bluuebunny/crossref_metadata_2025 huggingface dataset:
Copper-Doped Biphasic Calcium Phosphate Powders: Dopant Release, Cytotoxicity and Antibacterial Properties
Authors: Jacobs Aurélie , Renaudin Guillaume , Charbonnel Nicolas , Nedelec Jean-Marie , Forestier Christiane , Descamps Stéphane
Published: May 2021

Cytotoxicity and antibacterial properties associated with the dopant release of Cu-doped Biphasic Calcium Phosphate (BCP) powders, mainly composed of hydroxyapatite mixed with β-tricalcium phosphate powders, were investigated. Twelve BCP ceramics were synthesized at three different sintering temperatures (600 °C, 900 °C and 1200 °C) and four copper doping rates (x = 0.0, 0.05, 0.10 and 0.20, corresponding to the stoichiometric amount of copper in Ca10Cux(PO4)6(OH)2-2xO2x). Cytotoxicity assessments of Cu-doped BCP powders, using MTT assay with human-Mesenchymal Stem Cells (h-MSCs), indicated no cytotoxicity and the release of less than 12 ppm of copper into the biological medium. The antibacterial activity of the powders was determined against both Gram-positive (methicillin-sensitive (MS) and methicillin resistant (MR) Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. The Cu-doped biomaterials exhibited a strong antibacterial activity against MSSA, MRSA and E. coli, releasing approximatively 2.5 ppm after 24 h, whereas 10 ppm were required to induce an antibacterial effect against P. aeruginosa. This study also demonstrated that the culture medium used during experiments can directly impact the antibacterial effect observed; only 4 ppm of Cu2+ were effective for killing all the bacteria in a 1:500 diluted TS medium, whereas 20 ppm were necessary to achieve the same result in a rich, non-diluted standard marrow cell culture medium.
Control of Porous Layer Thickness in Thermophoretic Deposition of Nanoparticles
Authors: Schalk Malte , Pokhrel Suman , Schowalter Marco , Rosenauer Andreas , Mädler Lutz
Published: May 2021

The film thickness plays an important role in the performance of materials applicable to different technologies including chemical sensors, catalysis and/or energy materials. The relationship between the surface and volume of the functional layers is key to high performance evaluations. Here we demonstrate the thermophoretic deposition of different thicknesses of the functional layers designed using flame combustion of tin 2-ethylhexanoate dissolved in xylene, and measurement of thickness by scanning electron microscopy and focused ion beam. The parameters such as spray fluid concentration (differing Sn2+ content), substrate-nozzle distance and time of the spray were considered to investigate the layer growth. The results showed ≈ 23, 124 and 161 μm thickness of the SnO2 layer after flame spray of 0.1, 0.5 M and 1.0 M tin 2-EHA-Xylene solutions for 1200 s. While Sn2+ concentration was 0.5 M for all the flame sprays, the substrates placed at 250, 220 and 200 mm from the flame nozzle had layer thicknesses of 113, 116 and 132 µm, respectively. Spray time dependent thickness growth showed a linear increase from 8.5 to 152.1 µm when the substrates were flame sprayed for 30 s to 1200 s using 0.5 M tin 2-EHA-Xylene solutions. Changing the dispersion oxygen flow (3–7 L/min) had almost no effect on layer thickness. Layers fabricated were compared to a model found in literature, which seems to describe the thickness well in the domain of varied parameters. It turned out that primary particle size deposited on the substrate can be tuned without altering the layer thickness and with little effect on porosity. Applications depending on porosity, such as catalysis or gas sensing, can benefit from tuning the layer thickness and primary particle size.
Microtensile Bond Strength of Fiber-Reinforced and Particulate Filler Composite to Coronal and Pulp Chamber Floor Dentin
Authors: Baraba Anja , Cimic Samir , Basso Matteo , Ionescu Andrei C. , Brambilla Eugenio , Miletić Ivana
Published: May 2021

This ex vivo study aimed to compare the microtensile bond strength of fiber-reinforced and particulate filler composite to coronal and pulp chamber floor dentin using a self-etching adhesive system. Coronal dentin of 40 human molar teeth was exposed by cutting occlusal enamel with a low-speed saw. Teeth were then randomly divided into two groups (n = 20). The first group was left as is, while in the second group, pulp chamber floor dentin was exposed by trepanation. After placement of a self-etching adhesive system (G-aenial Bond, GC, Tokyo, Japan), groups were further divided into two sub-groups (n = 10) according to the type of composite: fiber-reinforced composite (EP, everX Posterior, GC, Tokyo, Japan) and particulate filler composite (GP, G-aenial Posterior, GC, Tokyo, Japan). Then, composite blocks were built up. Sticks (1.0 × 1.0 mm2) were obtained from each specimen by sectioning, then microtensile bond strength (μTBS) test was performed. Statistical analysis included one-way ANOVA test and Student’s t-test (p < 0.05). μTBS values were 22.91 ± 14.66 and 24.44 ± 13.72 MPa on coronal dentin, 14.00 ± 5.83 and 12.10 ± 8.89 MPa on pulp chamber floor dentin for EP and GP, respectively. Coronal dentin yielded significantly higher μTBS than pulp chamber floor dentin (p < 0.05), independently from the tested composites.
The Effect of the Activation Process and Metal Oxide Addition (CaO, MgO, SrO) on the Catalytic and Physicochemical Properties of Natural Zeolite in Transesterification Reaction
Authors: Mierczynski Pawel , Szkudlarek Lukasz , Chalupka Karolina , Maniukiewicz Waldemar , Wahono Satriyo K. , Vasilev Krasimir , Szynkowska-Jozwik Malgorzata I.
Published: May 2021

This work provides valuable information about unexplored catalytic systems tested in the transesterification reaction of vegetable oil with methanol. It was demonstrated that natural zeolite treatment leads to enhanced catalytic activity and yield of biodiesel production. The activation of the catalytic material in a mixture of 5% H2–95% Ar resulted in an improvement of the values of the TG conversion and fatty acid methyl esters (FAME) yield. In addition, it was proven that the incorporation of CaO, MgO and SrO oxides onto the natural zeolite surface improves the TG conversion and FAME yield values in the transesterification reaction.
A New Method for Compaction Quality Evaluation of Asphalt Mixtures with the Intelligent Aggregate (IA)
Authors: Zhang Chen , Wang Hainian
Published: May 2021

To provide a new method for the evaluation of the compaction quality of asphalt mixture, a real-time data acquisition and processing system (RDAPS) for the motion state of aggregate with a small volume and high precision is developed. The system consists of an intelligent aggregate (IA), analysis software and hardware equipment. The performance of the IA was tested by regarding data sensitivity, high-temperature resistance, and mechanical properties. A new evaluation method was proposed for evaluating the compaction quality of AC-25 and SMA-25 asphalt mixtures based on an IA. The results show that the best transmission baud rate for the IA was 9600 bps, and the corresponding signal transmission distance was 380 m. Only one IA was needed to complete the state data collection for the aggregate within the asphalt mixture in a circular area, with the IA layout point as the center of the circle and a radius of 5 m. The IA conducted reliable data transmission up to 200 °C; however, its compressive strength decreased with increasing temperature until reaching stability. Traditional aggregate could be replaced by an IA to withstand external forces and internal load transfer. Embedding an IA into AC-25 or SMA-25 asphalt mixtures did not have a significant impact on the original mechanical properties of the mixture. The effect of the gradation type of the asphalt mixture on the IA motion state was not significant. When the compaction degree met the specification requirements, the motion data of the IA did not reach a stable state, and the interlocking effect between aggregates in the asphalt mixture could be further optimized. An evaluation method is proposed based on the IA for the compaction quality of AC-25 and SMA-25 asphalt mixtures with the compaction degree as the main index and the spatial attitude angle and spatial acceleration of the IA as the auxiliary indexes.
On the Direct Extrusion of Solder Wire from 52In-48Sn Alloy
Authors: Faizov Sergei , Sarafanov Aleksandr , Erdakov Ivan , Gromov Dmitry , Svistun Alexandra , Glebov Lev , Bykov Vitaly , Bryk Anastasia , Radionova Liudmila
Published: May 2021

In this article, technology for producing wire and rod solder from 52In-48Sn alloy has been developed and investigated in the conditions of small-scale production. The use of direct extrusion of wire and rods instead of traditional technology for producing solder, which includes pressing, rolling and drawing, can significantly reduce the fleet of required equipment. Using only a melting furnace and a hydraulic press, solder wires and rods can be produced in various sizes. Shortening the production cycle allows you to quickly fulfill small orders and be competitive in sales. This article develops a mathematical model of direct extrusion, which allows you to calculate the extrusion ratio, extrusion speed and pressing force. The results of modeling the process of extrusion of wire Ø2.00 mm and rods Ø8.0 mm made of 52In-48Sn alloy are presented. The temperature of the solder and the tool is simulated in software QForm based on the finite element method. Experimental results of manufacturing Ø2.0 mm solder wire and Ø8.0 mm rods are presented. The microstructure of the direct extruded solder is a eutectic of phases γ and β. Energy-dispersive X-ray spectroscopy (EDS) mapping of the 52In-48Sn alloy showed that the solder obtained by direct extrusion has a uniform distribution of structural phases. The developed technology can be used in the manufacture of wires and rods from other low-melting alloys.
A Multi-Server Heterogeneous Queuing-Inventory System with Class-Dependent Inventory Access
Authors: Rasmi Karumbathil , Jacob Machuveettil Joseph , Rumyantsev Alexander S. , Krishnamoorthy Achyutha
Published: May 2021

In this paper, we consider a queuing inventory system with heterogeneous customers of K types arriving according to a marked Markovian arrival process. Each class of customers differs by nature of the service they seek and different priorities are assigned for each class resulting in different levels of inventory admitted to exhaust for customers of each class. A single service node is provided for each class with exponential services having class-dependent service rates. All classes of customers are served from a single source of inventory replenished according to (s,S) policy with exponentially distributed lead time. Stability condition and steady state probabilities are obtained by matrix-analytic method. Some important performance measures are also derived. Inventory recycle time was analyzed in detail. Useful cost function and numerical illustrations are also given. The optimization problem is interesting and can be solved in similar real scenario.
A Study of Spaces of Sequences in Fuzzy Normed Spaces
Authors: Kim Ju-Myung , Lee Keun-Young
Published: May 2021

In this paper, spaces of sequences in fuzzy normed spaces are considered. These spaces are a new concept in fuzzy normed spaces. We develop fuzzy norms for spaces of sequences in fuzzy normed spaces. Especially, we study the representation of the dual of a space of sequences in a fuzzy normed space. The approximation property in our context is investigated.
Time Series Clustering with Topological and Geometric Mixed Distance
Authors: Zhang Yunsheng , Shi Qingzhang , Zhu Jiawei , Peng Jian , Li Haifeng
Published: May 2021

Time series clustering is an essential ingredient of unsupervised learning techniques. It provides an understanding of the intrinsic properties of data upon exploiting similarity measures. Traditional similarity-based methods usually consider local geometric properties of raw time series or the global topological properties of time series in the phase space. In order to overcome their limitations, we put forward a time series clustering framework, referred to as time series clustering with Topological-Geometric Mixed Distance (TGMD), which jointly considers local geometric features and global topological characteristics of time series data. More specifically, persistent homology is employed to extract topological features of time series and to compute topological similarities among persistence diagrams. The geometric properties of raw time series are captured by using shape-based similarity measures such as Euclidean distance and dynamic time warping. The effectiveness of the proposed TGMD method is assessed by extensive experiments on synthetic noisy biological and real time series data. The results reveal that the proposed mixed distance-based similarity measure can lead to promising results and that it performs better than standard time series analysis techniques that consider only topological or geometrical similarity.
Debulking Surgery Combined with Low-Dose Oral Prednisolone and Azathioprine for Intractable IgG4-Related Orbital Disease: A Case Report
Authors: Kuo Hua-Hsuan , Chen Chen-Hung , Wu Shu-Ya
Published: May 2021

A case of intractable IgG4-related orbital disease (IgG4-ROD) was successfully treated by debulking surgery combined with low-dose prednisolone and azathioprine as maintenance therapy. A 64-year-old man visited our clinic with progressive bilateral upper eyelid swelling and right eye fullness of a year’s duration. He was previously treated with systemic corticosteroids for the IgG4-ROD and experienced a partial clinical response but relapsed upon prednisolone cessation. The patient underwent debulking surgery of the right lacrimal gland and right upper eyelid. His post-operative medication was oral prednisolone (5 mg) every other day and 50 mg azathioprine per day. The patient’s right eye remained asymptomatic during the 18 months of follow-up. Debulking surgery combined with low-dose prednisolone and azathioprine, as a maintenance therapy, is an effective and alternative treatment for the long-term control of intractable IgG4-ROD.
Cardiac Amyloidosis-Challenging Diagnosis and Unclear Clinical Picture
Authors: Kozak Sylwia , Ulbrich Krzysztof , Migacz Maciej , Szydło Krzysztof , Mizia-Stec Katarzyna , Holecki Michał
Published: May 2021

Cardiac amyloidosis (CA) is a rare systemic disease determined by the extracellular deposition of amyloid protein in the heart. The protein can accumulate in any part of the heart: myocardium, vessels, endocardium, valves, epicardium and parietal pericardium. The types of CA include the following types: light chain (AL), amyloidosis AA (Amyloid A) and transthyretin (ATTR). The detection of specific subtypes remains of great importance to implement the targeted treatment. We present the case of a 65-year-old woman, who was admitted with severe deterioration of exercise capacity, a bilateral reduction of physiological vesicular murmur, ascites and edema of lower extremities. CA was suspected due to echocardiographic examination results, which led to further examination and final diagnosis. The aim of this study is to improve the disease awareness among clinicians and shorten the delay between the first symptoms and the diagnosis establishment resulting in a better outcome.
Drug Utilization for Pain Management during Perioperative Period of Total Knee Arthroplasty in China: A Retrospective Research Using Real-World Data
Authors: Chen Xianwen , Yang Lisong , Liu Xueli , Zhu He , Yu Fei , Ung Carolina Oi Lam , Hu Hao , Chan Waisin , Shi Honghao , Han Sheng
Published: May 2021

Background and Objective: Total knee arthroplasty (TKA) is one of the most painful procedures and perioperative pain usually requires the use of many analgesics to relieve it. The appropriate use of analgesics to relieve patient pain is an important issue of TKA. To characterize the drug utilization for pain management during perioperative period of TKA in China using real-world data of electronic medical records. Materials and Methods: This research used the data of all inpatients who received TKA at 145 hospitals covered 31 provinces in China from 1 January 2016 to 31 December 2018. The exclusion criteria included pregnancy and cancer diagnosis. In the analysis of drug utilization mode (DUM), medicines were classified into 5 groups: non-steroidal anti-inflammatory drugs (NSAIDs), opioids, non-opioid central analgesics, acetaminophen and others. Results: Among the 2017 patients included in this study, there were 1537 (76.20%) female and 480 (23.80%) male, aged 65.77 ± 7.73 years. Regarding the surgery characteristics, 1658 (82.20%) were unilateral; 1220 (60.49%) was graded Level 4; 1312 (65.05%) used local anesthesia as the main anesthesia method, and 1450 (71.89%) lasted for more than 2 h. The most common DUM was “NSAIDs + opioids” (55.92%), followed by “NSAIDs only” (17.85%), and “NSAIDs + Opioids + Non-opioid central analgesics” (17.15%). The results of the Chi-square test showed that differences in DUM were associated with surgery types, surgery levels, surgery duration, and types of anesthesia used. Up to 81.14% of the total drug expenses for pain management was spent on NSAIDs. Due to the limitation of database, this study could not subdivide operation stages, anesthesia methods, dosage forms of drugs. Conclusion: In China, the use of analgesics in perioperative period of TKA was diversified and influenced by a number of surgery characteristics. The rational use of analgesics should be considered in combination with surgery type, surgery level, surgery duration and anesthesia method.
The Relationship between Advanced Oxidation Protein Products, Vascular Calcifications and Arterial Stiffness in Predialysis Chronic Kidney Disease Patients
Authors: Vinereanu Ion-Vlad , Peride Ileana , Niculae Andrei , Tiron Andreea Taisia , Caragheorgheopol Andra , Manda Dana , Checherita Ionel Alexandru
Published: May 2021

Background and Objectives: Cardiovascular morbidity and mortality are increased in patients with chronic kidney disease (CKD). It is likely that the accumulation of uremic toxins resulting in increased oxidative stress (OS) is a major contributing factor, but no clear link has been identified. The purpose of this research is to establish if advanced oxidation protein product (AOPP) levels in the serum of predialysis patients are a contributing factor to vascular calcification and increased arterial stiffness. Materials and Methods: After obtaining the informed consent, 46 predialysis patients (CKD stages G3–G5) were included in the study. In order to identify vascular calcifications, hand and pelvic radiographs were performed. Valvular calcifications were identified using cardiac ultrasound. AOPP were measured using a commercially available ELISA kit. The relationships between serum AOPP values and biochemical parameters relevant in the evaluation of CKD patients were analyzed. In addition to identifying the differences in AOPP levels between patients with/without vascular or valvular calcifications, the research focused on describing the relationship between OS and arterial stiffness assessed by oscillometric pulse-wave velocity (PWV) measurement. Results: No significant relationship between serum AOPP and vascular or valvular calcifications was highlighted, but significant correlations of AOPP with C-reactive protein (p = 0.025), HDL-cholesterol levels (p = 0.04), HbA1c (p = 0.05) and PWV values (p = 0.02) were identified. Conclusions: The usefulness of (OS) measurement in clinical practice remains debatable; however, the relationship between AOPP and arterial stiffness could be valuable in improving cardiovascular risk assessment of patients with CKD.
Effects of Slag Composition and Impurities of Alloys on the Inclusion Transformation during Industrial Ladle Furnace Refining
Authors: Liu Chunyang , Jia Yi , Hao Lixia , Han Shaowei , Huang Fuxiang , Yu Huixiang , Gao Xu , Ueda Shigeru , Kitamura Shin-ya
Published: May 2021

The inclusion of the MgO·Al2O3 (MA) spinel and CaO–Al2O3 are occasionally observed during the refining of Al–killed steel, even without the intentional additions of Ca and Mg. Many studies have focused on the source of Mg and Ca; however, especially for the formation of CaO–Al2O3–type inclusions, some recent results showed that Ca was difficult to dissolve from refining slag, even when the Al content in molten steel was high. To confirm these differences, industrial experiments were designed in this study, and the effects of the FeO and MnO contents, as well as the impurities of the alloying materials, were discussed. The results showed that, when the FeO and MnO contents in slag were high (about 10 mass%) at the start of LF (ladle furnace), all inclusions remained as Al2O3, despite alloying. Using the slag with low FeO + MnO content (<1~2 mass%), the Al2O3 inclusions changed to the MA spinel, but CaO–Al2O3 inclusions were not observed, indicating that CaO–Al2O3 inclusions were difficult to form by the steel/slag reactions under the current conditions. Only for the molten steel that contained a low level of dissolved oxygen and a large amount of Fe–Si, which contained Ca as the impurity was added, CaO–Al2O3 inclusions were generated.
An Evaluation Model for Selecting Part Candidates for Additive Manufacturing in the Transport Sector
Authors: Muvunzi Rumbidzai , Mpofu Khumbulani , Daniyan Ilesanmi
Published: May 2021

There is a need to develop guidelines for identifying situations where it is more beneficial to apply Additive Manufacturing (AM) as opposed to conventional methods of manufacturing. Thus, the aim of this paper is to propose a model for evaluating the sustainability of applying AM in the manufacture of transport equipment parts. A literature review was conducted to identify the parameters for selecting the part candidates. In the next stage, the criteria were ranked according to the needs of the transport equipment manufacturing industry using the Analytical Hierarchy Process (AHP) technique. The next stage featured the development of the decision matrix using the weights and classified levels. To validate the proposed decision matrix, different case studies from literature were used. The weights obtained from the case studies were in agreement with the proposed evaluation model. This study will add to the understanding of how the AM industries can effectively screen potential part candidates, thereby promoting the overall sustainability of the AM process in terms of material conservation, geometric complexity and functionality. There is still a dearth of information on the evaluation models capable of identifying the core functions of the products and the applicable environment. The work presents a proposed framework for part selection using the evaluation model.
Automated Sequential Analysis of Hydrophilic and Lipophilic Fractions of Biological Samples: Increasing Single-Injection Chemical Coverage in Untargeted Metabolomics
Authors: Pirttilä Kristian , Laurell Göran , Pettersson Curt , Hedeland Mikael
Published: May 2021

In order to increase metabolite coverage in LC–MS-based untargeted metabolomics, HILIC- and RPLC-mode separations are often combined. Unfortunately, these two techniques pose opposite requirements on sample composition, necessitating either dual sample preparations, increasing needed sample volume, or manipulation of the samples after the first analysis, potentially leading to loss of analytes. When sample material is precious, the number of analyses that can be performed is limited. To that end, an automated single-injection LC–MS method for sequential analysis of both the hydrophilic and lipophilic fractions of biological samples is described. Early eluting compounds in a HILIC separation are collected on a trap column and subsequently analyzed in the RPLC mode. The instrument configuration, composed of commercially available components, allows easy modulation of the dilution ratio of the collected effluent, with sufficient dilution to obtain peak compression in the RPLC column. Furthermore, the method is validated and shown to be fit for purpose for application in untargeted metabolomics. Repeatability in both retention times and peak areas was excellent across over 140 injections of protein-precipitated blood plasma. Finally, the method has been applied to the analysis of real perilymph samples collected in a guinea pig model. The QC sample injections clustered tightly in the PCA scores plot and showed a high repeatability in both retention times and peak areas for selected compounds.
Patterns and Associations of Essential Trace Elements (Cu, Fe and Zn) in Saudi Adults with Varying Levels of Glycemia
Authors: Yakout Sobhy , Faqeeh Fatimah , Al-Attas Omar , Hussain Syed D. , Al-Daghri Nasser M.
Published: May 2021

The homeostasis of trace elements were observed to contribute to certain diabetic outcomes. This cross-sectional study determined the differences and associations between serum levels of copper (Cu), iron (Fe) and zinc (Zn) in Saudi patients with and without type 2 diabetes mellitus (T2DM) as well as those with prediabetes. Anthropometrics were measured, and fasting blood samples were collected from 119 patients with T2DM (aged 41–64 years), 95 non-T2DM (aged 27–55 years) and 80 with prediabetes (aged 35–57 years). Circulating trace minerals were determined using an inductively coupled plasma–mass spectrometer. Serum levels of Cu and Fe were significantly lower in T2DM than non-T2DM (adjusted p-values < 0.001). There was no difference in the Zn levels of the T2DM and non-T2DM groups. The serum Cu levels were significantly lower in the prediabetes group than the non-T2DM group (p < 0.05). The serum levels of Cu, Fe and Zn were inversely associated with circulating glucose in the T2DM and prediabetes subjects (p-values < 0.001). In conclusion, the differences in circulating trace elements were observed in Saudi subjects with varying glycemic statuses, suggesting an inverse association between T2DM progression and the decreasing serum Cu, Fe and Zn levels. Intervention trials are warranted to determine whether early correction of trace mineral deficiencies is beneficial in populations at higher risk for T2DM.
Host Response of Atlantic Salmon (Salmo salar) Re-Inoculated with Paramoeba perurans
Authors: McCormack Michelle , Talbot Anita , Dillon Eugene , O’Connor Ian , MacCarthy Eugene
Published: May 2021

In aquaculture, recurrence rates of amoebic gill disease (AGD) caused by the ectoparasite Paramoeba perurans are high and no prophylactic strategies exist for disease prevention. In this study, Atlantic salmon (Salmo salar) were initially inoculated with P. perurans and following the development of amoebic gill disease were treated with freshwater immersion on day 21 and day 35 post inoculation. Fish were re-inoculated following a negative qPCR analysis for the presence of P. perurans. The gill host immune response was investigated at 7, 14, and 18 days post re-inoculation. Differential proteome expression of immune related proteins was assessed by comparison of each time point against naïve controls. In the gill, some proteins of the innate immune system were expressed in response to gill re-colonization by P. perurans, while no features of adaptive immunity were found to be differentially expressed. Many of the proteins identified are novel in the context of AGD and their expression profiles suggest that their roles in the response to disease development and progression in single or multiple infections warrant further investigation.
Low-Grade Phosphate Tailings Beneficiation via Organic Acid Leaching: Process Optimization and Kinetic Studies
Authors: Arroug Lamya , Elaatmani Mohamed , Zegzouti Abdelouahad , Aitbabram Mohamed
Published: May 2021

In this paper, the beneficiation of rejected phosphate washing sludges (Ps) was investigated using acid leaching methods. Chemical analysis showed that these sludges are a low-grade ore (15.84% P2O5). The optimum milling parameters have helped to increase the P2O5 grade to 18.51%. Then, the effects of three different organic acids (acetic, lactic, and citric acid), acid concentrations, reaction temperatures, reaction times, and solid concentrations on the beneficiation of P2O5 were evaluated. Single-factor experiments indicate that with the optimal conditions: leaching for 60 min with an acetic acid concentration of 7%, a solid concentration of 25%, and a temperature of 40 °C, Ps could reach 30.1% P2O5 with a CaO/P2O5 ratio of 0.58. Taguchi experimental design, Pareto plot, desirability function, and Analysis of Covariance (ANCOVA) showed that the acid type has the most significant impact on the leaching and the optimized leaching conditions: 7% of acetic acid, a solid concentration of 30%, a reaction time of 100 min, and a temperature of 40 °C, helped to produce a Ps with 30.7% P2O5. The kinetic study showed that the leaching process was controlled by a chemical reaction, with an activation energy of 48.9 kJ/Mol, which confirms the chemical reaction’s control of the process.
Quantitative Mass Spectrometry-Based Proteomics for Biomarker Development in Ovarian Cancer
Authors: Ryu Joohyun , Thomas Stefani N.
Published: May 2021

Ovarian cancer is the most lethal gynecologic malignancy among women. Approximately 70–80% of patients with advanced ovarian cancer experience relapse within five years and develop platinum-resistance. The short life expectancy of patients with platinum-resistant or platinum-refractory disease underscores the need to develop new and more effective treatment strategies. Early detection is a critical step in mitigating the risk of disease progression from early to an advanced stage disease, and protein biomarkers have an integral role in this process. The best biological diagnostic tool for ovarian cancer will likely be a combination of biomarkers. Targeted proteomics methods, including mass spectrometry-based approaches, have emerged as robust methods that can address the chasm between initial biomarker discovery and the successful verification and validation of these biomarkers enabling their clinical translation due to the robust sensitivity, specificity, and reproducibility of these versatile methods. In this review, we provide background information on the fundamental principles of biomarkers and the need for improved treatment strategies in ovarian cancer. We also provide insight into the ways in which mass spectrometry-based targeted proteomics approaches can provide greatly needed solutions to many of the challenges related to ovarian cancer biomarker development.
Identification of Molecules from Coffee Silverskin That Suppresses Myostatin Activity and Improves Muscle Mass and Strength in Mice
Authors: Kim Jeong Han , Kim Jae Hong , Jang Jun-Pil , Jang Jae-Hyuk , Jin Deuk-Hee , Kim Yong Soo , Jin Hyung-Joo
Published: May 2021

Coffee has been shown to attenuate sarcopenia, the age-associated muscle atrophy. Myostatin (MSTN), a member of the TGF-β growth/differentiation factor superfamily, is a potent negative regulator of skeletal muscle mass, and MSTN-inhibition increases muscle mass or prevents muscle atrophy. This study, thus, investigated the presence of MSTN-inhibitory capacity in coffee extracts. The ethanol-extract of coffee silverskin (CSE) but not other extracts demonstrated anti-MSTN activity in a pGL3-(CAGA)12-luciferase reporter gene assay. CSE also blocked Smad3 phosphorylation induced by MSTN but not by GDF11 or Activin A in Western blot analysis, demonstrating its capacity to block the binding of MSTN to its receptor. Oral administration of CSE significantly increased forelimb muscle mass and grip strength in mice. Using solvent partitioning, solid-phase chromatography, and reverse-phase HPLC, two peaks having MSTN-inhibitory capacity were purified from CSE. The two peaks were identified as βN-arachinoyl−5-hydroxytryptamide (C20−5HT) and βN-behenoyl−5-hydroxytryptamide (C22−5HT) using mass spectrometry and NMR analysis. In summary, the results show that CSE has the MSTN-inhibitory capacity, and C20−5HT and C22−5HT are active components of CSE-suppressing MSTN activity, suggesting the potential of CSE, C20−5HT, and C22−5HT being developed as agents to combat muscle atrophy and metabolic syndrome.
Cocrystal of Apixaban–Quercetin: Improving Solubility and Bioavailability of Drug Combination of Two Poorly Soluble Drugs
Authors: Zhang Li , Kong Dewen , Wang Hongjuan , Jiao Lingtai , Zhao Xiaoyue , Song Junke , Yang Dezhi , Yang Haiguang , Yang Shiying , Du Guanhua , Lu Yang
Published: May 2021

Drug combinations have been the hotspot of the pharmaceutical industry, but the promising applications are limited by the unmet solubility and low bioavailability. In this work, novel cocrystals, consisting of two antithrombotic drugs with poor solubility and low bioavailability in vivo, namely, apixaban (Apx) and quercetin (Que), were developed to discover a potential method to improve the poor solubility and internal absorption of the drug combination. Compared with Apx, the dissolution behavior of Apx–Que (1:1) and Apx–Que–2ACN (1:1:2) was enhanced significantly, while the physical mixture of the chemicals failed to exhibit the advantages. The dissolution improvements of Apx–Que–2ACN could be explained by the fact that the solid dispersion-like structure and column-shaped cage of Que accelerated the access of the solvent to the inner layer of Apx. The fracture of the hydrogen bonds of Apx, which was the joint of the adjacent Que chains, facilitated the break-up of the structures. Besides, the bioavailability of Apx–Que was increased compared with the physical mixture and Apx, and Apx–Que remained stable in high temperature and illumination conditions. Therefore, a drug–drug cocrystal of two antithrombotic agents with poor solubility was developed, which exhibited greatly improved solubility, bioavailability and superior stability, indicating a novel method to overcome the shortages of drug combination.
Investigation of the Stability of Methylammonium Lead Iodide (MAPbI3) Film Doped with Lead Cesium Triiodide (CsPbI3) Quantum Dots under an Oxygen Plasma Atmosphere
Authors: Huang Pao-Hsun , Wang Chi-Wei , Lien Shui-Yang , Lee Kuan-Wei , Wang Na-Fu , Huang Chien-Jung
Published: May 2021

In this study, we describe composited perovskite films based on the doping of lead cesium triiodide (CsPbI3) quantum dots (QDs) into methylammonium lead iodide (MAPbI3). CsPbI3 QDs and MAPbI3 were prepared by ligand-assisted re-precipitation and solution mixing, respectively. These films were optimized by oxygen plasma treatment, and the effect of powers from 0 to 80 W on the structural properties of the composited perovskite films is discussed. The experimental results showed that the light-harvesting ability of the films was enhanced at 20 W. The formation of the metastable state (lead(II) oxide and lead tetroxide) was demonstrated by peak differentiation-imitating. A low power enhanced the quality of the films due to the removal of organic impurities, whereas a high power caused surface damage in the films owing to the severe degradation of MAPbI3.
Human Serum Albumin Labelling with a New BODIPY Dye Having a Large Stokes Shift
Authors: Raskolupova Valeria I. , Popova Tatyana V. , Zakharova Olga D. , Nikotina Anastasia E. , Abramova Tatyana V. , Silnikov Vladimir N.
Published: May 2021

BODIPY dyes are photostable neutral derivatives of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene. These are widely used as chemosensors, laser materials, and molecular probes. At the same time, BODIPY dyes have small or moderate Stokes shifts like most other fluorophores. Large Stokes shifts are preferred for fluorophores because of higher sensitivity of such probes and sensors. The new boron containing BODIPY dye was designed and synthesized. We succeeded to perform an annulation of pyrrole ring with coumarin heterocyclic system and achieved a remarkable difference in absorption and emission maximum of obtained fluorophore up to 100 nm. This BODIPY dye was equipped with linker arm and was functionalized with a maleimide residue specifically reactive towards thiol groups of proteins. BODIPY residue equipped with a suitable targeting protein core can be used as a suitable imaging probe and agent for Boron Neutron Capture Therapy (BNCT). As the most abundant protein with a variety of physiological functions, human serum albumin (HSA) has been used extensively for the delivery and improvement of therapeutic molecules. Thiolactone chemistry provides a powerful tool to prepare albumin-based multimodal constructions. The released sulfhydryl groups of the homocysteine functional handle in thiolactone modified HSA were labeled with BODIPY dye to prepare a labeled albumin-BODIPY dye conjugate confirmed by MALDI-TOF-MS, UV-vis, and fluorescent emission spectra. Cytotoxicity of the resulting conjugate was investigated. This study is the basis for a novel BODIPY dye-albumin theranostic for BNCT. The results provide further impetus to develop derivatives of HSA for delivery of boron to cancer cells.
Superabsorbent Hydrogels Based to Polyacrylamide/Cashew Tree Gum for the Controlled Release of Water and Plant Nutrients
Authors: Rodrigues Sousa Heldeney , Lima Idglan Sá , Neris Lucas Matheus Lima , Silva Albert Santos , Santos Nascimento Ariane Maria Silva , Araújo Francisca Pereira , Ratke Rafael Felippe , Silva Durcilene Alves , Osajima Josy Anteveli , Bezerra Leilson Rocha , Silva-Filho Edson Cavalcanti
Published: May 2021

Agricultural production is influenced by the water content in the soil and availability of fertilizers. Thus, superabsorbent hydrogels, based on polyacrylamide, natural cashew tree gum (CG) and potassium hydrogen phosphate (PHP), as fertilizer and water releaser were developed. The structure, morphology, thermal stability and chemical composition of samples of polyacrylamide and cashew tree gum hydrogels with the presence of fertilizer (HCGP) and without fertilizer (HCG) were investigated, using X-ray diffractometry (XRD), Fourier Transformed Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis (TGA/DTG) and Energy Dispersive Spectroscopy (EDS). Swelling/reswelling tests, textural analysis, effect of pH, release of nutrients and kinetics were determined; the ecotoxicity of the hydrogels was investigated by the Artemia salina test. The results showed that PHP incorporation in the hydrogel favored the crosslinking of chains. This increased the thermal stability in HCGP but decreased the hardness and adhesion properties. The HCGP demonstrated good swelling capacity (~15,000 times) and an excellent potential for reuse after fifty-five consecutive cycles. The swelling was favored in an alkaline pH due to the ionization of hydrophilic groups. The sustained release of phosphorus in HCGP was described by the Korsmeyer–Peppas model, and Fickian diffusion is the main fertilizer release mechanism. Finally, the hydrogels do not demonstrate toxicity, and HCGP has potential for application in agriculture.
Recent Developments in Chitosan-Based Micro/Nanofibers for Sustainable Food Packaging, Smart Textiles, Cosmeceuticals, and Biomedical Applications
Authors: Tien Nguyen D. , Lyngstadaas Ståle Petter , Mano João F. , Blaker Jonathan James , Haugen Håvard J.
Published: May 2021

Chitosan has many useful intrinsic properties (e.g., non-toxicity, antibacterial properties, and biodegradability) and can be processed into high-surface-area nanofiber constructs for a broad range of sustainable research and commercial applications. These nanofibers can be further functionalized with bioactive agents. In the food industry, for example, edible films can be formed from chitosan-based composite fibers filled with nanoparticles, exhibiting excellent antioxidant and antimicrobial properties for a variety of products. Processing ‘pure’ chitosan into nanofibers can be challenging due to its cationic nature and high crystallinity; therefore, chitosan is often modified or blended with other materials to improve its processability and tailor its performance to specific needs. Chitosan can be blended with a variety of natural and synthetic polymers and processed into fibers while maintaining many of its intrinsic properties that are important for textile, cosmeceutical, and biomedical applications. The abundance of amine groups in the chemical structure of chitosan allows for facile modification (e.g., into soluble derivatives) and the binding of negatively charged domains. In particular, high-surface-area chitosan nanofibers are effective in binding negatively charged biomolecules. Recent developments of chitosan-based nanofibers with biological activities for various applications in biomedical, food packaging, and textiles are discussed herein.
Advances in the Synthesis of Ring-Fused Benzimidazoles and Imidazobenzimidazoles
Authors: Sweeney Martin , Conboy Darren , Mirallai Styliana I. , Aldabbagh Fawaz
Published: May 2021

This review article provides a perspective on the synthesis of alicyclic and heterocyclic ring-fused benzimidazoles, imidazo[4,5-f]benzimidazoles, and imidazo[5,4-f]benzimidazoles. These heterocycles have a plethora of biological activities with the iminoquinone and quinone derivatives displaying potent bioreductive antitumor activity. Synthesis is categorized according to the cyclization reaction and mechanisms are detailed. Nitrobenzene reduction, cyclization of aryl amidines, lactams and isothiocyanates are described. Protocols include condensation, cross-dehydrogenative coupling with transition metal catalysis, annulation onto benzimidazole, often using CuI-catalysis, and radical cyclization with homolytic aromatic substitution. Many oxidative transformations are under metal-free conditions, including using thermal, photochemical, and electrochemical methods. Syntheses of diazole analogues of mitomycin C derivatives are described. Traditional oxidations of o-(cycloamino)anilines using peroxides in acid via the t-amino effect remain popular.
Robust Hydrogel Adhesive with Dual Hydrogen Bond Networks
Authors: Jiang Zhiqiang , Li Ya , Shen Yirui , Yang Jian , Zhang Zongyong , You Yujing , Lv Zhongda , Yao Lihui
Published: May 2021

Hydrogel adhesives are attractive for applications in intelligent soft materials and tissue engineering, but conventional hydrogels usually have poor adhesion. In this study, we designed a strategy to synthesize a novel adhesive with a thin hydrogel adhesive layer integrated on a tough substrate hydrogel. The adhesive layer with positive charges of ammonium groups on the polymer backbones strongly bonds to a wide range of nonporous materials’ surfaces. The substrate layer with a dual hydrogen bond system consists of (i) weak hydrogen bonds between N,N-dimethyl acrylamide (DMAA) and acrylic acid (AAc) units and (ii) strong multiple hydrogen bonds between 2-ureido-4[1H]-pyrimidinone (UPy) units. The dual hydrogen-bond network endowed the hydrogel adhesives with unique mechanical properties, e.g., toughness, highly stretchability, and insensitivity to notches. The hydrogel adhesion to four types of materials like glass, 316L stainless steel, aluminum, Al2O3 ceramic, and two biological tissues including pig skin and pig kidney was investigated. The hydrogel bonds strongly to dry solid surfaces and wet tissue, which is promising for biomedical applications.
Design and Development of D‒α‒Tocopheryl Polyethylene Glycol Succinate‒block‒Poly(ε-Caprolactone) (TPGS−b−PCL) Nanocarriers for Solubilization and Controlled Release of Paclitaxel
Authors: Yusuf Osman , Ali Raisuddin , Alomrani Abdullah H. , Alshamsan Aws , Alshememry Abdullah K. , Almalik Abdulaziz M. , Lavasanifar Afsaneh , Binkhathlan Ziyad
Published: May 2021

The objective of this study was to synthesize and characterize a set of biodegradable block copolymers based on TPGS-block-poly(ε-caprolactone) (TPGS-b-PCL) and to assess their self-assembled structures as a nanodelivery system for paclitaxel (PAX). The conjugation of PCL to TPGS was hypothesized to increase the stability and the drug solubilization characteristics of TPGS micelles. TPGS-b-PCL copolymer with various PCL/TPGS ratios were synthesized via ring opening bulk polymerization of ε-caprolactone using TPGS, with different molecular weights of PEG (1–5 kDa), as initiators and stannous octoate as a catalyst. The synthesized copolymers were characterized using 1H NMR, GPC, FTIR, XRD, and DSC. Assembly of block copolymers was achieved via the cosolvent evaporation method. The self-assembled structures were characterized for their size, polydispersity, and CMC using dynamic light scattering (DLS) technique. The results from the spectroscopic and thermal analyses confirmed the successful synthesis of the copolymers. Only copolymers that consisted of TPGS with PEG molecular weights ≥ 2000 Da were able to self-assemble and form nanocarriers of ≤200 nm in diameter. Moreover, TPGS2000-b-PCL4000, TPGS3500-b-PCL7000, and TPGS5000-b-PCL15000 micelles enhanced the aqueous solubility of PAX from 0.3 µg/mL up to 88.4 ug/mL in TPGS5000-b-PCL15000. Of the abovementioned micellar formulations, TPGS5000-b-PCL15000 showed the slowest in vitro release of PAX. Specifically, the PAX-loaded TPGS5000-b-PCL15000 micellar formulation showed less than 10% drug release within the first 12 h, and around 36% cumulative drug release within 72 h compared to 61% and 100% PAX release, respectively, from the commercially available formulation (Ebetaxel®) at the same time points. Our results point to a great potential for TPGS-b-PCL micelles to efficiently solubilize and control the release of PAX.
Effect of Fish Bone Bioactive Peptides on Oxidative, Inflammatory and Pigmentation Processes Triggered by UVB Irradiation in Skin Cells
Authors: Iosageanu Andreea , Ilie Daniela , Craciunescu Oana , Seciu-Grama Ana-Maria , Oancea Anca , Zarnescu Otilia , Moraru Ionut , Oancea Florin
Published: May 2021

In the present study, we evaluated for the first time the photoprotective effect of fish bone bioactive peptides (FBBP) preparation isolated from silver carp (Hypophthalmichthys molitrix) discarded tissue using in vitro experimental models of skin cells exposed to ultraviolet B (UVB) irradiation and stressing agents. FBBP preparation was obtained by papain treatment of minced bones and centrifugal ultrafiltration, and the molecular weight (MW) distribution was characterized by size exclusion and reversed-phase high performance liquid chromatography (RP-HPLC). In vitro assessment of the effect of FBBP pretreatment in UVB-irradiated L929 fibroblasts and HaCaT keratinocytes revealed their cytoprotective activity. Their capacity to efficiently reduce reactive oxygen species (ROS) production and lipid peroxidation varied in a dose-dependent manner, and it was greater in fibroblasts. A decrease of proinflammatory cytokines secretion, in particular of tumor necrosis factor alpha (TNF-α), was found after FBBP pretreatment of THP-1-derived inflamed macrophages. Melanin production and tyrosinase activity investigated in UVB-irradiated Mel-Juso cells were lowered in direct relation to FBBP concentrations. FBBP fractions with high radical scavenging activity were separated by ion exchange chromatography, and two collagenic sequences were identified. All these results offer new scientific data on aquaculture fish bone-derived peptides confirming their ability to control the antioxidant, anti-inflammatory and pigmentation processes developed during UV irradiation of skin cells and recommend their use as valuable natural ingredients of photoprotective cosmeceutical products.