isoforms. CYP3A4 and CYP3A5 were identified as the major metabolic enzymes responsible for metabolite formation. Seongsanamide A did not inhibit the cytochrome P450 isoforms commonly involved in drug metabolism (IC50 > 10 µM). These results will contribute to further understanding the metabolism and drug interaction potential of various bicyclic peptides.
Insight into the Web of Stress Responses Triggered at Gene Expression Level by Porphyrin-PDT in HT29 Human Colon Carcinoma Cells
Authors: Dobre Maria , Boscencu Rica , Neagoe Ionela Victoria , Surcel Mihaela , Milanesi Elena , Manda Gina
Published: July 2021

Photodynamic therapy (PDT), a highly targeted therapy with acceptable side effects, has emerged as a promising therapeutic option in oncologic pathology. One of the issues that needs to be addressed is related to the complex network of cellular responses developed by tumor cells in response to PDT. In this context, this study aims to characterize in vitro the stressors and the corresponding cellular responses triggered by PDT in the human colon carcinoma HT29 cell line, using a new asymmetric porphyrin derivative (P2.2) as a photosensitizer. Besides investigating the ability of P2.2-PDT to reduce the number of viable tumor cells at various P2.2 concentrations and fluences of the activating light, we assessed, using qRT-PCR, the expression levels of 84 genes critically involved in the stress response of PDT-treated cells. Results showed a fluence-dependent decrease of viable tumor cells at 24 h post-PDT, with few cells that seem to escape from PDT. We highlighted following P2.2-PDT the concomitant activation of particular cellular responses to oxidative stress, hypoxia, DNA damage and unfolded protein responses and inflammation. A web of inter-connected stressors was induced by P2.2-PDT, which underlies cell death but also elicits protective mechanisms that may delay tumor cell death or even defend these cells against the deleterious effects of PDT.
Process Model Approach to Predict Tablet Weight Variability for Direct Compression Formulations at Pilot and Production Scale
Authors: Peddapatla Raghu V. G. , Sheridan Gerard , Slevin Conor , Swaminathan Shrikant , Browning Ivan , O’Reilly Clare , Worku Zelalem A. , Egan David , Sheehan Stephen , Crean Abina M.
Published: July 2021

Optimizing processing conditions to achieve a critical quality attribute (CQA) is an integral part of pharmaceutical quality by design (QbD). It identifies combinations of material and processing parameters ensuring that processing conditions achieve a targeted CQA. Optimum processing conditions are formulation and equipment-dependent. Therefore, it is challenging to translate a process design between formulations, pilot-scale and production-scale equipment. In this study, an empirical model was developed to determine optimum processing conditions for direct compression formulations with varying flow properties, across pilot- and production-scale tablet presses. The CQA of interest was tablet weight variability, expressed as percentage relative standard deviation. An experimental design was executed for three model placebo blends with varying flow properties. These blends were compacted on one pilot-scale and two production-scale presses. The process model developed enabled the optimization of processing parameters for each formulation, on each press, with respect to a target tablet weight variability of <1%RSD. The model developed was successfully validated using data for additional placebo and active formulations. Validation formulations were benchmarked to formulations used for model development, employing permeability index values to indicate blend flow.
Hierarchical Particle Approach for Co-Precipitated Amorphous Solid Dispersions for Use in Preclinical In Vivo Studies
Authors: Schenck Luke , Boyce Christopher , Frank Derek , Koranne Sampada , Ferguson Heidi M. , Strotman Neil
Published: July 2021

Amorphous solid dispersions (ASD) have become a well-established strategy to improve exposure for compounds with insufficient aqueous solubility. Of methods to generate ASDs, spray drying is a leading route due to its relative simplicity, availability of equipment, and commercial scale capacity. However, the broader industry adoption of spray drying has revealed potential limitations, including the inability to process compounds with low solubility in volatile solvents, inconsistent molecular uniformity of spray dried amorphous dispersions, variable physical properties across batches and scales, and challenges containing potent compounds. In contrast, generating ASDs via co-precipitation to yield co-precipitated amorphous dispersions (cPAD) offers solutions to many of those challenges and has been shown to achieve ASDs comparable to those manufactured via spray drying. This manuscript applies co-precipitation for early safety studies, developing a streamlined process to achieve material suitable for dosing as a suspension in conventional toxicity studies. Development targets involved achieving a rapid, safely contained process for generating ASDs with high recovery yields. Furthermore, a hierarchical particle approach was used to generate composite particles where the cPAD material is incorporated in a matrix of water-soluble excipients to allow for rapid re-dispersibility in the safety study vehicle to achieve a uniform suspension for consistent dosing. Adopting such an approach yielded a co-precipitated amorphous dispersion with comparable stability, thermal properties, and in vivo pharmacokinetics to spray dried amorphous materials of the same composition.
Correction: Huet, R.; Johanson, G. 1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling. Pharmaceutics 2020, 12, 997
Authors: Huet Raul , Johanson Gunnar
Published: July 2021

The authors wish to make the following corrections to this paper [...]
Polymeric Biomaterials for the Treatment of Cardiac Post-Infarction Injuries
Authors: Trombino Sonia , Curcio Federica , Cassano Roberta , Curcio Manuela , Cirillo Giuseppe , Iemma Francesca
Published: July 2021

Cardiac regeneration aims to reconstruct the heart contractile mass, preventing the organ from a progressive functional deterioration, by delivering pro-regenerative cells, drugs, or growth factors to the site of injury. In recent years, scientific research focused the attention on tissue engineering for the regeneration of cardiac infarct tissue, and biomaterials able to anatomically and physiologically adapt to the heart muscle have been proposed as valuable tools for this purpose, providing the cells with the stimuli necessary to initiate a complete regenerative process. An ideal biomaterial for cardiac tissue regeneration should have a positive influence on the biomechanical, biochemical, and biological properties of tissues and cells; perfectly reflect the morphology and functionality of the native myocardium; and be mechanically stable, with a suitable thickness. Among others, engineered hydrogels, three-dimensional polymeric systems made from synthetic and natural biomaterials, have attracted much interest for cardiac post-infarction therapy. In addition, biocompatible nanosystems, and polymeric nanoparticles in particular, have been explored in preclinical studies as drug delivery and tissue engineering platforms for the treatment of cardiovascular diseases. This review focused on the most employed natural and synthetic biomaterials in cardiac regeneration, paying particular attention to the contribution of Italian research groups in this field, the fabrication techniques, and the current status of the clinical trials.
Development of a Hydrophobicity-Controlled Delivery System Containing Levodopa Methyl Ester Hydrochloride Loaded into a Mesoporous Silica
Authors: Kiss Tamás , Katona Gábor , Mérai László , Janovák László , Deák Ágota , Kozma Gábor , Kónya Zoltán , Ambrus Rita
Published: July 2021

Background: The drug release of antiparkinsonian drugs is an important issue during the formulation process because proper release kinetics can help to reduce the off periods of Parkinson’s disease. A 2-factor, 3-level (32) full-factorial design was conducted to evaluate statistically the influence of the hydrophobicity of mesoporous silica on drug release. Methods: Hydrophobization was evaluated by different methods, such as contact angle measurement, infrared spectroscopy and charge titration. After loading the drug (levodopa methyl ester hydrochloride, melevodopa hydrochloride, LDME) into the mesopores, drug content, particle size, specific surface area and homogeneity of the products were also analyzed. The amorphous state of LDME was verified by X-ray diffractometry and differential scanning calorimetry. Results: Drug release was characterized by a model-independent method using the so-called initial release rate parameter, as detailed in the article. The adaptability of this method was verified; the model fitted closely to the actual release results according to the similarity factor, independently of the release kinetics. Conclusions: The API was successfully loaded into the silica, resulting in a reduced surface area. The release studies indicated that the release rate significantly decreased (p < 0.05) with increasing hydrophobicity. The products with controlled release can reduce the off period frequency.
Describing High-Order Harmonic Generation Using Quantum Optical Models
Authors: Földi Péter , Magashegyi István , Gombköto Ákos , Varró Sándor
Published: July 2021

Optical generation of high-order harmonics is a prototypical example of nonlinear light–matter interactions in the high-field regime. Quantum optical effects have recently been demonstrated to have a significant influence on this phenomenon. These findings underline the importance of understanding the dynamics of the quantized electromagnetic field during high-order harmonic generation. In the following, we discuss the challenges that are related to the theoretical description of this process and summarize the results that were obtained using the high-field, multimode generalization of well-known quantum optical models that are based on the concept of the two-level atom.
Adaptation of the Standard Off-Axis Digital Holographic Microscope to Achieve Variable Magnification
Authors: Fan Xin , Healy John J. , O’Dwyer Kevin , Winnik Julianna , Hennelly Bryan M.
Published: July 2021

Traditional microscopy provides only for a small set of magnifications using a finite set of microscope objectives. Here, a novel architecture is proposed for quantitative phase microscopy that requires only a simple adaptation of the traditional off-axis digital holographic microscope. The architecture has the key advantage of continuously variable magnification, resolution, and Field-of-View, by simply moving the sample. The method is based on combining the principles of traditional off-axis digital holographic microscopy and Gabor microscopy, which uses a diverging spherical wavefield for magnification. We present a proof-of-concept implementation and ray-tracing is used to model the magnification, Numerical Aperture, and Field-of-View as a function of sample position. Experimental results are presented using a micro-lens array and shortcomings of the method are highlighted for future work; in particular, the problem of aberration is highlighted, which results from imaging far from the focal plane of the infinity corrected microscope objective.
Perspectives on the Combined Effects of Ocimum basilicum and Trifolium pratense Extracts in Terms of Phytochemical Profile and Pharmacological Effects
Authors: Antonescu (Mintas) Andreea-Ina , Miere (Groza) Florina , Fritea Luminita , Ganea Mariana , Zdrinca Mihaela , Dobjanschi Luciana , Antonescu Angela , Vicas Simona Ioana , Bodog Florin , Sindhu Rakesh K. , Cavalu Simona
Published: July 2021

Nowadays, the tendency in pharmaceutical and food industries is to replace synthetic antioxidants with the natural ones. For this reason, there is a growing interest in analyzing natural, healthy and non-toxic additives as potential antioxidants. Some plants, which contain high levels of phenolic compounds, present an increasing interest for medicine due to their ability to scavenge free radicals, along with other pharmacological activities, such as antibacterial activity, wound healing and anti-inflammatory effect, to mention only a few. The aim of this review is to explore the therapeutic potential of Ocimum basilicum and Trifolium pratense in relation with their phytochemical profile and to highlight the pharmacological activity of aqueous or ethanol extracts. Special attention was devoted to the dermal pathology and wound healing effects, in the context of multiple skin conditions such as acne, eczema boils, psoriasis and rashes. Additionally, both extracts (Trifolium sp. and Ocimum sp.) are characterized by high content of antioxidant compounds, which are responsible for the radiance and resistance of the skin and slowing down of the aging process by maintaining estrogen levels. Moreover, the potential combined effect of the mixed extract is pointed out in terms of future applications for wound healing, based on some preliminary results obtained from a “scratch tests” assay performed with respect to human dermal fibroblasts.
Responses to Salinity in Four Plantago Species from Tunisia
Authors: Ltaeif Hela Belhaj , Sakhraoui Anis , González-Orenga Sara , Landa Faz Anbu , Boscaiu Monica , Vicente Oscar , Rouz Slim
Published: July 2021

The genus Plantago is particularly interesting for studying the mechanisms of salt tolerance in plants, as it includes both halophytes and glycophytes, as well as species adapted to xeric environments. In this study, the salt stress responses of two halophytes, P. crassifolia and P. coronopus, were compared with those of two glycophytes, P. ovata and P. afra. Plants obtained by seed germination of the four species, collected in different regions of Tunisia, were subjected to increasing salinity treatments for one month under greenhouse conditions. Morphological traits and biochemical parameters, such as ion accumulation and the leaf contents of photosynthetic pigments, osmolytes, oxidative stress markers and antioxidant metabolites, were measured after the treatments. Salt-induced growth inhibition was more pronounced in P. afra, and only plants subjected to the lowest applied NaCl concentration (200 mM) survived until the end of the treatments. The biochemical responses were different in the two groups of plants; the halophytes accumulated higher Na+ and proline concentrations, whereas MDA levels in their leaves decreased, indicating a lower level of oxidative stress. Overall, the results showed that P. coronopus and P. crassifolia are the most tolerant to salt stress, and P. afra is the most susceptible of the four species. Plantago ovata is also quite resistant, apparently by using specific mechanisms of tolerance that are more efficient than in the halophytes, such as a less pronounced inhibition of photosynthesis, the accumulation of higher levels of Cl− ions in the leaves, or the activation of K+ uptake and transport to the aerial part under high salinity conditions.
Genetic Diversity and Synergistic Modulation of Salinity Tolerance Genes in Aegilops tauschii Coss
Authors: Abbas Adeel , Yu Haiyan , Cui Hailan , Li Xiangju
Published: July 2021

Aegilops tauschii Coss. (2n = 2x = 14, DD) is a problematic weed and a rich source of genetic material for wheat crop improvement programs. We used physiological traits (plant height, dry weight biomass, Na+ and K+ concentration) and 14 microsatellite markers to evaluate the genetic diversity and salinity tolerance in 40 Ae. tauschii populations. The molecular marker allied with salinity stress showed polymorphisms, and a cluster analysis divided the populations into different groups, which indicated diversity among populations. Results showed that the expression level of AeHKT1;4 and AeNHX1 were significantly induced during salinity stress treatments (50 and 200 mM), while AeHKT1;4 showed relative expression in roots, and AeNHX1 was expressed in leaves under the control conditions. Compared with the control conditions, the expression level of AeHKT1;4 significantly increased 1.7-fold under 50 mM salinity stress and 4.7-fold under 200 mM salinity stress in the roots of Ae. tauschii. AeNHX1 showed a relative expression level of 1.6-fold under 50 mM salinity stress and 4.6-fold under 200 mM salinity stress compared with the control conditions. The results provide strong evidence that, under salinity stress conditions, AeHKT1;4 and AeNHX1 synergistically regulate the Na+ homeostasis through regulating Na+ transport in Ae. tauschii. AeNHX1 sequestrated the Na+ into vacuoles, which control the regulation of Na+ transport from roots to leaves under salinity stress conditions in Ae. tauschii.
Epoxy and Polyester Composites’ Characteristics under Tribological Loading Conditions
Authors: Alotaibi Jasem Ghanem , Eid Alajmi Ayedh , Mehoub Gabrel A. , Yousif Belal F.
Published: July 2021

This research examines the friction and dry wear behaviours of glass fibre-reinforced epoxy (GFRE) and glass fibre-reinforced polyester (GFRP) composites. Three fibre orientations—parallel orientation (P–O), anti-parallel orientation (AP–O), and normal orientation (N–O)—and various sliding distances from 0–15 km were examined. The experiments were carried out using a block-on-ring configuration at room temperature, an applied load of 30 N, and a sliding velocity of 2.8 m/s. During the sliding, interface temperatures and frictional forces were captured and recorded. Worn surfaces were examined using scanning electron microscopy to identify the damage. The highest wear rates for GFRE composites occurred in those with AP–O fibres, while the highest wear rates for GFRP composites occurred in those with P–O fibres. At longer sliding distances, composites with P–O and N–O fibres had the lowest wear rates. The highest friction coefficient was observed for composites with N–O and P–O fibres at higher sliding speeds. The lowest friction coefficient value (0.25) was for composites with AP–O fibres. GFRP composites with P–O fibres had a higher wear rate than those with N–O fibres at the maximum speed.
Fiber Selection for Reinforced Additive Manufacturing
Authors: Beckman Ivan , Lozano Christine , Freeman Elton , Riveros Guillermo
Published: July 2021

The purpose of this review is to survey, categorize, and compare the mechanical and thermal characteristics of fibers in order to assist designers with the selection of fibers for inclusion as reinforcing materials in the additive manufacturing process. The vast “family of fibers” is described with a Venn diagram to highlight natural, synthetic, organic, ceramic, and mineral categories. This review explores the history and practical uses of particular fiber types and explains fiber production methods in general terms. The focus is on short-cut fibers including staple fibers, chopped strands, and whiskers added to polymeric matrix resins to influence the bulk properties of the resulting printed materials. This review discusses common measurements for specific strength and tenacity in the textile and construction industries, including denier and tex, and discusses the proposed “yuri” measurement unit. Individual fibers are selected from subcategories and compared in terms of their mechanical and thermal properties, i.e., density, tensile strength, tensile stiffness, flexural rigidity, moisture regain, decomposition temperature, thermal expansion, and thermal conductivity. This review concludes with an example of the successful 3D printing of a large boat at the University of Maine and describes considerations for the selection of specific individual fibers used in the additive manufacturing process.
Electrospun Polylactide/Natural Rubber Fibers: Effect Natural Rubber Content on Fiber Morphology and Properties
Authors: Tertyshnaya Yulia , Karpova Svetlana , Moskovskiy Maksim , Dorokhov Aleksey
Published: July 2021

Non-woven polylactide-natural rubber fiber materials with a rubber content of 5, 10 and 15 wt.% were obtained by electrospinning. The thermal, dynamic, and mechanical properties of the fibers were determined. It was shown that the average fiber diameter increased with adding of the NR content, while the linear and surface densities changed slightly. Using the differential scanning calorimetry, the thermal characteristics were obtained. It was found that the glass transition temperature of polylactide increased by 2–5 °C, and the melting temperature increased by 2–4 °C in the presence of natural rubber in the samples. By the method of electronic paramagnetic resonance at T = 50 and 70 °C it was determined that the mobility of the amorphous phase in PLA/NR fibers increased with the addition of NR. The adding of NR at a content of 15 wt.% increased the value of elongation at break by 3.5 times compared to pure PLA.
Fire Retardancy, Water Absorption, and Viscoelasticity of Borated Wood—Polycarbonate Biocomposites
Authors: Zhang Jingfa , Koubaa Ahmed , Xing Dan , Godard François , Li Peng , Tao Yubo , Wang Xiang-Ming , Wang Haigang
Published: July 2021

Demand for high-performance biocomposites is increasing due to their ease of processing, low environmental impact, and in-service performance. This study investigated the effect of boric acid modification of wood flour on polycarbonate (PC) wood composites’ thermal stability, fire retardancy, water absorption, and creep behavior. The composites’ fire retardancy increased with increasing wood flour content, and their char residue increased by 102.3% compared to that of pure PC. However, the water absorption of the resulting composites increased due to the hydroxyl groups of the wood flour. Wood flour also improved the composites’ anti-creep properties. The excellent fire retardancy and anti-creep properties of wood–PC composites expand their use in the construction sector.