bluuebunny/crossref_metadata_2025 huggingface dataset:
Medication Prescribing Quality in Australian Primary Care Patients with Chronic Kidney Disease
Authors: Bezabhe Woldesellassie M. , Kitsos Alex , Saunder Timothy , Peterson Gregory M. , Bereznicki Luke R. , Wimmer Barbara C. , Jose Matthew , Radford Jan
Published: March 2020

Background: Australian patients with chronic kidney disease (CKD) are routinely managed in general practices with multiple medications. However, no nationally representative study has evaluated the quality of prescribing in these patients. The objective of this study was to examine the quality of prescribing in patients with CKD using nationally representative primary care data obtained from the NPS MedicineWise’s dataset, MedicineInsight. Methods: A cross-sectional analysis of general practice data for patients aged 18 years or older with CKD was performed from 1 February 2016 to 1 June 2016. The study examined the proportion of patients with CKD who met a set of 16 published indicators in two categories: (1) potentially appropriate prescribing of antihypertensives, renin-angiotensin system (RAS) inhibitors, phosphate binders, and statins; and (2) potentially inappropriate prescribing of nephrotoxic medications, such as non-steroidal anti-inflammatory drugs (NSAIDs), at least two RAS inhibitors, triple therapy (an NSAID, a RAS inhibitor and a diuretic), high-dose digoxin, and metformin. The proportion of patients meeting each quality indicator was stratified using clinical and demographic characteristics. Results: A total of 44,259 patients (24,165 (54.6%) female; 25,562 (57.8%) estimated glomerular filtration (eGFR) 45–59 mL/1.73 m2) with CKD stages 3–5 were included. Nearly one-third of patients had diabetes and were more likely to have their blood pressure and albumin-to-creatinine ratio monitored than those without diabetes. Potentially appropriate prescribing of antihypertensives was achieved in 79.9% of hypertensive patients with CKD stages 4–5. The prescribing indicators for RAS inhibitors in patients with microalbuminuria and diabetes and in patients with macroalbuminuria were achieved in 69.9% and 62.3% of patients, respectively. Only 40.8% of patients with CKD and aged between 50 and 65 years were prescribed statin therapy. The prescribing of a RAS inhibitor plus a diuretic was less commonly achieved, with the indicator met in 20.6% for patients with microalbuminuria and diabetes and 20.4% for patients with macroalbuminuria. Potentially inappropriate prescribing of NSAIDs, metformin, and at least two RAS inhibitors were apparent in 14.3%, 14.1%, and 7.6%, respectively. Potentially inappropriate prescribing tended to be more likely in patients aged ≥65 years, living in regional or remote areas, or with socio-economic indexes for areas (SEIFA) score ≤ 3. Conclusions: We identified areas for possible improvement in the prescribing of RAS inhibitors and statins, as well as deprescribing of NSAIDs and metformin in Australian general practice patients with CKD.
Far-Field Characteristics of Linear Water Waves Generated by a Submerged Landslide over a Flat Seabed
Authors: Jing Haixiao , Gao Yanyan , Liu Changgen , Hou Jingming
Published: March 2020

Understanding the propagation of landslide-generated water waves is of great help against tsunami hazards. In order to investigate the effects of landslide shapes on the far-field leading wave generated by a submerged landslide at a constant depth, three linear wave models with different degrees of dispersive properties are employed in this study. The linear fully dispersive model is then validated by comparing the results against the experimental data available for landslides with a low Froude number. Three simplified shapes of landslides with the same volume, which are unnatural for a body of incoherent material, are used to investigate the effects of landslide shapes on the far-field properties of the generated leading wave over a flat seabed. The results show that the far-field leading crest over a constant depth is independent of the exact landslide shape and is invalid at a shallow water depth. Therefore, the most popular non-dispersive model (also called the shallow water wave model) cannot be used to reproduce the phenomenon. The weakly dispersive wave model can predict this phenomenon well. If only the leading wave is considered, this model is accurate up to at least μ = h0/Lc = 0.6, where h0 is the water depth and Lc denotes the characteristic length of the landslide.
Existence Results for Langevin Equation Involving Atangana-Baleanu Fractional Operators
Authors: Baleanu Dumitru , Darzi Rahmat , Agheli Bahram
Published: March 2020

A new form of nonlinear Langevin equation (NLE), featuring two derivatives of non-integer orders, is studied in this research. An existence conclusion due to the nonlinear alternative of Leray-Schauder type (LSN) for the solution is offered first and, following that, the uniqueness of solution using Banach contraction principle (BCP) is demonstrated. Eventually, the derivatives of non-integer orders are elaborated in Atangana-Baleanu sense.
A New Individual-Based Model to Simulate Malware Propagation in Wireless Sensor Networks
Authors: Batista Farrah Kristel , Martín del Rey Angel , Queiruga-Dios Araceli
Published: March 2020

Wireless Sensor Networks (WSNs) are a set of sensor devices deployed in a given area that form a network without a pre-established architecture. Recently, malware has increased as a potential vulnerability for the Internet of Things, and consequently for these networks. The spread of malware on wireless sensor networks has been studied from different perspectives, excluding individual characteristics in most of the models proposed. The primary goal of this work is to introduce an Agent-Based Model for analysing malware propagation on these networks, and its agents, coefficients and transition rules are detailed. Finally, some simulations of the proposed model are included.
Effects of Seed Crystals on the Growth and Catalytic Performance of TS-1 Zeolite Membranes
Authors: Ding Wenjuan , Xiang Sitong , Ye Fei , Gui Tian , Li Yuqin , Zhang Fei , Hu Na , Zhu Meihua , Chen Xiangshu
Published: March 2020

Dense and good catalytic performance TS-1 zeolite membranes were rapidly prepared on porous mullite support by secondary hydrothermal synthesis. The properties of seed crystals were very important for the preparation of high-catalytic performance TS-1 zeolite membranes. Influences of seed crystals (Ti/Si ratios, size, morphology, and zeolites concentration of the seed suspension) on the growth and catalytic property of TS-1 zeolite membranes were investigated in details. High Ti/Si ratio, medium-size, and morphology of the seed crystals were critical for preparing the high-performance TS-1 zeolite membrane. Compared with the bi-layer TS-1 zeolite membrane (inner and outer of the mullite tube), the mono-layer TS-1 zeolite membrane had a better catalytic performance for Isopropanol IPA oxidation with H2O2. When the Ti/Si ratio, size, and morphology of the TS-1 zeolites were 0.030, 300 nm, ellipsoid, and the zeolites concentration of the seed suspension was 5%, the IPA conversion, and flux through the TS-1 zeolite membrane were 98.23% and 2.58 kg·m−2·h−1, respectively.
Magnetic Particles: Their Applications from Sample Preparations to Biosensing Platforms
Authors: Kim Seong-Eun , Tieu My Van , Hwang Sei Young , Lee Min-Ho
Published: March 2020

The growing interest in magnetic materials as a universal tool has been shown by an increasing number of scientific publications regarding magnetic materials and its various applications. Substantial progress has been recently made on the synthesis of magnetic iron oxide particles in terms of size, chemical composition, and surface chemistry. In addition, surface layers of polymers, silica, biomolecules, etc., on magnetic particles, can be modified to obtain affinity to target molecules. The developed magnetic iron oxide particles have been significantly utilized for diagnostic applications, such as sample preparations and biosensing platforms, leading to the selectivity and sensitivity against target molecules and the ease of use in the sensing systems. For the process of sample preparations, the magnetic particles do assist in target isolation from biological environments, having non-specific molecules and undesired molecules. Moreover, the magnetic particles can be easily applied for various methods of biosensing devices, such as optical, electrochemical, and magnetic phenomena-based methods, and also any methods combined with microfluidic systems. Here we review the utilization of magnetic materials in the isolation/preconcentration of various molecules and cells, and their use in various techniques for diagnostic biosensors that may greatly contribute to future innovation in point-of-care and high-throughput automation systems.
Application of a Novel Phage LPSEYT for Biological Control of Salmonella in Foods
Authors: Yan Ting , Liang Lu , Yin Ping , Zhou Yang , Mahdy Sharoba Ashraf , Lu Qun , Dong Xingxing , Liu Kun , Connerton Ian F. , Li Jinquan
Published: March 2020

Salmonella is a leading cause of foodborne diseases, and in recent years, many isolates have exhibited a high level of antibiotic resistance, which has led to huge pressures on public health. Phages are a promising strategy to control food-borne pathogens. In this study, one of our environmental phage isolates, LPSEYT, was to be able to restrict the growth of zoonotic Salmonella enterica in vitro over a range of multiplicity of infections. Phage LPSEYT exhibited wide-ranging pH and thermal stability and rapid reproductive activity with a short latent period and a large burst size. Phage LPSEYT demonstrated potential efficiency as a biological control agent against Salmonella in a variety of food matrices, including milk and lettuce. Morphological observation, comparative genomic, and phylogenetic analysis revealed that LPSEYT does not belong to any of the currently identified genera within the Myoviridae family, and we suggest that LPSEYT represents a new genus, the LPSEYTvirus. This study contributes a phage database, develops beneficial phage resources, and sheds light on the potential application value of phages LPSEYT on food safety.
Computational Modeling and Prediction on Viscosity of Slags by Big Data Mining
Authors: Huang Ao , Huo Yanzhu , Yang Juan , Gu Huazhi , Li Guangqiang
Published: March 2020

The viscosity of slag is a key factor affecting metallurgical efficiency and recycling, such as metal-slag reaction and separation, as well as slag wool processing. In order to comprehensively clarify the variation of the slag viscosity, various data mining methods have been employed to predict the viscosity of the slag. In this study, a more advanced dual-stage predictive modeling approach is proposed in order to accurately analyze and predict the viscosity of slag. Compared with the traditional single data mining approach, the proposed method performs better with a higher recall rate and low misclassification rate. The simulation results show that temperature, SiO2, Al2O3, P2O5, and CaO have greater influences on the slag’s viscosity. The critical temperature for onset of the important influence of slag composition is 980 °C. Furthermore, it is found that SiO2 and P2O5 have positive correlations with slag’s viscosity, while temperature, Al2O3, and CaO have negative correlations. A two-equation model of six-degree polynomial combined with Arrhenius formula is also established for the purpose of providing theoretical guidance for industrial application and reutilization of slag.
Raman Study of Barite and Celestine at Various Temperatures
Authors: Zhou Li , Mernagh Terrence P. , Mo Bing , Wang Li , Zhang Shuai , Wang Chunyao
Published: March 2020

The Raman spectra of barite and celestine were recorded from 25 to 600 °C at ambient pressure and both minerals were stable over the entire temperature range. Most of the Raman bands of barite decreased in wavenumber with increasing temperature with the exception of the ν2 modes and the ν4 band at 616 cm−1, which did not exhibit a significant temperature dependence. These vibrations may be constrained by the lower thermal expansion along the a-axis and b-axis of barite. Similar to barite, most of the Raman bands of celestine also decreased in wavenumber with increasing temperature, with the exception of the ν2 modes and the ν4 band at 622 cm−1, which showed very little variation with increasing temperature. Variations of Raman shift as a function of temperature and FWHM (full width at half maximum) as a function of Raman shift for the main, ν1 modes of barite and celestine show that both minerals have almost identical linear trends with a slope of −0.02 cm−1/°C and −0.5, respectively, which allows for the prediction of Raman shifts and FWHM up to much higher temperatures. The calculated isobaric and isothermal mode Grüneisen parameters and the anharmonicity parameters show that the M–O modes (M = Ba2+ and Sr2+) in barite and celestine exhibit much higher values of both mode Grüneisen parameters and anharmonicity than the SO4 tetrahedra. This indicates that the S–O distances and S–O–S angles are less sensitive to pressure and temperature increase than the M–O distances in the structure. Furthermore, the generally higher anharmonicity in celestine is due to the smaller size of the Sr2+ cation, which causes the celestine structure to be more distorted than the barite structure.
Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species
Authors: Khan Abdul Q. , Mohamed Elham A. N. , Hakeem Ishrat , Nazeer Aneeza , Kuttikrishnan Shilpa , Prabhu Kirti S. , Siveen Kodappully S. , Nawaz Zafar , Ahmad Aamir , Zayed Hatem , Uddin Shahab
Published: March 2020

Sanguinarine (SNG), a natural compound with an array of pharmacological activities, has promising therapeutic potential against a number of pathological conditions, including malignancies. In the present study, we have investigated the antiproliferative potential of SNG against two well-characterized papillary thyroid cancer (PTC) cell lines, BCPAP and TPC-1. SNG significantly inhibited cell proliferation of PTC cells in a dose and time-dependent manner. Western blot analysis revealed that SNG markedly attenuated deregulated expression of p-STAT3, without affecting total STAT3, and inhibited growth of PTC via activation of apoptotic and autophagy signaling cascade, as SNG treatment of PTC cells led to the activation of caspase-3 and caspase-8; cleavage of PARP and activation of autophagy markers. Further, SNG-mediated anticancer effects in PTC cells involved the generation of reactive oxygen species (ROS) as N-acetyl cysteine (NAC), an inhibitor of ROS, prevented SNG-mediated antiproliferative, apoptosis and autophagy inducing action. Interestingly, SNG also sensitized PTC cells to chemotherapeutic drug cisplatin, which was inhibited by NAC. Finally, SNG suppressed the growth of PTC thyrospheres and downregulated stemness markers ALDH2 and SOX2. Altogether, the findings of the current study suggest that SNG has anticancer potential against PTC cells as well its derived cancer stem-like cells, most likely via inactivation of STAT3 and its associated signaling molecules.
Melatonin Promotes the Proliferation of Chicken Sertoli Cells by Activating the ERK/Inhibin Alpha Subunit Signaling Pathway
Authors: Xu Ke , Wang Jun , Liu Hongyu , Zhao Jing , Lu Wenfa
Published: March 2020

Melatonin influences physiological processes such as promoting proliferation and regulating cell development and function, and its effects on chicken Sertoli cells are unknown. Therefore, we investigated the effects of melatonin on cell proliferation and its underlying mechanisms in chicken Sertoli cells. Chicken Sertoli cells were exposed to varying melatonin concentrations (1, 10, 100, and 1000 nM), and the melatonin-induced effects on cell proliferation were measured by Cell Counting Kit 8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), real-time qPCR, and western blotting. We found that 1000 nM melatonin significantly (p < 0.05) promoted cell proliferation in chicken Sertoli cells. Furthermore, melatonin significantly (p < 0.05) increased the expression of inhibin alpha subunit (INHA), and the silencing of INHA reversed the melatonin-induced effects on Sertoli cell proliferation. We also found that melatonin activates the extracellular-regulated protein kinase (ERK) signaling pathway. To explore the role of the ERK signaling pathway in melatonin-induced cell proliferation, PD98059 (an inhibitor of EKR1/2) was used to pre-treat chicken Sertoli cells. The melatonin-induced proliferation of chicken Sertoli cells was reversed by PD98059, with decreased cell viability, weakened cell proliferation, and down-regulated expression of the proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and INHA. In summary, our results indicate that melatonin promotes the proliferation of chicken Sertoli cells by activating the ERK/inhibin alpha subunit signaling pathway.
Development of the Method for Determination of Volatile Sulfur Compounds (VSCs) in Fruit Brandy with the Use of HS–SPME/GC–MS
Authors: Dziekońska-Kubczak Urszula , Pielech-Przybylska Katarzyna , Patelski Piotr , Balcerek Maria
Published: March 2020

Volatile sulfur compounds (VSCs) play an important role in the aroma profile of fermented beverages. However, because of their low concentration in samples, their analysis is difficult. The headspace solid-phase microextraction (HS–SPME) technique coupled with gas chromatography and mass spectrometry (GC–MS) is one of the methods successfully used to identify VSCs in wine and beer samples. However, this method encounters more obstacles when spirit beverages are analyzed, as the ethanol content of the matrix decreases the method sensitivity. In this work, different conditions applied during HS–SPME/GC–MS analysis, namely: ethanol concentration, salt addition, time and temperature of extraction, as well as fiber coating, were evaluated in regard to 19 sulfur compounds. The best results were obtained when 50/30 μm Divinylbenzene/Carboxen/Polydimethylsiloxane (DVB/CAR/PDMS) was used to preconcentrate the analytes from the sample at 35 °C for 30 min. The dilution of samples to 2.5% v/v ethanol and the addition of 20% w/v NaCl along with 1% EDTA significantly improves the sensitivity of extraction. The optimized method was applied to three fruit brandy samples (plum, pear, and apple) and quantification of VSCs was performed. A total of 10 compounds were identified in brandy samples and their concentration varied greatly depending on the raw material used from production. The highest concentration of identified VSCs was found in apple brandy (82 µg/L).
Surface Compositional Change of Iron Oxide Porous Nanorods: A Route for Tuning their Magnetic Properties
Authors: Casu Alberto , Loche Danilo , Lentijo-Mozo Sergio , Falqui Andrea
Published: March 2020

The capability of synthesizing specific nanoparticles (NPs) by varying their shape, size and composition in a controlled fashion represents a typical set of engineering tools that tune the NPs magnetic response via their anisotropy. In particular, variations in NP composition mainly affect the magnetocrystalline anisotropy component, while the different magnetic responses of NPs with isotropic (i.e., spherical) or elongated shapes are mainly caused by changes in their shape anisotropy. In this context, we propose a novel route to obtain monodispersed, partially hollow magnetite nanorods (NRs) by colloidal synthesis, in order to exploit their shape anisotropy to increase the related coercivity; we then modify their composition via a cation exchange (CE) approach. The combination of a synthetic and post-synthetic approach on NRs gave rise to dramatic variations in their magnetic features, with the pores causing an initial magnetic hardening that was further enhanced by the post-synthetic introduction of a manganese oxide shell. Indeed, the coupling of the core and shell ferrimagnetic phases led to even harder magnetic NRs.
HPLC-DAD-Guided Isolation of Diversified Chaetoglobosins from the Coral-Associated Fungus Chaetomium globosum C2F17
Authors: Luo Xiao-Wei , Gao Cheng-Hai , Lu Hu-Mu , Wang Jia-Min , Su Zi-Qi , Tao Hua-Ming , Zhou Xue-Feng , Yang Bin , Liu Yong-Hong
Published: March 2020

Cytochalasans have continuously aroused considerable attention among the chemistry and pharmacology communities due to their structural complexities and pharmacological significances. Sixteen structurally diverse chaetoglobosins, 10-(indol-3-yl)-[13]cytochalasans, including a new one, 6-O-methyl-chaetoglobosin Q (1), were isolated from the coral-associated fungus Chaetomium globosum C2F17. Their structures were accomplished by extensive spectroscopic analysis combined with single-crystal X-ray crystallography and ECD calculations. Meanwhile, the structures and absolute configurations of the previously reported compounds 6, 12, and 13 were confirmed by single-crystal X-ray analysis for the first time. Chaetoglobosins E (6) and Fex (11) showed significant cytotoxicity against a panel of cancer cell lines, K562, A549, Huh7, H1975, MCF-7, U937, BGC823, HL60, Hela, and MOLT-4, with the IC50 values ranging from 1.4 μM to 9.2 μM.
Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 Cells
Authors: Arumugam Asvinidevi , Ibrahim Muhammad Din , Kntayya Saie Brindha , Mohd Ain Nooraini , Iori Renato , Galletti Stefania , Ioannides Costas , Abdull Razis Ahmad Faizal
Published: March 2020

Gluconasturtiin, a glucosinolate present in watercress, is hydrolysed by myrosinase to form gluconasturtiin-isothiocyanate (GNST-ITC), which has potential chemopreventive effects; however, the underlying mechanisms of action have not been explored, mainly in human cell lines. The purpose of the study is to evaluate the cytotoxicity of GNST-ITC and to further assess its potential to induce apoptosis. GNST-ITC inhibited cell proliferation in both human hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7) cells with IC50 values of 7.83 µM and 5.02 µM, respectively. Morphological changes as a result of GNST-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GNST-ITC in a time-dependent manner. To delineate the mechanism of apoptosis, cell cycle arrest and expression of caspases were studied. GNST-ITC induced a time-dependent G2/M phase arrest, with reduction of 82% and 93% in HepG2 and MCF-7 cell lines, respectively. The same treatment also led to the subsequent expression of caspase-3/7 and -9 in both cells demonstrating mitochondrial-associated cell death. Collectively, these results reveal that GNST-ITC can inhibit cell proliferation and can induce cell death in HepG2 and MCF-7 cancer cells via apoptosis, highlighting its potential development as an anticancer agent.
Proteomic Analysis of the Early Development of the Phalaenopsis amabilis Flower Bud under Low Temperature Induction Using the iTRAQ/MRM Approach
Authors: Chen Cong , Zeng Lanting , Zhao Haiyi , Ye Qingsheng
Published: March 2020

Phalaenopsis amabilis, one of the most important plants in the international flower market due to its graceful shape and colorful flowers, is an orchid that undergoes vernalization and requires low-temperature treatment for flowering. There have been few reports on the proteomics of the development of flower buds. In this study, isobaric tags for relative and absolute quantification (iTRAQ) were used to identify 5064 differentially expressed proteins in P. amabilis under low-temperature treatment; of these, 42 were associated with early floral induction, and 18 were verified by mass spectrometry multi-reaction monitoring (MRM). The data are available via ProteomeXchange under identifier PXD013908. Among the proteins associated with the vernalization pathway, PEQU_11434 (glycine-rich RNA-binding protein GRP1A-like) and PEQU_19304 (FT, VRN3 homolog) were verified by MRM, and some other important proteins related to vernalization and photoperiod pathway that were detected by iTRAQ but not successfully verified by MRM, such as PEQU_11045 (UDP-N-acetylglucosamine diphosphorylase), phytochromes A (PEQU_13449, PEQU_35378), B (PEQU_09249), and C (PEQU_41401). Our data revealed a regulation network of the early development of flower buds in P. amabilis under low temperature induction.
Pharmacokinetics of Two Chlorine-Substituted Bis-Pyridinium Mono-Aldoximes with Regenerating Effect on Butyrylcholinesterase
Authors: Kalász Huba , Szimrók Zoltán , Karvaly Gellért , Adeghate Jennifer , Tekes Kornélia
Published: March 2020

Our aim was to find chlorine-substituted antidotes against organophosphate poisoning and compare their pharmacokinetics to their parent compound, K-203. White male Wistar rats were intramuscularly injected with K-203, K-867 or K-870. Serum, brain, kidneys, liver, lung, eyes, and testes tissues were taken after 5, 15, 30, 60, and 120 min and analyzed using reversed-phase high-performance liquid chromatography. K-203, K-867, or K-870 was present in every tissue that was analyzed, including the serum, the eyes, testes, liver, kidneys, lungs, and the brain. The serum levels of K-867 and K-870 (chlorine-substituted derivatives of K-203) were nearly constant between 15 and 30 min, while their parent compound (K-203) showed peak level at 15 min after the administration of 30 µmol/rat. Neither K-203, nor K-867 or K-870 were toxic at a dose of 100 µmol/200 g in rats. Chlorine-substitution of K-867 and K-870 produced limited absorbance and distribution compared to their parent compound, K203.
Synthesis and Structure-Activity Relationship Studies of Hydrazide-Hydrazones as Inhibitors of Laccase from Trametes versicolor
Authors: Maniak Halina , Talma Michał , Matyja Konrad , Trusek Anna , Giurg Mirosław
Published: March 2020

A series of hydrazide-hydrazones 1–3, the imine derivatives of hydrazides and aldehydes bearing benzene rings, were screened as inhibitors of laccase from Trametes versicolor. Laccase is a copper-containing enzyme which inhibition might prevent or reduce the activity of the plant pathogens that produce it in various biochemical processes. The kinetic and molecular modeling studies were performed and for selected compounds, the docking results were discussed. Seven 4-hydroxybenzhydrazide (4-HBAH) derivatives exhibited micromolar activity Ki = 24–674 µM with the predicted and desirable competitive type of inhibition. The structure–activity relationship (SAR) analysis revealed that a slim salicylic aldehyde framework had a pivotal role in stabilization of the molecules near the substrate docking site. Furthermore, the presence of phenyl and bulky tert-butyl substituents in position 3 in salicylic aldehyde fragment favored strong interaction with the substrate-binding pocket in laccase. Both 3- and 4-HBAH derivatives containing larger 3-tert-butyl-5-methyl- or 3,5-di-tert-butyl-2-hydroxy-benzylidene unit, did not bind to the active site of laccase and, interestingly, acted as non-competitive (Ki = 32.0 µM) or uncompetitive (Ki = 17.9 µM) inhibitors, respectively. From the easily available laccase inhibitors only sodium azide, harmful to environment and non-specific, was over 6 times more active than the above compounds.
Retention Modelling of Phenoxy Acid Herbicides in Reversed-Phase HPLC under Gradient Elution
Authors: Biancolillo Alessandra , Maggi Maria Anna , Bassi Sebastian , Marini Federico , D’Archivio Angelo Antonio
Published: March 2020

Phenoxy acid herbicides are used worldwide and are potential contaminants of drinking water. Reversed phase high-performance liquid chromatography (RP-HPLC) is commonly used to monitor phenoxy acid herbicides in water samples. RP-HPLC retention of phenoxy acids is affected by both mobile phase composition and pH, but the synergic effect of these two factors, which is also dependent on the structure and pKa of solutes, cannot be easily predicted. In this paper, to support the setup of RP-HPLC analysis of phenoxy acids under application of linear mobile phase gradients we modelled the simultaneous effect of the molecular structure and the elution conditions (pH, initial acetonitrile content in the eluent and gradient slope) on the retention of the solutes. In particular, the chromatographic conditions and the molecular descriptors collected on the analyzed compounds were used to estimate the retention factor k by Partial Least Squares (PLS) regression. Eventually, a variable selection approach, Genetic Algorithms, was used to reduce the model complexity and allow an easier interpretation. The PLS model calibrated on the retention data of 15 solutes and successively tested on three external analytes provided satisfying and reliable results.
[1,5]-Hydride Shift-Cyclization versus C(sp2)-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4- and 1,5-Benzoxazepines
Authors: Szalóki Vargáné Dóra , Tóth László , Buglyó Balázs , Kiss-Szikszai Attila , Mándi Attila , Mátyus Péter , Antus Sándor , Chen Yinghan , Li Dehai , Tao Lingxue , Zhang Haiyan , Kurtán Tibor
Published: March 2020

Domino cyclization reactions of N-aryl-1,4- and 1,5-benzoxazepine derivatives involving [1,5]-hydride shift or C(sp2)-H functionalization were investigated. Neuroprotective and acetylcholinesterase activities of the products were studied. Domino Knoevenagel-[1,5]-hydride shift-cyclization reaction of N-aryl-1,4-benzoxazepine derivatives with 1,3-dicarbonyl reagents having active methylene group afforded the 1,2,8,9-tetrahydro-7bH-quinolino [1,2-d][1,4]benzoxazepine scaffold with different substitution pattern. The C(sp3)-H activation step of the tertiary amine moiety occurred with complete regioselectivity and the 6-endo cyclization took place in a complete diastereoselective manner. In two cases, the enantiomers of the chiral condensed new 1,4-benzoxazepine systems were separated by chiral HPLC, HPLC-ECD spectra were recorded, and absolute configurations were determined by time-dependent density functional theory- electronic circular dichroism (TDDFT-ECD) calculations. In contrast, the analogue reaction of the regioisomeric N-aryl-1,5-benzoxazepine derivative did not follow the above mechanism but instead the Knoevenagel intermediate reacted in an SEAr reaction [C(sp2)-H functionalization] resulting in a condensed acridane derivative. The AChE inhibitory assays of the new derivatives revealed that the acridane derivative had a 6.98 μM IC50 value.
Special Issue: Development of Asymmetric Synthesis
Authors: Chinchilla Rafael
Published: March 2020

Biological systems usually respond differently to enantiomers of a chiral molecule due to the inherent chirality of the active receptor sites of enzymes in nature [...]
Assessment of Hepatoprotective Effect of Chokeberry Juice in Rats Treated Chronically with Carbon Tetrachloride
Authors: Piotrowska-Kempisty Hanna , Nowicki Michał , Jodynis-Liebert Jadwiga , Kurpik Monika , Ewertowska Małgorzata , Adamska Teresa , Oszmiański Jan , Kujawska Małgorzata
Published: March 2020

The aim of this study was to compare the protective effects of chokeberry juice and silymarin against chemical-induced liver fibrosis in rats. Liver fibrosis was induced by CCl4 administered two days a week for six weeks. Two groups of rats were co-treated with chokeberry juice, 10 mL/kg/day. or silymarin as a positive control, 100 mg/kg/day for six weeks. Hepatic lipid peroxidation was suppressed by 50% and the activity of hepatic antioxidant enzymes was increased by 19%–173% in rats co-treated with CCl4 and substances tested as compared to rats administered CCl4 alone. Hepatic hydroxyproline was decreased by 24% only in rats treated with silymarin. The messenger RNA (mRNA) expression levels of fibrosis-related molecules, procollagen I, α-SMA, TIMP-1, TGFβ, and TNFα, which were significantly increased in the liver of CCl4-treated rats, were not modulated by substances tested. Histological evaluation revealed a slight protective effect of silymarin against fibrosis. However, in CCl4 + chokeberry-treated rats, the density of vacuolated hepatocytes was significantly lower than that in silymarin administered animals. Chokeberry juice did not demonstrate an antifibrotic effect in the applied experimental model of fibrosis, and the effect of the known antifibrotic agent, silymarin, was very limited.
Phenolic Compounds, Antioxidant Activities, and Inhibitory Effects on Digestive Enzymes of Different Cultivars of Okra (Abelmoschus esculentus)
Authors: Wu Ding-Tao , Nie Xi-Rui , Shen Dan-Dan , Li Hong-Yi , Zhao Li , Zhang Qing , Lin De-Rong , Qin Wen
Published: March 2020

In this study, the phenolic profiles and bioactivities of five representative cultivars of okra collected in China were investigated. Noticeable variations of phenolic compounds and their bioactivities were observed among these different cultivars of okra. The contents of total flavonoids (TFC) in “Shuiguo”, “Kalong 8”, “Kalong 3”, “Wufu”, and “Royal red” ranged from 1.75 to 3.39 mg RE/g DW, of which “Shuiguo” showed the highest TFC. Moreover, five individual phenolic compounds were found in okra by high performance liquid chromatography analysis, including isoquercitrin, protocatechuic acid, quercetin-3-O-gentiobioside, quercetin, and rutin, while isoquercitrin and quercetin-3-O-gentiobioside were detected as the main phenolic compounds in okra. Moreover, all tested okra exhibited significant antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity, 2,2’-azino-bis (3-ethylenzthiazoline-6-sulphonic acid) radical scavenging capacity, and ferric reducing antioxidant power) and inhibitory effects on digestive enzymes (lipase, α-glucosidase, and α-amylase). Indeed, “Shuiguo” exhibited much better antioxidant activities and inhibitory activities on digestive enzymes, which might be attributed to its high TFC. Results suggested that okra, especially “Shuiguo”, could be developed as natural antioxidants and inhibitors against hyperlipidemia and hyperglycemia in the fields of functional foods and pharmaceuticals, which could meet the increasing demand for high-quality okra with health-promoting properties in China.
A Targeted Approach by High Resolution Mass Spectrometry to Reveal New Compounds in Raisins
Authors: Escobar-Avello Danilo , Olmo-Cunillera Alexandra , Lozano-Castellón Julián , Marhuenda-Muñoz María , Vallverdú-Queralt Anna
Published: March 2020

Raisins are dried grapes mostly obtained from cultivars of Vitis vinifera L. and are extensively consumed worldwide. They are rich in bioactive compounds such as polyphenols, which are associated with a broad range of health benefits. The aim of the present study was to compare the phenolic profiles of three different raisin varieties (Thompson seedless, Muscat, and sultanas). Total polyphenols (TPs) were evaluated by the Folin–Ciocalteu (F–C) assay and significant differences were observed among all raisin varieties. Furthermore, liquid chromatography coupled with electrospray ionization hybrid linear ion trap quadrupole-Orbitrap-mass spectrometry (LC/ESI-LTQ-Orbitrap-MS) was employed for the comprehensive identification of phenolic constituents. A total of 45 compounds were identified, including hydroxybenzoic and hydroxycinnamic acids, flavanoids, flavonoids, flavonols, flavones, and stilbenoids. The three varieties of raisins showed a similar phenolic profile, although the highest number of phenolic compounds was identified in Muscat raisins owing to the proanthocyanidins extracted from their seeds, while stilbenoids were not detected in the Thompson variety.
Effects of the Morphology, Surface Modification and Application Methods of ZnO-NPs on the Growth and Biomass of Tomato Plants
Authors: Pérez Velasco Eneida A. , Betancourt Galindo Rebeca , Valdez Aguilar Luis A. , González Fuentes José A. , Puente Urbina Bertha A. , Lozano Morales Samuel A. , Sánchez Valdés Saúl
Published: March 2020

Benefits of nanotechnology in agriculture include reduced fertilizer loss, improved seed germination rate and increased crops quality and yield. The objective of this research was to evaluate the effects of zinc oxide nanoparticles (ZnO-NPs), at 1500 ppm, on tomato (Solanum lycopersicum L.) growth. ZnO-NPs were synthetized to produce either spherical or hexagonal morphologies. In this research, we also studied two application methods (foliar and drench) and nanoparticles’ (NPs) surface modification with maltodextrin. The results obtained indicate that ZnO-NP-treated tomato plants significantly increased plant height, stem diameter and plant organs (leaves, stem and root) dry weight compared to plants without NP treatment.
2-Methylimidazole Copper Iminodiacetates for the Adsorption of Oxygen and Catalytic Oxidation of Cyclohexane
Authors: Chen Xi , An Dong-Li , Zhan Xin-Qi , Zhou Zhao-Hui
Published: March 2020

The mixed-ligand copper(II) iminodiacetates [Cu(ida)(2-mim)(H2O)2]·H2O (1), [Cu(ida)(2-mim)2]·2H2O (2), [Cu(ida)(2-mim)(H2O)]n·4.5nH2O (3), and [Cu2(ida)2(2-mim)2]n·nH2O (4) (H2ida = iminodiacetic acid, 2-mim = 2-methylimidazole) were obtained from neutral or alkaline solutions at different temperatures. The novel complex 4 contains very small holes with diameters of 2.9 Å, which can adsorb O2 selectively and reversibly between 1.89 to 29.90 bars, compared with the different gases of N2, H2, CO2, and CH4. This complex is stable up to 150 °C based on thermal analyses and XRD patterns. The four complexes show catalytic activities that facilitate the conversion of cyclohexane to cyclohexanol and cyclohexanone with hydrogen peroxide in a solution. The total conversion is 31% for 4.
Human Copper-Containing Amine Oxidases in Drug Design and Development
Authors: Vakal Serhii , Jalkanen Sirpa , Dahlström Käthe M. , Salminen Tiina A.
Published: March 2020

Two members of the copper-containing amine oxidase family are physiologically important proteins: (1) Diamine oxidase (hDAO; AOC1) with a preference for diamines is involved in degradation of histamine and (2) Vascular adhesion protein-1 (hVAP-1; AOC3) with a preference for monoamines is a multifunctional cell-surface receptor and an enzyme. hVAP-1-targeted inhibitors are designed to treat inflammatory diseases and cancer, whereas the off-target binding of the designed inhibitors to hDAO might result in adverse drug reactions. The X-ray structures for both human enzymes are solved and provide the basis for computer-aided inhibitor design, which has been reported by several research groups. Although the putative off-target effect of hDAO is less studied, computational methods could be easily utilized to avoid the binding of VAP-1-targeted inhibitors to hDAO. The choice of the model organism for preclinical testing of hVAP-1 inhibitors is not either trivial due to species-specific binding properties of designed inhibitors and different repertoire of copper-containing amine oxidase family members in mammalian species. Thus, the facts that should be considered in hVAP-1-targeted inhibitor design are discussed in light of the applied structural bioinformatics and structural biology approaches.
Zinc Binding to Fulvic acids: Assessing the Impact of pH, Metal Concentrations and Chemical Properties of Fulvic Acids on the Mechanism and Stability of Formed Soluble Complexes
Authors: Boguta Patrycja , Sokołowska Zofia
Published: March 2020

The aim of the study was defined as a complementary analysis of molecular interactions between zinc (Zn) and fulvic acids (FAs) at a broad pH range (3–7), different metal concentrations (0–50 mg dm−3) and chemical properties of FAs and their impact on the Zn binding mechanism, stability, and efficiency. The results showed that the complexation reaction prevailed at pH 6 and 7, whereas protons exchange dominated interactions at pH 3. Stability constant of the complexes increased along with pH (logK increased from ~3.8 to 4.2). Complexation was preferred by less-humidified structures of lower molecular mass containing more oxygen groups. The number of fluorophores available for Zn(II) increased from pH 3 to 7 by ~44%. Depending on the pH, complexation involved a bidentate chelate, monodentate and bidentate bridging mode. Zn(II) binding was insufficiently modeled by the classic Stern–Volmer equation and well described by the double logarithmic equation (R > 0.94) as well as by a modified Stern–Volmer formula assuming the existence of available and unavailable fluorophore populations (R > 0.98). The fluorescence ratio of different fluorophores was proposed as an indicator of the binding affinity of various structures. A positive relationship was found between the fraction of accessible fluorophores and Zn(II) binding at pH 7 determined based on proton release (R = 0.91–0.97). The obtained results can find application in controlling the mobility and bioavailability of Zn in different conditions.
Synthesis, Characterization, and Biological Evaluation of Novel 7-Oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic Acid Derivatives
Authors: Cai Dong , Li Tai , Xie Qian , Yu Xiaofei , Xu Wei , Chen Yu , Jin Zhe , Hu Chun
Published: March 2020

A series of novel 7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic acid derivatives was synthesized in good yields by a multi-step procedure that included the generation of the S-alkylated derivatives from 6-substituted arylmethyl-3-mercapto-1,2,4-triazin-5-ones with ethyl 2-chloroacetoacetate, intramolecular cyclization with microwave irradiation, hydrolysis and amidation. All of the target compounds were fully characterized through 1H-NMR, 13C-NMR and HRMS spectra. The intramolecular cyclization occurred regioselectively at the N2-position of 1,2,4-triazine ring, which was confirmed by compound 3e using single-crystal X-ray diffraction analysis. The antibacterial and antitubercular activities of the target compounds were evaluated. Compared with Ciprofloxacin and Rifampicin, compounds 5d, 5f and 5g containing the terminal amide fragment exhibited broad spectrum antibacterial activity, and carboxylic acid derivatives or its corresponding ethyl esters had less effect on antibacterial properties. The most potent compound 5f also displayed excellent in vitro antitubercular activity against Mycobacterium smegmatis (minimum inhibitory concentration (MIC) = 50 μg/mL) and better growth inhibition activity of leucyl-tRNA synthetase (78.24 ± 4.05% at 15 μg/mL).
Ionic Liquid-Based Ultrasonic-Assisted Extraction Coupled with HPLC and Artificial Neural Network Analysis for Ganoderma lucidum
Authors: Li Changqin , Cui Yiping , Lu Jie , Liu Cunyu , Chen Sitan , Ma Changyang , Liu Zhenhua , Wang Jinmei , Kang Wenyi
Published: March 2020

Ganoderma lucidum is widely used in traditional Chinese medicine (TCM). Ganoderic acid A and D are the main bioactive components with anticancer effects in G. lucidum. To obtain the maximum content of two compounds from G. lucidum, a novel extraction method, an ionic liquid-based ultrasonic-assisted method (ILUAE) was established. Ionic liquids (ILs) of different types and parameters, including the concentration of ILs, ultrasonic power, ultrasonic time, rotational speed, solid–liquid ratio, were optimized by the orthogonal experiment and variance analysis. Under these optimal conditions, the total extraction yield of the two compounds in G. lucidum was 3.31 mg/g, which is 36.21% higher than that of the traditional solvent extraction method. Subsequently, an artificial neural network (ANN) was developed to model the performance of the total extraction yield. The Levenberg–Marquardt back propagation algorithm with the sigmoid transfer function (logsig) at the hidden layer and a linear transfer function (purelin) at the output layer were used. Results showed that single hidden layer with 9 neurons presented the best values for the mean squared error (MSE) and the correlation coefficient (R), with respectively corresponding values of 0.09622 and 0.93332.
Effects of Annealing on Characteristics of Cu2ZnSnSe4/CH3NH3PbI3/ZnS/IZO Nanostructures for Enhanced Photovoltaic Solar Cells
Authors: Tseng Chzu-Chiang , Wu Gwomei , Chang Liann-Be , Jeng Ming-Jer , Feng Wu-Shiung , Chen Dave W. , Chen Lung-Chien , Lee Kuan-Lin
Published: March 2020

This paper presents new photovoltaic solar cells with Cu2ZnSnSe4/CH3NH3PbI3(MAPbI3)/ZnS/IZO/Ag nanostructures on bi-layer Mo/FTO (fluorine-doped tin oxide) glasssubstrates. The hole-transporting layer, active absorber layer, electron-transporting layer, transparent-conductive oxide layer, and top electrode-metal contact layer, were made of Cu2ZnSnSe4, MAPbI3 perovskite, zincsulfide, indium-doped zinc oxide, and silver, respectively. The active absorber MAPbI3 perovskite film was deposited on Cu2ZnSnSe4 hole-transporting layer that has been annealed at different temperatures. TheseCu2ZnSnSe4 filmsexhibitedthe morphology with increased crystal grain sizesand reduced pinholes, following the increased annealing temperature. When the perovskitefilm thickness was designed at 700 nm, the Cu2ZnSnSe4 hole-transporting layer was 160 nm, and the IZO (indium-zinc oxide) at 100 nm, and annealed at 650 °C, the experimental results showed significant improvements in the solar cell characteristics. The open-circuit voltage was increased to 1.1 V, the short-circuit current was improved to 20.8 mA/cm2, and the device fill factor was elevated to 76.3%. In addition, the device power-conversion efficiency has been improved to 17.4%. The output power Pmax was as good as 1.74 mW and the device series-resistance was 17.1 Ω.
NEAT1 Long Isoform Is Highly Expressed in Chronic Lymphocytic Leukemia Irrespectively of Cytogenetic Groups or Clinical Outcome
Authors: Ronchetti Domenica , Favasuli Vanessa , Monti Paola , Cutrona Giovanna , Fabris Sonia , Silvestris Ilaria , Agnelli Luca , Colombo Monica , Menichini Paola , Matis Serena , Gentile Massimo , Nurtdinov Ramil , Guigó Roderic , Baldini Luca , Fronza Gilberto , Ferrarini Manlio , Morabito Fortunato , Neri Antonino , Taiana Elisa
Published: March 2020

The biological role and therapeutic potential of long non-coding RNAs (lncRNAs) in chronic lymphocytic leukemia (CLL) are still open questions. Herein, we investigated the significance of the lncRNA NEAT1 in CLL. We examined NEAT1 expression in 310 newly diagnosed Binet A patients, in normal CD19+ B-cells, and other types of B-cell malignancies. Although global NEAT1 expression level was not statistically different in CLL cells compared to normal B cells, the median ratio of NEAT1_2 long isoform and global NEAT1 expression in CLL samples was significantly higher than in other groups. NEAT1_2 was more expressed in patients carrying mutated IGHV genes. Concerning cytogenetic aberrations, NEAT1_2 expression in CLL with trisomy 12 was lower with respect to patients without alterations. Although global NEAT1 expression appeared not to be associated with clinical outcome, patients with the lowest NEAT1_2 expression displayed the shortest time to first treatment; however, a multivariate regression analysis showed that the NEAT1_2 risk model was not independent from other known prognostic factors, particularly the IGHV mutational status. Overall, our data prompt future studies to investigate whether the increased amount of the long NEAT1_2 isoform detected in CLL cells may have a specific role in the pathology of the disease.