bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Mathematics Early Years Education in Spain, Portugal and Slovenia
Authors: Ancheta-Arrabal Ana , Segura Carlos
Published: July 2022

This work aims to examine how the learning of mathematics in early childhood is developed in different policies, particularly within the processes of formal education and care in early years institutions. A comparative analysis of early mathematics education policies across countries must consider cultural differences, teaching practice, structural differences and institutional framework conditions, as well as the initial training and professional knowledge of teachers and educators. Extracted from the official country regulations, the following pages include some of the main characteristics of the national systems of early childhood education and care (ECEC) in Portugal, Slovenia and Spain, as well as a comparison of the ECEC guidelines concerning mathematics education between these three countries. There is an international consensus on an approach to early mathematics education inspired by realistic mathematics education (RME), i.e., on the importance of working mathematically in context, as well as on the idea of doing so through play, developing the language to communicate mathematical ideas. However, we found that these three aspects are reflected very differently in the official regulations of the three countries: while in Spain the development is very detailed and emphasizes the holistic approach and the role of mathematics in exploring the environment, the Portuguese curriculum emphasizes the role of mathematics as a form of language. The Slovenian curriculum, at last, focuses on the concepts and procedures associated with each mathematical sense. Furthermore, there are structural features concerning the regulation and type of ECEC system that have an influence in the implementation of the curriculum.
Mesh Processing for Snapping Feature Points and Polylines in Orebody Modeling
Authors: Li Zhaopeng , Zhong Deyun , Wang Liguan , Tang Qiwang , Wu Zhaohao
Published: July 2022

The 3D refinement modeling of the orebody provides an important guarantee for the estimation of the resources and reserves of an ore deposit. Implicit modeling techniques can effectively improve the efficiency of orebody modeling and facilitate the dynamic updating of the model. However, due to the problems of ambiguity and missing features during implicit surface interpolation and implicit surface reconstruction, the mesh models of orebodies obtained by means of implicit modeling techniques do not easily snap to the geological feature points and feature polylines obtained based on geological sampling data. In essence, all models are inaccurate, but geological sampling data are very useful and valuable, which should be accurately and effectively involved in the orebody modeling process. This would help to improve the reliability of resource estimation and mining design. The main contribution of this paper is the proposal of a method for accurately snapping orebody features after implicit modeling. This method enables the orebody model to snap accurately to the geological feature points and feature polylines and realizes the accurate clipping of the model boundary. We tested the method with real geological datasets. The results showed that the method is applicable and effective when the geological feature points and feature polylines are close to those of the orebody mesh model and the shape trend changes little, and the model can thus meet the practical application requirements of mines.
Application of Monte Carlo Simulation to Study the Probability of Confidence Level under the PFMEA’s Action Priority
Authors: Sun Jia-Jeng , Yeh Tsu-Ming , Pai Fan-Yun
Published: July 2022

Failure mode and effects analysis (FMEA) is the most commonly used risk evaluation tool in industry and academia. After four revisions, the US Automotive Industry Action Groups (AIAG) and German Association of the Automotive Industry (VDA) issued the latest FMEA manual, called AIAG and VDA FMEA Handbook Edition 1, in June 2019. Risk priority number (RPN) in the old-edition FMEA is replaced with action priority (AP), where the numerical evaluation of severity (S), occurrence (O), and detection (D) are referred to in the AP form for judging high (H), medium (M), and low (L) priority in order to ensure appropriate actions for improving prevention or detection control. When evaluating design (D) or process (P) in FMEA, the FMEA team has to refer to the evaluation criteria for S, O, and D, so as to reduce the difference in the evaluation reference and fairness. Since the criteria evaluation form is the qualitative rating standard with semantic judgment, evaluation errors are likely to occur when the team judges S, O, and D. The FMEA cases in this study are preceded by the confidence level (CL) of the S, O, and D evaluation standards and the setting of a confidence interval (CI) for the actual evaluation events. With discrete nonuniform distribution as the simulation setting, Monte Carlo simulation is applied several times to evaluate the probability before and after the evaluation, which is compared with the AP form to confirm the probability values of high, medium, and low priority. It provides reference for the FMEA cross-functional team, improving the originally non-AP events. Finally, the AP calculated in the simulation is compared and analyzed with the RPN sequence to verify the judgment of better actions with AP.
120 GHz Frequency-Doubler Module Based on GaN Schottky Barrier Diode
Authors: Liu Honghui , Liang Zhiwen , Meng Jin , Liu Yuebo , Wang Hongyue , Yan Chaokun , Wu Zhisheng , Liu Yang , Zhang Dehai , Wang Xinqiang , Zhang Baijun
Published: July 2022

Traditional GaAs-based frequency multipliers still exhibit great challenges to meet the demand for solid-state high-power THz sources due to low breakdown voltage and heat dissipation of the Schottky barrier diode (SBD). In this study, a GaN SBD chain was fabricated with n−/n+-GaN structure. As a consequence, the breakdown voltage of 54.9 V at 1 μA and cut-off frequency of 587.5 GHz at zero bias were obtained. A 120 GHz frequency-doubler module based on the GaN SBD chain was designed and fabricated. When driven with 500 mW input power in a continuous wave, the output power of the frequency-doubler module was 15.1 mW at 120 GHz. Moreover, the experiments show that the frequency-doubler module can endure an input power of 2 W. In addition, it is worth noting that the SBD chain works well at an anode temperature of 337.2 °C.
Digital Tri-Axis Accelerometer with X/Y-Axial Resonators and Z-Axial Capacitive Seesaw
Authors: Xia Dunzhu , Yao Mohan , Li Jinhui
Published: July 2022

A tri-axis accelerometer with a digital readout circuit and communication system is introduced. It is composed of two resonant accelerometers in the x and y-axis, and a seesaw capacitive one in the z-axis. The device is encapsulated in air to ensure that the z-axis works in an over-damped state. Moreover, the closed-loop drive circuit establishes the x-axis and y-axis in resonant mode, and the z-axis in force balance mode. A miniaturized measurement based on FPGA is designed to collect these output signals. The phase noise of the resonance part and the amplitude noise of the seesaw part are studied by simulation. The model can predict the contribution of each part to the measurement error and Allan variance. Multiplied clock and Kalman filter in sliding window are used to reduce the frequency error. The test results show that the accelerometer has low bias instability (<30 μg), low cross-coupling error (<0.5%), and low nonlinearity (<0.1%). The tri-axis digital accelerometer with serial ports is more valuable than the previous works with large commercial instruments.
LC-MS/MS-Based Fungicide Accumulation Assay to Demonstrate Efflux Activity in the Wheat Pathogen Zymoseptoria tritici
Authors: Fouché Guillaume , Rosati Dominique , Venet Catherine , Josserand Hervé , Latorse Marie-Pascale , Debieu Danièle , Fillinger Sabine
Published: July 2022

Increased drug efflux compromises the efficacy of a large panel of treatments in the clinic against cancer or bacterial, fungal, and viral diseases, and in agriculture due to the emergence of multidrug-resistant pathogenic fungi. Until recently, to demonstrate increased drug efflux, the use of labeled drugs or fluorescent dyes was necessary. With the increasing sensitivity of detection devices, direct assessment of drug efflux has become realistic. Here, we describe a medium-throughput method to assess the intracellular drug concentration in the plant pathogenic fungus Zymoseptoria tritici cultivated in the presence of a sublethal fungicide concentration. As a model fungicide, we used the succinate-dehydrogenase inhibitor boscalid. The boscalid concentration was assessed in the different culture fractions using mass spectrometry linked to liquid chromatography (LC-MS/MS). The ratio between the intracellular and total boscalid amount was used as an inversed proxy for the efflux activity. Using isogenic mutant strains known for their differential efflux capacities, we validated the negative correlation between the intracellular boscalid concentration and efflux activity. In addition, intra-cellular fungicide accumulation explains the susceptibility of the tested strains to boscalid. This assay may be useful in lead development when a new molecule displays good inhibitory activity against its isolated target protein but fails to control the target organism.
Degrading Characterization of the Newly Isolated Nocardioides sp. N39 for 3-Amino-5-methyl-isoxazole and the Related Genomic Information
Authors: Yan Lei , Liang Bin , Qi Meng-Yuan , Wang Ai-Jie , Liu Zhi-Pei
Published: July 2022

3-amino-5-methyl-isoxazole (3A5MI) is a persistent and harmful intermediate in the degradation of antibiotic sulfamethoxazole. It was accumulated in the environments day by day and has caused great environmental risks due to its refractory characteristic. Microbial degradation is economic and environmentally friendly and a promising method to eliminate this pollutant. In this study, a bacterial strain, Nocardioides sp. N39, was isolated. N39 can grow on 3A5MI as the sole carbon, nitrogen and energy resource. The effect of different factors on 3A5MI degradation by N39 was explored, including initial 3A5MI concentration, temperature, pH value, dissolved oxygen and additional carbon or nitrogen source. The degradation ability of N39 to various 3A5MI analogs was also explored. Nevertheless, the degrading ability of N39 for 3A5MI is not permanent, and long-term storage would lead to the loss of this ability. This may result from the mobile genetic elements in the bacterium according to the genomic comparison of N39 and its degrading ability-lost strain, N40. Despite this, N39 could support a lot of useful information about the degradation of 3A5MI and highlight the importance of studies about the environmental effects and potential degradation mechanism.
Aspergillus Hydrophobins: Physicochemical Properties, Biochemical Properties, and Functions in Solid Polymer Degradation
Authors: Tanaka Takumi , Terauchi Yuki , Yoshimi Akira , Abe Keietsu
Published: July 2022

Hydrophobins are small amphipathic proteins conserved in filamentous fungi. In this review, the properties and functions of Aspergillus hydrophobins are comprehensively discussed on the basis of recent findings. Multiple Aspergillus hydrophobins have been identified and categorized in conventional class I and two non-conventional classes. Some Aspergillus hydrophobins can be purified in a water phase without organic solvents. Class I hydrophobins of Aspergilli self-assemble to form amphipathic membranes. At the air–liquid interface, RolA of Aspergillus oryzae self-assembles via four stages, and its self-assembled films consist of two layers, a rodlet membrane facing air and rod-like structures facing liquid. The self-assembly depends mainly on hydrophobin conformation and solution pH. Cys4–Cys5 and Cys7–Cys8 loops, disulfide bonds, and conserved Cys residues of RodA-like hydrophobins are necessary for self-assembly at the interface and for adsorption to solid surfaces. AfRodA helps Aspergillus fumigatus to evade recognition by the host immune system. RodA-like hydrophobins recruit cutinases to promote the hydrolysis of aliphatic polyesters. This mechanism appears to be conserved in Aspergillus and other filamentous fungi, and may be beneficial for their growth. Aspergilli produce various small secreted proteins (SSPs) including hydrophobins, hydrophobic surface–binding proteins, and effector proteins. Aspergilli may use a wide variety of SSPs to decompose solid polymers.
Changes in Amino Acid Metabolism of Staphylococcus aureus following Growth to the Stationary Phase under Adjusted Growth Conditions
Authors: Alreshidi Mousa , Dunstan Hugh , Roberts Tim , Bardakci Fevzi , Badraoui Riadh , Adnan Mohd , Saeed Mohd , Alreshidi Fayez , Albulaihed Yazeed , Snoussi Mejdi
Published: July 2022

The sharp increase in infections due to Staphylococcus aureus is associated with its ability to adapt to changes in its habitat. This study aimed to investigate the differences in the cytoplasmic amino acid profiles of a clinical strain of S. aureus under five combinations of stress-induced conditions representative of a wound site by varying temperature 35–37 °C, adding 0–5% NaCl and adjusting pH 6–8. The results indicated that aspartic acid, lysine, glutamic acid and histidine were the most abundant cytoplasmic amino acids in the control samples grown under optimal growth conditions. However, the magnitudes and levels of these amino acids were altered under the various wound site conditions, which led to differential cytoplasmic amino acid profiles as characterized by multivariate analyses (PLS-DA). The total cytoplasmic amino acid content was significantly reduced in the cells grown with 2.5% NaCl added at pH 7 and 37 °C relative to the control samples and other growth regimes. However, all combinations of enhanced stress conditions showed unique and characteristic changes in the concentration profiles of the cytoplasmic amino acids. These outcomes supported the hypothesis that bacterial cells of S. aureus maintain different metabolic homeostasis under various stress-induced conditions. The potent capability of S. aureus to constantly and rapidly acclimatize to variations within the environment may reflect the crucial feature supporting its virulence as an opportunistic pathogenic bacterium to invade the wound site. Understanding the control systems governing these marked changes in amino acids during the adaptation to the potential wound site conditions of this dangerous bacterium may offer new clinical controls to combat infection.
Prediction of the Adaptability of Using Continuous Extraction and Continuous Backfill Mining Method to Sequestrate CO2-A Case Study
Authors: Xu Yujun , Ma Liqiang , Ngo Ichhuy , Wang Yangyang , Zhai Jiangtao , Hou Lixiao
Published: July 2022

The consumption of coal resources has caused an increase in CO2 emissions. A scientific concept that can realize CO2 sequestration, the harmless treatment of solid wastes, and coal extraction under buildings, railways, and water bodies (BRW) is proposed. First, a novel CO2 mineralized filling body (CMFB) is developed by employing CO2 gas, fly ash, silicate additives, and cement. It is then injected into the mined-out mining roadways (MRs) of the continuous extracting and continuous backfill (CECB) mining method to ameliorate the overburden migration and thus extract the coal body under the BRW. The AHP-fuzzy comprehensive evaluation method was employed to construct a prediction model for the suitability of this concept. Subsequently, the evaluation model is generalized and applied to the Yu-Shen mining area. Each indicator affecting adaptability is plotted on a thematic map, and the corresponding membership degree is determined. The aptness for 400 boreholes distributed in the entire area was determined and a zoning map which divides the whole area into good, moderate, slightly poor, and extremely poor suitability was drawn. This paper puts forward a mathematical model for predicting the suitability of using CECB and CMFB to sequestrate CO2. Research results can provide references for determining the site of CO2 sequestration under the premise of maximizing the economic and ecological benefits, which is conducive to constructing ecological, green, and sustainable coal mines.
Recent Ostracod Fauna of the Western Ross Sea (Antarctica): A Poorly Known Ingredient of Polar Carbonate Factories
Authors: Salvi Gianguido , Anderson John B. , Bertoli Marco , Castagno Pasquale , Falco Pierpaolo , Fernetti Michele , Montagna Paolo , Taviani Marco
Published: July 2022

Ostracoda are a minor but recurrent component of Southern Ocean marine carbonate factories, and their low-Mg calcitic skeletal mineralogy helps in ensuring a noteworthy post-mortem resilience. Our study, based upon surface sediment occurrences, contributes to the better definition of their distribution vs. potential controlling factors in Antarctic waters. The ostracod fauna from the Western Ross Sea Shelf appears dominated by Australicythere polylyca, Australicythere devexa, Xestoleberis rigusa, Loxoreticulatum fallax, Cativella bensoni, Austrotrachyleberis antarctica and Patagonacythere longiducta, colonizing a variety of shelf environments along a wide bathymetric range. The abundance and richness values correlate well to nutrient distribution and sediment supply, primarily related to the circulation of different oceanographic regimes affecting the floor of the Ross Sea Shelf. Circumpolar Deep Water could represent the main factor controlling the distribution of ostracods. Similar results (high abundance and richness in ostracod values) were also recorded in the Terra Nova Bay and in a nearby area characterized by warm water rich in nutrients and composed of water of circumpolar origin flowing from the open ocean southwards onto the continental shelf. Particulate Fe (pFe), in suspended particulate matter (SPM), and other particulate trace metals in TNB could support the hypothesis that biogenic iron may significantly contribute to the bioavailable iron pool, sustaining both primary production and ostracod fauna richness in this area.
Analysis of Citrus Bioflavonoid Content and Dipeptidyl Peptidase-4 Inhibitory Potential of Commercially Available Supplements
Authors: Gupta Ankit , Al-Aubaidy Hayder A. , Narkowicz Christian K. , Jelinek Herbert F. , Nichols David S. , Burgess John R. , Jacobson Glenn A.
Published: July 2022

Citrus bioflavonoids are polyphenolic plant-derived pigments found in high levels in oranges, lemons, grapefruits and other citrus fruits. The three most abundant types of citrus bioflavonoids are hesperidin, naringenin and eriocitrin. Citrus bioflavonoids have long been known to possess powerful free radical-scavenging properties and cardioprotective effects. The study involved the analysis of 10 commercially available citrus bioflavonoid supplements from three different countries: Australia, the United States and Canada. The supplements were tested for their citrus bioflavonoid content which varied from 0.8 to 33.3% w/w. The daily bioflavonoid dose varied from 19 mg to 560 mg. Hesperidin was the major citrus bioflavonoid in nine out of ten supplements. One supplement was found to contain less than 10% of the quantity of rutin claimed to have been added. The DPP-4 inhibitory potential, compared through an estimation of rutin equivalence, ranged from 1.9 mg to 400 mg per day. This data highlights the variability between the supplements in their potential to inhibit DPP-4 for subsequent health benefits.
The Anti-Inflammatory Activities of Fermented Curcuma That Contains Butyrate Mitigate DSS-Induced Colitis in Mice
Authors: Bayazid Al Borhan , Jeong Soo Ah , Park Chae Won , Kim Da Hee , Lim Beong Ou
Published: July 2022

Inflammatory bowel disease is characterized by a radical imbalance of inflammatory signaling pathways in the gastrointestinal tract, and it is categorized into two diseases, such as Crohn’s disease and ulcerative colitis. In this study, we investigated anti-inflammatory activities using fermented Curcuma that contains butyrate (FB). Nitric oxide production in RAW 264.7 cells and the expression of inducible nitric oxide synthase in the intestinal mucosa appears to be enhanced in active ulcerative colitis. Here, the cytotoxicity, physiological activity, and anti-inflammatory efficacy of FB in colitis animals were investigated. To verify the anti-inflammatory effect, this study was conducted using the dextran sulfate sodium (DSS)-induced colitis mice model. As a result, non-toxicity was confirmed, and anti-inflammatory effects were revealed by inducing a reduction of LPS-induced NO production. In the DSS-induced colitis, reduced weight was recovered and a decrease in inflammatory factors Ig-E and TNF-α in the mesenteric lymph node (MLN) and spleen was induced, and it was confirmed to help with the morphological remodeling of the intestine. In conclusion, this paper suggests that FB can help to alleviate intestinal inflammation and to improve the intestinal environment, with the help of morphological remodeling.
Annellated 1,3,4,2-Triazaphospholenes-Simple Modular Synthesis and a First Exploration of Ligand Properties
Authors: Richter Ferdinand , Birchall Nicholas , Feil Christoph M. , Nieger Martin , Gudat Dietrich
Published: July 2022

The successful use of 1,3,4,2-triazaphospholenes (TAPs) as organo-catalysts stresses the need for efficient synthetic routes to these molecules. In this study, we establish the [1 + 4]-cycloaddition of PBr3 to azo-pyridines as a new approach to preparing pyrido-annellated TAPs in a single step from easily available precursors. The modular assembly of the azo-component via condensation of primary amines and nitroso compounds along with the feasibility of post-functionalization at the P–Br bond under conservation of the heterocyclic structure allows, in principle, to address a wide range of target molecules, which is illustrated by prototypical examples. The successful synthesis of a transition metal complex confirms for the first time the ability of a TAP to act as a P-donor ligand. Crystallographic studies suggest that hyperconjugation effects and intermolecular interactions induce a qualitatively similar ionic polarization of the P–Br bonds in TAPs as in better known isoelectronic diazaphospholenes.
Tungsten-Based Nanocatalysts: Research Progress and Future Prospects
Authors: Ke Shaorou , Min Xin , Liu Yangai , Mi Ruiyu , Wu Xiaowen , Huang Zhaohui , Fang Minghao
Published: July 2022

The high price of noble metal resources limits its commercial application and stimulates the potential for developing new catalysts that can replace noble metal catalysts. Tungsten-based catalysts have become the most important substitutes for noble metal catalysts because of their rich resources, friendly environment, rich valence and better adsorption enthalpy. However, some challenges still hinder the development of tungsten-based catalysts, such as limited catalytic activity, instability, difficult recovery, and so on. At present, the focus of tungsten-based catalyst research is to develop a satisfactory material with high catalytic performance, excellent stability and green environmental protection, mainly including tungsten atomic catalysts, tungsten metal nanocatalysts, tungsten-based compound nanocatalysts, and so on. In this work, we first present the research status of these tungsten-based catalysts with different sizes, existing forms, and chemical compositions, and further provide a basis for future perspectives on tungsten-based catalysts.
Peptide Biomarkers Discovery for Seven Species of Deer Antler Using LC-MS/MS and Label-Free Approach
Authors: Xue Fei , Wang Bing , Guo Dong-Xiao , Jiao Yang , Yin Xue , Cui Wei-Liang , Zhou Qian-Qian , Yu Feng-Rui , Lin Yong-Qiang
Published: July 2022

Deer antler is a globally widely used precious natural medicine and the material of deer horn gelatin. However, identification of deer antler species based on traditional approaches are problematic because of their similarity in appearance and physical-chemical properties. In this study, we performed a comprehensive antler peptidome analysis using a label-free approach: nano LC-Orbitrap MS was applied to discover peptide biomarkers in deer adult beta-globin (HBBA), and HPLC-Triple Quadrupole MS was used to verify their specificity. Nineteen peptide biomarkers were found, on which foundation a strategy for antlers and a strategy for antler mixtures such as flakes or powder are provided to identify seven species of deer antler including Eurasian elk (Alces alces), reindeer (Rangifer tarandus), white-tailed deer (Odocoileus viginianus), white-lipped deer (Przewalskium albirostris), fallow deer (Dama dama), sika deer (Cervus nippon), and red deer (Cervus elaphus) simultaneously. It is worth noting that our search found that the HBBA gene of sika deer, red deer, and North American wapiti (Cervus canadensis) in China may have undergone severe genetic drifts.
Comparative Characterization and Immunomodulatory Activities of Polysaccharides Extracted from the Radix of Platycodon grandiflorum with Different Extraction Methods
Authors: Xiao Wanwan , Zhou Pingfan , Wang Xiaoshuang , Zhao Ruizhi , Wang Yan
Published: July 2022

Platycodon grandiflorum is an edible and medicinal plant, and polysaccharides are one of its important components. To further improve the utilization rate of P. grandiflorum, we investigated the effects of four different extraction methods, including hot water, ultrasonic-assisted, acid-assisted, and alkali-assisted extractions, on the polysaccharides, which were named PG-H, PG-U, PG-C, and PG-A. The findings indicated that the extraction method had a significant impact on the yield, characteristics, and immunoregulatory activity. We observed that the yields decreased in the following order: PG-H, PG-U, PG-C, and PG-A. Galacturonic acid, glucose, galactose, and arabinose were the most prevalent monosaccharides in the four PGs. However, their proportions varied. In addition, the difference between the content of glucose and galacturonic acid was more significant. PG-U had the highest glucose content, whereas PG-C had the lowest. Galacturonic acid content was highest in PG-A, while the lowest in PG-U. The molecular weight decreased in the order of PG-U, PG-H, PG-C, and PG-A; the particle size was in the order of PG-U, PG-A, PG-H, and PG-C. Moreover, the extraction method had a great impact on immunoregulatory activity. The ability to stimulate the immune function of macrophages was as follows: PG-A > PG-C > PG-U > PG-H. The results indicated that PGs, with lower molecular weights and higher GalA content, exhibited better immune-stimulating activity. And more important the AAE method was a good way to extract polysaccharides from Platycodon grandiflorum for use as a functional product and immunological adjuvant.
A High-Throughput Clinical Laboratory Methodology for the Therapeutic Monitoring of Ibrutinib and Dihydrodiol Ibrutinib
Authors: Karvaly Gellért Balázs , Vincze István , Balogh Alexandra , Köllő Zoltán , Bödör Csaba , Vásárhelyi Barna
Published: July 2022

Ibrutinib (IBR) is an oral anticancer medication that inhibits Bruton tyrosine kinase irreversibly. Due to the high risk of adverse effects and its pharmacokinetic variability, the safe and effective use of IBR is expected to be facilitated by precision dosing. Delivering suitable clinical laboratory information on IBR is a prerequisite of constructing fit-for-purpose population and individual pharmacokinetic models. The validation of a dedicated high-throughput method using liquid chromatography–mass spectrometry is presented for the simultaneous analysis of IBR and its pharmacologically active metabolite dihydrodiol ibrutinib (DIB) in human plasma. The 6 h benchtop stability of IBR, DIB, and the active moiety (IBR + DIB) was assessed in whole blood and in plasma to identify any risk of degradation before samples reach the laboratory. In addition, four regression algorithms were tested to determine the optimal assay error equations of IBR, DIB, and the active moiety, which are essential for the correct estimation of the error of their future nonparametric pharmacokinetic models. The noncompartmental pharmacokinetic properties of IBR and the active moiety were evaluated in three patients diagnosed with chronic lymphocytic leukemia to provide a proof of concept. The presented methodology allows clinical laboratories to efficiently support pharmacokinetics-based precision pharmacotherapy with IBR.
Potential Applications of Thyroid Hormone Derivatives in Obesity and Type 2 Diabetes: Focus on 3,5-Diiodothyronine (3,5-T2) in Psammomys obesus (Fat Sand Rat) Model
Authors: Bouazza Asma , Favier Roland , Fontaine Eric , Leverve Xavier , Koceir Elhadj-Ahmed
Published: July 2022

3,5-Diiodothyronine (3,5-T2) has been shown to exert pleiotropic beneficial effects. In this study we investigated whether 3,5-T2 prevent several energy metabolism disorders related to type 2 diabetes mellitus (T2DM) in gerbils diabetes-prone P. obesus. 157 male gerbils were randomly to Natural Diet (ND-controlled) or a HED (High-Energy Diet) divided in: HED- controlled, HED-3,5-T2 and HED- Placebo groups. 3,5-T2 has been tested at 25 µg dose and was administered under subcutaneous pellet implant during 10 weeks. Isolated hepatocytes were shortly incubated with 3,5-T2 at 10−6 M and 10−9 M dose in the presence energetic substrates. 3,5-T2 treatment reduce visceral adipose tissue, prevent the insulin resistance, attenuated hyperglycemia, dyslipidemia, and reversed liver steatosis in diabetes P. obesus. 3,5-T2 decreased gluconeogenesis, increased ketogenesis and enhanced respiration capacity. 3,5-T2 potentiates redox and phosphate potential both in cytosol and mitochondrial compartment. The use of 3,5-T2 as a natural therapeutic means to regulate cellular energy metabolism. We suggest that 3,5-T2 may help improve the deleterious course of obesity and T2DM, but cannot replace medical treatment.
Exploring the Binding Interaction of Active Compound of Pineapple against Foodborne Bacteria and Novel Coronavirus (SARS-CoV-2) Based on Molecular Docking and Simulation Studies
Authors: Abuzinadah Mohammed F. , Ahmad Varish , Al-Thawdi Salwa , Zakai Shadi Ahmed , Jamal Qazi Mohammad Sajid
Published: July 2022

Natural resources, particularly plants and microbes, are an excellent source of bioactive molecules. Bromelain, a complex enzyme mixture found in pineapples, has numerous pharmacological applications. In a search for therapeutic molecules, we conducted an in silico study on natural phyto-constituent bromelain, targeting pathogenic bacteria and viral proteases. Docking studies revealed that bromelain strongly bound to food-borne bacterial pathogens and SARS-CoV-2 virus targets, with a high binding energy of −9.37 kcal/mol. The binding interaction was mediated by the involvement of hydrogen bonds, and some hydrophobic interactions stabilized the complex and molecular dynamics. Simulation studies also indicated the stable binding between bromelain and SARS-CoV-2 protease as well as with bacterial targets which are essential for DNA and protein synthesis and are required to maintain the integrity of membranous proteins. From this in silico study, it is also concluded that bromelain could be an effective molecule to control foodborne pathogen toxicity and COVID-19. So, eating pineapple during an infection could help to interfere with the pathogen attaching and help prevent the virus from getting into the host cell. Further, research on the bromelain molecule could be helpful for the management of COVID-19 disease as well as other bacterial-mediated diseases. Thus, the antibacterial and anti-SARS-CoV-2 virus inhibitory potentials of bromelain could be helpful in the management of viral infections and subsequent bacterial infections in COVID-19 patients.
The Effect of Laminaria japonica on Metabolic Syndrome: A Systematic Review of Its Efficacy and Mechanism of Action
Authors: Lee In-Seon , Ko Seok-Jae , Lee Yu Na , Lee Gahyun , Rahman Md. Hasanur , Kim Bonglee
Published: July 2022

Metabolic syndrome (MetS) is a medical condition characterized by abdominal obesity, insulin resistance, high blood pressure, and hyperlipidemia. An increase in the incidence of MetS provokes an escalation in health care costs and a downturn in quality of life. However, there is currently no cure for MetS, and the absence of immediate treatment for MetS has prompted the development of novel therapies. In accordance with recent studies, the brown seaweed Laminaria japonica (LJP) has anti-inflammatory and antioxidant properties, and so forth. LJP contains bioactive compounds used as food globally, and it has been used as a medicine in East Asian countries. We conducted a systematic review to examine whether LJP could potentially be a useful therapeutic drug for MetS. The following databases were searched from initiation to September 2021: PubMed, Web of Science, EMBASE, and Cochrane Central Register of Controlled Trials Library. Clinical trials and in vivo studies evaluating the effects of LJP on MetS were included. LJP reduces the oxidative stress-related lipid mechanisms, inflammatory cytokines and macrophage-related chemokines, muscle cell proliferation, and migration. Bioactive-glucosidase inhibitors reduce diabetic complications, a therapeutic target in obesity and type 2 diabetes. In obesity, LJP increases AMP-activated protein kinase and decreases acetyl-CoA carboxylase. Based on our findings, we suggest that LJP could treat MetS, as it has pharmacological effects on MetS.
Food Additives Associated with Gut Microbiota Alterations in Inflammatory Bowel Disease: Friends or Enemies?
Authors: Liu Caiguang , Zhan Shukai , Tian Zhenyi , Li Na , Li Tong , Wu Dongxuan , Zeng Zhirong , Zhuang Xiaojun
Published: July 2022

During the 21st century, the incidence and prevalence of inflammatory bowel disease (IBD) is rising globally. Despite the pathogenesis of IBD remaining largely unclear, the interactions between environmental exposure, host genetics and immune response contribute to the occurrence and development of this disease. Growing evidence implicates that food additives might be closely related to IBD, but the involved molecular mechanisms are still poorly understood. Food additives may be categorized as distinct types in accordance with their function and property, including artificial sweeteners, preservatives, food colorant, emulsifiers, stabilizers, thickeners and so on. Various kinds of food additives play a role in modifying the interaction between gut microbiota and intestinal inflammation. Therefore, this review comprehensively synthesizes the current evidence on the interplay between different food additives and gut microbiome alterations, and further elucidates the potential mechanisms of food additives–associated microbiota changes involved in IBD.
Association between Dietary Niacin Intake and Migraine among American Adults: National Health and Nutrition Examination Survey
Authors: Liu Huanxian , Wang Lu , Chen Chunfu , Dong Zhao , Yu Shengyuan
Published: July 2022

Migraine is related to brain energy deficiency. Niacin is a required coenzyme in mitochondrial energy metabolism. However, the relationship between dietary niacin and migraines remains uncertain. We aimed to evaluate the relationship between dietary niacin and migraine. This study used cross-sectional data from people over 20 years old who took part in the National Health and Nutrition Examination Survey between 1999 and 2004, collecting details on their severe headaches or migraines, dietary niacin intake, and several other essential variables. There were 10,246 participants, with 20.1% (2064/10,246) who experienced migraines. Compared with individuals with lower niacin consumption Q1 (≤12.3 mg/day), the adjusted OR values for dietary niacin intake and migraine in Q2 (12.4–18.3 mg/day), Q3 (18.4–26.2 mg/day), and Q4 (≥26.3 mg/day) were 0.83 (95% CI: 0.72–0.97, p = 0.019), 0.74 (95% CI: 0.63–0.87, p < 0.001), and 0.72 (95% CI: 0.58–0.88, p = 0.001), respectively. The association between dietary niacin intake and migraine exhibited an L-shaped curve (nonlinear, p = 0.011). The OR of developing migraine was 0.975 (95% CI: 0.956–0.994, p = 0.011) in participants with niacin intake < 21.0 mg/day. The link between dietary niacin intake and migraine in US adults is L-shaped, with an inflection point of roughly 21.0 mg/day.
Combined Cytotoxic Effect of Inhibitors of Proteostasis on Human Colon Cancer Cells
Authors: Nikotina Alina D. , Vladimirova Snezhana A. , Kokoreva Nadezhda E. , Komarova Elena Y. , Aksenov Nikolay D. , Efremov Sergey , Leonova Elizaveta , Pavlov Rostislav , Kartsev Viktor G. , Zhang Zhichao , Margulis Boris A. , Guzhova Irina V.
Published: July 2022

Despite significant progress in the diagnosis and treatment of colorectal cancer, drug resistance continues to be a major limitation of therapy. In this regard, studies aimed at creating combination therapy are gaining popularity. One of the most promising adjuvants are inhibitors of the proteostasis system, chaperone machinery, and autophagy. The main HSP regulator, HSF1, is overactivated in cancer cells and autophagy sustains the survival of malignant cells. In this work, we focused on the selection of combination therapy for the treatment of rectal cancer cells obtained from patients after tumor biopsy without prior treatment. We characterized the migration, proliferation, and chaperone status in the resulting lines and also found them to be resistant to a number of drugs widely used in the clinic. However, these cells were sensitive to the autophagy inhibitor, chloroquine. For combination therapy, we used an HSF1 activity inhibitor discovered earlier in our laboratory, the cardenolide CL-43, which has already been proven as an auxiliary component of combined therapy in established cell lines. CL-43 effectively suppressed HSF1 activity and Hsp70 expression in all investigated cells. We tested the autophagy inhibitor, chloroquine, in combination with CL-43. Our results indicate that the use of an inhibitor of HSF1 activity in combination with an autophagy inhibitor results in effective cancer cell death, therefore, this therapeutic approach may be a promising treatment regimen for certain patients.
Dry Powder Comprised of Isoniazid-Loaded Nanoparticles of Hyaluronic Acid in Conjugation with Mannose-Anchored Chitosan for Macrophage-Targeted Pulmonary Administration in Tuberculosis
Authors: Mukhtar Mahwash , Csaba Noemi , Robla Sandra , Varela-Calviño Rubén , Nagy Attila , Burian Katalin , Kókai Dávid , Ambrus Rita
Published: July 2022

Marketed dosage forms fail to deliver anti-tubercular drugs directly to the lungs in pulmonary Tuberculosis (TB). Therefore, nanomediated isoniazid (INH)-loaded dry powder for inhalation (Nano-DPI) was developed for macrophage-targeted delivery in TB. Mannosylated chitosan (MC) and hyaluronic acid (HA) with an affinity for the surface mannose and CD44 receptors of macrophages were used in conjugation to prepare hybrid nanosuspension by ionic gelation method using cross-linker, sodium tri-polyphosphate (TPP) followed by freeze-drying to obtain a dry powder composed of nanoparticles (INH-MC/HA NPs). Nanoformulations were evaluated for aerodynamic characteristics, cytotoxicity, hemocompatibility, macrophage phenotype analysis, and immune regulation. Cellular uptake imaging was also conducted to evaluate the uptake of NPs. The nanopowders did not pose any significant toxicity to the cells, along with good compatibility with red blood cells (RBCs). The pro-inflammatory costimulatory markers were upregulated, demonstrating the activation of T-cell response. Moreover, the NPs did not show any tolerogenic effect on the macrophages. Furthermore, confocal imaging exhibited the translocation of NPs in the cells. Altogether, the findings present that nano-DPI was found to be a promising vehicle for targeting macrophages.
Enhancement of Storage Stability and Masking Effect of Curcumin by Turmeric Extract-Loaded Nanoemulsion and Water-Soluble Chitosan Coating
Authors: Lee Bom Nae , Hong Su Jung , Yu Mi Hee , Shin Gye Hwa , Kim Jun Tae
Published: July 2022

This study focused on improving curcumin stability in various pHs and NaCl concentrations and reducing the strong scent of turmeric by the nanoemulsions system and further coating with water-soluble chitosan (WSC). Turmeric extract-loaded nanoemulsions (TE-NEs) were firstly prepared by mixing an oil phase containing turmeric extract, MCT oil, and lecithin, and an aqueous phase containing tween 80 using an ultrasonication method. TE-NEs were further coated with WSC in the ratio of TE-NEs and WSC (1:1 to 1:10). The optimum WSC-TE-NEs exhibited an average particle size of 182 nm, a PDI of 0.317, and a zeta potential of +30.42 mV when WSC-TE-NEs were prepared in the ratio of 1:1. The stability of the WSC-TE-NEs was also assessed by determining the remained curcumin content. The remained curcumin contents of the TE-NEs and the WSC-TE-NEs were higher than that of the turmeric extract (TE) at pH 2~7 and NaCl concentrations of 100~400 mM. Fourier transform infrared (FT-IR) spectra, transmission electron microscope (TEM), and confocal laser scanning microscope (CLSM) images confirmed that the TE-NEs were successfully encapsulated with a WSC coating. As a result of GC analysis, the content of aromatic-turmerone was significantly decreased in the TE-NEs and the WSC-TE-NEs compared to the pristine TE, but there was no significant difference between the TE-NEs and the WSC-TE-NEs. These results suggest that water-soluble chitosan-coated nanoemulsions may be suitable for improving the chemical stability and masking effect of curcumin to facilitate its application in food.
Bio-Priming of Soybean with Bradyrhizobium japonicum and Bacillus megaterium: Strategy to Improve Seed Germination and the Initial Seedling Growth
Authors: Miljaković Dragana , Marinković Jelena , Tamindžić Gordana , Đorđević Vuk , Tintor Branislava , Milošević Dragana , Ignjatov Maja , Nikolić Zorica
Published: July 2022

Bio-priming is a new technique of seed treatment that improves seed germination, vigor, crop growth and yield. The objective of this study was to evaluate the effectiveness of Bradyrhizobium japonicum (commercial strains) and Bacillus megaterium (newly isolated strains) as a single inoculant and co-inoculant during seed bio-priming to improve seed germination and initial seedling growth of two soybean cultivars. The treated seeds were subjected to germination test (GT), cold test (CT) and accelerated aging test (AAT). B. megaterium significantly improved all parameters in GT and CT; final germination, shoot length, root length, root dry weight, and seedling vigor index in AAT, as compared to control. In addition, co-inoculation significantly increased all parameters except shoot dry weight in GT; all parameters in CT; germination energy, shoot length, root length, and seedling vigor index in AAT, in comparison to the control. Moreover, Br. japonicum significantly improved the germination energy, shoot length, shoot dry weight, root dry weight, and seedling vigor index in GT; all parameters in CT; shoot length, root length, and seedling vigor index in AAT, compared with non-primed seeds. Thus, B. megaterium strains could be used in soybean bio-priming as a potential single inoculant and co-inoculant, following proper field evaluation.
Evaluation of the Antibacterial Activity of Eco-Friendly Hybrid Composites on the Base of Oyster Shell Powder Modified by Metal Ions and LLDPE
Authors: Widakdo Januar , Chen Tsan-Ming , Lin Meng-Chieh , Wu Jia-Hao , Lin Tse-Ling , Yu Pin-Ju , Hung Wei-Song , Lee Kueir-Rarn
Published: July 2022

Transforming biological waste into high-value-added materials is currently attracting extensive research interest in the medical and industrial treatment fields. The design and use of new antibacterial systems are urgently needed. In this study, we used discarded oyster shell powder (OSP) to prepare calcium oxide (CaO). CaO was mixed with silver (Ag), zinc (Zn), and copper (Cu) ions as a controlled release and antibacterial system to test the antibacterial activity. The inhibition zones of various modified metals were between 22 and 29 mm for Escherichia coli (E. coli) and between 21 and 24 mm for Staphylococcus aureus (S. aureus). In addition, linear low-density polyethylene (LLDPE) combined with CaO and metal ion forms can be an excellent alternative to a hybrid composite. The strength modulus at 1% LLDPE to LLDPE/CaO Ag increased from 297 to 320 MPa. In addition, the antimicrobial activity of LLDPE/CaO/metal ions against E. coli had an antibacterial effect of about 99.9%. Therefore, this hybrid composite material has good potential as an antibacterial therapy and biomaterial suitable for many applications.
Fabrication and Evaluation of Electrospun Silk Fibroin/Halloysite Nanotube Biomaterials for Soft Tissue Regeneration
Authors: Mohammadzadehmoghadam Soheila , LeGrand Catherine F. , Wong Chee-Wai , Kinnear Beverley F. , Dong Yu , Coombe Deirdre R.
Published: July 2022

The production of nanofibrous materials for soft tissue repair that resemble extracellular matrices (ECMs) is challenging. Electrospinning uniquely produces scaffolds resembling the ultrastructure of natural ECMs. Herein, electrospinning was used to fabricate Bombyx mori silk fibroin (SF) and SF/halloysite nanotube (HNT) composite scaffolds. Different HNT loadings were examined, but 1 wt% HNTs enhanced scaffold hydrophilicity and water uptake capacity without loss of mechanical strength. The inclusion of 1 wt% HNTs in SF scaffolds also increased the scaffold’s thermal stability without altering the molecular structure of the SF, as revealed by thermogravimetric analyses and Fourier transform infrared spectroscopy (FTIR), respectively. SF/HNT 1 wt% composite scaffolds better supported the viability and spreading of 3T3 fibroblasts and the differentiation of C2C12 myoblasts into aligned myotubes. These scaffolds coated with decellularised ECM from 3T3 cells or primary human dermal fibroblasts (HDFs) supported the growth of primary human keratinocytes. However, SF/HNT 1 wt% composite scaffolds with HDF-derived ECM provided the best microenvironment, as on these, keratinocytes formed intact monolayers with an undifferentiated, basal cell phenotype. Our data indicate the merits of SF/HNT 1 wt% composite scaffolds for applications in soft tissue repair and the expansion of primary human keratinocytes for skin regeneration.
Fluorescein Derivative Immobilized Optical Hydrogels: Fabrication and Its Application for Detection of H2O2
Authors: Qu Zixiang , Zhang Demeng , Wang Chuane , Tian Sheng , Deng Yunlong , Qin Dawei , Duan Hongdong
Published: July 2022

A novel fluorescein-based probe FLA-Boe was developed for detecting H2O2. Modified by 2-Bromomethylphenylboronic acid pinacol ester, FLA-Boe is a Fluorescein derivative with eminent photostability and remarkable H2O2 sensitivity and selectivity. FLA-Boe was utilized to synthesize hydrogel sensors in the manner of guest–host interaction by taking advantage of its aforementioned features. The hydrogel sensor can be used to detect H2O2 effectively in both flowing and static water environments with satisfactory performance. It is expected that this application may open a new page to develop a neoteric fluorescent property analysis method aiming at H2O2 detection.