bluuebunny/crossref_metadata_2025 huggingface dataset:
GCase and LIMP2 Abnormalities in the Liver of Niemann Pick Type C Mice
Authors: van der Lienden Martijn J. C. , Aten Jan , Marques André R. A. , Waas Ingeborg S. E. , Larsen Per W. B. , Claessen Nike , van der Wel Nicole N. , Ottenhoff Roelof , van Eijk Marco , Aerts Johannes M. F. G.
Published: March 2021

The lysosomal storage disease Niemann–Pick type C (NPC) is caused by impaired cholesterol efflux from lysosomes, which is accompanied by secondary lysosomal accumulation of sphingomyelin and glucosylceramide (GlcCer). Similar to Gaucher disease (GD), patients deficient in glucocerebrosidase (GCase) degrading GlcCer, NPC patients show an elevated glucosylsphingosine and glucosylated cholesterol. In livers of mice lacking the lysosomal cholesterol efflux transporter NPC1, we investigated the expression of established biomarkers of lipid-laden macrophages of GD patients, their GCase status, and content on the cytosol facing glucosylceramidase GBA2 and lysosomal integral membrane protein type B (LIMP2), a transporter of newly formed GCase to lysosomes. Livers of 80-week-old Npc1−/− mice showed a partially reduced GCase protein and enzymatic activity. In contrast, GBA2 levels tended to be reciprocally increased with the GCase deficiency. In Npc1−/− liver, increased expression of lysosomal enzymes (cathepsin D, acid ceramidase) was observed as well as increased markers of lipid-stressed macrophages (GPNMB and galectin-3). Immunohistochemistry showed that the latter markers are expressed by lipid laden Kupffer cells. Earlier reported increase of LIMP2 in Npc1−/− liver was confirmed. Unexpectedly, immunohistochemistry showed that LIMP2 is particularly overexpressed in the hepatocytes of the Npc1−/− liver. LIMP2 in these hepatocytes seems not to only localize to (endo)lysosomes. The recent recognition that LIMP2 harbors a cholesterol channel prompts the speculation that LIMP2 in Npc1−/− hepatocytes might mediate export of cholesterol into the bile and thus protects the hepatocytes.
Secondary Metabolites of Plants as Modulators of Endothelium Functions
Authors: Bartáková Anna , Nováková Marie
Published: March 2021

According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time—from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide–cyclic guanosine monophosphate activation, prostacyclin–cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition. In this review, plants are summarized as sources of biologically active substances affecting the endothelium. This paper compares individual substances and mechanisms that are known to affect the endothelium, and which subsequently may cause the development of cardiovascular disorders.
Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma
Authors: Marrugal Ángela , Ferrer Irene , Gómez-Sánchez David , Quintanal-Villalonga Álvaro , Pastor María Dolores , Ojeda Laura , Paz-Ares Luis , Molina-Pinelo Sonia
Published: March 2021

Heat shock protein 90 (HSP90) plays an essential role in lung adenocarcinoma, acting as a key chaperone involved in the correct functioning of numerous highly relevant protein drivers of this disease. To this end, HSP90 inhibitors have emerged as promising therapeutic strategies, even though responses to them have been limited to date. Given the need to maximize treatment efficacy, the objective of this study was to use isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic techniques to identify proteins in human lung adenocarcinoma cell lines whose basal abundances were correlated with response to HSP90 inhibitors (geldanamycin and radicicol derivatives). From the protein profiles identified according to response, the relationship between lactate dehydrogenase B (LDHB) and DNA topoisomerase 1 (TOP1) with respect to sensitivity and resistance, respectively, to geldanamycin derivatives is noteworthy. Likewise, rhotekin (RTKN) and decaprenyl diphosphate synthase subunit 2 (PDSS2) were correlated with sensitivity and resistance to radicicol derivatives. We also identified a relationship between resistance to HSP90 inhibition and the p53 pathway by glucose deprivation. In contrast, arginine biosynthesis was correlated with sensitivity to HSP90 inhibitors. Further study of these outcomes could enable the development of strategies to improve the clinical efficacy of HSP90 inhibition in patients with lung adenocarcinoma.
Gender-Specific Effects of Two Treatment Strategies in a Mouse Model of Niemann-Pick Disease Type C1
Authors: Holzmann Carsten , Witt Martin , Rolfs Arndt , Antipova Veronica , Wree Andreas
Published: March 2021

In a mouse model of Niemann-Pick disease type C1 (NPC1), a combination therapy (COMBI) of miglustat (MIGLU), the neurosteroid allopregnanolone (ALLO) and the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPßCD) has previously resulted in, among other things, significantly improved motor function. The present study was designed to compare the therapeutic effects of the COMBI therapy with that of MIGLU or HPßCD alone on body and brain weight and the behavior of NPC1−/− mice in a larger cohort, with special reference to gender differences. A total of 117 NPC1−/− and 123 NPC1+/+ mice underwent either COMBI, MIGLU only, HPßCD only, or vehicle treatment (Sham), or received no treatment at all (None). In male and female NPC1−/− mice, all treatments led to decreased loss of body weight and, partly, brain weight. Concerning motor coordination, as revealed by the accelerod test, male NPC1−/− mice benefited from COMBI treatment, whereas female mice benefited from COMBI, MIGLU, and HPßCD treatment. As seen in the open field test, the reduced locomotor activity of male and female NPC1−/− mice was not significantly ameliorated in either treatment group. Our results suggest that in NPC1−/− mice, each drug treatment scheme had a beneficial effect on at least some of the parameters evaluated compared with Sham-treated mice. Only in COMBI-treated male and female NPC+/+ mice were drug effects seen in reduced body and brain weights. Upon COMBI treatment, the increased dosage of drugs necessary for anesthesia in Sham-treated male and female NPC1−/− mice was almost completely reduced only in the female groups.
Synthesis of Densely Immobilized Gold-Assembled Silica Nanostructures
Authors: Seong Bomi , Bock Sungje , Hahm Eunil , Huynh Kim-Hung , Kim Jaehi , Lee Sang Hun , Pham Xuan-Hung , Jun Bong-Hyun
Published: March 2021

In this study, dense gold-assembled SiO2 nanostructure (SiO2@Au) was successfully developed using the Au seed-mediated growth. First, SiO2 (150 nm) was prepared, modified by amino groups, and incubated by gold nanoparticles (ca. 3 nm Au metal nanoparticles (NPs)) to immobilize Au NPs to SiO2 surface. Then, Au NPs were grown on the prepared SiO2@Au seed by reducing chloroauric acid (HAuCl4) by ascorbic acid (AA) in the presence of polyvinylpyrrolidone (PVP). The presence of bigger (ca. 20 nm) Au NPs on the SiO2 surface was confirmed by transmittance electronic microscopy (TEM) images, color changes to dark blue, and UV-vis spectra broadening in the range of 450 to 750 nm. The SiO2@Au nanostructure showed several advantages compared to the hydrofluoric acid (HF)-treated SiO2@Au, such as easy separation, surface modification stability by 11-mercaptopundecanoic acid (R-COOH), 11-mercapto-1-undecanol (R-OH), and 1-undecanethiol (R-CH3), and a better peroxidase-like catalysis activity for 5,5′-Tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2) reaction. The catalytic activity of SiO2@Au was two times better than that of HF-treated SiO2@Au. When SiO2@Au nanostructure was used as a surface enhanced Raman scattering (SERS) substrate, the signal of 4-aminophenol (4-ATP) on the surface of SiO2@Au was also stronger than that of HF-treated SiO2@Au. This study provides a potential method for nanoparticle preparation which can be replaced for Au NPs in further research and development.
Neuropeptidergic Control of Feeding: Focus on the Galanin Family of Peptides
Authors: Marcos P. , Coveñas R.
Published: March 2021

Obesity/overweight are important health problems due to metabolic complications. Dysregulation of peptides exerting orexigenic/anorexigenic effects must be investigated in-depth to understand the mechanisms involved in feeding behaviour. One of the most important and studied orexigenic peptides is galanin (GAL). The aim of this review is to update the mechanisms of action and physiological roles played by the GAL family of peptides (GAL, GAL-like peptide, GAL message-associated peptide, alarin) in the control of food intake and to review the involvement of these peptides in metabolic diseases and food intake disorders in experimental animal models and humans. The interaction between GAL and NPY in feeding and energy metabolism, the relationships between GAL and other substances involved in food intake mechanisms, the potential pharmacological strategies to treat food intake disorders and obesity and the possible clinical applications will be mentioned and discussed. Some research lines are suggested to be developed in the future, such as studies focused on GAL receptor/neuropeptide Y Y1 receptor interactions in hypothalamic and extra-hypothalamic nuclei and sexual differences regarding the expression of GAL in feeding behaviour. It is also important to study the possible GAL resistance in obese individuals to better understand the molecular mechanisms by which GAL regulates insulin/glucose metabolism. GAL does not exert a pivotal role in weight regulation and food intake, but this role is crucial in fat intake and also exerts an important action by regulating the activity of other key compounds under conditions of stress/altered diet.
Effect of the Genotypic Variation of an Aphid Host on the Endosymbiont Associations in Natural Host Populations
Authors: Zepeda-Paulo Francisca , Lavandero Blas
Published: March 2021

Understanding the role of facultative endosymbionts on the host’s ecology has been the main aim of the research in symbiont–host systems. However, current research on host–endosymbiont dynamics has failed to examine the genetic background of the hosts and its effect on host–endosymbiont associations in real populations. We have addressed the seasonal dynamic of facultative endosymbiont infections among different host clones of the grain aphid Sitobion avenae, on two cereal crops (wheat and oat) and whether their presence affects the total hymenopteran parasitism of aphid hosts at the field level. We present evidence of rapid seasonal shifts in the endosymbiont frequency, suggesting a positive selection of endosymbionts at the host-level (aphids) through an agricultural growing season, by two mechanisms; (1) an increase of aphid infections with endosymbionts over time, and (2) the seasonal replacement of host clones within natural populations by increasing the prevalence of aphid clones closely associated to endosymbionts. Our results highlight how genotypic variation of hosts can affect the endosymbiont prevalence in the field, being an important factor for understanding the magnitude and direction of the adaptive and/or maladaptive responses of hosts to the environment.
Abnormal Liver Function Test in Patients Infected with Coronavirus (SARS-CoV-2): A Retrospective Single-Center Study from Spain
Authors: Benedé-Ubieto Raquel , Estévez-Vázquez Olga , Flores-Perojo Vicente , Macías-Rodríguez Ricardo U. , Ruiz-Margáin Astrid , Martínez-Naves Eduardo , Regueiro José R. , Ávila Matías A. , Trautwein Christian , Bañares Rafael , Bosch Jaume , Cubero Francisco Javier , Nevzorova Yulia A.
Published: March 2021

The outbreak of the novel coronavirus SARS-CoV-2 epidemic has rapidly spread and still poses a serious threat to healthcare systems worldwide. In the present study, electronic medical records containing clinical indicators related to liver injury in 799 COVID-19-confirmed patients admitted to a hospital in Madrid (Spain) were extracted and analyzed. Correlation between liver injury and disease outcome was also evaluated. Serum levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyltransferase (GGT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) and AST/ALT ratio were elevated above the Upper Limit of Normal (ULN) in 25.73%, 49.17%, 34.62%, 24.21%, 55.84% and 75% of patients, respectively. Interestingly, significant positive correlation between LDH levels and the AST/ALT ratio with disease outcome was found. Our data showed that SARS-CoV-2 virus infection leads to mild, but significant changes in serum markers of liver injury. The upregulated LDH levels as well as AST/ALT ratios upon admission may be used as additional diagnostic characteristic for COVID-19 patients.
Seizures and Sepsis: A Narrative Review
Authors: Alessandri Francesco , Badenes Rafael , Bilotta Federico
Published: March 2021

Patients with sepsis-associated encephalopathy (SAE) can develop convulsive or nonconvulsive seizures. The cytokine storm and the overwhelming systemic inflammation trigger the electric circuits that promote seizures. Several neurologic symptoms, associated with this disease, range from mild consciousness impairment to coma. Focal or generalized convulsive seizures are frequent in sepsis, although nonconvulsive seizures (NCS) are often misdiagnosed and prevalent in SAE. In order to map the trigger zone in all patients that present focal or generalized seizures and also to detect NCS, EEG is indicated but continuous EEG (cEEG) is not very widespread; timing, duration, and efficacy of this tool are still unknown. The long-term risk of seizures in survivors is increased. The typical stepwise approach of seizures management begins with benzodiazepines and follows with anticonvulsants up to anesthetic drugs such as propofol or thiopental, which are able to induce burst suppression and interrupt the pathological electrical circuits. This narrative review discusses pathophysiology, clinical presentation, diagnosis and treatment of seizures in sepsis.
On the Use of Mechano-Chemically Modified Ground Tire Rubber (GTR) as Recycled and Sustainable Filler in Styrene-Butadiene Rubber (SBR) Composites
Authors: Araujo-Morera Javier , Verdugo-Manzanares Reyes , González Sergio , Verdejo Raquel , Lopez-Manchado Miguel Angel , Hernández Santana Marianella
Published: March 2021

The management of end-of-life tires (ELTs) is one of the main environmental issues that society faces nowadays. Recycling of ELTs appears as one feasible option for tackling the problem, although their incorporation as ground tire rubber (GTR) in other rubber matrices is limited due to poor compatibility. In this research, we report a successful combination of a cryo-grinding process with a chemical treatment for modifying the surface of GTR. Various cryo-grinding protocols were studied until a particle size of 100–150 µm was achieved. Chemical treatments with different acids were also analyzed, resulting in the optimal modification with sulfuric acid (H2SO4). Modified GTR was added to a styrene-butadiene rubber (SBR) matrix. The incorporation of 10 phr of this filler resulted in a composite with improved mechanical performance, with increments of 115% and 761% in tensile strength and elongation at break, respectively. These results validate the use of a recycled material from tire waste as sustainable filler in rubber composites.
Three New Derivatives of Zopfinol from Pseudorhypophila Mangenotii gen. et comb. nov.
Authors: Harms Karen , Milic Andrea , Stchigel Alberto M. , Stadler Marc , Surup Frank , Marin-Felix Yasmina
Published: March 2021

Triangularia mangenotti was analyzed for the production of secondary metabolites, resulting in the isolation of known zopfinol (1) and its new derivatives zopfinol B–C (2–4), the 10-membered lactones 7-O-acetylmultiplolide A (5) and 8-O-acetylmultiplolide A (6), together with sordarin (7), sordarin B (8), and hypoxysordarin (9). The absolute configuration of 1 was elucidated by the synthesis of MPTA-esters. Compound 1 showed antimicrobial activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus and the fungus Mucor hiemalis. While 4 was weakly antibacterial, 3 showed stronger antibiotic activity against the Gram-positive bacteria and weak antifungal activity against M. hiemalis and Rhodotorula glutinis. We furthermore observed the cytotoxicity of 1, 3 and 4 against the mammalian cell lines KB3.1 and L929. Moreover, the new genus Pseudorhypophila is introduced herein to accommodate Triangularia mangenotii together with several species of Zopfiella—Z. marina, Z. pilifera, and Z. submersa. These taxa formed a well-supported monophyletic clade in the recently introduced family Navicularisporaceae, located far from the type species of the respective original genera, in a phylogram based on the combined dataset sequences of the internal transcribed spacer region (ITS), the nuclear rDNA large subunit (LSU), and fragments of the ribosomal polymerase II subunit 2 (rpb2) and β-tubulin (tub2) genes. Zopfiella submersa is synonymized with P. marina due to the phylogenetic and morphological similarity. The isolation of zopfinols 1–4 and sordarins 7–9 confirms the potential of this fungal order as producers of bioactive compounds and suggests these compounds as potential chemotaxonomic markers.
Mapping Brain Microstructure and Network Alterations in Depressive Patients with Suicide Attempts Using Generalized Q-Sampling MRI
Authors: Chen Vincent Chin-Hung , Kao Chun-Ju , Tsai Yuan-Hsiung , McIntyre Roger S. , Weng Jun-Cheng
Published: March 2021

Depressive disorder is one of the leading causes of disability worldwide, with a high prevalence and chronic course. Depressive disorder carries an increased risk of suicide. Alterations in brain structure and networks may play an important role in suicidality among depressed patients. Diffusion magnetic resonance imaging (MRI) is a noninvasive method to map white-matter fiber orientations and provide quantitative parameters. This study investigated the neurological structural differences and network alterations in depressed patients with suicide attempts by using generalized q-sampling imaging (GQI). Our study recruited 155 participants and assigned them into three groups: 44 depressed patients with a history of suicide attempts (SA), 56 depressed patients without a history of suicide attempts (D) and 55 healthy controls (HC). We used the GQI to analyze the generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA) values in voxel-based statistical analysis, topological parameters in graph theoretical analysis and subnetwork connectivity in network-based statistical analysis. GFA indicates the measurement of neural anisotropy and represents white-matter integrity; NQA indicates the amount of anisotropic spins that diffuse along fiber orientations and represents white-matter compactness. In the voxel-based statistical analysis, we found lower GFA and NQA values in the SA group than in the D and HC groups and lower GFA and NQA values in the D group than in the HC group. In the graph theoretical analysis, the SA group demonstrated higher local segregation and lower global integration among the three groups. In the network-based statistical analysis, the SA group showed stronger subnetwork connections in the frontal and parietal lobes, and the D group showed stronger subnetwork connections in the parietal lobe than the HC group. Alternations were found in the structural differences and network measurements in healthy controls and depressed patients with and without a history of suicide attempt.
The Relationship between the Concentration of Magnesium and the Presence of Depressive Symptoms and Selected Metabolic Disorders among Men over 50 Years of Age
Authors: Rotter Iwona , Wiatrak Adrian , Rył Aleksandra , Kotfis Katarzyna , Sipak-Szmigiel Olimpia , Ptak Magdalena , Tomska Natalia , Szylińska Aleksandra
Published: March 2021

Background: changes in the concentration of magnesium influence numerous processes in the body, such as hormone and lipid metabolism, nerve conduction, a number of biochemical pathways in the brain, and metabolic cycles. As a result, changes in magnesium concentration may contribute to the emergence of such pathologies as depressive and metabolic disorders, including hypertension, diabetes, and dyslipidemia. Methods: blood samples were taken from 342 men whose mean age was 61.66 ± 6.38 years. The concentrations of magnesium, lipid parameters, and glucose were determined using the spectrophotometric method. Anthropometric measurements were performed to determine each participant’s body mass index (BMI). Additionally, all participants completed two questionnaires: the Beck Depression Inventory and the author’s questionnaire. Results: abnormal levels of magnesium were found in 78 people. The analysis showed that these subjects more often suffered from metabolic disorders such as diabetes mellitus (p < 0.001), hypertension (p < 0.001), and depressive symptoms (p = 0.002) than participants with normal magnesium levels. Conclusion: our research showed that there is a relationship between abnormal levels of magnesium and the presence of self-reported conditions, such as diabetes, hypertension, and depressive symptoms among aging men. These findings may contribute to the improvement of the diagnosis and treatment of patients with these conditions.
In-Situ Calibrated Modeling of Residual Stresses Induced in Machining under Various Cooling and Lubricating Environments
Authors: Schoop Julius
Published: March 2021

Although many functional characteristics, such as fatigue life and damage resistance depend on residual stresses, there are currently no industrially viable ‘Digital Process Twin’ models (DPTs) capable of efficiently and quickly predicting machining-induced stresses. By leveraging advances in ultra-high-speed in-situ experimental characterization of machining and finishing processes under plane strain (orthogonal/2D) conditions, we have developed a set of physics-based semi-analytical models to predict residual stress evolution in light of the extreme gradients of stress, strain and temperature, which are unique to these thermo-mechanical processes. Initial validation trials of this novel paradigm were carried out in Ti-6Al4V and AISI 4340 alloy steel. A variety dry, cryogenically cooled and oil lubricated conditions were evaluated to determine the model’s ability to capture the tribological changes induced due to lubrication and cooling. The preliminarily calibrated and validated model exhibited an average correlation of better than 20% between the predicted stresses and experimental data, with calculation times of less than a second. Based on such fast-acting DPTs, the authors envision future capabilities in pro-active surface engineering of advanced structural components (e.g., turbine blades).
Markovian Approximation of the Rough Bergomi Model for Monte Carlo Option Pricing
Authors: Zhu Qinwen , Loeper Grégoire , Chen Wen , Langrené Nicolas
Published: March 2021

The recently developed rough Bergomi (rBergomi) model is a rough fractional stochastic volatility (RFSV) model which can generate a more realistic term structure of at-the-money volatility skews compared with other RFSV models. However, its non-Markovianity brings mathematical and computational challenges for model calibration and simulation. To overcome these difficulties, we show that the rBergomi model can be well-approximated by the forward-variance Bergomi model with wisely chosen weights and mean-reversion speed parameters (aBergomi), which has the Markovian property. We establish an explicit bound on the L2-error between the respective kernels of these two models, which is explicitly controlled by the number of terms in the aBergomi model. We establish and describe the affine structure of the rBergomi model, and show the convergence of the affine structure of the aBergomi model to the one of the rBergomi model. We demonstrate the efficiency and accuracy of our method by implementing a classical Markovian Monte Carlo simulation scheme for the aBergomi model, which we compare to the hybrid scheme of the rBergomi model.
Hyperbolic Center of Mass for a System of Particles in a Two-Dimensional Space with Constant Negative Curvature: An Application to the Curved 2-Body Problem
Authors: Ortega Palencia Pedro Pablo , Ortiz Ortiz Ruben Dario , Marin Ramirez Ana Magnolia
Published: March 2021

In this article, a simple expression for the center of mass of a system of material points in a two-dimensional surface of Gaussian constant negative curvature is given. By using the basic techniques of geometry, we obtained an expression in intrinsic coordinates, and we showed how this extends the definition for the Euclidean case. The argument is constructive and serves to define the center of mass of a system of particles on the one-dimensional hyperbolic sphere LR1.
Descriptors of Secondary Active Transporter Function and How They Relate to Partial Reactions in the Transport Cycle
Authors: Schicker Klaus , Bhat Shreyas , Farr Clemens , Burtscher Verena , Horner Andreas , Freissmuth Michael , Sandtner Walter
Published: March 2021

Plasmalemmal solute carriers (SLCs) gauge and control solute abundance across cellular membranes. By virtue of this action, they play an important role in numerous physiological processes. Mutations in genes encoding the SLCs alter amino acid sequence that often leads to impaired protein function and onset of monogenic disorders. To understand how these altered proteins cause disease, it is necessary to undertake relevant functional assays. These experiments reveal descriptors of SLC function such as the maximal transport velocity (Vmax), the Michaelis constant for solute uptake (KM), potencies for inhibition of transporter function (IC50/EC50), and many more. In several instances, the mutated versions of different SLC transporters differ from their wild-type counterparts in the value of these descriptors. While determination of these experimental parameters can provide conjecture as to how the mutation gives rise to disease, they seldom provide any definitive insights on how a variant differ from the wild-type transporter in its operation. This is because the experimental determination of association between values of the descriptors and several partial reactions a transporter undergoes is casual, but not causal, at best. In the present study, we employ kinetic models that allow us to derive explicit mathematical terms and provide experimental descriptors as a function of the rate constants used to parameterize the kinetic model of the transport cycle. We show that it is possible to utilize these mathematical expressions to deduce, from experimental outcomes, how the mutation has impinged on partial reactions in the transport cycle.
Evaluation of the Stress Concentration Factor in Butt Welded Joints: A Comparative Study
Authors: Randić Miroslav , Pavletić Duško , Fabić Marko
Published: March 2021

Surface cracks in butt-welded joints usually occur in places with increased stress concentrations. The stress concentration factor (SCF) can be calculated using an empirical equation, with five geometric parameters of a butt-welded joint (thickness of the base material, toe radius, weld toe angle, weld width, and reinforcement height). However, in an industrial environment, it is impractical and sometimes even impossible to measure all five geometric parameters with sufficient accuracy. In this study, eight experiments on butt-welded joints were performed. All samples were scanned with a 3D scanner, and the geometric sizes of the welded joints were measured using computer software. A modified empirical expression proposed by Ushirokawa and Nakayama was used to calculate the SCF; the expression was adjusted in such a way that the SCF was calculated by knowing only the toe radius. In addition, four new expressions were proposed for the calculation of the SCF by knowing the toe radius in relation to the weld toe angle; the expressions were then compared and analyzed. Additionally, the values of the stress concentrations in the butt-welded joints were obtained using a finite element method (FEM). The SCFs calculated using the four methods were compared and further discussed. Our data suggested a new accurate and straightforward approach for calculating the SCF by knowing only the weld toe radius.
Effect of Active Screen Plasma Nitriding on Mechanical Properties of Spheroidal Graphite Cast Iron
Authors: Hoshiyama Yasuhiro , Chiba Keisuke , Maruoka Tomoki
Published: March 2021

Spheroidal graphite cast iron is a material with a wide range of uses such as in automobile parts. By applying active screen plasma nitriding (ASPN) treatment, the use of spheroidal graphite cast iron is expanded, and it can be expected to be used under special load conditions. In this study, we evaluated the effect of ASPN treatment on the mechanical properties of spheroidal graphite cast iron. With ASPN treatment, a nitride layer was formed on the sample surface and a diffusion layer was formed further inside the nitride layer. The thickness of nitride layer increased as the treatment temperature increased. The hardness was improved by ASPN treatment. The abrasion resistance was improved by ASPN treatment, and longer treatment time resulted in higher abrasion resistance. The fatigue strength was improved by ASPN treatment, and longer treatment time resulted in higher fatigue strength. ASPN treatment also improved the corrosion resistance.
Developing a Yeast Platform Strain for an Enhanced Taxadiene Biosynthesis by CRISPR/Cas9
Authors: Utomo Joseph C. , Chaves Fabio C. , Bauchart Philippe , Martin Vincent J. J. , Ro Dae-Kyun
Published: March 2021

Paclitaxel is an important diterpenoid commonly used as an anticancer drug. Although the paclitaxel biosynthetic pathway has been mostly revealed, some steps remain to be elucidated. The difficulties in plant transformations and the scarcity of the precursor of paclitaxel, (+)-taxa-4(5), 11(12)-diene (taxadiene), have hindered the full comprehension of paclitaxel biochemistry and, therefore, its production by biotechnological approaches. One solution is to use the budding yeast, Saccharomyces cerevisiae, as a platform to elucidate the paclitaxel biosynthesis. As taxadiene is a diterpenoid, its common precursor, geranylgeranyl pyrophosphate (GGPP), needs to be increased in yeast. In this study, we screened various GGPP synthases (GGPPS) to find the most suitable GGPPS for taxadiene production in yeast. We also optimized the taxadiene production by increasing the flux toward the terpenoid pathway. Finally, to remove selection markers, we integrated the required genes using a CRISPR/Cas9 system in the yeast genome. Our result showed that a titer of 2.02 ± 0.40 mg/L (plasmid) and 0.41 ± 0.06 mg/L (integrated) can be achieved using these strategies. This platform strain can be used to readily test the gene candidates for microbial paclitaxel biosynthesis in the future.
Dual Demodulation of Temperature and Refractive Index Using Ring Core Fiber Based Mach-Zehnder Interferometer
Authors: Yuan Weihao , Yu Changyuan
Published: March 2021

We report the ring core fiber spliced with single mode fiber and no core fiber which is used for temperature and refractive index (RI) sensing. The Mach-Zehnder interferometer (MZI) is formed with this kind of sandwich fiber structure and the maximum extinction ratio of the interference spectra reaches 27 dB with the free spectra range of 12 nm. The MZI fiber sensor is applied for temperature sensing with the sensitivity of 69 pm/°C and 0.051 dB/°C. The RI sensitivity reaches 182.07 dB/RIU and −31.44 nm/RIU with the RI ranging from 1.33 to 1.38. The RI value can be directly demodulated with the interference dip intensity which shows insensitivity to temperature. The demodulation of temperature can be achieved by using the linear equations between dip wavelength shift with the variation of temperature and RI.
Electrical Characterizations of Planar Ga2O3 Schottky Barrier Diodes
Authors: Zhang Shiyu , Liu Zeng , Liu Yuanyuan , Zhi Yusong , Li Peigang , Wu Zhenping , Tang Weihua
Published: March 2021

In this work, a Schottky barrier diode (SBD) is fabricated and demonstrated based on the edge-defined film-fed grown (EFG) Ga2O3 crystal substrate. At the current stage, for high resistance un-doped Ga2O3 films and/or bulk substrates, the carrier concentration (and other electrical parameters) is difficult to be obtained by using the conventional Hall measurement. Therefore, we extracted the electrical parameters such as on-state resistance (Ron), Schottky barrier height (ϕB), the ideal factor (n), series resistance (Rs) and the carrier concentration (Nd) by analyzing the current density–voltage (J–V) and capacitance–voltage (C–V) curves of the Ga2O3-based SBD, systematically. The detailed measurements and theoretical analysis are displayed in this paper.
A Narrative Review of the W, X, Y, E, and NG of Meningococcal Disease: Emerging Capsular Groups, Pathotypes, and Global Control
Authors: Tzeng Yih-Ling , Stephens David S.
Published: March 2021

Neisseria meningitidis, carried in the human nasopharynx asymptomatically by ~10% of the population, remains a leading cause of meningitis and rapidly fatal sepsis, usually in otherwise healthy individuals. The epidemiology of invasive meningococcal disease (IMD) varies substantially by geography and over time and is now influenced by meningococcal vaccines and in 2020–2021 by COVID-19 pandemic containment measures. While 12 capsular groups, defined by capsular polysaccharide structures, can be expressed by N. meningitidis, groups A, B, and C historically caused most IMD. However, the use of mono-, bi-, and quadrivalent-polysaccharide-conjugate vaccines, the introduction of protein-based vaccines for group B, natural disease fluctuations, new drugs (e.g., eculizumab) that increase meningococcal susceptibility, changing transmission dynamics and meningococcal evolution are impacting the incidence of the capsular groups causing IMD. While the ability to spread and cause illness vary considerably, capsular groups W, X, and Y now cause significant IMD. In addition, group E and nongroupable meningococci have appeared as a cause of invasive disease, and a nongroupable N. meningitidis pathotype of the hypervirulent clonal complex 11 is causing sexually transmitted urethritis cases and outbreaks. Carriage and IMD of the previously “minor” N. meningitidis are reviewed and the need for polyvalent meningococcal vaccines emphasized.
Covalent Histone Modification by an Electrophilic Derivative of the Anti-HIV Drug Nevirapine
Authors: Harjivan Shrika G. , Charneira Catarina , Martins Inês L. , Pereira Sofia A. , Espadas Guadalupe , Sabidó Eduard , Beland Frederick A. , Marques M. Matilde , Antunes Alexandra M. M.
Published: March 2021

Nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor widely used in combined antiretroviral therapy and to prevent mother-to-child transmission of the human immunodeficiency virus type 1, is associated with several adverse side effects. Using 12-mesyloxy-nevirapine, a model electrophile of the reactive metabolites derived from the NVP Phase I metabolite, 12-hydroxy-NVP, we demonstrate that the nucleophilic core and C-terminal residues of histones are targets for covalent adduct formation. We identified multiple NVP-modification sites at lysine (e.g., H2BK47, H4K32), histidine (e.g., H2BH110, H4H76), and serine (e.g., H2BS33) residues of the four histones using a mass spectrometry-based bottom-up proteomic analysis. In particular, H2BK47, H2BH110, H2AH83, and H4H76 were found to be potential hot spots for NVP incorporation. Notably, a remarkable selectivity to the imidazole ring of histidine was observed, with modification by NVP detected in three out of the 11 histidine residues of histones. This suggests that NVP-modified histidine residues of histones are prospective markers of the drug’s bioactivation and/or toxicity. Importantly, NVP-derived modifications were identified at sites known to determine chromatin structure (e.g., H4H76) or that can undergo multiple types of post-translational modifications (e.g., H2BK47, H4H76). These results open new insights into the molecular mechanisms of drug-induced adverse reactions.
Alginate Bioconjugate and Graphene Oxide in Multifunctional Hydrogels for Versatile Biomedical Applications
Authors: Cirillo Giuseppe , Pantuso Elvira , Curcio Manuela , Vittorio Orazio , Leggio Antonella , Iemma Francesca , De Filpo Giovanni , Nicoletta Fiore Pasquale
Published: March 2021

In this work, we combined electrically-conductive graphene oxide and a sodium alginate-caffeic acid conjugate, acting as a functional element, in an acrylate hydrogel network to obtain multifunctional materials designed to perform multiple tasks in biomedical research. The hybrid material was found to be well tolerated by human fibroblast lung cells (MRC-5) (viability higher than 94%) and able to modify its swelling properties upon application of an external electric field. Release experiments performed using lysozyme as the model drug, showed a pH and electro-responsive behavior, with higher release amounts and rated in physiological vs. acidic pH. Finally, the retainment of the antioxidant properties of caffeic acid upon conjugation and polymerization processes (Trolox equivalent antioxidant capacity values of 1.77 and 1.48, respectively) was used to quench the effect of hydrogen peroxide in a hydrogel-assisted lysozyme crystallization procedure.
Ag Nanoparticle-Decorated MoS2 Nanosheets for Enhancing Electrochemical Performance in Lithium Storage
Authors: Nguyen Thang Phan , Kim Il Tae
Published: March 2021

Metallic phase 1T MoS2 is a well-known potential anode for enhancing the electrochemical performance of lithium-ion batteries owing to its mechanical/chemical stability and high conductivity. However, during the lithiation/delithiation process, MoS2 nanosheets (NSs) tend to restack to form bulky structures that deteriorate the cycling performance of bare MoS2 anodes. In this study, we prepared Ag nanoparticle (NP)-decorated 1T MoS2 NSs via a liquid exfoliation method with lithium intercalation and simple reduction of AgNO3 in NaBH4. Ag NPs were uniformly distributed on the MoS2 surface with the assistance of 3-mercapto propionic acid. Ag NPs with the size of a few nanometers enhanced the conductivity of the MoS2 NS and improved the electrochemical performance of the MoS2 anode. Specifically, the anode designated as Ag3@MoS2 (prepared with AgNO3 and MoS2 in a weight ratio of 1:10) exhibited the best cycling performance and delivered a reversible specific capacity of 510 mAh·g−1 (approximately 73% of the initial capacity) after 100 cycles. Moreover, the rate performance of this sample had a remarkable recovery capacity of ~100% when the current decreased from 1 to 0.1 A·g−1. The results indicate that the Ag nanoparticle-decorated 1T MoS2 can be employed as a high-rate capacity anode in lithium-ion storage applications.
Modulation of the Magnetic Hyperthermia Response Using Different Superparamagnetic Iron Oxide Nanoparticle Morphologies
Authors: Reyes-Ortega Felisa , Delgado Ángel , Iglesias Guillermo
Published: March 2021

The use of magnetic nanoparticles in hyperthermia, that is, heating induced by alternating magnetic fields, is gaining interest as a non-invasive, free of side effects technique that can be considered as a co-adjuvant of other cancer treatments. Having sufficient control on the field characteristics, within admissible limits, the focus is presently on the magnetic material. In the present contribution, no attempt has been made of using other composition than superparamagnetic iron oxide nanoparticles (SPION), or of applying surface functionalization, which opens a wider range of choices. We have used a hydrothermal synthesis route that allows preparing SPION nanoparticles in the 40 nm size range, with spherical, cuboidal or rod-like shapes, by minor changes in the synthesis steps. The three kinds of particles (an attempt to produce star-shaped colloids yielded hematite) were demonstrated to have the magnetite (or maghemite) crystallinity. Magnetization cycles showed virtually no hysteresis and demonstrated the superparamagnetic nature of the particles, cuboidal ones displaying saturation magnetization comparable to bulk magnetite, followed by rods and spheres. The three types were used as hyperthermia agents using magnetic fields of 20 kA/m amplitude and frequency in the range 136–205 kHz. All samples demonstrated to be able to raise the solution temperature from room values to 45 °C in a mere 60 s. Not all of them performed the same way, though. Cuboidal magnetic nanoparticles (MNPs) displayed the maximum heating power (SAR or specific absorption rate), ranging in fact among the highest reported with these geometries and raw magnetite composition.
A Molecularly Imprinted Sol-Gel Electrochemical Sensor for Naloxone Determination
Authors: Shaabani Narges , Chan Nora W. C. , Jemere Abebaw B.
Published: March 2021

A molecularly imprinted sol-gel is reported for selective and sensitive electrochemical determination of the drug naloxone (NLX). The sensor was developed by combining molecular imprinting and sol-gel techniques and electrochemically grafting the sol solution onto a functionalized multiwall carbon nanotube modified indium-tin oxide (ITO) electrode. The sol-gel layer was obtained from acid catalyzed hydrolysis and condensation of a solution composed of triethoxyphenylsilane (TEPS) and tetraethoxysilane (TES). The fabrication, structure and properties of the sensing material were characterized via scanning electron microscopy, spectroscopy and electrochemical techniques. Parameters affecting the sensor’s performance were evaluated and optimized. A sensor fabricated under the optimized conditions responded linearly between 0.0 µM and 12 µM NLX, with a detection limit of 0.02 µM. The sensor also showed good run-to-run repeatability and batch-to-batch performance reproducibility with relative standard deviations (RSD) of 2.5–7.8% (n = 3) and 9.2% (n = 4), respectively. The developed sensor displayed excellent selectivity towards NLX compared to structurally similar compounds (codeine, fentanyl, naltrexone and noroxymorphone), and was successfully used to measure NLX in synthetic urine samples yielding recoveries greater than 88%.
Fructo-Oligosaccharides and Pectins Enhance Beneficial Effects of Raspberry Polyphenols in Rats with Nonalcoholic Fatty Liver
Authors: Fotschki Bartosz , Juśkiewicz Jerzy , Jurgoński Adam , Sójka Michał
Published: March 2021

In recent years, nonalcoholic fatty liver disorders have become one of the most common liver pathologies; therefore, it is necessary to investigate the dietary compounds that may support the regulation of liver metabolism and related inflammatory processes. The present study examines the effect of raspberry polyphenolic extract (RE) combined with fructo-oligosaccharides (FOSs) or pectins (PECs) on caecal microbial fermentation, liver lipid metabolism and inflammation in rats with fatty liver induced by an obesogenic diet. The combination of RE with FOSs or PECs reduced the production of short-chain fatty acids in the caecum. RE combined with FOSs exerted the most favourable effects on liver lipid metabolism by decreasing liver fat, cholesterol, triglyceride content and hepatic steatosis. RE and FOSs reduced lobular and portal inflammatory cell infiltration and IL-6 plasma levels. These effects might be related to a decrease in the hepatic expressions of PPARγ and ANGPTL4. In conclusion, PECs and FOSs enhanced the effects of RE against disorders related to nonalcoholic fatty liver; however, the most effective dietary treatment in the regulation of liver lipid metabolism and inflammation caused by an obesogenic diet was the combination of RE with FOSs.
Effectiveness of Oral Nutritional Supplements on Older People with Anorexia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Li Mengqi , Zhao Si , Wu Shuang , Yang Xiufen , Feng Hui
Published: March 2021

Background: Nutrition plays an important role in maintaining the overall health of older people. Inadequate intake may lead to impaired body function, higher morbidity, and mortality. Oral nutritional supplements (ONS) showed positive effect on the nutritional status of the elderly; however, systematic evidence is currently lacking on the effect of ONS on the elderly with anorexia. Aims: The current systematic review and meta-analysis included randomized controlled trial (RCT) articles to investigate the effectiveness of ONS on the main aspects of anorexia of aging (AA). Methods: By using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method, researchers independently searched PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and other gray literature resources for publications that met the inclusion criteria by October 2020. The Cochrane Risk of Bias Tools were used for quality assessment. The inverse-variance method was used for the fixed model (FM) while the DerSimonian–Laird method was used for the random model (RM). Respective 95% confidence intervals (95% CIs), mean difference (MD) or standardized mean difference (SMD) was used for indices in terms of effect size (ES). Results: 2497 records were found through the systematic search, while 17 RCTs (n = 1204) were included, with a mean age of 81.9 years (range: 74–87 years). Supplementation occurred in the morning, mid-day, and evening, while the times varied from one to three times a day. The results of meta-analysis showed that, generally, ONS had a positive effect on the overall appetite, MD = 0.18, 95% CI (0.03, 0.33), p = 0.02, and consumption, MD = 1.43, 95% CI (0.01, 2.86), p = 0.05; but not significant in terms of other aspects of appetite: hunger, p = 0.73; fullness, p = 0.60; desire to eat, p = 0.80; preoccupation, p = 0.15. Additionally, it showed an increase in the overall energy intake, SMD = 0.46, 95% CI (0.29, 0.63), p < 0.001, in protein intake, SMD = 0.59, 95% CI (0.16, 1.02), p = 0.007, and in fat intake, MD = 3.47, 95% CI (1.98, 4.97), p < 0.001, while no positive effect was found on carbohydrates intake, p = 0.06. Significance differences were also found in the body weight, SMD = 0.53, 95% CI (0.41, 0.65), p < 0.001, and body mass index (BMI), MD = 0.53, 95% CI (0.12, 0.95), p = 0.01. Moreover, subgroup analyses were conducted according to the nutrient density with no positive results showed except for the low-density ONS on overall energy intake. Conclusions: The results of the present study indicated that ONS had beneficial effects on overall appetite, energy intake, body weight and BMI.