bluuebunny/crossref_metadata_2025 huggingface dataset:
Geological Controls on Enrichment of Rare Earth Elements and Yttrium (REY) in Late Permian Coals and Non-Coal Rocks in the Xian’an Coalfield, Guangxi Province
Authors: Zhang Fuqiang , Li Baoqing , Zhuang Xinguo , Querol Xavier , Moreno Natalia , Shangguan Yunfei , Zhou Jinming , Liao Jialong
Published: March 2021

The highly elevated concentrations of the rare earth elements and yttrium (REY), U, Mo, Se, and Pb in late Permian coals in some coalfields in Guangxi Province, South China, have been widely investigated; however, the mode of occurrence and enrichment mechanism of these critical elements are still under debate. This study investigates the mineralogical and geochemical compositions of coals and non-coal rocks from the Xian’an Coalfield in Guangxi Province to discuss the geological factors influencing the distribution of critical elements. The mineral in the studied coals consists mainly of quartz, and to a lesser extent, muscovite and kaolinite, with a trace amount of anatase. The coals are significantly enriched in REY, Pb, Se, Mo, and U and display the REY–U–Se–Mo–Pb-enrichment horizon (Horizon I) and U–Mo-enrichment horizon (Horizon II) adjacent to the host rocks or partings. The REY, U, Se, and Pb show organic association while Mo is primarily hosted by Fe-sulfides within Horizon I. The U and Mo have a phosphate affinity within Horizon II. Both the input of pyroclastic and epiclastic materials and the leaching of acidic solutions jointly govern the distribution of the REY–U–Se–Mo–Pb-enrichment horizon (Horizon I) and the U–Mo-enrichment horizon (Horizon II). The concentrations of REY in Horizon I exceed the cutoff grade of REY, and, therefore, the coals in the Horizon I can be regarded as promising raw materials of REY.
Comparative Study of CoFe2O4 Nanoparticles and CoFe2O4-Chitosan Composite for Congo Red and Methyl Orange Removal by Adsorption
Authors: Simonescu Claudia Maria , Tătăruş Alina , Culiţă Daniela Cristina , Stănică Nicolae , Ionescu Ioana Alexandra , Butoi Bogdan , Banici Ana-Maria
Published: March 2021

(1) Background: A comparative research study to remove Congo Red (CR) and Methyl Orange (MO) from single and binary solutions by adsorption onto cobalt ferrite (CoFe2O4) and cobalt ferrite–chitosan composite (CoFe2O4-Chit) prepared by a simple coprecipitation method has been performed. (2) Methods: Structural, textural, morphology, and magnetic properties of the obtained magnetic materials were examined by X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, N2 adsorption–desorption analysis, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and magnetic measurements. The optimal operating conditions of the CR and MO removal processes were established in batch experiments. The mathematical models used to describe the processes at equilibrium were Freundlich and Langmuir adsorption isotherms. (3) Results: Cobalt ferrite–chitosan composite has a lower specific surface area (SBET) and consequently a lower adsorption capacity than cobalt ferrite. CoFe2O4 and CoFe2O4–Chit particles exhibited a superparamagnetic behavior which enabled their efficient magnetic separation after the adsorption process. The research indicates that CR and MO adsorption onto prepared magnetic materials takes place as monolayer onto a homogeneous surface. According to Langmuir isotherm model that best fits the experimental data, the maximum CR/MO adsorption capacity is 162.68/94.46 mg/g for CoFe2O4 and 15.60/66.18 mg/g for CoFe2O4–Chit in single solutions. The results of the kinetics study revealed that in single-component solutions, both pseudo-first-order and pseudo-second-order kinetics models represent well the adsorption process of CR/MO on both magnetic adsorbents. In binary solutions, adsorption of CR/MO on CoFe2O4 better follows the pseudo-second-order kinetics model, while the kinetic of CR/MO adsorption on CoFe2O4–Chit is similar to that of the dyes in single-component solutions. Acetone and ethanol were successfully used as desorbing agents. (4) Conclusions: Our study revealed that CoFe2O4 and CoFe2O4–Chit particles are good candidates for dye-contaminated wastewater remediation.
Robust Copper Metal–Organic Framework-Embedded Polysiloxanes for Biomedical Applications: Its Antibacterial Effects on MRSA and In Vitro Cytotoxicity
Authors: Gwon Kihak , Kim Youngmee , Cho Hyunjun , Lee Seonhwa , Yang So-Hyeon , Kim Sung-Jin , Lee Do Nam
Published: March 2021

Polysiloxanes (PSs) have been widely utilized in the industry as lubricants, varnishes, paints, release agents, adhesives, and insulators. In addition, their applications have been expanded to include the development of new biomedical materials. To modify PS for application in therapeutic purposes, a flexible antibacterial Cu-MOF (metal–organic framework) consisting of glutarate and 1,2-bis(4-pyridyl)ethane ligands was embedded in PS via a hydrosilylation reaction of vinyl-terminated and H-terminated PSs at 25 °C. The bactericidal activities of the resulting Cu-MOF-embedded PS (PS@Cu-MOF) and the control polymer (PS) were tested against Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. PS@Cu-MOF exhibited more than 80% bactericidal activity toward the tested bacteria at a concentration of 100 μg⋅mL−1 and exhibited a negligible cytotoxicity toward mouse embryonic fibroblasts at the same concentration. Release tests of the Cu(II) ion showed PS@Cu-MOF to be particularly stable in a phosphate-buffered saline solution. Furthermore, its physical and thermal properties, including the phase transition, rheological measurements, swelling ratio, and thermogravimetric profile loss, were similar to those of the control polymer. Moreover, the low cytotoxicity and bactericidal activities of PS@Cu-MOF render it a promising candidate for use in medicinal applications, such as in implants, skin-disease treatment, wound healing, and drug delivery.
Selective Oxidation of Transient Organic Radicals in the Presence of Gold Nanoparticles
Authors: Shcherbakov Viacheslav , Denisov Sergey A. , Mostafavi Mehran
Published: March 2021

The ability of gold nanoparticles (AuNPs) to catalyze reactions involving radicals is poorly studied. However, AuNPs are used in applications where chemical reactions involving transient radicals occur. Herein, we investigate AuNPs’ catalytic effect on 2-propanol oxidation and acetanilide hydroxylation in aqueous solutions under ionizing radiation at room temperature. In both cases, the presence of AuNPs led to selective oxidation of organic radicals, significantly changing the products’ composition and ratio. Based on these observations, we stress how AuNPs’ catalytic activity can affect the correctness of reactive oxygen species concentration determination utilizing organic dyes. We also provide a discussion on the role of AuNPs’ catalytic activity in the radiosensitization effect actively studied for radiotherapy.
Optical Platform to Analyze a Model Drug-Loading and Releasing Profile Based on Nanoporous Anodic Alumina Gradient Index Filters
Authors: Kapruwan Pankaj , Acosta Laura K. , Ferré-Borrull Josep , Marsal Lluis F.
Published: March 2021

In this work, a methodology that exploits the optical properties of the nanoporous anodic alumina gradient index filters (NAA-GIFs) has been developed and applied to evaluate in real time the release dynamics of a cargo molecule, acting as a model drug, filling the pores. NAA-GIFs with two photonic stopbands (PSBs) were prepared with one of its stop bands in the same absorption wavelength range of the cargo molecule, whereas the second stopband away from this absorption range. Numerical simulation and experiments confirm that the relative height of the high reflectance bands in the reflectance spectra of NAA-GIFs filled with the drug can be related to the relative amount of drug filling the pores. This property has been applied in a flow cell setup to measure in real-time the release dynamics of NAA-GIFs with the inner pore surface modified by layer-by-layer deposition of polyelectrolytes and loaded with the cargo molecule. The methodology developed in this work acts as a tool for the study of drug delivery from porous nanostructures.
Tunable Transparency and NIR-Shielding Properties of Nanocrystalline Sodium Tungsten Bronzes
Authors: Chao Luomeng , Sun Changwei , Dou Jianyong , Li Jiaxin , Liu Jia , Ma Yonghong , Xiao Lihua
Published: March 2021

The NaxWO3 nanoparticles with different x were synthesized by a solvothermal method and the absorption behavior in visible and near-infrared light (NIR) region was studied. Well-crystallized nanoparticles with sizes of several tens of nanometers were confirmed by XRD, SEM and TEM methods. The absorption valley in visible region shifted from 555 nm to 514 nm and the corresponding absorption peak in NIR region shifted from 1733 nm to 1498 nm with the increasing x. In addition, the extinction behavior of NaxWO3 nanoparticles with higher x values were simulated by discrete dipole approximation method and results showed that the changing behavior of optical properties was in good agreement with the experimental results. The experimental and theoretical data indicate that the transparency and NIR-shielding properties of NaxWO3 nanoparticles in the visible and NIR region can be continuously adjusted by x value in the whole range of 0 < x < 1. These tunable optical properties of nanocrystalline NaxWO3 will expand its application in the fields of transparent heat-shielding materials or optical filters.
Lactobacillus reuteri in Its Biofilm State Improves Protection from Experimental Necrotizing Enterocolitis
Authors: Al-Hadidi Ameer , Navarro Jason , Goodman Steven D. , Bailey Michael T. , Besner Gail E.
Published: March 2021

Necrotizing enterocolitis (NEC) is a devastating disease predominately found in premature infants that is associated with significant morbidity and mortality. Despite decades of research, medical management with broad spectrum antibiotics and bowel rest has remained relatively unchanged, with no significant improvement in patient outcomes. The etiology of NEC is multi-factorial; however, gastrointestinal dysbiosis plays a prominent role in a neonate’s vulnerability to and development of NEC. Probiotics have recently emerged as a new avenue for NEC therapy. However, current delivery methods are associated with potential limitations, including the need for at least daily administration in order to obtain any improvement in outcomes. We present a novel formulation of enterally delivered probiotics that addresses the current limitations. A single enteral dose of Lactobacillus reuteri delivered in a biofilm formulation increases probiotic survival in acidic gastric conditions, increases probiotic adherence to gastrointestinal epithelial cells, and reduces the incidence, severity, and neurocognitive sequelae of NEC in experimental models.
Nutrition Transition with Accelerating Urbanization? Empirical Evidence from Rural China
Authors: Ren Yanjun , Castro Campos Bente , Peng Yanling , Glauben Thomas
Published: March 2021

Although rapid urbanization is often considered as one of the most important drivers for changing dietary patterns, little attention has been paid to rural areas despite the profound transformation they have undergone. Using longitudinal data from the China Health and Nutrition Survey (CHNS) for the period from 2004 to 2011, this study seeks to better understand the relationship between the urbanization of rural areas and dietary transition, with the focus on nutrition intake and dietary quality. Our results suggest that with increasing urbanization, rural residents tend to have on average lower calorie intakes but higher dietary quality. Specifically, increasing urbanization consistently reduces carbohydrate consumption and reduces fat consumption after a turning point; protein consumption first decreases and then increases after the turning point with increasing urbanization. Urbanization shows a significant and positive effect on the Healthy Eating Index (HEI). In addition to sociodemographic changes, we find that changing consumer preferences and knowledge serve as important determinants in explaining the dietary transition in rural China from 2004 to 2011. In our study, urbanization appears to positively affect rural residents’ healthy food preferences and dietary knowledge. This study is a first attempt for better understanding the nutrition transition resulting from accelerating urbanization in rural China; several limitations and areas for future research have been highlighted.
Development and Reliability of the Oxford Meat Frequency Questionnaire
Authors: Stewart Cristina , Frie Kerstin , Piernas Carmen , Jebb Susan A.
Published: March 2021

Reliable and valid measurements of meat intake are needed to advance understanding of its health effects and to evaluate interventions to reduce meat consumption. Here, we describe the development and reliability of the Oxford Meat Frequency Questionnaire (MFQ). It asks individuals to report the number of servings of meat and seafood products they consumed in the last 24 h and is administered daily over 7 days. The MFQ combines food portion size data from the UK Food Standards Agency with estimates of meat content in composite dishes from the UK’s National Diet and Nutrition Survey. Adults who self-reported to eat meat (n = 129) completed a 3-week web-based test–retest reliability study assessing the MFQ twice, with a wash-out week in the middle. Two-way random intraclass correlation coefficients (ICC) revealed moderate to good agreement on all meat outcomes (total meat ICC = 0.716; minimum–maximum individual components = 0.531–0.680), except for fish and seafood (ICC = 0.257). Participants reported finding the questionnaire easy to use and, on average, completed it in less than 2 min. This new MFQ offers a quick, acceptable, and reliable method to measure changes in an individual’s meat intake in a UK population.
Role of the Intestinal Microbiome, Intestinal Barrier and Psychobiotics in Depression
Authors: Trzeciak Paulina , Herbet Mariola
Published: March 2021

The intestinal microbiota plays an important role in the pathophysiology of depression. As determined, the microbiota influences the shaping and modulation of the functioning of the gut–brain axis. The intestinal microbiota has a significant impact on processes related to neurotransmitter synthesis, the myelination of neurons in the prefrontal cortex, and is also involved in the development of the amygdala and hippocampus. Intestinal bacteria are also a source of vitamins, the deficiency of which is believed to be related to the response to antidepressant therapy and may lead to exacerbation of depressive symptoms. Additionally, it is known that, in periods of excessive activation of stress reactions, the immune system also plays an important role, negatively affecting the tightness of the intestinal barrier and intestinal microflora. In this review, we have summarized the role of the gut microbiota, its metabolites, and diet in susceptibility to depression. We also describe abnormalities in the functioning of the intestinal barrier caused by increased activity of the immune system in response to stressors. Moreover, the presented study discusses the role of psychobiotics in the prevention and treatment of depression through their influence on the intestinal barrier, immune processes, and functioning of the nervous system.
Milk Ingredients in Meat Products: Can Autoclaving and In Vitro Gastroduodenal Digestion Mitigate Their IgE-Binding Capacity?
Authors: Villa Caterina , Bavaro Simona L. , De Angelis Elisabetta , Pilolli Rosa , Costa Joana , Barni Simona , Novembre Elio , Mafra Isabel , Monaci Linda
Published: March 2021

The food industry commonly uses milk ingredients as technological aids in an uncounted number of products. On the other hand, milk contains allergenic proteins causing adverse allergic reactions in sensitized/allergic individuals. This work intends to evaluate the effect of autoclaving and in vitro digestion on the allergenicity of milk proteins incurred in meat products. Protein profiles of raw and autoclaved sausages without and with the addition of 10% of milk protein concentrates were analyzed by gel electrophoresis and liquid chromatography–mass spectrometry. Additionally, residual IgE-reactivity was evaluated by immunoblot analysis using pooled sera of cow’s-milk-allergic individuals followed by bioinformatic analysis. Results showed that autoclaving led to an increase in protein fragmentation (higher number of short peptides) and consequently to a higher digestion rate, that was found to be more pronounced in β-casein. The IgE-binding capacity of milk proteins seems to be reduced after autoclaving prior to digestion, with a residual reactivity in caseins, but was eliminated following digestion. This study highlights the importance of autoclaving as a processing strategy to produce hypoallergenic formulas.
Assessment of Health Claims Related to Folic Acid in Food Supplements for Pregnant Women According to the European Regulation
Authors: Domínguez Laura , Fernández-Ruiz Virginia , Morales Patricia , Sánchez-Mata María-Cortes , Cámara Montaña
Published: March 2021

Pregnant women are a vulnerable group with increased nutritional requirements. The daily intake of folic acid, a crucial vitamin for embryonic development, must be reinforced through supplementation, as sometimes diets are not well equilibrated. As consumers increasingly rely on food supplements, it is vital to properly inform them about the health benefits provided by supplements’ consumption to ensure their safe use. The objective of this work was to assess the compliance level of health claims related to folic acid in food supplements commercialized in Spain according to the European regulation. Authors performed (1) a review of health-related claims approved for folic acid in Europe, (2) a market research of food supplements commercialized in Spain with those claims, and (3) a selection of food supplements for chemical analysis in the lab to assess these claims. The results showed that nine health-related claims are currently approved for folic acid in Europe. The analytical results for folic acid content in the selected samples were consistent with the declared values and within the tolerance ranges established in the European Guidance document. All samples included accurate dosages and met the legal requirements (European Regulations 1924/2006, 432/2012, 1169/2011) for all approved claims for folic acid.
A Multi-Mineral Intervention to Modulate Colonic Mucosal Protein Profile: Results from a 90-Day Trial in Human Subjects
Authors: Aslam Muhammad N. , McClintock Shannon D. , Jawad-Makki Mohamed Ali H. , Knuver Karsten , Ahmad Haris M. , Basrur Venkatesha , Bergin Ingrid L. , Zick Suzanna M. , Sen Ananda , Turgeon D. Kim , Varani James
Published: March 2021

The overall goal of this study was to determine whether Aquamin®, a calcium-, magnesium-, trace element-rich, red algae-derived natural product, would alter the expression of proteins involved in growth-regulation and differentiation in colon. Thirty healthy human subjects (at risk for colorectal cancer) were enrolled in a three-arm, 90-day interventional trial. Aquamin® was compared to calcium alone and placebo. Before and after the interventional period, colonic biopsies were obtained. Biopsies were evaluated by immunohistology for expression of Ki67 (proliferation marker) and for CK20 and p21 (differentiation markers). Tandem mass tag-mass spectrometry-based detection was used to assess levels of multiple proteins. As compared to placebo or calcium, Aquamin® reduced the level of Ki67 expression and slightly increased CK20 expression. Increased p21 expression was observed with both calcium and Aquamin®. In proteomic screen, Aquamin® treatment resulted in many more proteins being upregulated (including pro-apoptotic, cytokeratins, cell–cell adhesion molecules, and components of the basement membrane) or downregulated (proliferation and nucleic acid metabolism) than placebo. Calcium alone also altered the expression of many of the same proteins but not to the same extent as Aquamin®. We conclude that daily Aquamin® ingestion alters protein expression profile in the colon that could be beneficial to colonic health.
Potential Antimetastatic Effect of Timosaponin AIII against Human Osteosarcoma Cells through Regulating the Integrin/FAK/Cofilin Axis
Authors: Hsieh Yi-Hsien , Hsu Wen-Hung , Yang Shun-Fa , Liu Chung-Jung , Lu Ko-Hsiu , Wang Pei-Han , Lin Renn-Chia
Published: March 2021

Timosaponin AIII (TSAIII) is a steroidal saponin which demonstrates anti-tumour activities. However, the effect of TSAIII on human osteosarcoma cells remains largely unknown. In this study, we demonstrated that TSAIII exerted a significant inhibitory effect on the distribution of cytoskeletal F-actin and cytoskeletal-related proteins, which contributed to the suppression of cell migration and invasion, without inhibiting cell growth or apoptosis. In the synergistic inhibitory analysis, cotreatment of TSAIII with αVβ3 integrin inhibitor [Cyclo(RGDyK)] or focal adhesion kinase (FAK) inhibitor (PF-573228) exerted greater synergistic inhibitory effects on the expression of Intergin αVβ3/FAK/cofilin axis, thus inhibiting the migration and invasion capacities of human osteosarcoma cells. TSAIII was demonstrated to significantly inhibit the pulmonary metastasis formation of human osteosarcoma cells in vivo in metastasis animal models. These findings reveal the inhibitory effects of TSAIII on the metastasis progression of human osteosarcoma cells and the regulation of integrin-αVβ3-FAK-Src and TESK1/p-cofilin mediated cytoskeletal F-actin pathway. Therefore, TSAIII might represent a novel strategy for the auxiliary treatment of human osteosarcoma cells.
Effect of Methyl–β–Cyclodextrin and Trehalose on the Freeze–Drying and Spray–Drying of Sericin for Cosmetic Purposes
Authors: Giovannelli Lorella , Milanesi Andrea , Ugazio Elena , Fracchia Letizia , Segale Lorena
Published: March 2021

Sericin is a protein extracted from Bombyx mori silk cocoons. Over the last decade, this wastewater product of the textile industry has shown many interesting biological properties. This protein is widely used in the cosmetic and biomedical fields. In this study, sericin has been obtained via a High–Temperature High–Pressure degumming process, and was dried using the freeze–drying (fd) and spray–drying (sd) techniques. Proteins tend to collapse during drying, hence, sericin has been dried in the presence of two selected carrier agents: methyl–β–cyclodextrin and trehalose. The obtained powders have been analyzed using thermal investigation, microscopy (optical, SEM), and granulometric and spectroscopic analyses. Moreover, the percentage yield of the spray–drying process has been calculated. Both the agents were able to significantly improve the drying process, without altering the physico–chemical properties of the protein. In particular, the co–spray–drying of sericin with methyl–β–cyclodextrin and trehalose gave good process yields and furnished a powder with low moisture content and handling properties that are better than those of the other studied dried products. These characteristics seem to be appropriate and fruitful for the manufacturing of cosmetic raw materials.
Old Drug, New Trick: Tilorone, a Broad-Spectrum Antiviral Drug as a Potential Anti-Fibrotic Therapeutic for the Diseased Heart
Authors: Horlock Duncan , Kaye David M. , Winbanks Catherine E. , Gao Xiao-Ming , Kiriazis Helen , Donner Daniel G. , Gregorevic Paul , McMullen Julie R. , Bernardo Bianca C.
Published: March 2021

Cardiac fibrosis is associated with most forms of cardiovascular disease. No reliable therapies targeting cardiac fibrosis are available, thus identifying novel drugs that can resolve or prevent fibrosis is needed. Tilorone, an antiviral agent, can prevent fibrosis in a mouse model of lung disease. We investigated the anti-fibrotic effects of tilorone in human cardiac fibroblasts in vitro by performing a radioisotopic assay for [3H]-proline incorporation as a proxy for collagen synthesis. Exploratory studies in human cardiac fibroblasts treated with tilorone (10 µM) showed a significant reduction in transforming growth factor-β induced collagen synthesis compared to untreated fibroblasts. To determine if this finding could be recapitulated in vivo, mice with established pathological remodelling due to four weeks of transverse aortic constriction (TAC) were administered tilorone (50 mg/kg, i.p) or saline every third day for eight weeks. Treatment with tilorone was associated with attenuation of fibrosis (assessed by Masson’s trichrome stain), a favourable cardiac gene expression profile and no further deterioration of cardiac systolic function determined by echocardiography compared to saline treated TAC mice. These data demonstrate that tilorone has anti-fibrotic actions in human cardiac fibroblasts and the adult mouse heart, and represents a potential novel therapy to treat fibrosis associated with heart failure.
DNA Double-Strand Breaks Affect Chromosomal Rearrangements during Methotrexate-Mediated Gene Amplification in Chinese Hamster Ovary Cells
Authors: Baik Jong , Han Hye-Jin , Lee Kelvin
Published: March 2021

Methotrexate (MTX)-mediated gene amplification has been widely used in Chinese hamster ovary (CHO) cells for the biomanufacturing of therapeutic proteins. Although many studies have reported chromosomal instability and extensive chromosomal rearrangements in MTX-mediated gene-amplified cells, which may be associated with cell line instability issues, the mechanisms of chromosomal rearrangement formation remain poorly understood. We tested the impact of DNA double-strand breaks (DSBs) on chromosomal rearrangements using bleomycin, a DSB-inducing reagent. Bleomycin-treated CHO-DUK cells, which are one of the host cell lines deficient in dihydrofolate reductase (Dhfr) activity, exhibited a substantial number of cells containing radial formations or non-radial formations with chromosomal rearrangements, suggesting that DSBs may be associated with chromosomal rearrangements. To confirm the causes of DSBs during gene amplification, we tested the effects of MTX treatment and the removal of nucleotide base precursors on DSB formation in Dhfr-deficient (i.e., CHO-DUK) and Dhfr-expressing (i.e., CHO-K1) cells. Immunocytochemistry demonstrated that MTX treatment did not induce DSBs per se, but a nucleotide shortage caused by the MTX-mediated inhibition of Dhfr activity resulted in DSBs. Our data suggest that a nucleotide shortage caused by MTX-mediated Dhfr inhibition in production cell lines is the primary cause of a marked increase in DSBs, resulting in extensive chromosomal rearrangements after gene amplification processes.
LipoParticles: Lipid-Coated PLA Nanoparticles Enhanced In Vitro mRNA Transfection Compared to Liposomes
Authors: Ayad Camille , Libeau Pierre , Lacroix-Gimon Céline , Ladavière Catherine , Verrier Bernard
Published: March 2021

The approval of two mRNA vaccines as urgent prophylactic treatments against Covid-19 made them a realistic alternative to conventional vaccination methods. However, naked mRNA is rapidly degraded by the body and cannot effectively penetrate cells. Vectors capable of addressing these issues while allowing endosomal escape are therefore needed. To date, the most widely used vectors for this purpose have been lipid-based vectors. Thus, we have designed an innovative vector called LipoParticles (LP) consisting of poly(lactic) acid (PLA) nanoparticles coated with a 15/85 mol/mol DSPC/DOTAP lipid membrane. An in vitro investigation was carried out to examine whether the incorporation of a solid core offered added value compared to liposomes alone. To that end, a formulation strategy that we have named particulate layer-by-layer (pLbL) was used. This method permitted the adsorption of nucleic acids on the surface of LP (mainly by means of electrostatic interactions through the addition of LAH4-L1 peptide), allowing both cellular penetration and endosomal escape. After a thorough characterization of size, size distribution, and surface charge— and a complexation assessment of each vector—their transfection capacity and cytotoxicity (on antigenic presenting cells, namely DC2.4, and epithelial HeLa cells) were compared. LP have been shown to be significantly better transfecting agents than liposomes through pLbL formulation on both HeLa and DC 2.4 cells. These data illustrate the added value of a solid particulate core inside a lipid membrane, which is expected to rigidify the final assemblies and makes them less prone to early loss of mRNA. In addition, this assembly promoted not only efficient delivery of mRNA, but also of plasmid DNA, making it a versatile nucleic acid carrier that could be used for various vaccine applications. Finally, if the addition of the LAH4-L1 peptide systematically leads to toxicity of the pLbL formulation on DC 2.4 cells, the optimization of the nucleic acid/LAH4-L1 peptide mass ratio becomes an interesting strategy—essentially reducing the peptide intake to limit its cytotoxicity while maintaining a relevant transfection efficiency.
Surfactants, Nanomedicines and Nanocarriers: A Critical Evaluation on Clinical Trials
Authors: Dri Diego Alejandro , Marianecci Carlotta , Carafa Maria , Gaucci Elisa , Gramaglia Donatella
Published: March 2021

Advances, perspectives and innovation in drug delivery have increased in recent years; however, there is limited information available regarding the actual presence of surfactants, nanomedicines and nanocarriers in investigational medicinal products submitted as part of a request for authorization of clinical trials, particularly for those authorized in the European Economic Area. We retrieve, analyze and report data available at the Clinical Trial Office of the Italian Medicines Agency (AIFA), increasing the transparency and availability of relevant information. An analysis of quality documentation submitted along with clinical trials authorized by the AIFA in 2018 was carried out, focusing on the key terms “surfactant”, “nanomedicine” and “nanocarrier”. Results suggest potential indications and inputs for further reflection and actions for regulators to actively and safely drive innovation from a regulatory perspective and to transpose upcoming evolution of clinical trials within a strong regulatory framework.
Novel PEGylated Lipid Nanoparticles Have a High Encapsulation Efficiency and Effectively Deliver MRTF-B siRNA in Conjunctival Fibroblasts
Authors: Sanghani Amisha , Kafetzis Konstantinos N. , Sato Yusuke , Elboraie Salsabil , Fajardo-Sanchez Julia , Harashima Hideyoshi , Tagalakis Aristides D. , Yu-Wai-Man Cynthia
Published: March 2021

The master regulator of the fibrosis cascade is the myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway, making it a key target for anti-fibrotic therapeutics. In the past, inhibitors and small interfering RNAs (siRNAs) targeting the MRTF-B gene have been deployed to counter fibrosis in the eye, with the latter showing promising results. However, the biggest challenge in implementing siRNA therapeutics is the method of delivery. In this study, we utilised the novel, pH-sensitive, cationic lipid CL4H6, which has previously demonstrated potent targeting of hepatocytes and endosomal escape, to safely and efficiently deliver an MRTF-B siRNA into human conjunctival fibroblasts. We prepared two lipid nanoparticle (LNP) formulations, incorporating targeting cleavable peptide cY in one of them, and measured their physicochemical properties and silencing effect in human conjunctival fibroblasts. Both proved to be non-cytotoxic at a concentration of 50 nM and effectively silenced the MRTF-B gene in vitro, with the targeting cleavable peptide not affecting the silencing efficiency [LNP with cY: 62.1% and 81.5% versus LNP without cY: 77.7% and 80.2%, at siRNA concentrations of 50 nM (p = 0.06) and 100 nM (p = 0.09), respectively]. On the other hand, the addition of the targeting cleavable peptide significantly increased the encapsulation efficiency of the LNPs from 92.5% to 99.3% (p = 0.0005). In a 3D fibroblast-populated collagen matrix model, both LNP formulations significantly decreased fibroblast contraction after a single transfection. We conclude that the novel PEGylated CL4H6-MRTF-B siRNA-loaded LNPs represent a promising therapeutic approach to prevent conjunctival fibrosis after glaucoma filtration surgery.
Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation
Authors: Tsai Tung-Hu , Chen Yu-Jen , Wang Li-Ying , Hsieh Chen-Hsi
Published: March 2021

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).
Photothermal, Photoelectric, and Photothermoelectric Effects in Bi-Sb Thin Films in the Terahertz Frequency Range at Room Temperature
Authors: Khodzitsky Mikhail K. , Demchenko Petr S. , Zykov Dmitry V. , Zaitsev Anton D. , Makarova Elena S. , Tukmakova Anastasiia S. , Tkhorzhevskiy Ivan L. , Asach Aleksei V. , Novotelnova Anna V. , Kablukova Natallya S.
Published: March 2021

The terahertz frequency range is promising for solving various practically important problems. However, for the terahertz technology development, there is still a problem with the lack of affordable and effective terahertz devices. One of the main tasks is to search for new materials with high sensitivity to terahertz radiation at room temperature. Bi1−xSbx thin films with various Sb concentrations seem to be suitable for such conditions. In this paper, the terahertz radiation influence onto the properties of thermoelectric Bi1−xSbx 200 nm films was investigated for the first time. The films were obtained by means of thermal evaporation in vacuum. They were affected by terahertz radiation at the frequency of 0.14 terahertz (THz) in the presence of thermal gradient, electric field or without these influences. The temporal dependencies of photoconductivity, temperature difference and voltage drop were measured. The obtained data demonstrate the possibility for practical use of Bi1−xSbx thin films for THz radiation detection. The results of our work promote the usage of these thermoelectric materials, as well as THz radiation detectors based on them, in various areas of modern THz photonics.
Insights into the Thermo-Mechanical Treatment of Brewers’ Spent Grain as a Potential Filler for Polymer Composites
Authors: Hejna Aleksander , Marć Mariusz , Kowalkowska-Zedler Daria , Pladzyk Agnieszka , Barczewski Mateusz
Published: March 2021

This paper investigated the impact of twin-screw extrusion parameters on the properties of brewers’ spent grain. The chemical structure, antioxidant activity, particle size, and color properties, as well as the emission of volatile organic compounds during extrusion, were investigated. The main compounds detected in the air during modifications were terpenes and terpenoids, such as α-pinene, camphene, 3-carene, limonene, or terpinene. They could be considered as a potential threat to human health and the environment. Changes in the chemical structure, antioxidant activity, and color of materials after modification indicated the Maillard reactions during extrusion, which resulted in the generation of melanoidins, especially at higher temperatures. This should be considered an exciting feature of this treatment method because modified brewers’ spent grain may improve the thermooxidative stability of polymer materials. Moreover, the impact of the brewers’ spent grain particle size on color and browning index used to determine the melanoidins content was investigated. The presented results show that proper adjustment of extrusion parameters enables the preparation of brewers’ spent grain with the desired appearance and chemical properties, which could maximize the efficiency of the modification process.
Synergistic Effects of Graphene and Ammonium Polyphosphate Modified with Vinyltrimethoxysilane on the Properties of High-Impact Polystyrene Composites
Authors: Shi Xianghui , Pan Yong , Wang Yuguo , Jia Zhimeng , Chen Tingting , Gong Junhui , Jiang Juncheng
Published: March 2021

Ammonium polyphosphate (APP) was modified with a silane coupling agent (vinyltrimethoxysilane, Si-171), and then the synergistic flame retarding effect of graphene and surface-modified APP (APP@Si-171) on high-impact polystyrene (HIPS) was investigated. Surface modification and thermal stability characterization of APP were analyzed by Fourier transform infrared spectroscopy (FTIR), energy dispersive spectrometer (EDS), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The results showed that surface-modified APP (APP@Si-171) exhibited significantly better dispersion and less agglomeration tendencies compared with pure APP. A series of target HIPS composites containing different mass fractions of the two flame retardants were prepared by melt blending. TGA and cone calorimeter tests (CCT) were conducted to quantitatively investigate the thermal and flammability properties of the composites, respectively. Results from TGA and CCT demonstrated that the addition of the flame retardants delayed the onset and peak temperatures in differential thermogravimetry (DTG) curves and weakened the peak heat release rate (PHRR) and total heat release (THR). Moreover, the synergistic effect index (SE) was employed to quantify the synergistic behavior between the two fillers, and the results showed that APP@Si-171 and graphene had a synergistic effect on improving the thermal stability and flame retardancy of HIPS.
Complications of Poly-l-Lactic Acid and Polyglycolic Acid (PLLA/PGA) Osteosynthesis Systems for Maxillofacial Surgery: A Retrospective Clinical Investigation
Authors: Matsuda Yuhei , Karino Masaaki , Okui Tatsuo , Kanno Takahiro
Published: March 2021

Two second-generation PLLA/PGA bioresorbable osteosynthetic plate systems for oral and maxillofacial surgery are available in Japan. The two systems have different PLLA-PGA component ratios (RapidSorb®, 85:15; Lactosorb®, 82:18) and plate and screw shapes. We conducted a retrospective study to compare our clinical evaluation and examine the incidence of postoperative complications between the two plate systems. A retrospective survey was conducted in 148 patients (midfacial fracture/trauma (68.2%) and dentofacial deformity patients (31.8%); males (54.7%); median age, 37.5 years) treated using maxillofacial osteosynthetic plate systems. The complications included plate exposure (7.4%), infection, (2.7%), and plate breakage (0.7%). Multivariate logistic regression analysis showed a significant correlation between sex (female), plate system (Lactosorb®), number of plates, and pyriform aperture and periorbital sites of plate placement (p < 0.05). Additionally, the propensity score-adjusted model showed a significant correlation between Lactosorb® and postoperative complications (odds ratio 1.007 (95% confidence interval, 1.001–1.055), p < 0.01). However, the two plate systems showed a low incidence rate of complications, and the plate integration and survivability were similar using 2.0-mm or 1.5-mm resorbable plate regardless of the plate system. Our findings suggest that female sex and a greater number of plates are risk factors for postoperative complications, whereas pyriform aperture and periorbital plate placements reduce the risk.
By-Products from Food Industry as a Promising Alternative for the Conventional Fillers for Wood–Polymer Composites
Authors: Hejna Aleksander , Korol Jerzy , Kosmela Paulina , Kuzmin Anton , Piasecki Adam , Kulawik Arkadiusz , Chmielnicki Błażej
Published: March 2021

The present paper describes the application of two types of food-industry by-products, brewers’ spent grain (BSG), and coffee silverskin (ŁK) as promising alternatives for the conventional beech wood flour (WF) for wood–polymer composites. The main goal was to investigate the impact of partial and complete WF substitution by BSG and ŁK on the processing, structure, physicochemical, mechanical, and thermal properties of resulting composites. Such modifications enabled significant enhancement of the melt flowability, which could noticeably increase the processing throughput. Replacement of WF with BSG and ŁK improved the ductility of composites, which affected their strength however. Such an effect was attributed to the differences in chemical composition of fillers, particularly the presence of proteins and lipids, which acted as plasticizers. Composites containing food-industry by-products were also characterized by the lower thermal stability compared to conventional WF. Nevertheless, the onset of decomposition exceeding 215 °C guarantees a safe processing window for polyethylene-based materials.
Hydroponic Farm Wastewater Treatment Using an Indigenous Consortium
Authors: Delrue Florian , Ribeiro de Jesus Cerqueira Matheus , Compadre Ana , Alvarez Pablo , Fleury Gatien , Escoffier Camille , Sassi Jean-François
Published: March 2021

Hydroponic farms produce wastewater that need to be treated before being released into the environment. A three-step screening process (microplate, batch, and semi-continuous flasks experiments) initially designed to select an efficient microalgae strain allowed the isolation of a consortium that naturally developed in the hydroponic farm wastewater. During the non-optimized semi-continuous experiments, the best performing microalgae strain, Scenedesmus obliquus UTEX393 and the wastewater-born consortium cultures achieved good average linear growth rate (0.186 and 0.198/d, respectively) and high average nitrogen removal rates (23.5 mgN/L/d and 21.9 mgN/L/d, respectively). Phosphorus removal was very high probably due to precipitation. An integrated process was designed to treat the hydroponic farm wastewater using the wastewater-born consortium. Despite relatively low coagulation efficiencies in the preliminary tests, when integrated in a continuous process, chitosan was efficient to harvest the naturally wastewater-born consortium. The process was also efficient for removing nitrate and phosphate in less than seven days (average removal of 98.2 and 87.1% for nitrate and phosphate, respectively). These very promising results will help to define a pre-industrial pilot process.
The Relationship of Moisture and Temperature to the Concentration of O2 and CO2 during Biodrying in Semi-Static Piles
Authors: Contreras-Cisneros Rosa María , Orozco-Álvarez Carlos , Piña-Guzmán Ana Belem , Ballesteros-Vásquez Luis Carlos , Molina-Escobar Liliana , Alcántara-García Sandra Sharo , Robles-Martínez Fabián
Published: March 2021

Biodrying was studied over 46 days in two piles (P1 and P2) composed of orange peel and two structuring materials (mulch: P1; sugarcane bagasse: P2). The oxygen and carbon dioxide levels were recorded at different depths (0.1 to 0.6 m). From the beginning to days 33–35 the drying was carried out by a combination of microbial heat, convection, and solar irradiance; moisture reached 30%, corresponding to a water activity (aw) of 0.88–0.9, which was insufficient to maintain microbial activity. Additionally, the O2 and CO2 levels (21% and 0%, respectively) evidenced the end of the biological phase of the process. After day 35, the drying occurred only by convection and solar irradiance. At the end, moisture reached 14% (P1) and 12% (P2), showing that the turning frequency, as well as the type and proportion of the structuring materials, were adequate and significantly influenced moisture reduction, allowing the aeration necessary for biodrying. At the end, a material with an average calorific value of 15,500 kJ/kg was obtained, comparable to wood and other fuels obtained from orange peel, making the biodrying process a suitable option for the stabilization and energy recovery of agricultural and agro-industrial waste with high moisture content.
Fe2+ and UV Catalytically Enhanced Ozonation of Selected Environmentally Persistent Antibiotics
Authors: Gotvajn Andreja Žgajnar , Rozman Ula , Antončič Teja , Urbanc Teja , Vrabeľ Martin , Derco Ján
Published: March 2021

The aim of the study was to determine oxidation potential of selected persistent, environmentally relevant antibiotics (Amoxicillin, Levofloxacin, and their mixture with Vancomycin) to reduce their environmental emissions. Ozonation (O3) and indirect ozonation at pH 9.5 (O3/pH9.5) were catalytically enhanced by addition of Fe2+ (O3/Fe2+) and photocatalytic ozonation in combination with Fe2+ and UV-A black light (O3/Fe2+/UV) at two temperatures using total organic carbon (TOC) and chemical oxygen demand (COD) to identify formation of by-products. Oxidative degradation followed pseudo-first order consecutive reactions. Initial phase of oxidation was more intensive than mineralisation at 21 and 40 °C: up to 57.3% and 69.2%, respectively. After 120 min mineralization at 21 °C was up to 64.9% while at 40 °C it was up to 84.6%. Oxidation reached up to 86.6% and 93.4% at 21 °C and 40 °C, respectively. The most efficient processes were indirect ozonation at pH 9.5 (O3/pH9.5) (up to 93.4%) and photocatalytic enhanced ozonation with Fe2+ and UV-A black light (O3/Fe2+/UV) (up to 89.8%). The lowest efficiency was determined in experiments with direct ozonation (up to 75.5%). Amoxicillin was the only one completely mineralised. Study confirmed that ozonation with addition of Fe2+ and UV radiation has the potential to improve efficiency of the antibiotic-removal processes. Further experiments varying amounts of Fe2+ and other experimental conditions should be accomplished to set up more general methodological approach for reduction of antibiotics emissions.