Miracle-dz/UniFAR-FTUs huggingface dataset:
Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation

Phenolic compounds are thought to be important to prevent neurodegenerative diseases (ND). Parkinson’s Disease (PD) is a neurodegenerative disorder known for its typical motor features, the deposition of α-synuclein (αsyn)-positive inclusions in the brain, and for concomitant cellular pathologies that include oxidative stress and neuroinflammation. Neuroprotective activity of fisetin, a dietary flavonoid, was evaluated against main hallmarks of PD in relevant cellular models. At physiologically relevant concentrations, fisetin protected SH-SY5Y cells against oxidative stress overtaken by tert-butyl hydroperoxide (t-BHP) and against methyl-4-phenylpyridinuim (MPP+)-induced toxicity in dopaminergic neurons, the differentiated Lund human Mesencephalic (LUHMES) cells. In this cellular model, fisetin promotes the increase of the levels of dopamine transporter. Remarkably, fisetin reduced the percentage of cells containing αsyn inclusions as well as their size and subcellular localization in a yeast model of αsyn aggregation. Overall, our data show that fisetin exerts modulatory activities toward common cellular pathologies present in PD; remarkably, it modulates αsyn aggregation, supporting the idea that diets rich in this compound may prove beneficial.
Novel MRI-Based CAD System for Early Detection of Thyroid Cancer Using Multi-Input CNN

Early detection of thyroid nodules can greatly contribute to the prediction of cancer burdening and the steering of personalized management. We propose a novel multimodal MRI-based computer-aided diagnosis (CAD) system that differentiates malignant from benign thyroid nodules. The proposed CAD is based on a novel convolutional neural network (CNN)-based texture learning architecture. The main contribution of our system is three-fold. Firstly, our system is the first of its kind to combine T2-weighted MRI and apparent diffusion coefficient (ADC) maps using a CNN to model thyroid cancer. Secondly, it learns independent texture features for each input, giving it more advanced capabilities to simultaneously extract complex texture patterns from both modalities. Finally, the proposed system uses multiple channels for each input to combine multiple scans collected into the deep learning process using different values of the configurable diffusion gradient coefficient. Accordingly, the proposed system would enable the learning of more advanced radiomics with an additional advantage of visualizing the texture patterns after learning. We evaluated the proposed system using data collected from a cohort of 49 patients with pathologically proven thyroid nodules. The accuracy of the proposed system has also been compared against recent CNN models as well as multiple machine learning (ML) frameworks that use hand-crafted features. Our system achieved the highest performance among all compared methods with a diagnostic accuracy of 0.87, specificity of 0.97, and sensitivity of 0.69. The results suggest that texture features extracted using deep learning can contribute to the protocols of cancer diagnosis and treatment and can lead to the advancement of precision medicine.
Emerging Immunogenicity and Genotoxicity Considerations of Adeno-Associated Virus Vector Gene Therapy for Hemophilia

Adeno-associated viral (AAV) vector gene therapy has shown promise as a possible cure for hemophilia. However, immune responses directed against AAV vectors remain a hurdle to the broader use of this gene transfer platform. Both innate and adaptive immune responses can affect the safety and efficacy of AAV vector–mediated gene transfer in humans. These immune responses may be triggered by the viral capsid, the vector’s nucleic acid payload, or other vector contaminants or excipients, or by the transgene product encoded by the vector itself. Various preclinical and clinical strategies have been explored to overcome the issues of AAV vector immunogenicity and transgene-related immune responses. Although results of these strategies are encouraging, more efficient approaches are needed to deliver safe, predictable, and durable outcomes for people with hemophilia. In addition to durability, long-term follow-up of gene therapy trial participants will allow us to address potential safety concerns related to vector integration. Herein, we describe the challenges with current methodologies to deliver optimal outcomes for people with hemophilia who choose to undergo AAV vector gene therapy and the potential opportunities to improve on the results.
Deep UV Formation of Long-Term Stable Optical Bragg Gratings in Epoxy Waveguides and Their Biomedical Sensing Potentials

In this article, we summarize our investigations on optimized 248 nm deep ultraviolet (UV) fabrication of highly stable epoxy polymer Bragg grating sensors and their application for biomedical purposes. Employing m-line spectroscopy, deep UV photosensitivity of cross-linked EpoCore thin films in terms of responding refractive index change is determined to a maximum of Δn = + (1.8 ± 0.2) × 10−3. All-polymer waveguide Bragg gratings are fabricated by direct laser irradiation of lithographic EpoCore strip waveguides on compatible Topas 6017 substrates through standard +1/-1-order phase masks. According near-field simulations of realistic non-ideal phase masks provide insight into UV dose-dependent characteristics of the Bragg grating formation. By means of online monitoring, arising Bragg reflections during grating inscription via beforehand fiber-coupled waveguide samples, an optimum laser parameter set for well-detectable sensor reflection peaks in respect of peak strength, full width at half maximum and grating attenuation are derived. Promising blood analysis applications of optimized epoxy-based Bragg grating sensors are demonstrated in terms of bulk refractive index sensing of whole blood and selective surface refractive index sensing of human serum albumin.
Collagen–Alginate Composite Hydrogel: Application in Tissue Engineering and Biomedical Sciences

Alginate (ALG), a polysaccharide derived from brown seaweed, has been extensively investigated as a biomaterial not only in tissue engineering but also for numerous biomedical sciences owing to its wide availability, good compatibility, weak cytotoxicity, low cost, and ease of gelation. Nevertheless, alginate lacks cell-binding sites, limiting long-term cell survival and viability in 3D culture. Collagen (Col), a major component protein found in the extracellular matrix (ECM), exhibits excellent biocompatibility and weak immunogenicity. Furthermore, collagen contains cell-binding motifs, which facilitate cell attachment, interaction, and spreading, consequently maintaining cell viability and promoting cell proliferation. Recently, there has been a growing body of investigations into collagen-based hydrogel trying to overcome the poor mechanical properties of collagen. In particular, collagen–alginate composite (CAC) hydrogel has attracted much attention due to its excellent biocompatibility, gelling under mild conditions, low cytotoxicity, controllable mechanic properties, wider availability as well as ease of incorporation of other biomaterials and bioactive agents. This review aims to provide an overview of the properties of alginate and collagen. Moreover, the application of CAC hydrogel in tissue engineering and biomedical sciences is also discussed.
Minor Intron Splicing from Basic Science to Disease

Pre-mRNA splicing is an essential step in gene expression and is catalyzed by two machineries in eukaryotes: the major (U2 type) and minor (U12 type) spliceosomes. While the majority of introns in humans are U2 type, less than 0.4% are U12 type, also known as minor introns (mi-INTs), and require a specialized spliceosome composed of U11, U12, U4atac, U5, and U6atac snRNPs. The high evolutionary conservation and apparent splicing inefficiency of U12 introns have set them apart from their major counterparts and led to speculations on the purpose for their existence. However, recent studies challenged the simple concept of mi-INTs splicing inefficiency due to low abundance of their spliceosome and confirmed their regulatory role in alternative splicing, significantly impacting the expression of their host genes. Additionally, a growing list of minor spliceosome-associated diseases with tissue-specific pathologies affirmed the importance of minor splicing as a key regulatory pathway, which when deregulated could lead to tissue-specific pathologies due to specific alterations in the expression of some minor-intron-containing genes. Consequently, uncovering how mi-INTs splicing is regulated in a tissue-specific manner would allow for better understanding of disease pathogenesis and pave the way for novel therapies, which we highlight in this review.
Y2O3 Nanoparticles and X-ray Radiation-Induced Effects in Melanoma Cells

The innovative strategy of using nanoparticles in radiotherapy has become an exciting topic due to the possibility of simultaneously improving local efficiency of radiation in tumors and real-time monitoring of the delivered doses. Yttrium oxide (Y2O3) nanoparticles (NPs) are used in material science to prepare phosphors for various applications including X-ray induced photodynamic therapy and in situ nano-dosimetry, but few available reports only addressed the effect induced in cells by combined exposure to different doses of superficial X-ray radiation and nanoparticles. Herein, we analyzed changes induced in melanoma cells by exposure to different doses of X-ray radiation and various concentrations of Y2O3 NPs. By evaluation of cell mitochondrial activity and production of intracellular reactive oxygen species (ROS), we estimated that 2, 4, and 6 Gy X-ray radiation doses are visibly altering the cells by inducing ROS production with increasing the dose while at 6 Gy the mitochondrial activity is also affected. Separately, high-concentrated solutions of 25, 50, and 100 µg/mL Y2O3 NPs were also found to affect the cells by inducing ROS production with the increase of concentration. Additionally, the colony-forming units assay evidenced a rather synergic effect of NPs and radiation. By adding the NPs to cells before irradiation, a decrease of the number of proliferating cell colonies was observed with increase of X-ray dose. DNA damage was evidenced by quantifying the γ-H2AX foci for cells treated with Y2O3 NPs and exposed to superficial X-ray radiation. Proteomic profile confirmed that a combined effect of 50 µg/mL Y2O3 NPs and 6 Gy X-ray dose induced mitochondria alterations and DNA changes in melanoma cells.
The Association of Post-Concussion and Post-Traumatic Stress Disorder Symptoms with Health-Related Quality of Life, Health Care Use and Return-to-Work after Mild Traumatic Brain Injury

Patients with mild traumatic brain injury (mTBI) are at risk for post-concussion (PC) symptoms and post-traumatic stress disorder (PTSD). The co-occurrence of PC and PTSD symptoms after mTBI in relation to health-related quality of life (HRQoL), health care utilization, and return to work has not yet been investigated. PC and PTSD symptoms were measured six months post-TBI by respectively the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). Of the 1566 individuals after mTBI who met the inclusion criteria, 26.1% experienced PC symptoms (RPQ ≥16). Additionally, 9.8% experienced PTSD symptoms (PCL-5 ≥ 33), of which the vast majority (81%) also reported experiencing PC symptoms. Differences between patients with no/mild symptoms, with only PC, only PTSD, and both PC and PTSD symptoms in HRQoL, return to work, and rehabilitation were analyzed using logistic and linear regression analyses. Patients with PC and/or PTSD symptoms reported lower HRQoL, higher rates of rehabilitation, and lower return to work rates compared to patients with no/mild symptoms. Patients with both PC and PTSD symptoms reported significantly lower HRQoL (B = −2.73, CI = −4.65; −0.83, p < 0.001) compared to those with only PC symptoms, while there were no significant differences in their ongoing rehabilitation care (OR = 1.39, CI = 0.77–2.49, p = 0.272) and return to work rates (OR = 0.49, CI = 0.15–1.63, p = 0.246) at six months. These results underline the importance of the diagnosis and appropriate treatment of patients with mTBI, experiencing PC and/or PTSD symptoms.
Recent Applications of Deep Learning Methods on Evolution- and Contact-Based Protein Structure Prediction

The new advances in deep learning methods have influenced many aspects of scientific research, including the study of the protein system. The prediction of proteins’ 3D structural components is now heavily dependent on machine learning techniques that interpret how protein sequences and their homology govern the inter-residue contacts and structural organization. Especially, methods employing deep neural networks have had a significant impact on recent CASP13 and CASP14 competition. Here, we explore the recent applications of deep learning methods in the protein structure prediction area. We also look at the potential opportunities for deep learning methods to identify unknown protein structures and functions to be discovered and help guide drug–target interactions. Although significant problems still need to be addressed, we expect these techniques in the near future to play crucial roles in protein structural bioinformatics as well as in drug discovery.
Biological Age in Relation to Somatic, Physiological, and Swimming Kinematic Indices as Predictors of 100 m Front Crawl Performance in Young Female Swimmers

Background: Some swimmers reach high performance level at a relatively young age. The purpose of this study is to determine the relationship between adolescent female swimmers’ 100 m front crawl race (Vtotal100) and several anthropometry, body composition, and physiological and specific strength indices. Methods: Nineteen adolescent female swimmers were examined for biological age (BA) and body composition. Oxygen uptake was measured during water-flume stage-test front crawl swimming with ventilatory thresholds examination. Specific strength indices were assessed during 30 s of tethered swimming. Stroke rate (SR), stroke length (SL), and stroke index (SI) were also examined. Results: BA was strongly correlated with anthropometrics and tethered swimming strength indices, and showed moderate to strong correlation with ventilatory thresholds. Speed of swimming in the race was moderately to largely correlated with speed at V˙O2 max−VV˙O2max (r = 0.47–0.55; p < 0.05)—ventilatory thresholds (VAT, VRCP) (r = 0.50–0.85; p < 0.05), SL (r = 0.58–0.62; p < 0.05), and SI (r = 0.79–0.81; p < 0.01). Conclusion: Results confirmed a significant role of biological maturation mediation on body composition and body size, ventilatory indices, and specific strength indices. BA was not a significant mediation factor influencing the swimming kinematics (SL, SI) and speeds of VAT, VRCP or VV˙O2 max, which were strong predictors of the 100 m race.
Phytochemical Characterization and Bioactivity of Asparagus acutifolius: A Focus on Antioxidant, Cytotoxic, Lipase Inhibitory and Antimicrobial Activities

The phytochemical composition of leaves, stems, pericarps and rhizomes ethanolic extracts of Asparagus acutifolius were characterized by HPLC-DAD-MS. A. acutifolius samples contain at least eleven simple phenolics, one flavonon, two flavonols and six steroidal saponins. The stem extracts showed the highest total phenolic acid and flavonoid contents, where cafeic acid and rutin were the main compounds. No flavonoids were detected in the leaf, pericarp or rhizome while caffeic acid and ferulic acid were the predominant. Steroidal saponins were detected in the different plant parts of A. acutifolius, and the highest contents were found in the rhizome extracts. The stem extracts exhibited the highest antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) and the highest 2,2-azino-bis (3 ethylbenzothiazoline-6-sulphonic acid) (ABTS) scavenging activity was found in the pericarp extracts. The rhizome and leaf extracts showed a potent cytotoxic activity against HCT-116 and HepG2 cell lines. Moreover, the pericarp and rhizome extracts revealed a moderate lipase inhibitory activity. The leaf and rhizome extracts were screened for their antimicrobial activity against human pathogenic isolates. The leaf extract exhibited a powerful inhibitory activity against all the bacteria and fungi tested.
Effect of Soybean and Soybean Koji on Obesity and Dyslipidemia in Rats Fed a High-Fat Diet: A Comparative Study

Soybean koji refers to steamed soybeans inoculated with microbial species. Soybean fermentation improves the health benefits of soybeans. Obesity is a serious health concern owing to its increasing incidence rate and high association with other metabolic diseases. Therefore, we investigated the effects of soybean and soybean koji on high-fat diet-induced obesity in rats. Five-week-old male Sprague-Dawley rats were randomly divided into four groups (n = 8/group) as follows: (1) regular diet (RD), (2) high-fat diet (HFD), (3) HFD + steamed soybean (HFD+SS), and (4) HFD + soybean koji (HFD+SK). SK contained more free amino acids and unsaturated fatty acids than SS. In a rat model of obesity, SK consumption significantly alleviated the increase in weight of white adipose tissue and mRNA expression of lipogenic genes, whereas SS consumption did not. Both SS and SK reduced serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, and increased high-density lipoprotein cholesterol levels. SS and SK also inhibited lipid accumulation in the liver and white adipose tissue and reduced adipocyte size. Although both SS and SK could alleviate HFD-induced dyslipidemia, SK has better anti-obesity effects than SS by regulating lipogenesis. Overall, SK is an excellent functional food that may prevent obesity.
X-ray Computed Tomography Procedures to Quantitatively Characterize the Morphological Features of Triply Periodic Minimal Surface Structures

Additively manufactured (AM) metallic sheet-based Triply Periodic Minimal Surface Structures (TPMSS) meet several requirements in both bio-medical and engineering fields: Tunable mechanical properties, low sensitivity to manufacturing defects, mechanical stability, and high energy absorption. However, they also present some challenges related to quality control, which can prevent their successful application. In fact, the optimization of the AM process is impossible without considering structural characteristics as manufacturing accuracy, internal defects, as well as surface topography and roughness. In this study, the quantitative non-destructive analysis of TPMSS manufactured from Ti-6Al-4V alloy by electron beam melting was performed by means of X-ray computed tomography (XCT). Several advanced image analysis workflows are presented to evaluate the effect of build orientation on wall thicknesses distribution, wall degradation, and surface roughness reduction due to the chemical etching of TPMSS. It is shown that the manufacturing accuracy differs for the structural elements printed parallel and orthogonal to the manufactured layers. Different strategies for chemical etching show different powder removal capabilities and both lead to the loss of material and hence the gradient of the wall thickness. This affects the mechanical performance under compression by reduction of the yield stress. The positive effect of the chemical etching is the reduction of the surface roughness, which can potentially improve the fatigue properties of the components. Finally, XCT was used to correlate the amount of retained powder with the pore size of the functionally graded TPMSS, which can further improve the manufacturing process.
An Investigation into the Potential of Targeting Escherichia coli rne mRNA with Locked Nucleic Acid (LNA) Gapmers as an Antibacterial Strategy

The increase in antibacterial resistance is a serious challenge for both the health and defence sectors and there is a need for both novel antibacterial targets and antibacterial strategies. RNA degradation and ribonucleases, such as the essential endoribonuclease RNase E, encoded by the rne gene, are emerging as potential antibacterial targets while antisense oligonucleotides may provide alternative antibacterial strategies. As rne mRNA has not been previously targeted using an antisense approach, we decided to explore using antisense oligonucleotides to target the translation initiation region of the Escherichia coli rne mRNA. Antisense oligonucleotides were rationally designed and were synthesised as locked nucleic acid (LNA) gapmers to enable inhibition of rne mRNA translation through two mechanisms. Either LNA gapmer binding could sterically block translation and/or LNA gapmer binding could facilitate RNase H-mediated cleavage of the rne mRNA. This may prove to be an advantage over the majority of previous antibacterial antisense oligonucleotide approaches which used oligonucleotide chemistries that restrict the mode-of-action of the antisense oligonucleotide to steric blocking of translation. Using an electrophoretic mobility shift assay, we demonstrate that the LNA gapmers bind to the translation initiation region of E. coli rne mRNA. We then use a cell-free transcription translation reporter assay to show that this binding is capable of inhibiting translation. Finally, in an in vitro RNase H cleavage assay, the LNA gapmers facilitate RNase H-mediated mRNA cleavage. Although the challenges of antisense oligonucleotide delivery remain to be addressed, overall, this work lays the foundations for the development of a novel antibacterial strategy targeting rne mRNA with antisense oligonucleotides.
Gender Differences in Physical Fitness Characteristics in Professional Padel Players

The aims of the present study were to examine the fitness characteristics of professional padel players and to determine differences in physical performance regarding players’ gender. Thirty professional padel players (men: n = 15, age = 27.4 ± 6.8 years, height = 177.9 ± 4.0 cm; women: n = 15, age = 30.0 ± 4.2 years, height = 166.6 ± 4.8 cm) completed a 4-day evaluation process, including: isometric handgrip strength, sit and reach, 10 × 5 shuttle test, countermovement jump (CMJ), squat jump (SJ), Abalakov test, one-repetition maximum test (bench press, leg extension, leg curl, lat pulldowns, overhead press, and shoulder press), anthropometry and VO2 max tests. The men players had higher values in terms of weight, height, one maximum repetition, jump tests (CMJ and ABK) and VO2 max test than the women (p < 0.005). By contrast, the women had higher values for fat mass (p = 0.005; ES: 2.49). The values from this multifaceted test battery can be a useful guide for coaches regarding players’ development in future evaluations and monitoring.