bluuebunny/crossref_metadata_2025 huggingface dataset:
Luteolin-7-O-rutinoside Protects RIN-5F Cells from High-Glucose-Induced Toxicity, Improves Glucose Homeostasis in L6 Myotubes, and Prevents Onset of Type 2 Diabetes
Authors: Subash-Babu Pandurangan , Abdulaziz AlSedairy Sahar , Abdulaziz Binobead Manal , Alshatwi Ali A.
Published: February 2023

Luteolin-7-O-rutinoside (lut-7-O-rutin), a flavonoid commonly present in Mentha longifolia L. and Olea europaea L. leaves has been used as a flavoring agent with some biological activity. The present study is the first attempt to analyze the protective effect of lut-7-O-rutin on high-glucose-induced toxicity to RIN-5F cells in vitro. We found that lut-7-O-rutin improved insulin secretion in both normal and high-glucose conditions in a dose-dependent manner, without toxicity observed. In addition, 20 µmol of lut-7-O-rutin improves insulin sensitization and glucose uptake significantly (p ≤ 0.01) in L6 myotubes cultured in a high-glucose medium. Lut-7-O-rutin has shown a significant (p ≤ 0.05) effect on glucose uptake in L6 myotubes compared to the reference drug, rosiglitazone (20 µmol). Gene expression analysis confirmed significantly lowered CYP1A, TNF-α, and NF-κb expressions in RIN-5F cells, and increased mitochondrial thermogenesis-related LPL, Ucp-1 and PPARγC1A mRNA expressions in L6 myotubes after 24 h of lut-7-O-rutin treatment. The levels of signaling proteins associated with intracellular glucose uptakes, such as cAMP, ChREBP-1, and AMPK, were significantly increased in L6 myotubes. In addition, the levels of the conversion rate of glucose to lactate and fatty acids were raised in insulin-stimulated conditions; the rate of glycerol conversion was found to be higher at the basal level in L6 myotubes. In conclusion, lut-7-O-rutin protects RIN-5F cells from high-glucose-induced toxicity, stimulates insulin secretion, and promotes glucose absorption and homeostasis via molecular mechanisms.
Diurnal Valley Winds in a Deep Alpine Valley: Model Results
Authors: Schmidli Juerg , Quimbayo-Duarte Julian
Published: February 2023

Thermally driven local winds are ubiquitous in deep Alpine valleys during fair weather conditions resulting in a unique wind climatology for any given valley. The accurate forecasting of these local wind systems is challenging, as they are the result of complex and multi-scale interactions. Even more so, if the aim is an accurate forecast of the winds from the near-surface to the free atmosphere, which can be considered a prerequisite for the accurate prediction of mountain weather. This study combines the evaluation of the simulated surface winds in several Alpine valleys with a more detailed evaluation of the wind evolution for a particular location in the Swiss Rhone valley, at the town of Sion during the month of September 2016. Four numerical simulations using the COSMO model are evaluated, two using a grid spacing of 1.1 km and two with a grid spacing of 550 m. For each resolution, one simulation is initialised with the soil moisture from the COSMO analysis and one with an increased soil moisture (+30%). In a first part, a comparison with observations from the operational measurement network of MeteoSwiss is used to evaluate the model performance, while, in a second part, data from a wind profiler stationed at Sion airport is used for a more detailed evaluation of the valley atmosphere near the town of Sion. The analysis focuses on 18 valley wind days observed in the Sion region in September 2016. Only the combination of an increased soil moisture and a finer grid spacing resulted in a significant improvement of the simulated flow patterns in the Sion region. This includes a stronger and more homogeneous along-valley wind in the Wallis and a more realistic cross-valley wind and temperature profile near the town of Sion. It is shown that the remaining differences between the observed and simulated near-surface wind are likely due to very local topographic features. Small-scale hills, not resolved on even the finer model grid, result in a constriction of the valley cross section and an acceleration of the observed low-level up-valley wind in the region of Sion.
Antimicrobial Exposure in Critically Ill Patients with Sepsis-Associated Multi-Organ Dysfunction Requiring Extracorporeal Organ Support: A Narrative Review
Authors: Cutuli Salvatore Lucio , Cascarano Laura , Lazzaro Paolo , Tanzarella Eloisa Sofia , Pintaudi Gabriele , Grieco Domenico Luca , De Pascale Gennaro , Antonelli Massimo
Published: February 2023

Sepsis is a leading cause of disability and mortality worldwide. The pathophysiology of sepsis relies on the maladaptive host response to pathogens that fosters unbalanced organ crosstalk and induces multi-organ dysfunction, whose severity was directly associated with mortality. In septic patients, etiologic interventions aiming to reduce the pathogen load via appropriate antimicrobial therapy and the effective control of the source infection were demonstrated to improve clinical outcomes. Nonetheless, extracorporeal organ support represents a complementary intervention that may play a role in mitigating life-threatening complications caused by sepsis-associated multi-organ dysfunction. In this setting, an increasing amount of research raised concerns about the risk of suboptimal antimicrobial exposure in critically ill patients with sepsis, which may be worsened by the concomitant delivery of extracorporeal organ support. Accordingly, several strategies have been implemented to overcome this issue. In this narrative review, we discussed the pharmacokinetic features of antimicrobials and mechanisms that may favor drug removal during renal replacement therapy, coupled plasma filtration and absorption, therapeutic plasma exchange, hemoperfusion, extracorporeal CO2 removal and extracorporeal membrane oxygenation. We also provided an overview of evidence-based strategies that may help the physician to safely prescribe effective antimicrobial doses in critically ill patients with sepsis-associated multi-organ dysfunction who receive extracorporeal organ support.
Screening of Staphylococcus aureus for Disinfection Evaluation and Transcriptome Analysis of High Tolerance to Chlorine-Containing Disinfectants
Authors: Li Yixiao , Song Yang , Huang Zhenzhou , Mei Li , Jiang Mengnan , Wang Duochun , Wei Qiang
Published: February 2023

The nonstandard use of disinfectants can lead to the disinfectant resistance of bacteria and even increase antibiotic resistance. However, compared with the study of antibiotic resistance, studies of bacterial resistance to disinfectants are relatively few in number. In this study, we explored the standard strain screening procedure for the evaluation of disinfection efficacy. Staphylococcus aureus strains with different sources and substrates were selected from the National Pathogen Resource Center of China and screened the standard strains that could evaluate the long-term bacteriostatic effect of the chlorine-containing disinfectants through the determination of the physical properties, genome-based safety evaluation, and disinfection test evaluation. In this process, one S. aureus strain was more resistant to the long-term bacteriostasis of chlorine-containing disinfectants than the other strains. This strain and the standard strain ATCC 6538 were cultured in the medium containing a low concentration of chlorine-containing disinfectant synchronously. Then, comparative transcriptome analysis was carried out to investigate the potential mechanism of a high tolerance to chlorine-containing disinfectants. The pathway of significant differential expression is related to the oxocarboxylic acid metabolic mechanism, amino acid metabolic mechanism, and pyrimidine mechanism, which may be the molecular mechanism of S. aureus evolution to adapt to chlorine-containing disinfectants. Our study established a technical process for screening and evaluating standard strains for disinfection, which also provided a reference for studying the bacterial evolution mechanism toward chlorine tolerance.
Periodic Characteristics of the Paleogene Tectonic Activity and Sedimentation Responses in the Deep-Water of Qiongdongnan Basin, South China Sea
Authors: Xu Meng , Song Guangzeng , Li Zengxue , Wang Dongdong , Sun Rui , Chen Ying
Published: February 2023

In this study, the periodic evolution and characteristics of the Palaeogene tectonic activity in the deep-water area of the Qiongdongnan Basin were revealed through the identification and analysis of the regional angular unconformity and the characteristics of the periodic fault activity. In addition to a comprehensive analysis of the controls on sedimentary paleogeomorphologic background, sedimentary characteristics and evolution by periodic rifting are systematically discussed. The studies have shown that the tectonic activity of the Paleogene Qiongdongnan Basin underwent three separate rifting phases: Phase-I (T100–T80), Phase-II (T80–T70), and Phase-III (T70–T60). The early phase of rifting was dominated by strong differential block-fault settlement, while the later phase was gradually replaced by homogeneous settlement controlled by regional depressions and a small amount of fault activity, characterized by a weak-strong-weak evolution. From Phase-I to Phase-III, the paleo-geomorphology margin changed from a large gradient to a gentle gradient, the subsidence center moved from the initial basin margin to the later basin center, and the basin-marginal fans extended finitely before developing on a large lateral scale in the later Phase-III. Analyzing the characteristics of periodic tectonic evolution and sedimentation response is important for petroleum exploration in marine basins, such as locating economic reservoirs.
An Early Warning System for Landslide Risks in Ion-Adsorption Rare Earth Mines: Based on Real-Time Monitoring of Water Level Changes in Slopes
Authors: Han Min , Rao Yunzhang , Nie Wen , Wang Dan , Wu Fuyu , Shi Liang
Published: February 2023

During the in situ leaching process of ion-adsorption rare earths, leaching solution needs to be constantly injected to the mine slopes. As a consequence, landslides are highly likely to occur due to the increasing water level of soil mass. To solve this problem, we conducted a mechanical analysis on the rising water level after solution injection, which shed light on the mechanical principle of slope instability brought about by rising water level. With water level variation as the major factor, we established an early warning system for landslide risks on the basis of the real-time monitoring of water level. Within the system, a self-designed landslide early warning model is embedded. In addition to monitoring the water level variation in slopes, this system can be employed for real-time data processing. With the integration of early warning model algorithm, the real-time graded early warning of slope landslide risks is achieved within the mining process of ion-adsorption rare earths. By discussing the real-time monitoring method, framework of landslide early warning system, FIFC landslide early warning model, optimization method of water level, and selection of landslide-inducing factors, this research provides an effective solution to the landslide early warning within the mining process of ion-adsorption rare earth minerals. Thus, it can be employed as a favorable reference for other types of early warning systems.
Major and Trace Element Compositions of Clinopyroxene Phenocrysts in Altered Basaltic Rocks from Yüksekova Complex within Bitlis Suture Zone (Elazığ, Eastern Turkey): Implications for the Tholeiitic to Calc-Alkaline Magmatism
Authors: Ural Melek
Published: February 2023

This paper presents major and trace element compositions of the clinopyroxene phenocrysts from variably altered basaltic rocks from the Yüksekova Complex from E Anatolia (Elazığ) to reveal the geochemical affinity of the basaltic magmatism and the intensive parameters during magmatic crystallization. The Yüksekova Complex crops out over extensive areas to the north of the Bitlis suture. The investigated samples come from an area of ca. 2500 km2 in the Elazığ province. Petrographically, the basaltic rocks are represented by basalt, porphyric basalt and dolerite. The rocks are characterized by plagioclase, clinopyroxene, magnetite and ilmenite and are devoid of any hornblende and biotite, whereby clinopyroxene and plagioclase form phenocrysts. Generally, the groundmass is variably altered, whereas clinophenocrysts are comparatively fresh. The clinopyroxene is represented by the composition Wo37–48En43–53Fs4–17, with Mg/(Mg + Fe2+) ratios of 0.93–0.73. Compositionally, the clinopyroxenes resemble those from island arc tholeiitic, calc-alkaline and anorogenic tholeiitic rocks. Clinopyroxene-melt geothermobarometry yielded temperatures of 1146 and 1193 °C and pressures of 1.4 to 7.0 kbar, suggesting that the clinopyroxene phenocrysts started to grow at variable crustal depths. There is no apparent difference of magma temperatures between different magma affinities. The Fe–Mg partition coefficient between clinopyroxene and melt (KD Fe−MgCpx-Melt = 0.27) suggests that the parental magmas in equilibrium with clinopyroxene were mostly primitive, with Mg# of 65–79. The REE patterns of parental melts in equilibrium with clinopyroxene phenocrysts resemble those of low-K tholeiitic to middle- to high-K calc-alkaline rocks from the magmatic arcs. The results of this study are mostly consistent with the inferences from the whole-rock geochemistry, and indicate that the major and trace element geochemistry can be effectively used to infer the geochemical affinities of the highly altered basaltic rocks.
One-Pot Synthesis of Melamine Formaldehyde Resin-Derived N-Doped Porous Carbon for CO2 Capture Application
Authors: Yu Qiyun , Bai Jiali , Huang Jiamei , Demir Muslum , Farghaly Ahmed A. , Aghamohammadi Parya , Hu Xin , Wang Linlin
Published: February 2023

The design and synthesis of porous carbons for CO2 adsorption have attracted tremendous interest owing to the ever-soaring concerns regarding climate change and global warming. Herein, for the first time, nitrogen-rich porous carbon was prepared with chemical activation (KOH) of commercial melamine formaldehyde resin (MF) in a single step. It has been shown that the porosity parameters of the as-prepared carbons were successfully tuned by controlling the activating temperature and adjusting the amount of KOH. Thus, as-prepared N-rich porous carbon shows a large surface area of 1658 m2/g and a high N content of 16.07 wt%. Benefiting from the unique physical and textural features, the optimal sample depicted a CO2 uptake of up to 4.95 and 3.30 mmol/g at 0 and 25 °C under 1 bar of pressure. More importantly, as-prepared adsorbents show great CO2 selectivity over N2 and outstanding recyclability, which was prominently important for CO2 capture from the flue gases in practical application. An in-depth analysis illustrated that the synergetic effect of textural properties and surface nitrogen decoration mainly determined the CO2 capture performance. However, the textural properties of carbons play a more important role than surface functionalities in deciding CO2 uptake. In view of cost-effective synthesis, outstanding textural activity, and the high adsorption capacity together with good selectivity, this advanced approach becomes valid and convenient in fabricating a unique highly efficient N-rich carbon adsorbent for CO2 uptake and separation from flue gases.
Determination of d- and l-Amino Acids in Garlic Foodstuffs by Liquid Chromatography–Tandem Mass Spectrometry
Authors: Onozato Mayu , Nakanoue Haruna , Sakamoto Tatsuya , Umino Maho , Fukushima Takeshi
Published: February 2023

Black garlic is currently attracting interest as a health food and constituent of commercial supplements; however, no data regarding the d-amino acids within black garlic have been reported. Therefore, the amino acid compositions of methanol extracts from fresh and black garlic were compared herein. We investigated the contents of the d- and l-forms of amino acids in commercial fresh, black, and freeze-dried garlic foodstuffs by liquid chromatography–tandem mass spectrometry (LC–MS/MS) using a pre-column chiral derivatization reagent, succinimidyl 2-(3-((benzyloxy)carbonyl)-1-methyl-5-oxoimidazolidin-4-yl) acetate. Several d-amino acids, namely, the d-forms of Asn, Ala, Ser, Thr, Glu, Asp, Pro, Arg, Phe, Orn, Lys, and Tyr, were observed in the methanol extract of black garlic, whereas only d-Ala was detected in that of fresh garlic foodstuffs. These data suggest that several d-amino acids can be produced during fermentation for preparing black garlic.
Green Drug Discovery: Novel Fragment Space from the Biomass-Derived Molecule Dihydrolevoglucosenone (CyreneTM)
Authors: Dekker Tom , Harteveld Jaap W. , Wágner Gábor , de Vries Max C. M. , Custers Hans , van de Stolpe Andrea C. , de Esch Iwan J. P. , Wijtmans Maikel
Published: February 2023

Biomass-derived molecules can provide a basis for sustainable drug discovery. However, their full exploration is hampered by the dominance of millions of old-fashioned screening compounds in classical high-throughput screening (HTS) libraries frequently utilized. We propose a fragment-based drug discovery (FBDD) approach as an efficient method to navigate biomass-derived drug space. Here, we perform a proof-of-concept study with dihydrolevoglucosenone (CyreneTM), a pyrolysis product of cellulose. Diverse synthetic routes afforded a 100-membered fragment library with a diversity in functional groups appended. The library overall performs well in terms of novelty, physicochemical properties, aqueous solubility, stability, and three-dimensionality. Our study suggests that Cyrene-based fragments are a valuable green addition to the drug discovery toolbox. Our findings can help in paving the way for new hit drug candidates that are based on renewable resources.
A Synergetic Strategy for Brand Characterization of Colla Corii Asini (Ejiao) by LIBS and NIR Combined with Partial Least Squares Discriminant Analysis
Authors: Xia Ziyi , Che Xiaoqing , Ye Lei , Zhao Na , Guo Dongxiao , Peng Yanfang , Lin Yongqiang , Liu Xiaona
Published: February 2023

A synergetic strategy was proposed to address the critical issue in the brand characterization of Colla corii asini (Ejiao, CCA), a precious traditional Chinese medicine (TCM). In all brands of CCA, Dong’e Ejiao (DEEJ) is an intangible cultural heritage resource. Seventy-eight CCA samples (including forty DEEJ samples and thirty-eight samples from other different manufacturers) were detected by laser-induced breakdown spectroscopy (LIBS) and near-infrared spectroscopy (NIR). Partial least squares discriminant analysis (PLS-DA) models were built first considering individual techniques separately, and then fusing LIBS and NIR data at low-level. The statistical parameters including classification accuracy, sensitivity, and specificity were calculated to evaluate the PLS-DA model performance. The results demonstrated that two individual techniques show good classification performance, especially the NIR. The PLS-DA model with single NIR spectra pretreated by the multiplicative scatter correction (MSC) method was preferred as excellent discrimination. Though individual spectroscopic data obtained good classification performance. A data fusion strategy was also attempted to merge atomic and molecular information of CCA. Compared to a single data block, data fusion models with SNV and MSC pretreatment exhibited good predictive power with no misclassification. This study may provide a novel perspective to employ a comprehensive analytical approach to brand discrimination of CCA. The synergetic strategy based on LIBS together with NIR offers atomic and molecular information of CCA, which could be exemplary for future research on the rapid discrimination of TCM.
A Review of Current Trends on Polyvinyl Alcohol (PVA)-Based Solid Polymer Electrolytes
Authors: Dennis John Ojur , Shukur M. F. , Aldaghri Osamah A. , Ibnaouf Khalid Hassan , Adam Abdullahi Abbas , Usman Fahad , Hassan Yarima Mudassir , Alsadig A. , Danbature Wilson L. , Abdulkadir Bashir Abubakar
Published: February 2023

Presently, the rising concerns about the fossil fuel crisis and ecological deterioration have greatly affected the world economy and hence have attracted attention to the utilization of renewable energies. Among the renewable energy being developed, supercapacitors hold great promise in broad applications such as electric vehicles. Presently, the main challenge facing supercapacitors is the amount of energy stored. This, however, does not satisfy the increasing demand for higher energy storage devices, and therefore, intensive research is being undertaken to overcome the challenges of low energy density. The purpose of this review is to report on solid polymer electrolytes (SPEs) based on polyvinyl alcohol (PVA). The review discussed the PVA as a host polymer in SPEs followed by a discussion on the influence of conducting salts. The formation of SPEs as well as the ion transport mechanism in PVA SPEs were discussed. The application and development of PVA-based polymer electrolytes on supercapacitors and other energy storage devices were elucidated. The fundamentals of electrochemical characterization for analyzing the mechanism of supercapacitor applications, such as EIS, LSV and dielectric constant, are highlighted. Similarly, thermodynamic transport models of ions and their mechanism about temperature based on Arrhenius and Vogel–Tammann–Fulcher (VTF) are analyzed. Methods for enhancing the electrochemical performance of PVA-based SPEs were reported. Likely challenges facing the current electrolytes are well discussed. Finally, research directions to overcome the present challenges in producing SPEs are proposed. Therefore, this review is expected to be source material for other researchers concerned with the development of PVA-based SPE material.
Synthesis of Multi-Stimuli Responsive Fe3O4 Coated with Diamonds Nanocomposite for Magnetic Assisted Chemo-Photothermal Therapy
Authors: Li Yang , Kong Jichuan , Zhao Huan , Liu Yao
Published: February 2023

Nanodiamonds with magnetic resonance imaging (MRI) and targeted drug delivery to exert combined effects for biomedical applications have been considered to be an urgent challenge. Herein, a novel bio-nanoarchitectonics (Fe3O4@NDs) with simultaneous imaging and therapeutic capacities was fabricated by covalently conjugating nanodiamonds (NDs) with Fe3O4. Fe3O4@NDs exhibited better biocompatibility and excellent photothermal stability with superb photothermal conversion performance (37.2%). Fe3O4@NDs has high doxorubicin (DOX) loading capacity (193 mg/g) with pH and NIR-responsive release characteristics. Fe3O4@NDs loading DOX showed a combined chemo-photothermal inhibitory effect on the tumor cells. Enhanced T2-weighted MRI contrast toward the tumor, with the assistance of a magnetic field, convinced the Fe3O4@NDs gathered in the tumor more efficiently and could be used for MRI-based cancer diagnosis. Our results revealed an effective strategy to achieve a stimuli-sensitive nanoplatform for multifunctional theranostics by the combined action.
The Synergistic Effects between Sulfobetaine and Hydrophobically Modified Polyacrylamide on Properties Related to Enhanced Oil Recovery
Authors: Sun Qi , Hu Fu-Tang , Han Lu , Zhu Xiu-Yu , Zhang Fan , Ma Gui-Yang , Zhang Lei , Zhou Zhao-Hui , Zhang Lu
Published: February 2023

In order to explore the mechanism responsible for the interactions in the surfactant–polymer composite flooding and broaden the application range of the binary system in heterogeneous oil reservoirs, in this paper, the influences of different surfactants on the viscosity of two polymers with similar molecular weights, partially hydrolyzed polyacrylamide (HPAM) and hydrophobically modified polyacrylamide (HMPAM), were studied at different reservoir environments. In addition, the relationship between the surfactant–polymer synergistic effects and oil displacement efficiency was also investigated. The experimental results show that for HPAM, surfactants mainly act as an electrolyte to reduce its viscosity. For HMPAM, SDBS and TX-100 will form aggregates with the hydrophobic blocks of polymer molecules, reducing the bulk viscosity. However, zwitterionic surfactant aralkyl substituted alkyl sulfobetaine BSB molecules can build “bridges” between different polymer molecules through hydrogen bonding and electrostatic interaction. After forming aggregates with HMPAM molecules, the viscosity will increase. The presence of two polymers all weakened the surfactant oil–water interfacial membrane strength to a certain extent, but had little effect on the interfacial tension. The synergistic effect of the “bridge” between HMPAM and BSB under macroscopic conditions also occurs in the microscopic pores of the core, which has a beneficial effect on improving oil recovery.
3D Active Brownian Motion of Single Dust Particles Induced by a Laser in a DC Glow Discharge
Authors: Svetlov Anton , Vasiliev Mikhail , Kononov Evgeniy , Petrov Oleg , Trukhachev Fedor
Published: February 2023

The active Brownian motion of single dust particles of various types in the 3D electrostatic DC discharge trap under the action of laser radiation is studied experimentally. Spherical dust particles with a homogeneous surface, as well as Janus particles, are used in the experiment. The properties of the active Brownian motion of all types of dust particles are studied. In particular, the 3D analysis of trajectories of microparticles is carried out, well as an analysis of their root mean square displacement. The mean kinetic energy of motion of the dust particle of various types in a 3D trap is determined for different laser powers. Differences in the character of active Brownian motion in electrostatic traps with different spatial dimensions are found.
Characterization of Electrospinning Prepared Nitrocellulose (NC)-Ammonium Dinitramide (ADN)-Based Composite Fibers
Authors: Wang Qiong , Xu Lu-ping , Deng Chong-qing , Yao Er-gang , Chang Hai , Pang Wei-qiang
Published: February 2023

Nanoscale composite energetic materials (CEMs) based on oxidizer and fuel have potential advantages in energy adjustment and regulation through oxygen balance (OB) change. The micro- and nanosized fibers based on nano nitrocellulose (NC)-ammonium dinitramide (ADN) were prepared by the electrospinning technique, and the morphology, thermal stability, combustion behaviors, and mechanical sensitivity of the fibers were characterized by means of scanning electron microscope (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), gas pressure measurement of thermostatic decomposition, laser ignition, and sensitivity tests. The results showed that the prepared fibers with fluffy 3D macrostructure were constructed by the overlap of micro/nanofibers with the energetic particles embedded in the NC matrix. The first exothermic peak temperature (Tp) of the samples containing ADN decreased by 10.1 °C at most compared to that of ADN, and the pressure rise time of all the samples containing ADN moved forward compared to that of the sample containing NC only. Furthermore, ADN can decrease the ignition delay time of NC-based fibers under atmosphere at room temperature from 33 ms to 9 ms and can enhance the burning intensity of NC-based fibers under normal pressure. In addition, compared to the single high explosive CL-20 or RDX, the mechanical sensitivities of the composite materials containing high explosive CL-20 or RDX were much decreased. The positive oxygen balance of ADN and the intensive interactions between ADN and NC can reduce the ignition delay time and promote the burning reaction intensity of NC-based composite fibers, while the mechanical sensitivities of composite fibers could be improved.
Ingested Polystyrene Nanospheres Translocate to Placenta and Fetal Tissues in Pregnant Rats: Potential Health Implications
Authors: Cary Chelsea M. , DeLoid Glen M. , Yang Zhenning , Bitounis Dimitrios , Polunas Marianne , Goedken Michael J. , Buckley Brian , Cheatham Byron , Stapleton Phoebe A. , Demokritou Philip
Published: February 2023

Recent studies in experimental animals found that oral exposure to micro- and nano-plastics (MNPs) during pregnancy had multiple adverse effects on outcomes and progeny, although no study has yet identified the translocation of ingested MNPs to the placenta or fetal tissues, which might account for those effects. We therefore assessed the placental and fetal translocation of ingested nanoscale polystyrene MNPs in pregnant rats. Sprague Dawley rats (N = 5) were gavaged on gestational day 19 with 10 mL/kg of 250 µg/mL 25 nm carboxylated polystyrene spheres (PS25C) and sacrificed after 24 h. Hyperspectral imaging of harvested placental and fetal tissues identified abundant PS25C within the placenta and in all fetal tissues examined, including liver, kidney, heart, lung and brain, where they appeared in 10–25 µm clusters. These findings demonstrate that ingested nanoscale polystyrene MNPs can breach the intestinal barrier and subsequently the maternal–fetal barrier of the placenta to access the fetal circulation and all fetal tissues. Further studies are needed to assess the mechanisms of MNP translocation across the intestinal and placental barriers, the effects of MNP polymer, size and other physicochemical properties on translocation, as well as the potential adverse effects of MNP translocation on the developing fetus.
Adherence to the Mediterranean Diet and Ultra-Processed Foods Consumption in a Group of Italian Patients with Celiac Disease
Authors: Tristan Asensi Marta , Pagliai Giuditta , Lotti Sofia , Corrao Abigail , Colombini Barbara , Giangrandi Ilaria , Sofi Francesco , Dinu Monica
Published: February 2023

Evidence on the consumption of ultra-processed foods (UPF) in adults with celiac disease (CD) and its impact on Mediterranean Diet (MD) adherence is still limited. Our aim was to determine UPF consumption and its relationship with MD adherence in a group of adults, according to the presence of CD. This case-control study included 103 adults with CD and 312 without CD. UPF intake was assessed using the NOVA Food Frequency Questionnaire (NFFQ), while MD adherence was assessed using the Medi-Lite score. UPF represented 14.5% of the diet of participants with CD (246 g/day) and came mainly from cereals-based products (29%) and sweets (24.2%). UPF consumption did not differ with the presence of CD, but participants with CD had significantly (p < 0.05) higher consumption of precooked pasta and pre-packaged breads. Participants with CD also reported a significantly lower MD adherence than participants without CD (9.4 vs. 10.4), with higher intake of meat and dairy products, and lower consumption of vegetables and fish. An inverse trend was found between UPF consumption and MD adherence in adults with CD, although not statistically significant. These findings highlight the importance of improving nutrition education for subjects with CD, which should not only focus on gluten exclusion.
Modulation of Beta-Amyloid-Activated Primary Human Neutrophils by Dietary Phenols from Virgin Olive Oil
Authors: Rivero-Pino Fernando , Grao-Cruces Elena , Lopez-Enriquez Soledad , Alba Gonzalo , Marquez-Paradas Elvira , Claro-Cala Carmen M. , Santa-Maria Consuelo , Montserrat-de la Paz Sergio
Published: February 2023

The defense mechanism against harmful stimuli is inflammation. Indeed, neurodegenerative disorders can arise as a result of a persistent neuroinflammation. Beta-amyloid (Aβ1-42) is an early trigger in the origination of Alzheimer’s disease, leading to synaptic and cognitive impairments. Virgin olive oil (VOO) is correlated with a decreased risk of developing immune-inflammatory disorders, but the potential effects of the phenolic fraction (PF) from VOO in the modulation of neuroinflammatory processes in neutrophils remain unknown. In this study, we investigated the ability of the PF to modulate the activation of Aβ1-42-stimulated primary human neutrophils, focusing on the expression of gene and surface markers and the release of pro-inflammatory and chemoattractant mediators. Down-regulation of pro-inflammatory cytokine gene expression in Aβ1-42-treated neutrophils, among other changes, was reported. Furthermore, pretreatment with PF prevented neutrophil activation. The beneficial effects in the modulation of inflammatory responses show the relevance of VOO to achieve a healthier diet that can help prevent inflammatory diseases.
Dietary Supplements Potentially Target Plasma Glutathione Levels to Improve Cardiometabolic Health in Patients with Diabetes Mellitus: A Systematic Review of Randomized Clinical Trials
Authors: Dludla Phiwayinkosi V. , Ziqubu Khanyisani , Mabhida Sihle E. , Mazibuko-Mbeje Sithandiwe E. , Hanser Sidney , Nkambule Bongani B. , Basson Albertus K. , Pheiffer Carmen , Tiano Luca , Kengne André P.
Published: February 2023

Cardiovascular diseases (CVDs) continue to be the leading cause of death in people with diabetes mellitus. Severely suppressed intracellular antioxidant defenses, including low plasma glutathione (GSH) levels, are consistently linked with the pathological features of diabetes such as oxidative stress and inflammation. In fact, it has already been established that low plasma GSH levels are associated with increased risk of CVD in people with diabetes. Dietary supplements are widely used and may offer therapeutic benefits for people with diabetes at an increased risk of developing CVDs. However, such information remains to be thoroughly scrutinized. Hence, the current systematic review explored prominent search engines, including PubMed and Google Scholar, for updated literature from randomized clinical trials reporting on the effects of dietary supplements on plasma GSH levels in people with diabetes. Available evidence indicates that dietary supplements, such as coenzyme Q10, selenium, curcumin, omega-3 fatty acids, and vitamin E or D, may potentially improve cardiometabolic health in patients with diabetes. Such beneficial effects are related to enhancing plasma GSH levels and reducing cholesterol, including biomarkers of oxidative stress and inflammation. However, available evidence is very limited and additional clinical studies are still required to validate these findings, including resolving issues related to the bioavailability of these bioactive compounds.
An Oxylipin-Related Nutrient Pattern and Risk of Type 1 Diabetes in the Diabetes Autoimmunity Study in the Young (DAISY)
Authors: Buckner Teresa , Johnson Randi K. , Vanderlinden Lauren A. , Carry Patrick M. , Romero Alex , Onengut-Gumuscu Suna , Chen Wei-Min , Fiehn Oliver , Frohnert Brigitte I. , Crume Tessa , Perng Wei , Kechris Katerina , Rewers Marian , Norris Jill M.
Published: February 2023

Oxylipins, pro-inflammatory and pro-resolving lipid mediators, are associated with the risk of type 1 diabetes (T1D) and may be influenced by diet. This study aimed to develop a nutrient pattern related to oxylipin profiles and test their associations with the risk of T1D among youth. The nutrient patterns were developed with a reduced rank regression in a nested case-control study (n = 335) within the Diabetes Autoimmunity Study in the Young (DAISY), a longitudinal cohort of children at risk of T1D. The oxylipin profiles (adjusted for genetic predictors) were the response variables. The nutrient patterns were tested in the case-control study (n = 69 T1D cases, 69 controls), then validated in the DAISY cohort using a joint Cox proportional hazards model (n = 1933, including 81 T1D cases). The first nutrient pattern (NP1) was characterized by low beta cryptoxanthin, flavanone, vitamin C, total sugars and iron, and high lycopene, anthocyanidins, linoleic acid and sodium. After adjusting for T1D family history, the HLA genotype, sex and race/ethnicity, NP1 was associated with a lower risk of T1D in the nested case-control study (OR: 0.44, p = 0.0126). NP1 was not associated with the risk of T1D (HR: 0.54, p-value = 0.1829) in the full DAISY cohort. Future studies are needed to confirm the nested case-control findings and investigate the modifiable factors for oxylipins.
Identification and Evaluation of Hub Long Noncoding RNAs and mRNAs in High Fat Diet Induced Liver Steatosis
Authors: Sui Jing , Pan Da , Yu Junhui , Wang Ying , Sun Guiju , Xia Hui
Published: February 2023

Nonalcoholic fatty liver disease (NAFLD) is considered the most prevalent chronic liver disease, but the understanding of the mechanism of NAFLD is still limited. The aim of our study was to explore hub lncRNAs and mRNAs and pathological processes in high-fat diet (HFD)-induced and lycopene-intervened liver steatosis. We analyzed the gene profiles in the GSE146627 dataset from the Gene Expression Omnibus (GEO) database to identify differentially expressed lncRNAs and mRNAs, and we constructed coexpression networks based on weighted gene coexpression network analysis (WGCNA). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized for functional enrichment analysis. We found that the turquoise, blue, brown, yellow, green, and black modules were significantly correlated with NAFLD. Functional enrichment analysis revealed that some hub lncRNAs (Smarca2, Tacc1, Flywch1, and Mef2c) might be involved in the regulation of the inflammatory and metabolic pathways (such as TNF signaling, metabolic, mTOR signaling, MAPK signaling, and p53 signaling pathways) in NAFLD. The establishment of an NAFLD mouse model confirmed that lycopene supply attenuated hepatic steatosis in HFD-induced NAFLD. Our analysis revealed that the inflammatory and metabolic pathways may be crucially involved in the pathogenesis of NAFLD, and hub lncRNAs provide novel biomarkers, therapeutic ideas, and targets for NAFLD. Moreover, lycopene has the potential to be a phytochemical for the prevention of HFD-induced liver steatosis.
Immunotherapy Using Immunogenic Mimotopes Selected by Phage Display plus Amphotericin B Inducing a Therapeutic Response in Mice Infected with Leishmania amazonensis
Authors: Soyer Tauane G. , Ramos Fernanda F. , Pereira Isabela A. G. , Lage Daniela P. , Bandeira Raquel S. , de Jesus Marcelo M. , Costa Guilherme P. , Machado Amanda S. , Freitas Camila S. , Vale Danniele L. , Martins Vívian T. , Galdino Alexsandro S. , Chávez-Fumagalli Miguel A. , Menezes-Souza Daniel , Duarte Mariana C. , Roatt Bruno M. , Coelho Eduardo A. F. , Tavares Grasiele S. V.
Published: February 2023

Leishmania amazonensis can cause cutaneous and visceral clinical manifestations of leishmaniasis in infected hosts. Once the treatment against disease is toxic, presents high cost, and/or there is the emergence of parasite-resistant strains, alternative means through which to control the disease must be developed. In this context, immunotherapeutics combining known drugs with immunogens could be applied to control infections and allow hosts to recover from the disease. In this study, immunotherapeutics protocols associating mimotopes selected by phage display and amphotericin B (AmpB) were evaluated in L. amazonensis-infected mice. Immunogens, A4 and A8 phages, were administered alone or associated with AmpB. Other animals received saline, AmpB, a wild-type phage (WTP), or WTP/AmpB as controls. Evaluations performed one and thirty days after the application of immunotherapeutics showed that the A4/AmpB and A8/AmpB combinations induced the most polarized Th1-type immune responses, which reflected in significant reductions in the lesion’s average diameter and in the parasite load in the infected tissue and distinct organs of the animals. In addition, the combination also reduced the drug toxicity, as compared to values found using it alone. In this context, preliminary data presented here suggest the potential to associate A4 and A8 phages with AmpB to be applied in future studies for treatment against leishmaniasis.
Inflammatory Immune Process and Depression-like Behavior in Hypothyroid Rats: A [18F] DPA-714 Micro Positron Emission Tomography Study
Authors: Wang Yizhen , Tian Aijuan , Zhang Fang , Yu Jing , Ling Jianer
Published: February 2023

Hypothyroidism is closely related to mental disorders, mainly depression, through an as-yet-unknown mechanism. The cerebral inflammatory immune process has been implied to play a pivotal role in the onset of affective symptoms in several conditions. In order to gain insight into the mechanism underlying the depressive behaviors in hypothyroid rats, brain microglial activation was evaluated using micro positron emission tomography imaging with a translocator protein (TSPO) radioligand. Hypothyroidism was induced in adult male Wistar rats by administration of 0.05% propylthiouracil in drinking water for five weeks. Open field, forced swimming and tail suspension tests were employed to evaluate the depressive behavior in hypothyroid rats, and the relationship between the behavioral changes and brain microglial activation was evaluated using [18F] DPA-714 micro positron emission tomography imaging. The open field test revealed significantly reduced first-minute activity and rearing behavior in the hypothyroid group, as well as significantly increased immobility in the forced swimming test and the tail suspension test. Hypothyroidism induced significantly increased microglial activation in the hippocampus. The radioligand uptake in the hippocampus correlated negatively with first-minute activity in the open field test (p < 0.05), and the radioligand uptake in the hippocampus correlated positively with changes in the immobility time in the forced swimming test and the tail suspension test (p < 0.05). Immunohistochemistry also confirmed the activation of microglia and inflammatory bodies in hypothyroid rats. The results indicate that hypothyroidism can induce depressive behavior in adult Wistar rats, microglial activation in the hippocampus plays an important role in the depressive behavior in hypothyroid rats and the inflammatory immune mechanism may underlie the behavioral abnormalities in thyroid dysfunction. Furthermore, the findings in the present study suggest there might be a common mechanism underlying depressive behavior in adult-onset hypothyroidism and depression.
Critical Analysis and Optimization of Stoichiometric Ratio of Drug-Coformer on Cocrystal Design: Molecular Docking, In Vitro and In Vivo Assessment
Authors: Dhibar Manami , Chakraborty Santanu , Basak Souvik , Pattanayak Paramita , Chatterjee Tanmay , Ghosh Balaram , Raafat Mohamed , Abourehab Mohammed A. S.
Published: February 2023

In this present research, an attempt has been made to address the influence of drug-coformer stoichiometric ratio on cocrystal design and its impact on improvement of solubility and dissolution, as well as bioavailability of poorly soluble telmisartan. The chemistry behind cocrystallization and the optimization of drug-coformer molar ratio were explored by the molecular docking approach, and theoretical were implemented practically to solve the solubility as well as bioavailability related issues of telmisartan. A new multicomponent solid form, i.e., cocrystal, was fabricated using different molar ratios of telmisartan and maleic acid, and characterized by SEM, DSC and XRD studies. The molecular docking study suggested that specific molar ratios of drug-coformer can successfully cluster with each other and form a specific geometry with favourable energy conformation to form cocrystals. Synthesized telmisartan-maleic acid cocrystals showed remarkable improvement in solubility and dissolution of telmisartan by 9.08-fold and 3.11-fold, respectively. A SEM study revealed the formation of cocrystals of telmisartan when treated with maleic acid. DSC and XRD studies also confirmed the conversion of crystalline telmisartan into its cocrystal state upon treating with maleic acid. Preclinical investigation revealed significant improvement in the efficacy of optimized cocrystals in terms of plasma drug concentration, indicating enhanced bioavailability through improved solubility as well as dissolution of telmisartan cocrystals. The present research concluded that molecular docking is an important path in selecting an appropriate stoichiometric ratio of telmisartan: maleic acid to form cocrystals and improve the solubility, dissolution, and bioavailability of poorly soluble telmisartan.
Therapeutic Potential of Zeolites/Vitamin B12 Nanocomposite on Complete Freund’s Adjuvant-Induced Arthritis as a Bone Disorder: In Vivo Study and Bio-Molecular Investigations
Authors: Belal Amany , Mahmoud Rehab , Taha Mohamed , Halfaya Fatma , Hassaballa Ahmed , Elbanna Esraa , Khaled Esraa , Farghali Ahmed , Abo El-Ela Fatma , Mahgoub Samar , Ghoneim Mohammed , Zaky Mohamed
Published: February 2023

Rheumatoid arthritis (RA) is a long-term autoimmune disease. As nanotechnology has advanced, a growing number of nanodrugs have been used in the treatment of RA due to their unique physical and chemical properties. The purpose of this study was to assess the therapeutic potential of a novel zeolite/vitamin B12 nanocomposite (Nano ZT/Vit B12) formulation in complete Freund’s adjuvant (CFA)-induced arthritis. The newly synthesized Nano ZT/Vit B12 was fully characterized using various techniques such as XRD, FT-IR, BET analysis, HERTEM, SEM, practical size, zeta potential, XRF, and EDX. The anti-arthritic, anti-inflammatory, and antioxidant activities as well as the immunomodulation effect of Nano ZT/Vit B12 on the CFA rat model of arthritis were examined. Histopathologic ankle joint injuries caused by CFA intrapedal injection included synovium hyperplasia, inflammatory cell infiltration, and extensive cartilage deterioration. The arthritic rats’ Nano ZT/Vit B12 supplementation significantly improved these effects. Furthermore, in arthritic rats, Nano ZT/Vit B12 significantly reduced serum levels of RF and CRP, as well as the levels of IL-1β, TNF-α, IL-17, and ADAMTS-5, while increasing IL-4 and TIMP-3 levels. Nano-ZT/Vit B12 significantly declined the LPO level and increased antioxidant activities, such as GSH content and GST activity, in the arthritic rats. In arthritic rats, Nano ZT/Vit B12 also reduced TGF-β mRNA gene expression and MMP-13 protein levels. Collectively, Nano ZT/Vit B12 seems to have anti-arthritic, anti-inflammatory, and antioxidant properties, making it a promising option for RA in the future.
Cytochalasin B Influences Cytoskeletal Organization and Osteogenic Potential of Human Wharton’s Jelly Mesenchymal Stem Cells
Authors: Pampanella Luca , Abruzzo Provvidenza Maria , Tassinari Riccardo , Alessandrini Andrea , Petrocelli Giovannamaria , Ragazzini Gregorio , Cavallini Claudia , Pizzuti Valeria , Collura Nicoletta , Canaider Silvia , Facchin Federica , Ventura Carlo
Published: February 2023

Among perinatal stem cells of the umbilical cord, human Wharton’s jelly mesenchymal stem cells (hWJ-MSCs) are of great interest for cell-based therapy approaches in regenerative medicine, showing some advantages over other MSCs. In fact, hWJ-MSCs, placed between embryonic and adult MSCs, are not tumorigenic and are harvested with few ethical concerns. Furthermore, these cells can be easily cultured in vitro, maintaining both stem properties and a high proliferative rate for several passages, as well as trilineage capacity of differentiation. Recently, it has been demonstrated that cytoskeletal organization influences stem cell biology. Among molecules able to modulate its dynamics, Cytochalasin B (CB), a cyto-permeable mycotoxin, influences actin microfilament polymerization, thus affecting several cell properties, such as the ability of MSCs to differentiate towards a specific commitment. Here, we investigated for the first time the effects of a 24 h-treatment with CB at different concentrations (0.1–3 μM) on hWJ-MSCs. CB influenced the cytoskeletal organization in a dose-dependent manner, inducing changes in cell number, proliferation, shape, and nanomechanical properties, thus promoting the osteogenic commitment of hWJ-MSCs, as confirmed by the expression analysis of osteogenic/autophagy markers.