bluuebunny/crossref_metadata_2025 huggingface dataset:
CD4+ T-Cell Plasticity in Non-Infectious Retinal Inflammatory Disease
Authors: Chen Yi-Hsing , Lightman Sue , Calder Virginia L.
Published: September 2021

Non-infectious uveitis (NIU) is a potentially sight-threatening disease. Effector CD4+ T cells, especially interferon-γ-(IFNγ) producing Th1 cells and interleukin-17-(IL-17) producing Th17 cells, are the major immunopathogenic cells, as demonstrated by adoptive transfer of disease in a model of experimental autoimmune uveitis (EAU). CD4+FoxP3+CD25+ regulatory T cells (Tregs) were known to suppress function of effector CD4+ T cells and contribute to resolution of disease. It has been recently reported that some CD4+ T-cell subsets demonstrate shared phenotypes with another CD4+ T-cell subset, offering the potential for dual function. For example, Th17/Th1 (co-expressing IFNγ and IL-17) cells and Th17/Treg (co-expressing IL-17 and FoxP3) cells have been identified in NIU and EAU. In this review, we have investigated the evidence as to whether these ‘plastic CD4+ T cells’ are functionally active in uveitis. We conclude that Th17/Th1 cells are generated locally, are resistant to the immunosuppressive effects of steroids, and contribute to early development of EAU. Th17/Treg cells produce IL-17, not IL-10, and act similar to Th17 cells. These cells were considered pathogenic in uveitis. Future studies are needed to better clarify their function, and in the future, these cell subsets may in need to be taken into consideration for designing treatment strategies for disease.
Regulation of the Golgi Apparatus by p38 and JNK Kinases during Cellular Stress Responses
Authors: Nordgaard Cathrine , Tollenaere Maxim A. X. , Val Ana Martinez Del , Bekker-Jensen Dorte B. , Blasius Melanie , Olsen Jesper V. , Bekker-Jensen Simon
Published: September 2021

p38 and c-Jun N-terninal kinase (JNK) are activated in response to acute stress and inflammatory signals. Through modification of a plethora of substrates, these kinases profoundly re-shape cellular physiology for the optimal response to a harmful environment and/or an inflammatory state. Here, we utilized phospho-proteomics to identify several hundred substrates for both kinases. Our results indicate that the scale of signaling from p38 and JNK are of a similar magnitude. Among the many new targets, we highlight the regulation of the transcriptional regulators grb10-interacting GYF protein 1 and 2 (GIGYF1/2) by p38-dependent MAP kinase-activated protein kinase 2 (MK2) phosphorylation and 14–3–3 binding. We also show that the Golgi apparatus contains numerous substrates, and is a major target for regulation by p38 and JNK. When activated, these kinases mediate structural rearrangement of the Golgi apparatus, which positively affects protein flux through the secretory system. Our work expands on our knowledge about p38 and JNK signaling with important biological ramifications.
Proanthocyanidins Maintain Cardiac Ionic Homeostasis in Aldosterone-Induced Hypertension and Heart Failure
Authors: de las Heras Natalia , Galiana Adrián , Ballesteros Sandra , Olivares-Álvaro Elena , Fuller Peter J. , Lahera Vicente , Martín-Fernández Beatriz
Published: September 2021

Excess aldosterone promotes pathological remodeling of the heart and imbalance in cardiac ion homeostasis of sodium, potassium and calcium. Novel treatment with proanthocyanidins in aldosterone-treated rats has resulted in downregulation of cardiac SGK1, the main genomic aldosterone-induced intracellular mediator of ion handling. It therefore follows that proanthocyanidins could be modulating cardiac ion homeostasis in aldosterone-treated rats. Male Wistar rats received aldosterone (1 mg kg−1 day−1) +1% NaCl for three weeks. Half of the animals in each group were simultaneously treated with the proanthocyanidins-rich extract (80% w/w) (PRO80, 5 mg kg−1 day−1). PRO80 prevented cardiac hypertrophy and decreased calcium content. Expression of ion channels (ROMK, NHE1, NKA and NCX1) and calcium transient mediators (CAV1.2, pCaMKII and oxCaMKII) were reduced by PRO80 treatment in aldosterone-treated rats. To conclude, our data indicate that PRO80 may offer an alternative treatment to conventional MR-blockade in the prevention of aldosterone-induced cardiac pathology.
Optogenetic Activation of Astrocytes—Effects on Neuronal Network Function
Authors: Gerasimov Evgenii , Erofeev Alexander , Borodinova Anastasia , Bolshakova Anastasia , Balaban Pavel , Bezprozvanny Ilya , Vlasova Olga L.
Published: September 2021

Optogenetics approach is used widely in neurobiology as it allows control of cellular activity with high spatial and temporal resolution. In most studies, optogenetics is used to control neuronal activity. In the present study optogenetics was used to stimulate astrocytes with the aim to modulate neuronal activity. To achieve this goal, light stimulation was applied to astrocytes expressing a version of ChR2 (ionotropic opsin) or Opto-α1AR (metabotropic opsin). Optimal optogenetic stimulation parameters were determined using patch-clamp recordings of hippocampal pyramidal neurons’ spontaneous activity in brain slices as a readout. It was determined that the greatest increase in the number of spontaneous synaptic currents was observed when astrocytes expressing ChR2(H134R) were activated by 5 s of continuous light. For the astrocytes expressing Opto-α1AR, the greatest response was observed in the pulse stimulation mode (T = 1 s, t = 100 ms). It was also observed that activation of the astrocytic Opto-a1AR but not ChR2 results in an increase of the fEPSP slope in hippocampal neurons. Based on these results, we concluded that Opto-a1AR expressed in hippocampal astrocytes provides an opportunity to modulate the long-term synaptic plasticity optogenetically, and may potentially be used to normalize the synaptic transmission and plasticity defects in a variety of neuropathological conditions, including models of Alzheimer’s disease and other neurodegenerative disorders.
Mice with Whole-Body Disruption of AMPK-Glycogen Binding Have Increased Adiposity, Reduced Fat Oxidation and Altered Tissue Glycogen Dynamics
Authors: Janzen Natalie R. , Whitfield Jamie , Murray-Segal Lisa , Kemp Bruce E. , Hawley John A. , Hoffman Nolan J.
Published: September 2021

The AMP-activated protein kinase (AMPK), a central regulator of cellular energy balance and metabolism, binds glycogen via its β subunit. However, the physiological effects of disrupting AMPK-glycogen interactions remain incompletely understood. To chronically disrupt AMPK-glycogen binding, AMPK β double knock-in (DKI) mice were generated with mutations in residues critical for glycogen binding in both the β1 (W100A) and β2 (W98A) subunit isoforms. We examined the effects of this DKI mutation on whole-body substrate utilization, glucose homeostasis, and tissue glycogen dynamics. Body composition, metabolic caging, glucose and insulin tolerance, serum hormone and lipid profiles, and tissue glycogen and protein content were analyzed in chow-fed male DKI and age-matched wild-type (WT) mice. DKI mice displayed increased whole-body fat mass and glucose intolerance associated with reduced fat oxidation relative to WT. DKI mice had reduced liver glycogen content in the fed state concomitant with increased utilization and no repletion of skeletal muscle glycogen in response to fasting and refeeding, respectively, despite similar glycogen-associated protein content relative to WT. DKI liver and skeletal muscle displayed reductions in AMPK protein content versus WT. These findings identify phenotypic effects of the AMPK DKI mutation on whole-body metabolism and tissue AMPK content and glycogen dynamics.
Laboratory Selection and Assessment of Resistance Risk in Drosophila suzukii (Diptera: Drosophilidae) to Spinosad and Malathion
Authors: Disi Joseph Onwusemu , Sial Ashfaq A.
Published: September 2021

Drosophila suzukii (Matsumura) is one of the most economically important pests of soft-skinned fruits worldwide. Repeated insecticide applications commonly used to prevent fruit infestations increase the risk of resistance development in D. suzukii. Assessment of resistance risk in D. suzukii using artificial selection can be valuable in developing proactive resistance management strategies to retain susceptibility in the field populations. Here, we artificially selected a colony of field-collected D. suzukii for resistance against spinosad and malathion. A quantitative genetic approach was then used to estimate realized heritability (h2) of resistance and predict the rates of resistance development. After 10 and 11 generations of selection, resistance to spinosad and malathion in D. suzukii females significantly increased by 7.55- and 2.23-fold, respectively. Based on the predicted rates of resistance development, assuming h2 = 0.14 (mean h2 of spinosad resistance in this study) and 90% of population was killed at each generation, 10-fold increase in LC50 of D. suzukii females would be expected in nine generations for spinosad. However, 10-fold increase in LC50 of D. suzukii females for malathion would be expected in 37 generations, assuming h2 = 0.08 (mean h2 of malathion resistance) and 90% of population was killed at each generation. These results indicate that the risk of resistance in D. suzukii populations exists against both spinosad and malathion. However, resistance would develop faster against spinosad as compared to malathion. Thus, resistance management strategies should be implemented proactively to maintain the effectiveness of these insecticides to control D. suzukii.
Transcatheter Tricuspid Valve-in-Valve Procedure—An Illustrative Case Report and Review
Authors: Montenegro da Costa Márcio José , Quintella Edgard Freitas , Kohn Luiz , Lacoste Maximiliano Otero , Leite Gustavo Lycurgo , Hadid Leonardo , Kruczan Dany David , Zajdenverg Ricardo , de Castro Sabino Hugo , da Motta Paulo Antônio Marra
Published: September 2021

Severe tricuspid commitment is no longer understood as merely a marker of disease but is now widely thought of as a significant contributor to cardiac morbidity and mortality. However, isolated tricuspid valve surgery remains rare and to this day continues to be associated with the highest surgical risk among all valve procedures and high operative mortality rates, especially in reoperations. Therefore, the development of tricuspid transcatheter procedures is as necessary as it was for the other valves a couple of years ago. Recently, multiple percutaneous therapies have been developed for the management of severe tricuspid disease, initially only repair and more recently replacement, thus creating a new branch for the management of patients who have already undergone surgery and who present with dysfunctional bioprostheses. The purpose of this review and report is to demonstrate current and possible future challenges, and to show that the valve-in-valve procedure of the tricuspid valve is feasible and safe, and now can be performed in all its range, in the smallest to the largest sizes of presentation, without incurring the untoward risks of conventional surgery.
Hemoglobin–Polyaniline Composite and Electrochemical Field Effective Transistors
Authors: Ichikawa Mai , Goto Hiromasa
Published: September 2021

A composite of hemoglobin/polyaniline was prepared. The chemical structure of this obtained composite was confirmed using infrared absorption spectroscopy measurement. The luminol reaction of the composite manifested chemical emissions from the composite. Furthermore, electrochemical transistors using the composite were created. The hemoglobin/polyaniline-based electrochemical transistor could switch to external current flow via an electrochemical reaction. The color of the transistor surface changed from green to red upon applying electrochemical potential.
Width Dependent Elastic Properties of Graphene Nanoribbons
Authors: Kalosakas George , Lathiotakis Nektarios N. , Papagelis Konstantinos
Published: September 2021

The mechanical response of graphene nanoribbons under uniaxial tension, as well as its dependence on the nanoribbon width, is presented by means of numerical simulations. Both armchair and zigzag edged graphene nanoribbons are considered. We discuss results obtained through two different theoretical approaches, viz. density functional methods and molecular dynamics atomistic simulations using empirical force fields especially designed to describe interactions within graphene sheets. Apart from the stress-strain curves, we calculate several elastic parameters, such as the Young’s modulus, the third-order elastic modulus, the intrinsic strength, the fracture strain, and the Poisson’s ratio versus strain, presenting their variation with the width of the nanoribbon.
Springback Analysis for Warm Bending of Titanium Tube Based on Coupled Thermal-Mechanical Simulation
Authors: Li Guangjun , He Zirui , Ma Jun , Yang Heng , Li Heng
Published: September 2021

Titanium bent tubular parts attract extensive applications, thus meeting the ever-growing demands for light weight, high reliability, and long service life, etc. To improve bending limit and forming quality, local-heat-assisted bending has been developed. However, significant springback seriously reduces the dimensional accuracy of the bent tubular parts even under elevated forming temperatures, and coupled thermal-mechanical working conditions make springback behavior more complex and difficult to control in warm bending of titanium tubular materials. In this paper, using warm bending of thin-walled commercial pure titanium tube as a case, a coupled thermal-mechanical finite element model of through-process heating-bending-unloading is constructed and verified, for predicting the springback behavior in warm bending. Based on the model, the time-dependent evolutions of springback angle and residual stress distribution during thermal-mechanical unloading are studied. In addition, the influences of forming temperature and bending angle on springback angle, thickness variation, and cross-section flattening of bent tubes are clarified. This research provides a fundamental understanding of the thermal-mechanical-affected springback behavior upon local-heat-assisted bending for improving the forming accuracy of titanium bent tubular parts and structures.
Evaluation of Clustering Techniques to Predict Surface Roughness during Turning of Stainless-Steel Using Vibration Signals
Authors: Abu-Mahfouz Issam , Banerjee Amit , Rahman Esfakur
Published: September 2021

In metal-cutting processes, the interaction between the tool and workpiece is highly nonlinear and is very sensitive to small variations in the process parameters. This causes difficulties in controlling and predicting the resulting surface finish quality of the machined surface. In this work, vibration signals along the major cutting force direction in the turning process are measured at different combinations of cutting speeds, feeds, and depths of cut using a piezoelectric accelerometer. The signals are processed to extract features in the time and frequency domains. These include statistical quantities, Fast Fourier spectral signatures, and various wavelet analysis extracts. Various feature selection methods are applied to the extracted features for dimensionality reduction, followed by applying several outlier-resistant unsupervised clustering algorithms on the reduced feature set. The objective is to ascertain if partitions created by the clustering algorithms correspond to experimentally obtained surface roughness data for specific combinations of cutting conditions. We find 75% accuracy in predicting surface finish from the Noise Clustering Fuzzy C-Means (NC-FCM) and the Density-Based Spatial Clustering Applications with Noise (DBSCAN) algorithms, and upwards of 80% accuracy in identifying outliers. In general, wrapper methods used for feature selection had better partitioning efficacy than filter methods for feature selection. These results are useful when considering real-time steel turning process monitoring systems.
Study on Concrete Deterioration in Different NaCl-Na2SO4 Solutions and the Mechanism of Cl− Diffusion
Authors: Zhang Fei , Hu Zhiping , Wei Feng , Wen Xin , Li Xiaoguang , Dai Li , Liu Long
Published: September 2021

The diffusion of sulfate (SO42−) and chloride (Cl−) ions from rivers, salt lakes and saline soil into reinforced concrete is one of the main factors that contributes to the corrosion of steel reinforcing bars, thus reducing their mechanical properties. This work experimentally investigated the corrosion process involving various concentrations of NaCl-Na2SO4 leading to the coupled erosion of concrete. The appearance, weight, and mechanical properties of the concrete were measured throughout the erosion process, and the Cl− and SO42− contents in concrete were determined using Cl− rapid testing and spectrophotometry, respectively. Scanning electron microscopy, energy spectrometry, X-ray diffractometry, and mercury porosimetry were also employed to analyze microstructural changes and complex mineral combinations in these samples. The results showed that with higher Na2SO4 concentration and longer exposure time, the mass, compressive strength, and relative dynamic elastic modulus gradually increased and large pores gradually transitioned to medium and small pores. When the Na2SO4 mass fraction in the salt solution was ≥10 wt%, there was a downward trend in the mechanical properties after exposure for a certain period of time. The Cl− diffusion rate was thus related to Na2SO4 concentration. When the Na2SO4 mass fraction in solution was ≤5 wt% and exposure time short, SO42− and cement hydration/corrosion products hindered Cl− migration. In a concentrated Na2SO4 environment (≥10 wt%), the Cl− diffusion rate was accelerated in the later stages of exposure. These experiments further revealed that the Cl− migration rate was higher than that of SO42−.
Thermal Processing Map and Microstructure Evolution of Inconel 625 Alloy Sheet Based on Plane Strain Compression Deformation
Authors: Song Yuelin , Fan Jiangkun , Liu Xudong , Zhang Peizhe , Li Jinshan
Published: September 2021

Plane strain compression tests were used to study the deformation behavior of an Inconel 625 alloy sheet at various temperatures and strain rates. The peak stress was selected to establish the constitutive equation, and the processing maps under different strains were drawn. The results show that the effective stress–strain curve of Inconel 625 has typical dynamic recrystallization (DRX) characteristics. With the increasing deformation temperature and the decreasing strain rate, the softening effect is significantly enhanced. The parameters of the constitutive equation are calculated, and the average error of the constitutive equation is 5.68%. Through the analysis of the processing map, a deformation temperature of 950–960 °C with a strain rate of 0.007–0.05 s−1 were determined as the unstable region, and obvious local plastic-rheological zones were found in the unstable region. The optimum deformation condition was found to be 1020–1060 °C/0.005–0.03 s−1. Through electron backscattered diffraction (EBSD) characterization, it was found that both the increase of temperature and the decrease of strain rate significantly promote the recrystallization process. At a low strain rate, the main recrystallization mechanism is discontinuous dynamic recrystallization (DDRX). It is expected that the above results can provide references for the optimization of the rolling process and microstructure control of an Inconel 625 alloy sheet.
0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 Phosphate Composites: Dielectric and Ferroelectric Properties
Authors: Plyushch Artyom , Mačiulis Nerijus , Sokal Aliaksei , Grigalaitis Robertas , Macutkevič Jan , Kudlash Alexander , Apanasevich Natalia , Lapko Konstantin , Selskis Algirdas , Maksimenko Sergey A. , Kuzhir Polina , Banys Juras
Published: September 2021

Composite materials with 83 wt.% of the 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 distributed in phosphate-bonded ceramics were prepared at three different pressures. A phosphate matrix comprises a mixture of an aluminum phosphate binder and melted periclase, MgO. All samples demonstrate a homogeneous distribution of the ferroelectric perovskite phase and are thermally stable up to 900 K. At higher temperatures, the pyrochlore cubic phase forms. It has been found that the density of the composites non-monotonously depends on the pressure. The dielectric permittivity and losses substantially increase with the density of the samples. The fabricated composites demonstrate diffused ferroelectric–paraelectric transition and prominent piezoelectric properties.
Multistep Chemical Processing of Crickets Leading to the Extraction of Chitosan Used for Synthesis of Polymer Drug Carriers
Authors: Głąb Magdalena , Kudłacik-Kramarczyk Sonia , Drabczyk Anna , Guigou Martin Duarte , Sobczak-Kupiec Agnieszka , Mierzwiński Dariusz , Gajda Paweł , Walter Janusz , Tyliszczak Bożena
Published: September 2021

Chitosan belongs to the group of biopolymers with increasing range of potential applications therefore searching for new raw materials as well as new techniques of obtaining of this polysaccharide are currently a subject of interest of many scientists. Presented manuscript describes preparation of chitosan from crickets. Obtainment of final product required a number of processes aimed at removal of undesirable substances such as waxes, mineral salts, proteins or pigments from above-mentioned insects. Chemical structure of fractions obtained after each step was compared with the structure of commercial chitosan by means of techniques such as X-ray diffraction and FT-IR spectroscopy. Final product was subsequently used for preparation of polymer capsules that were modified with active substance characterized by antibacterial and anticancer activity—nisin. Next, sorption capacity of obtained materials was evaluated as well as a release profile of active substance in different environments. Based on the conducted research it can be concluded that crickets constitute an alternative for shellfish and other conventional sources of chitosan. Furthermore, obtained capsules on the basis of such prepared chitosan can be considered as drug delivery systems which efficiency of release of active substance is bigger in alkaline environments.
Bioinformatic Analysis for Influential Core Gene Identification and Prognostic Significance in Advanced Serous Ovarian Carcinoma
Authors: Song Changho , Kim Kyoung-Bo , Lee Jae-Ho , Kim Shin
Published: September 2021

Background and objectives: Ovarian cancer is one of the leading causes of death among women worldwide. Most newly diagnosed ovarian cancer patients are diagnosed in advanced stages of the disease. Despite various treatments, most patients with advanced stage ovarian cancer, including serous ovarian cancer (the most common subtype of ovarian cancer), experience recurrence, which is associated with extremely poor prognoses. In the present study, we aimed to identify core genes involved in ovarian cancer and their associated molecular mechanisms, as well as to investigate related clinicopathological implications in ovarian cancer. Materials and methods: Three gene expression cohorts (GSE14407, GSE36668, and GSE38666) were obtained from the Gene Expression Omnibus databases to explore potential therapeutic biomarkers for ovarian cancer. Nine up-regulated and six down-regulated genes were screened. Three publicly available gene expression datasets (GSE14407, GSE36668, and GSE38666) were analyzed. Results: A total of 14 differently expressed genes (DEGs) were identified, among which nine genes were upregulated (BIRC5, CDCA3, CENPF, KIF4A, NCAPG, RRM2, UBE2C, VEGFA, and NR2F6) and were found to be significantly enriched in cell cycle regulation by gene ontology analysis. Further protein–protein interaction network analysis revealed seven hub genes among these DEGs. Moreover, Kaplan–Meier survival analysis showed that a higher expression of CDCA3 and UBE2C was associated with poor overall patient survival regardless of tumor stage and a higher tumor histologic grade. Conclusion: Altogether, our study suggests that CDCA3 and UBE2C may be valuable biomarkers for predicting the outcome of patients with advanced serous ovarian cancer.
Reply to Otter et al. Comment on “Bernard et al. Association between Urinary Metabolites and the Exposure of Intensive Care Newborns to Plasticizers of Medical Devices Used for Their Care Management. Metabolites 2021, 11, 252”
Authors: Bernard Lise , Bouattour Yassine , Masse Morgane , Boeuf Benoît , Decaudin Bertrand , Genay Stéphanie , Lambert Céline , Moreau Emmanuel , Pereira Bruno , Pinguet Jérémy , Richard Damien , Sautou Valérie ,   for the ARMED Study Group
Published: September 2021

The comments written by R. Otter et al. [...]
Measurement of Residual Stress and Young’s Modulus on Micromachined Monocrystalline 3C-SiC Layers Grown on <111> and <100> Silicon
Authors: Sapienza Sergio , Ferri Matteo , Belsito Luca , Marini Diego , Zielinski Marcin , La Via Francesco , Roncaglia Alberto
Published: September 2021

3C-SiC is an emerging material for MEMS systems thanks to its outstanding mechanical properties (high Young’s modulus and low density) that allow the device to be operated for a given geometry at higher frequency. The mechanical properties of this material depend strongly on the material quality, the defect density, and the stress. For this reason, the use of SiC in Si-based microelectromechanical system (MEMS) fabrication techniques has been very limited. In this work, the complete characterization of Young’s modulus and residual stress of monocrystalline 3C-SiC layers with different doping types grown on <100> and <111> oriented silicon substrates is reported, using a combination of resonance frequency of double clamped beams and strain gauge. In this way, both the residual stress and the residual strain can be measured independently, and Young’s modulus can be obtained by Hooke’s law. From these measurements, it has been observed that Young’s modulus depends on the thickness of the layer, the orientation, the doping, and the stress. Very good values of Young’s modulus were obtained in this work, even for very thin layers (thinner than 1 μm), and this can give the opportunity to realize very sensitive strain sensors.
Improving the External Quantum Efficiency of High-Power GaN-Based Flip-Chip LEDs by Using Sidewall Composite Reflective Micro Structure
Authors: Xu Liang , Fan Kaiping , Sun Huiqing , Guo Zhiyou
Published: September 2021

For high-power applications, it is important to improve the light extraction efficiency and light output of the vertical direction of LEDs. Flip-chip LEDs (FCLEDs) with an Ag/SiO2/distributed Bragg reflector/SiO2 composite reflection micro structure (CRS) were fabricated. Compared with the normal Ag-based FCLEDs, the light output power of the CRS-FCLEDs was increased by 6.3% at an operational current of 1500 mA, with the corresponding external quantum efficiency improved by 6.0%. Further investigation proved that the CRS structure exhibited higher reflectance compared with the commonly used Ag-mirror reflective structure, which originates from the increased reflective area in the sidewall and partial area of the n-GaN contact orifices. It exhibited markedly smaller optical degradation and thus higher device reliability as compared to normal Ag-based FCLED. Moreover, the light emission intensity distributions and far-field angular light emission measurements show that the CRS-FCLED has a strengthened light output in the vertical direction, which shows great potential for applications in high-power fields, such as headlamps for automobiles.
Comprehensive Evaluation of Amino Acids and Polyphenols in 69 Varieties of Green Cabbage (Brassica oleracea L. var. capitata L.) Based on Multivariate Statistical Analysis
Authors: Jin Ning , Jin Li , Luo Shilei , Tang Zhongqi , Liu Zeci , Wei Shouhui , Liu Fanhong , Zhao Xiaoqiang , Yu Jihua , Zhong Yuan
Published: September 2021

The biological activities of the primary metabolites and secondary metabolites of 69 green cabbage varieties were tested. The LC-MS detection method was used to determine the content of 19 free amino acids (lysine, tryptophan, phenylalanine, methionine, threonine, isoleucine, leucine, valine, arginine, asparagine, glycine, proline, tyrosine, glutamine, alanine, aspartic acid, serine, and glutamate). The content of 10 polyphenols (chlorogenic acid, gallic acid, 4-coumaric acid, ferulic acid, gentisic acid, cymarin, erucic acid, benzoic acid, rutin, and kaempferol) was determined by the HPLC detection method. Considering the complexity of the data obtained, variance analysis, diversity analysis, correlation analysis, hierarchical cluster analysis (HCA), and principal component analysis (PCA) were used to process and correlate amino acid or polyphenol data, respectively. The results showed that there were significant differences between the different amino acids and polyphenols of the 69 cabbage varieties. The most abundant amino acids and polyphenols were Glu and rutin, respectively. Both amino acids and polyphenols had a high genetic diversity, and multiple groups of significant or extremely significant correlations. The 69 cabbage varieties were divided into two groups, according to 19 amino acid indexes, by PCA. Among them, seven varieties with high amino acid content all fell into the fourth quadrant. The HCA of amino acids also supports this view. Based on 10 polyphenols, the 69 cabbage varieties were divided into two groups by HCA. Based on 29 indexes of amino acids and polyphenols, 69 cabbage varieties were evaluated and ranked by PCA. Therefore, in this study, cabbage varieties were classified in accordance with the level of amino acids and polyphenols, which provided a theoretical basis for the genetic improvement of nutritional quality in cabbage.
Modeling Alleviative Effects of Ca, Mg, and K on Cu-Induced Oxidative Stress in Grapevine Roots Grown Hydroponically
Authors: Juang Kai-Wei , Lo Yu-Jin , Chen Bo-Ching
Published: September 2021

The aim of this study was to determine the pattern of alleviation effects of calcium (Ca), magnesium (Mg), and potassium (K) on copper (Cu)-induced oxidative toxicity in grapevine roots. Root growth, Cu and cation accumulation, reactive oxygen species (ROS) production, and antioxidant activities were examined in grapevine roots grown in nutrient solutions. The experimental setting was divided into three sets; each set contained a check (Hoagland solution only) and four treatments of simultaneous exposure to 15 μM Cu with four cation levels (i.e., Ca set: 0.5, 2.5, 5, and 10 mM Ca; Mg set: 0.2, 2, 4, and 8 mM Mg; K set: 0.6, 2.4, 4.8, and 9.6 mM K). A damage assessment model (DAM)-based approach was then developed to construct the dose-effect relationship between cation levels and the alleviation effects on Cu-induced oxidative stress. Model parameterization was performed by fitting the model to the experimental data using a nonlinear regression estimation. All data were analyzed by a one-way analysis of variance (ANOVA), followed by multiple comparisons using the least significant difference (LSD) test. The results showed that significant inhibitory effects on the elongation of roots occurred in grapevine roots treated with 15 μM Cu. The addition of Ca and Mg significantly mitigated phytotoxicity in root growth, whereas no significant effect of K treatment on root growth was found. With respect to oxidative stress, ROS and malondialdehyde (MDA) contents, as well as antioxidant (superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX)) activities, were stimulated in the roots after exposure to 15 μM Cu for three days. Moreover, H2O2 levels decreased significantly as Ca, Mg, and K concentrations increased, indicating that the coexistence of these cations effectively alleviated Cu-induced oxidative stress; however, alleviative effects were not observed in the assessment of the MDA content and antioxidant enzyme activities. Based on the DAM, an exponential decay equation was developed and successfully applied to characterize the alleviative effects of Ca, Mg, and K on the H2O2 content induced by Cu in the roots. In addition, compared with Mg and K, Ca was the most effective cation in the alleviation of Cu-induced ROS. Based on the results, it could be concluded that Cu inhibited root growth and Ca and Mg absorption in grapevines, and stimulated the production of ROS, lipid peroxidation, and antioxidant enzymes. Furthermore, the alleviation effects of cations on Cu-induced ROS were well described by the DAM-based approach developed in the present study.
Prediction of Drug–Target Interactions by Combining Dual-Tree Complex Wavelet Transform with Ensemble Learning Method
Authors: Pan Jie , Li Li-Ping , You Zhu-Hong , Yu Chang-Qing , Ren Zhong-Hao , Chen Yao
Published: September 2021

Identification of drug–target interactions (DTIs) is vital for drug discovery. However, traditional biological approaches have some unavoidable shortcomings, such as being time consuming and expensive. Therefore, there is an urgent need to develop novel and effective computational methods to predict DTIs in order to shorten the development cycles of new drugs. In this study, we present a novel computational approach to identify DTIs, which uses protein sequence information and the dual-tree complex wavelet transform (DTCWT). More specifically, a position-specific scoring matrix (PSSM) was performed on the target protein sequence to obtain its evolutionary information. Then, DTCWT was used to extract representative features from the PSSM, which were then combined with the drug fingerprint features to form the feature descriptors. Finally, these descriptors were sent to the Rotation Forest (RoF) model for classification. A 5-fold cross validation (CV) was adopted on four datasets (Enzyme, Ion Channel, GPCRs (G-protein-coupled receptors), and NRs (Nuclear Receptors)) to validate the proposed model; our method yielded high average accuracies of 89.21%, 85.49%, 81.02%, and 74.44%, respectively. To further verify the performance of our model, we compared the RoF classifier with two state-of-the-art algorithms: the support vector machine (SVM) and the k-nearest neighbor (KNN) classifier. We also compared it with some other published methods. Moreover, the prediction results for the independent dataset further indicated that our method is effective for predicting potential DTIs. Thus, we believe that our method is suitable for facilitating drug discovery and development.
Crystalline Forms of Trazodone Dihydrates
Authors: Plater M. John , Harrison William T. A.
Published: September 2021

In this study, treatment of anhydrous trazodone powder with ammonium carbamate in warm water crystallised two new polymorphs or dihydrates of trazodone after 5 h, whose structures were determined by X-ray single crystal diffraction. Each dihydrate contains infinite zigzag hydrogen-bonded chains of water molecules, which are stabilised by the N4 acceptor atom of the piperazine ring and the pendant carbonyl O1 atom of the triazole ring, as well as other water molecules. The strong dipole moment expected for the O1 atom makes it a good hydrogen bond acceptor for stabilising the chains of water molecules. Each molecule of trazodone has a similar conformation in both hydrates, except for the propyl chains, which adopt different conformations: anti-gauche in the β hydrate (triazole N-C-C-C and C-C-C-piperazine N) and anti-anti in the γ hydrate. Both piperazine rings adopt chair conformations, and the exocyclic N-C bonds are in equatorial orientations. The Hirshfeld surfaces and two-dimensional fingerprint plots for the polymorphs were calculated using CrystalExplorer17, which indicated contacts significantly shorter than the sum of the van der Waals radii in the vicinity of the piperazine N4 and triazole O1 atoms corresponding to the strong hydrogen bonds accepted by these atoms.
Supported TiO2 in Ceramic Materials for the Photocatalytic Degradation of Contaminants of Emerging Concern in Liquid Effluents: A Review
Authors: Danfá Sadjo , Martins Rui C. , Quina Margarida J. , Gomes João
Published: September 2021

The application of TiO2 as a slurry catalyst for the degradation of contaminants of emerging concern (CEC) in liquid effluents has some drawbacks due to the difficulties in the catalyst reutilization. Thus, sophisticated and expensive separation methods are required after the reaction step. Alternatively, several types of materials have been used to support powder catalysts, so that fixed or fluidized bed reactors may be used. In this context, the objective of this work is to systematize and analyze the results of research inherent to the application of ceramic materials as support of TiO2 in the photocatalytic CEC removal from liquid effluents. Firstly, an overview is given about the treatment processes able to degrade CEC. In particular, the photocatalysts supported in ceramic materials are analyzed, namely the immobilization techniques applied to support TiO2 in these materials. Finally, a critical review of the literature dedicated to photocatalysis with supported TiO2 is presented, where the performance of the catalyst is considered as well as the main drivers and barriers for implementing this process. A focal point in the future is to investigate the possibility of depurating effluents and promote water reuse in safe conditions, and the supported TiO2 in ceramic materials may play a role in this scope.
Sensitization to Drug Treatment in Precursor B-Cell Acute Lymphoblastic Leukemia Is Not Achieved by Stromal NF-κB Inhibition of Cell Adhesion but by Stromal PKC-Dependent Inhibition of ABC Transporters Activity
Authors: Ruiz-Aparicio Paola Fernanda , Uribe Gloria Inés , Linares-Ballesteros Adriana , Vernot Jean-Paul
Published: September 2021

Cell adhesion to stromal support and the associated intracellular signaling are central to drug resistance, therefore blocking both has been effective in increasing drug sensitization in leukemia. The stromal Ser/Thr protein kinase C (PKC) has been found to be important for conferring protection to leukemic cells. We aimed at elucidating the intracellular signals connected to cell adhesion and to stromal PKC. We found that NF-κB and Akt were up-regulated in mesenchymal stem cells (MSC) after binding of B-cell acute lymphoblastic leukemia (B-ALL) cells. Nevertheless, Akt inhibition did not induce B-ALL cell detachment. In spite of a clear activation of the NF-κB signaling pathway after B-ALL cell binding (up-regulation NF-κB1/2, and down-regulation of the IKBε and IKBα inhibitors) and an important reduction in cell adhesion after NF-κB inhibition, sensitization to the drug treatment was not observed. This was opposite to the PKC inhibitors Enzastaurin and HKPS, a novel chimeric peptide inhibitor, that were able to increase sensitization to dexamethasone, methotrexate, and vincristine. PLCγ1, Erk1/2, and CREB appear to be related to PKC signaling and PKC effect on drug sensitization since they were contra-regulated by HKPS when compared to dexamethasone-treated cells. Additionally, PKC inhibition by HKPS, but not by Enzastaurin, in MSC reduced the activity of three ABC transporters in leukemic cells treated with dexamethasone, a new indirect mechanism to increase sensitization to drug treatment in B-ALL cells. Our results show the validity of targeting the functional characteristic acquired and modulated during cell-to-cell interactions occurring in the leukemic niche.
A Structure Based Study of Selective Inhibition of Factor IXa over Factor Xa
Authors: Kundu Sibsankar , Wu Sangwook
Published: September 2021

Blood coagulation is an essential physiological process for hemostasis; however, abnormal coagulation can lead to various potentially fatal disorders, generally known as thromboembolic disorders, which are a major cause of mortality in the modern world. Recently, the FDA has approved several anticoagulant drugs for Factor Xa (FXa) which work via the common pathway of the coagulation cascade. A main side effect of these drugs is the potential risk for bleeding in patients. Coagulation Factor IXa (FIXa) has recently emerged as the strategic target to ease these risks as it selectively regulates the intrinsic pathway. These aforementioned coagulation factors are highly similar in structure, functional architecture, and inhibitor binding mode. Therefore, it remains a challenge to design a selective inhibitor which may affect only FIXa. With the availability of a number of X-ray co-crystal structures of these two coagulation factors as protein–ligand complexes, structural alignment, molecular docking, and pharmacophore modeling were employed to derive the relevant criteria for selective inhibition of FIXa over FXa. In this study, six ligands (three potent, two selective, and one inactive) were selected for FIXa inhibition and six potent ligands (four FDA approved drugs) were considered for FXa. The pharmacophore hypotheses provide the distribution patterns for the principal interactions that take place in the binding site. None of the pharmacophoric patterns of the FXa inhibitors matched with any of the patterns of FIXa inhibitors. Based on pharmacophore analysis, a selectivity of a ligand for FIXa over FXa may be defined quantitatively as a docking score of lower than −8.0 kcal/mol in the FIXa-grids and higher than −7.5 kcal/mol in the FXa-grids.
A Comparative Study of the Chemical Composition by SPME-GC/MS and Antiradical Activity of Less Common Citrus Species
Authors: Vitalini Sara , Iriti Marcello , Vinciguerra Vittorio , Garzoli Stefania
Published: September 2021

Citrus secondary metabolites, such as terpene compounds, are very important for human health due to their bioactivity including anti-inflammatory, anti-cancer, and antioxidant effects. In this work, for the first time, the volatile chemical composition of peels and juices from four different Citrus species (C. junos, Citrus × aurantium, C. aurantium ‘Bizzarria’ and C. medica ‘Florentina’, commonly known as Yuzu jeune, Oni Yuzu, Bizzarria orange and Florence cedar, respectively) was investigated by Solid-Phase Microextraction-Gas Chromatography/Mass Spectrometry (SPME-GC/MS) technique and the antiradical activity was also examined. The results showed that limonene and γ-terpinene were the main volatile substances detected both in the juices and in the peels, followed by other minority compounds responsible for the phyto-complex of the unique aromas which characterize each individual analyzed Citrus species. Principal component analysis (PCA), performed on volatile compounds, showed both some correlation as well as a clear separation between the juice and the peel of each species. Among them, Oni Yuzu juice was found to be the richest in total polyphenols and flavonoids while its capacity to scavenge ABTS•+ and DPPH• radicals was similar to that of Yuzu Jeune and Bizzarria orange.
Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine
Authors: Leitão Maria Inês P. S. , Francescato Giulia , Gomes Clara S. B. , Petronilho Ana
Published: September 2021

Organometallic derivatization of nucleosides is a highly promising strategy for the improvement of the therapeutic profile of nucleosides. Herein, a methodology for the synthesis of metalated adenosine with a deprotected ribose moiety is described. Platinum(II) N-heterocyclic carbene complexes based on adenosine were synthesized, namely N-heterocyclic carbenes bearing a protected and unprotected ribose ring. Reaction of the 8-bromo-2′,3′,5′-tri-O-acetyladenosine with Pt(PPh3)4 by C8−Br oxidative addition yielded complex 1, with a PtII centre bonded to C-8 and an unprotonated N7. Complex 1 reacted at N7 with HBF4 or methyl iodide, yielding protic carbene 2 or methyl carbene 3, respectively. Deprotection of 1 to yield 4 was achieved with NH4OH. Deprotected compound 4 reacted at N7 with HCl solutions to yield protic NHC 5 or with methyl iodide yielding methyl carbene 6. Protic N-heterocyclic carbene 5 is not stable in DMSO solutions leading to the formation of compound 7, in which a bromide was replaced by chloride. The cis-influence of complexes 1–7 was examined by 31P{1H} and 195Pt NMR. Complexes 2, 3, 5, 6 and 7 induce a decrease of 1JPt,P of more than 300 Hz, as result of the higher cis-influence of the N-heterocyclic carbene when compared to the azolato ligand in 1 and 4.
Bypassing the Resistance Mechanisms of the Tumor Ecosystem by Targeting the Endoplasmic Reticulum Stress Pathway Using Ruthenium- and Osmium-Based Organometallic Compounds: An Exciting Long-Term Collaboration with Dr. Michel Pfeffer
Authors: Gaiddon Christian , Gross Isabelle , Meng Xiangjun , Sidhoum Marjorie , Mellitzer Georg , Romain Benoit , Delhorme Jean-Batiste , Venkatasamy Aïna , Jung Alain C. , Pfeffer Michel
Published: September 2021

Metal complexes have been used to treat cancer since the discovery of cisplatin and its interaction with DNA in the 1960’s. Facing the resistance mechanisms against platinum salts and their side effects, safer therapeutic approaches have been sought through other metals, including ruthenium. In the early 2000s, Michel Pfeffer and his collaborators started to investigate the biological activity of organo-ruthenium/osmium complexes, demonstrating their ability to interfere with the activity of purified redox enzymes. Then, they discovered that these organo-ruthenium/osmium complexes could act independently of DNA damage and bypass the requirement for the tumor suppressor gene TP53 to induce the endoplasmic reticulum (ER) stress pathway, which is an original cell death pathway. They showed that other types of ruthenium complexes—as well complexes with other metals (osmium, iron, platinum)—can induce this pathway as well. They also demonstrated that ruthenium complexes accumulate in the ER after entering the cell using passive and active mechanisms. These particular physico-chemical properties of the organometallic complexes designed by Dr. Pfeffer contribute to their ability to reduce tumor growth and angiogenesis. Taken together, the pioneering work of Dr. Michel Pfeffer over his career provides us with a legacy that we have yet to fully embrace.
Porphyrin N-Pincer Pd(II)-Complexes in Water: A Base-Free and Nature-Inspired Protocol for the Oxidative Self-Coupling of Potassium Aryltrifluoroborates in Open-Air
Authors: Prasad Sana Siva , Naidu Bandameeda Ramesh , Hanafiah Marlia M. , Lakshmidevi Jangam , Marella Ravi Kumar , Lakkaboyana Sivarama Krishna , Venkateswarlu Katta
Published: September 2021

Metalloporphyrins (and porphyrins) are well known as pigments of life in nature, since representatives of this group include chlorophylls (Mg-porphyrins) and heme (Fe-porphyrins). Hence, the construction of chemistry based on these substances can be based on the imitation of biological systems. Inspired by nature, in this article we present the preparation of five different porphyrin, meso-tetraphenylporphyrin (TPP), meso-tetra(p-anisyl)porphyrin (TpAP), tetrasodium meso-tetra(p-sulfonatophenyl)porphyrin (TSTpSPP), meso-tetra(m-hydroxyphenyl)porphyrin (TmHPP), and meso-tetra(m-carboxyphenyl)porphyrin (TmCPP) as well as their N-pincer Pd(II)-complexes such as Pd(II)-meso-tetraphenylporphyrin (PdTPP), Pd(II)-meso-tetra(p-anisyl)porphyrin (PdTpAP), Pd(II)-tetrasodium meso-tetra(p-sulfonatophenyl)porphyrin (PdTSTpSPP), Pd(II)-meso-tetra(m-hydroxyphenyl)porphyrin (PdTmHPP), and Pd(II)-meso-tetra(m-carboxyphenyl)porphyrin (PdTmCPP). These porphyrin N-pincer Pd(II)-complexes were studied and found to be effective in the base-free self-coupling reactions of potassium aryltrifluoroborates (PATFBs) in water at ambient conditions. The catalysts and the products (symmetrical biaryls) were characterized using their spectral data. The high yields of the biaryls, the bio-mimicking conditions, good substrate feasibility, evading the use of base, easy preparation and handling of catalysts, and the application of aqueous media, all make this protocol very attractive from a sustainability and cost-effective standpoint.