Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro Model to Investigate Communication between Dorsal Root Ganglion and Spinal Cord Glia

Chronic discogenic back pain is associated with increased inflammatory cytokine levels that can influence the proximal peripheral nervous system, namely the dorsal root ganglion (DRG). However, transition to chronic pain is widely thought to involve glial activation in the spinal cord. In this study, an in vitro model was used to evaluate the communication between DRG and spinal cord glia. Primary neonatal rat DRG cells were treated with/without inflammatory cytokines (TNF-α, IL-1β, and IL-6). The conditioned media were collected at two time points (12 and 24 h) and applied to spinal cord mixed glial culture (MGC) for 24 h. Adult bovine DRG and spinal cord cell cultures were also tested, as an alternative large animal model, and results were compared with the neonatal rat findings. Compared with untreated DRG-conditioned medium, the second cytokine-treated DRG-conditioned medium (following medium change, thus containing solely DRG-derived molecules) elevated CD11b expression and calcium signal in neonatal rat microglia and enhanced Iba1 expression in adult bovine microglia. Cytokine treatment induced a DRG-mediated microgliosis. The described in vitro model allows the use of cells from large species and may represent an alternative to animal pain models (3R principles).
Novel Approach Combining Transcriptional and Evolutionary Signatures to Identify New Multiciliation Genes

Multiciliogenesis is a complex process that allows the generation of hundreds of motile cilia on the surface of specialized cells, to create fluid flow across epithelial surfaces. Dysfunction of human multiciliated cells is associated with diseases of the brain, airway and reproductive tracts. Despite recent efforts to characterize the transcriptional events responsible for the differentiation of multiciliated cells, a lot of actors remain to be identified. In this work, we capitalize on the ever-growing quantity of high-throughput data to search for new candidate genes involved in multiciliation. After performing a large-scale screening using 10 transcriptomics datasets dedicated to multiciliation, we established a specific evolutionary signature involving Otomorpha fish to use as a criterion to select the most likely targets. Combining both approaches highlighted a list of 114 potential multiciliated candidates. We characterized these genes first by generating protein interaction networks, which showed various clusters of ciliated and multiciliated genes, and then by computing phylogenetic profiles. In the end, we selected 11 poorly characterized genes that seem like particularly promising multiciliated candidates. By combining functional and comparative genomics methods, we developed a novel type of approach to study biological processes and identify new promising candidates linked to that process.
Nutritional Composition and Health Benefits of Various Botanical Types of Melon (Cucumis melo L.)

Characterizing the diverse melon cultivars for nutrition aids in crop improvement and promoting a healthy diet. Here, we used in vitro assays to characterize the nutritional qualities and health-beneficial effects of 30 melon (Cucumis melo L.) genotypes, including 10 improved cultivars, 16 landraces, and 4 wild types collected from different parts of India. Two landraces (Sidoota and Alper Green) had the highest (12.20 and 11.25) total soluble solids (TSS) contents. The Sidoota and Pappusa landraces had high reducing sugar contents (2.84 and 2.81 mg g−1 fresh weight [FW]). The highest polyphenols contents (22.0 mg g−1 FW) were observed in the landraces Mage Kaayi-2, Budamekaayi, and Small Melon. Reflecting on the primary and secondary metabolite contents, the Mekke Kaayi and Giriyala landraces exhibited high 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (97.6 and 91% at 100 μg mL−1). Additionally, seven of the landraces showed significant nitric oxide (NO) induction activity (>80% inhibition at 200 μg mL−1), indicating their potential health benefits, and seven showed considerable angiotensin-converting enzyme (ACE) inhibition activity (highest in Kashi Madhu), indicating their potential usefulness in reducing hypertension. Genotypes with high health beneficial compounds identified in this study can be used for breeding improved melon cultivars to promote these fruits as well as a healthy diet.
Design of a Single-Material Complex Structure Anthropomorphic Robotic Hand

In the field of robotic hand design, soft body and anthropomorphic design are two trends with a promising future. Designing soft body anthropomorphic robotic hands with human-like grasping ability, but with a simple and reliable structure, is a challenge that still has not been not fully solved. In this paper, we present an anatomically correct robotic hand 3D model that aims to realize the human hand’s functionality using a single type of 3D-printable material. Our robotic hand 3D model is combined with bones, ligaments, tendons, pulley systems, and tissue. We also describe the fabrication method to rapidly produce our robotic hand in 3D printing, wherein all parts are made by elastic 50 A (shore durometer) resin. In the experimental section, we show that our robotic hand has a similar motion range to a human hand with substantial grasping strength and compare it with the latest other designs of anthropomorphic robotic hands. Our new design greatly reduces the fabrication cost and assembly time. Compared with other robotic hand designs, we think our robotic hand may induce a new approach to the design and production of robotic hands as well as other related mechanical structures.
Functions of SMC2 in the Development of Zebrafish Liver

SMC2 (structural maintenance of chromosomes 2) is the core subunit of condensins, which play a central role in chromosome organization and segregation. However, the functions of SMC2 in embryonic development remain poorly understood, due to the embryonic lethality of homozygous SMC2−/− mice. Herein, we explored the roles of SMC2 in the liver development of zebrafish. The depletion of SMC2, with the CRISPR/Cas9-dependent gene knockout approach, led to a small liver phenotype. The specification of hepatoblasts was unaffected. Mechanistically, extensive apoptosis occurred in the liver of SMC2 mutants, which was mainly associated with the activation of the p53-dependent apoptotic pathway. Moreover, an aberrant activation of a series of apoptotic pathways in SMC2 mutants was involved in the defective chromosome segregation and subsequent DNA damage. Therefore, our findings demonstrate that SMC2 is necessary for zebrafish liver development.
Advanced Bioelectrical Signal Processing Methods: Past, Present, and Future Approach—Part III: Other Biosignals

Analysis of biomedical signals is a very challenging task involving implementation of various advanced signal processing methods. This area is rapidly developing. This paper is a Part III paper, where the most popular and efficient digital signal processing methods are presented. This paper covers the following bioelectrical signals and their processing methods: electromyography (EMG), electroneurography (ENG), electrogastrography (EGG), electrooculography (EOG), electroretinography (ERG), and electrohysterography (EHG).
Validation of an Index for Functionally Important Respiratory Symptoms among Adults in the Nationally Representative Population Assessment of Tobacco and Health Study, 2014–2016

The purpose of this study is to validate the seven-item wheezing module from the International Study of Asthma and Allergies in Children (ISAAC) in the nationally representative Population Assessment of Tobacco and Health Study. Adult participants with complete Wave 2–3 data were selected, including those with asthma but excluding those with COPD and other respiratory diseases (n = 16,295). We created a nine-point respiratory symptom index from the ISAAC questions, assessed the reliability of the index, and examined associations with self-reported asthma diagnosis. Threshold values were assessed for association with functional outcomes. The weighted prevalence for one or more respiratory symptom was 18.0% (SE = 0.5) for adults without asthma, 70.1% (SE = 1.3) for those with lifetime asthma, 75.7% (SE = 3.7) for adults with past-year asthma not on medications, and 92.6% (SE = 1.6) for those on medications. Cronbach’s alpha for the respiratory symptom index was 0.86. Index scores of ≥2 or ≥3 yielded functionally important respiratory symptom prevalence of 7–10%, adequate sensitivity and specificity for identifying asthma, and consistent independent associations with all functional outcomes and tobacco use variables. Respiratory symptom index scores of ≥2 or ≥3 are indicative of functionally important respiratory symptoms and could be used to assess the relationship between tobacco use and respiratory health.
Beyond Activation: Characterizing Microglial Functional Phenotypes

Classically, the following three morphological states of microglia have been defined: ramified, amoeboid and phagocytic. While ramified cells were long regarded as “resting”, amoeboid and phagocytic microglia were viewed as “activated”. In aged human brains, a fourth, morphologically novel state has been described, i.e., dystrophic microglia, which are thought to be senescent cells. Since microglia are not replenished by blood-borne mononuclear cells under physiological circumstances, they seem to have an “expiration date” limiting their capacity to phagocytose and support neurons. Identifying factors that drive microglial aging may thus be helpful to delay the onset of neurodegenerative diseases, such as Alzheimer’s disease (AD). Recent progress in single-cell deep sequencing methods allowed for more refined differentiation and revealed regional-, age- and sex-dependent differences of the microglial population, and a growing number of studies demonstrate various expression profiles defining microglial subpopulations. Given the heterogeneity of pathologic states in the central nervous system, the need for accurately describing microglial morphology and expression patterns becomes increasingly important. Here, we review commonly used microglial markers and their fluctuations in expression in health and disease, with a focus on IBA1 low/negative microglia, which can be found in individuals with liver disease.
The Transporter-Mediated Cellular Uptake and Efflux of Pharmaceutical Drugs and Biotechnology Products: How and Why Phospholipid Bilayer Transport Is Negligible in Real Biomembranes

Over the years, my colleagues and I have come to realise that the likelihood of pharmaceutical drugs being able to diffuse through whatever unhindered phospholipid bilayer may exist in intact biological membranes in vivo is vanishingly low. This is because (i) most real biomembranes are mostly protein, not lipid, (ii) unlike purely lipid bilayers that can form transient aqueous channels, the high concentrations of proteins serve to stop such activity, (iii) natural evolution long ago selected against transport methods that just let any undesirable products enter a cell, (iv) transporters have now been identified for all kinds of molecules (even water) that were once thought not to require them, (v) many experiments show a massive variation in the uptake of drugs between different cells, tissues, and organisms, that cannot be explained if lipid bilayer transport is significant or if efflux were the only differentiator, and (vi) many experiments that manipulate the expression level of individual transporters as an independent variable demonstrate their role in drug and nutrient uptake (including in cytotoxicity or adverse drug reactions). This makes such transporters valuable both as a means of targeting drugs (not least anti-infectives) to selected cells or tissues and also as drug targets. The same considerations apply to the exploitation of substrate uptake and product efflux transporters in biotechnology. We are also beginning to recognise that transporters are more promiscuous, and antiporter activity is much more widespread, than had been realised, and that such processes are adaptive (i.e., were selected by natural evolution). The purpose of the present review is to summarise the above, and to rehearse and update readers on recent developments. These developments lead us to retain and indeed to strengthen our contention that for transmembrane pharmaceutical drug transport “phospholipid bilayer transport is negligible”.
A Simple Synthesis Route for Selectively Methylated β-Cyclodextrin Using a Copper Complex Sandwich Protecting Strategy

This communication reports a novel synthesis route for the preparation of monofunctionalized β-cyclodextrin in a single stage. The approach involves only the in-situ protection of secondary hydroxyl groups as an excellent alternative to the classical procedure involving a series of five steps of protection and deprotection of hydroxyl groups (both primary and secondary ones) belonging to β-cyclodextrin.
PEG Coated Fe3O4/RGO Nano-Cube-Like Structures for Cancer Therapy via Magnetic Hyperthermia

Superparamagnetic iron oxide nanoparticles (SPIONs) have high saturation magnetization and are promising candidates for hyperthermia. They may act as magnetic heating agents when subjected to magnetic field in nano-based hyperthermia. In this work, cube-like Fe3O4 nanoparticles (labelled as cubic SPIONs) with reduced graphene oxide (RGO) nanocomposites were prepared by a microwave hydrothermal method. The shape and size of magnetic nanoparticles were controlled by varying synthesis parameters, including reaction time, pressure and microwave power. This study successfully synthesized cubic SPIONs nanocomposites with an average particle size between 24–34 nm. Poly-(ethylene) glycol (PEG) was used as a coating material on SPIONs to enhance biocompatibility. The RGO sheets provided a high surface area-to-volume ratio for SPIONs to be dispersed on their surface, and hence, they prevented aggregation of the SPIONs in the nanocomposites. Magnetically induced heating studies on the optimized nanocomposite (Fe3O4/RGO/PEG) demonstrated heating capabilities for magnetic hyperthermia application with a promising specific absorption rate (SAR) value of 58.33 W/g in acidic solution. Cytotoxicity tests were also performed to ensure low nanoparticle toxicity before incorporation into the human body. The results of the standard assay for the toxicity determination of the nanocomposites revealed over 70% cell survival after 48 h, suggesting the feasibility of using the synthesized nanocomposites for magnetic hyperthermia.
Reinitiation and Subsequent Discontinuation of Antiplatelet Treatment in Nonpersistent Older Patients with Peripheral Arterial Disease

The successful treatment of peripheral arterial disease (PAD) depends on adequate adherence to medications including antiplatelet agents. The aims of this study were (a) to identify the proportion of nonpersistent patients who reinitiated antiplatelet therapy and how many of them discontinued therapy after reinitiation, and (b) to identify patient- and medication-related characteristics associated with the likelihood of reinitiation and discontinuation among reinitiators. The analysis of reinitiation was conducted on 3032 nonpersistent users of antiplatelet agents aged ≥65 years, with PAD newly diagnosed in 2012. Discontinuation (i.e., a treatment gap of ≥6 months without antiplatelet medication prescription) was analysed in 2006 reinitiating patients. To identify factors associated with the likelihood of reinitiation and discontinuation, Cox regression with time-dependent covariates was used. Reinitiation was recorded in 2006 (66.2%) of 3032 patients who had discontinued antiplatelet medication. Among these 2006 reinitiators, 1078 (53.7%) patients discontinued antiplatelet therapy again. Ischemic stroke and myocardial infarction during nonpersistence and bronchial asthma/chronic obstructive pulmonary disease were associated with an increased likelihood of reinitiation. University education was associated with discontinuation among reinitiators. Factors associated with the probability of reinitiation and discontinuation in reinitiators make it possible to identify older PAD patients in whom “stop-starting” behaviour may be expected.
Serum Albumin: A Multifaced Enzyme

Human serum albumin (HSA) is the most abundant protein in plasma, contributing actively to oncotic pressure maintenance and fluid distribution between body compartments. HSA acts as the main carrier of fatty acids, recognizes metal ions, affects pharmacokinetics of many drugs, provides the metabolic modification of some ligands, renders potential toxins harmless, accounts for most of the anti-oxidant capacity of human plasma, and displays esterase, enolase, glucuronidase, and peroxidase (pseudo)-enzymatic activities. HSA-based catalysis is physiologically relevant, affecting the metabolism of endogenous and exogenous compounds including proteins, lipids, cholesterol, reactive oxygen species (ROS), and drugs. Catalytic properties of HSA are modulated by allosteric effectors, competitive inhibitors, chemical modifications, pathological conditions, and aging. HSA displays anti-oxidant properties and is critical for plasma detoxification from toxic agents and for pro-drugs activation. The enzymatic properties of HSA can be also exploited by chemical industries as a scaffold to produce libraries of catalysts with improved proficiency and stereoselectivity for water decontamination from poisonous agents and environmental contaminants, in the so called “green chemistry” field. Here, an overview of the intrinsic and metal dependent (pseudo-)enzymatic properties of HSA is reported to highlight the roles played by this multifaced protein.
Transcriptomic Analysis of the Differential Nephrotoxicity of Diverse Brominated Flame Retardants in Rat and Human Renal Cells

Brominated flame retardants (BFRs) are environmentally persistent, are detected in humans, and some have been banned due to their potential toxicity. BFRs are developmental neurotoxicants and endocrine disruptors; however, few studies have explored their potential nephrotoxicity. We addressed this gap in the literature by determining the toxicity of three different BFRs (tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD), and tetrabromodiphenyl ether (BDE-47)) in rat (NRK 52E) and human (HK-2 and RPTEC) tubular epithelial cells. All compounds induced time- and concentration-dependent toxicity based on decreases in MTT staining and changes in cell and nuclear morphology. The toxicity of BFRs was chemical- and cell-dependent, and human cells were more susceptible to all three BFRs based on IC50s after 48 h exposure. BFRs also had chemical- and cell-dependent effects on apoptosis as measured by increases in annexin V and PI staining. The molecular mechanisms mediating this toxicity were investigated using RNA sequencing. Principal components analysis supported the hypothesis that BFRs induce different transcriptional changes in rat and human cells. Furthermore, BFRs only shared nine differentially expressed genes in rat cells and five in human cells. Gene set enrichment analysis demonstrated chemical- and cell-dependent effects; however, some commonalities were also observed. Namely, gene sets associated with extracellular matrix turnover, the coagulation cascade, and the SNS-related adrenal cortex response were enriched across all cell lines and BFR treatments. Taken together, these data support the hypothesis that BFRs induce differential toxicity in rat and human renal cell lines that is mediated by differential changes in gene expression.
Comparison of Nutritional and Nutraceutical Properties of Burdock Roots Cultivated in Fengxian and Peixian of China

This study aimed to analyze and compare the nutritional quality of powders of burdock root from Fengxian (FX) and Peixian (PX) in China. The nutrient composition including carbohydrates, protein, amino acids, vitamin C, carotenoids, as well as total phenols, total flavonoids and phenolic compounds were investigated in addition to in vitro antioxidant capacity. The results showed that the basic nutrients of burdock root powder (BRP) in both locations did not have significant differences (p > 0.05), although the in vitro antioxidant capacity of BRP of Fengxian (F-BRP) was greater than that of PX (p < 0.05). The burdock root peel powder (BRPP) possessed more phenolics and stronger in vitro antioxidant capacity than the burdock root powder (BRP) and peeled burdock root powder (PBRP) (p < 0.05). Moreover, better quality burdock root was obtained from FX. F-BRP was consequently analyzed by ultra-performance liquid chromatography tandem mass spectrometry for its phenolic composition. Seventeen phenolics, mainly caffeoylquinic acids, were detected. In addition, a total of 181 volatile compounds belonging to eight types were detected including alcohols, aldehydes, ketones, alkenes, esters, acids, linear or aromatic hydrocarbons, and others. The diverse compounds found in this study can provide a theoretical basis for the development and utilization of burdock in the food industry.
A Feasibility and Efficacy Randomized Controlled Trial of Two Exercise Programs in Severe AECOPD Patients with Resting Hypoxemia

Resting hypoxemia is the most severe stage of Chronic Obstructive Pulmonary Disease (COPD). Due to their impairments during the exacerbation, these patients are limited to traditional exercise rehabilitation and are excluded from the majority of the studies. The aim of this study was to assess the feasibility and the efficacy of two exercise programs in Acute Exacerbation of COPD (AECOPD) patients with resting hypoxemia. In this randomized clinical trial, patients hospitalized due to an acute exacerbation of COPD with hypoxemia at rest were included. Patients were randomly assigned into three groups. A Control Group (pharmacological treatment), a Global Exercise Group (GEG), and a Functional Electrostimulation Group (FEG). Patients were treated during the hospitalization period. The main outcomes were lower limb strength (assessed by a dynamometer), balance (assessed by the one leg standing balance test), health related quality of life (assessed by the EQ-5D), adverse events and adherence. At the end of the intervention, there were significant differences in all the variables in favour of the experimental groups (p < 0.05). We concluded that conducting an exercise program is feasible and improves lower limb strength, balance, and health related quality of life in AECOPD patients with resting hypoxemia.
Fault Detection of Wind Turbine Electric Pitch System Based on IGWO-ERF

It is difficult to optimize the fault model parameters when Extreme Random Forest is used to detect the electric pitch system fault model of the double-fed wind turbine generator set. Therefore, Extreme Random Forest which was optimized by improved grey wolf algorithm (IGWO-ERF) was proposed to solve the problems mentioned above. First, IGWO-ERF imports the Cosine model to nonlinearize the linearly changing convergence factor α to balance the global exploration and local exploitation capabilities of the algorithm. Then, in the later stage of the algorithm iteration, α wolf generates its mirror wolf based on the lens imaging learning strategy to increase the diversity of the population and prevent local optimum of the population. The electric pitch system fault detection method of the wind turbine generator set sets the generator power of the variable pitch system as the main state parameter. First, it uses the Pearson correlation coefficient method to eliminate the features with low correlation with the electric pitch system generator power. Then, the remaining features are ranked by the importance of the RF features. Finally, the top N features are selected to construct the electric pitch system fault data set. The data set is divided into a training set and a test set. The training set is used to train the proposed fault detection model, and the test set is used for testing. Compared with other parameter optimization algorithms, the proposed method has lower FNR and FPR in the electric pitch system fault detection of the wind turbine generator set.