bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted Urine Metabolomics for Monitoring Renal Allograft Injury and Immunosuppression in Pediatric Patients
Authors: Sigdel Tara K. , Schroeder Andrew W. , Yang Joshua Y. C. , Sarwal Reuben D. , Liberto Juliane M. , Sarwal Minnie M.
Published: July 2020

Despite new advancements in surgical tools and therapies, exposure to immunosuppressive drugs related to non-immune and immune injuries can cause slow deterioration and premature failure of organ transplants. Diagnosis of these injuries by non-invasive urine monitoring would be a significant clinical advancement for patient management, especially in pediatric cohorts. We investigated the metabolomic profiles of biopsy matched urine samples from 310 unique kidney transplant recipients using gas chromatography–mass spectrometry (GC-MS). Focused metabolite panels were identified that could detect biopsy confirmed acute rejection with 92.9% sensitivity and 96.3% specificity (11 metabolites) and could differentiate BK viral nephritis (BKVN) from acute rejection with 88.9% sensitivity and 94.8% specificity (4 metabolites). Overall, targeted metabolomic analyses of biopsy-matched urine samples enabled the generation of refined metabolite panels that non-invasively detect graft injury phenotypes with high confidence. These urine biomarkers can be rapidly assessed for non-invasive diagnosis of specific transplant injuries, opening the window for precision transplant medicine.
Adaptive Designs: Lessons for Inflammatory Bowel Disease Trials
Authors: D'Amico Ferdinando , Danese Silvio , Peyrin-Biroulet Laurent
Published: July 2020

In recent decades, scientific research has considerably evolved in the field of inflammatory bowel diseases (IBD) and clinical studies have become increasingly complex, including new outcomes, different study populations, and additional techniques of re-randomization and centralized control. In this context, randomized clinical trials are the gold standard for new drugs’ development. However, traditional study designs are time-consuming, expensive, and only a small percentage of the tested therapies are approved. For this reason, a new study design called “adaptive design” has been introduced, allowing to accumulate data during the study and to make predefined adjustments based on the results of scheduled interim analysis. Our aim is to clarify the advantages and drawbacks of adaptive designs in order to properly interpret study results and to identify their role in upcoming IBD trials.
Gender Differences in Association between Air Pollution and Daily Mortality in the Capital of the Green Lungs of Poland–Population-Based Study with 2,953,000 Person-Years of Follow-Up
Authors: Kuźma Łukasz , Struniawski Krzysztof , Pogorzelski Szymon , Bachórzewska-Gajewska Hanna , Dobrzycki Sławomir
Published: July 2020

(1) Introduction: air pollution is considered to be one of the main risk factors for public health. According to the European Environment Agency (EEA), air pollution contributes to the premature deaths of approximately 500,000 citizens of the European Union (EU), including almost 5000 inhabitants of Poland every year. (2) Purpose: to assess the gender differences in the impact of air pollution on the mortality in the population of the city of Bialystok—the capital of the Green Lungs of Poland. (3) Materials and Methods: based on the data from the Central Statistical Office, the number—and causes of death—of Białystok residents in the period 2008–2017 were analyzed. The study utilized the data recorded by the Provincial Inspectorate for Environmental Protection station and the Institute of Meteorology and Water Management during the analysis period. Time series regression with Poisson distribution was used in statistical analysis. (4) Results: A total of 34,005 deaths had been recorded, in which women accounted for 47.5%. The proportion of cardiovascular-related deaths was 48% (n = 16,370). An increase of SO2 concentration by 1-µg/m3 (relative risk (RR) 1.07, 95% confidence interval (CI) 1.02–1.12; p = 0.005) and a 10 °C decrease of temperature (RR 1.03, 95% CI 1.01–1.05; p = 0.005) were related to an increase in the number of daily deaths. No gender differences in the impact of air pollution on mortality were observed. In the analysis of the subgroup of cardiovascular deaths, the main pollutant that was found to have an effect on daily mortality was particulate matter with a diameter of 2.5 μm or less (PM2.5); the RR for 10-µg/m3 increase of PM2.5 was 1.07 (95% CI 1.02–1.12; p = 0.01), and this effect was noted only in the male population. (5) Conclusions: air quality and atmospheric conditions had an impact on the mortality of Bialystok residents. The main air pollutant that influenced the mortality rate was SO2, and there were no gender differences in the impact of this pollutant. In the male population, an increased exposure to PM2.5 concentration was associated with significantly higher cardiovascular mortality. These findings suggest that improving air quality, in particular, even with lower SO2 levels than currently allowed by the World Health Organization (WHO) guidelines, may benefit public health. Further studies on this topic are needed, but our results bring questions whether the recommendations concerning acceptable concentrations of air pollutants should be stricter, or is there a safe concentration of SO2 in the air at all.
Endothelial Dysfunction in Chronic Kidney Disease, from Biology to Clinical Outcomes: A 2020 Update
Authors: Roumeliotis Stefanos , Mallamaci Francesca , Zoccali Carmine
Published: July 2020

The vascular endothelium is a dynamic, functionally complex organ, modulating multiple biological processes, including vascular tone and permeability, inflammatory responses, thrombosis, and angiogenesis. Endothelial dysfunction is a threat to the integrity of the vascular system, and it is pivotal in the pathogenesis of atherosclerosis and cardiovascular disease. Reduced nitric oxide (NO) bioavailability is a hallmark of chronic kidney disease (CKD), with this disturbance being almost universal in patients who reach the most advanced phase of CKD, end-stage kidney disease (ESKD). Low NO bioavailability in CKD depends on several mechanisms affecting the expression and the activity of endothelial NO synthase (eNOS). Accumulation of endogenous inhibitors of eNOS, inflammation and oxidative stress, advanced glycosylation products (AGEs), bone mineral balance disorders encompassing hyperphosphatemia, high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23), and low levels of the active form of vitamin D (1,25 vitamin D) and the anti-ageing vasculoprotective factor Klotho all impinge upon NO bioavailability and are critical to endothelial dysfunction in CKD. Wide-ranging multivariate interventions are needed to counter endothelial dysfunction in CKD, an alteration triggering arterial disease and cardiovascular complications in this high-risk population.
Adipose-Derived Stem Cells Reduce Lipopolysaccharide-Induced Myelin Degradation and Neuroinflammatory Responses of Glial Cells in Mice
Authors: Yatsenko Kateryna , Lushnikova Iryna , Ustymenko Alina , Patseva Maryna , Govbakh Iryna , Kyryk Vitalii , Tsupykov Oleg
Published: July 2020

Brain inflammation is a key event triggering the pathological process associated with many neurodegenerative diseases. Current personalized medicine and translational research in neurodegenerative diseases focus on adipose-derived stem cells (ASCs), because they are patient-specific, thereby reducing the risk of immune rejection. ASCs have been shown to exert a therapeutic effect following transplantation in animal models of neuroinflammation. However, the mechanisms by which transplanted ASCs promote cell survival and/or functional recovery are not fully understood. We investigated the effects of ASCs in in vivo and in vitro lipopolysaccharide (LPS)-induced neuroinflammatory models. Brain damage was evaluated immunohistochemically using specific antibody markers of microglia, astroglia and oligodendrocytes. ASCs were used for intracerebral transplantation, as well as for non-contact co-culture with brain slices. In both in vivo and in vitro models, we found that LPS caused micro- and astroglial activation and oligodendrocyte degradation, whereas the presence of ASCs significantly reduced the damaging effects. It should be noted that the observed ASCs protection in a non-contact co-culture suggested that this effect was due to humoral factors via ASC-released biomodulatory molecules. However, further clinical studies are required to establish the therapeutic mechanisms of ASCs, and optimize their use as a part of a personalized medicine strategy.
Functional Coatings for Orthodontic Archwires—A Review
Authors: Bącela Justyna , Łabowska Magdalena Beata , Detyna Jerzy , Zięty Anna , Michalak Izabela
Published: July 2020

In this literature review, the current state-of-art of coatings for orthodontic archwires’ increasing antimicrobial and relevant mechanical properties, such as surface topography, friction or corrosion resistance, has been presented. There is a growing request for orthodontic appliances, therefore, most researchers focus on innovative functional coatings to cover orthodontic archwires and brackets. Orthodontic appliances are exposed to the unfavorable oral cavity environment, consisting of saliva flow, food, temperature and appliance force. As a consequence, friction or biocorrosion processes may occur. This can affect the functionality of the orthodontic elements, causing changes in their microstructure, surface topography and mechanical properties. Furthermore, the material which the orthodontic archwire is made from is of particular importance in terms of the possible corrosion resistance. This is especially important for patients who are hypersensitive to metals, for example, nickel, which causes allergic reactions. In the literature, there are some studies, carried out in vitro and in vivo, mostly examining the antibacterial, antiadherent, mechanical and roughness properties of functional coatings. They are clinically acceptable but still some properties have to be studied and be developed for better results. In this paper the influence of additives such as nanoparticles of silver and nitrogen-doped TiO2 applied on orthodontic brackets by different methods on the antimicrobial properties was analyzed. Future improvement of coating techniques as well as modification of the archwire composition can reduce the release of nickel ions and eliminate friction and bacterial adhesion problems, thus accelerating treatment time.
Ionic Liquids and Calcium Oxide Grafted with Allylmalonic Acid Applied to Support the Peroxide Crosslinking of an Ethylene–Propylene Copolymer
Authors: Maciejewska Magdalena
Published: July 2020

Nanosized calcium oxide (CaO) featuring a surface grafted with allylmalonic acid (ALA) was used to increase the efficiency of the peroxide crosslinking of an ethylene–propylene copolymer (EPM) filled with silica nanoparticles. In this study, 1-butyl-3-methylimidazolium ionic liquids (ILs) with different anions were applied to improve the dispersion of CaO/ALA and silica nanoparticles in the EPM copolymer, as well as to catalyze the interfacial crosslinking reactions. In this article, we discuss the effects of CaO/ALA and ILs on the curing characteristics, vulcanization temperature, crosslink density, mechanical properties, and thermal stability of EPM, as well as the resistance of EPM to weather aging. The CaO/ALA with ILs reduced the vulcanization time of the rubber compounds without a significant effect on the vulcanization temperature. Their application resulted in an increased vulcanizate crosslink density, as well as improved tensile strength compared to the pure peroxide system. The influence of 1-butyl-3-methylimidazolium ILs on EPM vulcanization and performance depends on the anion present in the molecules of the ionic liquid. The most active IL seems to be that with the tetrafluoroborate anion.
Luminescence Quenching Behavior of Hydrothermally Grown YVO4:Eu3+ Nanophosphor Excited under Low Temperature and Vacuum Ultra Violet Discharge
Authors: Wu Mihye , Park Hyemin , Lee Eun Gyu , Lee Sanghun , Hong Yu Jin , Choi Sungho
Published: July 2020

The luminescence quenching behavior and energy transfer process in hydrothermally grown Eu3+-doped YVO4 nanophosphors were studied using low temperature photoluminescence spectroscopy. The luminescence efficiency of nanophosphor is dependent on the acidity of its solution media and the post annealing condition after hydrothermal processing. The overall results suggest that the abnormal luminescence behavior of Eu3+-doped nanocrystalline YVO4 under low temperature photoexcitation is due to the incorporated non-radiative hydroxyl groups often encountered in hydrothermal synthesis as well as to the inefficient energy transfer to luminescent ions from vanadate groups.
Fatigue Life Assessment of the Shell Structure of Purified Terephthalic Acid Filter Press
Authors: Song Ming , Zhang Weiya , Jiang Wenchun , Wang Jinguang , Zhao Xu , Zhai Xiangnan
Published: July 2020

The filter press is one of the most important devices in purified terephthalic acid (PTA) refinement, and it is of great significance to ensure the fatigue strength of the structure in operation. In this study, the fatigue life prediction of the shell structure of the PTA filter press was investigated through numerical and experimental methods. Firstly, the accurate stress at the critical area of the stiffener was obtained based on the thermomechanical model and submodel approach proposed. Subsequently, the fatigue life was evaluated by the fatigue strength reduction method and hot spot stress method. Finally, the shell structure is optimized by increasing the size of the axial stiffener and continuous hoop stiffener. The results unveil that both thermal load and outer structure constraints have little effect on the radial displacement and stress amplitude of the shell structure. Through modifying the fatigue design curve of the fatigue strength reduction method, the shell structure of the PTA filter press has 42.0% and 0.3% failure probabilities in the previous and present cyclic pressure conditions. Furthermore, the hoop stiffener plays an important role in reducing radial displacement and stress amplitude, among which three hoop stiffeners exhibit the most satisfactory optimization.
Validated Finite Element Models of Premolars: A Scoping Review
Authors: Richert Raphaël , Farges Jean-Christophe , Tamimi Faleh , Naouar Naim , Boisse Philippe , Ducret Maxime
Published: July 2020

Finite element (FE) models are widely used to investigate the biomechanics of reconstructed premolars. However, parameter identification is a complex step because experimental validation cannot always be conducted. The aim of this study was to collect the experimentally validated FE models of premolars, extract their parameters, and discuss trends. A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Records were identified in three electronic databases (MEDLINE [PubMed], Scopus, The Cochrane Library) by two independent reviewers. Twenty-seven parameters dealing with failure criteria, model construction, material laws, boundary conditions, and model validation were extracted from the included articles. From 1306 records, 214 were selected for eligibility and entirely read. Among them, 19 studies were included. A heterogeneity was observed for several parameters associated with failure criteria and model construction. Elasticity, linearity, and isotropy were more often chosen for dental and periodontal tissues with a Young’s modulus mostly set at 18–18.6 GPa for dentine. Loading was mainly simulated by an axial force, and FE models were mostly validated by in vitro tests evaluating tooth strains, but different conditions about experiment type, sample size, and tooth status (intact or restored) were reported. In conclusion, material laws identified herein could be applied to future premolar FE models. However, further investigations such as sensitivity analysis are required for several parameters to clarify their indication.
Crystallization Behavior of the Low-Temperature Mineralization Sintering Process for Glass Nanoparticles
Authors: Seo Yeongjun , Goto Tomoyo , Cho Sunghun , Sekino Tohru
Published: July 2020

Bioactive glasses are promising materials for various applications, such as bone grafts and implants. The development of sintering techniques for bioactive glasses is one of the most important ways to expand the application to biomaterials. In this paper, we demonstrate the low-temperature mineralization sintering process (LMSP) of glass nanoparticles and their crystallization behavior. LMSP is a novel process employed to densify glass nanoparticles at an extremely low temperature of 120 °C. For this new approach, the hydrothermal condition, mineralization, and the nanosize effect are integrated into LMSP. To induce mineralization in LMSP, bioactive glass nanoparticles (BGNPs, 55SiO2-40CaO-5P2O5, mol%), prepared by the sol-gel process, were mixed with a small amount of simulated body fluid (SBF) solution. As a result, 93% dense BGNPs were realized under a temperature of 120 °C and a uniaxial pressure of 300 MPa. Due to the effect of mineralization, crystalline hydroxyapatite (HAp) was clearly formed at the boundaries of BGNPs, filling particles and interstitials. As a result, the relative density was remarkably close to that of the BGNPs conventionally sintered at 1050 °C. Additionally, the Vickers hardness value of LMSP samples varied from 2.10 ± 0.12 GPa to 4.28 ± 0.11 GPa, and was higher than that of the BGNPs conventionally sintered at 850 °C (2.02 ± 0.11 GPa). These results suggest that, in addition to LMSP being an efficient densification method for obtaining bulk bioactive glasses at a significantly lower temperature level, this process has great potential for tissue engineering applications, such as scaffolds and implants.
Modulation of Glial Responses by Furanocembranolides: Leptolide Diminishes Microglial Inflammation in Vitro and Ameliorates Gliosis In Vivo in a Mouse Model of Obesity and Insulin Resistance
Authors: Corraliza-Gómez Miriam , Gallardo Amalia B. , Díaz-Marrero Ana R. , de la Rosa José M. , D’Croz Luis , Darias José , Arranz Eduardo , Cózar-Castellano Irene , Ganfornina María D. , Cueto Mercedes
Published: July 2020

Neurodegenerative diseases are age-related disorders caused by progressive neuronal death in different regions of the nervous system. Neuroinflammation, modulated by glial cells, is a crucial event during the neurodegenerative process; consequently, there is an urgency to find new therapeutic products with anti-glioinflammatory properties. Five new furanocembranolides (1−5), along with leptolide, were isolated from two different extracts of Leptogorgia sp., and compound 6 was obtained from chemical transformation of leptolide. Their structures were determined based on spectroscopic evidence. These seven furanocembranolides were screened in vitro by measuring their ability to modulate interleukin-1β (IL-1β) production by microglial BV2 cells after LPS (lipopolysaccharide) stimulation. Leptolide and compounds 3, 4 and 6 exhibited clear anti-inflammatory effects on microglial cells, while compound 2 presented a pro-inflammatory outcome. The in vitro results prompted us to assess anti-glioinflammatory effects of leptolide in vivo in a high-fat diet-induced obese mouse model. Interestingly, leptolide treatment ameliorated both microgliosis and astrogliosis in this animal model. Taken together, our results reveal a promising direct biological effect of furanocembranolides on microglial cells as bioactive anti-inflammatory molecules. Among them, leptolide provides us a feasible therapeutic approach to treat neuroinflammation concomitant with metabolic impairment.
Hollow Fiber Membranes of PCL and PCL/Graphene as Scaffolds with Potential to Develop In Vitro Blood—Brain Barrier Models
Authors: Mantecón-Oria Marián , Diban Nazely , Berciano Maria T. , Rivero Maria J. , David Oana , Lafarga Miguel , Tapia Olga , Urtiaga Ane
Published: July 2020

There is a huge interest in developing novel hollow fiber (HF) membranes able to modulate neural differentiation to produce in vitro blood–brain barrier (BBB) models for biomedical and pharmaceutical research, due to the low cell-inductive properties of the polymer HFs used in current BBB models. In this work, poly(ε-caprolactone) (PCL) and composite PCL/graphene (PCL/G) HF membranes were prepared by phase inversion and were characterized in terms of mechanical, electrical, morphological, chemical, and mass transport properties. The presence of graphene in PCL/G membranes enlarged the pore size and the water flux and presented significantly higher electrical conductivity than PCL HFs. A biocompatibility assay showed that PCL/G HFs significantly increased C6 cells adhesion and differentiation towards astrocytes, which may be attributed to their higher electrical conductivity in comparison to PCL HFs. On the other hand, PCL/G membranes produced a cytotoxic effect on the endothelial cell line HUVEC presumably related with a higher production of intracellular reactive oxygen species induced by the nanomaterial in this particular cell line. These results prove the potential of PCL HF membranes to grow endothelial cells and PCL/G HF membranes to differentiate astrocytes, the two characteristic cell types that could develop in vitro BBB models in future 3D co-culture systems.
Carbide to Graphite Transition Control by Thermal Analysis in Grey Cast Irons
Authors: Neacsu Elena Loredana , Riposan Iulian , Cojocaru Ana Maria , Stan Stelian , Stan Iuliana
Published: July 2020

The present work compared the solidification pattern of un-inoculated and inoculated hypoeutectic grey cast irons (3.7–3.8% CE), focused on carbide to graphite formation transition, by the use of an adequate experimental technique, able to measure real stable (Tst) and metastable (Tmst) eutectic temperatures. Have been used three ceramic cups for investigating thermal analysis: (i) for normal solidification; (ii) with addition of Te for Tmst measurement; (iii) with more inoculant addition for Tst measurement. As a general rule, measured values appear to be lower compared with calculated values (as chemical composition effects), with an average difference at 14.4 °C for Tst and 8.3 °C for Tmst. It is found a good relationship between the undercooling degree at the lowest eutectic temperature (ΔT1) and at the end of solidification (ΔT3), reported to measured Tmst. The free carbides formation (chill tendency) is in good relationship with the undercooling degree during the eutectic reaction, reported to measured Tmst, especially for thin and medium wall thickness castings. The real measured Tmst instead of calculated Tmst is compulsory for the thin wall castings production, very sensitive to carbides to graphite transition. In the present experimental conditions, no visible relationship appears to be between chill tendency and undercooling at the end of solidification (ΔT3).
Review of Laser Powder Bed Fusion of Gamma-Prime-Strengthened Nickel-Based Superalloys
Authors: Adegoke Olutayo , Andersson Joel , Brodin Håkan , Pederson Robert
Published: July 2020

This paper reviews state of the art laser powder bed fusion (L-PBF) manufacturing of γ′ nickel-based superalloys. L-PBF resembles welding; therefore, weld-cracking mechanisms, such as solidification, liquation, strain age, and ductility-dip cracking, may occur during L-PBF manufacturing. Spherical pores and lack-of-fusion voids are other defects that may occur in γ′-strengthened nickel-based superalloys manufactured with L-PBF. There is a correlation between defect formation and the process parameters used in the L-PBF process. Prerequisites for solidification cracking include nonequilibrium solidification due to segregating elements, the presence of liquid film between cells, a wide critical temperature range, and the presence of thermal or residual stress. These prerequisites are present in L-PBF processes. The phases found in L-PBF-manufactured γ′-strengthened superalloys closely resemble those of the equivalent cast materials, where γ, γ′, and γ/γ′ eutectic and carbides are typically present in the microstructure. Additionally, the sizes of the γ′ particles are small in as-built L-PBF materials because of the high cooling rate. Furthermore, the creep performance of L-PBF-manufactured materials is inferior to that of cast material because of the presence of defects and the small grain size in the L-PBF materials; however, some vertically built L-PBF materials have demonstrated creep properties that are close to those of cast materials.
Comprehensive Vitamer Profiling of Folate Mono- and Polyglutamates in Baker’s Yeast (Saccharomyces cerevisiae) as a Function of Different Sample Preparation Procedures
Authors: Gmelch Lena , Wirtz Daniela , Witting Michael , Weber Nadine , Striegel Lisa , Schmitt-Kopplin Philippe , Rychlik Michael
Published: July 2020

Folates are a group of B9 vitamins playing an important role in many metabolic processes such as methylation reactions, nucleotide synthesis or oxidation and reduction processes. However, humans are not able to synthesize folates de novo and thus rely on external sources thereof. Baker’s yeast (Saccharomyces cerevisiae) has been shown to produce high amounts of this vitamin but extensive identification of its folate metabolism is still lacking. Therefore, we optimized and compared different sample preparation and purification procedures applying solid phase extraction (SPE). Strong anion exchange (SAX), C18 and hydrophilic–lipophilic-balanced (HLB) materials were tested for their applicability in future metabolomics studies. SAX turned out to be the preferred material for the quantitative purification of folates. Qualification of several folate vitamers was achieved by ultra-high pressure liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-Q-ToF-MS) measurements and quantification was performed by liquid chromatography tandem mass spectrometry (LC-MS/MS) applying stable isotope dilution assays (SIDAs). The oxidation product s-pyrazino-triazine (MeFox) was included into the SIDA method for total folate determination and validation. Applying the best protocol (SAX) in regard to folate recovery, we analyzed 32 different vitamers in different polyglutamate states up to nonaglutamates, of which we could further identify 26 vitamers based on tandem-MS (MS2) spectra. Total folate quantification revealed differences in formyl folate contents depending on the cartridge chemistry used for purification. These are supposedly a result of interconversion reactions occurring during sample preparation due to variation in pH adjustments for the different purification protocols. The occurrence of interconversion and oxidation reactions should be taken into consideration in sample preparation procedures for metabolomics analyses with a focus on folates.
Using a Dielectrophoretic Microfluidic Biochip Enhanced Fertilization of Mouse Embryo in Vitro
Authors: Huang Hong-Yuan , Kao Wei-Lun , Wang Yi-Wen , Yao Da-Jeng
Published: July 2020

Droplet microfluidics has appealed to many interests for its capability to epitomize cells in a microscale environment and it is also a forceful technique for high-throughput single-cell epitomization. A dielectrophoretic microfluidic system imitates the oviduct of mammals with a microchannel to achieve fertilization in vitro (IVF) of an imprinting control-region (ICR) mouse. We applied a microfluidic chip and a positive dielectrophoretic (p-DEP) force to capture and to screen the sperm for the purpose of manipulating the oocyte. The p-DEP responses of the oocyte and sperm were exhibited under applied bias conditions (waveform AC 10 Vpp, 1 MHz) for trapping 1 min. The insemination concentration of sperm nearby the oocyte was increased to enhance the probability of natural fertilization through the p-DEP force trapping. A simulation tool (CFDRC-ACE+) was used to simulate and to analyze the distribution of the electric field. The DEP microfluidic devices were fabricated using poly (dimethylsiloxane) (PDMS) and ITO (indium tin oxide)-glass with electrodes. We discuss the requirement of sperm in a DEP microfluidic chip at varied concentrations to enhance the future rate of fertilization in vitro for an oligozoospermia patient. The result indicates that the rate of fertility in our device is 17.2 ± 7.5% (n = 30) at about 3000 sperms, compatible with traditional droplet-based IVF, which is 14.2 ± 7.5% (n = 28).
Comparison of Three Approaches for Bioleaching of Rare Earth Elements from Bauxite
Authors: Barnett Megan J. , Palumbo-Roe Barbara , Deady Eimear A. , Gregory Simon P.
Published: July 2020

Approximately 300 million tonnes of bauxite are processed annually, primarily to extract alumina, and can contain moderate rare earth element (REE) concentrations, which are critical to a green energy future. Three bioleaching techniques (organic acid, reductive and oxidative) were tested on three karst bauxites using either Aspergillus sp. (organic acid bioleaching) or Acidithiobacillus ferrooxidans (reductive and oxidative bioleaching). Recovery was highest in relation to middle REE (generally Nd to Gd), with maximum recovery of individual REE between 26.2% and 62.8%, depending on the bauxite sample. REE recovery occurred at low pH (generally < 3), as a result of organic acids produced by Aspergillus sp. or sulphuric acid present in A. ferrooxidans growth media. Acid production was seen when A. ferrooxidans was present. However, a clear increase in REE recovery in the presence of A. ferrooxidans (compared to the control) was only seen with one bauxite sample (clay-rich) and only under oxidative conditions. The complex and varied nature of REE-bearing minerals in bauxite provides multiple targets for bioleaching, and although the majority of recoverable REE can be leached by organic and inorganic acids, there is potential for enhanced recovery by bioleaching.
Mineralogy and Metallogenesis of the Sanbao Mn–Ag (Zn-Pb) Deposit in the Laojunshan Ore District, SE Yunnan Province, China
Authors: Du Shengjiang , Wen Hanjie , Liu Shirong , Qin Chaojian , Yan Yongfeng , Yang Guangshu , Feng Pengyu
Published: July 2020

The Sanbao Mn–Ag (Zn-Pb) deposit located in the Laojunshan ore district is one of the most important deposits that has produced most Ag and Mn metals in southeastern Yunnan Province, China. Few studies are available concerning the distribution and mineralization of Ag, restricting further resource exploration. In this study, detailed mineralogy, chronology, and geochemistry are examined with the aim of revealing Ag occurrence and its associated primary base-metal and supergene mineralization. Results show that manganite and romanèchite are the major Ag-bearing minerals. Cassiterite from the Mn–Ag ores yielded a U–Pb age of 436 ± 17 Ma, consistent with the Caledonian age of the Nanwenhe granitic pluton. Combined with other geochemical proxies (Zn-Pb-Cu-Sn), the Sanbao Mn–Ag deposit may originally be of magmatic hydrothermal origin, rather than sedimentary. The Ag-rich (Zn-Pb (Sn)-bearing) ore-forming fluids generated during the intrusion of the granite flowed through fractures and overprinted the earlier Mn mineralization. Secondary Ag (and possibly other base-metals) enrichment occurred through later supergene weathering and oxidation.
Numerical Modeling of a Laboratory-Scale Waste Rock Pile Featuring an Engineered Cover System
Authors: Raymond Katherine E. , Seigneur Nicolas , Su Danyang , Poaty Bissé , Plante Benoît , Bussière Bruno , Mayer K. Ulrich
Published: July 2020

Improved design to reduce contaminant mass loadings from waste rock piles is an increasingly important consideration. In certain cases, an engineered cover system containing a flow control layer (FCL) may be used to mitigate the release of metals out of a pile using capillary barrier effects (CBEs), diverting water away from reactive materials below. In this study, a reactive transport model was calibrated to observational data from a laboratory experiment designed to evaluate a cover system. The results show that the numerical model is capable of capturing flow rates out of multiple drainage ports and matching key effluent concentrations by including the spatial distribution of hydraulic parameters and mineral weathering rates. Simulations were also useful for characterizing the internal flow pathways within the laboratory experiment, showing the effectiveness of the cover in diverting the flow away from the reactive waste rock and identifying secondary CBEs between different rock types. The numerical model proved beneficial in building an improved understanding of the processes controlling the metal release and conceptualizing the system. The model was expanded to investigate the robustness of the cover system as a function of the applied infiltration rate, supporting that water diversion will occur with infiltration rates representative of field conditions.
Dissolution Test Protocol for Estimating Water Quality Changes in Minerals Processing Plants Operating With Closed Water Circulation
Authors: Le Thi , Schreithofer Nóra , Dahl Olli
Published: July 2020

To save freshwater resources and comply with environmental regulations, minerals processing operations are transitioning to partially or fully closed water circulation. However, the accumulation of electrolytes and the addition of reagents lead to changes in water composition and may compromise flotation performance and plant maintenance. As a consequence, costly modifications are often required to cope with these challenges. Therefore, knowledge about water quality variation owing to closed water circulation and its potential effect on the flotation performance is crucial. The experimental methodology presented in this paper targeted three main objectives: (1) predicting the tendency of the accumulation of elements and compounds into the process water during comminution, flotation, and storage in tailings facilities; (2) establishing a relationship between laboratory results and plant historical water quality data; and (3) predicting the potential effect of recycling water on flotation performance. The results obtained with Boliden Kevitsa ore showed a good correlation between the water matrix of the actual process water on-site and that obtained in the ore dissolution tests done in the laboratory. The final water composition came close to the process water in terms of major elements and some of the minor elements. Additionally, the work presented in this paper demonstrated that a dissolution loop allowed us to predict the potential impact of the recycling water on the ore flotability. This methodology could serve as an aid for predicting water quality matrix variation and designing closed water circulation systems at existing and new plants.
Benzylideneacetophenone Derivative Alleviates Arthritic Symptoms via Modulation of the MAPK Signaling Pathway
Authors: Sur Bongjun , Kim Mijin , Villa Thea , Oh Seikwan
Published: July 2020

The benzylideneacetophenone derivative 3-(4-hydroxy-3-methoxy-phenyl)-1-{3-[1]-phenyl}-propenone (JC3 dimer) was synthesized through the dimerization of JC3. To investigate the inhibitory effects of JC3 dimer, the carrageenan/kaolin (C/K)-induced knee arthritis rat model was used in vivo and rheumatoid arthritis (RA) patient-derived fibroblast-like synoviocytes (FLS) were used in vitro. In the C/K rat model, JC3 dimer was given after arthritis induction for 6 days at the concentrations of 1, 5, or 10 mg/kg/day. Manifestation of arthritis was evaluated using knee thickness, weight distribution ratio (WDR), and squeaking test. The levels of prostaglandin E2 (PGE2), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in the serum of JC3 dimer-treated arthritic rats were also analyzed. Histological examination of the knee joints was also done. For the FLS, the cells were stimulated using IL-1β and concentrations of 1, 5, and 10 μg/mL JC3 dimer were used. The levels of IL-8, IL-6, and PGE2 were measured in stimulated FLS treated with JC3 dimer. At days 5 to 6 after arthritis induction, JC3 dimer treatment significantly decreased arthritic symptoms and reduced the inflammation in the knee joints in the histology of knee tissues in C/K-arthritic rats. In stimulated FLS, JC3 dimer suppressed the increase of IL-8, IL-6, and PGE2. These findings suggest that JC3 dimer has suppressive effects on arthritis, and that JC3 dimer can be a potential agent for arthritis therapy.
Inside Perspective of the Synthetic and Computational Toolbox of JAK Inhibitors: Recent Updates
Authors: Coricello Adriana , Mesiti Francesco , Lupia Antonio , Maruca Annalisa , Alcaro Stefano
Published: July 2020

The mechanisms of inflammation and cancer are intertwined by complex networks of signaling pathways. Dysregulations in the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway underlie several pathogenic conditions related to chronic inflammatory states, autoimmune diseases and cancer. Historically, the potential application of JAK inhibition has been thoroughly explored, thus triggering an escalation of favorable results in this field. So far, five JAK inhibitors have been approved by the Food and Drug Administration (FDA) for the treatment of different diseases. Considering the complexity of JAK-depending processes and their involvement in multiple disorders, JAK inhibitors are the perfect candidates for drug repurposing and for the assessment of multitarget strategies. Herein we reviewed the recent progress concerning JAK inhibition, including the innovations provided by the release of JAKs crystal structures and the improvement of synthetic strategies aimed to simplify of the industrial scale-up.
Effects of Melatonin on Lipid Metabolism and Circulating Irisin in Sprague-Dawley Rats with Diet-Induced Obesity
Authors: Tung Yu-Tang , Chiang Pei-Chin , Chen Ya-Ling , Chien Yi-Wen
Published: July 2020

Melatonin, a pivotal photoperiodic signal transducer, may work as a brown-fat inducer that regulates energy balance. Our study aimed to investigate the effects of melatonin treatment on the body fat accumulation, lipid profiles, and circulating irisin of rats with high-fat diet-induced obesity (DIO). Methods: 30 male Sprague-Dawley rats were divided into five groups and treated for 8 weeks: vehicle control (VC), positive control (PC), MEL10 (10 mg melatonin/kg body weight (BW)), MEL20 (20 mg/kg BW), and MEL50 (50 mg/kg BW). The vehicle control group was fed a control diet, and the other groups were fed a high-fat and high-calorie diet for 8 weeks to induce obesity before the melatonin treatment began. Melatonin reduced weight gain without affecting the food intake, reduced the serum total cholesterol level, enhanced the fecal cholesterol excretion, and increased the circulating irisin level. Melatonin downregulated the fibronectin type III domain containing 5 (FNDC5) and lipoprotein lipase (LPL) mRNA expressions of inguinal white adipose tissue (iWAT) and induced the browning of iWAT in both the MEL10 and MEL20 groups. Conclusion: Chronic continuous melatonin administration in drinking water reduced weight gain and the serum total cholesterol levels. Additionally, it enhanced the circulating irisin, which promoted brite/beige adipocyte recruitment together with cholesterol excretion and contributed to an anti-obesity effect.
Lignin Precipitation and Fractionation from OrganoCat Pulping to Obtain Lignin with Different Sizes and Chemical Composition
Authors: Weidener Dennis , Holtz Arne , Klose Holger , Jupke Andreas , Leitner Walter , Grande Philipp M.
Published: July 2020

Fractionation of lignocellulose into its three main components, lignin, hemicelluloses, and cellulose, is a common approach in modern biorefinery concepts. Whereas the valorization of hemicelluloses and cellulose sugars has been widely discussed in literature, lignin utilization is still challenging. Due to its high heterogeneity and complexity, as well as impurities from pulping, it is a challenging feedstock. However, being the most abundant source of renewable aromatics, it remains a promising resource. This work describes a fractionation procedure that aims at stepwise precipitating beech wood (Fagus sp.) lignin obtained with OrganoCat technology from a 2-methyltetrahydrofuran solution, using n-hexane and n-pentane as antisolvents. By consecutive antisolvent precipitation and filtration, lignin is fractionated and then characterized to elucidate the structure of the different fractions. This way, more defined and purified lignin fractions can be obtained. Narrowing down the complexity of lignin and separately valorizing the fractions might further increase the economic viability of biorefineries.
Synthesis of α-Aminophosphonic Acid Derivatives Through the Addition of O- and S-Nucleophiles to 2H-Azirines and Their Antiproliferative Effect on A549 Human Lung Adenocarcinoma Cells
Authors: Carramiñana Victor , Ochoa de Retana Ana M. , Palacios Francisco , de los Santos Jesús M.
Published: July 2020

This work reports a straightforward regioselective synthetic methodology to prepare α-aminophosphine oxides and phosphonates through the addition of oxygen and sulfur nucleophiles to the C–N double bond of 2H-azirine derivatives. Determined by the nature of the nucleophile, different α-aminophosphorus compounds may be obtained. For instance, aliphatic alcohols such as methanol or ethanol afford α-aminophosphine oxide and phosphonate acetals after N–C3 ring opening of the intermediate aziridine. However, addition of 2,2,2-trifluoroethanol, phenols, substituted benzenthiols or ethanethiol to 2H-azirine phosphine oxides or phosphonates yields allylic α-aminophosphine oxides and phosphonates in good to high general yields. In some cases, the intermediate aziridine attained by the nucleophilic addition of O- or S-nucleophiles to the starting 2H-azirine may be isolated and characterized before ring opening. Additionally, the cytotoxic effect on cell lines derived from human lung adenocarcinoma (A549) and non-malignant cells (MCR-5) was also screened. Some α-aminophosphorus derivatives exhibited very good activity against the A549 cell line in vitro. Furthermore, selectivity towards cancer cell (A549) over non-malignant cells (MCR-5) has been detected in almost all compounds tested.
Efficient Removal of Volatile Organic Compounds by FAU-Type Zeolite Coatings
Authors: Diboune Mathieu , Nouali Habiba , Soulard Michel , Patarin Joël , Rioland Guillaume , Faye Delphine , Daou T. Jean
Published: July 2020

Silicone and pure organic binders were used to develop FAU-type zeolite coatings applied on pre-treated aluminum substrates by using a spraying method and then cured under specific conditions. The influence of the amount of binder on adhesion properties of zeolite coatings was first investigated to determine the optimum ratio between zeolite and binder. Zeolite coatings were then elaborated with a high zeolite content (between 70 and 80 wt.%) to ensure high adsorption capacities. The amount of binders involved in different zeolite coatings was sufficient to achieve interesting adhesion and cohesion properties. The accessibility of zeolite microporosity was studied by nitrogen adsorption-desorption measurements, which revealed a very small or no loss of the micropore volume for the optimized coatings. Volatile Organic Compounds (VOCs) adsorption measurements were carried out using n-hexane as probe molecule. FAU-type zeolite in powder form adsorbs 180 mg/ganhydrous zeolite, whereas the amounts of n-hexane adsorbed by zeolite coatings ranged from 131 to 175 mg/ganhydrous zeolite.
Acyclic Triterpenoid Isolated from Alpinia katsumadai Alleviates Formalin-Induced Chronic Mouse Paw Inflammation by Inhibiting the Phosphorylation of ERK and NF-κB
Authors: Lim Hyung Jin , Bak Seon Gyeong , Lim Hee Ju , Lee Seung Woong , Lee Soyoung , Ku Sae-Kwang , Park Sang-Ik , Lee Seung-Jae , Rho Mun-Chual
Published: July 2020

Chronic and excessive inflammation can destroy host organs and cause inflammatory diseases such as inflammatory bowel disease, asthma, and rheumatoid arthritis. In this study, we investigated the anti-inflammatory effects of Alpinia katsumadai seed-derived 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (PHT) using lipopolysaccharide (LPS)-stimulated J774 cells and a formalin-induced chronic paw inflammation mouse model. The in vitro results showed that PHT exhibited no cytotoxicity and decreased LPS-induced NO secretion. Additionally, PHT inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. The quantitative real-time PCR results showed that PHT downregulated the gene expression of the proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). PHT inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). In a mouse model, oral administration of 50 mg/kg PHT significantly alleviated both mouse paw thickness and volume. These results indicate that PHT has potential anti-inflammatory effects and should be considered a possible functional material.
Hyperpolarization of Nitrile Compounds Using Signal Amplification by Reversible Exchange
Authors: Kim Sarah , Min Sein , Chae Heelim , Jeong Hye Jin , Namgoong Sung Keon , Oh Sangwon , Jeong Keunhong
Published: July 2020

Signal Amplification by Reversible Exchange (SABRE), a hyperpolarization technique, has been harnessed as a powerful tool to achieve useful hyperpolarized materials by polarization transfer from parahydrogen. In this study, we systemically applied SABRE to a series of nitrile compounds, which have been rarely investigated. By performing SABRE in various magnetic fields and concentrations on nitrile compounds, we unveiled its hyperpolarization properties to maximize the spin polarization and its transfer to the next spins. Through this sequential study, we obtained a ~130-fold enhancement for several nitrile compounds, which is the highest number ever reported for the nitrile compounds. Our study revealed that the spin polarization on hydrogens decreases with longer distances from the nitrile group, and its maximum polarization is found to be approximately 70 G with 5 μL of substrates in all structures. Interestingly, more branched structures in the ligand showed less effective polarization transfer mechanisms than the structural isomers of butyronitrile and isobutyronitrile. These first systematic SABRE studies on a series of nitrile compounds will provide new opportunities for further research on the hyperpolarization of various useful nitrile materials.