Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness of Albumin-Fused Thioredoxin against 6-Hydroxydopamine-Induced Neurotoxicity In Vitro

Parkinson’s disease (PD) is a neurodegenerative disorder caused by oxidative stress-dependent loss of dopaminergic neurons in the substantia nigra and elevated microglial inflammatory responses. Recent studies show that cell loss also occurs in the hypothalamus in PD. However, effective treatments for the disorder are lacking. Thioredoxin is the major protein disulfide reductase in vivo. We previously synthesized an albumin–thioredoxin fusion protein (Alb–Trx), which has a longer plasma half-life than thioredoxin, and reported its effectiveness in the treatment of respiratory and renal diseases. Moreover, we reported that the fusion protein inhibits trace metal-dependent cell death in cerebrovascular dementia. Here, we investigated the effectiveness of Alb–Trx against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro. Alb–Trx significantly inhibited 6-OHDA-induced neuronal cell death and the integrated stress response. Alb–Trx also markedly inhibited 6-OHDA-induced reactive oxygen species (ROS) production, at a concentration similar to that inhibiting cell death. Exposure to 6-OHDA perturbed the mitogen-activated protein kinase pathway, with increased phosphorylated Jun N-terminal kinase and decreased phosphorylated extracellular signal-regulated kinase levels. Alb–Trx pretreatment ameliorated these changes. Furthermore, Alb–Trx suppressed 6-OHDA-induced neuroinflammatory responses by inhibiting NF-κB activation. These findings suggest that Alb–Trx reduces neuronal cell death and neuroinflammatory responses by ameliorating ROS-mediated disruptions in intracellular signaling pathways. Thus, Alb–Trx may have potential as a novel therapeutic agent for PD.
Nonlinear Dynamic Response of Nanocomposite Microbeams Array for Multiple Mass Sensing

A nonlinear MEMS multimass sensor is numerically investigated, designed as a single input-single output (SISO) system consisting of an array of nonlinear microcantilevers clamped to a shuttle mass which, in turn, is constrained by a linear spring and a dashpot. The microcantilevers are made of a nanostructured material, a polymeric hosting matrix reinforced by aligned carbon nanotubes (CNT). The linear as well as the nonlinear detection capabilities of the device are explored by computing the shifts of the frequency response peaks caused by the mass deposition onto one or more microcantilever tips. The frequency response curves of the device are obtained by a pathfollowing algorithm applied to the reduced-order model of the system. The microcantilevers are described by a nonlinear Euler-Bernoulli inextensible beam theory, which is enriched by a meso-scale constitutive law of the nanocomposite. In particular, the microcantilever constitutive law depends on the CNT volume fraction suitably used for each cantilever to tune the frequency bandwidth of the whole device. Through an extensive numerical campaign, the mass sensor sensitivity estimated in the linear and nonlinear dynamic range shows that, for relatively large displacements, the accuracy of the added mass detectability can be improved due to the larger nonlinear frequency shifts at resonance (up to 12%).
Elaboration of the Effective Multi-Target Therapeutic Platform for the Treatment of Alzheimer’s Disease Based on Novel Monoterpene-Derived Hydroxamic Acids

Novel monoterpene-based hydroxamic acids of two structural types were synthesized for the first time. The first type consisted of compounds with a hydroxamate group directly bound to acyclic, monocyclic and bicyclic monoterpene scaffolds. The second type included hydroxamic acids connected with the monoterpene moiety through aliphatic (hexa/heptamethylene) or aromatic linkers. An in vitro analysis of biological activity demonstrated that some of these molecules had powerful HDAC6 inhibitory activity, with the presence of a linker area in the structure of compounds playing a key role. In particular, it was found that hydroxamic acids containing a hexa- and heptamethylene linker and (-)-perill fragment in the Cap group exhibit excellent inhibitory activity against HDAC6 with IC50 in the submicromolar range from 0.56 ± 0.01 µM to 0.74 ± 0.02 µM. The results of the study of antiradical activity demonstrated the presence of moderate ability for some hydroxamic acids to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2ROO• radicals. The correlation coefficient between the DPPH radical scavenging activity and oxygen radical absorbance capacity (ORAC) value was R2 = 0.8400. In addition, compounds with an aromatic linker based on para-substituted cinnamic acids, having a monocyclic para-menthene skeleton as a Cap group, 35a, 38a, 35b and 38b, demonstrated a significant ability to suppress the aggregation of the pathological β-amyloid peptide 1-42. The 35a lead compound with a promising profile of biological activity, discovered in the in vitro experiments, demonstrated neuroprotective effects on in vivo models of Alzheimer’s disease using 5xFAD transgenic mice. Together, the results obtained demonstrate a potential strategy for the use of monoterpene-derived hydroxamic acids for treatment of various aspects of Alzheimer’s disease.
Zooming into Gut Dysbiosis in Parkinson’s Disease: New Insights from Functional Mapping

Gut dysbiosis has been involved in the pathogenesis and progression of Parkinson’s disease (PD), but the mechanisms through which gut microbiota (GM) exerts its influences deserve further study. Recently, we proposed a two-hit mouse model of PD in which ceftriaxone (CFX)-induced dysbiosis amplifies the neurodegenerative phenotype generated by striatal 6-hydroxydopamine (6-OHDA) injection in mice. Low GM diversity and the depletion of key gut colonizers and butyrate producers were the main signatures of GM alteration in this model. Here, we used the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) to unravel candidate pathways of cell-to-cell communication associated with dual-hit mice and potentially involved in PD progression. We focused our analysis on short-chain fatty acids (SCFAs) metabolism and quorum sensing (QS) signaling. Based on linear discriminant analysis, combined with the effect size results, we found increased functions linked to pyruvate utilization and a depletion of acetate and butyrate production in 6-OHDA+CFX mice. The specific arrangement of QS signaling as a possible result of the disrupted GM structure was also observed. With this exploratory study, we suggested a scenario in which SCFAs metabolism and QS signaling might represent the effectors of gut dysbiosis potentially involved in the designation of the functional outcomes that contribute to the exacerbation of the neurodegenerative phenotype in the dual-hit animal model of PD.
Estudios de exactitud diagnóstica: Herramientas para su Interpretación

Abstract: The aim of this paper is to provide basic tools for the interpretation of diagnostic accuracy stu-dies, by analyzing the data that the contingency table provides. Concepts are given in the application and meaning of sensitivity, specificity, positive and negative predictive values. Furthermore, by analyzing the pre-test and post-test probabilities, construction and implementation of the likelihood ratio are explained. The diagnostic odds ratio and its limitations are described. Finally, the importance of calculating confidence intervals is explained. Understanding the contingency table and the construction of the parameters that we can calculate from this, is essential for the critical evaluation and development of diagnostic accuracy studies, as well as their application in daily clinical work.Keywords (MeSH): Biostatistics, Diagnostic, Diagnostic accuracy, Likelihood ratio, Predictive value, Sen -sibility, Specificity. Resumen: El objetivo del presente articulo es entregar herramientas basicas para la interpretacion de los estudios de exactitud diagnostica, mediante el analisis de los datos que entrega la tabla de contingencia. Se entregan conceptos en la aplicacion y significado de sensibilidad, especificidad, valores predictivos positivo y negativo. Ademas, mediante el analisis de las probabilidades pre-test y post-test, se explica la construccion e implementacion de los likelihood ratio o razones de verosimilitud. Se describe el odds ratio diagnostico y sus limitaciones. Por ultimo, se explica la importancia del calculo de intervalos de confianza.Entender la tabla de contingencia y la construccion de los parametros que de esta podemos calcular es fundamental para la valoracion critica y desarrollo de estudios de exactitud diagnostica, asi como para su aplicacion en el quehacer clinico diario.Palabras clave (MeSH): Bioestadistica, Diagnostico, Especificidad, Exactitud diagnostica, Indice de pro-babilidad, Sensibilidad, Valores predictivos.
Antioxidant Activities of Essential Oils and Their Major Components in Scavenging Free Radicals, Inhibiting Lipid Oxidation and Reducing Cellular Oxidative Stress

Highlights What are the main findings? The essential oils from cinnamon, thyme, clove and their main components, eugenol and thymol, exhibited the highest antioxidant activity in the FOE and RBC systems. It was found that the antioxidant activity of essential oils was positively correlated to the content of eugenol and thymol. What is the implication of the main finding? Valuable evidence for the potential use of essential oils to improve human health was provided. Cinnamon, clove and thyme oils are expected to prevent fish oil oxidation. Abstract Antioxidant activities of five essential oils (cinnamon, thyme, clove, lavender and peppermint oils) and their major components (eugenol, thymol, linalool, and menthol) were evaluated on scavenging DPPH (2,2-diphenyl-1 picrylhydrazyl) free radicals, inhibiting polyunsaturated fatty acid oxidation in fish oil emulsion (FOE), and reducing oxidative stress in human red blood cells (RBC). The essential oils from cinnamon, thyme, clove and their main components, eugenol and thymol, exhibited the highest antioxidant activity in the FOE and RBC systems. It was found that the antioxidant activity of essential oils was positively correlated to the content of eugenol and thymol, while lavender and peppermint oils and their main components, linalool and menthol, had very low antioxidant activity. Compared with scavenging DPPH free radical activity, the antioxidant activity in FOE and RBC systems could better reflect the actual antioxidant potential of essential oil in preventing lipid oxidation and reducing oxidative stress in biological system.
Towards a More Efficient In and Ex Situ Conservation of Sri Lankan Wild Rice Species

Five species of wild Oryza (O. nivara, O. rufipogon, O. eichengeri, O. rhizomatis and O. granulata), including the endemic species O. rhizomatis, have been recorded in Sri Lanka. These species are facing continuous decline in their populations due to natural and anthropogenic processes, with habitat loss being the main threat. This study aimed to provide information on the distribution, the current status of ex situ and in situ conservation, and to identify high-priority species and sites of wild rice in Sri Lanka, in order to improve the effectiveness of conservation efforts. Occurrence records of Sri Lankan wild rice species were collected from literature, gene banks, and field surveys. The distribution of these species was mapped, and areas with high species richness were identified. A gap analysis was conducted to determine the high-priority areas and species for ex situ and in situ conservation. It was found that about 23% of the wild rice populations in Sri Lanka were within protected areas, and by expanding these protected areas by 1 km, an additional 22% of the populations located on the border of these areas could be effectively conserved. Our analysis also revealed that 62% of Sri Lankan wild rice populations were not represented in gene banks. The species-rich areas were found to be in only two districts (Polonnaruwa and Monaragala), and less than 50% of these areas were within protected areas. Based on these findings, O. rhizomatis, O. eichengeri, and O. rufipogon were identified as high-priority species for in situ conservation. Ex situ collections were also deemed necessary for O. granulata and O. rhizomatis to ensure diversity representation in gene banks.
Translation and Psychometric Properties of the Strategies Used by People to Promote a Health Instrument for the Assessment of Self-Care Self-Efficacy among Patients Undergoing Hemodialysis in Vietnam

Self-care and self-efficacy play an important role in predicting quality of life among patients undergoing hemodialysis, but there currently is a lack of an instrument in the Vietnamese language for assessing self-care and self-efficacy. This limits the ability of researchers to explore and determine the confidence patients have in their ability to perform relevant self-care activities. The purpose of this investigation was to assess the validity and reliability of the Strategies Used by People to Promote Health questionnaire-Vietnamese version. This cross-sectional study involved translation, validation, and cultural adaptation of the questionnaire into Vietnamese and a trial with 127 patients undergoing hemodialysis in Bach Mai Hospital (Hanoi, Vietnam). The questionnaire was translated by bilingual translators and validated by three experts. Internal consistency and confirmatory factor analysis were applied. This questionnaire demonstrated good content validity and a Cronbach’s alpha of 0.95 for the total scale. Confirmatory factor analysis of the three-factor model showed moderate model fit (comparative fit index = 0.84, Tucker–Lewis coefficient = 0.82, root mean square error of approximation = 0.09). Overall, this questionnaire exhibited acceptable validity and reliability for measuring self-care and self-efficacy among patients undergoing hemodialysis.
A Comprehensive Review of Pathological Mechanisms and Natural Dietary Ingredients for the Management and Prevention of Sarcopenia

Sarcopenia is characterized by an age-related loss of skeletal muscle mass and function and has been recognized as a clinical disease by the World Health Organization since 2016. Substantial evidence has suggested that dietary modification can be a feasible tool to combat sarcopenia. Among various natural dietary ingredients, the present study focused on botanical and marine extracts, phytochemicals, and probiotics. Aims of this review were (1) to provide basic concepts including the definition, diagnosis, prevalence, and adverse effects of sarcopenia, (2) to describe possible pathological mechanisms including protein homeostasis imbalance, inflammation, mitochondrial dysfunction, and satellite cells dysfunction, and (3) to analyze recent experimental studies reporting potential biological functions against sarcopenia. A recent literature review for dietary ingredients demonstrated that protein homeostasis is maintained via an increase in the PI3K/Akt pathway and/or a decrease in the ubiquitin–proteasome system. Regulation of inflammation has primarily targeted inhibition of NF-κB signaling. Elevated Pgc-1α or Pax7 expression reverses mitochondrial or satellite cell dysfunction. This review provides the current knowledge on dietary components with the potential to assist sarcopenia prevention and/or treatment. Further in-depth studies are required to elucidate the role of and develop various dietary materials for healthier aging, particularly concerning muscle health.
A Note on "Level Schedules for Mixed-Model Assembly Lines in Just-in-Time Production Systems"

This note formulates an assignment problem for obtaining optimal level schedules for mixed-model assembly lines in JIT production systems. The problem was formulated as a quadratic integer programming problem in a recent paper by Miltenburg 1989 where, however, only enumerative algorithms and heuristics were proposed for its solution. Our assignment formulation can also be extended to more general objective functions than the one used by Miltenburg.
Disruption of everyday life in times of crises – explanatory factors of well-being among students during COVID-19

This article examines explanatory factors behind well-being among Danish students during the COVID-19 crisis. The empirical analyses are based on a two round panel survey among students at Roskilde University in Denmark. Using fixed effect regression and random effect regression our results show that, amongst the variables included in the analysis, the level of self-assessed structure in everyday life has the strongest positive effect on the self-assessed level of well-being. We briefly discuss this finding which is supported by qualitative data from the survey. The article concludes that the major changes in everyday life, caused by the COVID-19 crisis and societal lockdown, for example, isolation, virtual classes etc., makes it more difficult to draw upon internalized habits and navigate socially, which may contribute negatively to well-being. Conceptually, the article calls for a deeper engagement with the role of everyday life structure and its effects on well-being at a more general level.
Feature Tracking on the Unit Sphere

Abstract Techniques used in a previous study of the objective identification and tracking of meteorological features in model data are extended to the unit sphere. An alternative feature detection scheme is described based on cubic interpolation for the sphere and local maximization. The extension of the tracking technique, used in the previous study, to the unit sphere is described. An example of the application of these techniques to a global relative vorticity field from a model integration are presented and discussed.
The Effect of Polymeric Nanofibers Used for 3D-Printed Scaffolds on Cellular Activity in Tissue Engineering: A Review

Promising scaffolds for developing advanced tissue engineering architectures have emerged in recent years through the use of nanofibers and 3D printing technologies. Despite this, structural integrity and cell proliferation are highlighted as fundamental challenges for design scaffolds and future prospects. As a biomimetic scaffold, the nanofiber-reinforced hydrogels demonstrated a better compressive modulus and cell growth. Our review focuses on recent promising advances in the development of 3D-printed hydrogels containing polymeric nanofibers that can improve cell-material interaction in biomedical applications. Moreover, an effort has been made to induce studies with diverse types of scaffolds for various cells. Additionally, we discuss the challenges and future prospects of 3D-bioprinted reinforced hydrogels with nanofibers in the medical field, as well as high-performance bioinks.
Structural and Spectroscopic Study of New Copper(II) and Zinc(II) Complexes of Coumarin Oxyacetate Ligands and Determination of Their Antimicrobial Activity

Tackling antimicrobial resistance is of increasing concern in a post-pandemic world where overuse of antibiotics has increased the threat of another pandemic caused by antimicrobial-resistant pathogens. Derivatives of coumarins, a naturally occurring bioactive compound, and its metal complexes have proven therapeutic potential as antimicrobial agents and in this study a series of copper(II) and zinc(II) complexes of coumarin oxyacetate ligands were synthesised and characterised by spectroscopic techniques (IR, 1H, 13C NMR, UV-Vis) and by X-ray crystallography for two of the zinc complexes. The experimental spectroscopic data were then interpreted on the basis of molecular structure modelling and subsequent spectra simulation using the density functional theory method to identify the coordination mode in solution for the metal ions in the complexes. Interestingly, the solid-state coordination environment of the zinc complexes is in good agreement with the simulated solution state, which has not been the case in our previous studies of these ligands when coordinated to silver(I). Previous studies had indicated excellent antimicrobial activity for Ag(I) analogues of these ligands and related copper and zinc complexes of coumarin-derived ligands, but in this study none of the complexes displayed antimicrobial activity against the clinically relevant methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and Candida albicans.
Masitinib Inhibits Hepatitis A Virus Replication

The hepatitis A virus (HAV) infection causes acute hepatitis. HAV also induces acute liver failure or acute-on-chronic liver failure; however, no potent anti-HAV drugs are currently available in clinical situations. For anti-HAV drug screening, more convenient and useful models that mimic HAV replication are needed. In the present study, we established HuhT7-HAV/Luc cells, which are HuhT7 cells stably expressing the HAV HM175-18f genotype IB subgenomic replicon RNA harboring the firefly luciferase gene. This system was made by using a PiggyBac-based gene transfer system that introduces nonviral transposon DNA into mammalian cells. Then, we investigated whether 1134 US Food and Drug Administration (FDA)-approved drugs exhibited in vitro anti-HAV activity. We further demonstrated that treatment with tyrosine kinase inhibitor masitinib significantly reduced both HAV HM175-18f genotype IB replication and HAV HA11-1299 genotype IIIA replication. Masitinib also significantly inhibited HAV HM175 internal ribosomal entry-site (IRES) activity. In conclusion, HuhT7-HAV/Luc cells are adequate for anti-HAV drug screening, and masitinib may be useful for the treatment of severe HAV infection.
Wind Inhomogeneities in Wolf-Rayet Stars. III. Unusual Emission-Line Profile Variations in Velorum

We investigate the possibility that, in γ2 Vel, these broad variable subpeaks arise from the shock-cone region, at the interface where the wind from the WR star collides with that of its O companion. We find no convincing evidence to support this hypothesis, although we suspect that there could be a relation between the existence of broad LPV subpeaks and the presence of the more massive O companion.
A Self-Coordinating Controller with Balance-Guiding Ability for Lower-Limb Rehabilitation Exoskeleton Robot

The restricted posture and unrestricted compliance brought by the controller during human–exoskeleton interaction (HEI) can cause patients to lose balance or even fall. In this article, a self-coordinated velocity vector (SCVV) double-layer controller with balance-guiding ability was developed for a lower-limb rehabilitation exoskeleton robot (LLRER). In the outer loop, an adaptive trajectory generator that follows the gait cycle was devised to generate a harmonious hip–knee reference trajectory on the non-time-varying (NTV) phase space. In the inner loop, velocity control was adopted. By searching the minimum L2 norm between the reference phase trajectory and the current configuration, the desired velocity vectors in which encouraged and corrected effects can be self-coordinated according to the L2 norm were obtained. In addition, the controller was simulated using an electromechanical coupling model, and relevant experiments were carried out with a self-developed exoskeleton device. Both simulations and experiments validated the effectiveness of the controller.