bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Volatiles in the Evolution of a Carbonatitic Melt in Peridotitic Mantle: Experimental Constraints at 6.3 GPa and 1200–1450 °C
Authors: Kruk Aleksei , Sokol Alexander
Published: April 2022

Reconstruction of the mechanisms of carbonatitic melt evolution is extremely important for understanding metasomatic processes at the base of the continental lithospheric mantle (CLM). We have studied the interaction between garnet lherzolite and a carbonatitic melt rich in molecular CO2 and H2O in experiments at 6.3 GPa and 1200–1450 °C. The interaction with garnet lherzolite and H2O-bearing carbonatite melt leads to wehrlitization of lherzolite, without its carbonation. Introduction of molecular CO2 and H2O initiates carbonation of olivine and clinopyroxene with the formation of orthopyroxene and magnesite. Partial carbonation leads to the formation of carbonate–silicate melts that are multiphase saturated with garnet harzburgite. Upon complete carbonation of olivine already at 1200 °C, melts with 27–31 wt% SiO2 and MgO/CaO ≈ 1 are formed. At 1350–1450 °C, the interaction leads to an increase in the melt fraction and the MgO/CaO ratio to 2–4 and a decrease in the SiO2 concentration. Thus, at conditions of a thermally undisturbed CLM base, molecular CO2 and H2O dissolved in metasomatic agents, due to local carbonation of peridotite, can provide the evolution of agent composition from carbonatitic to hydrous silicic, i.e., similar to the trends reconstructed for diamond-forming high density fluids (HDFs) and genetically related proto-kimberlite melts.
Geochemistry of Early Diagenesis in Sediments of Russian Arctic Glacial Lakes (Norilo–Pyasinskaya Water System)
Authors: Maltsev Anton E. , Krivonogov Sergey K. , Vosel Yuliya S. , Bychinsky Valery A. , Miroshnichenko Leonid V. , Shavekin Alexei S. , Leonova Galina A. , Solotchin Paul A.
Published: April 2022

The Russian Arctic region is lacking in studies on geochemical changes reflecting early sediment diagenesis in lake environments. The paper presents new data on the compositions of bottom sediments and sediment pore water from two lakes of the Norilo–Pyasinskaya water system in Arctic Siberia. Lakes Pyasino and Melkoye occupy basins left by glaciers that originated from the Putorana Plateau during the Last Glacial Maximum (LGM). Clayey sediments were continuously deposited in the lakes, and the depositional environment has changed only slightly for the last ca. 20 ka. Two sediment cores with lengths of 4.0 and 3.2 m were collected in Lakes Pyasino and Melkoye, respectively, with a Livingstone-type piston corer providing undisturbed, stratigraphically consistent sedimentary sequences. Their analyses revealed a change from oxidized to reduced conditions at a depth of ~10 cm. The concentrations of Ca2+, Mg2+, Na+, and K+, as well as the HCO3−/Ca2+ ratio in pore water, showed a depthward increase indicating the progressive degradation of organic matter. Another trend was the gradual decrease in SO42− alongside increasing HCO3−/SO42− caused by bacterial sulfate reduction, although this was rather weak, judging by the low concentrations of S (II) bound to Fe-sulfides, H2S, etc. Additionally, the microbial digestion of organic matter caused a release of its mobile components, which led to the enrichment of the water in NO3−, PO43−, and DOC. Most of the analyzed elements (Al, B, Ba, Co, Cu, Mo, Ni, Si, Sr, V, and Zn) reach higher concentrations in the pore water than in the lake water above the water-sediment boundary, which is evidence of diagenetic processes. As a result of redox change, immobile Fe (III) and Mn (IV) natural oxides were reduced to mobile Fe (II) and Mn (II) species and migrated from the solid phase to the pore water, and eventually precipitated as authigenic Fe sulfides and Mn carbonates. The results are useful for better understanding the early diagenesis processes in different geographical settings over the huge Eurasian continent.
The Potential Antipyretic Mechanism of Ellagic Acid with Brain Metabolomics Using Rats with Yeast-Induced Fever
Authors: Xie Fengfeng , Xu Liba , Zhu Hua , Chen Yaling , Li Yinlan , Nong Lizhen , Zeng Yanfang , Cen Sijie
Published: April 2022

Fever is caused by an increase in the heat production process when the body is under the action of a heat source or the dysfunction of the temperature center. Ellagic acid (EA) is a polyphenol dilactone that has anti-inflammatory, anti-tumor, and antioxidant activities. Male Sprague-Dawley rats were injected yeast to reproduce an experimental fever model (150 ± 20 g), and the rectal temperature and its change values were subsequently taken 19 h later; the excessive production of interleukin-1β (IL-1β) and prostaglandin2 (PGE2) induced by yeast was regulated to normal by EA administration. Rat brain metabolomics investigation of pyrexia and the antipyretic anti-inflammatory effect of EA was performed using Ultra-High-Performance Liquid Chromatography–Mass spectrometry (UPLC-MS). Twenty-six metabolites, as potential biomarkers, significantly altered metabolites that were found in pyretic rats, and eleven metabolites, as biomarkers of the antipyretic mechanism of EA, were significantly adjusted by EA to help relieve pyrexia, which was involved in glycerophospholipid metabolism and sphingolipid metabolism, etc. In conclusion, potential metabolic biomarkers in the brain shed light on the mechanism of EA’s antipyretic effects, mainly involving metabolic pathways, which may contribute to a further understanding of the therapeutic mechanisms of fever and therapeutic mechanism of EA.
Videogame-Based Learning: A Comparison of Direct and Indirect Effects across Outcomes
Authors: Sanchez Diana R.
Published: April 2022

Videogame research needs to identify how game features impact learning outcomes. This study explored the impact of the game feature–human interaction on training outcomes (i.e., affective states and declarative knowledge), and examined possible mechanisms (i.e., perceived value and active learning) that mediate this relationship. Participants included 385 undergraduate students: 122 trained alone and 263 trained with a team. All participants completed a computer-based training with four learning objectives (i.e., accessing the game, using the main controls, playing the game scenarios, knowing the game stations) prior to playing the game. After accounting for the indirect effects in the model, human interaction (i.e., playing with a team) had a significant direct effect on affective states, but not declarative knowledge. Learners who trained with a team reported greater positive affective states (indicated by psychological meaning, perceived enjoyment, motivation, and emotional engagement), but no difference in declarative knowledge (i.e., participants knowledge of team roles and responsibilities). Further analyses showed game-based training with a team impacted the affective states of learners through mechanisms of perceived value and active learning, while only active learning mediated the relationship between human interaction and declarative knowledge.
Acid-Assisted Ball Mill Synthesis of Carboxyl-Functional-Group-Modified Prussian Blue as Sodium-Ion Battery Cathode
Authors: Luo Yu , Peng Jiayu , Yin Shengming , Xue Lihong , Yan Youwei
Published: April 2022

Prussian blue attracts the attention of many researchers as a promising candidate for use in sodium-ion battery cathodes due to its open frameworks and high working potential. However, the interstitial water in its crystal structure and its poor electronic conductivity limits its performance in practical sodium-ion batteries. Here, acid-assisted ball milling synthesis was employed as a versatile method for the production of surface-modified Prussian blue. With (CH3COO)2Fe being used as the raw material, the Prussian blue produced using ball milling synthesis was modified by the carboxyl functional group on its surface, which resulted in lower interstitial water content and enhanced electrochemical cycling performance. In addition, ball milling synthesis provided the as-prepared Prussian blue with a large surface area, improving its electrochemical rate performance. When used as the cathode of sodium-ion batteries, as-prepared Prussian blue delivered a specific capacity of 145.3 mAh g−1 at 0.2 C and 113.7 mAh g−1 at 1 C, maintaining 54.5% of the initial capacity after 1000 cycles at 1 C (1 C = 170 mA g−1). Furthermore, a solid-state sodium-ion battery was mounted, with as-prepared Prussian blue being employed as the cathode and Na metal as the anode, which delivered a high specific capacity of 128.7 mAh g−1 at 0.2 C. The present study put forward an effective solution to overcome the limitations of Prussian blue for its commercial application.
Impact of Nano- and Micro-Sized Chromium(III) Particles on Cytotoxicity and Gene Expression Profiles Related to Genomic Stability in Human Keratinocytes and Alveolar Epithelial Cells
Authors: Schumacher Paul , Fischer Franziska , Sann Joachim , Walter Dirk , Hartwig Andrea
Published: April 2022

Exposure to Cr(VI) compounds has been consistently associated with genotoxicity and carcinogenicity, whereas Cr(III) is far less toxic, due to its poor cellular uptake. However, contradictory results have been published in relation to particulate Cr2O3. The aim of the present study was to investigate whether Cr(III) particles exerted properties comparable to water soluble Cr(III) or to Cr(VI), including two nano-sized and one micro-sized particles. The morphology and size distribution were determined by TEM, while the oxidation state was analyzed by XPS. Chromium release was quantified via AAS, and colorimetrically differentiated between Cr(VI) and Cr(III). Furthermore, the toxicological fingerprints of the Cr2O3 particles were established using high-throughput RT-qPCR and then compared to water-soluble Cr(VI) and Cr(III) in A549 and HaCaT cells. Regarding the Cr2O3 particles, two out of three exerted only minor or no toxicity, and the gene expression profiles were comparable to Cr(III). However, one particle under investigation released considerable amounts of Cr(VI), and also resembled the toxicity profiles of Cr(VI); this was also evident in the altered gene expression related to DNA damage signaling, oxidative stress response, inflammation, and cell death pathways. Even though the highest toxicity was found in the case of the smallest particle, size did not appear to be the decisive parameter, but rather the purity of the Cr(III) particles with respect to Cr(VI) content.
CTAB Enhanced Room-Temperature Detection of NO2 Based on MoS2-Reduced Graphene Oxide Nanohybrid
Authors: Li Wenbo , Li Hao , Qian Rong , Zhuo Shangjun , Ju Pengfei , Chen Qiao
Published: April 2022

A new NO2 nanohybrid of a gas sensor (CTAB-MoS2/rGO) was constructed for sensitive room-temperature detection of NO2 by 3D molybdenum disulfide (MoS2) and reduced graphene oxide (rGO), assisted with hexadecyl trimethyl ammonium bromide (CTAB). In comparison with MoS2 and MoS2/rGO, the BET and SEM characterization results depicted the three-dimensional structure of the CTAB-MoS2/rGO nanohybrid, which possessed a larger specific surface area to provide more active reaction sites to boost its gas-sensing performance. Observations of the gas-sensing properties indicated that the CTAB-MoS2/rGO sensor performed a high response of 45.5% for 17.5 ppm NO2, a remarkable selectivity of NO2, an ultra-low detection limit of 26.55 ppb and long-term stability for a 30-day measurement. In addition, the response obtained for the CTAB-MoS2/rGO sensor was about two to four times that obtained for the MoS2/rGO sensor and the MoS2 sensor toward 8 ppm NO2, which correlated with the heterojunction between MoS2 and rGO, and the improvement in surface area and conductivity correlated with the introduction of CTAB and rGO. The excellent performance of the CTAB-MoS2/rGO sensor further suggested the advantage of CTAB in assisting a reliable detection of trace NO2 and an alternative method for highly efficiently detecting NO2 in the environment.
One-Step Hydrothermal Synthesis of Nanostructured MgBi2O6/TiO2 Composites for Enhanced Hydrogen Production
Authors: Xu Feng , Hu Chaohao , Zhu Di , Wang Dianhui , Zhong Yan , Tang Chengying , Zhou Huaiying
Published: April 2022

A highly efficient MgBi2O6 (MBO)/TiO2 heterostructured photocatalyst for the evolution of H2 was successfully prepared using a one-step hydrothermal method. The phase structure, microstructure and optical properties of the MBO/TiO2 composites were investigated by various experimental techniques. A series of H2 production experiments were performed under visible light. The measured results indicated that the nanostructured MBO/TiO2 composite, with a stoichiometric molar ratio of MBO:TiO2 = 0.2%, displayed the best H2 production rate of 3413 μmol h−1 g−1. The excellent photocatalytic performance of the obtained composite material was due to the heterojunction formed between MBO and TiO2, which reduced the charge transfer resistance and accelerated the separation efficiency of the photogenerated electron–hole pairs. The reaction mechanism was also discussed in detail.
Multifunctional Magnetic Nanowires and Nanotubes
Authors: Proenca Mariana P.
Published: April 2022

Low-dimensional magnetic nanostructures are promising materials for applications in many different fields, for example, in medicine (for drug delivery, biomimetic devices, contrast agents in magnetic resonance imaging, hyperthermia, cell manipulation, etc [...]
Tannic Acid Coating Augments Glioblastoma Cellular Uptake of Magnetic Nanoparticles with Antioxidant Effects
Authors: Świętek Małgorzata , Ma Yunn-Hwa , Wu Nian-Ping , Paruzel Aleksandra , Tokarz Waldemar , Horák Daniel
Published: April 2022

Coating of nanoparticles with gallates renders them antioxidant and enhances cellular internalization. In this study, (amino)silica magnetic particles modified with tannic acid (TA) and optionally with chitosan (CS) were developed, and their physicochemical properties and antioxidant activity were evaluated. The results demonstrated that the TA-modified aminosilica-coated particles, as well as the silica-coated particles with a double TA layer, exhibited high antioxidant activity, whereas the silica-coated particles with no or only a single TA layer were well-internalized by LN-229 cells. In addition, a magnet placed under the culture plates greatly increased the cellular uptake of all TA-coated magnetic nanoparticles. The coating thus had a considerable impact on nanoparticle–cell interactions and particle internalization. The TA-coated magnetic nanoparticles have great potential as intracellular carriers with preserved antioxidant activity.
Damage Accumulation Phenomena in Multilayer (TiAlCrSiY)N/(TiAlCr)N, Monolayer (TiAlCrSiY)N Coatings and Silicon upon Deformation by Cyclic Nanoindentation
Authors: Kovalev Anatoly I. , Vakhrushev Vladimir O. , Beake Ben D. , Konovalov Egor P. , Wainstein Dmitry L. , Dmitrievskii Stanislav A. , Fox-Rabinovich German S. , Veldhuis Stephen
Published: April 2022

The micromechanism of the low-cycle fatigue of mono- and multilayer PVD coatings on cutting tools was investigated. Multilayer nanolaminate (TiAlCrSiY)N/(TiAlCr)N and monolayer (TiAlCrSiY)N PVD coatings were deposited on the cemented carbide ball nose end mills. Low-cycle fatigue resistance was studied using the cyclic nanoindentation technique. The obtained results were compared with the behaviour of the polycrystalline silicon reference sample. The fractal analysis of time-resolved curves for indenter penetration depth demonstrated regularities of damage accumulation in the coatings at the early stage of wear. The difference in low-cycle fatigue of the brittle silicon and nitride wear-resistant coatings is shown. It is demonstrated that when distinguished from the single layer (TiAlCrSiY)N coating, the nucleation and growth of microcracks in the multilayer (TiAlCrSiY)N/(TiAlCr)N coating is accompanied by acts of microplastic deformation providing a higher fracture toughness of the multilayer nanolaminate (TiAlCrSiY)N/(TiAlCr)N.
Transverse Magnetoresistance Induced by the Nonuniformity of Superconductor
Authors: Zhao Duo , Zhao Zhiyuan , Xu Yaohan , Tong Shucheng , Lu Jun , Wei Dahai
Published: April 2022

The transverse magnetoresistance (Rxy) caused by inhomogeneous superconductivity is symmetric about the magnetic field around the critical magnetic field region. This has caused many disturbances during the study of vortex dynamics by Hall signals. Here, we found that the peak of Rxy measured in our samples was induced by the nonuniformity of the superconductors. The peak values of Rxy decrease with increasing applied current and temperature, which can be described by the theory of superconductivity inhomogeneity. Based on this, we have proposed and verified a method for separating the transverse voltage caused by the inhomogeneity of superconductivity. Additionally, quantity ΔB(0) can also be used to characterize the uniformity of superconductivity. This clears up the obstacles for studying vortex motion dynamics and reveals a way to study the influence of the domain wall on superconductivity.
Diversity of Metal—Fullerene Framework Structures Regulated by Metal Salts
Authors: Wang Jingjing , Yao Yang-Rong , Yang Shaoting , Zhou Xinyi , Yu Ao , Peng Ping , Li Fang-Fang
Published: April 2022

Taking into account the diversity of fullerene ligands and metal salts, metal–fullerene frameworks (MFFs) present a variety of structures. Currently, the structural control of MFFs mainly relies on the design and synthesis of fullerene ligands, while the influence of metal building units on the structures has been rarely studied. The present work represents a systematical investigation of fullerene-linked supramolecular architectures incorporating different metal salts. Treatment of a bidentate N,N-donors fullerene ligand (L1) with six metal salts ([Zn(NO3)2·6H2O, Cd(NO3)2·4H2O, Cu(NO3)2·3H2O, Cu(OAc)2·H2O, FeCl2·4H2O and FeCl3·6H2O]) produced six one-dimensional MFFs, i.e., ZnL1(NO3)2(H2O)2 (1), CdL1(NO3)2 (2), Cu(L1)(H2O)2(NO3)2 (3), CuL1(OAc)(CH3O) (4), FeL1Cl2 (5) and FeL1Cl2(FeCl4) (6). Compounds 1–3, built with nitrates with different metal centers (M(NO3)2, M = Zn, Cd, Cu), present a 1D stair-like, 1D zigzag, and 1D linear chain structure, respectively. Compound 4, synthesized with another Cu(II) salt, Cu(OAc)2, displays a dinuclear Cu-Cu connected 1D stair-like chain structure, rather than the single Cu linked 1D linear chain obtained from Cu(NO3)2. Compounds 5 and 6, assembled from iron chloride of different oxidation states (Fe(II)Cl2 and Fe(III)Cl3) reveal a 1D zigzag and a 1D stair-like chain structure, respectively. The results demonstrate the significant influences of metal salts on the structures of metal–fullerene frameworks.
Differentiation of the Nutritional Risk of Polish Elderly People According to Selected Demographic Characteristics and Declared Socioeconomic Status
Authors: Gajda Robert , Raczkowska Ewa , Wyka Joanna , Suliga Edyta , Sobaś Kamila
Published: April 2022

Nutritional risk screening in older people can help to not only identify health risks but also to treat them effectively. The aim of this work was to assess the relationship between the demographic characteristics (age, gender and place of residence) and socioeconomic status of older people in the community and nutritional risk. The Seniors in the Community: Risk Evaluation for Eating and Nutrition (SCREEN-14) questionnaire was used to evaluate the nutritional risk. The study was conducted in 417 people (312 women and 105 men) between 60 and 95 years old (70.8 ± 6.73 years). Multivariate correspondence analysis (MCA) was used to determine the relationships between the categories of variables describing the level of nutritional risk, demographic characteristics and the value of the socioeconomic status (SES) index. To assess the relationship between identified nutritional risks, demographics and SES index variables, we used logistic regression analysis. Based on these studies, nutritional risk factors for older people in Poland were identified. It has been shown that larger cities and low socioeconomic status are closely linked to higher nutritional risk. At the same time, age and gender were not significant factors influencing nutritional risk. Identifying the factors that increase the nutritional risk of older people can help to improve their quality of life.
Association between Dietary Diversity and All-Cause Mortality: A Multivariable Model in a Mediterranean Population with 18 Years of Follow-Up
Authors: Torres-Collado Laura , García-de la Hera Manuela , Cano-Ibañez Naomi , Bueno-Cavanillas Aurora , Vioque Jesús
Published: April 2022

We evaluated the relationship between the dietary diversity score (DDS) and all-cause, CVD and cancer mortality in an adult Mediterranean population. We analyzed the data of 1540 participants from the Valencia Nutrition Survey. The DDS was estimated using a validated food frequency questionnaire and was categorized into quartiles (Q), where the first quartile indicates the lowest dietary diversity. Deaths were ascertained during an 18-year follow-up period. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). There were 403 deaths during the follow-up period (40% due to CVD). An inverse association was observed between the DDS and all-cause and CVD mortality. Compared with participants in the lowest DDS quartile (Q1), participants in the highest DDS quartile (Q4) showed 32% and 45% less risk of death for all-cause and CVD mortality, in sex- and age-adjusted models, respectively. Regarding the food groups in the DDS, an inverse association was identified between total vegetable consumption diversity and all-cause and CVD mortality in the highest quartiles, (Q3 vs. Q1, HR: 0.70; 95% CI: 0.50, 0.99) and (Q4 vs. Q1, HR: 0.52; 95% CI: 0.30, 0.91), respectively. This study suggests that a higher diversity in food intake, particularly in vegetables, may be associated with a lower risk of all-cause and CVD mortality. This association should be further investigated in other wider populations.
Vitamin D Deficiency in Women with Breast Cancer: A Correlation with Osteoporosis? A Machine Learning Approach with Multiple Factor Analysis
Authors: de Sire Alessandro , Gallelli Luca , Marotta Nicola , Lippi Lorenzo , Fusco Nicola , Calafiore Dario , Cione Erika , Muraca Lucia , Maconi Antonio , De Sarro Giovambattista , Ammendolia Antonio , Invernizzi Marco
Published: April 2022

Breast cancer (BC) is the most frequent malignant tumor in women in Europe and North America, and the use of aromatase inhibitors (AIs) is recommended in women affected by estrogen receptor-positive BCs. AIs, by inhibiting the enzyme that converts androgens into estrogen, cause a decrement in bone mineral density (BMD), with a consequent increased risk of fragility fractures. This study aimed to evaluate the role of vitamin D3 deficiency in women with breast cancer and its correlation with osteoporosis and BMD modifications. This observational cross-sectional study collected the following data regarding bone health: osteoporosis and osteopenia diagnosis, lumbar spine (LS) and femoral neck bone mineral density (BMD), serum levels of 25-hydroxyvitamin D3 (25(OH)D3), calcium and parathyroid hormone. The study included 54 women with BC, mean age 67.3 ± 8.16 years. Given a significantly low correlation with the LS BMD value (r2 = 0.30, p = 0.025), we assessed the role of vitamin D3 via multiple factor analysis and found that BMD and vitamin D3 contributed to the arrangement of clusters, reported as vectors, providing similar trajectories of influence to the construction of the machine learning model. Thus, in a cohort of women with BC undergoing Ais, we identified a very low prevalence (5.6%) of patients with adequate bone health and a normal vitamin D3 status. According to our cluster model, we may conclude that the assessment and management of bone health and vitamin D3 status are crucial in BC survivors.
Antimicrobial Susceptibility of Microbiota in Bacterial Vaginosis Using Fluorescence In Situ Hybridization
Authors: Swidsinski Alexander , Guschin Alexander , Corsini Lorenzo , Loening-Baucke Vera , Tisakova Lenka Podpera , Swidsinski Sonja , Sobel Jack D. , Dörffel Yvonne
Published: April 2022

Background: Testing of antibiotic resistance of intact vaginal microbiota in pure culture is not feasible. METHODS: Metronidazole, antiseptic octenisept®, antimycotic ciclopirox, bacterial probiotic Lactobacillus crispatus, yeast probiotic Saccharomyces boulardii, Gardnerella-phage-endolysin named phagolysin and phagolysin in combination with probiotics were tested for bacteriolytic activity. Included were vaginal swabs from 38 random women with Amsel-confirmed bacterial vaginosis (BV). Test aliquots were incubated by 37° for 2 and 24 h. Gardnerella, low G+C, Atopobium, lactobacilli, Lactobacillus iners and crispatus, Prevotella-Bacteroides, and Gammaproteobacteria microbial groups were quantified using fluorescence in situ hybridization (FISH). Results: The probiotic strain Lactobacillus crispatus demonstrated the weakest bacteriolytical effects, followed by metronidazole. Both had no impact on Gardnerella species, instead lysing Prevotella-Bacteroides, Enterobacteriaceae (by L.crispatus) or LGC, Atopobium and Prevotella-Bacteroides (by metronidazole) groups of the microbiota. Cytolytic activity on Gardnerella was highly pronounced and increased from octenisept to ciclopirox, phagolysin, phagolysin with L.crispatus, being best in the combination of phagolysin with S.boulardii. Universally active ciclopirox and octenisept® suppressed nearly all microbial groups including those which are regarded as beneficial. Phagolysin had no effect on naturally occurring Lactobacillus crispatus. Conclusions: FISH susceptibility testing allows unique efficacy evaluation of individually adjusted topical therapy without microbial isolation facilitating optimal therapy choice.
Transcriptomic Analysis of Fumarate Compounds Identifies Unique Effects of Isosorbide Di-(Methyl Fumarate) on NRF2, NF-kappaB and IRF1 Pathway Genes
Authors: Swindell William R. , Bojanowski Krzysztof , Chaudhuri Ratan K.
Published: April 2022

Dimethyl fumarate (DMF) has emerged as a first-line therapy for relapsing-remitting multiple sclerosis (RRMS). This treatment, however, has been limited by adverse effects, which has prompted development of novel derivatives with improved tolerability. We compared the effects of fumarates on gene expression in astrocytes. Our analysis included diroximel fumarate (DRF) and its metabolite monomethyl fumarate (MMF), along with a novel compound isosorbide di-(methyl fumarate) (IDMF). Treatment with IDMF resulted in the largest number of differentially expressed genes. The effects of DRF and MMF were consistent with NRF2 activation and NF-κB inhibition, respectively. IDMF responses, however, were concordant with both NRF2 activation and NF-κB inhibition, and we confirmed IDMF-mediated NF-κB inhibition using a reporter assay. IDMF also down-regulated IRF1 expression and IDMF-decreased gene promoters were enriched with IRF1 recognition sequences. Genes altered by each fumarate overlapped significantly with those near loci from MS genetic association studies, but IDMF had the strongest overall effect on MS-associated genes. These results show that next-generation fumarates, such as DRF and IDMF, have effects differing from those of the MMF metabolite. Our findings support a model in which IDMF attenuates oxidative stress via NRF2 activation, with suppression of NF-κB and IRF1 contributing to mitigation of inflammation and pyroptosis.
Add Sugar to Chitosan: Mucoadhesion and In Vitro Intestinal Permeability of Mannosylated Chitosan Nanocarriers
Authors: Ejaz Sadaf , Hogg Bridget , Hristov Delyan R. , Brayden David J. , Imran Muhammad , Bhattacharjee Sourav
Published: April 2022

Crosslinked chitosan nanocarriers (140–160 nm) entrapping coumarin-6 (λex/em = 455/508 nm) with or without surface mannosylation were synthesized and assessed for cytotoxicity, adherence and cellular uptake in Caco-2 cells, flux across Caco-2 monolayers, and mucoadhesion to porcine mucin. Mannosylated and non-mannosylated nanocarriers demonstrated biocompatibility with slow release of coumarin-6 at pH 6.8 and 7.4 over 24 h. Adherence of the non-mannosylated nanocarriers (50 and 150 µg/mL) to Caco-2 cells was ~10% over 24 h, whereas cellular uptake of 25–30% was noted at 4 h. The mannosylated nanocarriers showed a similar adherence to non-mannosylated nanocarriers after 24 h, but a lower cellular uptake (~20%) at 1 h, comparable uptake at 4 h, and a higher uptake (~25–30%) at 24 h. Overall, the nanocarriers did not affect the integrity of Caco-2 monolayers. Mannosylated nanocarriers elicited higher Papp of 1.6 × 10−6 cm/s (50 µg/mL) and 1.2 × 10−6 (150 µg/mL) than the non-mannosylated ones: 9.8 × 10−7 cm/s (50 µg/mL) and 1.0 × 10−6 (150 µg/mL) after 2 h. Non-mannosylated chitosan nanocarriers elicited enhanced adhesion to porcine gut mucin via mucin-filled microchannels due to higher cationic charge density. These results underpin the importance of surface chemistry in the biological interactions of nanocarriers, while highlighting the role of surface hydrophilicity in mucopermeation due to mannosylation.
Fundamental Aspects of Lipid-Based Excipients in Lipid-Based Product Development
Authors: Nakmode Deepa , Bhavana Valamla , Thakor Pradip , Madan Jitender , Singh Pankaj Kumar , Singh Shashi Bala , Rosenholm Jessica M. , Bansal Kuldeep K. , Mehra Neelesh Kumar
Published: April 2022

Poor aqueous solubility of drugs is still a foremost challenge in pharmaceutical product development. The use of lipids in designing formulations provides an opportunity to enhance the aqueous solubility and consequently bioavailability of drugs. Pre-dissolution of drugs in lipids, surfactants, or mixtures of lipid excipients and surfactants eliminate the dissolution/dissolving step, which is likely to be the rate-limiting factor for oral absorption of poorly water-soluble drugs. In this review, we exhaustively summarize the lipids excipients in relation to their classification, absorption mechanisms, and lipid-based product development. Methodologies utilized for the preparation of solid and semi-solid lipid formulations, applications, phase behaviour, and regulatory perspective of lipid excipients are discussed.
Recent Advances in the Treatment of Alzheimer’s Disease Using Nanoparticle-Based Drug Delivery Systems
Authors: Poudel Prashant , Park Soyeun
Published: April 2022

Alzheimer’s disease (AD) is an irreversible and progressive neurodegenerative disorder. Most existing treatments only provide symptomatic solutions. Here, we introduce currently available commercial drugs and new therapeutics, including repositioned drugs, to treat AD. Despite tremendous efforts, treatments targeting the hallmarks of AD show limited efficacy. Challenges in treating AD are partly caused by difficulties in penetrating the blood–brain barrier (BBB). Recently, nanoparticle (NP)-based systems have shown promising potential as precision medicines that can effectively penetrate the BBB and enhance the targeting ability of numerous drugs. Here, we describe how NPs enter the brain by crossing, avoiding, or disrupting the BBB. In addition, we provide an overview of the action of NPs in the microenvironment of the brain for the treatment of AD. Diverse systems, including liposomes, micelles, polymeric NPs, solid-lipid NPs, and inorganic NPs, have been investigated for NP drug loading to relieve AD symptoms, target AD hallmarks, and target moieties to diagnose AD. We also highlight NP-based immunotherapy, which has recently gained special attention as a potential treatment option to disrupt AD progression. Overall, this review focuses on recently investigated NP systems that represent innovative strategies to understand AD pathogenesis and suggests treatment and diagnostic modalities to cure AD.
Lipid-Based Nanocarriers for Neurological Disorders: A Review of the State-of-the-Art and Therapeutic Success to Date
Authors: Witika Bwalya Angel , Poka Madan Sai , Demana Patrick Hulisani , Matafwali Scott Kaba , Melamane Siyabonga , Malungelo Khamanga Sandile Maswazi , Makoni Pedzisai Anotida
Published: April 2022

Neurodegenerative disorders including Alzheimer’s, Parkinson’s, and dementia are chronic and advanced diseases that are associated with loss of neurons and other related pathologies. Furthermore, these disorders involve structural and functional defections of the blood-brain barrier (BBB). Consequently, advances in medicines and therapeutics have led to a better appreciation of various pathways associated with the development of neurodegenerative disorders, thus focusing on drug discovery and research for targeted drug therapy to the central nervous system (CNS). Although the BBB functions as a shield to prevent toxins in the blood from reaching the brain, drug delivery to the CNS is hindered by its presence. Owing to this, various formulation approaches, including the use of lipid-based nanocarriers, have been proposed to address shortcomings related to BBB permeation in CNS-targeted therapy, thus showing the potential of these carriers for translation into clinical use. Nevertheless, to date, none of these nanocarriers has been granted market authorization following the successful completion of all stages of clinical trials. While the aforementioned benefits of using lipid-based carriers underscores the need to fast-track their translational development into clinical practice, technological advances need to be initiated to achieve appropriate capacity for scale-up and the production of affordable dosage forms.
Preclinical Therapeutic Assessment of a New Chemotherapeutics [Dichloro(4,4’-Bis(2,2,3,3-Tetrafluoropropoxy) Methyl)-2,2’-Bipryridine) Platinum] in an Orthotopic Patient-Derived Xenograft Model of Triple-Negative Breast Cancers
Authors: Kan Tzu-Chun , Lin Mei-Hsiang , Cheng Chun-Chia , Lu Jeng-Wei , Sheu Ming-Thau , Ho Yuan-Soon , Rahayu Sri , Chang Jungshan
Published: April 2022

Cisplatin is one of the most common therapeutics used in treatments of several types of cancers. To enhance cisplatin lipophilicity and reduce resistance and side effects, a polyfluorinated bipyridine-modified cisplatin analogue, dichloro[4,4’-bis(2,2,3,3-tetrafluoropropoxy)methyl)-2,2’-bipryridine] platinum (TFBPC), was synthesized and therapeutic assessments were performed. TFBPC displayed superior effects in inhibiting the proliferation of several cisplatin-resistant human cancer cell lines, including MDA-MB-231 breast cancers, COLO205 colon cancers and SK-OV-3 ovarian cancers. TFBPC bound to DNA and formed DNA crosslinks that resulted in DNA degradation, triggering the cell death program through the PARP/Bax/Bcl-2 apoptosis and LC3-related autophagy pathway. Moreover, TFBPC significantly inhibited tumor growth in both animal models which include a cell line-derived xenograft model (CDX) of cisplatin-resistant MDA-MB-231, and a patient-derived xenograft (PDX) model of triple-negative breast cancers (TNBCs). Furthermore, the biopsy specimen from TFBPC-treated xenografts revealed decreased expressions of P53, Ki-67 and PD-L1 coupled with higher expression of cleaved caspase 3, suggesting TFBPC treatment was effective and resulted in good prognostic indications. No significant pathological changes were observed in hematological and biochemistry tests in blood and histological examinations from the specimen of major organs. Therefore, TFBPC is a potential candidate for treatments of patients suffering from TNBCs as well as other cisplatin-resistant cancers.
A Single-Pixel Imaging Scheme with Obstacle Detection
Authors: Li Peiming , Zhao Haixiao , Jiang Wenjie , Zhang Zexin , Sun Baoqing
Published: April 2022

Single-pixel imaging (SPI) utilizes a second-order correlation of structured illumination light field and a single-pixel detector to form images. As the single-pixel detector provides no spatial resolution, a structured illumination light field generated by devices such as a spatial light modulator substitutes the role of array camera to retrieve pixel-wise spatial information. Due to its unique imaging modality, SPI has certain advantages. Meanwhile, its counterintuitive configuration and reciprocity relation to traditional array cameras have been studied to understand its fundamental principle. According to previous studies, the non-spatial detection property makes it possible for SPI to resist scattering in the detection part. In this work, we study the influence of an obstacle aperture in the detection part of SPI. We notice that such an obstacle aperture can restrict the field-of-view (FOV) of SPI, which can be diminished by a scattering process. We investigate these properties with experiment results and analysis under geometry optics. We believe that our study will be helpful in understanding the counterintuitive configuration of SPI and its reciprocity to traditional imaging.
Insights into Fluctuations of Structure of Proteins: Significance of Intermediary States in Regulating Biological Functions
Authors: Parray Zahoor Ahmad , Shahid Mohammad , Islam Asimul
Published: April 2022

Proteins are indispensable to cellular communication and metabolism. The structure on which cells and tissues are developed is deciphered from proteins. To perform functions, proteins fold into a three-dimensional structural design, which is specific and fundamentally determined by their characteristic sequence of amino acids. Few of them have structural versatility, allowing them to adapt their shape to the task at hand. The intermediate states appear momentarily, while protein folds from denatured (D) ⇔ native (N), which plays significant roles in cellular functions. Prolific effort needs to be taken in characterizing these intermediate species if detected during the folding process. Protein folds into its native structure through definite pathways, which involve a limited number of transitory intermediates. Intermediates may be essential in protein folding pathways and assembly in some cases, as well as misfolding and aggregation folding pathways. These intermediate states help to understand the machinery of proper folding in proteins. In this review article, we highlight the various intermediate states observed and characterized so far under in vitro conditions. Moreover, the role and significance of intermediates in regulating the biological function of cells are discussed clearly.
Partial Biodegradable Blend with High Stability against Biodegradation for Fused Deposition Modeling
Authors: Harris Muhammad , Mohsin Hammad , Potgieter Johan , Ishfaq Kashif , Archer Richard , Chen Qun , De Silva Karnika , Guen Marie-Joo Le , Wilson Russell , Arif Khalid Mahmood
Published: April 2022

This research presents a partial biodegradable polymeric blend aimed for large-scale fused deposition modeling (FDM). The literature reports partial biodegradable blends with high contents of fossil fuel-based polymers (>20%) that make them unfriendly to the ecosystem. Furthermore, the reported polymer systems neither present good mechanical strength nor have been investigated in vulnerable environments that results in biodegradation. This research, as a continuity of previous work, presents the stability against biodegradability of a partial biodegradable blend prepared with polylactic acid (PLA) and polypropylene (PP). The blend is designed with intended excess physical interlocking and sufficient chemical grafting, which has only been investigated for thermal and hydrolytic degradation before by the same authors. The research presents, for the first time, ANOVA analysis for the statistical evaluation of endurance against biodegradability. The statistical results are complemented with thermochemical and visual analysis. Fourier transform infrared spectroscopy (FTIR) determines the signs of intermolecular interactions that are further confirmed by differential scanning calorimetry (DSC). The thermochemical interactions observed in FTIR and DSC are validated with thermogravimetric analysis (TGA). Scanning electron microscopy (SEM) is also used as a visual technique to affirm the physical interlocking. It is concluded that the blend exhibits high stability against soil biodegradation in terms of high mechanical strength and high mass retention percentage.
Triboelectric Enhancement of Polyvinylidene Fluoride Membrane Using Magnetic Nanoparticle for Water-Based Energy Harvesting
Authors: Vu Duy-Linh , Ahn Kyoung-Kwan
Published: April 2022

Produced by magnetic material dispersed in a viscous environment for the purpose of collecting and converting energy, magnetic rheological compounds greatly strengthen the development of skin-attachable and wearable electrical equipment. Given that magnetic nanomaterial anisotropy has a substantial influence on the interface polarizing of polyvinylidene fluoride (PVDF), it is critical to explore the function of magnetic polymer compounds in the triboelectric layer of triboelectric nanogenerator (TENG) output power. In this study, ferromagnetic cobalt ferrite, CoFe2O4 (CFO), nanoparticles, and PVDF were employed to create a triboelectric composite membrane to improve TENG energy output. The content of β phase in PVDF increased significantly from 51.2% of pure PVDF membrane to 77.7% of 5 wt% CFO nanoparticles in the PVDF matrix, which further increase the dielectric constant and negative charge of the membrane. As a consequence, the energy output of CFO/PVDF-5 TENG increased significantly with a voltage of 17.2 V, a current of 2.27 μA, and a power density of 90.3 mW/m2, which is 2.4 times the performance of pure PVDF TENG. Finally, the proposal for TENG hopes that its extraordinary stability and durability will provide additional views on hydrodynamic power generation in the future.
Composite Fish Collagen-Hyaluronate Based Lyophilized Scaffolds Modified with Sodium Alginate for Potential Treatment of Chronic Wounds
Authors: Afzali Meena , Boateng Joshua Siaw
Published: April 2022

Chronic wounds are characterized by both decreased collagen deposition and increased collagen breakdown. It is reasonable to hypothesize that exogenous collagen can potentially promote wound healing by reducing degradation enzymes in the wound environment and disrupting the cycle of chronicity. Therefore, this study aimed to develop an optimal combination of fish collagen (FCOL), sodium alginate (SA), and hyaluronic acid (HA) loaded with bovine serum albumin (BSA) as a model protein fabricated as lyophilized scaffolds. The effects of sodium alginate (SA#) with higher mannuronic acid (M) were compared to sodium alginate (SA*) with higher guluronic acid (G). The SA* with higher G resulted in elegant scaffolds with hardness ranging from 3.74 N–4.29 N that were able to withstand the external force due to the glycosidic bonds in guluronic acid. Furthermore, the high G content also had a significant effect on the pore size, pore shape, and porosity. The water absorption (WA) ranged from 380–1382 (%) and equilibrium water content (EWC) 79–94 (%) after 24 h incubation at 37 °C. The SA* did not affect the water vapor transmission rate (WVTR) but incorporating BSA significantly increased the WVTR making these wound dressing scaffolds capable of absorbing about 50% exudate from a heavily exuding chronic wound. The protein released from the composite systems was best explained by the Korsmeyer–Peppas model with regression R2 values ranging from 0.896 to 0.971 and slope or n < 0.5 indicating that the BSA release mechanism was governed by quasi-Fickian diffusion. Cell viability assay showed that the scaffolds did not inhibit the proliferation of human dermal fibroblasts and human epidermal keratinocytes, and are therefore biocompatible. In vitro blood analysis using human whole blood confirmed that the BSA-loaded SA*:FCOL:HA scaffolds reduced the blood clotting index (BCI) by up to 20% compared to a commercially available sponge for chronic wounds. These features confirm that SA*:FCOL:HA scaffolds could be applied as a multifunctional wound dressing.
Highly Efficient Recovery of Ruthenium from Aqueous Solutions by Adsorption Using Dibenzo-30-Crown-10 Doped Chitosan
Authors: Ciopec Mihaela , Grad Oana , Negrea Adina , Duţeanu Narcis , Negrea Petru , Vodă Raluca , Ianăşi Cătălin
Published: April 2022

Ruthenium, as an industrial by-product or from natural sources, represents an important economical resource due to its specific applications. A complex problem is represented by ruthenium separation during reprocessing operations, therefore, different materials and methods have been proposed. The present study aims to develop a new material with good adsorbent properties able to be used for ruthenium recovery by adsorption from aqueous solutions. Absorbent material was obtained using chitosan (Ch) surface modification with dibenzo-30-crown-10 ether (DB30C10). Chitosan represents a well-known biopolymer with applicability in different adsorptive processes due to the presence of hydroxyl-, carboxyl-, and nitrogen-containing groups in the structure. Additionally, crown ethers are macromolecules with a good complexation capacity for metallic ions. It is expected that the adsorptive efficiency of newly prepared material will be superior to that of the individual components. New synthesized material was characterized using scanning electron microscopy coupled with energy dispersive X-ray (SEM–EDX), Fourier transform infrared spectroscopy (FT-IR), Brunauer–Emmett–Teller surface area analysis (BET), and determination of point of zero charge (pZc). Results obtained from the performed kinetic, thermodynamic, and equilibrium studies confirmed the good adsorptive capacity of the prepared material, Ch-DB30C10, obtaining a maximum adsorption capacity of 52 mg Ru(III) per gram. This adsorption capacity was obtained using a solution with an initial concentration of 275 mg L−1, at pH 2, and 298 K. Ru(III) adsorption kinetics were studied by modeling the obtained experimental data with pseudo-first order and pseudo-second order models. Desorption studies established that the optimum eluent was represented by the 5M HNO3 solution. Based on the performed studies, a mechanism for recovery of ruthenium by adsorption was proposed.
Electrospun Biodegradable α-Amino Acid-Substituted Poly(organophosphazene) Fiber Mats for Stem Cell Differentiation towards Vascular Smooth Muscle Cells
Authors: Wang Meng , Lin Shigang , Mequanint Kibret
Published: April 2022

Mesenchymal stem cells, derived from human-induced pluripotent stem cells (iPSC), are valuable for generating smooth muscle cells (SMCs) for vascular tissue engineering applications. In this study, we synthesized biodegradable α-amino acid-substituted poly(organophosphazene) polymers and electrospun nano-fibrous scaffolds (~200 nm diameter) to evaluate their suitability as a matrix for differentiation of iPSC-derived mesenchymal stem cells (iMSC) into mature contractile SMCs. Both the polymer synthesis approach and the electrospinning parameters were optimized. Three types of cells, namely iMSC, bone marrow derived mesenchymal stem cells (BM-MSC), and primary human coronary artery SMC, attached and spread on the materials. Although L-ascorbic acid (AA) and transforming growth factor-beta 1 (TGF-β1) were able to differentiate iMSC along the smooth muscle lineage, we showed that the electrospun fibrous mats provided material cues for the enhanced differentiation of iMSCs. Differentiation of iMSC to SMC was characterized by increased transcriptional levels of early to late-stage smooth muscle marker proteins on electrospun fibrous mats. Our findings provide a feasible strategy for engineering functional vascular tissues.